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Artículos originales (todos) *** Original articles (all)
Pancreatic cancer.
February - March 2013
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[1]
TÍTULO / TITLE: - Case records of the Massachusetts General Hospital. Case 6-2013. A 54-year-old man with recurrent diarrhea.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - N Engl J Med. 2013 Feb 21;368(8):757-65. doi: 10.1056/NEJMcpc1208149.
●● Enlace al texto completo (gratuito o de pago) 1056/NEJMcpc1208149
AUTORES / AUTHORS: - Simmons LH; Guimaraes AR; Zukerberg LR
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Massachusetts General Hospital, Boston, USA.
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[2]
TÍTULO / TITLE: - Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Oncol. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1093/annonc/mdt066
AUTORES / AUTHORS: - Wolpin BM; O’Reilly EM; Ko YJ; Blaszkowsky LS; Rarick M; Rocha-Lima CM; Ritch P; Chan E; Spratlin J; Macarulla T; McWhirter E; Pezet D; Lichinitser M; Roman L; Hartford A; Morrison K; Jackson L; Vincent M; Reyno L; Hidalgo M
INSTITUCIÓN / INSTITUTION: - Dana-Farber Cancer Institute, Boston.
RESUMEN / SUMMARY: - BackgroundWe evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer.Patients and methodsPatients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m2 weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression.ResultsBetween April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup.ConclusionsThis randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma.ClinicalTrials.gov identifier: NCT00902291.
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[3]
TÍTULO / TITLE: - Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nature. 2013 Apr 4;496(7443):101-5. doi: 10.1038/nature12040. Epub 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1038/nature12040
AUTORES / AUTHORS: - Son J; Lyssiotis CA; Ying H; Wang X; Hua S; Ligorio M; Perera RM; Ferrone CR; Mullarky E; Shyh-Chang N; Kang Y; Fleming JB; Bardeesy N; Asara JM; Haigis MC; DePinho RA; Cantley LC; Kimmelman AC
INSTITUCIÓN / INSTITUTION: - Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
RESUMEN / SUMMARY: - Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.
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[4]
TÍTULO / TITLE: - Dormant Cancer Cells Contribute to Residual Disease in a Model of Reversible Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 15;73(6):1821-1830. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-2067
AUTORES / AUTHORS: - Lin WC; Rajbhandari N; Liu C; Sakamoto K; Zhang Q; Triplett AA; Batra SK; Opavsky R; Felsher DW; Dimaio DJ; Hollingsworth MA; Morris JP 4th; Hebrok M; Witkiewicz AK; Brody JR; Rui H; Wagner KU
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Eppley Institute for Research in Cancer and Allied Diseases; Departments of Biochemistry and Molecular Biology and Pathology and Microbiology, University of Nebraska Medical Center, Nebraska Medical Center, Omaha; Departments of Cancer Biology, Pathology, and Surgery, Thomas Jefferson University, Philadelphia, Philadelphia; Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford; and Diabetes Center, Department of Medicine, University of California, San Francisco, California.
RESUMEN / SUMMARY: - The initiation and progression of pancreatic ductal adenocarcinoma (PDAC) is governed by a series of genetic and epigenetic changes, but it is still unknown whether these alterations are required for the maintenance of primary and metastatic PDAC. We show here that the c-Myc oncogene is upregulated throughout the entire process of neoplastic progression in human PDAC and in genetically engineered mice that express mutant Kras. To experimentally address whether c-Myc is essential for the growth and survival of cancer cells, we developed a novel mouse model that allows a temporally and spatially controlled expression of this oncogene in pancreatic progenitors and derived lineages of the exocrine pancreas. Unlike previous reports, upregulation of c-Myc was sufficient to induce the formation of adenocarcinomas after a short latency without additional genetic manipulation of cell survival pathways. Deficiency in Cdkn2a increased the rate of metastasis but had no effect on tumor latency or c-Myc-mediated cancer maintenance. Despite a macroscopically complete regression of primary, metastatic, and transplantable tumors following the ablation of c-Myc, some cancer cells remained dormant. A significant number of these residual neoplastic cells expressed cancer stem cell markers, and re-expression of exogenous c-Myc in these cells led to rapid cancer recurrence. Collectively, the results of this study suggest that c-Myc plays a significant role in the progression and maintenance of PDAC, but besides targeting this oncogene or its downstream effectors, additional therapeutic strategies are necessary to eradicate residual cancer cells to prevent disease recurrence. Cancer Res; 73(6); 1821-30. ©2012 AACR.
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[5]
TÍTULO / TITLE: - Immunohistochemically Detected Expression of 3 Major Genes (CDKN2A/p16, TP53, and SMAD4/DPC4) Strongly Predicts Survival in Patients With Resectable Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e3182827a65
AUTORES / AUTHORS: - Oshima M; Okano K; Muraki S; Haba R; Maeba T; Suzuki Y; Yachida S
INSTITUCIÓN / INSTITUTION: - *Departments of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan daggerDepartment of Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan double daggerDepartment of Laboratory Medicine, Social Insurance Ritsurin Hospital, Takamatsu, Kagawa, Japan section signDepartment of Surgery, Social Insurance Ritsurin Hospital, Takamatsu, Kagawa, Japan paragraph signDivision of Refractory Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
RESUMEN / SUMMARY: - OBJECTIVE:: The goal of this retrospective study was to clarify the clinical implications of the status of the 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4). BACKGROUND:: Recent whole-exome sequencing had shown that the landscape of the pancreatic ductal adenocarcinoma (PDAC) genome is notable for 4 frequently mutated genes (KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4). METHODS:: We determined immunohistochemically the status of TP53, CDKN2A/p16, and SMAD4/DPC4 among the 4 genes because the KRAS gene is mutated in virtually all PDAC patients, and analyzed relationships with clinicopathological findings, including survival and patterns of disease progression, in 106 patients with PDAC undergoing radical surgery. RESULTS:: Abnormal immunolabeling of p53 was detected in 81.1% of PDACs and was significantly associated with tumor dedifferentiation (P = 0.022) and the presence of locoregional recurrence (P = 0.020). Loss of p16 and Smad4/Dpc4 immunolabeling was identified in 67.0% and 60.4%, respectively. Loss of p16 immunolabeling was associated with lymphatic invasion (P = 0.012) and postoperative widespread metastases (P < 0.001). A significant correlation was found between Smad4/Dpc4 immunolabeling and tumor size (P = 0.006), lymphatic invasion (P = 0.033), and lymph node metastasis (P = 0.006). Interestingly, all of the 6 patients demonstrating 5-year survival had intact SMAD4/DPC4. Kaplan-Meier survival analysis showed that lymph node metastasis (P = 0.001), lymphatic invasion (P = 0.008), the tumor (T) factor (T3 vs. T1/T2, P = 0.004), loss of p16 immunolabeling (P = 0.029), and loss of Smad4/Dpc4 immunolabeling (P < 0.001) were significantly associated with shorter overall survival. Multivariate analysis revealed that loss of Smad4/Dpc4 immunolabeling was an independent and significant poor prognostic factor for overall and disease-free survival. On analysis of combinations of the status of these 3 genes, increasing number of alterations reflected poorer survival. CONCLUSIONS:: Genetic alterations of these 3 genes and their accumulation are strongly associated with malignant behavior of PDAC. Their immunohistochemical assessment at the time of diagnosis may provide a new prognostic tool, assisting in deciding optimal therapeutic strategies for patients.
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[6]
TÍTULO / TITLE: - Circulating tumor cells in pancreatic cancer patients: Methods of detection and clinical implications.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 28. doi: 10.1002/ijc.28134.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28134
AUTORES / AUTHORS: - Tjensvoll K; Nordgard O; Smaaland R
INSTITUCIÓN / INSTITUTION: - Department of Haematology and Oncology, Stavanger University Hospital, N-4068, Stavanger, Norway.
RESUMEN / SUMMARY: - The poor prognosis of pancreatic cancer patients is associated with the frequent and early dissemination of the disease, as well as late detection due to unspecific and late symptoms from the primary tumor. Pancreatic cancers frequently spread to the liver, lung and skeletal system, suggesting that pancreatic tumor cells must be able to intravasate and travel through the circulation to distant organs. Circulating tumor cells (CTCs) are tumor cells that have acquired the ability to enter the circulatory system; this cell population is ultimately responsible for the development of metastases in distant organs. Clinical studies have revealed that the presence of CTCs in blood is correlated with disease progression for other cancers, such as breast, colorectal and prostate cancer. However, as CTCs are extremely rare, both enrichment and sensitive methods of detection are required for their enumeration. This review highlights various enrichment procedures and methods for the detection of CTCs. Furthermore, we systematically review previously reported studies of the clinical relevance of CTC detection in pancreatic cancer patients. There is evidence that the presence of CTCs also correlates with an unfavorable outcome in pancreatic cancer patients. However, technical/methodological issues may explain why some studies only show a trend toward an association between CTC detection and disease progression. Larger studies, as well as characterization of the CTC population, are required to achieve further insight into the clinical implications of CTC detection in pancreatic cancer patients.
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[7]
TÍTULO / TITLE: - Whole blood interferon-gamma levels predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 19. doi: 10.1002/ijc.28117.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28117
AUTORES / AUTHORS: - Ishikawa T; Kokura S; Sakamoto N; Okayama T; Endo M; Tsuchiya R; Okajima M; Matsuyama T; Adachi S; Kamada K; Katada K; Uchiyama K; Handa O; Takagi T; Yagi N; Ando T; Uno K; Naito Y; Yoshikawa T
INSTITUCIÓN / INSTITUTION: - Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Cancer ImmunoCell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
RESUMEN / SUMMARY: - A core challenge in administering immune-based treatments for cancer is the establishment of easily accessible immunological assays that can predict patients’ clinical responses to immunotherapy. In this study, our aim was to predict the therapeutic effects of adoptive T-cell therapy in patients with advanced pancreatic cancer. To do this, we evaluated whole blood cytokine levels and peripheral regulatory T cells (Tregs) in 46 patients with unresectable or recurrent pancreatic cancer who received adoptive T-cell therapy at 2-week intervals. To test immune function, venous blood was obtained from patients before the start of therapy and 2 weeks after the 4th treatment. Whole blood interferon (IFN)-alpha levels (after stimulation with the Sendai virus) were evaluated, as well as the levels of 9 cytokines stimulated with phytohemagglutinin [interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, tumor necrosis factor-alpha, IFN-gamma, and granulocyte-monocyte colony-stimulating factor]. Peripheral Tregs were analyzed by flow cytometry. Using the obtained data, we then observed the relationship between these immunological parameters and clinical outcome of patients. We found that the whole blood production of IFN-gamma, IL-2, IL-4, IL-5 and IL-13 significantly increased after adoptive T-cell therapy, whereas the number of peripheral Tregs did not change. Multivariate Cox proportional hazards analyses indicated that the number of peripheral Tregs before receiving adoptive T-cell therapy and the change in IFN-gamma levels after adoptive T-cell therapy were independent variables predicting overall survival. The findings of this study indicate that the assay of whole blood IFN-gamma production offers promise for evaluating the clinical response of patients to cancer immunotherapy.
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[8]
TÍTULO / TITLE: - Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar;71(3):765-75. doi: 10.1007/s00280-013-2070-8. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2070-8
AUTORES / AUTHORS: - Welsh JL; Wagner BA; van’t Erve TJ; Zehr PS; Berg DJ; Halfdanarson TR; Yee NS; Bodeker KL; Du J; Roberts LJ 2nd; Drisko J; Levine M; Buettner GR; Cullen JJ
INSTITUCIÓN / INSTITUTION: - Department of Surgery, 1528 JCP-UIHC, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
RESUMEN / SUMMARY: - BACKGROUND: Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma. DESIGN: Nine subjects received twice-weekly intravenous ascorbate (15-125 g) employing Simon’s accelerated titration design to achieve a targeted post-infusion plasma level of >/=350 mg/dL (>/=20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored. RESULTS: Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 +/- 0.02 vs. 0.78 +/- 0.09 mg/dL, i.e., 83 vs. 44 muM, p < 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (n = 4) and dry mouth (n = 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 +/- 2 months. CONCLUSIONS: Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.
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[9]
TÍTULO / TITLE: - Pancreatic cancer associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-4601
AUTORES / AUTHORS: - Mace TA; Ameen Z; Collins A; Wojcik SE; Mair M; Young GS; Fuchs JR; Eubank TD; Frankel WL; Bekaii-Saab T; Bloomston M; Lesinski GB
INSTITUCIÓN / INSTITUTION: - Internal Medicine, The Ohio State University.
RESUMEN / SUMMARY: - Pancreatic stellate cells (PSC) are a subset of pancreatic cancer-associated fibroblasts. These cells provide pro-survival signals to tumors, however little is known regarding their interactions with immune cells within the tumor microenvironment. We hypothesized that factors produced by human PSC could enhance myeloid-derived suppressor cell (MDSC) differentiation and function, which promotes an immunosuppressive microenvironment. Primary PSC cell lines (n=7) were generated from human specimens and phenotypically confirmed via expression of vimentin, alpha-smooth muscle actin (alpha-SMA), and glial fibrillary acidic protein (GFAP). Luminex analysis indicated that PSC but not human fetal primary pancreatic fibroblast cells (HPF; negative controls) produced MDSC-promoting cytokines (IL-6, VEGF, M-CSF) and chemokines (SDF-1, MCP-1). Culture of peripheral blood mononuclear cells (PBMC, n=3 donors) with PSC supernatants or IL-6/GM-CSF (positive control) for 7 days promoted PBMC differentiation into an MDSC (CD11b+CD33+) phenotype and a sub-population of polymorphonuclear CD11b+CD33+CD15+ cells. The resulting CD11b+CD33+ cells functionally suppressed autologous T lymphocyte proliferation. In contrast, supernatants from HPF did not induce an MDSC phenotype in PBMCs. Culture of normal PBMCs with PSC supernatants led to STAT3 but not STAT1 or STAT5 phosphorylation. IL-6 was an important mediator as its neutralization inhibited PSC supernatant-mediated STAT3 phosphorylation and MDSC differentiation. Finally, the FLLL32 STAT3 inhibitor abrogated PSC supernatant-mediated MDSC differentiation, PSC viability, and reduced autocrine IL-6 production indicating these processes are STAT3 dependent. These results identify a novel role for PSC in driving immune escape in pancreatic cancer and extend the evidence that STAT3 acts as a driver of stromal immunosuppression to enhance its interest as a therapeutic target.
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[10]
TÍTULO / TITLE: - Borderline Resectable Pancreatic Cancer: Need for Standardization and Methods for Optimal Clinical Trial Design.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2886-9
AUTORES / AUTHORS: - Katz MH; Marsh R; Herman JM; Shi Q; Collison E; Venook AP; Kindler HL; Alberts SR; Philip P; Lowy AM; Pisters PW; Posner MC; Berlin JD; Ahmad SA
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA, mhgkatz@mdanderson.org.
RESUMEN / SUMMARY: - BACKGROUND: Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included an absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy. METHODS: In this manuscript, we review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed. RESULTS: We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed. CONCLUSIONS: Rigorous standards of clinical trial design incorporated into trials of other disease stages must be adopted in all future studies of borderline resectable pancreatic cancer. The Intergroup trial should serve as a paradigm for such investigations.
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[11]
TÍTULO / TITLE: - Phase II trial of erlotinib plus capecitabine as first-line treatment for metastatic pancreatic cancer (XELTA study).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):717-23.
AUTORES / AUTHORS: - Lopez R; Mendez CM; Fernandez MJ; Reinoso CR; Aldana GQ; Fernandez MS; DE LA Camara Gomez J; Lopez MR; Vazquez MR; Folgar SC
INSTITUCIÓN / INSTITUTION: - Servicio de Oncologia Medica, Complejo Hospitalario Universitario de Santiago de Compostela, Travesia de Choupana s/n. 15706 Santiago de Compostela, España. Rafael.Lopez.Lopez@sergas.es
RESUMEN / SUMMARY: - AIM: To evaluate the efficacy and safety of erlotinib plus capecitabine for metastatic pancreatic cancer. PATIENTS AND METHODS: This was a multicenter, uncontrolled, phase II trial. Patients with untreated metastatic pancreatic cancer received oral capecitabine at 1,000 mg/m(2) twice daily on days 1-14, of a 21-day treatment cycle; and oral erlotinib at 150 mg daily. RESULTS: Thirty-two patients were enrolled. The overall response rate (ORR) was 6%, with a median time to treatment failure of 2.1 months. The median follow-up was 7.6 months. The median progression-free survival was 2.1 months and median overall survival was 4.3 months. The one-year survival rate was 22%. Major grade 1 and 2 non-hematological toxicities were skin rash (34%), asthenia (31%) and diarrhea (31%). Grade 3 hematological toxicity was <13%. No grade 4 toxicities were detected. None of the patients died due to treatment toxicity. CONCLUSION: The combination of capecitabine with erlotinib is an active regimen with a favorable safety profile for patients with metastatic pancreatic cancer.
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[12]
TÍTULO / TITLE: - Disrupting Cytokine Signaling in Pancreatic Cancer: A Phase I/II Study of Etanercept in Combination With Gemcitabine in Patients With Advanced Disease.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279b87f
AUTORES / AUTHORS: - Wu C; Fernandez SA; Criswell T; Chidiac TA; Guttridge D; Villalona-Calero M; Bekaii-Saab TS
INSTITUCIÓN / INSTITUTION: - From the *Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research, Institute; daggerCenter for Biostatistics, The Ohio State University; and double daggerMark H Zangmeister Center, Columbus, OH.
RESUMEN / SUMMARY: - OBJECTIVES: Etanercept blocks tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine that plays a role in cancer-related cachexia and tumor growth. A phase I/II study was conducted to assess the tolerability and efficacy of gemcitabine and etanercept in advanced pancreatic cancer. METHODS: Twenty-five patients received etanercept 25 mg subcutaneously twice weekly with gemcitabine. A control cohort of 8 patients received gemcitabine alone. The primary end point was progression-free survival at 6 months. Blood specimens were analyzed for TNF-alpha, IL-1beta, IL-6, interferon-gamma, IL-10, and NF-kappabeta activation. The trial is registered with ClinicalTrials.gov, number NCT00201838. RESULTS: Thirty-eight patients participated in this study. In the gemcitabine-etanercept cohort, grade ¾ drug-related toxicities included leucopenia (3) and neutropenia (6). There were 3 (12%) patients with partial response and 8 (32%) patients with stable disease. The rate of progression-free survival at 6 months was 28% [n = 7; 95% confidence interval (CI), 20%-36%]. Median time to progression was 2.23 months (95% CI, 1.86-4.36 months) and median overall survival was 5.43 months (95% CI, 3.30-10.23 months). Clinical benefit rate was 33% of the evaluable patients. A correlation was seen between IL-10 levels and clinical benefit. CONCLUSIONS: Etanercept added to gemcitabine is safe but did not show significant enhancement of gemcitabine in patients with advanced pancreatic cancer.
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[13]
TÍTULO / TITLE: - Enhancer of Zeste Homolog 2 Silences MicroRNA-218 in Human Pancreatic Ductal Adenocarcinoma Cells by Inducing Formation of Heterochromatin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastroenterology. 2013 Feb 7. pii: S0016-5085(13)00154-6. doi: 10.1053/j.gastro.2013.01.058.
●● Enlace al texto completo (gratuito o de pago) 1053/j.gastro.2013.01.058
AUTORES / AUTHORS: - Li CH; To KF; Tong JH; Xiao Z; Xia T; Lai PA; Chow SC; Zhu YX; Chan SL; Marquez VE; Chen Y
INSTITUCIÓN / INSTITUTION: - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
RESUMEN / SUMMARY: - BACKGROUND & AIMS: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is overexpressed by pancreatic ductal adenocarcinoma (PDAC) cells and increases their aggressiveness. We identified microRNAs (miRs) that are regulated by EZH2 and studied their functions in PDAC cells. METHODS: We performed miR profile analysis of PDAC cells incubated with EZH2 inhibitor 3-deazaneplanocin A, and pancreatic ductal epithelial cells that overexpressed EZH2. Expression levels of miRs and the targets of miRs were analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. We expressed different forms of EZH2 to analyze functional domains and used small interfering RNAs to reduce its level in PDAC cells. RESULTS: Expression of miR-218 was repressed by EZH2 in PDAC cells. Levels of miR-218 were significantly reduced in primary PDAC tumor samples compared with paired, adjacent nontumor tissue. Overexpression of miR-218 in SW1990 cells reduced their proliferation and tumor formation and metastasis in nude mice. Loss of miR-218 from SW1990 cells increased levels of UDP-glycosyltransferase 8 and miR-218 was found to bind to its 3’ -UTR. Levels of UDP-glycosyltransferase protein and messenger RNA were associated with the metastatic potential of PDAC cell lines and progression of tumors in patients. EZH2 was found to silence miR-218 by binding to its promoter, promoting heterochromatin formation, and recruiting the DNAs methyltransferase 1, 3A, and 3B. CONCLUSIONS: EZH2 is up-regulated in PDAC samples from patients and silences miR-218. MicroRNA-218 prevents proliferation of PDAC cells in culture, and tumor growth and metastasis in nude mice. MicroRNA-218 reduces levels of UDP-glycosyltransferase, which is associated with the metastatic potential of PDAC tumors in mice and progression of human PDAC.
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[14]
TÍTULO / TITLE: - Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Lancet Oncol. 2013 Mar 5. pii: S1470-2045(13)70021-4. doi: 10.1016/S1470-2045(13)70021-4.
●● Enlace al texto completo (gratuito o de pago) 1016/S1470-2045(13)70021-4
AUTORES / AUTHORS: - Mukherjee S; Hurt CN; Bridgewater J; Falk S; Cummins S; Wasan H; Crosby T; Jephcott C; Roy R; Radhakrishna G; McDonald A; Ray R; Joseph G; Staffurth J; Abrams RA; Griffiths G; Maughan T
INSTITUCIÓN / INSTITUTION: - Gray Institute for Radiation Oncology and Biology, University of Oxford, NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk.
RESUMEN / SUMMARY: - BACKGROUND: In the UK, chemotherapy is the standard treatment for inoperable, locally advanced, non-metastatic pancreatic cancer. Chemoradiotherapy is also an acceptable treatment option, for which gemcitabine, fluorouracil, or capecitabine can be used as concurrent chemotherapy agents. We aimed to assess the activity, safety, and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer. METHODS: In this open-label, randomised, two-arm, phase 2 trial, patients aged 18 years or older with histologically proven, locally advanced pancreatic cancer (with a tumour diameter of 7 cm or less) were recruited from 28 UK centres between Dec 24, 2009 and Oct 25, 2011. After 12 weeks of induction gemcitabine and capecitabine chemotherapy (three cycles of gemcitabine [1000 mg/m2 on days 1, 8, 15 of a 28-day cycle] and capecitabine [830 mg/m2 twice daily on days 1-21 of a 28-day cycle]), patients with stable or responding disease, tumour diameter of 6 cm or less, and WHO performance status 0-1 were randomly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine (300 mg/m2 once per week) or capecitabine (830 mg/m2 twice daily, Monday to Friday only), both in combination with radiation (50.4 Gy in 28 fractions). Randomisation (1:1) was done via a central computerised system and used stratified minimisation. The primary endpoint was 9-month progression-free survival, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ISRCTN, number 96169987. FINDINGS: 114 patients were registered and 74 were randomly allocated (38 to the gemcitabine group and 36 to the capecitabine group). After 9 months, 22 of 35 assessable patients (62.9%, 80% CI 50.6-73.9) in the capecitabine group and 18 of 35 assessable patients (51.4%, 39.4-63.4) in the gemcitabine group had not progressed. Median overall survival was 15.2 months (95% CI 13.9-19.2) in the capecitabine group and 13.4 months (95% CI 11.0-15.7) in the gemcitabine group (adjusted hazard ratio [HR] 0.39, 95% CI 0.18-0.81; p=0.012). 12-month overall survival was 79.2% (95% CI 61.1-89.5) in the capecitabine group and 64.2 (95% CI 46.4-77.5) in the gemcitabine group. Median progression-free survival was 12.0 months (95% CI 10.2-14.6) in the capecitabine group and 10.4 months (95% CI 8.9-12.5) in the gemcitabine group (adjusted HR 0.60, 95% CI 0.32-1.12; p=0.11). Eight patients in the capecitabine group had an objective response at 26 weeks, as did seven in the gemcitabine group. More patients in the gemcitabine group than in the capecitabine group had grade 3-4 haematological toxic effects (seven [18%] vs none, p=0.008) and non-haematological toxic effects (ten [26%] vs four [12%], p=0.12) during chemoradiation treatment; the most frequent events were leucopenia, neutropenia, and fatigue. Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy. Of the 34 patients in the capecitabine group who received chemoradiotherapy, 25 (74%) received the full protocol dose of radiotherapy, compared with 26 (68%) of 38 patients in the gemcitabine group. Quality-of-life scores were not significantly different between the treatment groups. INTERPRETATION: Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer. However, these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small. FUNDING: Cancer Research UK.
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[15]
TÍTULO / TITLE: - Pathohistological Subtype Predicts Survival in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e318287ab73
AUTORES / AUTHORS: - Distler M; Kersting S; Niedergethmann M; Aust DE; Franz M; Ruckert F; Ehehalt F; Pilarsky C; Post S; Saeger HD; Grutzmann R
INSTITUCIÓN / INSTITUTION: - *Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany daggerDepartment of General Surgery, Alfred Krupp Hospital, Essen, Germany double daggerInstitute for Pathology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany section signDepartment of Surgery, University Hospital Mannheim, Mannheim, Germany.
RESUMEN / SUMMARY: - OBJECTIVE:: To investigate different subtypes of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and their prognostic value. BACKGROUND:: IPMNs of the pancreas are estimated to have a better prognosis than pancreatic ductal adenocarcinomas (PDACs). In addition to the different growth types (ie, main duct vs. branch duct types), the histological subtypes of IPMNs (ie, intestinal, pancreatobiliary, gastric, and oncocytic type) are prognostically relevant. These subtypes can be characterized by different mucin (MUC) expression patterns. In this study, we analyzed the IPMNs from 2 pancreatic cancer referral centers by correlating the MUC expression, histological subtype, and clinical outcome. METHODS:: We re-evaluated all resections due to a pancreatic tumor over a period of 15 years. Cases with IPMNs were identified, and the subtypes were distinguished using histopathological analysis, including the immunohistochemical analysis of MUC (ie, MUC1, MUC2, and MUC5AC) expression. Furthermore, we determined clinical characteristics and patient outcome. RESULTS:: A total of 103 IPMNs were identified. On the basis of the MUC profile, histopathological subtypes were classified into the following categories: intestinal type [n = 45 (44%)], pancreatobiliary type [n = 41 (40%)], gastric type [n = 13 (12%)], and oncocytic type [n = 4 (4%)]. The following types of resections were performed: pancreatic head resections [n = 77 (75%)], tail resections [n = 16 (15%)], total pancreatectomies [n = 5 (5%)], and segment resections [n = 5 (5%)]. The 5-year survival of patients with intestinal IPMNs was significantly better than pancreatobiliary IPMNs (86.6% vs. 35.6%; P < 0.001). The pancreatobiliary subtype was strongly associated with malignancy [odds ratio (OR): 6.76], recurrence (P < 0.001), and long-term survival comparable with that of PDAC patients. CONCLUSIONS:: Evaluation of IPMN subtypes supports postoperative patient prognosis prediction. Therefore, subtype differentiation could lead to improvements in clinical management. Potentially identifying subgroups with the need for adjuvant therapy may be possible.
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[16]
TÍTULO / TITLE: - A prospective, comparative trial to optimize sampling techniques in EUS-guided FNA of solid pancreatic masses.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastrointest Endosc. 2013 Feb 21. pii: S0016-5107(12)03062-3. doi: 10.1016/j.gie.2012.12.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2012.12.009
AUTORES / AUTHORS: - Lee JK; Choi JH; Lee KH; Kim KM; Shin JU; Lee JK; Lee KT; Jang KT
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Dongguk University Ilsan Hospital, College of Medicine, Dongguk University, Seoul, Republic of Korea.
RESUMEN / SUMMARY: - BACKGROUND: There is no standardization of the use of suction during puncturing of a target in pancreatic EUS-guided FNA (EUS-FNA). It is also debatable whether expressing aspirates from the needle by the traditional method of reinserting the stylet is more effective than by air flushing, which is easier and safer. OBJECTIVE: To optimize sampling techniques in pancreatic EUS-FNA. DESIGN: Prospective, comparative trial. SETTING: Tertiary-care referral center. PATIENTS: Eighty-one consecutive patients with solid pancreatic masses. INTERVENTION: Four punctures were performed for each mass in random order by a 2 x 2 factorial design. Sample quality and diagnostic yield were compared between samples with suction (S+) versus no suction (S-) and expressed by reinserting the stylet (RS) versus air flushing (AF). MAIN OUTCOME MEASUREMENTS: Sample quality by the number of diagnostic samples, cellularity, bloodiness, and air-drying artifact; diagnostic yield by accuracy, sensitivity, and specificity. RESULTS: The number of diagnostic samples (72.8% vs 58.6%; P = .001), cellularity (odds ratio [OR] 2.12; 95% confidence interval [CI], 1.37-3.30; P < .001), bloodiness (OR 1.46; CI, 1.28-1.68; P < .001), accuracy (85.2% vs 75.9%; P = .004), and sensitivity (82.4% vs 72.1%; P = .005) were higher in S+ than in S-. Bloodiness was lower in AF than in RS (OR 1.16; CI, 1.03-1.30; P = .017). LIMITATIONS: Single-center trial, 2 kinds of needle gauges, and no immediate cytopathology evaluation. CONCLUSION: Puncturing with suction and expressing by air flushing may be used preferentially in pancreatic EUS-FNA because they were more effective and convenient techniques. (Clinical trial registration number: NCT01354795.).
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[17]
TÍTULO / TITLE: - Phase II randomised proof-of-concept study of the urokinase inhibitor upamostat (WX-671) in combination with gemcitabine compared with gemcitabine alone in patients with non-resectable, locally advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 5;108(4):766-70. doi: 10.1038/bjc.2013.62. Epub 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.62
AUTORES / AUTHORS: - Heinemann V; Ebert MP; Laubender RP; Bevan P; Mala C; Boeck S
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, D-81377 Munich, Germany.
RESUMEN / SUMMARY: - Background:To evaluate the efficacy and tolerability of the urokinase plasminogen activator (uPA) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma (LAPC).Methods:Within a prospective multicenter study, LAPC patients were randomly assigned to receive 1000 mg m of gemcitabine IV weekly either alone (arm A) or in combination with 200 mg (arm B) or 400 mg (arm C) oral upamostat daily. Efficacy endpoints of this proof-of-concept study included response rate, time to first metastasis, progression-free and overall survival (OS).Results:Of the 95 enroled patients, 85 were evaluable for response and 93 for safety. Median OS was 12.5 months (95% CI 8.2-18.2) in arm C, 9.7 months (95% CI 8.4-17.1) in arm B and 9.9 months (95% CI 7.4-12.1) in arm A; corresponding 1-year survival rates were 50.6%, 40.7% and 33.9%, respectively. More patients achieved a partial remission (confirmed responses by RECIST) with upamostat combination therapy (arm C: 12.9%; arm B: 7.1%; arm A: 3.8%). Overall, only 12 patients progressed by developing detectable distant metastasis (arm A: 4, arm B: 6, arm C: 2). The most common adverse events considered to be related to upamostat were asthenia, fever and nausea.Conclusion:In this proof-of-concept study targeting the uPA system in LAPC, the addition of upamostat to gemcitabine was tolerated well; similar survival results were observed for the three treatment arms.
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[18]
TÍTULO / TITLE: - Up-regulation of p21WAF1/CIP1 by small activating RNA inhibits the in vitro and in vivo growth of pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumori. 2012 Nov;98(6):804-11. doi: 10.1700/1217.13507.
●● Enlace al texto completo (gratuito o de pago) 1700/1217.13507
AUTORES / AUTHORS: - Zhang Z; Wang Z; Liu X; Wang J; Li F; Li C; Shan B
INSTITUCIÓN / INSTITUTION: - Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, 324 Jing Wu Road, Jinan, China.
RESUMEN / SUMMARY: - AIMS AND BACKGROUND: To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo. METHODS AND STUDY DESIGN: A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed. RESULTS: The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western blotting (P <0.01, compared with controls). The inhibitory effect on cell proliferation was confirmed by the MTT test (P <0.05, compared with controls). The apoptosis rate of PANC-1 cells treated with dsP21 was significantly higher than that of the control cells (P <0.01). Our experimental data showed that dsP21-mediated up-regulation of p21 expression exerted an apparent growth inhibitory effect on PANC-1 cells in vivo. CONCLUSIONS: dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.
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[19]
TÍTULO / TITLE: - Randomized trial comparing fanning with standard technique for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic mass lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endoscopy. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326268
AUTORES / AUTHORS: - Bang JY; Magee SH; Ramesh J; Trevino JM; Varadarajulu S
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
RESUMEN / SUMMARY: - Background and study aims: The fanning technique for endoscopic ultrasound-guided fine-needle aspiration (EUS - FNA) involves sampling multiple areas within a lesion with each pass. The aim of this study was to compare the fanning and standard techniques for EUS - FNA of solid pancreatic masses.Patients and methods: Consecutive patients with solid pancreatic mass lesions were randomized to undergo EUS - FNA using either the standard or the fanning technique. The main outcome measure was the median number of passes required to establish diagnosis. The secondary outcome measures were the diagnostic accuracy, technical failure, and complication rate of the two techniques.Results: Of 54 patients, 26 were randomized to the standard technique and 28 to the fanning technique. There was no difference in diagnostic accuracy (76.9 % vs. 96.4 %; P = 0.05), technical failure or complication rates (none in either cohort). There was a significant difference in both the number of passes required to establish diagnosis (median 1 [interquartile range 1 - 3] vs. 1 [1 - 1]; P = 0.02) and the percentage of patients in whom a diagnosis was achieved on pass one (57.7 % vs. 85.7 %; P = 0.02) between the standard and fanning groups, respectively.Conclusions: The fanning technique of FNA was superior to the standard approach because fewer passes were required to establish the diagnosis. If these promising data are confirmed by other investigators, consideration should be given to incorporating the fanning technique into routine practice of EUS - FNA. Registered at Clinical Trials.gov (NCT 01501903).
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[20]
TÍTULO / TITLE: - Histone deacetylase inhibitors and pancreatic cancer: Are there any promising clinical trials?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Feb 28;19(8):1173-81. doi: 10.3748/wjg.v19.i8.1173.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i8.1173
AUTORES / AUTHORS: - Koutsounas I; Giaginis C; Theocharis S
INSTITUCIÓN / INSTITUTION: - Ioannis Koutsounas, Constantinos Giaginis, Stamatios Theocharis, Department of Forensic Medicine and Toxicology, Medical School, University of Athens, GR-11527 Athens, Greece.
RESUMEN / SUMMARY: - Pancreatic cancer, although not very frequent, has an exceptionally high mortality rate, making it one of the most common causes of cancer mortality in developed countries. Pancreatic cancer is difficult to diagnose, allowing few patients to have the necessary treatment at a relatively early stage. Despite a marginal benefit in survival, the overall response of pancreatic cancer to current systemic therapy continues to be poor, and new therapies are desperately needed. Histone deacetylase (HDAC) enzymes play an important role in the development and progression of cancer and HDAC inhibitors (HDACIs) have been shown to induce differentiation and cell cycle arrest, activate the extrinsic or intrinsic pathways of apoptosis, and inhibit invasion, migration and angiogenesis in different cancer cell lines. As a result of promising preclinical data, various HDACIs are being tested as either monotherapeutic agents or in combination regimens for both solid and hematological malignancies. Vorinostat was the first HDACI approved by the Food and Drug Administration for patients with cutaneous T-cell lymphoma. The use of HDACIs in clinical trials, in pretreated and relapsed patients suffering from advanced pancreatic cancer is discussed. Unfortunately, clinical data for HDACIs in patients with pancreatic cancer are inadequate, because only a few studies have included patients suffering from this type of neoplasm and the number of pancreatic cancer patients that entered HDACIs phase II/III trials, among others with advanced solid tumors, is very limited. More studies recruiting patients with pancreatic cancer remain to determine the efficiency of these therapies.
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[21]
TÍTULO / TITLE: - Restoration of Mannose-Binding Lectin Complement Activity Is Associated With Improved Outcome in Patients With Advanced Pancreatic Cancer Treated With Gemcitabine and Intravenous omega-3 Fish Oil.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JPEN J Parenter Enteral Nutr. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1177/0148607113476304
AUTORES / AUTHORS: - Arshad A; Chung W; Isherwood J; Steward W; Metcalfe M; Dennison A
INSTITUCIÓN / INSTITUTION: - Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.
RESUMEN / SUMMARY: - Background: Pancreatic cancer has an extremely poor clinical outcome. Surrogate biomarkers for outcome are scarce. There is mixed evidence for the association of high mannose-binding lectin (MBL) complement activity with cancer outcomes, including reduced survival and increased infectious complications. omega-3-rich fatty acids (omega-3FA) attenuate production of proinflammatory cytokines and potentially manipulate complement activity. Materials and Methods: As part of a single-arm phase II trial in a university hospital, patients with advanced pancreatic adenocarcinoma were treated with weekly omega-3FA-rich intravenous infusion (Lipidem [B. Braun Melsungen AG, Melsungen, Germany]: up to 100 g/wk) plus gemcitabine chemotherapy until withdrawal or tumor progression. Primary outcome measure was objective response rate. Changes in complement activity, which were a secondary outcome measure, were analyzed and relation to clinical outcome determined. Results: Twenty-three patients were assessable for time to progression (TTP), overall survival (OS), and complement activity. No hypoactivity in alternative and classical pathways was demonstrated. Baseline MBL was low in 10 of 23 patients (43.5%). There was no difference in OS or TTP between low- and high-baseline MBL patients. Of these 10 patients, 5 were classified as MBL responders. MBL responders had a tendency toward improved OS over nonresponders (8.9 vs 4.4 months, P = .07). MBL responders had significantly improved TTP over nonresponders (10.6 vs 5.3 months, P = .03). Conclusion: MBL restoration had an association with improved outcome in the cohort of patients with low MBL activity at baseline. The independent contribution of omega-3FA to this effect warrants further investigation in the form of randomized clinical trials.
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[22]
TÍTULO / TITLE: - Phosphorylation on Ser-279 and Ser-282 of connexin43 regulates endocytosis and gap junction assembly in pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Biol Cell. 2013 Mar;24(6):715-33. doi: 10.1091/mbc.E12-07-0537. Epub 2013 Jan 30.
●● Enlace al texto completo (gratuito o de pago) 1091/mbc.E12-07-0537
AUTORES / AUTHORS: - Johnson KE; Mitra S; Katoch P; Kelsey LS; Johnson KR; Mehta PP
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology and Department of Oral Biology, Eppley Institute for Research in Cancer and Allied Diseases, Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198.
RESUMEN / SUMMARY: - The molecular mechanisms regulating the assembly of connexins (Cxs) into gap junctions are poorly understood. Using human pancreatic tumor cell lines BxPC3 and Capan-1, which express Cx26 and Cx43, we show that, upon arrival at the cell surface, the assembly of Cx43 is impaired. Connexin43 fails to assemble, because it is internalized by clathrin-mediated endocytosis. Assembly is restored upon expressing a sorting-motif mutant of Cx43, which does not interact with the AP2 complex, and by expressing mutants that cannot be phosphorylated on Ser-279 and Ser-282. The mutants restore assembly by preventing clathrin-mediated endocytosis of Cx43. Our results also document that the sorting-motif mutant is assembled into gap junctions in cells in which the expression of endogenous Cx43 has been knocked down. Remarkably, Cx43 mutants that cannot be phosphorylated on Ser-279 or Ser-282 are assembled into gap junctions only when connexons are composed of Cx43 forms that can be phosphorylated on these serines and forms in which phosphorylation on these serines is abolished. Based on the subcellular fate of Cx43 in single and contacting cells, our results document that the endocytic itinerary of Cx43 is altered upon cell-cell contact, which causes Cx43 to traffic by EEA1-negative endosomes en route to lysosomes. Our results further show that gap-junctional plaques formed of a sorting motif-deficient mutant of Cx43, which is unable to be internalized by the clathrin-mediated pathway, are predominantly endocytosed in the form of annular junctions. Thus the differential phosphorylation of Cx43 on Ser-279 and Ser-282 is fine-tuned to control Cx43’s endocytosis and assembly into gap junctions.
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[23]
TÍTULO / TITLE: - Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3919-24. doi: 10.1073/pnas.1219555110. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1073/pnas.1219555110
AUTORES / AUTHORS: - Guillaumond F; Leca J; Olivares O; Lavaut MN; Vidal N; Berthezene P; Dusetti NJ; Loncle C; Calvo E; Turrini O; Iovanna JL; Tomasini R; Vasseur S
INSTITUCIÓN / INSTITUTION: - Centre de Recherche en Cancerologie de Marseille (CRCM), Unite 1068, Institut National de la Sante et de la Recherche Medicale, F-13009 Marseille, France.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma is one of the most intractable and fatal cancer. The decreased blood vessel density displayed by this tumor not only favors its resistance to chemotherapy but also participates in its aggressiveness due to the consequent high degree of hypoxia. It is indeed clear that hypoxia promotes selective pressure on malignant cells that must develop adaptive metabolic responses to reach their energetic and biosynthetic demands. Here, using a well-defined mouse model of pancreatic cancer, we report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. We also show that hypoxia increases the “glycolytic” switch of pancreatic cancer cells from oxydative phosphorylation to lactate production and we demonstrate that increased lactate efflux from hypoxic cancer cells favors the growth of normoxic cancer cells. In addition, we show that glutamine metabolization by hypoxic pancreatic tumor cells is necessary for their survival. Metabolized glucose and glutamine converge toward a common pathway, termed hexosamine biosynthetic pathway, which allows O-linked N-acetylglucosamine modifications of proteins. Here, we report that hypoxia increases transcription of hexosamine biosynthetic pathway genes as well as levels of O-glycosylated proteins and that O-linked N-acetylglucosaminylation of proteins is a process required for hypoxic pancreatic cancer cell survival. Our results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate and hexosamine biosynthetic pathway activation, favor hypoxic and normoxic cancer cell survival and correlate with pancreatic ductal adenocarcinoma aggressiveness.
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[24]
TÍTULO / TITLE: - ABO blood groups and pancreatic cancer risk and survival: results from the PANcreatic Disease ReseArch (PANDoRA) consortium.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1637-44. doi: 10.3892/or.2013.2285. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2285
AUTORES / AUTHORS: - Rizzato C; Campa D; Pezzilli R; Soucek P; Greenhalf W; Capurso G; Talar-Wojnarowska R; Heller A; Jamroziak K; Khaw KT; Key TJ; Bambi F; Landi S; Mohelnikova-Duchonova B; Vodickova L; Buchler MW; Bugert P; Vodicka P; Neoptolemos JP; Werner J; Hoheisel JD; Bauer AS; Giese N; Canzian F
INSTITUCIÓN / INSTITUTION: - Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
RESUMEN / SUMMARY: - There is strong epidemiologic evidence indicating that common genetic variability could be implicated in pancreatic cancer risk and, to date, various loci have been proposed. In particular, there is increasing evidence of the involvement of ABO gene variability and pancreatic cancer risk. In a large multicentric study of 1,028 pancreatic ductal adenocarcinoma cases and 2,257 controls in the context of the PANcreatic Disease ReseArch (PANDoRA) consortium, we investigated the suggested association with increased risk for carriers of single nucleotide polymorphisms (SNPs) determining the A or B allele in comparison with the O allele, which encodes for a non-functional enzyme. Since glycosyltransferase activity, encoded by ABO, is higher for the A1 variant compared with the A2 variant, we investigated the hypothesis that A1 carriers were at an increased risk of pancreatic cancer. In our analysis, carriers of the A1 were indeed at greater risk of developing the disease. In addition, we investigated the possible influence that genetic variability at the ABO locus may have in pancreatic cancer survival, but we observed no effect in our population.
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[25]
TÍTULO / TITLE: - Hypoglycemia reduces vascular endothelial growth factor a production by pancreatic Beta cells as a regulator of Beta cell mass.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Biol Chem. 2013 Mar 22;288(12):8636-46. doi: 10.1074/jbc.M112.422949. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1074/jbc.M112.422949
AUTORES / AUTHORS: - Xiao X; Guo P; Chen Z; El-Gohary Y; Wiersch J; Gaffar I; Prasadan K; Shiota C; Gittes GK
INSTITUCIÓN / INSTITUTION: - From the Division of Pediatric Surgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224.
RESUMEN / SUMMARY: - VEGF-A expression in beta cells is critical for pancreatic development, formation of islet-specific vasculature, and Insulin secretion. However, two key questions remain. First, is VEGF-A release from beta cells coupled to VEGF-A production in beta cells? Second, how is the VEGF-A response by beta cells affected by metabolic signals? Here, we show that VEGF-A secretion, but not gene transcription, in either cultured islets or purified pancreatic beta cells, was significantly reduced early on during low glucose conditions. In vivo, a sustained hypoglycemia in mice was induced with Insulin pellets, resulting in a significant reduction in beta cell mass. This loss of beta cell mass could be significantly rescued with continuous delivery of exogenous VEGF-A, which had no effect on beta cell mass in normoglycemic mice. In addition, an increase in apoptotic endothelial cells during hypoglycemia preceded an increase in apoptotic beta cells. Both endothelial and beta cell apoptosis were prevented by exogenous VEGF-A, suggesting a possible causative relationship between reduced VEGF-A and the loss of islet vasculature and beta cells. Furthermore, in none of these experimental groups did beta cell proliferation and islet vessel density change, suggesting a tightly regulated balance between these two cellular compartments. The average islet size decreased in hypoglycemia, which was also prevented by exogenous VEGF-A. Taken together, our data suggest that VEGF-A release in beta cells is independent of VEGF-A synthesis. Beta cell mass can be regulated through modulated release of VEGF-A from beta cells based on physiological need.
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[26]
TÍTULO / TITLE: - An unusual cause of pancreatic mass lesion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastroenterology. 2013 Apr;144(4):e3-4. doi: 10.1053/j.gastro.2012.11.029. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1053/j.gastro.2012.11.029
AUTORES / AUTHORS: - Panic N; Inzani F; Larghi A
INSTITUCIÓN / INSTITUTION: - Digestive Endoscopy Unit, Catholic University, Rome, Italy; Department of Public Health, Catholic University, Rome, Italy; University of Belgrade, Belgrade, Serbia.
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[27]
TÍTULO / TITLE: - Microparticle-associated tissue factor activity in patients with pancreatic cancer: correlation with clinicopathological features.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Clin Invest. 2013 Mar;43(3):277-85. doi: 10.1111/eci.12042. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1111/eci.12042
AUTORES / AUTHORS: - Thaler J; Ay C; Mackman N; Metz-Schimmerl S; Stift J; Kaider A; Mullauer L; Gnant M; Scheithauer W; Pabinger I
INSTITUCIÓN / INSTITUTION: - Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
RESUMEN / SUMMARY: - BACKGROUND: Patients with pancreatic cancer have an unfavourable prognosis. A central role in pancreatic cancer progression has been suggested for tissue factor (TF), the main initiator of the blood coagulation cascade. We hypothesized that elevated levels of plasma microparticle (MP)-associated TF activity might indicate the presence of poorly differentiated pancreatic cancer, disease dissemination and infiltration of peripancreatic vessels. METHODS: MP-TF activity was measured in 73 pancreatic cancer patients and 22 healthy controls. Abdominal computerized tomography (CT) scans performed at study inclusion were investigated for probability of tumoural vascular invasion. In addition, intratumoural TF expression, D-dimer and CA 19-9 levels were determined. RESULTS: MP-TF activity (pg/mL) was significantly higher in patients (median: 0.37 [range: 0.00-11.91]) than in controls (median: 0.05 [range: 0.00-0.76]; P < 0.001). When pancreatic cancer patients were compared with regard to stage and grade, significantly elevated levels of MP-TF activity were only present in those with poorly differentiated metastatic nonresectable tumours (n = 11, median: 2.95 [range: 0.25-11.91]). In three patients with poorly differentiated tumours, a high probability of vascular invasion was found (MP-TF activity in these cases: 2.95, 7.00 and 10.34). MP-TF activity correlated strongly with CA 19-9 (r = 0.60) and weakly with D-dimer (r = 0.33) levels. Immunohistochemical staining for TF was positive in 14 of 15 resected tumours. MP-TF activity was associated with an increased risk of mortality (HR: 1.8 per doubling in MP-TF activity, [95% CI: 1.4-2.4, P < 0.001]). CONCLUSION: MP-TF activity might represent a biomarker for a poorly differentiated and invasive pancreatic cancer phenotype and poor survival.
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[28]
TÍTULO / TITLE: - Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 1;73(5):1449-53. doi: 10.1158/0008-5472.CAN-12-3923. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3923
AUTORES / AUTHORS: - Yao JC; Phan AT; Jehl V; Shah G; Meric-Bernstam F
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Gastrointestinal Medical Oncology and Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Novartis Pharmaceuticals Corporation, Basel, Switzerland; and Novartis Pharmaceuticals Corporation, Florham Park, New Jersey.
RESUMEN / SUMMARY: - The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo. Cancer Res; 73(5); 1449-53. ©2013 AACR.
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[29]
TÍTULO / TITLE: - KRAS mutation status is not predictive for objective response to anti-EGFR treatment with erlotinib in patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastroenterol. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s00535-013-0767-4
AUTORES / AUTHORS: - Boeck S; Jung A; Laubender RP; Neumann J; Egg R; Goritschan C; Ormanns S; Haas M; Modest DP; Kirchner T; Heinemann V
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany, stefan.boeck@med.uni-muenchen.de.
RESUMEN / SUMMARY: - BACKGROUND: It has not yet been defined if KRAS has a prognostic value or is a predictive biomarker for the efficacy of erlotinib in advanced pancreatic cancer (PC). METHODS: AIO-PK0104 was a phase III trial comparing gemcitabine/erlotinib followed by capecitabine with capecitabine/erlotinib followed by gemcitabine in advanced PC. For this post hoc subgroup analysis, biomarker data on the KRAS exon 2 mutation status were correlated with objective response to 1st-line therapy and with overall survival after start of 2nd-line chemotherapy (OSc). RESULTS: KRAS codon 12 was mutated in 121 of 173 (70 %) patients. The KRAS status showed no association with objective response (p = 0.40), but KRAS wildtype patients had an improved OS (HR 1.68, p = 0.005). A trend for a survival benefit was also observed during (non-erlotinib containing) 2nd-line chemotherapy, with a HR of 1.47 (p = 0.10) for the OSc. CONCLUSION: This post hoc analysis of AIO-PK0104 supports the assumption that KRAS is rather a prognostic than a predictive biomarker in PC.
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[30]
TÍTULO / TITLE: - Bitter melon juice activates cellular energy sensor AMP-activated protein kinase causing apoptotic death of human pancreatic carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt081
AUTORES / AUTHORS: - Kaur M; Deep G; Jain AK; Raina K; Agarwal C; Wempe MF; Agarwal R
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences and.
RESUMEN / SUMMARY: - Prognosis of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and associated mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells both in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC-3, MiaPaCa-2, AsPC-1 and Capan-2 cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide, cell death enzyme-linked immunosorbent assay and annexin/propidium iodide assays. BMJ effect on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa-2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Results showed that BMJ (2-5% v/v) decreases cell viability in all four pancreatic carcinoma cell lines by inducing strong apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl-2 family members and cytochrome-c release into the cytosol. Additionally, BMJ decreased survivin and X-linked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogen-activated protein kinases (extracellular signal-regulated kinase ½ and p38) levels. Importantly, BMJ activated adenosine monophosphate-activated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJ-induced caspase-3 activation suggesting activated AMPK involvement in BMJ-induced apoptosis. In vivo, oral administration of lyophilized BMJ (5mg in 100 microl water/day/mouse) for 6 weeks inhibited MiaPaCa-2 tumor xenograft growth by 60% (P < 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa-2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. Overall, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, both in vitro and in vivo, suggesting its clinical usefulness.
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[31]
TÍTULO / TITLE: - Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diabetes. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 2337/db12-1686
AUTORES / AUTHORS: - Butler AE; Campbell-Thompson M; Gurlo T; Dawson DW; Atkinson M; Butler PC
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California.
RESUMEN / SUMMARY: - Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic beta cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age matched organ donors with type 2 diabetes (DM) treated by incretin therapy (n=8) or other therapy (n=12) and non diabetic controls (n=14) reveals a approximately 40% increased pancreatic mass in DM treated with incretin therapy with both increased exocrine cell proliferation (p<0.0001) and dysplasia (increased pancreatic intraepithelia neoplasia, p<0.01). Pancreas in DM treated with incretin therapy was notable for alpha cell hyperplasia and glucagon expressing microadenomas (3/8) and a neuroendocrine tumor. beta cell mass was reduced by approximately 60% in those with DM, yet a 6 fold increase was observed in incretin treated subjects although diabetes persists. Endocrine cells co-staining for insulin and glucagon were increased in DM compared to non diabetic controls (p<0.05) and markedly further increased by incretin therapy (p<0.05). In conclusion, in humans, incretin therapy resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia, the latter by alpha cell hyperplasia with the potential for evolution into neuroendocrine tumors.
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[32]
TÍTULO / TITLE: - Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: Potential role in therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Mar 21. pii: S0304-3835(13)00245-0. doi: 10.1016/j.canlet.2013.03.017.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.017
AUTORES / AUTHORS: - Shimizu T; Torres MP; Chakraborty S; Souchek JJ; Rachagani S; Kaur S; Macha M; Ganti AK; Hauke RJ; Batra SK
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
RESUMEN / SUMMARY: - There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-kappaB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future.
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[33]
TÍTULO / TITLE: - Safety and efficacy of neoadjuvant FOLFIRINOX treatment in a series of patients with borderline resectable pancreatic ductal adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Oncol. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2013.771821
AUTORES / AUTHORS: - Tinchon C; Hubmann E; Pichler A; Keil F; Pichler M; Rabl H; Uggowitzer M; Jilek K; Leitner G; Bauernhofer T
INSTITUCIÓN / INSTITUTION: - Department of Hemato-Oncology , General Hospital Leoben , Austria.
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[34]
TÍTULO / TITLE: - Targeting miR-21 for the Therapy of Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Ther. 2013 Mar 12. doi: 10.1038/mt.2013.35.
●● Enlace al texto completo (gratuito o de pago) 1038/mt.2013.35
AUTORES / AUTHORS: - Sicard F; Gayral M; Lulka H; Buscail L; Cordelier P
INSTITUCIÓN / INSTITUTION: - 1] INSERM U1037, Cancer Research Center of Toulouse, Toulouse, France [2] Universite Paul Sabatier Toulouse III, Toulouse, France.
RESUMEN / SUMMARY: - Despite tremendous efforts worldwide from clinicians and cancer scientists, pancreatic ductal adenocarcinoma (PDA) remains a deadly disease for which no cure is available. Recently, microRNAs (miRNAs) have emerged as key actors in carcinogenesis and we demonstrated that microRNA-21 (miR-21), oncomiR is expressed early during PDA. In the present study, we asked whether targeting miR-21 in human PDA-derived cell lines using lentiviral vectors (LVs) may impede tumor growth. We demonstrated that LVs-transduced human PDA efficiently downregulated miR-21 expression, both in vitro and in vivo. Consequently, cell proliferation was strongly inhibited and PDA-derived cell lines died by apoptosis through the mitochondrial pathway. In vivo, miR-21 depletion stopped the progression of a very aggressive model of PDA, to induce cell death by apoptosis; furthermore, combining miR-21 targeting and chemotherapeutic treatment provoked tumor regression. We demonstrate herein for the first time that targeting oncogenic miRNA strongly inhibit pancreatic cancer tumor growth both in vitro and in vivo. Because miR-21 is overexpressed in most human tumors; therapeutic delivery of miR-21 antagonists may still be beneficial for a large number of cancers for which no cure is available.Molecular Therapy (2013); doi:10.1038/mt.2013.35.
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[35]
TÍTULO / TITLE: - KRAS Mutations and Their Correlation With Survival of Patients With Advanced Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Apr;42(3):543-544.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826b388b
AUTORES / AUTHORS: - Bournet B; Muscari F; Guimbaud R; Cordelier P; Buscail L
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology and INSERM U1037 University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France Department of Digestive Surgery University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France Department of Oncology University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France INSERM U1037 University Hospital Center Rangueil-Larrey University Paul Sabatier Toulouse, France Department of Gastroenterology and INSERM U1037 University Hospital Center Rangueil-Larrey CHU of Toulouse University Paul Sabatier Toulouse, France Buscail.L@chu-toulouse.fr.
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[36]
TÍTULO / TITLE: - Alkaline Phosphatase ALPPL-2 Is a Novel Pancreatic Carcinoma-Associated Protein.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Mar 15;73(6):1934-45. doi: 10.1158/0008-5472.CAN-12-3682. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3682
AUTORES / AUTHORS: - Dua P; Kang HS; Hong SM; Tsao MS; Kim S; Lee DK
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Department of Medical Biotechnology, Dongguk University; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul; Global Research Laboratory of RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Korea; and Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Canada.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very low median survival rate. The lack of early sensitive diagnostic markers is one of the main causes of PDAC-associated lethality. Therefore, to identify novel pancreatic cancer biomarkers that can facilitate early diagnosis and also help in the development of effective therapeutics, we developed RNA aptamers targeting pancreatic cancer by Cell-systematic evolution of ligands by exponential enrichment (SELEX) approach. Using a selection strategy that could generate aptamers for 2 pancreatic cancer cell lines in one selection scheme, we identified an aptamer SQ-2 that could recognize pancreatic cancer cells with high specificity. Next, by applying 2 alternative approaches: (i) aptamer-based target pull-down and (ii) genome-wide microarray-based identification of differentially expressed mRNAs in aptamer-positive and -negative cells, we identified alkaline phosphatase placental-like 2 (ALPPL-2), an oncofetal protein, as the target of SQ-2. ALPPL-2 was found to be ectopically expressed in many pancreatic cancer cell lines at both mRNA and protein levels. RNA interference-mediated ALPPL-2 knockdown identified novel tumor-associated functions of this protein in pancreatic cancer cell growth and invasion. In addition, the aptamer-mediated identification of ALPPL-2 on the cell surface and cell secretions of pancreatic cancer cells supports its potential use in the serum- and membrane-based diagnosis of PDAC. Cancer Res; 73(6); 1934-45. ©2012 AACR.
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[37]
TÍTULO / TITLE: - Anxiety and perception of cancer risk in patients undergoing endoscopic ultrasonography for pancreas cystic lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Apr;42(3):548-9. doi: 10.1097/MPA.0b013e31826b39bb.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826b39bb
AUTORES / AUTHORS: - Shieh FK; Siddiqui UD; Padda M; Dharan M; Rossi F; Aslanian HR
INSTITUCIÓN / INSTITUTION: - Section of Digestive DiseasesYale University New Haven, CT fshieh@gmail.com.
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[38]
TÍTULO / TITLE: - Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diabetologia. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s00125-013-2847-7
AUTORES / AUTHORS: - Schafer MK; Hartwig NR; Kalmbach N; Klietz M; Anlauf M; Eiden LE; Weihe E
INSTITUCIÓN / INSTITUTION: - Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University Marburg, Robert-Koch-Strasse 8, 35037, Marburg, Germany, mkh.schafer@staff.uni-marburg.de.
RESUMEN / SUMMARY: - AIMS/HYPOTHESIS: Imaging of beta cell mass (BCM) is a major challenge in diabetes research. The vesicular monoamine transporter 2 (VMAT2) is abundantly expressed in human beta cells. Radiolabelled analogues of tetrabenazine (TBZ; a low-molecular-weight, cell-permeant VMAT2-selective ligand) have been employed for pancreatic islet imaging in humans. Since reports on TBZ-based VMAT2 imaging in rodent pancreas have been fraught with confusion, we compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimise TBZ imaging in humans. METHODS: We used a panel of highly sensitive VMAT2 antibodies developed against equivalently antigenic regions of the transporter from each species in combination with immunostaining for insulin and species-specific in situ hybridisation probes. Individual pancreatic islets were obtained by laser-capture microdissection and subjected to analysis of mRNA expression of VMAT2. RESULTS: The VMAT2 protein was not expressed in beta cells in the adult pancreas of common mouse or rat laboratory strains, in contrast to its expression in beta cells (but not other pancreatic endocrine cell types) in the pancreas of pigs and humans. VMAT2- and tyrosine hydroxylase co-positive (catecholaminergic) innervation was less abundant in humans than in rodents. VMAT2-positive mast cells were identified in the pancreas of all species. CONCLUSIONS/INTERPRETATION: Primates and pigs are suitable models for TBZ imaging of beta cells. Rodents, because of a complete lack of VMAT2 expression in the endocrine pancreas, are a ‘null’ model for assessing interference with BCM measurements by VMAT2-positive mast cells and sympathetic innervation in the pancreas.
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[39]
TÍTULO / TITLE: - Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Gene Ther. 2013 Mar 8. doi: 10.1038/cgt.2013.9.
●● Enlace al texto completo (gratuito o de pago) 1038/cgt.2013.9
AUTORES / AUTHORS: - Camp ER; Wang C; Little EC; Watson PM; Pirollo KF; Rait A; Cole DJ; Chang EH; Watson DK
INSTITUCIÓN / INSTITUTION: - 1] Department of Surgery, Medical University of South Carolina, Charleston, SC, USA [2] Ralph H Johnson VA Medical Center, Charleston, SC, USA.
RESUMEN / SUMMARY: - To overcome gene therapy barriers such as low transfection efficiency and nonspecific delivery, liposomal nanoparticles targeted by a single-chain antibody fragment to the transferrin receptor (TfRscFv) delivering wild-type (wt) human p53 (SGT-53) were developed for tumor-specific targeting. We hypothesize that SGT-53 in combination with gemcitabine will demonstrate enhanced therapeutic benefit in an in vivo metastatic pancreatic cancer model. Intrasplenic injection of 1 x 106 Panc02 murine pancreatic cancer cells was used to generate in vivo hepatic metastatic tumors. Nanoparticle localization was assessed by tail vein injection of TfRscFv with fluorescently labeled oligonucleotides (6-carboxyfluorescein phosphoramidite (6FAM) ODN) imaged by Xenogen IVIS 200 scan. SGT-53 (equivalent to 30 mug of p53 intravenously) and gemcitabine (20 mg/kg intraperitoneally) alone and in combination were administered biweekly and compared with untreated mice. Survival was determined by blinded daily assessment of morbidity. Human wtp53 expression and transferrin levels in the tumors were assessed by western blot analysis. Tumor burden was quantified by liver weight. Xenogen imaging demonstrated tumor-specific uptake of TfRscFv-6FAM ODN. Exogenous human wtp53 protein was detected in the SGT-53-treated tumors compared with control. Compared with untreated mice with metastatic tumors demonstrating median survival of 20 days, SGT-53, gemcitabine and the combination demonstrated improved median survival of 29, 30 and 37 days, respectively. The combination treatment prolonged median survival when compared with single drug treatment and decreased tumor burden. The tumor targeting liposomal-based SGT-53 nanoparticle is capable of sensitizing pancreatic cancer to conventional chemotherapy in pancreatic cancer models. This approach has the potential to be translated into a new, more effective therapy for pancreatic cancer. Further optimization is ongoing, moving towards a Phase 1B/2 clinical trial.Cancer Gene Therapy advance online publication, 8 March 2013; doi:10.1038/cgt.2013.9.
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[40]
TÍTULO / TITLE: - MAZ-binding G4-decoy with locked nucleic acid and twisted intercalating nucleic acid modifications suppresses KRAS in pancreatic cancer cells and delays tumor growth in mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nucleic Acids Res. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1093/nar/gkt127
AUTORES / AUTHORS: - Cogoi S; Zorzet S; Rapozzi V; Geci I; Pedersen EB; Xodo LE
INSTITUCIÓN / INSTITUTION: - Department of Medical and Biological Sciences, School of Medicine, P.le Kolbe 4, 33100 Udine, Italy, Department of Life Science, University of Trieste, Via Giorgieri 7-9, 34100 Trieste, Italy and Nucleic Acid Center, Institute of Physics, Chemistry and Pharmacy University of Southern Denmark, DK-5230 Odense M, Denmark.
RESUMEN / SUMMARY: - KRAS mutations are primary genetic lesions leading to pancreatic cancer. The promoter of human KRAS contains a nuclease-hypersensitive element (NHE) that can fold in G4-DNA structures binding to nuclear proteins, including MAZ (myc-associated zinc-finger). Here, we report that MAZ activates KRAS transcription. To knockdown oncogenic KRAS in pancreatic cancer cells, we designed oligonucleotides that mimic one of the G-quadruplexes formed by NHE (G4-decoys). To increase their nuclease resistance, two locked nucleic acid (LNA) modifications were introduced at the 3’-end, whereas to enhance the folding and stability, two polycyclic aromatic hydrocarbon units (TINA or AMANY) were inserted internally, to cap the quadruplex. The most active G4-decoy (2998), which had two para-TINAs, strongly suppressed KRAS expression in Panc-1 cells. It also repressed their metabolic activity (IC50 = 520 nM), and it inhibited cell growth and colony formation by activating apoptosis. We finally injected 2998 and control oligonucleotides 5153, 5154 (2 nmol/mouse) intratumorally in SCID mice bearing a Panc-1 xenograft. After three treatments, 2998 reduced tumor xenograft growth by 64% compared with control and increased the Kaplan-Meier median survival time by 70%. Together, our data show that MAZ-specific G4-decoys mimicking a KRAS quadruplex are promising for pancreatic cancer therapy.
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[41]
TÍTULO / TITLE: - Risk factors for pancreatic ductal adenocarcinoma specifically stimulate pancreatic duct glands in mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Pathol. 2013 Mar;182(3):965-74. doi: 10.1016/j.ajpath.2012.11.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.11.016
AUTORES / AUTHORS: - Bobrowski A; Spitzner M; Bethge S; Mueller-Graf F; Vollmar B; Zechner D
INSTITUCIÓN / INSTITUTION: - Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
RESUMEN / SUMMARY: - Diabetes mellitus type 2 and chronic pancreatitis are regarded as risk factors for pancreatic cancer. Pancreatic duct glands (PDGs) were recently described as a new compartment of the major duct in humans and mice. To evaluate the influence of diabetes and chronic pancreatitis on PDGs, cerulein was injected i.p., repetitively over 10 weeks, in mice exhibiting obesity and a type 2 diabetes-like syndrome (B6.V-Lep(ob/ob)) and in lean littermates. By using 5-bromo-2’-deoxyuridine (BrdU), a label-retaining cell population was characterized in PDGs. Cerulein administration led to more BrdU(+) cells in PDGs of obese mice compared with lean mice. The observed increase was specific to PDGs, because BrdU incorporation in cells of the pancreatic duct was not increased. In addition, the expression of distinct tumor markers in PDGs was characterized by Muc5ac, S100P, regenerating islet-derived 3beta, 14-3-3 sigma, and prostate stem cell antigen immunochemistry. Type 2 diabetes-like syndrome, accompanied by chronic pancreatitis, enhanced nuclear localization of S100P. Both risk factors for pancreatic cancer also induced the production of Muc5ac and the nuclear localization of S100P. These results demonstrate that diabetes and chronic pancreatitis jointly enhance BrdU incorporation and production of pancreatic cancer-specific proteins in PDGs. The observed alterations suggest that pancreatic tumors might originate from the newly discovered histomorphological structures, called PDGs, which could represent a target for future anticancer therapies.
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[42]
TÍTULO / TITLE: - Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Semin Oncol. 2013 Feb;40(1):56-68. doi: 10.1053/j.seminoncol.2012.11.006.
●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.006
AUTORES / AUTHORS: - Toumpanakis C; Caplin ME
INSTITUCIÓN / INSTITUTION: - Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK.
RESUMEN / SUMMARY: - Somatostatin analogs (SA) are the standard of care for controlling symptoms of patients with functional gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). SA control symptoms in more than 70% of patients with carcinoid syndrome. Similar results are obtained in patients with functional, hormone-secreting, pancreatic NETs. The use of SA as antiproliferative agents has been established only recently. Retrospective studies have shown stabilization of tumor growth in >50% of patients with progressive disease. The results of a recent randomized phase III trial (PROMID) demonstrated that the median time to progression in patients with midgut carcinoid tumors treated with octreotide LAR (Long-Acting-Repeatable, Novartis, Basel, Switzerland) was more than twice as long compared to that of patients treated with placebo. The results of a phase III study of lanreotide versus placebo in nonfunctional NETs are not yet available. More studies are needed to determine whether combining SA with novel targeted treatments will result in enhanced antiproliferative activity compared to treatment with a SA alone. Studies are ongoing using pan-receptor agonists (eg, pasireotide) and chimeric dimers, which possess features of somatostatin and dopamine agonists (dopastatins) and are thought to enhance symptom control by binding multiple receptors (somatostatin and dopamine receptors). Somatostatin receptor antagonists are also currently being developed for clinical use. Peptide receptor radionuclide therapy (PRRT), consisting of yttrium-90 and lutetium-177 isotopes conjugated with SA appear to be efficacious in advanced NETs. Randomized studies are needed to definitively establish the safety and efficacy of this strategy compared to other available treatments, and to determine which radiolabeled isotopes or combinations are most effective.
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[43]
TÍTULO / TITLE: - Erlotinib prolongs survival in pancreatic cancer by blocking gemcitabine-induced MAPK signals.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Apr 1;73(7):2221-34. doi: 10.1158/0008-5472.CAN-12-1453. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-1453
AUTORES / AUTHORS: - Miyabayashi K; Ijichi H; Mohri D; Tada M; Yamamoto K; Asaoka Y; Ikenoue T; Tateishi K; Nakai Y; Isayama H; Morishita Y; Omata M; Moses HL; Koike K
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Gastroetnterology and Molecular Pathology, Graduate School of Medicine, Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo; Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba; Yamanashi Prefectural Hospital Organization, Yamanashi, Japan; and Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, Tennessee.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers worldwide. Although many regimens have been used for PDAC treatment, the combination of the EGF receptor (EGFR) inhibitor erlotinib with gemcitabine has been the only molecular-targeted drug tested so far that has been superior to gemcitabine alone. The mechanism underlying this effective combinational regimen remains unknown. Here, we show that the combination is superior to gemcitabine alone in blocking progression and prolonging survival in a murine model of PDAC (Kras activation with Tgfbr2 knockout). We found that gemcitabine induced mitogen-activated protein kinase signaling, which was dramatically inhibited by erlotinib even in the Kras-activated PDAC cells in the mouse model. Mechanistic investigations suggested that gemcitabine induces EGFR ligand expression and ERBB2 activation by increasing heterodimer formation with EGFR, thereby maintaining high levels of ERBB2 protein in PDAC cells. Overall, our findings suggest a significant role of ERBB in PDAC treatment. Cancer Res; 73(7); 2221-34. ©2013 AACR.
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[44]
TÍTULO / TITLE: - Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 14. doi: 10.1038/bjc.2013.108.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.108
AUTORES / AUTHORS: - Eto K; Kawakami H; Kuwatani M; Kudo T; Abe Y; Kawahata S; Takasawa A; Fukuoka M; Matsuno Y; Asaka M; Sakamoto N
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
RESUMEN / SUMMARY: - Background:Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC.Methods:The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription-polymerase chain reactions and examined for correlations with GEM sensitivity.Results:The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively).Conclusion:hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.British Journal of Cancer advance online publication, 14 March 2013; doi:10.1038/bjc.2013.108 www.bjcancer.com.
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[45]
TÍTULO / TITLE: - Growth inhibition of pancreatic cancer cells by Histone Deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NFkB, and mTOR signaling in vitro and in vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Carcinog. 2013 Mar 8. doi: 10.1002/mc.22024.
●● Enlace al texto completo (gratuito o de pago) 1002/mc.22024
AUTORES / AUTHORS: - Chien W; Lee DH; Zheng Y; Wuensche P; Alvarez R; Wen DL; Aribi AM; Thean SM; Doan NB; Said JW; Koeffler HP
INSTITUCIÓN / INSTITUTION: - Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403, Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1alpha at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P = 0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. © 2013 Wiley Periodicals, Inc.
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[46]
TÍTULO / TITLE: - Cost-Utility Estimations of Palliative Care in Patients With Pancreatic Adenocarcinoma: A Retrospective Analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg. 2013 Mar 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-2003-z
AUTORES / AUTHORS: - Ljungman D; Hyltander A; Lundholm K
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden.
RESUMEN / SUMMARY: - BACKGROUND: We earlier reported cost-utility estimates in patients who undergo resection aimed at cure for pancreatic carcinoma. The present study describes similar information on patients with unresectable tumors who experienced palliative care only. METHODS: A population-based cohort of patients with exocrine pancreatic adenocarcinoma during 1998-2005 was evaluated retrospectively (n = 444). Total direct health care costs at departments of surgery and oncology, for primary health care, and at hospice were achieved. Self-estimated health-related quality of life (HRQL) was assessed by the SF-36. A single preference-based utility index, SF-6D, was derived from SF-36 items to estimate quality-adjusted life years (QALYs). Results were compared to similar findings in a previously reported group of patients with pancreatic carcinoma resected for cure (n = 31). RESULTS: Palliative care patients (n = 305) had impaired HRQL particularly related to physical domains. The mean preference-based health utility index at diagnosis was 0.65 +/- 0.02 [95 % confidence interval (CI) 0.61-0.69] compared to 0.77 +/- 0.02 (95 % CI 0.75-0.79) in healthy reference individuals. Total direct health care costs were 50 % in patients on palliative care compared to costs for surgical R0 resections (23,701 and 50,950<euro>, respectively). QALYs for 1 year from diagnosis were 0.2 (95 % CI 0.17-0.23) in patients on palliative care and 0.48 (95 % CI 0.44-0.54) in resection patients. Costs per QALY were 118,418<euro> and 106,146<euro>, respectively (95 % CI 103,048-139,418<euro> and 94,352-115,795<euro>). CONCLUSIONS: Optimized palliative care of patients with exocrine pancreatic carcinoma had costs per achieved utility similar to those for surgical resections aimed at cure.
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[47]
TÍTULO / TITLE: - FDG PET or PET/CT in patients with pancreatic cancer: when does it add to diagnostic CT or MRI?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Imaging. 2013 Mar;37(2):295-301. doi: 10.1016/j.clinimag.2012.07.005. Epub 2012 Aug 24.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.07.005
AUTORES / AUTHORS: - Javery O; Shyn P; Mortele K
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Electronic address: ojavery@partners.org.
RESUMEN / SUMMARY: - OBJECTIVE: Assess the impact of FDG-PET or PET/CT (PI) on pancreatic cancer management when added to CT or MRI (CDI). MATERIALS AND METHODS: Forty-nine patients underwent 79 PI exams. Discordant findings on PI and CDI were assessed for clinical impact. RESULTS: Fifteen of 79 PI-CDI pairs were discordant. Ten of 79 PI favorably and 5 of 79 unfavorably altered management. PI favorably altered management more often when ordered for therapy monitoring compared to staging [risk ratio 13.00 (95% CI 1.77-95.30)] or restaging [risk ratio 18.5 (95% CI 2.50-137.22)]. CONCLUSION: PI favorably alters management more often when used for therapy monitoring compared to staging or restaging.
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[48]
TÍTULO / TITLE: - Risk Factors for Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: A Multicentre Case-Control Study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Gastroenterol. 2013 Mar 5. doi: 10.1038/ajg.2013.42.
●● Enlace al texto completo (gratuito o de pago) 1038/ajg.2013.42
AUTORES / AUTHORS: - Capurso G; Boccia S; Salvia R; Del Chiaro M; Frulloni L; Arcidiacono PG; Zerbi A; Manta R; Fabbri C; Ventrucci M; Tarantino I; Piciucchi M; Carnuccio A; Boggi U; Leoncini E; Costamagna G; Delle Fave G; Pezzilli R; Bassi C; Larghi A
INSTITUCIÓN / INSTITUTION: - Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy.
RESUMEN / SUMMARY: - OBJECTIVES:To investigate environmental, personal, and hereditary risk factors associated with the occurrence of intraductal papillary mucinous neoplasms of the pancreas (IPMNs).METHODS:Multicentre case-control study. Risk factors were identified from a questionnaire collecting data on family and medical history, and environmental factors. Cases were prevalent IPMNs seen at the participating units within an 18-month timeframe. Matched controls were enrolled alongside patients seen at outpatient clinics.RESULTS:Three-hundred and ninety patients with IPMN and 390 matched controls (166 males, mean age 65 in each group) were enrolled. Of the IPMNs, 310 had branch-duct involvement and 80 main-duct involvement. The only cancer with a 1st degree family history significantly higher in IPMN was pancreatic ductal adenocarcinoma (PDAC) (5.4% vs. 1.5%). Previous history of diabetes (13.6% vs. 7.5%), chronic pancreatitis (CP) (3.1% vs. 0.3%), peptic ulcer (7.2% vs. 4.3%), and insulin use (4.9% vs. 1.1%) were all more frequent with IPMNs. Logistic regression multivariate analysis revealed that history of diabetes (odds ratio (OR): 1.79, confidence interval (CI) 95%: 1.08-2.98), CP (OR: 10.10, CI 95%: 1.30-78.32), and family histories of PDAC (OR: 2.94, CI 95%: 1.17-7.39) were all independent risk factors. However, when analysis was restricted to diabetics who had taken insulin, risk of IPMN became stronger (OR: 6.03, CI 95%: 1.74-20.84). The association with all these risk factors seemed stronger for the subgroup with main duct involvement.CONCLUSIONS:A previous history of diabetes, especially with insulin use, CP, and family history of PDAC are all relevant risk factors for the development of IPMN. These results suggest an overlap between certain risk factors for PDAC and IPMN.Am J Gastroenterol advance online publication, 5 March 2013; doi:10.1038/ajg.2013.42.
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[49]
TÍTULO / TITLE: - Phase I/II study of albumin-bound nab-paclitaxel plus gemcitabine administered to Chinese patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Apr;71(4):1065-72. doi: 10.1007/s00280-013-2102-4. Epub 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2102-4
AUTORES / AUTHORS: - Zhang DS; Wang DS; Wang ZQ; Wang FH; Luo HY; Qiu MZ; Wang F; Li YH; Xu RH
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dong Feng Road East, Guangzhou, 510060, China.
RESUMEN / SUMMARY: - PURPOSE: The primary objective of this study was to evaluate the dose-limiting toxicities (DLTs) and identify the maximum-tolerated dose (MTD) and recommended dose of nab-paclitaxel plus gemcitabine as a first-line treatment in Chinese patients with advanced pancreatic ductal adenocarcinoma (PDA). METHODS: Patients with previously untreated advanced PDA were treated with nab-paclitaxel followed by gemcitabine (1,000 mg/m(2)) administered intravenously for 30 min on days 1 and 8 and repeated every 21 days. RESULTS: Patients received nab-paclitaxel at the following dose levels: 80 mg/m(2) (n = 3), 100 mg/m(2) (n = 6), and 120 mg/m(2) (n = 12). The DLTs evaluated were elevated alanine aminotransferase and febrile neutropenia. However, there had no two out of three to six patients experienced DLTs, the MTD was not met. A total of 93 cycles were administered. The most common grade ¾ toxicities were neutropenia (9.52 %), thrombocytopenia (4.76 %), and sensory neuropathy (4.76 %). For 12 patients receiving 120 mg/m(2), the overall response rate and disease control rate were 41.67 and 83.33 %, respectively, and the median progression-free survival and overall survival were 5.23 and 12.17 months, respectively. CONCLUSIONS: Treatment with albumin-bound nab-paclitaxel (120 mg/m(2)) plus gemcitabine has a favorable safety profile with an encouraging antitumor effect in Chinese patients.
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[50]
TÍTULO / TITLE: - Toxicity study of gemcitabine, oxaliplatin, and bevacizumab, followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy, in patients with locally advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2147-4
AUTORES / AUTHORS: - Sohal DP; Metz JM; Sun W; Giantonio BJ; Plastaras JP; Ginsberg G; Kochman ML; Teitelbaum UR; Harlacker K; Heitjan DF; Feldman MD; Drebin JA; O’Dwyer PJ
INSTITUCIÓN / INSTITUTION: - Cleveland Clinic, Taussig Cancer Institute, 9500 Euclid Avenue, R35, Cleveland, OH, 44195, USA, sohald@ccf.org.
RESUMEN / SUMMARY: - PURPOSE: Platinum compounds or bevacizumab, in combination with gemcitabine, achieved good response rates in early studies in advanced pancreatic cancer. This prompted an evaluation of an aggressive approach to allow better local control and resectability in locally advanced disease. METHODS: We piloted a combination of gemcitabine/oxaliplatin/bevacizumab Q2w for four cycles, followed by oxaliplatin and bevacizumab added to infusional 5-FU and radiotherapy, in patients with locally advanced pancreatic cancer. RESULTS: Nineteen patients were treated, of whom 17 completed the protocol-specified treatment. Median age was 60 years. Fifteen had unresectable, and four had borderline resectable disease. Toxicity of chemotherapy was moderate: grade III neutropenia (5) and grade I/II nausea, vomiting, fatigue, and neuropathy. During chemoradiation, major grade III toxicities were nausea and vomiting (3 each). One patient had intractable pain early on, necessitating treatment cessation. Response rate for 18 evaluable patients was 11 % (by RECIST); five patients (4 inoperable, 1 borderline, 26 %) went on to have surgery. One-year overall survival was 58 % and progression-free survival was 37 %. CONCLUSIONS: This combination, associated with higher response rates in metastatic disease, had a lower than expected response rate in primary tumors. Although tolerable, our approach failed to affect clinical outcomes meaningfully.
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[51]
TÍTULO / TITLE: - New Syndrome of Paraganglioma and Somatostatinoma Associated With Polycythemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Oncol. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1200/JCO.2012.47.1912
AUTORES / AUTHORS: - Pacak K; Jochmanova I; Prodanov T; Yang C; Merino MJ; Fojo T; Prchal JT; Tischler AS; Lechan RM; Zhuang Z
INSTITUCIÓN / INSTITUTION: - Karel Pacak, Ivana Jochmanova, and Tamara Prodanov, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Maria J. Merino and Tito Fojo, National Cancer Institute; Chunzhang Yang and Zhengping Zhuang, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Josef T. Prchal, University of Utah School of Medicine and VA Hospital, Salt Lake City, UT; and Arthur S. Tischler and Ronald M. Lechan, Tufts Medical Center, Boston, MA.
RESUMEN / SUMMARY: - PURPOSEThe occurrence of >/= two distinct types of tumors, one of them paraganglioma (PGL), is unusual in an individual patient, except in hereditary cancer syndromes. PATIENTS AND METHODSFour unrelated patients were investigated, with thorough clinical evaluation. Plasma and tissue catecholamines and metanephrines were measured by high-performance liquid chromatography. Anatomic and functional imaging were performed for tumor visualization. Germline and tumor tissue DNA were analyzed for hypoxia-inducible factor 2 alpha (HIF2A) mutations. The prolyl hydroxylation and stability of the mutant HIF2alpha protein, transcriptional activity of mutant HIF2A, and expression of hypoxia-related genes were also investigated. Immunohistochemical staining for HIF1/2alpha was performed on formalin-fixed, paraffin-embedded tumor tissue.ResultsPatients were found to have polycythemia, multiple PGLs, and duodenal somatostatinomas by imaging or biochemistry with somatic gain-of-function HIF2A mutations. Each patient carried an identical unique mutation in both types of tumors but not in germline DNA. The HIF2A mutations in these patients were clustered adjacent to an oxygen-sensing proline residue, affecting HIF2alpha interaction with the prolyl hydroxylase domain 2-containing protein, decreasing the hydroxylation of HIF2alpha, and reducing HIF2alpha affinity for the von Hippel-Lindau protein and its degradation. An increase in the half-life of HIF2alpha was associated with upregulation of the hypoxia-related genes EPO, VEGFA, GLUT1, and END1 in tumors. CONCLUSIONOur findings indicate the existence of a new syndrome with multiple PGLs and somatostatinomas associated with polycythemia. This new syndrome results from somatic gain-of-function HIF2A mutations, which cause an upregulation of hypoxia-related genes, including EPO and genes important in cancer biology.
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[52]
TÍTULO / TITLE: - Differences in the pattern of structural abnormalities on CT in patients with cystic fibrosis and pancreatic sufficiency or insufficiency.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chest. 2013 Feb 7. doi: 10.1378/chest.12-1226.
●● Enlace al texto completo (gratuito o de pago) 1378/chest.12-1226
AUTORES / AUTHORS: - Simanovsky N; Cohen-Cymberknoh M; Shoseyov D; Gileles-Hillel A; Wilschanski M; Kerem E; Hiller N
INSTITUCIÓN / INSTITUTION: - Dr. Simanovsky and Dr. Cohen-Cymberknoh contributed equally to the preparation of this manuscript.
RESUMEN / SUMMARY: - ABSTRACT BACKGROUND Cystic fibrosis (CF) genotypes characterized by pancreatic sufficiency (CF-PS) are generally associated with milder disease versus those with pancreatic insufficiency (CF-PI); however, the correlation between pancreatic status and type and severity of structural lung changes has not been studied. We aimed to evaluate differences in the severity and distribution of pulmonary manifestations of CF, in patients with PS vs PI. METHODS We retrospectively evaluated changes in individual lobes and in the whole lung on chest CT using the modified Brody score in 84 CF patients (39 females, 45 males; ages 4-68 years, mean 20.5) treated from 2000-2010. Our IRB waived the requirement for informed consent. The severity of lung changes and distribution of pulmonary disease were compared for 28 patients with CF-PS and 56 with CF-PI using the Student’s t-test, nonparametric Pearson chi-square, or mixed-design ANOVA. Correlations were evaluated with the Pearson (continuous variables) or Spearman’s rho (nonparametric variables) tests. A linear regression model was used for multivariate analyses. RESULTS In comparison to patients with CF-PS, those with CF-PI had more severe lung disease (p=0.001) with predominant upper lobe involvement (p=0.002), and significant differences in Brody scores for bronchiectasis and bronchial wall thickening. Lung manifestations in patients with CF-PS did not show predominant involvement of any one area (p=0.133). CONCLUSIONS In patients with CF-PI, structural lung changes are more severe with upper lobe predominance, prominent bronchiectasis, and bronchial wall thickening versus lower severity and more general distribution of changes in those with CF-PS.
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[53]
TÍTULO / TITLE: - Comparative proteomic and phosphoproteomic profiling of pancreatic adenocarcinoma cells treated with CB1 or CB2 agonists.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Electrophoresis. 2013 Mar 6. doi: 10.1002/elps.201200402.
●● Enlace al texto completo (gratuito o de pago) 1002/elps.201200402
AUTORES / AUTHORS: - Brandi J; Dando I; Palmieri M; Donadelli M; Cecconi D
INSTITUCIÓN / INSTITUTION: - Department of Biotechnology, Proteomics and Mass Spectrometry Laboratory.
RESUMEN / SUMMARY: - The pancreatic adenocarcinoma cell line Panc1 was treated with cannabinoid receptor ligands (ACPA or GW405833) in order to elucidate the molecular mechanism of their anticancer effect. A proteomic approach was used to analyse the protein and phosphoprotein profiles. Western blot and functional data mining were also employed in order to validate results, classify proteins, and explore their potential relationships. We demonstrated that the two cannabinoids act through a widely common mechanism involving up and down-regulation of proteins related to energetic metabolism and cell growth regulation. Overall, the results reported might contribute to the development of a therapy based on cannabinoids for pancreatic adenocarcinoma.
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[54]
TÍTULO / TITLE: - Structure-Based Design and Evaluation of Naphthalene Diimide G-Quadruplex Ligands As Telomere Targeting Agents in Pancreatic Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Med Chem. 2013 Apr 2.
●● Enlace al texto completo (gratuito o de pago) 1021/jm301899y
AUTORES / AUTHORS: - Micco M; Collie GW; Dale AG; Ohnmacht SA; Pazitna I; Gunaratnam M; Reszka AP; Neidle S
INSTITUCIÓN / INSTITUTION: - The School of Pharmacy, University College London, London WC1N 1AX, U.K.
RESUMEN / SUMMARY: - Tetra-substituted naphthalene diimide (ND) derivatives with positively charged termini are potent stabilizers of human telomeric and gene promoter DNA quadruplexes and inhibit the growth of human cancer cells in vitro and in vivo. The present study reports the enhancement of the pharmacological properties of earlier ND compounds using structure-based design. Crystal structures of three complexes with human telomeric intramolecular quadruplexes demonstrate that two of the four strongly basic N-methyl-piperazine groups can be replaced by less basic morpholine groups with no loss of intermolecular interactions in the grooves of the quadruplex. The new compounds retain high affinity to human telomeric quadruplex DNA but are 10-fold more potent against the MIA PaCa-2 pancreatic cancer cell line, with IC50 values of approximately 10 nM. The lead compound induces cellular senescence but does not inhibit telomerase activity at the nanomolar dosage levels required for inhibition of cellular proliferation. Gene array qPCR analysis of MIA PaCa-2 cells treated with the lead compound revealed significant dose-dependent modulation of a distinct subset of genes, including strong induction of DNA damage responsive genes CDKN1A, DDIT3, GADD45A/G, and PPM1D, and repression of genes involved in telomere maintenance, including hPOT1 and PARP1.
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[55]
TÍTULO / TITLE: - Is it necessary to follow patients after resection of a benign pancreatic intraductal papillary mucinous neoplasm?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Am Coll Surg. 2013 Apr;216(4):657-65. doi: 10.1016/j.jamcollsurg.2012.12.026. Epub 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jamcollsurg.2012.12.026
AUTORES / AUTHORS: - He J; Cameron JL; Ahuja N; Makary MA; Hirose K; Choti MA; Schulick RD; Hruban RH; Pawlik TM; Wolfgang CL
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD.
RESUMEN / SUMMARY: - BACKGROUND: Little is known about the risk of subsequently developing a new or progressive intraductal papillary mucinous neoplasm (IPMN) after partial pancreatic resection of a noninvasive IPMN. STUDY DESIGN: One hundred thirty patients with more than 1 year of follow-up after resection were included in this analysis. RESULTS: At a median follow-up of 38 months, 22 (17%) developed imaging evidence of a new or progressive IPMN. Eleven (8%) underwent completion resection. Three of the 11 patients had invasive adenocarcinoma. Two other patients developed metastatic pancreatic adenocarcinoma and did not undergo resection. All 5 patients (4%) with cancer had negative margins at initial operation. Sixteen of 100 patients (16%) with negative margins for IPMN at the initial operation developed a new IPMN vs 6 of 30 patients (20%) with margins positive for IPMN (p = ns). Five of 22 patients (23%) with a new IPMN had a family history of pancreatic cancer, while 8 of 108 patients (7%) without a new IPMN had a family history (p < 0.05). Overall, the chances of developing a new IPMN at 1, 5, and 10 years after the initial surgery were 4%, 25%, and 62%, respectively, and of requiring surgery were 1.6%, 14%, and 18%, respectively. The estimated chances of developing invasive pancreatic cancer were 0%, 7%, and 38% at 1, 5, and 10 years, respectively. CONCLUSIONS: Patients who have undergone resection for noninvasive IPMN require indefinite close surveillance because of the risks of developing a new IPMN, of requiring surgery, and of developing cancer. A family history of pancreatic cancer, but not margin status or degree of dysplasia, is associated with a risk of development of a new or progressive IPMN.
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[56]
TÍTULO / TITLE: - Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Mar 25. doi: 10.1038/onc.2013.68.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.68
AUTORES / AUTHORS: - Goicoechea SM; Garcia-Mata R; Staub J; Valdivia A; Sharek L; McCulloch CG; Hwang RF; Urrutia R; Yeh JJ; Kim HJ; Otey CA
INSTITUCIÓN / INSTITUTION: - Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
RESUMEN / SUMMARY: - The stromal compartment surrounding epithelial-derived pancreatic tumors is thought to have a key role in the aggressive phenotype of this malignancy. Emerging evidence suggests that cancer-associated fibroblasts (CAFs), the most abundant cells in the stroma of pancreatic tumors, contribute to the tumor’s invasion, metastasis and resistance to therapy, but the precise molecular mechanisms that regulate CAFs behavior are poorly understood. In this study, we utilized immortalized human pancreatic CAFs to investigate molecular pathways that control the matrix-remodeling and invasion-promoting activity of CAFs. We showed previously that palladin, an actin-associated protein, is expressed at high levels in CAFs of pancreatic tumors and other solid tumors, and also in an immortalized line of human CAFs. In this study, we found that short-term exposure of CAFs to phorbol esters reduced the number of stress fibers and triggered the appearance of individual invadopodia and invadopodial rosettes in CAFs. Molecular analysis of invadopodia revealed that their composition resembled that of similar structures (that is, invadopodia and podosomes) described in other cell types. Pharmacological inhibition and small interfering RNA knockdown experiments demonstrated that protein kinase C, the small GTPase Cdc42 and palladin were necessary for the efficient assembly of invadopodia by CAFs. In addition, GTPase activity assays showed that palladin contributes to the activation of Cdc42. In mouse xenograft experiments using a mixture of CAFs and tumor cells, palladin expression in CAFs promoted the rapid growth and metastasis of human pancreatic tumor cells. Overall, these results indicate that high levels of palladin expression in CAFs enhance their ability to remodel the extracellular matrix by regulating the activity of Cdc42, which in turn promotes the assembly of matrix-degrading invadopodia in CAFs and tumor cell invasion. Together, these results identify a novel molecular signaling pathway that may provide new molecular targets for the inhibition of pancreatic cancer metastasis.Oncogene advance online publication, 25 March 2013; doi:10.1038/onc.2013.68.
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[57]
TÍTULO / TITLE: - Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Immunol. 2013 Apr 1;190(7):3798-805. doi: 10.4049/jimmunol.1203194. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 4049/jimmunol.1203194
AUTORES / AUTHORS: - Neyen C; Pluddemann A; Mukhopadhyay S; Maniati E; Bossard M; Gordon S; Hagemann T
INSTITUCIÓN / INSTITUTION: - Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
RESUMEN / SUMMARY: - Alternatively activated macrophages express the pattern recognition receptor scavenger receptor A (SR-A). We demonstrated previously that coculture of macrophages with tumor cells upregulates macrophage SR-A expression. We show in this study that macrophage SR-A deficiency inhibits tumor cell migration in a coculture assay. We further demonstrate that coculture of tumor-associated macrophages and tumor cells induces secretion of factors that are recognized by SR-A on tumor-associated macrophages. We tentatively identified several potential ligands for the SR-A receptor in tumor cell-macrophage cocultures by mass spectrometry. Competing with the coculture-induced ligand in our invasion assay recapitulates SR-A deficiency and leads to similar inhibition of tumor cell invasion. In line with our in vitro findings, tumor progression and metastasis are inhibited in SR-A(-/-) mice in two in vivo models of ovarian and pancreatic cancer. Finally, treatment of tumor-bearing mice with 4F, a small peptide SR-A ligand able to compete with physiological SR-A ligands in vitro, recapitulates the inhibition of tumor progression and metastasis observed in SR-A(-/-) mice. Our observations suggest that SR-A may be a potential drug target in the prevention of metastatic cancer progression.
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[58]
TÍTULO / TITLE: - Sirtuin-1 Regulates Acinar-to-Ductal Metaplasia and Supports Cancer Cell Viability in Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Apr 1;73(7):2357-2367. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3359
AUTORES / AUTHORS: - Wauters E; Sanchez-Arevalo Lobo VJ; Pinho AV; Mawson A; Herranz D; Wu J; Cowley MJ; Colvin EK; Njicop EN; Sutherland RL; Liu T; Serrano M; Bouwens L; Real FX; Biankin AV; Rooman I
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Cancer Research Program, Garvan Institute of Medical Research, Sydney, Australia; Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium; St Vincent’s Clinical School, University New South Wales, Australia; Programa de Patologia Molecular and Programa de Oncologia Molecular, CNIO (Spanish National Cancer Research Center), Madrid, España; Children’s Cancer Institute Australia for Medical Research, Randwick, Australia; and Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, España.
RESUMEN / SUMMARY: - The exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma (PDAC) can arise. The NAD+-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1 in different stages of pancreatic carcinogenesis, i.e. ADM models and established PDAC. In addition, we analyzed the expression of KIAA1967, a key mediator of Sirt1 function, along with potential Sirt1 downstream targets. Sirt1 was co-expressed with KIAA1967 in the nuclei of normal pancreatic acinar cells. In ADM, Sirt1 underwent a transient nuclear-to-cytoplasmic shuttling. Experiments where during ADM, we enforced repression of Sirt1 shuttling, inhibition of Sirt1 activity or modulation of its expression, all underscore that the temporary decrease of nuclear and increase of cytoplasmic Sirt1 stimulate ADM. Our results further underscore that important transcriptional regulators of acinar differentiation, that is, Pancreatic transcription factor-1a and beta-catenin can be deacetylated by Sirt1. Inhibition of Sirt1 is effective in suppression of ADM and in reducing cell viability in established PDAC tumors. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1/2 inhibitor Tenovin-6. In PDAC, acetylation of beta-catenin is not affected, unlike p53, a well-characterized Sirt1-regulated protein in tumor cells. Our results reveal that Sirt1 is an important regulator and potential therapeutic target in pancreatic carcinogenesis. Cancer Res; 73(7); 2357-67. ©2012 AACR.
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[59]
TÍTULO / TITLE: - PARI overexpression promotes genomic instability and pancreatic tumorigenesis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Res. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1158/0008-5472.CAN-12-3313
AUTORES / AUTHORS: - O’Connor KW; Dejsuphong D; Park E; Nicolae CM; Kimmelman AC; D’Andrea AD; Moldovan GL
INSTITUCIÓN / INSTITUTION: - Dept. Radiation Oncology, Dana-Farber Cancer Institute.
RESUMEN / SUMMARY: - Treatment options for patients with pancreatic ductal adenocarcinoma remain limited. Therapeutic targets of interest include mutated molecules that predispose to pancreatic cancer such as KRAS and TP53. Here we show that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI (PARPBP), is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell cycle alterations associated with S phase delay, perturbed DNA replication and activation of the DNA damage response pathway in the absence of DNA damage stimuli. Conversely, PARI overexpression produced tolerance to DNA damage by promoting replication of damaged DNA. In a mouse xenograft model of pancreatic cancer, PARI silencing was sufficient to reduce pancreatic tumor growth in vivo. Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat pancreatic ductal adenocarcinoma.
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[60]
TÍTULO / TITLE: - Metastatic Gastrinoma in a Pediatric Patient With Zollinger-Ellison Syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pediatr Hematol Oncol. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1097/MPH.0b013e318282dadf
AUTORES / AUTHORS: - Massaro SA; Emre SH
INSTITUCIÓN / INSTITUTION: - *Section of Hematology/Oncology, Department of Pediatrics daggerYale Stem Cell Center, Yale University School of Medicine double daggerSection of Transplantation and Immunology, Department of Surgery section signYale New Haven Transplant Center, New Haven, CT.
RESUMEN / SUMMARY: - Metastatic neuroendocrine tumors of childhood are extremely rare, and as such present diagnostic and therapeutic challenges. Here, we report a case of gastrinoma with extensive hepatic metastases in a pediatric patient with Zollinger-Ellison Syndrome who underwent orthotopic liver transplant followed by cytotoxic chemotherapy, somatostatin analog therapy, and immune modulation.
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[61]
TÍTULO / TITLE: - Risk of pancreatic cancer in breast cancer families from the Breast Cancer Family Registry.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Epidemiol Biomarkers Prev. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-0195
AUTORES / AUTHORS: - Mocci E; Milne RL; Yuste Mendez-Villamil E; Hopper JL; John EM; Andrulis IL; Chung WK; Daly MB; Buys SS; Malats N; Goldgar DE
INSTITUCIÓN / INSTITUTION: - 1Spanish National Cancer Research Centre (CNIO).
RESUMEN / SUMMARY: - BACKGROUND: Increased risk of pancreatic cancer (PC) has been reported in breast cancer (BC) families carrying BRCA1and BRCA2 mutations; however, PC risk in mutation-negative (BRCAX) families has not been explored to date. The aim of this study was to estimate PC risk in high-risk BC families according to the BRCA mutation status. METHODS: A retrospective cohort analysis was applied to estimate standardized incidence ratios (SIR) for PC. A total of 5,799 families with >/=1 BC case tested for mutations in BRCA1 and/or BRCA2 were eligible. Families were divided into four classes: BRCA1, BRCA2, BRCAX with >/=2 BC diagnosed before age 50 (class 3), and the remaining BRCAX families (class 4). RESULTS: BRCA1 mutation carriers were at increased risk of PC (SIR= 4.11; 95% confidence interval [CI], 2.94-5.76) as were BRCA2 mutation carriers (SIR=5.79; 95% CI, 4.28-7.84). BRCAX family members were also at increased PC risk, which did not appear to vary by number of members with early-onset breast cancer (SIR=1.31; 95%CI, 1.06-1.63 for Class 3 and SIR=1.30; 95%CI, 1.13-1.49 for class 4). CONCLUSIONS: Germline mutations in BRCA1 and BRCA2 are associated with an increased risk of PC. Members of BRCAX families are also at increased risk of PC, pointing to the existence of other genetic factors that increase the risk of both PC and BC. Impact:This study clarifies the relationship between familial breast cancer and pancreatic cancer. Given its high mortality, PC should be included in risk assessment in familial breast cancer counseling.
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[62]
TÍTULO / TITLE: - Predictors of Malignancy in Intraductal Papillary Mucinous Neoplasm of the Pancreas: Analysis of 310 Pancreatic Resection Patients at Multiple High-Volume Centers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827a7b84
AUTORES / AUTHORS: - Shimizu Y; Yamaue H; Maguchi H; Yamao K; Hirono S; Osanai M; Hijioka S; Hosoda W; Nakamura Y; Shinohara T; Yanagisawa A
INSTITUCIÓN / INSTITUTION: - From the *Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya; daggerThe Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama; double daggerCenter for Gastroenterology, Teine-Keijinkai Hospital, Sapporo; Departments of section signGastroenterology and parallelPathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya; paragraph signDepartment of Clinical Laboratory Medicine, Wakayama Medical University, School of Medicine, Wakayama; #Department of Pathology, Teine-Keijinkai Hospital, Sapporo; and **Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. RESULTS: Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). CONCLUSIONS: The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.
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[63]
TÍTULO / TITLE: - Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Apr;42(3):511-5. doi: 10.1097/MPA.0b013e31826c6aee.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826c6aee
AUTORES / AUTHORS: - Hubner RA; Worsnop F; Cunningham D; Chau I
INSTITUCIÓN / INSTITUTION: - From the *Department of Medical Oncology, Christie Hospital Foundation Trust, Manchester; daggerDepartment of Medicine, Royal Marsden Hospital, London, United Kingdom.
RESUMEN / SUMMARY: - OBJECTIVES: Gemcitabine in combination with capecitabine (GEMCAP) is a treatment option for patients with advanced pancreatic cancer (APC), but data are lacking concerning outcomes in unselected patients not enrolled to a randomized trial. METHODS: Baseline demographic, clinical, toxicity, tumor response, and survival data were collected for previously untreated patients with APC receiving off-protocol GEMCAP at a single institution between 2005 and 2009. RESULTS: Data from 113 patients were included in the study. The mean age was 65 years; 51% of patients had metastatic disease; and 80% were of World Health Organization performance status 0 or 1. Patients received a mean of 20 weeks of chemotherapy. The objective response rate was 9.7%; the median overall survival was 8.7 months (95% confidence interval, 6.7-10.7), and 34% of patients were alive 1 year after starting treatment. Performance status (0 or 1 vs 2) was a significant prognostic factor (P < 0.0001). Grade 3 or 4 adverse events, excluding nonfebrile neutropenia, were experienced by 37 patients (33%), the commonest being lethargy (8%), hand-foot syndrome (8%), diarrhea (7%), thrombocytopenia (4%), and febrile neutropenia (6%). CONCLUSIONS: Gemcitabine in combination with capecitabine is effective and tolerable in unselected patients with APC, and outcomes are comparable with those of patients receiving GEMCAP in clinical trials.
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[64]
TÍTULO / TITLE: - Simultaneous 68Ga-DOTATOC PET/MRI in Patients With Gastroenteropancreatic Neuroendocrine Tumors: Initial Results.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Invest Radiol. 2013 Mar 13.
●● Enlace al texto completo (gratuito o de pago) 1097/RLI.0b013e3182871a7f
AUTORES / AUTHORS: - Beiderwellen KJ; Poeppel TD; Hartung-Knemeyer V; Buchbender C; Kuehl H; Bockisch A; Lauenstein TC
INSTITUCIÓN / INSTITUTION: - From the Departments of *Diagnostic and Interventional Radiology and Neuroradiology, and daggerNuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Essen; and double daggerDepartment of Diagnostic and Interventional Radiology, University of Dusseldorf, Dusseldorf, Germany.
RESUMEN / SUMMARY: - OBJECTIVES: The aim of this pilot study was to demonstrate the potential of simultaneously acquired 68-Gallium-DOTA-D-Phe1-Tyr-octreotide (Ga-DOTATOC) positron emission tomography/magnetic resonance imaging (PET/MRI) in comparison with Ga-DOTATOC PET/computed tomography (PET/CT) in patients with known gastroenteropancreatic neuroendocrine tumors (NETs). MATERIALS AND METHODS: Eight patients (4 women and 4 men; mean [SD] age, 54 [17] years; median, 55 years; range 25-74 years) with histopathologically confirmed NET and scheduled Ga-DOTATOC PET/CT were prospectively enrolled for an additional integrated PET/MRI scan. Positron emission tomography/computed tomography was performed using a triple-phase contrast-enhanced full-dose protocol. Positron emission tomography/magnetic resonance imaging encompassed a diagnostic, contrast-enhanced whole-body MRI protocol. Two readers separately analyzed the PET/CT and PET/MRI data sets including their subscans in random order regarding lesion localization, count, and characterization on a 4-point ordinal scale (0, not visible; 1, benign; 2, indeterminate; and 3, malignant). In addition, each lesion was rated in consensus on a binary scale (allowing for benign/malignant only). Clinical imaging, existing prior examinations, and histopathology (if available) served as the standard of reference. In PET-positive lesions, the standardized uptake value (SUVmax) was measured in consensus. A descriptive, case-oriented data analysis was performed, including determination of frequencies and percentages in detection of malignant, benign, and indeterminate lesions in connection to their localization. In addition, percentages in detection by a singular modality (such as PET, CT, or MRI) were calculated. Interobserver variability was calculated (Cohen’s kappa). The SUVs in the lesions in PET/CT and PET/MRI were measured, and the correlation coefficient (Pearson, 2-tailed) was calculated. RESULTS: According to the reference standard, 5 of the 8 patients had malignant NET lesions at the time of the examination. A total of 4 patients were correctly identified by PET/CT, with the PET and CT component correctly identifying 3 patients each. All 5 patients positive for NET disease were correctly identified by PET/MRI, with the MRI subscan identifying all 5 patients and the PET subscan identifying 3 patients. All lesions considered as malignant in PET/CT were equally depicted in and considered using PET/MRI. One liver lesion rated as “indetermined” in PET/CT was identified as metastasis in PET/MRI because of a diffusion restriction in diffusion-weighted imaging. Of the 4 lung lesions characterized in PET/CT, only 1 was depicted in PET/MRI. Of the 3 lymph nodes depicted in PET/CT, only 1 was characterized in PET/MRI. Interobserver reliability was equally very good in PET/CT (kappa = 0.916) and PET/MRI (kappa = 1.0). The SUVmax measured in PET/CT and in PET/MRI showed a strong correlation (Pearson correlation coefficient, 0.996). CONCLUSIONS: This pilot study demonstrates the potential of Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic NET, with special advantages in the characterization of abdominal lesions yet certain weaknesses inherent to MRI, such as lung metastases and hypersclerotic bone lesions.
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[65]
TÍTULO / TITLE: - Aberrant Expression of Mucin Core Proteins and O-Linked Glycans Associated with Progression of Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Apr 3.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2662
AUTORES / AUTHORS: - Remmers N; Anderson JM; Linde EM; Dimaio DJ; Lazenby AJ; Wandall HH; Mandel U; Clausen H; Yu F; Hollingsworth MA
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of Biochemistry and Molecular Biology and Pathology and Microbiology; Eppley Institute for Research in Cancer and Allied Diseases; Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine; and School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
RESUMEN / SUMMARY: - PURPOSE: Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy for pancreatic cancer and other adenocarcinomas. We investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma-sialyl Tn (STn), Tn, T antigen, sialyl Lewis A (CA19-9), sialyl Lewis C (SLeC), Lewis X (LeX), and sialyl LeX (SLeX)-during the progression of pancreatic cancer from early stages to metastatic disease.EXPERIMENTAL DESIGN: Immunohistochemical analyses of mucin and associated glycan expression on primary tumor and liver metastatic tumor samples were conducted with matched sets of tissues from 40 autopsy patients diagnosed with pancreatic adenocarcinoma, 14 surgically resected tissue samples, and 8 normal pancreata.RESULTS: There were significant changes in mucin expression patterns throughout disease progression. MUC1 and MUC4 were differentially glycosylated as the disease progressed from early pancreatic intraepithelial neoplasias to metastatic disease. De novo expression of several mucins correlated with increased metastasis indicating a potentially more invasive phenotype, and we show the expression of MUC6 in acinar cells undergoing acinar to ductal metaplasia. A “cancer field-effect” that included changes in mucin protein expression and glycosylation in the adjacent normal pancreas was also seen.CONCLUSIONS: There are significant alterations in mucin expression and posttranslational processing during progression of pancreatic cancer from early lesions to metastasis. The results are presented in the context of how mucins influence the biology of tumor cells and their microenvironment during progression of pancreatic cancer. Clin Cancer Res; 19(8); 1-13. ©2013 AACR.
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[66]
TÍTULO / TITLE: - Inflammatory Plasma Markers and Pancreatic Cancer Risk: a Prospective Study of 5 U.S. Cohorts.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Epidemiol Biomarkers Prev. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1158/1055-9965.EPI-12-1458
AUTORES / AUTHORS: - Bao Y; Giovannucci E; Kraft P; Qian ZR; Wu C; Ogino S; Gaziano JM; Stampfer MJ; Ma J; Buring JE; Sesso H; Lee IM; Rifai N; Pollak MN; Jiao L; Lessin LS; Cochrane BB; Manson JE; Fuchs CS; Wolpin BM
INSTITUCIÓN / INSTITUTION: - 1Department of Medicine, Brigham and Women’s Hospital.
RESUMEN / SUMMARY: - BACKGROUND: Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. METHODS: In a prospective, nested case-control study of 470 cases and 1094 controls from Health Professionals Follow-up Study, Nurses’ Health Study, Physicians’ Health Study, Women’s Health Initiative, and Women’s Health Study, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha-receptor II (TNF-alphaR2) with subsequent pancreatic cancer risk. The median follow-up time of cases was 7.2 years (range 1-26 years). RESULTS: No association was observed between plasma CRP, IL6, and TNF-alphaR2 and risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 (95% CI, 0.74-1.63; Ptrend= 0.81) for CRP, 1.19 (95% CI, 0.81-1.76; Ptrend = 0.08) for IL6, and 0.88 (95% CI, 0.58-1.33; Ptrend = 0.57) for TNF-alphaR2. CONCLUSIONS: Pre-diagnostic levels of circulating CRP, IL6, and TNF-alphaR2 were not associated with risk of pancreatic cancer. Impact: Systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer.
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[67]
TÍTULO / TITLE: - Role of SUVmax obtained by 18F-FDG PET/CT in patients with a solitary pancreatic lesion: predicting malignant potential and proliferation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nucl Med Commun. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1097/MNM.0b013e328360668a
AUTORES / AUTHORS: - Hu SL; Yang ZY; Zhou ZR; Yu XJ; Ping B; Zhang YJ
INSTITUCIÓN / INSTITUTION: - Departments of aNuclear Medicine bDiagnostic Radiology cPancreas & Hepatobililary Surgery dPathology, Fudan University Shanghai Cancer Center eDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
RESUMEN / SUMMARY: - OBJECTIVES: Maximum standardized uptake value (SUVmax) is a marker of tumor glucose metabolism detected by [F]-fluorodeoxyglucose (F-FDG) PET/computed tomography (PET/CT) and reflects tumor aggressiveness. The aim of the study was to evaluate the value of SUVmax in differentiating benign from malignant solitary pancreatic lesions and explore the correlation between SUVmax and tumor proliferative activity. MATERIALS AND METHODS: F-FDG PET/CT scans were performed in 80 patients with solitary pancreatic lesions who were scheduled for resective surgery. The relationships between SUVmax and postoperative pathologic diagnosis, histologic grade, and Ki-67 proliferation index (PI) were analyzed. RESULTS: Of these 80 patients, 54 had malignant lesions. The SUVmax of malignant tumors (6.3+/-2.4) was significantly greater than that of benign lesions (2.9+/-2.0) (P<0.001). Receiver-operating characteristic curve analysis showed that the SUVmax cutoff value of 3.5 had a high sensitivity (92.6%) and specificity (76.9%) for the diagnosis of malignancies. Among pancreatic cancers with low (Ki-67<5%), moderate (5%</=Ki-67<50%), and high (Ki-67>/=50%) PI, SUVmax increased significantly from 4.2+/-1.2, through 6.0+/-1.7, to 8.6+/-2.5 (P<0.001). The SUVmax had a positive correlation with Ki-67 PI (P<0.001, r=0.60). CONCLUSION: The SUVmax of F-FDG PET/CT can be used in the differential diagnosis of solitary pancreatic lesions and can also aid in the prediction of proliferative activity of pancreatic cancer.
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[68]
TÍTULO / TITLE: - Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocrine. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9910-5
AUTORES / AUTHORS: - Tamagno G; Sheahan K; Skehan SJ; Geoghegan JG; Fennelly D; Collins CD; Maguire D; Traynor O; Brophy DP; Cantwell C; Swan N; McGowan L; O’Toole D; O’Shea D
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology & Diabetes Mellitus, St Vincent’s University Hospital-University College Dublin, 4 Elm Park, Dublin 4, Ireland, gianlucatamagno@tiscali.it.
RESUMEN / SUMMARY: - According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.
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[69]
TÍTULO / TITLE: - Targeting the NF-kappaB and mTOR pathways with a quinoxaline urea analog that inhibits IKKbeta for pancreas cancer therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Cancer Res. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1078-0432.CCR-12-2909
AUTORES / AUTHORS: - Radharkrishnan P; Bryant VC; Blowers EC; Rajule R; Gautham N; Anwar MM; Mohr AM; Grandgenett PM; Bunt S; Arnst JL; Lele SM; Alnouti Y; Hollingsworth MT; Natarajan A
INSTITUCIÓN / INSTITUTION: - Eppley Cancer Center, University of Nebraska Medical Center.
RESUMEN / SUMMARY: - PURPOSE: The presence of TNFalpha in ~ 50% of surgically resected tumors suggests that the canonical NF-kappaB and the mTOR pathways are activated. IkappaB kinase beta (IKKbeta) acts as the signaling node that regulates transcription via the p-IkappaBalpha / NF-kappaB axis and regulates translation via the mTOR / p-S6K / p-eIF4EBP axis. A kinome screen identified a quinoxaline urea analog 13-197 as an IKKbeta inhibitor. We hypothesized that targeting the NF-kappaB and mTOR pathways with 13-197 will be effective in malignancies driven by these pathways. EXPERIMENTAL DESIGN: Retrospective clinical and preclinical studies in pancreas cancers have implicated NF-kappaB. We examined the effects of 13-197, on the downstream targets of the NF-kappaB and mTOR pathways in pancreatic cancer cells, pharmacokinetics, toxicity and tumor growth and metastases in vivo. RESULTS: 13-197 inhibited the kinase activity of IKKbeta in vitro and TNFalpha mediated NF-kappaB transcription in cells with low-muM potency. 13-197 inhibited the phosphorylation of IkappaBalpha, S6K and eIF4EBP, induced G1 arrest and down regulated the expression of antiapoptotic proteins in pancreatic cancer cells. Prolonged administration of 13-197 did not induce granulocytosis and protected mice from LPS-induced death. Results also show that 13-197 is orally available with extensive distribution to peripheral tissues and inhibited tumor growth and metastasis in an orthotopic pancreatic cancer model without any detectable toxicity. CONCLUSIONS: These results suggest that 13-197 targets IKKbeta and thereby inhibits mTOR and NF-kappaB pathways. Oral availability along with in vivo efficacy without obvious toxicities makes this quinoxaline urea chemotype, a viable cancer therapeutic.
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[70]
TÍTULO / TITLE: - New-onset diabetic patients need pancreatic cancer screening.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Gastroenterol. 2013 Apr;47(4):372. doi: 10.1097/MCG.0b013e318275895b.
●● Enlace al texto completo (gratuito o de pago) 1097/MCG.0b013e318275895b
AUTORES / AUTHORS: - Lai SW; Liao KF
INSTITUCIÓN / INSTITUTION: - *School of Medicine, China Medical University daggerDepartment of Family Medicine, China Medical University Hospital double daggerDepartment of Internal Medicine Taichung Tzu Chi General Hospital parallelDepartment of Health Care Administration, Central Taiwan University of Science and Technology, Taichung section signGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
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[71]
TÍTULO / TITLE: - Safety evaluation of high-intensity focused ultrasound in patients with pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onkologie. 2013;36(3):88-92. doi: 10.1159/000348530. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1159/000348530
AUTORES / AUTHORS: - Wang K; Zhu H; Meng Z; Chen Z; Lin J; Shen Y; Gao H
INSTITUCIÓN / INSTITUTION: - Department of Integrated Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
RESUMEN / SUMMARY: - Introduction: This study was performed to analyze the safety of high-intensity focused ultrasound (HIFU) for treating pancreatic cancer. Methods: 224 cases with advanced pancreatic cancer were enrolled into this study. Real-time sonographic images were taken, and vital signs, liver and kidney function, skin burns, local reactions, and systemic effects were monitored and recorded before, during, and after HIFU. Computed tomography or magnetic resonance imaging (MRI) was also performed before and after HIFU. Results: Serum amylase level increased in 16 cases (7.1%) 1 day after HIFU treatment, and 9 of these cases also had abnormal urinary amylase levels. Gastrointestinal (GI) dysfunction such as abdominal distension and anorexia with slight nausea was observed in 10 cases (4.5%) after HIFU treatment. 1 case with pancreatic head cancer developed obstructive jaundice 2 weeks after HIFU treatment. Vertebral injury, identified by MRI, occurred in 2 cases, although no symptoms were seen. No severe complications such as skin burns, lesion bleeding, GI tract bleeding or GI perforation were observed in any of the cases. Conclusion: For specific patients, HIFU treatment is a safe, non-invasive treatment for pancreatic cancer but requires careful preoperative preparation and exact operative performance.
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[72]
TÍTULO / TITLE: - Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Mar 7;19(9):1451-7. doi: 10.3748/wjg.v19.i9.1451.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i9.1451
AUTORES / AUTHORS: - Xu B; Ding WX; Jin DY; Wang DS; Lou WH
INSTITUCIÓN / INSTITUTION: - Bin Xu, Wei-Xing Ding, Department of General Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China.
RESUMEN / SUMMARY: - AIM: To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. RESULTS: CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. CONCLUSION: Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.
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[73]
TÍTULO / TITLE: - Mechanistic insights into self-reinforcing processes driving abnormal histogenesis during the development of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Pathol. 2013 Apr;182(4):1078-86. doi: 10.1016/j.ajpath.2012.12.004. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ajpath.2012.12.004
AUTORES / AUTHORS: - Iovanna JL; Marks DL; Fernandez-Zapico ME; Urrutia R
INSTITUCIÓN / INSTITUTION: - Cancer Research Center of Marseille, Inserm U1068, CNRS, UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, Marseille, France.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma, one of the most feared lethal and painful diseases, is increasing in incidence. The poor prognosis of pancreatic ductal adenocarcinoma-affected patients primarily is owing to our inability to develop effective therapies. Mechanistic studies of genetic, epigenetic, and cell-to-cell signaling events are providing clues to molecular pathways that can be targeted in an attempt to cure this disease. The current review article seeks to draw inferences from available mechanistic knowledge to build a theoretical framework that can facilitate these approaches. This conceptual model considers pancreatic cancer as a tissue disease rather than an isolated epithelial cell problem, which develops and progresses in large part as a result of three positive feedback loops: i) genetic and epigenetic changes in epithelial cells modulate their interaction with mesenchymal cells to generate a dynamically changing process of abnormal histogenesis, which drives more changes; ii) the faulty tissue architecture of neoplastic lesions results in unsynchronized secretion of signaling molecules by cells, which generates an environment that is poor in oxygen and nutrients; and iii) the increased metabolic needs of rapidly dividing cells serve as an evolutionary pressure for them to adapt to this adverse microenvironment, leading to the emergence of resistant clones. We discuss how these concepts can guide mechanistic studies, as well as aid in the design of novel experimental therapeutics.
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[74]
TÍTULO / TITLE: - Protein kinase Calpha inhibitor protects against downregulation of claudin-1 during epithelial-mesenchymal transition of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 18.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt057
AUTORES / AUTHORS: - Kyuno D; Kojima T; Yamaguchi H; Ito T; Kimura Y; Imamura M; Takasawa A; Murata M; Tanaka S; Hirata K; Sawada N
INSTITUCIÓN / INSTITUTION: - Department of Surgery and.
RESUMEN / SUMMARY: - Protein kinase Calpha (PKCalpha) is highly expressed in pancreatic cancer. However, the effects of PKCalpha on Snail and claudin-1, which play crucial roles in epithelial cell polarity during epithelial-mesenchymal transition (EMT), remain unclear. In this study, we investigated the mechanisms of regulation of Snail and claudin-1 via a PKCalpha signal pathway during EMT in pancreatic cancer cells and in normal human pancreatic duct epithelial cells (HPDEs). By immunostaining, overexpression of PKCalpha and downregulation of claudin-1 were observed in poorly differentiated human pancreatic cancer tissues and the pancreatic cancer cell line PANC-1. Treatment with the PKCalpha inhibitor Go6976 transcriptionally decreased Snail and increased claudin-1 in PANC-1 cells. The PKCalpha inhibitor prevented upregulation of Snail and downregulation of claudin-1 during EMT induced by transforming growth factor-beta1 (TGF-beta1) treatment and under hypoxia in PANC-1 cells. The effects of the PKCalpha inhibitor were in part regulated via an extracellular signal-regulated kinase (ERK) signaling pathway. The PKCalpha inhibitor also prevented downregulation of the barrier function and fence function during EMT in well-differentiated pancreatic cancer cell line HPAC. In normal HPDEs, the PKCalpha inhibitor transcriptionally induced not only claudin-1 but also claudin-4, -7 and occludin without a change of Snail. Treatment with the PKCalpha inhibitor in normal HPDEs prevented downregulation of claudin-1 and occludin by TGF-beta1 treatment and enhanced upregulation of claudin-1, -4, -7 and occludin under hypoxia. These findings suggest that PKCalpha regulates claudin-1 via Snail- and mitogen-activated protein kinase/ERK-dependent pathways during EMT in pancreatic cancer. Thus, PKCalpha inhibitors may be potential therapeutic agents against the malignancy of human pancreatic cancer cells.
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[75]
TÍTULO / TITLE: - Characteristics of Notch2 pancreatic cancer stem-like cells and the relationship with centroacinar cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Biol Int. 2013 Mar 28. doi: 10.1002/cbin.10102.
●● Enlace al texto completo (gratuito o de pago) 1002/cbin.10102
AUTORES / AUTHORS: - Ni QX
INSTITUCIÓN / INSTITUTION: - 270 Dongan Road, Shanghai, China, 200032.
RESUMEN / SUMMARY: - Notch2, a surface marker in cell lines, is used to isolate, identify and localize pancreatic cancer stem-like cells and is a target for therapy of these cells. Sphere formation was induced in Panc-1 and Bxpc-3 pancreatic cancer cell lines, and Notch2+ cells were separated from Bxpc-3 and Panc-1 cell lines by magnetic activated cell sorting (MACS). Expression of stem cell-related markers, OCT4, Nanog and PDX1, were measured by immunofluoresent (IF) staining. Expression of Notch2 was also determined immunohistochemically in pancreatic tissues. Notch2+ cells were transplanted in subcutaneous of mice. AQP1 and AQP5 were also measured by IF in Bxpc-3 cells. The Notch signal pathway inhibitor, Compound E (CE), was used to treat Notch2+ Bxpc-3 cells, and their vitalities were subsequently measured by the CCK-8 method. Positive expression of OCT4, Nanog and PDX1 was observed in Notch2+ cells. Notch2+ cells at centroacinar cell (CAC) and terminal ductal locations expressed AQP1 and AQP5. They were strongly tumorigenic in mice, and CE inhibited proliferation of Notch2+ Bxpc-3 cells to some degree. OCT4 and Nanog can be used as markers of self-renewal in pancreatic cancer stem cells. Notch2+ cells in human pancreatic cancer Bxpc-3 and Panc-1 cell lines had the properties of cancer stem cells. The results suggest that Notch2+ pancreatic cancer stem-like cells had a close relationship with CAC.
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[76]
TÍTULO / TITLE: - The Cost-Effectiveness of Neoadjuvant Chemoradiation is Superior to a Surgery-First Approach in the Treatment of Pancreatic Head Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2882-0
AUTORES / AUTHORS: - Abbott DE; Tzeng CW; Merkow RP; Cantor SB; Chang GJ; Katz MH; Bentrem DJ; Bilimoria KY; Crane CH; Varadhachary GR; Abbruzzese JL; Wolff RA; Lee JE; Evans DB; Fleming JB
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA.
RESUMEN / SUMMARY: - BACKGROUND: In treating pancreatic cancer, there is no clearly defined optimal sequence of chemotherapy, radiation therapy and surgery. Therefore, cost-effectiveness should be considered. The objective of this study was to compare cost and outcomes between a surgery-first approach versus neoadjuvant chemoradiation followed by surgery for resectable pancreatic head cancer. METHODS: A decision analytic model was constructed to compare the 2 approaches. Data from the National Cancer Database, National Surgical Quality Improvement Program, and literature populated the surgery-first arm. Data from our prospectively maintained institutional pancreatic cancer database populated the neoadjuvant arm. Costs were estimated by Medicare payment (2011 U.S. dollars). Survival was reported in quality-adjusted life-months (QALMs). RESULTS: The neoadjuvant chemoradiation arm consisted of 164 patients who completed preoperative therapy. Of these, 36 (22 %) did not proceed to surgery; 12 (7 %) underwent laparotomy but had unresectable disease; and 116 (71 %) underwent definitive resection. The surgery-first approach cost $46,830 and yielded survival of 8.7 QALMs; the neoadjuvant chemoradiation approach cost $36,583 and yielded survival of 18.8 QALMs. In the neoadjuvant arm, costs and survival times for patients not undergoing surgery, those with unresectable disease at laparotomy, and those completing surgery were $12,401 and 7.7 QALMs, $20,380 and 7.1 QALMs, and $45,673 and 23.4 QALMs, respectively. CONCLUSIONS: Neoadjuvant chemoradiation for pancreatic cancer identifies patients with early metastases or poor performance status, who can be spared an ineffective or prohibitively morbid operation, and is associated with improved survival at significantly lower cost than a surgery-first approach. Neoadjuvant chemoradiation followed by surgery is a strategy that provides more cost-effective care than a surgery-first approach.
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[77]
TÍTULO / TITLE: - Do patient- and tumor-related factors predict the peritoneal spread of pancreatic adenocarcinoma?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Today. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s00595-013-0546-0
AUTORES / AUTHORS: - Konigsrainer I; Zieker D; Symons S; Horlacher K; Konigsrainer A; Beckert S
INSTITUCIÓN / INSTITUTION: - Department of General, Visceral and Transplant Surgery, University of Tubingen Comprehensive Cancer Center, Hoppe-Seyler-Strasse 3, 72076, Tubingen, Germany, ingmar.koenigsrainer@med.uni-tuebingen.de.
RESUMEN / SUMMARY: - PURPOSE: In pancreatic cancer, the presence of peritoneal carcinomatosis (PC) precludes the possibility of a surgical cure, irrespective of the resectability of the primary tumor. However, peritoneal spread cannot be reliably detected radiographically during preoperative tumor staging. METHODS: The pancreatic adenocarcinoma database of the Tubingen Comprehensive Cancer Center included 29 patients in whom PC was incidentally detected during the surgery. These patients were retrospectively compared for patient- and tumor-related factors with 29 randomly selected patients without PC who underwent curative resection. RESULTS: Clinical jaundice and diarrhea were more frequently present in patients without PC. The CA 19-9 levels were significantly higher in patients with PC compared to those in patients without PC. No other differences were observed in the patient- or tumor-related factors between the two groups. CONCLUSION: In pancreatic cancer patients, markedly elevated CA 19-9 levels may serve as surrogate marker for peritoneal dissemination, irrespective of the local resectability of the tumor. In such patients, laparoscopy should be considered as an additional staging tool to rule out peritoneal carcinomatosis.
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[78]
TÍTULO / TITLE: - Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nutr Cancer. 2013;65(1):157-64. doi: 10.1080/01635581.2012.725502.
●● Enlace al texto completo (gratuito o de pago) 1080/01635581.2012.725502
AUTORES / AUTHORS: - Chan JM; Gong Z; Holly EA; Bracci PM
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94158-9001, USA. june.chan@ucsf.edu
RESUMEN / SUMMARY: - Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.51, 95% confidence intervals (CI) = 0.31-0.84, P trend = 0.001] and women (OR = 0.51, 95% CI = 0.29-0.90, P trend = 0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI = 1.3-4.2, P trend = 0.008) but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the prudent diet had a threefold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer.
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[79]
TÍTULO / TITLE: - Functional activity and tumor-specific expression of dual oxidase 2 in pancreatic cancer cells and human malignancies characterized with a novel monoclonal antibody.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1229-38. doi: 10.3892/ijo.2013.1821. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1821
AUTORES / AUTHORS: - Wu Y; Antony S; Hewitt SM; Jiang G; Yang SX; Meitzler JL; Juhasz A; Lu J; Liu H; Doroshow JH; Roy K
INSTITUCIÓN / INSTITUTION: - Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
RESUMEN / SUMMARY: - Dual oxidase 2 (Duox2), one of the seven members of the NADPH oxidase gene family, plays a critical role in generating H2O2 for thyroid hormone biosynthesis and as an integral part of the host defense system of the respiratory epithelium and the gastrointestinal tract. Recent evidence suggests that the regulation of Duox2 expression is under the control of pro-inflammatory cytokines and that Duox2-induced reactive oxygen species (ROS) contribute to the inflammation-related tissue injury that occurs in two pre-malignant, inflammatory conditions: chronic pancreatitis and inflammatory bowel disease. Because no reliable Duox antibodies are commercially available, we report the development of a murine monoclonal antibody (MAb) to Duox2 (clone Duox S-12) and its use for the characterization of Duox2 expression in human tumors, tumor cell lines and normal tissues. Duox S-12 specifically detected both endogenously- and ectopically-expressed Duox2 protein by immunoblotting, immunofluorescence microscopy and immunohistochemistry (where both membranous and cytoplasmic staining were present). Duox2 expression detected by Duox S-12 was functionally coupled to the generation of H2O2 in pancreatic cancer cells that expressed Duox2 and its cognate maturation factor DuoxA2. Although Duox S-12 recognizes ectopically expressed Duox1 protein because of the extensive amino acid homology between Duox1 and Duox2, the lack of substantial Duox1 mRNA expression in human tumors (except thyroid cancer) allowed us to evaluate Duox2 expression across a wide range of normal and malignant tissues by immuno-histochemistry. Duox2 was expressed at elevated levels in many human cancers, most notably tumors of the prostate, lung, colon and breast while brain tumors and lymphomas demonstrated the lowest frequency of expression. The Duox-specific monoclonal antibody described here provides a promising tool for the further examination of the role of Duox-dependent reactive oxygen production in inflammation-related carcinogenesis, where alterations in oxidant tone play a critical role in cell growth and proliferation.
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[80]
TÍTULO / TITLE: - Heparin-binding epidermal growth factor-like growth factor eliminates constraints on activated Kras to promote rapid onset of pancreatic neoplasia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Feb 4. doi: 10.1038/onc.2013.3.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.3
AUTORES / AUTHORS: - Ray KC; Moss ME; Franklin JL; Weaver CJ; Higginbotham J; Song Y; Revetta FL; Blaine SA; Bridges LR; Guess KE; Coffey RJ; Crawford HC; Washington MK; Means AL
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
RESUMEN / SUMMARY: - Pancreatic cancer remains as one of the most deadly cancers with few treatment options at late stages and little information about how it develops through earlier stages. Activating mutation of the Kras gene has been implicated in, but is not sufficient for, tumorigenesis. In mouse models of pancreatic cancer, loss of tumor suppressor genes in conjunction with Kras mutation leads to gradual stochastic acquisition of neoplastic precursors and carcinomas, whereas many cells remain phenotypically unaltered in younger mice. Here, we demonstrate that two oncogenic events, mutation of Kras and production of the growth factor heparin-binding epidermal growth factor-like growth factor (HB-EGF), are sufficient for rapid and complete neoplastic transformation of the exocrine pancreas. We found that macrophages are the major source of HB-EGF production in pancreatic cancer tissue samples, and that macrophages are present in high density and in close association with human pancreatic cancer lesions. In a mouse model, high macrophage density was observed at the earliest stages of neoplastic transformation. The consequence of elevated HB-EGF signaling was investigated without the confounding effects of other macrophage-produced factors via transgenic overexpression of the active form of HB-EGF. In this model, HB-EGF was sufficient to promote Kras-initiated tumorigenesis, inducing rapid and complete neoplastic transformation of the entire exocrine pancreas shortly after birth. HB-EGF overexpression and Kras(G12D) together, but neither alone, increased proliferation with increased cyclinD1 and decreased Cdkn2a/2d (p16/p19(Ink4A/Arf)). These findings establish the importance of oncogenic synergy in cancer initiation and promotion, and establish a molecular link between inflammation and the earliest stages of tumor induction.Oncogene advance online publication, 4 February 2013; doi:10.1038/onc.2013.3.
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[81]
TÍTULO / TITLE: - Frequency and Intensity of Postoperative Surveillance After Curative Treatment of Pancreatic Cancer: A Cost-Effectiveness Analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg Oncol. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1245/s10434-013-2889-6
AUTORES / AUTHORS: - Tzeng CW; Abbott DE; Cantor SB; Fleming JB; Lee JE; Pisters PW; Varadhachary GR; Abbruzzese JL; Wolff RA; Ahmad SA; Katz MH
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, cdtzeng@mdanderson.org.
RESUMEN / SUMMARY: - BACKGROUND: Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy. METHODS: We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars). RESULTS: The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies’ absolute costs but not the relative ranks of their ICERs. CONCLUSIONS: Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.
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[82]
TÍTULO / TITLE: - Exploiting inflammation for therapeutic gain in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 19;108(5):997-1003. doi: 10.1038/bjc.2013.24. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.24
AUTORES / AUTHORS: - Steele CW; Jamieson NB; Evans TR; McKay CJ; Sansom OJ; Morton JP; Carter CR
INSTITUCIÓN / INSTITUTION: - 1] The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK [2] Department of Surgery, West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G4 0SF, UK.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC.
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[83]
TÍTULO / TITLE: - Added value of diffusion-weighted imaging to MR cholangiopancreatography with unenhanced MR imaging for predicting malignancy or invasiveness of intraductal papillary mucinous neoplasm of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Magn Reson Imaging. 2013 Feb 6. doi: 10.1002/jmri.24022.
●● Enlace al texto completo (gratuito o de pago) 1002/jmri.24022
AUTORES / AUTHORS: - Kang KM; Lee JM; Shin CI; Baek JH; Kim SH; Yoon JH; Han JK; Choi BI
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea.
RESUMEN / SUMMARY: - PURPOSE: To investigate the added value of diffusion-weighted imaging (DWI) to magnetic resonance cholangiopancreatography (MRCP) with unenhanced MR imaging for predicting the malignancy or invasiveness of intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS: Following Institutional Review Board (IRB) approval, this retrospective study included 52 patients with surgically resected IPMNs and who underwent MRCP, unenhanced MRI, and DWI. Three blinded radiologists evaluated the two image sets, ie, MRCP with unenhanced MR images vs. the combined set with MRCP, unenhanced MR images, and DWI, and scored their confidence for malignancy or for invasiveness of IPMNs. The mean apparent diffusion coefficient (ADC) values of benign IPMNs and of intraductal mucinous carcinomas (IPMCs) were compared. The diagnostic accuracy was calculated using receiver operating characteristic (ROC) curve analysis. ESULTS: The mean ADC of malignant IPMNs (2.05 +/- 0.66 x 10(-3) mm(2) /sec) was significantly lower than that of benign IPMNs (2.95 +/- 0.32 x 10(-3) mm(2) /sec, P < 0.0001). Invasive IPMCs (1.51 +/- 0.32 x 10(-3) mm(2) /sec) showed significantly lower ADC than that of noninvasive IPMCs (2.67 +/- 0.23 x 10(-3) mm(2) /sec, P = 0.0003). The area of diffusion restriction was more frequently seen in malignant IPMNs than in benign IPMNs (P < 0.00001). The addition of DWI to MRCP with unenhanced MRI did not show a significant improvement for predicting malignant IPMN (P> 0.05), but resulted in a tendency to improve the diagnostic accuracy for the prediction of invasive IPMN in two observers (P = 0.072, P = 0.085). CONCLUSION: The addition of DWI to MRCP with unenhanced MRI may improve the diagnosis of malignant IPMN and further increase the prediction of invasive IPMC. J. Magn. Reson. Imaging 2013. Esta es una cita bibliográfica que va por delante de la publicación en papel. La fecha indicada en la cita provista, NO corresponde con la fecha o la cita bibliográfica de la publicación en papel. La cita bibliográfica definitiva (con el volumen y su paginación) saldrá en 1 ó 2 meses a partir de la fecha de la emisión electrónica-online. *** This is a bibliographic record ahead of the paper publication. The given date in the bibliographic record does not correspond to the date or the bibliographic citation on the paper publication. The publisher will provide the final bibliographic citation (with the volume, and pagination) within 1 or 2 months from the date the record was published online. © 2013 Wiley Periodicals, Inc.
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[84]
TÍTULO / TITLE: - LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochem Biophys Res Commun. 2013 Apr 5;433(2):157-62. doi: 10.1016/j.bbrc.2013.02.038. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbrc.2013.02.038
AUTORES / AUTHORS: - Amsterdam A; Raanan C; Schreiber L; Polin N; Givol D
INSTITUCIÓN / INSTITUTION: - Department of Molecular Cell Biology, The Weizmann Institute of Science, 234, Herzl Street, Rehovot 76100, Israel. Electronic address: abraham.amsterdam@weizmann.ac.il.
RESUMEN / SUMMARY: - Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet’s beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer.
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[85]
TÍTULO / TITLE: - A case of primary pancreatic Burkitt’s lymphoma diagnosed by EUS-guided FNA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastrointest Endosc. 2013 Mar 20. pii: S0016-5107(13)00096-5. doi: 10.1016/j.gie.2013.01.039.
●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2013.01.039
AUTORES / AUTHORS: - Nakaji S; Hirata N; Yoshimura S; Shiratori T; Kobayashi M; Ishii E; Matsue K
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Kameda Medical Center, Kamogawa City, Chiba, Japan.
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[86]
TÍTULO / TITLE: - WNT7B mediates autocrine Wnt/beta-catenin signaling and anchorage-independent growth in pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Feb 18. doi: 10.1038/onc.2013.23.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.23
AUTORES / AUTHORS: - Arensman MD; Kovochich AN; Kulikauskas RM; Lay AR; Yang PT; Li X; Donahue T; Major MB; Moon RT; Chien AJ; Dawson DW
INSTITUCIÓN / INSTITUTION: - Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
RESUMEN / SUMMARY: - Developmental and cancer models show Wnt/beta-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/beta-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/beta-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/beta-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally generated, pancreas-specific gene expression signature of Wnt/beta-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early-stage PDAC tumors (N=41). In this cohort, higher Wnt/beta-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease-specific survival (median survival time 20.3 versus 43.9 months, log-rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/beta-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small-molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/beta-catenin activity. Gene-knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B-mediated cell autonomous Wnt/beta-catenin activation, as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/beta-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/beta-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members.Oncogene advance online publication, 18 February 2013; doi:10.1038/onc.2013.23.
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[87]
TÍTULO / TITLE: - Systems Biology Approaches to Pancreatic Cancer Detection, Prevention and Treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Pharm Des. 2013 Mar 19.
AUTORES / AUTHORS: - Alian OM; Philip PA; Sarkar FH; Azmi AS
INSTITUCIÓN / INSTITUTION: - Department of Pathology Wayne State University School of Medicine 4100 John R HWCRC Room 732 Detroit MI, 48201 USA. azmia@karmanos.org.
RESUMEN / SUMMARY: - Pancreatic cancer [PC] is a complex disease harboring multiple genetic alterations. It is now well known that deregulation in the expression and function of oncogenes and tumor suppressor genes contributes to the development and progression of PC. The last 40 years have not seen any major improvements in the dismal overall cure rate for PC where drug resistance is an emerging and recurring obstacle for successful treatment of PC. Additionally, the lack of molecular biomarkers for patient selection limits drug availabilities for tailored therapy for patients diagnosed with PC. The very high failure rate of new drugs in Phase III clinical trials in PC calls for a more robust pre-clinical and clinical testing of new compounds. In order to rationally choose combinations of targeted agents that may improve therapeutic outcome by overcoming drug resistance, one needs to apply newer research tools such as systems and network biology. These newer tools are expected to assist in the design of effective drug combinations for the treatment of PC and are expected to become an important part in any future clinical trials. In this review we will provide background information on the current state of PC research, the reasons for drug failure and how to overcome these issues using systems sciences. We conclude this review with an example on how systems and network methodologies can help design efficacious drug combinations for this deadly and by far incurable disease.
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[88]
TÍTULO / TITLE: - Multiple KRAS Mutations in Pancreatic Adenocarcinoma: Molecular Features of Neoplastic Clones Indicate the Selection of Divergent Populations of Tumor Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Surg Pathol. 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1177/1066896912475073
AUTORES / AUTHORS: - Visani M; de Biase D; Baccarini P; Fabbri C; Polifemo AM; Zanini N; Pession A; Tallini G
RESUMEN / SUMMARY: - KRAS is one of the most common genes mutated in pancreatic adenocarcinoma. Multiple KRAS mutations may be detected within the same pancreatic adenocarcinoma, but it is usually unclear whether the different mutations represent biologically irrelevant molecular events or whether they indicate the coexistence of distinct sizable neoplastic clones within a given tumor. We identified a case of pancreatic adenocarcinoma with 5 different mutations in the KRAS gene and have been able to characterize the allelic distribution of the KRAS mutations and the size of the neoplastic clones using allele-specific locked nucleic acid polymerase chain reaction and next-generation sequencing (454 GS-Junior). The results indicate that the tumor is composed of 5 distinct cell populations: one is KRAS G12V mutated (~38% of neoplastic cells), the second is KRAS G12V in one allele and KRAS G12D in the other (~32%), the third is KRAS G12V in one allele and KRAS G12R in the other (~24%), and the fourth is KRAS G12V in one allele and KRAS G12C in the other (~6%). The fifth clone, representing a minority of neoplastic cells, has a KRAS Q61H mutation in addition to one of the above alterations. Microsatellite analysis identified mutation of the NR21 marker out of the 13 tested, indicating that the tumor has a defect in maintaining DNA integrity different from loss of conventional DNA mismatch repair. These results are consistent with the successive selection of divergent populations of tumor cells and underscore the relevance of nucleotide instability in pancreatic adenocarcinoma.
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[89]
TÍTULO / TITLE: - Metabolomic and transcriptomic profiling of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Carcinogenesis. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1093/carcin/bgt053
AUTORES / AUTHORS: - Yabushita S; Fukamachi K; Tanaka H; Fukuda T; Sumida K; Deguchi Y; Mikata K; Nishioka K; Kawamura S; Uwagawa S; Suzui M; B Alexander D; Tsuda H
INSTITUCIÓN / INSTITUTION: - Environmental Health Science Laboratory, Sumitomo Chemical Co., Osaka 554-8558, Japan.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is one of the most debilitating malignancies in humans, and one of the reasons for this is the inability to diagnose this disease early in its development. To search for biomarkers that can be used for early diagnosis of PDAC, we established a rat model of human PDAC in which expression of a human K-rasG12V oncogene and induction of PDAC are regulated by the Cre/lox system. In the present study, transgenic rats bearing PDAC and control transgenic rats with normal pancreatic tissues were used for metabolomic analysis of serum and pancreatic tissue by non-targeted and targeted gas chromatography-mass spectrometry and transcriptomic analysis of pancreatic tissue by microarray. Comparison of the metabolic profiles of the serum and pancreatic tissue of PDAC-bearing and control rats identified palmitoleic acid as a metabolite, which was significantly decreased in the serum of PDAC-bearing animals. Transcriptomic analysis indicated that several transcripts involved in anaerobic glycolysis and nucleotide degradation were increased and transcripts involved in the trichloroacetic acid cycle were decreased. Other transcripts that were changed in PDAC-bearing rats were adenosine triphosphate citrate lyase (decreased: fatty acid biosynthesis), fatty acid synthase (increased: fatty acid biosynthesis) and arachidonate 5-lipoxygenase activating protein (increased: arachidonic acid metabolism). Overall, our results suggest that the decreased serum levels of palmitoleic acid in rats with PDAC was likely due to its decrease in pancreatic tissue and that palmitoleic acid should be investigated in human samples to assess its diagnostic significance as a serum biomarker for human PDAC.
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[90]
TÍTULO / TITLE: - Prognostic Significance of Autophagy-Related Protein Expression in Resected Pancreatic Ductal Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279d0dc
AUTORES / AUTHORS: - Ko YH; Cho YS; Won HS; Jeon EK; An HJ; Hong SU; Park JH; Lee MA
INSTITUCIÓN / INSTITUTION: - From the Divisions of *Oncology and daggerGastroenterology, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, Catholic University, Uijeongbu-si; double daggerDepartment of Maritime Medicine, Maritime Medical Center, Jinhae; section signDepartment of Biomedical Science, College of Medicine, Catholic University; and parallelDivision of Oncology, Department of Internal Medicine, Seoul St Mary’s Hospital, Catholic University, Seoul, South Korea.
RESUMEN / SUMMARY: - OBJECTIVES: Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. RESULTS: Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270, P = 0.022, respectively). CONCLUSIONS: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.
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[91]
TÍTULO / TITLE: - Preoperative Histological Subtype Classification of Intraductal Papillary Mucinous Neoplasms (IPMN) by Pancreatic Juice Cytology With MUC Stain.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e318281b824
AUTORES / AUTHORS: - Hara T; Ikebe D; Odaka A; Sudo K; Nakamura K; Yamamoto H; Itami M; Hirata T; Kashimura J; Yamaguchi T
INSTITUCIÓN / INSTITUTION: - *Division of Endoscopy, Chiba Cancer Center, Chiba, Japan daggerDivision of Gastroenterology, Chiba Cancer Center, Chiba, Japan double daggerDivision of Surgical Pathology, Chiba Cancer Center, Chiba, Japan section signDivision of Gastroenterological Surgery, Chiba Cancer Center, Chiba, Japan paragraph signInternal Medicine, Mito Saiseikai General Hospital, Ibaraki, Japan.
RESUMEN / SUMMARY: - OBJECTIVE:: To prospectively evaluate the diagnostic value of preoperative histological subtyping of intraductal papillary mucinous neoplasms (IPMNs) by pancreatic juice cytology (PJC) with mucin (MUC) stain. BACKGROUND:: IPMNs are classified into four subtypes based on their histomorphology and mucin phenotype, and varied degrees of malignant nature and prognosis among these subtypes have been shown. METHODS:: The subjects were 36 patients with surgically confirmed IPMNs, who underwent PJC preoperatively by endoscopic retrograde cholangiopancreatography. Histological subtyping of cytological samples with or without MUC stain (MUC1, MUC2, and MUC5AC) was compared with that of resected specimens. RESULTS:: Histologically, low-grade dysplasia was found in 4 patients, intermediate in 10, high grade in 11, and invasive carcinoma in 11. Gastric, intestinal, pancreatobiliary, and oncocytic subtypes corresponded to 16, 14, 5, and 1 patient, respectively. The rate of high-grade dysplasia (HGD) and/or invasive IPMNs was 25% for gastric subtype, 85.7% for intestinal subtype, and 100% for both pancreatobiliary and oncocytic subtypes, showing a significant correlation between histological subtype and rate of HGD and/or invasive IPMN (P < 0.01 for gastric vs nongastric).Histological subtype was successfully diagnosed by PJC in 42% (15/36) without MUC stain, and the rate was significantly improved to 89% (32/36) with MUC stain (P < 0.01). The sensitivity, specificity, and overall accuracy of PJC with MUC stain were 86%, 100%, and 94% for intestinal subtype, respectively. When cytological grade was combined with MUC stain, the diagnosis of HGD/invasive IPMN showed 77.2% sensitivity, 85.7% specificity, and 80.5% accuracy. CONCLUSIONS:: Preoperative PJC with MUC stain proved to be highly reliable for identifying the histological subtype of IPMN and may provide useful information for deciding surgical indication.
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[92]
TÍTULO / TITLE: - Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Surg. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1097/SLA.0b013e31828cd008
AUTORES / AUTHORS: - Ideno N; Ohtsuka T; Kono H; Fujiwara K; Oda Y; Aishima S; Ito T; Ishigami K; Tokunaga S; Ohuchida K; Takahata S; Nakamura M; Mizumoto K; Tanaka M
INSTITUCIÓN / INSTITUTION: - Departments of *Surgery and Oncology, daggerAnatomic Pathology, double daggerMedicine and Bioregulatory Science, and, section signClinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, paragraph signMedical Information Center, Kyushu University Hospital, Fukuoka, Japan ||Department of Gastrointestinal Surgery, Kawasaki Medical School, Okayama, Japan.
RESUMEN / SUMMARY: - OBJECTIVE:: To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes. BACKGROUND:: Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types. METHODS:: Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs. RESULTS:: Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC. CONCLUSIONS:: Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.
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[93]
TÍTULO / TITLE: - Treatment with the Radiolabelled Somatostatin Analog Lu-DOTATATE for Advanced Pancreatic Neuroendocrine Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuroendocrinology. 2013 Feb 2.
●● Enlace al texto completo (gratuito o de pago) 1159/000348394
AUTORES / AUTHORS: - Sansovini M; Severi S; Ambrosetti A; Monti M; Nanni O; Sarnelli A; Bodei L; Garaboldi L; Bartolomei M; Paganelli G
INSTITUCIÓN / INSTITUTION: - Unit of Radiometabolic Medicine, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, Italy.
RESUMEN / SUMMARY: - Background: We evaluated the activity and safety profile of (177)Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced G1-G2 pancreatic neuroendocrine tumors (P-NETs). Patients and Methods: Fifty-two consecutive patients were treated at two different therapeutic dosages of 18.5 GBq or 27.8 GBq in five cycles, according to the patient’s kidney function and bone marrow reserve, which are known to be the critical organs in PRRT. Results: Twenty-six patients received a mean full dosage (FD) of 25.5 GBq (range 20.7-27.8) and 26 a mean reduced dosage (RD) of 17.8 GBq (range 11.1-19.9). Both therapeutic dosages resulted in antitumor activity (Disease Control Rate in the entire case series 81%), with 12% complete response (CR), 27% partial response (PR) and 46% stable disease (SD) in the FD group, whereas we observed 4% CR, 15% PR and 58% SD in the RD group. Median progression-free survival (PFS) was not reached in the FD group and was 20 months in the RD group. No major acute or delayed hematological toxicity occurred. Conclusion: Lu-PRRT showed antitumor activity in advanced P-NETs even at a reduced total activity of 18.5 GBq. However, PFS was significantly longer (p = 0.05) after a total activity of 27.8 GBq, which can thus be considered the recommended dosage in eligible patients.
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[94]
TÍTULO / TITLE: - Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 7. doi: 10.1002/ijc.28078.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28078
AUTORES / AUTHORS: - Avan A; Pacetti P; Reni M; Milella M; Vasile E; Mambrini A; Vaccaro V; Caponi S; Cereda S; Peters GJ; Cantore M; Giovannetti E
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
RESUMEN / SUMMARY: - The use of platinated agents in combination chemotherapy regimens for advanced pancreatic cancer is controversial owing to the lack of an outstanding impact on the outcome and a substantial increase in hematologic and extra-hematologic toxicities. Pharmacogenetic studies to identify patients who could benefit most from such therapies are urgently needed. The Xeroderma-Pigmentosum group-D polymorphism at codon-751 (XPD-Lys751Gln) emerged as the most significant independent predictor for death- and progression-risk in our previous study on functional polymorphisms in 122 advanced pancreatic cancer patients treated with cisplatin-docetaxel-capecitabine-gemcitabine and cisplatin-epirubicin-capecitabine-gemcitabine (or EC-GemCap). To confirm the prognostic role of this variable, we further evaluated the correlation of XPD-Lys751Gln with outcome in another 125 patients treated with the same regimens, and 90 treated with gemcitabine monotherapy. Genotyping was successfully carried out in the vast majority of DNA samples. Genotype frequencies followed Hardy-Weinberg equilibrium, and XPD-Lys751Gln was associated with differential progression-free and overall-survival. Multivariate analysis confirmed its prognostic significance in platinum-based regimens. In particular, XPD-Gln751Gln was significantly associated with risk of death (hazard ratio, HR = 1.7, 95% confidence interval [CI], 1.1-2.6, p = 0.011) and risk of progression (HR = 1.7, 95% CI, 1.1-2.5, p = 0.013). No correlation was observed in gemcitabine monotherapy-treated patients. The analysis of DNA damage using extra-long-PCR in lymphocytes supported the association of XPD-Gln751Gln with greater resistance to cisplatin-induced damage. The increasing evidence of XPD-Lys751Gln impact on the outcome of gemcitabine-cisplatin-based polychemotherapy leads to plan prospective studies to validate the role of this polymorphism as a new tool for optimization of the currently available treatments in pancreatic cancer.
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[95]
TÍTULO / TITLE: - miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Feb 21. doi: 10.3892/or.2013.2297.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2297
AUTORES / AUTHORS: - Cai B; An Y; Lv N; Chen J; Tu M; Sun J; Wu P; Wei J; Jiang K; Miao Y
INSTITUCIÓN / INSTITUTION: - Institute of Tumor Biology, Jiangsu Province Academy of Clinical Medicine, Nanjing, Jiangsu 210029, P.R. China.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease and is usually resistant to chemotherapy. MicroRNA181b (miR-181b) has been reported to be associated with chemoresistance in various types of cancer. In this study, we investigated the effects of miR-181b on the chemosensitivity of PDAC cells to gemcitabine and the underlying molecular events. miR-181b mimics and inhibitors were synthesized for transient gene transfection in vitro. Lentivirus carrying miR-181b mimics were used to infect PDAC cells for nude mouse xenograft assays by implanting infected PDAC cells into recipient mice. Cell viability was determined by MTT assays, while gene expression was assessed using qRT-PCR, western blot analysis and enzyme-linked immunosorbent assay (ELISA). miR-181b targeting BCL-2 expression was assessed by a dual-luciferase activity assay. The data showed that miRNA-181b expression sensitized PDAC cells to gemcitabine treatment. Although gemcitabine-resistant PDAC cell sublines (SW1990/GR and CFPAC-1/GR) expressed higher levels of miRNA-181b, gemcitabine induced higher levels of apoptosis in PDAC cells transfected with miRNA-181b mimics. The nude mouse xenograft assay data showed that miR-181b transfection also sensitized the cells to gemcitabine treatment in vivo. Molecularly, bioinformatics data predicted that miR-181b was able to bind to BCL-2 mRNA 3’UTR. The dual luciferase activity assay revealed that miRNA-181b downregulated BCL-2 expression. The results from western blot analysis showed a reduced BCL-2 expression following miR-181b transfection but an enhanced caspase-3 activity in miRNA-181b mimic-transfected PDAC cells. This study demonstrates that miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.
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[96]
TÍTULO / TITLE: - Evolution and dynamics of pancreatic cancer progression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncogene. 2013 Feb 18. doi: 10.1038/onc.2013.29.
●● Enlace al texto completo (gratuito o de pago) 1038/onc.2013.29
AUTORES / AUTHORS: - Yachida S; Iacobuzio-Donahue CA
INSTITUCIÓN / INSTITUTION: - 1] Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA [2] Division of Refractory Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
RESUMEN / SUMMARY: - Efficient metastasis is believed as the result of multiple genetic, epigenetic and/or post-translational events in the lifetime of a carcinoma. At the genetic level, these events may be categorized into those that occur during carcinogenesis, and those that occur during subclonal evolution. This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs, many features of which can be extrapolated to other solid tumor types. The implications of these findings to personalize genome analyses of an individual patient’s tumor are also discussed.Oncogene advance online publication, 18 February 2013; doi:10.1038/onc.2013.29.
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[97]
TÍTULO / TITLE: - The differential diagnosis of squamous cells in pancreatic aspirates: from contamination to adenosquamous carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Cytol. 2013;57(2):139-46. doi: 10.1159/000346326. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1159/000346326
AUTORES / AUTHORS: - Olson MT; Siddiqui MT; Ali SZ
INSTITUCIÓN / INSTITUTION: - Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
RESUMEN / SUMMARY: - BACKGROUND: This study was conducted to describe the frequency and significance of squamous cells in fine needle aspiration (FNA) specimens of the pancreas in benign and malignant processes. METHODS: A retrospective review was performed of 102 patients with squamous cells in their pancreatic FNA specimens from 1986 to 2012. The malignant cases were classified as adenosquamous carcinoma (ASqC) or metastatic squamous cell carcinoma, and a double institutional review of the ASqC cases was undertaken to characterize the clinical and pathological features and survival statistics of patients who present with unresectable or metastatic ASqC and have no follow-up surgery. Survival analyses were performed. RESULTS: Of the 4,094 pancreas FNA procedures performed in the study, squamous features were found in 102 (2.5%) of all cases, and 48% of these cases represented ASqC. The other cases were contamination (52%) or atypical (<1%). ASqC constituted 4.5% (46/1,025) of all primary pancreatic exocrine malignancies. When compared with conventional adenocarcinoma, ASqC demonstrated a significantly poorer overall median survival (11.0 vs. 6.51 months; p = 0.023), and this difference was also seen in patients presenting with metastatic disease (median survival of 9.1 vs. 4.2 months; p = 0.025). CONCLUSIONS: Squamous cells in FNA specimens from the pancreas have a broad differential diagnosis that ranges from contamination to ASqC.
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[98]
TÍTULO / TITLE: - The Differentiation of Pancreatic Tumor-Initiating Cells by Vitronectin Can Be Blocked by Cilengitide.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279d568
AUTORES / AUTHORS: - Cabarcas SM; Sun L; Mathews L; Thomas S; Zhang X; Farrar WL
INSTITUCIÓN / INSTITUTION: - From the *Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick; daggerNational Center for Translational Therapeutics, National Chemical Genomics Center National Human Genome Research Institute, Rockville; double daggerMedImmune, Gaithersburg; and section signSAIC-Frederick Inc, Frederick National Laboratory for Cancer Research, Frederick, MD.
RESUMEN / SUMMARY: - OBJECTIVE: Pancreatic cancer is a leading cancer type and its molecular pathology is poorly understood. The only potentially curative therapeutic option available is complete surgical resection; however, this is inadequate as most of the patients are diagnosed at an advanced or metastatic stage. Tumor-initiating cells (TICs) constitute a subpopulation of cells within a solid tumor that sustain tumor growth, metastasis, and chemo/radioresistance. Within pancreatic cancer, TICs have been identified based on the expression of specific cell surface markers. METHODS: We use a sphere formation assay to enrich putative TICs and use human serum as a driver of differentiation. We demonstrate by using specific blocking reagents that we can inhibit the differentiation process and maintain TIC-associated markers and genes. RESULTS: We can induce differentiation of pancreatospheres with the addition of human serum, and we identified vitronectin as an inducer of differentiation. We inhibit differentiation by human serum using an arginine-glycine-aspartate-specific peptide, which is Cilengitide; hence, demonstrating this differentiation is mediated via specific integrin receptors. CONCLUSIONS: Overall, our studies further the definition of pancreatic TICs and provide further insight into both the maintenance and differentiation of this lethal population.
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[99]
TÍTULO / TITLE: - Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastrointest Endosc. 2013 Mar 21. pii: S0016-5107(13)00097-7. doi: 10.1016/j.gie.2013.01.040.
●● Enlace al texto completo (gratuito o de pago) 1016/j.gie.2013.01.040
AUTORES / AUTHORS: - Wang W; Shpaner A; Krishna SG; Ross WA; Bhutani MS; Tamm EP; Raju GS; Xiao L; Wolff RA; Fleming JB; Lee JH
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Hepatology, and Nutrition, MD Anderson Cancer Center, Houston, Texas, USA.
RESUMEN / SUMMARY: - BACKGROUND: Diagnosis of pancreatic neoplasm is challenging in patients with inconclusive findings on pancreatic multidetector row CT (MDCT). OBJECTIVE: To determine the diagnostic accuracy and to identify predictors of pancreatic neoplasm by EUS with FNA in this setting. DESIGN: Retrospective chart review during the study period of January 2002 to December 2010. SETTING: Tertiary referral center. PATIENTS: Of the 1046 patients who underwent pancreatic EUS, 116 patients were selected because their clinical presentation was suspicious for pancreatic malignancy, but their MDCT findings were inconclusive. INTERVENTION: EUS with FNA. MAIN OUTCOME MEASUREMENTS: Diagnostic yield of malignancy and significance of clinical variables. RESULTS: When surgical pathology or subsequent clinical course was used as the criterion standard, EUS with FNA had a sensitivity, specificity, positive predictive value, and accuracy of 87.3%, 98.3%, 98.5%, and 92.1%, respectively, in diagnosing a pancreatic neoplasm that was indeterminate on MDCT. Factors significantly associated with EUS detection of pancreatic ductal adenocarcinoma were total bilirubin level greater than 2 mg/dL (P < .001), CT finding of pancreatic duct dilation (P < .001), bile duct stricture (P < .001), and tumor size 1.5 cm or larger detected by EUS (P = .004). Among them, pancreatic duct dilation on CT (odds ratio 4.10; 95% confidence interval, 1.52-11.05), and tumor size 1.5 cm or larger detected by EUS (odds ratio 8.46; 95% confidence interval, 2.02-35.45) were independent risk factors. LIMITATIONS: Retrospective design and patient referral bias. CONCLUSIONS: When MDCT is indeterminate, EUS is a highly sensitive and accurate modality for the detection of pancreatic neoplasm, especially when the tumor is smaller than 2.0 cm.
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[100]
TÍTULO / TITLE: - Synthesis and evaluation of cholecystokinin trimers: A multivalent approach to pancreatic cancer detection and treatment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Bioorg Med Chem Lett. 2013 Apr 15;23(8):2422-5. doi: 10.1016/j.bmcl.2013.02.022. Epub 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bmcl.2013.02.022
AUTORES / AUTHORS: - Brabez N; Nguyen KL; Saunders K; Lacy R; Xu L; Gillies RJ; Lynch RM; Chassaing G; Lavielle S; Hruby VJ
INSTITUCIÓN / INSTITUTION: - UPMC Paris 06, UMR 7203, Laboratoire des BioMolecules, Universite P. et M. Curie, 75005 Paris, France; CNRS, UMR 7203, France; ENS, UMR 7203, Departement de Chimie, Ecole Normale Superieure, 75005 Paris, France; University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721, USA.
RESUMEN / SUMMARY: - In the quest for novel tools for early detection and treatment of cancer, we propose the use of multimers targeting overexpressed receptors at the cancer cell surface. Indeed, multimers are prone to create multivalent interactions, more potent and specific than their corresponding monovalent versions, thus enabling the potential for early detection. There is a lack of tools for early detection of pancreatic cancer, one of the deadliest forms of cancer, but CCK2-R overexpression on pancreatic cancer cells makes CCK based multimers potential markers for these cells. In this Letter, we describe the synthesis and evaluation of CCK trimers targeting overexpressed CCK2-R.
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[101]
TÍTULO / TITLE: - Prognosis of Minimally Invasive Carcinoma Arising in Mucinous Cystic Neoplasms of the Pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Surg Pathol. 2013 Apr;37(4):601-605.
●● Enlace al texto completo (gratuito o de pago) 1097/PAS.0b013e318273f3b0
AUTORES / AUTHORS: - Lewis GH; Wang H; Bellizzi AM; Klein AP; Askin FB; Schwartz LE; Schulick RD; Wolfgang CL; Cameron JL; O’Reilly EM; Yu KH; Hruban RH
INSTITUCIÓN / INSTITUTION: - Departments of *Pathology parallelEpidemiology paragraph signOncology **Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD daggerDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX double daggerDepartment of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA section signDepartment of Pathology, Brigham and Women’s Hospital, Boston, MA #Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA daggerdaggerDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
RESUMEN / SUMMARY: - Although patients with surgically resected noninvasive mucinous cystic neoplasms (MCNs) of the pancreas are cured, the behavior of surgically resected minimally invasive adenocarcinomas arising in MCN has not been well established. We report 16 surgically resected MCNs with minimal invasion defined as unifocal or multifocal microscopic invasive adenocarcinoma confined to the ovarian stroma of the MCN without capsular or pancreatic parenchymal invasion. Pathologic findings were correlated with patient demographics, type of surgery, and long-term follow-up. Our study included 15 women and 1 man ranging in age from 25 to 66 years. The patients were followed up for a mean of 48.6 months (range, 12 to 148 mo). The MCNs ranged in size from 3.5 to 25 cm and were all located in the body/tail of the gland. Lymphovascular invasion was not identified in any of the cases, and all lymph nodes were negative for tumor. Ten neoplasms had unifocal invasion, whereas 6 had multifocal invasion. Twelve of the neoplasms were partially submitted for microscopic examination, whereas 4 were submitted entirely. Only 1 of the 16 minimally invasive MCNs recurred, and that tumor had been lighlty sampled pathologically. Our study demonstrates that the majority of patients with minimally invasive adenocarcinoma arising in MCNs are cured by surgery, particularly if the neoplasms are completely examined histologically.
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[102]
TÍTULO / TITLE: - Senescence in pancreatic carcinogenesis: from signalling to chromatin remodelling and epigenetics.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gut. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1136/gutjnl-2012-302793
AUTORES / AUTHORS: - Singh SK; Ellenrieder V
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Philipps University of Marburg, , Marburg, Germany.
RESUMEN / SUMMARY: - Mutational activation of K-Ras is a key genetic event involved in the initiation of pancreatic carcinogenesis. However, K-Ras generally fails to transform precursor lesions into invasive cancers due to activation of powerful fail-safe programmes that counteract transformation and growth. The importance of cellular senescence, a permanent cell growth arrest, is increasingly being recognised as a critical fail-safe programme in pancreatic carcinogenesis. Emerging evidence suggests that oncogene-induced senescence requires transcriptional induction of the CDKN2A gene locus as well as comprehensive chromatin modifications involved in epigenetic silencing of pro-proliferative genes. Moreover, recent work in pancreatic cancer mouse models proposes that inactivation of the CDKN2A tumour suppressor locus is the molecular switch required for senescence evasion and unleashed K-Ras driven malignant transformation in the pancreas.
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[103]
TÍTULO / TITLE: - Molecular analysis of the inhibitory effect of N-acetyl-L-cysteine on the proliferation and invasiveness of pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Jun;24(5):504-18. doi: 10.1097/CAD.0b013e32836009d7.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e32836009d7
AUTORES / AUTHORS: - Mezencev R; Wang L; Xu W; Kim B; Sulchek TA; Daneker GW; McDonald JF
INSTITUCIÓN / INSTITUTION: - aSchool of Biology and the Petit Institute of Bioengineering and Bioscience bThe George W. Woodruff School of Mechanical Engineering cThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta dCancer Treatment Centers of America, Newnan, Georgia, USA.
RESUMEN / SUMMARY: - Preliminary studies have suggested that the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) may be effective in inhibiting the growth of pancreatic cancer cells. In-depth cellular and molecular analyses were carried out to determine NAC’s mode of action in inhibiting the growth of a well-characterized pancreatic cancer cell line (AsPC-1). Standardized assays were used to monitor cellular growth, apoptosis, levels of ROS, cellular senescence, migration, and invasiveness. Cell stiffness was measured using atomic force microscopy. Gene expression was monitored by quantitative PCR. NAC significantly inhibits the growth and metastatic potential of AsPC-1 cells by inducing cell-cycle arrest in G1 and subsequent cellular senescence and decreased invasiveness. These anticancer properties are associated with an unexpected increase in the intracellular concentrations of ROS. NAC does not decrease the susceptibility of AsPC-1 cells to the anticancer drugs gemcitabine, mitomycin C, and doxorubicin. NAC-induced changes in gene expression are consistent with the onset of mesenchymal-to-epithelial transition. In conclusion, our findings indicate that NAC induces an integrated series of responses in AsPC-1 cells that make it a highly promising candidate for development as a pancreatic cancer therapeutic.
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[104]
TÍTULO / TITLE: - A comparison between intraductal papillary neoplasms of the biliary tract (BT-IPMNs) and intraductal papillary mucinous neoplasms of the pancreas (P-IPMNs) reveals distinct clinical manifestations and outcomes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Surg Oncol. 2013 Mar 15. pii: S0748-7983(13)00261-8. doi: 10.1016/j.ejso.2013.02.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejso.2013.02.016
AUTORES / AUTHORS: - Minagawa N; Sato N; Mori Y; Tamura T; Higure A; Yamaguchi K
INSTITUCIÓN / INSTITUTION: - Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) has been increasingly recognized as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas (P-IPMN). However, there is limited information regarding whether BT-IPMNs and P-IPMNs behave in a similar fashion. METHODS: We retrospectively compared clinicopathological variables between 9 patients with BT-IPMN and 44 patients with P-IPMN. RESULTS: There was no significant difference in age between patients with BT-IPMN and those with P-IPMN. The male/female ratio was significantly higher in patients with P-IPMN than in those with BT-IPMN (P = 0.012). Clinical presentation with jaundice was more common in patients with BT-IPMN (67%) than in those with P-IPMN (4.5%, P = 0.002). In addition, serum levels of CEA and CA19-9 were higher in patients with BT-IPMN than in those with P-IPMN (P = 0.019 and P = 0.002, respectively). The pathological diagnosis of malignancy was significantly more common in patients with BT-IPMN (89%) than in those with P-IPMN (23%, P = 0.002). The association with invasive carcinoma was significantly more frequent in patients with BT-IPMN (44.4%) than in those with P-IPMN (6.8%, P = 0.008). Furthermore, survival time after surgical resection was significantly shorter in patients with BT-IPMN than in those with P-IPMN (P = 0.002). CONCLUSION: These findings reveal differences in clinicopathological features and prognosis between BT-IPMN and P-IPMN, thereby suggesting distinct biological pathways underlying the pathogenesis of these neoplasms.
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[105]
TÍTULO / TITLE: - Systemic delivery of gemcitabine triphosphate via LCP nanoparticles for NSCLC and pancreatic cancer therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomaterials. 2013 Apr;34(13):3447-58. doi: 10.1016/j.biomaterials.2013.01.063. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.biomaterials.2013.01.063
AUTORES / AUTHORS: - Zhang Y; Kim WY; Huang L
INSTITUCIÓN / INSTITUTION: - Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7571, USA.
RESUMEN / SUMMARY: - Nucleoside analogs are a significant class of anti-cancer agent. As prodrugs, they terminate the DNA synthesis upon transforming to their active triphosphate metabolites. We have encapsulated a biologically activate nucleotide analog (i.e. gemcitabine triphosphate (GTP)), instead of the nucleoside (i.e. gemcitabine) derivative, into a novel Lipid/Calcium/Phosphate nanoparticle (LCP) platform. The therapeutic efficacy of LCP-formulated GTP was evaluated in a panel of human non-small-cell lung cancer (NSCLC) and human pancreatic cancer models after systemic administrations. GTP-loaded LCPs induced cell death and arrested the cell cycle in the S phase. In vivo efficacy studies showed that intravenously injected GTP-loaded LCPs triggered effective apoptosis of tumor cells, significant reduction of tumor cell proliferation and cell cycle progression, leading to dramatic inhibition of tumor growth, with little in vivo toxicity. Broadly speaking, the current study offers preclinical proof-of-principle that many active nucleotide or phosphorylated nucleoside analogs could be encapsulated in the LCP nanoplatform and delivered systemically for a wide variety of therapeutic applications.
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[106]
TÍTULO / TITLE: - MicroRNA-100 regulates IGF1-receptor expression in metastatic pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biotech Histochem. 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 3109/10520295.2012.762460
AUTORES / AUTHORS: - Huang J; Egger M; Grizzle W; McNally L
INSTITUCIÓN / INSTITUTION: - University of Louisville , Louisville , Kentucky.
RESUMEN / SUMMARY: - Patients with pancreatic adenocarcinoma have the lowest 5 year survival rate and yearly rates of incidence are nearly equal to the mortality rates. Long term cure rates by standard therapies are disappointing owing to disseminated disease at diagnosis and chemotherapeutic resistance. New therapeutic targets are necessary to decrease the progression of pancreatic cancer and the ability to identify targets specific to metastasis would improve patient care. We evaluated the levels of microRNA of metastatic and non-metastatic cell lines. The expression levels of microRNAs and mRNAs were determined using microarray analysis to examine and compare five pancreatic cancer cell lines, two that can metastasize in vivo (S2VP10 and S2CP9) and three that do not metastasize (MiaPaCa2, Panc-1 and ASPC-1). MicroRNA analysis indicated an increase in miR-100 and a decrease in miR-138 expression in metastatic cancer cells. Microarray analysis of different expressions of mRNAs in metastatic and non-metastatic pancreatic cell lines also indicated significantly increased insulin growth factor-1 receptor (IGF1-R) expression in metastatic pancreatic cancer cell lines compared to non-metastatic pancreatic cancer cell lines. To confirm microarray analysis results, western blot and immunocytochemistry were performed. Western blot revealed that IGF1-R expression exhibited in metastatic cancer cell lines a seven-fold increase compared to non-metastatic cell lines. In addition, downstream expressions of the proteins, GRB2 and phosphorylated PI3K, also were increased in aggressive cancer cell lines. Immunocytochemistry confirmed the linkage of IGF1-R to miR-100, because cells transfected with miR-100 inhibitor showed a decrease in IGF1-R. Cells transfected with a miR-138 mimic, however, did not affect IGF1-R expression.
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[107]
TÍTULO / TITLE: - Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Feb 13.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0679-1
AUTORES / AUTHORS: - Rong Y; Wu W; Ni X; Kuang T; Jin D; Wang D; Lou W
INSTITUCIÓN / INSTITUTION: - Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan University, 180th Feng Lin Road, Shanghai, 200031, China.
RESUMEN / SUMMARY: - The prognosis for pancreatic cancer is very poor, and developing new therapeutic strategies for this cancer is needed. Recently, the Warburg effect (aerobic glycolysis) has attracted much attention for its function in the tumorigenesis. Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression. However, the function of LDHA in pancreatic cancer has not been studied. Here, we found that the expression of LDHA was elevated in the clinical pancreatic cancer samples. Forced expression of LDHA promoted the growth of pancreatic cancer cells, while knocking down the expression of LDHA inhibited cell growth dramatically. Moreover, silencing the expression of LDHA inhibited the tumorigenicity of pancreatic cancer cells in vivo. Mechanistically, knocking down the expression of LDHA activated apoptosis pathway. Taken together, our study revealed the oncogenic role of LDHA in pancreatic cancer and suggested that LDHA might be a potential therapeutic target.
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[108]
TÍTULO / TITLE: - The gep Proto-Oncogene Galpha13 Mediates Lysophosphatidic Acid-Mediated Migration of Pancreatic Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279c577
AUTORES / AUTHORS: - Gardner JA; Ha JH; Jayaraman M; Dhanasekaran DN
INSTITUCIÓN / INSTITUTION: - From the *Penn State Milton S. Hershey Medical Center, Hershey, PA; daggerCollege of Pharmacy, Seoul National University, Seoul, Republic of Korea; and double daggerPeggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
RESUMEN / SUMMARY: - OBJECTIVES: Tumor microenvironment, defined by a variety of growth factors including lysophosphatidic acid (LPA), whose levels are increased in pancreatic cancer patients, plays a major role in the genesis and progression of pancreatic cancer. Because the gep proto-oncogenes, Galpha12 and Galpha13, are implicated in LPA-stimulated oncogenic signaling, this study is focused on evaluating the role of these proto-oncogenes in LPA-stimulated invasive migration of pancreatic cancer cells. METHODS: Effect of LPA on the migration and proliferation of pancreatic cancer cells was assessed using BxPC3, Dan-G, MDAPanc-28, Panc-1, and PaCa-2 cell lines. The role of Galpha13 in the migration of pancreatic cancer cells was interrogated by disrupting lysophosphatidic acid receptor-Galpha13 interaction using CT13, a dominant negative mutant of Galpha13, and by silencing the expression of Galpha13. RESULTS: Results indicate that LPA stimulates the migration of pancreatic cancer cells and such LPA-stimulated migratory response is mediated by Galpha13. Furthermore, the results establish that the silencing of Galpha13, but not Galpha12, abrogates LPA-stimulated invasive migration of pancreatic cancer cells. CONCLUSIONS: These results report for the first time a critical role for Galpha13 in LPA-stimulated invasive migration of pancreatic cancer cells. These findings identify LPA-lysophosphatidic acid receptor-Galpha13 signaling node as a novel therapeutic target for pancreatic cancer treatment and control.
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[109]
TÍTULO / TITLE: - Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 10. pii: S0304-3835(13)00119-5. doi: 10.1016/j.canlet.2013.01.054.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.01.054
AUTORES / AUTHORS: - Yabuuchi S; Pai SG; Campbell NR; de Wilde RF; De Oliveira E; Korangath P; Streppel MM; Rasheed ZA; Hidalgo M; Maitra A; Rajeshkumar NV
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: s1-yabuuchi@surg1.med.tohoku.ac.jp.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDA) remains a lethal human malignancy with historically limited success in treatment. The role of aberrant Notch signaling, which requires the constitutive activation of gamma-secretase, in the initiation and progression of PDA is well defined and inhibitors of this pathway are currently in clinical trials. Here we investigated the in vivo therapeutic effect of PF-03084014, a selective gamma-secretase inhibitor, alone and in combination with gemcitabine in pancreatic cancer xenografts. PF-03084014 treatment inhibited the cleavage of nuclear Notch 1 intracellular domain and Notch targets Hes-1 and Hey-1. Gemcitabine treatment showed good response but not capable of inducing tumor regressions and targeting the tumor-resident cancer stem cells (CD24(+)CD44(+) and ALDH(+) tumor cells). A combination of PF-03084014 and gemcitabine treatment resulted tumor regression in 3 of 4 subcutaneously implanted xenograft models. PF-03084014, and in combination with gemcitabine reduced putative cancer stem cells, indicating that PF-03084014 target the especially dangerous and resilient cancer stem cells within pancreatic tumors. Tumor re-growth curves plotted after drug treatments demonstrated that the effect of the combination therapy was sustainable than that of gemcitabine. Notably, in a highly aggressive orthotopic model, PF-03084014 and gemcitabine combination was effective in inducing apoptosis, inhibition of tumor cell proliferation and angiogenesis, resulting in the attenuation of primary tumor growth as well as controlling metastatic dissemination, compared to gemcitabine treatment. In summary, our preclinical data suggest that PF-03084014 has greater anti-tumor activity in combination with gemcitabine in PDA and provides rationale for further investigation of this combination in PDA.
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[110]
TÍTULO / TITLE: - Interfractional dose variations in the stomach and the bowels during breathhold intensity-modulated radiotherapy for pancreatic cancer: Implications for a dose-escalation strategy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Phys. 2013 Feb;40(2):021701. doi: 10.1118/1.4773033.
●● Enlace al texto completo (gratuito o de pago) 1118/1.4773033
AUTORES / AUTHORS: - Nakamura A; Shibuya K; Nakamura M; Matsuo Y; Shiinoki T; Nakata M; Mizowaki T; Hiraoka M
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology and Image-applied Therapy, Kyoto University, Kyoto, Japan.
RESUMEN / SUMMARY: - PURPOSE: This study aims to evaluate the interfractional dose variations in the organs-at-risk (OARs) during pancreatic breathhold intensity-modulated radiotherapy (IMRT) and to assess the impacts of “planning organs-at-risk volume” (POV) structures generated by isotropically expanding the dose-limiting OARs, based on the comparison of the interfractional doses to the OARs between IMRT plans and conventional three-dimensional-conformal radiotherapy (3D-CRT) plans. METHODS: Thirty repeat CT scans were acquired from ten consecutive patients who were receiving chemoradiotherapy for pancreatic cancer. Six IMRT plans for each patient with two levels of prescription (45 and 51 Gy in 15 fractions) and 3 POV margin sizes (5, 7, and 10 mm) were generated based on the initial CT scan under predetermined constraints. Two 3D-CRT plans (39 and 42 Gy in 15 fractions) were simultaneously generated. The dose distribution of all of the treatment plans was recalculated with the repeat CT scans. The interfractional dose variations in the three OARs (stomach, duodenum, and small intestine) were evaluated, and the absolute volumes >/=39 Gy (V39Gy) of the OARs in the IMRT plans were compared to those in the 3D-CRT plans. Regression analyses were performed to assess the relative impact of the factors of interest on the interfractional dose variations of the OARs. RESULTS: Substantial dose excesses to the three OARs were observed at all of the prescription dose levels and the POV margin sizes on the repeat CT scans. The safety threshold based on the mean stomach V39Gy on the recalculated 39 Gy-3D-CRT plans was 1.9 ml. Statistically significant and marginally insignificant mean V39Gy values above the safety thresholds were observed in the stomach in the 51 Gy-IMRT plans (2.6 and 2.1 ml with the 5- and 7-mm PRV margins, respectively (P = 0.015 and 0.085)). Only in the case of the 10-mm POV margin did the metric fall below the safety threshold to 1.5 ml (P = 0.634). The duodenum and the small intestine did not violate the safety thresholds (1.4 and 3.8 ml, respectively). From the multiple regression analyses, only the margin size (P < 0.001) and the POV V39Gy (P < 0.001) were significantly associated with the distribution of recalculated V39Gy for the stomach. Multiple factors, including the margin size (P = 0.020) and the POV V39Gy (P < 0.001) were associated with the recalculated V39Gy for the duodenum. However, none of the POV parameters for the small intestine were associated with the recalculated V39Gy. CONCLUSIONS: Considerable interfractional dose variation was observed in three critical OARs. At the escalated prescription dose of breathhold IMRT, the dose variations could exceed the dose variations using 3D-CRT at the safe prescription dose level, indicating that a dose-escalation strategy based solely on the initial advantageous dose distribution in a breathhold IMRT can be problematic. Given the current limitations for predicting or coping with variation throughout the treatment course, the use of POV should be considered for safely delivering escalated doses to patients with pancreatic cancer.
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[111]
TÍTULO / TITLE: - ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mod Pathol. 2013 Mar 15. doi: 10.1038/modpathol.2013.40.
●● Enlace al texto completo (gratuito o de pago) 1038/modpathol.2013.40
AUTORES / AUTHORS: - Agaimy A; Erlenbach-Wunsch K; Konukiewitz B; Schmitt AM; Rieker RJ; Vieth M; Kiesewetter F; Hartmann A; Zamboni G; Perren A; Kloppel G
INSTITUCIÓN / INSTITUTION: - Institute of Pathology, University Hospital, Erlangen, Germany.
RESUMEN / SUMMARY: - The human insulin gene enhancer-binding protein islet-1 (ISL1) is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. Recent studies identified ISL1 as a marker for pancreatic well-differentiated neuroendocrine neoplasms. However, little is known about ISL1 expression in pancreatic poorly differentiated and in extrapancreatic well and poorly differentiated neuroendocrine neoplasms. We studied the immunohistochemical expression of ISL1 in 124 neuroendocrine neoplasms. Among pancreatic neuroendocrine neoplasms, 12/13 with poor differentiation were negative, whereas 5/7 with good differentiation but a Ki67 >20% were positive. In extrapancreatic neuroendocrine neoplasms, strong positivity was found in Merkel cell carcinomas (25/25), pulmonary small cell neuroendocrine carcinomas (21/23), medullary thyroid carcinomas (9/9), paragangliomas/pheochromocytomas (6/6), adrenal neuroblastomas (8/8) and head and neck neuroendocrine carcinomas (4/5), whereas no or only weak staining was recorded in pulmonary carcinoids (3/15), olfactory neuroblastomas (1/4) and basaloid head and neck squamous cell carcinomas (0/15). ISL1 stained the neuroendocrine carcinoma component of 5/8 composite carcinomas and also normal neuroendocrine cells in the thyroid, adrenal medulla, stomach and colorectum. Poorly differentiated neuroendocrine neoplasms, regardless of their ISL1 expression, were usually TP53 positive. Our results show the almost ubiquitous expression of ISL1 in extrapancreatic poorly differentiated neuroendocrine neoplasms and neuroblastic malignancies and its common loss in pancreatic poorly differentiated neuroendocrine neoplasms. These findings modify the role of ISL1 as a marker for pancreatic neuroendocrine neoplasms and suggest that ISL1 has a broader involvement in differentiation and growth of neuroendocrine neoplasms than has so far been assumed.Modern Pathology advance online publication, 15 March 2013; doi:10.1038/modpathol.2013.40.
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[112]
TÍTULO / TITLE: - Sunitinib for the Treatment of Metastatic Paraganglioma and Vasoactive Intestinal Polypeptide-Producing Tumor (VIPoma).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar;42(2):348-52. doi: 10.1097/MPA.0b013e31825c53fa.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825c53fa
AUTORES / AUTHORS: - Bourcier ME; Vinik AI
INSTITUCIÓN / INSTITUTION: - From the Strelitz Diabetes Center and Neuroendocrine Unit, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA.
RESUMEN / SUMMARY: - OBJECTIVES: Gastroenteropancreatic neuroendocrine tumors (NETs) are rare tumors of the endocrine and nervous systems. Whereas early surgical resection can significantly reduce tumor mass, there are few data available concerning the control of hormonal secretion and associated symptoms. Studies have shown that the tyrosine kinase inhibitor sunitinib significantly prolongs progression-free survival in patients with pancreatic NETs. Here, we present 2 case reports of sunitinib in patients with different types of NETs. METHODS: The patients were a 12-year-old boy with metastatic vasoactive intestinal polypeptide-producing tumor (VIPoma) and a 70-year-old woman with metastatic paraganglioma/NET. Both were treated in an outpatient clinical setting. Sunitinib was titrated to 37.5 mg on a continuous daily dosing schedule in the patient with VIPoma, and the dose was 50 mg/d (4 weeks on, 2 weeks off) in the patient with the paraganglioma/NET. RESULTS: The patient with the paraganglioma/NET had a confirmed complete radiographic response and the patient with VIPoma had a confirmed partial response (Response Evaluation Criteria in Solid Tumors). In both patients, improvements were observed in biochemical tumor markers, clinical responses, and quality of life. CONCLUSIONS: In these patients, sunitinib reduced biochemical markers and stabilized or reduced tumor bulk and may therefore be a potential therapeutic option for these tumor types.
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[113]
TÍTULO / TITLE: - EpCAM-associated claudin-7 supports lymphatic spread and drug resistance in rat pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Cancer. 2013 Feb 6. doi: 10.1002/ijc.28085.
●● Enlace al texto completo (gratuito o de pago) 1002/ijc.28085
AUTORES / AUTHORS: - Thuma F; Zoller M
INSTITUCIÓN / INSTITUTION: - Department of Tumor Cell Biology, University Hospital of Surgery, Heidelberg, Germany.
RESUMEN / SUMMARY: - Pancreatic cancer has a dismal prognosis because of early metastatic spread, a suggested feature of cancer-initiating cells (CIC). To control for a functional contribution of the pancreatic CIC-marker EpCAM, we explored metastasis formation by a stable EpCAM-knockdown (ASML-EpCkd ) of the rat pancreatic adenocarcinoma line BSp73ASML (ASMLwt ). As EpCAM associates with claudin-7, an ASML-claudin-7-knockdown (ASML-cld7kd ) was included to differentiate between EpC- and EpC-cld7-mediated effects. The metastatic capacity of ASML-EpCkd and more pronounced ASML-cld7kd cells is strikingly reduced. EpC-associated cld7 interferes with EpC-mediated cell-cell adhesion and supports migration. This requires cld7 phosphorylation and formation of an EpC-cld7-tetraspanin-alpha6beta4 complex in glycolipid-enriched membrane domains (GEM), where cld7 associates via the tetraspanin-alpha6beta4 complex with phosphorylated ezrin. The association of cld7 with alpha6beta4 and cytoskeleton strongly stimulates tumor cell migration. However, EpC does not actively contribute. Instead, GEM-located cld7 associates with presenilin-2, which facilitates EpC cleavage and thereby tumor cell proliferation. Finally, the EpC-cld7 complex promotes drug resistance. Both EpC and cld7 support MAPK and JNK activation, such that in ASML-EpCkd and ASML-cld7kd cells an undue expansion of proapoptotic molecules is observed. Only cld7 promotes activation of the PI3K/Akt pathway by a strong downregulation of Pten. Accordingly, cisplatin treatment prolongs the survival time of ASML-cld7kd -bearing rats. Taken together, cld7 supports tumorigenic features of EpC by provoking EpC cleavage and thereby its cotranscription factor activity. On the other hand, only cld7 is directly engaged in motility and apoptosis resistance. Thus, at least in concern of migrating CIC, it is cld7 that acts as a CIC biomarker.
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[114]
TÍTULO / TITLE: - Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Apr;42(3):429-35. doi: 10.1097/MPA.0b013e318264d073.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318264d073
AUTORES / AUTHORS: - Yu R; Jih L; Zhai J; Nissen NN; Colquhoun S; Wolin E; Dhall D
INSTITUCIÓN / INSTITUTION: - From the *Division of Endocrinology,Departments of daggerPathology, double daggerSurgery, and section signDivision of Oncology, Cedars-Sinai Medical Center, Los Angeles, CA.
RESUMEN / SUMMARY: - OBJECTIVE: The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. METHODS: This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. RESULTS: Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. CONCLUSIONS: Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.
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[115]
TÍTULO / TITLE: - Recurrent pancreatitis caused by pancreatic ductal villous adenoma treated with endoscopic snare polypectomy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endoscopy. 2013;45 Suppl 2 UCTN:E23-4. doi: 10.1055/s-0032-1326108. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326108
AUTORES / AUTHORS: - Ramesh J; Council L; Wilcox CM
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. j1ramesh@gmail.com
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[116]
TÍTULO / TITLE: - Inhibition of AKT in Human Pancreatic, Renal and Colorectal Cancer Cells by Four Cardiac Hormones.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Mar;33(3):785-90.
AUTORES / AUTHORS: - Skelton WP 4th; Skelton M; Vesely DL
INSTITUCIÓN / INSTITUTION: - Director, USF Cardiac Hormone Center, J.A. Haley Veterans Medical Center-151, 13000 Bruce B. Downs Blvd., Tampa, FL 33612, U.S.A. david.vesely@va.gov.
RESUMEN / SUMMARY: - BACKGROUND: Protein kinase-B (AKT) is a serine/threonine protein kinase that has a key role in cell proliferation and cancer cell invasiveness. Four cardiac peptide hormones, namely vessel dilator, atrial natriuretic peptide (ANP), kaliuretic peptide, and long-acting natriuretic peptide (LANP) have anticancer effects both in vitro and in vivo. MATERIALS AND METHODS: Four cardiac hormones were examined for their ability to inhibit AKT, measured with a solid-phase enzyme-linked immunosorbent assay (ELISA) in human colorectal, pancreatic, and renal cancer cells. RESULTS: Vessel dilator, kaliuretic peptide, ANP, and LANP maximally reduced the concentration of AKT by 47%, 45%, 52%, and 46% in human colorectal cancer cells (p<0.0001), by 60%, 61%, 64%, and 59% in human pancreatic carcinoma cells (p<0.0001), and by 31%, 32%, 31%, and 31% in renal adenocarcinoma cells (p<0.001). CONCLUSION: These four cardiac hormones are significant inhibitors of AKT in human cancer cells, as part of their anticancer mechanism(s) of action.
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[117]
TÍTULO / TITLE: - PI3K/Akt/mTOR pathway inhibitors in the therapy of pancreatic neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 16. pii: S0304-3835(13)00128-6. doi: 10.1016/j.canlet.2013.02.016.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.016
AUTORES / AUTHORS: - Wolin EM
INSTITUCIÓN / INSTITUTION: - Division of Hematology/Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA. Electronic address: edward.wolin@cshs.org.
RESUMEN / SUMMARY: - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is implicated in the pathogenesis of pancreatic neuroendocrine tumors (pNETs). Activation of this pathway is driven by aberrant tyrosine kinase receptor activities. Mutations in the PI3K/Akt/mTOR pathway occur in 15% of pNETs, and expression of genes of the PI3K/Akt/mTOR pathway is altered in the majority of pNETs. The mTOR inhibitor everolimus has been approved by the FDA for the treatment of pNET, but its efficacy may be limited by its inability to prevent mTORC2-mediated activation of Akt. Specific inhibitors of PI3K, Akt, or other pathway nodes, and their concomitant use with mTOR inhibitors, or agents with dual activity, may be more effective. Preclinical studies demonstrate that inhibitors of the PI3K pathway have antitumor activity in pNET cells, either through direct inhibition of individual pathway nodes or indirect inhibition of molecular chaperones such as heat-shock protein 90. Clinical studies are underway evaluating individual node and dual node inhibitors.
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[118]
TÍTULO / TITLE: - Differential ezrin and phosphorylated ezrin expression profiles between pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and invasive ductal carcinoma of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hum Pathol. 2013 Mar 1. pii: S0046-8177(12)00449-2. doi: 10.1016/j.humpath.2012.12.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.humpath.2012.12.001
AUTORES / AUTHORS: - Oda Y; Aishima S; Morimatsu K; Hayashi A; Shindo K; Fujino M; Mizuuchi Y; Hattori M; Tanaka M; Oda Y
INSTITUCIÓN / INSTITUTION: - Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
RESUMEN / SUMMARY: - Intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanINs) are important premalignant lesions of pancreatic cancer. Ezrin is a member of the ezrin, radixin, and moesin protein family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton. We investigated the roles of ezrin during carcinogenesis in IPMN and invasive ductal carcinoma and examined whether ezrin was a prognostic factor. We examined ezrin and phosphorylated ezrin (p-ezrin) expression in 131 IPMNs, 47 PanINs, and 59 invasive ductal carcinomas by immunohistochemical staining. Ezrin and p-ezrin (tyr354) expressions were significantly higher in IPMN with an associated invasive carcinoma, compared with those in IPMN with high-grade dysplasia (P = .03 and P = .0007, respectively). In all grades of PanINs, ezrin and p-ezrin (tyr353) were highly expressed. In patients with invasive ductal carcinoma, the presence of PanIN-2 or PanIN-3 was significantly correlated with positive ezrin and p-ezrin (tyr353) expression of the invasive ductal carcinoma component (P = .01 and P = .0004). The negative p-ezrin (tyr353) expression group of invasive ductal carcinoma showed a significantly worse prognosis than did the positive p-ezrin (tyr353) expression group by survival analysis (P = .04) and was a statistically significant adverse prognostic factor by both univariate and multivariate analyses (P = .048 and P = .015). Ezrin phosphorylation sites differ between the developments of IPMN and PanIN. Although p-ezrin (tyr354) expression in IPMNs is associated with tumor invasion, p-ezrin (tyr353) expression in invasive ductal carcinoma plays an important role not in tumor invasion and metastasis but in the early development of PanINs.
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[119]
TÍTULO / TITLE: - Proton therapy with concomitant capecitabine for pancreatic and ampullary cancers is associated with a low incidence of gastrointestinal toxicity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Oncol. 2013 Apr;52(3):498-505. doi: 10.3109/0284186X.2012.762997.
●● Enlace al texto completo (gratuito o de pago) 3109/0284186X.2012.762997
AUTORES / AUTHORS: - Nichols RC Jr; George TJ; Zaiden RA Jr; Awad ZT; Asbun HJ; Huh S; Ho MW; Mendenhall NP; Morris CG; Hoppe BS
INSTITUCIÓN / INSTITUTION: - University of Florida Proton Therapy Institute , Jacksonville, Florida , USA.
RESUMEN / SUMMARY: - Abstract Background. To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution. Material and methods. From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE. Results. Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure. Discussion. Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.
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[120]
TÍTULO / TITLE: - Evaluation of Clinical Meaning of Histological Subtypes of Intraductal Papillary Mucinous Neoplasm of the Pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827cddbc
AUTORES / AUTHORS: - Kang MJ; Lee KB; Jang JY; Han IW; Kim SW
INSTITUCIÓN / INSTITUTION: - From the *Department of Surgery and Cancer Research Institute and daggerDepartment of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
RESUMEN / SUMMARY: - OBJECTIVES: Prognostic value of histological subtypes of pancreatic intraductal papillary mucinous neoplasm (IPMN) has been reported to have conflicting results. The authors investigated the clinicopathological characteristics and prognostic significance of the histological subtypes of IPMNs with various degrees of dysplasia. METHODS: Two hundred thirteen patients with surgically treated pancreatic IPMN at a single tertiary care referral center were included. Pathological slides were thoroughly reviewed by a specialized pathologist. RESULTS: Of the 213 patients, 38 low-grade, 97 intermediate-grade, and 18 high-grade dysplasia and 59 IPMNs with an associated invasive carcinoma (invasive IPMN) were identified. Histological subtypes consisted of 135 gastric (63.4%), 38 intestinal (17.8%), 38 pancreatobiliary (17.8%), and 2 oncocytic types (0.9%). Histological subtypes were associated with radiological type (P < 0.001), degree of dysplasia (P < 0.001), and T stage (P < 0.001). The proportions of invasive IPMN were 14.1%, 42.1%, 57.9%, and 100% of gastric, intestinal, pancreatobiliary, and oncocytic types, respectively. Disease-specific survival was not affected by histological subtype in overall patients (P = 0.881). For invasive IPMNs, histological subtypes had a marginal significance on survival (P = 0.050), which lost statistical significance after multivariate analysis (P = 0.341). CONCLUSIONS: Although histological subtypes are associated with the degree of dysplasia, histological subtypes have limited prognostic value for pancreatic IPMNs.
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[121]
TÍTULO / TITLE: - Protein-bound polysaccharide decreases invasiveness and proliferation in pancreatic cancer by inhibition of hedgehog signaling and HIF-1alpha pathways under hypoxia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Feb 26. pii: S0304-3835(13)00167-5. doi: 10.1016/j.canlet.2013.02.041.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.02.041
AUTORES / AUTHORS: - Onishi H; Morisaki T; Nakao F; Odate S; Morisaki T; Katano M
INSTITUCIÓN / INSTITUTION: - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: ohnishi@surg1.med.kyushu-u.ac.jp.
RESUMEN / SUMMARY: - To develop an effective therapeutic approach to pancreatic ductal adenocarcinoma (PDAC), we focused on the antitumor mechanism of protein-bound polysaccharide (PSK) under hypoxia. PSK decreased proliferation in PDAC cells under hypoxia but not normoxia. PSK also showed anti-tumor effects in vivo, inhibited invasiveness of PDAC cells, and decreased the expression of HIF-1alpha and hedgehog (Hh) signaling-related molecules under hypoxia. Inhibition of HIF-1alpha and Hh signaling reduced proliferation and invasiveness in PDAC cells under hypoxia. In conclusion, we found new PSK-related pathways in invasiveness and proliferation in PDAC under hypoxia. PSK may be a promising therapeutic drug to treat refractory PDAC.
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[122]
TÍTULO / TITLE: - MTA2 expression is a novel prognostic marker for pancreatic ductal adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Tumour Biol. 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s13277-013-0685-3
AUTORES / AUTHORS: - Chen DW; Fan YF; Li J; Jiang XX
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, The PLA 117 Hospital, No. 14, Lingyin Rd., Hangzhou, 310013, China.
RESUMEN / SUMMARY: - The aim of this study was to detect MTA2 expression in pancreatic ductal adenocarcinoma (PDA) and to analyze its association with prognosis of PDA patients. MTA2 mRNA and protein expression were determined by real-time quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry in specimens of primary cancer and their adjacent noncancerous tissues in PDA patients. We found that MTA2 mRNA and protein expression levels were both significantly upregulated in PDA lesions compared with adjacent noncancerous tissues. Immunohistochemistry showed that high MTA2 expression was correlated with poor tumor differentiation, TNM stage, and lymph node metastasis. Kaplan-Meier survival analysis showed that patients with high expression levels of MTA2 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high MTA2 protein expression was an independent prognostic factor for PDA patients. Our study suggests that overexpression of MTA2 may play an important role in the progression of PDA and MTA2 expression may serve as a biomarker for poor prognosis for PDA.
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[123]
TÍTULO / TITLE: - FDG PET/CT Detects Clinically Occult Pancreatic Cancer in a Case of Von Hippel-Lindau Syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31826c0de9
AUTORES / AUTHORS: - Kulkarni M; Purandare N; Zade A; Agrawal A; Shah S; Rangarajan V
INSTITUCIÓN / INSTITUTION: - From the Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Parel, Mumbai, India.
RESUMEN / SUMMARY: - Von Hippel-Lindau (VHL) disease is a rare, inherited, multisystem disorder that is characterized by development of a variety of benign and malignant tumors. We report an incidental detection of clinically occult pancreatic malignancy on FDG PET/CT in a patient of VHL who underwent restaging for a previously treated endolymphatic sac tumor.
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[124]
TÍTULO / TITLE: - Metastatic Pancreatic Insulinoma with Treatment-limiting Thrombocytopenia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am Surg. 2013 Mar;79(3):124-6.
AUTORES / AUTHORS: - Nguyen AH; Donahue TR
INSTITUCIÓN / INSTITUTION: - Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
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[125]
TÍTULO / TITLE: - Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Cell Physiol. 2013 Mar 4. doi: 10.1002/jcp.24343.
●● Enlace al texto completo (gratuito o de pago) 1002/jcp.24343
AUTORES / AUTHORS: - Gilabert M; Vaccaro MI; Fernandez-Zapico ME; Calvo EL; Turrini O; Secq V; Garcia S; Moutardier V; Lomberk G; Dusetti N; Urrutia R; Iovanna JL
INSTITUCIÓN / INSTITUTION: - Cancer Research Center of Marseille, Inserm U1068; Institut Paoli-Calmettes; Aix-Marseille University; CNRS, UMR7258, F-13288, Marseille, France.
RESUMEN / SUMMARY: - We hypothesized that inhibiting molecules that mediate the adaptation response to cellular stress can antagonize the resistance of pancreatic cancer cells to chemotherapeutic drugs. Toward this end, here, we investigated how VMP1, a stress-induced autophagy-associated protein, modulate stress responses triggered by chemotherapeutic agents in PDAC. We find that VMP1 is particularly over-expressed in poorly differentiated human pancreatic cancer. Pharmacological studies show that drugs that work, in part, via the endoplasmic reticulum stress response, induce VMP1 expression. Similarly, VMP1 is induced by known endoplasmic reticulum stress activators. Genetic inactivation of VMP1 using RNAi-based antagonize the pancreatic cancer stress response to antitumoral agents. Functionally, we find that VMP1 regulates both autophagy and chemotherapeutic resistance even in the presence of chloroquin, ATG5 or Beclin 1 siRNAs, or a Beclin 1-binding VMP1 mutant. In addition, VMP1 modulates endoplasmic reticulum stress independently of its coupling to the molecular and cellular autophagy machinery. Preclinical studies demonstrate that xenografts expressing an inducible and tractable form of VMP1 show increased resistance to the gemcitabine treatment. These results underscore a novel role for VMP1 as a potential therapeutic target for combinatorial therapies aimed at sensitizing pancreatic cancer cells to chemotherapeutic agents as well as provide novel molecular mechanisms to better understand this phenomenon. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
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[126]
TÍTULO / TITLE: - Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Mar 14;19(10):1582-92. doi: 10.3748/wjg.v19.i10.1582.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i10.1582
AUTORES / AUTHORS: - Tang XP; Tang GD; Fang CY; Liang ZH; Zhang LY
INSTITUCIÓN / INSTITUTION: - Xi-Ping Tang, Guo-Du Tang, Chun-Yun Fang, Zhi-Hai Liang, Lu-Yi Zhang, Department of Gastroenterology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
RESUMEN / SUMMARY: - AIM: To investigate the effects of ginsenoside Rh2 on the human pancreatic cancer cell line Bxpc-3. METHODS: The human pancreatic cancer cell line Bxpc-3 was cultured in vitro and treated with or without ginsenoside Rh2. Growth rates for Bxpc-3 cells were assessed by methyl thiazolyl tetrazolium (MTT) and colony formation assays. Cell cycle changes were analyzed by flow cytometry. Apoptosis was measured by flow cytometry and Hoechst 33258 fluorescence staining. A scratch assay and a Matrigel invasion assay were used to detect cell migration and invasion. Expression of Bax, Bcl-2, survivin, cyclin D1, matrix metalloproteinase (MMP)-2, MMP-9, cleaved caspase-3, caspase-8, and caspase-9 mRNA were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Bax, Bcl-2, survivin, cyclin D1, cleaved caspase-3, caspase-8 and caspase-9 protein levels were examined by western blotting. Expression of MMP-2 and MMP-9 proteins in culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Rh2 significantly inhibited Bxpc-3 cell proliferation in a dose- and time-dependent manner, as evaluated by the MTT (P < 0.05) and colony formation assays (P < 0.05). Compared to the control group, Rh2 significantly increased the percentage of Bxpc-3 cells in the G0/G1 phase from 43.32% +/- 2.17% to 71.32% +/- 1.16%, which was accompanied by a decrease in S phase (from 50.86% +/- 1.29% to 28.48% +/- 1.18%) and G2/M phase (from 5.81% +/- 1.19% to 0.20% +/- 0.05%) in a dose-dependent manner (P < 0.05), suggesting that Rh2 arrested cell cycle progression at the G0/G1 phase, as measured by flow cytometry. Compared to the control group, cells treated with Rh2 showed significantly higher apoptosis ratios in a dose-dependent manner (percentage of early apoptotic cells: from 5.29% +/- 2.28% to 38.90% +/- 3.42% (F = 56.20, P < 0.05); percentage of late apoptotic cells: from 4.58% +/- 1.42% to 36.32% +/- 2.73% (F = 86.70, P < 0.05). Rh2 inhibited Bxpc-3 cell migration and invasion, as detected by scratch wound healing assay and Matrigel invasion assay [percentages of scratch wound healing for 12 h, 24 h and 48 h (control vs experimental group): 37.3% +/- 4.8% vs 18.30% +/- 1.65%, 58.7% +/- 3.5% vs 38.00% +/- 4.09% and 93.83% +/- 4.65% vs 65.50% +/- 4.09%, respectively; t = 6.489, t = 6.656 and t = 7.926, respectively, P < 0.05; the number of cells invading at various concentrations (0 mumol/L, 35 mumol/L, 45 mumol/L and 55 mumol/L): 81.10 +/- 9.55, 46.40 +/- 6.95, 24.70 +/- 6.88 and 8.70 +/- 3.34, respectively (F = 502.713, P < 0.05)]. RT-PCR, western blotting or ELISA showed that mRNA and protein expression of Bax, cleaved caspase-3 and caspase-9 were upregulated (P < 0.05), while mRNA and protein expression of Bcl-2, survivin, cyclin D1, MMP-2 and MMP-9 were downregulated (P < 0.05). CONCLUSION: Ginsenoside Rh2 inhibits proliferation, migration and invasion and induces apoptosis of the human pancreatic cancer cell line Bxpc-3.
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[127]
TÍTULO / TITLE: - CacyBP/SIP enhances multidrug resistance of pancreatic cancer cells by regulation of P-gp and Bcl-2.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Apoptosis. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1007/s10495-013-0831-9
AUTORES / AUTHORS: - Chen X; Zheng P; Xue Z; Li J; Wang W; Chen X; Xie F; Yu Z; Ouyang X
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China, cxzpc81@gmail.com.
RESUMEN / SUMMARY: - Our former report indicates that calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP) is over-expressed in the SGC7901/ADR cell line. However, the potential role of CacyBP/SIP in the development of multidrug resistance (MDR) of pancreatic cancer is still uncertain. In this paper, we investigated the role of CacyBP/SIP in MDR of pancreatic cancer cells and its possible underlying mechanisms, and found that CacyBP/SIP was over-expressed in the Gemcitabine induced MDR pancreatic cancer cell PC-3/Gem compared with its parental cell PC-3. Up-regulation of CacyBP/SIP expression could enhance resistance of chemotherapy drugs on PC-3 cells and inhibit Adriamycin-induced apoptosis accompanied by decreased accumulation of intracellular Adriamycin. Furthermore, CacyBP/SIP could significantly up-regulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene. In addition, the decrease of CacyBP/SIP expression using RNA interference or P-gp inhibitor could partially reverse CacyBP/SIP-mediated MDR. In brief, our study demonstrated that CacyBP/SIP could enhance the MDR phenotype of pancreatic cancer cells by increasing the expression of P-gp and Bcl-2, thus inhibiting apoptosis of pancreatic cancer cell.
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[128]
TÍTULO / TITLE: - Distinct claudin expression profiles of hepatocellular carcinoma and metastatic colorectal and pancreatic carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Histochem Cytochem. 2013 Apr;61(4):294-305. doi: 10.1369/0022155413479123. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1369/0022155413479123
AUTORES / AUTHORS: - Holczbauer A; Gyongyosi B; Lotz G; Szijarto A; Kupcsulik P; Schaff Z; Kiss A
INSTITUCIÓN / INSTITUTION: - 2nd Department of Pathology (AH,BG,GL,ZS,AK), Semmelweis University, Budapest, Hungary.
RESUMEN / SUMMARY: - Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.
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[129]
TÍTULO / TITLE: - Systemic therapy for advanced pancreatic neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Semin Oncol. 2013 Feb;40(1):75-83. doi: 10.1053/j.seminoncol.2012.11.010.
●● Enlace al texto completo (gratuito o de pago) 1053/j.seminoncol.2012.11.010
AUTORES / AUTHORS: - Kulke MH
INSTITUCIÓN / INSTITUTION: - Program in Neuroendocrine and Carcinoid Tumors, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA. Matthew_Kulke@dfci.harvard.edu
RESUMEN / SUMMARY: - Neuroendocrine tumors (NETs) occur throughout the body, and share similar histologic characteristics. However, it has become increasingly evident that pancreatic NETs tend to respond differently to therapeutic agents than do other NET subtypes. In most cases, systemic therapy has been more effective in NETs of pancreatic origin than in NETs arising from other locations. Traditional systemic treatment options for pancreatic NETs include somatostatin analogs or cytotoxic chemotherapy. Recently, the biologically targeted agents everolimus and sunitinib were approved for use in patients with metastatic disease. Novel agents, as well as novel drug combinations, are currently under investigation.
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[130]
TÍTULO / TITLE: - Follow-up after curative surgery for pancreatic ductal adenocarcinoma: Asymptomatic recurrence is associated with improved survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Surg Oncol. 2013 Mar 13. pii: S0748-7983(13)00265-5. doi: 10.1016/j.ejso.2013.02.020.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ejso.2013.02.020
AUTORES / AUTHORS: - Nordby T; Hugenschmidt H; Fagerland MW; Ikdahl T; Buanes T; Labori KJ
INSTITUCIÓN / INSTITUTION: - Department for Hepato-Pancreato-Biliary Surgery, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Sognsvannsveien 20, N-0027 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
RESUMEN / SUMMARY: - AIM: There is no consensus on the optimal follow-up schedule of patients after surgery for pancreatic cancer. In this retrospective study, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. Patient, tumor and treatment characteristics that predicted the length of postrecurrence survival were identified. METHODS: Clinical records of 164 patients who underwent a pancreatic resection (R0/R1) for pancreatic ductal adenocarcinoma from January 2000 to December 2010 were retrieved. Patients underwent a systematic follow-up program. Patient, tumor and treatment characteristics were compared between patients with asymptomatic and symptomatic recurrence. RESULTS: Of 164 consecutive patients, 144 patients (88%) had recurrence (29 asymptomatic, 115 symptomatic). The most frequent reported symptoms were abdominal pain, fatigue/weakness, back pain, weight loss, nausea/loss of appetite and jaundice. Median time to recurrence was 12.0 months for asymptomatic and 7.0 months for symptomatic patients (P = 0.036). Median postrecurrence survival was 10.0 months for asymptomatic and 4.0 months for symptomatic patients (P < 0.0001). Median overall survival was 24.5 months for asymptomatic and 11.0 months for symptomatic patients (P < 0.0001). Symptomatic recurrence, disease free survival <12 months, and no adjuvant chemotherapy were the only independent predictors of poor postrecurrence survival. 72% of asymptomatic and 37% of symptomatic patients received oncological treatment. CONCLUSIONS: Patients with asymptomatic pancreatic cancer recurrence have improved recurrence-free, postrecurrence and overall survival. Symptoms when recurrence is diagnosed are a good surrogate marker of biological aggressiveness. Detection of asymptomatic recurrence may facilitate patient eligibility for investigational studies or other forms of treatment.
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[131]
TÍTULO / TITLE: - Kindlin-2 Expression in Peritumoral Stroma Is Associated With Poor Prognosis in Pancreatic Ductal Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 15.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279bd66
AUTORES / AUTHORS: - Mahawithitwong P; Ohuchida K; Ikenaga N; Fujita H; Zhao M; Kozono S; Shindo K; Ohtsuka T; Mizumoto K; Tanaka M
INSTITUCIÓN / INSTITUTION: - From the *Departments of Surgery and Oncology, and daggerAnatomic Pathology, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: Kindlin-2 is a novel focal adhesion protein reported to be expressed in breast, lung, and gastric cancers. This study aimed to investigate the significance of kindlin-2 expression in pancreatic ductal adenocarcinomas (PDACs). METHODS: We performed immunohistochemical analysis on kindlin-2 on PDAC samples from 95 patients. We investigated the association between kindlin-2 expression and clinicopathological parameters of PDAC and the survival time of patients with PDAC who underwent pancreatectomy. RESULTS: Kindlin-2 was highly expressed in the peritumoral stroma of PDACs. Stromal kindlin-2 expression was related to nodal metastasis (P = 0.03). Univariate analysis showed that patients with positive kindlin-2 expression had significantly shorter survival times than those with negative kindlin-2 expression (P = 0.01). In addition, multivariate analysis revealed that kindlin-2 expression was an independent factor of poor prognosis in patients with PDAC after R0 resection (RR = 2.15; P = 0.04). CONCLUSIONS: Kindlin-2 expression in stromal components is significantly associated with poor prognosis of patients with PDAC, suggesting that kindlin-2 is a prognostic marker for patients with PDAC.
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[132]
TÍTULO / TITLE: - Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Br J Cancer. 2013 Mar 5;108(4):914-23. doi: 10.1038/bjc.2013.32. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1038/bjc.2013.32
AUTORES / AUTHORS: - Ino Y; Yamazaki-Itoh R; Shimada K; Iwasaki M; Kosuge T; Kanai Y; Hiraoka N
INSTITUCIÓN / INSTITUTION: - Division of Molecular Pathology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
RESUMEN / SUMMARY: - Background:The host immune reaction is represented by immune/inflammatory cell infiltrates. Here we systematically analysed tumour-infiltrating immune/inflammatory cells in pancreatic ductal carcinoma (PDC) and evaluated their clinicopathological impact.Methods:Using immunohistochemistry, we examined tumour-infiltrating CD68 pan-macrophages, HLA-DRCD68 M1 macrophages (M1), CD163 or CD204 M2 macrophages (M2), CD66b neutrophils (Neu), CD4 T cells (CD4T), CD8 T cells (CD8T), and FOXP3CD4 regulatory T cells (Treg) in 212 cases of PDC, and conducted correlation and survival analyses using the Kaplan-Meier method and Cox proportional hazards model.Results:Higher levels of tumour-infiltrating pan-macrophages, M2, Neu, or the ratio of Tregs to CD4T (%Treg) were significantly associated with shorter survival, whereas higher levels of tumour-infiltrating CD4T, CD8T, or the ratio of M1 to pan-macrophages (%M1) were significantly associated with longer survival. Survival analysis of pairs of these variables revealed that some of the resulting patient groups had exclusively longer survival. We then connected the apparently related factors, and two significant variables emerged: tumour-infiltrating CD4T/CD8T/%Treg and tumour-infiltrating %M1/M2. Multivariate survival analysis revealed that these variables were significantly correlated with longer survival and had a higher hazard ratio.Conclusion:Tumour-infiltrating CD4T/CD8T/%Treg and %M1/M2 are independent prognosticators useful for evaluating the immune microenvironment of PDC.
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[133]
TÍTULO / TITLE: - Molecular biology of adenocarcinoma of the pancreatic duct, current state and future therapeutic avenues.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Oncol. 2013 Feb 15. pii: S0960-7404(12)00092-8. doi: 10.1016/j.suronc.2012.12.002.
●● Enlace al texto completo (gratuito o de pago) 1016/j.suronc.2012.12.002
AUTORES / AUTHORS: - Abbas S
INSTITUCIÓN / INSTITUTION: - Deakin University, Barwon Health, Bellerine St, Geelong 3200, Vic, Australia. Electronic address: salehabbas@yahoo.com.
RESUMEN / SUMMARY: - Pancreatic adenocarcinoma is a lethal disease; currently surgery offers five years survival of less than 5%. Any improvement in the outcome is likely to be through novel therapeutic agents that will target the genetic machinery of the cell. Knowledge of genetic alterations in the process of carcinogenesis is expanding rapidly, the targeted therapy, however, is progressing slowly. Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lend the cancer cells their ability not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes involve genetic alteration in oncogenes, cancer suppressor genes, changes in cell cycle, pathways of apoptosis and also changes in epithelial to mesenchymal transition. Monotherapeutic targeted agents seem(s) to have limited effect on cancer cells. The near future is likely to show an improvement in the treatment outcome, which is likely to be a result of the combination of targeted agents with surgery and chemotherapy.
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[134]
TÍTULO / TITLE: - Controversial issues of neoadjuvant treatment in borderline resectable pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Oncol. 2013 Mar 18. pii: S0960-7404(13)00025-X. doi: 10.1016/j.suronc.2013.02.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.suronc.2013.02.007
AUTORES / AUTHORS: - Kang CM; Hwang HK; Choi SH; Lee WJ
INSTITUCIÓN / INSTITUTION: - 50 Yonsei-ro, Seodaemun-gu, Department of Surgery, Yonsei University College of Medicine, Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, Seoul 120752, Republic of Korea.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma is known as one of the most fatal malignant diseases in gastrointestinal system. Approximately 20% of patients are deemed resectable at the time of diagnosis. Preoperative neoadjuvant therapy to the borderline resectable pancreatic cancer (BRPC) has been challenged to achieve down-staging of cancer, to avoid unnecessary major operation if the pancreatic cancer progresses and distant metastasis develops during preoperative treatment, and to avoid delayed adjuvant treatment after major operation due to postoperative complications and poor general condition after major surgery. However, there are some controversial issues influencing the clinical interpretation of surgical and oncologic outcomes of pancreatectomy following neoadjuvant treatment in managing BRPC. This manuscript reviews the current controversial issues in managing BRPC in order to enhance proper understanding the current status and potential role of neoadjuvant treatment in managing BRPC.
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[135]
TÍTULO / TITLE: - Kindlin-1 expression is involved in migration and invasion of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Oncol. 2013 Apr;42(4):1360-6. doi: 10.3892/ijo.2013.1838. Epub 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 3892/ijo.2013.1838
AUTORES / AUTHORS: - Mahawithitwong P; Ohuchida K; Ikenaga N; Fujita H; Zhao M; Kozono S; Shindo K; Ohtsuka T; Aishima S; Mizumoto K; Tanaka M
INSTITUCIÓN / INSTITUTION: - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - Kindlin-1 is a novel focal adhesion protein that belongs to the kindlin family. Expression of kindlin-1 has recently been reported in lung and colon cancers, but there have been no studies on its expression in pancreatic cancer. This study aimed to investigate the expression and function of kindlin-1 in pancreatic cancer. Quantitative RT-PCR of Kindlin-1 mRNA was performed in various pancreatic cancer cell lines as well as normal pancreatic epithelial cells and fibroblasts. Immunohistochemical analysis of kindlin-1 was performed for pancreatic cancer tissues. The effects of kindlin-1 on the proliferation, migration and invasion of pancreatic cancer cells were investigated using an RNA interference technique. Kindlin-1 mRNA was highly expressed in the pancreatic cancer cell lines, but only slightly expressed in normal pancreatic epithelial cells and fibroblasts. The Kindlin-1 protein was heterogeneously expressed in the cytoplasm and membrane of pancreatic cancer cells, while normal ductal epithelial cells and stromal cells showed no expression. In vitro experiments involving knockdown of kindlin-1 in AsPC-1 and KP-2 cells revealed that the migratory and invasive abilities of the cells were significantly decreased (P<0.001), while the proliferation abilities were not affected. The present findings suggest that kindlin-1 expression is involved in the progression of pancreatic cancer via enhancement of cell migration and invasion.
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[136]
TÍTULO / TITLE: - Delayed Small Bowel Transit in Children with Cystic Fibrosis and Pancreatic Insufficiency.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Pediatr Gastroenterol Nutr. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1097/MPG.0b013e318290d112
AUTORES / AUTHORS: - Rovner AJ; Schall JI; Mondick JT; Zhuang H; Mascarenhas MR
INSTITUCIÓN / INSTITUTION: - *Division of Gastroenterology, Hepatology and Nutrition daggerDepartment of Radiology double daggerThe Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Metrum Institute, Tariffville, CT.
RESUMEN / SUMMARY: - OBJECTIVE:: Gastrointestinal (GI) disturbances are common in people with cystic fibrosis (CF); however, motility studies in this population have yielded inconsistent results.This study examined gastric emptying (GE) and small bowel transit (SBT) time in children with CF and pancreatic insufficiency (PI) compared to a healthy adult reference group. METHODS:: Participants consumed an 8-ounce liquid test meal (approximately 550 calories, 32 grams of fat) labeled with 300 uCi 99m Technetium (Tc) sulfur colloid. Subjects with CF received a standard dose of pancreatic enzymes prior to consuming the test meal. GE and SBT were measured using a standard nuclear medicine scan. GE was determined after correcting for 99mTc decay in both anterior and posterior images. SBT was determined by following the movement of the tracer from the stomach to the cecum. The percent arrival of total small bowel activity at the terminal ileum and cecum/ascending colon at 6 hours was used as an index of SBT. A one way analysis of covariance (ANCOVA) was performed for comparisons between groups after adjustment forage, gender and BMI. RESULTS:: Subjects with CF (n = 16) had similar GE compared to the healthy reference group (n = 12). However, subjects with CF had significantly prolonged SBT time. At 6 hours 37.2 +/- 25.4% (95%CI: 23.7, 50.7) of the tracer reached the terminal ileum and colon compared to 68.6 +/- 13.1% (95%CI: 60.2, 76.9) for the reference group (p < 0.001). After controlling forgender, age and BMI this difference remained statistically significant (F = 12.06, adjusted R = 0.44, p < 0.002). CONCLUSIONS:: Children with CF and PI had unaltered GE but delayed SBT time when taking pancreatic enzymes.
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[137]
TÍTULO / TITLE: - A potential window onto early pancreatic cancer development: evidence of cancer stem cell growth after exposure to cadmium chloride in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Environ Health Perspect. 2012 Sep;120(9):A363.
AUTORES / AUTHORS: - Barrett JR
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[138]
TÍTULO / TITLE: - Vascular proliferation is associated with survival in pancreatic ductal adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - APMIS. 2013 Mar 13. doi: 10.1111/apm.12057.
●● Enlace al texto completo (gratuito o de pago) 1111/apm.12057
AUTORES / AUTHORS: - Hoem D; Straume O; Immervoll H; Akslen LA; Molven A
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway.
RESUMEN / SUMMARY: - In pancreatic ductal adenocarcinoma (PDAC), the benefit of current chemotherapy and radiation therapy is very limited, even in radically resected patients. New treatment strategies, for example based on the inhibition of the tumour’s blood supply, need to be explored. We have investigated angiogenesis markers and their associations with relapse and survival in 52 histologically confirmed cases of PDAC. Angiogenesis in the primary tumour was evaluated by microvessel density (MVD), vascular proliferation index (VPI) and the presence of glomeruloid microvascular proliferations (GMP). These features were analysed in the context of clinicopathological variables, KRAS mutation status, relapse location and survival. MVD (median 134 microvessels/mm2 , range 88-177) and VPI (median 3.2%, range 1.6-4.9) were associated with larger tumour size and lymph node metastasis. MVD was also related to the occurrence of liver metastases. Both variables were associated with survival in univariate and multivariate analyses. GMPs were present in 32 (62%) of the cases. Patients who exhibited MVD and VPI values above median, and GMP positivity, had a median survival of only 4.2 months after surgery. In conclusion, the angiogenesis markers MVD and VPI have a significant impact on survival. By also including GMP, a subgroup of PDAC patients with particularly short survival could be identified.
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[139]
TÍTULO / TITLE: - Preoperative evaluation of the cystic duct for laparoscopic cholecystectomy: comparison of navigator-gated prospective acquisition correction- and conventional respiratory-triggered techniques at free-breathing 3D MR cholangiopancreatography.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Radiol. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s00330-013-2790-5
AUTORES / AUTHORS: - Itatani R; Namimoto T; Kajihara H; Yoshimura A; Katahira K; Nasu J; Matsushita I; Sakamoto F; Kidoh M; Yamashita Y
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Kumamoto Chuo Hospital, 1-5-1, Tainoshima, Kumamoto, 862-0965, Japan.
RESUMEN / SUMMARY: - OBJECTIVE: To evaluate the quality of magnetic resonance cholangiopancreatography (MRCP) images obtained with a three-dimensional navigator-gated (NG) technique and compare findings with conventional respiratory-triggered (RT) images in pre-laparoscopic cholecystectomy patients. METHODS: Turbo-spin-echo (TSE) RT-MRCP (average 242 s) and balanced turbo-field-echo (bTFE) NG-MRCP (average 263 s) were acquired at 1.5-T MRI for 49 pre-laparoscopic cholecystectomy patients. Two radiologists independently assessed image quality, visibility of anatomical structures, common bile duct (CBD) stones, and signal-to-noise ratios (SNRs). Interobserver agreement was also evaluated. RESULTS: The anatomical details of the cystic duct were clearly demonstrated in 33 (67.3 %, reader A) and 35 (71.4 %, reader B) patients on RT-MRCP, and in 45 (91.8 %) and 44 (89.7 %) patients on NG-MRCP. On NG-MRCP, visualisation of the cystic duct (3.22/3.12), its origin (3.57/3.55), and the gallbladder(3.61/3.59) was statistically better than on RT-MRCP (2.90/2.78, 3.29/3.12, 2.98/2.88, respectively). The overall image quality was statistically better on NG-MRCP than RT-MRCP. Each technique identified the presence of CBD stones in all affected patients. The SNR was significantly higher on NG-MRCP (CHD 22.40, gallbladder 17.13) than RT-MRCP (CHD 17.05, gallbladder 9.30). Interobserver agreement was fair to perfect. CONCLUSION: Navigator-gated MRCP is more useful than respiratory-triggered MRCP for evaluating the gallbladder and cystic duct in patients scheduled for laparoscopic cholecystectomy. KEY POINTS : * Magnetic resonance cholangiopancreatography (MRCP) provides important cystic duct information before laparoscopic cholecystectomy. * Navigator-gated (NG) MRCP images were better than conventional respiratory-triggered (RT) MRCP. * The signal-to-noise ratio was significantly higher for NG-MRCP than for conventional RT-MRCP. * Balanced turbo-field-echo NG-MRCP is useful for evaluating the gallbladder and cystic duct.
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[140]
TÍTULO / TITLE: - Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar;42(2):193-7. doi: 10.1097/MPA.0b013e31825e354d.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31825e354d
AUTORES / AUTHORS: - Poruk KE; Firpo MA; Scaife CL; Adler DG; Emerson LL; Boucher KM; Mulvihill SJ
INSTITUCIÓN / INSTITUTION: - From the *Department of Surgery, daggerHuntsman Cancer Institute, double daggerDivision of Gastroenterology and Hepatology, Department of Internal Medicine, section signDepartment of Pathology, and parallelDepartment of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, UT.
RESUMEN / SUMMARY: - OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of 5%. There is an urgent need for early detection while the tumors are small and surgically resectable. We assessed serum osteopontin (OPN) and tissue inhibitor of metalloproteinase 1 (TIMP-1) as possible diagnostic and prognostic biomarkers in a novel cohort of patients with pancreatic cancer. METHODS: Osteopontin and TIMP-1 levels were determined in sera from 86 patients with PDAC, 86 healthy control subjects, and 48 patients with chronic pancreatitis. Regression models were used to relate OPN and TIMP-1 to sex, age, stage, class, and treatment. Survival analyses were performed using univariate and multivariate Cox models. RESULTS: The serum levels of both OPN and TIMP-1 distinguished PDAC from chronic pancreatitis (P </= 0.0001) and healthy control subjects (P < 0.0001). The serum levels of both OPN and TIMP-1 also distinguished early-stage resectable PDAC cases from chronic pancreatitis (P < 0.04) and healthy control subjects (P < 0.01). High serum levels of OPN were significantly correlated with reduced patient survival. CONCLUSIONS: Serum OPN and TIMP-1 have use as diagnostic biomarkers in PDAC. Our data suggest a potential benefit of using OPN, TIMP-1, and CA 19-9 in a panel to improve diagnostic accuracy in PDAC.
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[141]
TÍTULO / TITLE: - Spontaneous rupture of solid pseudopapillary neoplasm of the pancreas during pregnancy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Obstet Gynecol. 2013 Feb;121(2 Pt 2 Suppl 1):486-8. doi: 10.1097/AOG.0b013e31826d292f.
AUTORES / AUTHORS: - Huang SC; Wu TH; Chen CC; Chen TC
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Taoyuan, Taiwan.
RESUMEN / SUMMARY: - BACKGROUND: Spontaneous rupture of solid pseudopapillary neoplasm of the pancreas is an unusual complication during pregnancy. CASE: At 19 weeks of gestation, a 29-year-old woman presented with a pancreatic mass and upper abdominal pain radiating to the back. On the third day of admission, shock and peritoneal signs developed. Exploratory laparotomy and subsequent subtotal pancreatectomy were performed for a bleeding tumor. Solid pseudopapillary neoplasm was confirmed by pathological examination. The patient delivered a healthy full-term girl vaginally. Eight months postoperatively, the clinical courses of both mother and infant have been uneventful. CONCLUSION: Ruptured solid pseudopapillary neoplasms can cause an acute abdomen during pregnancy. The expression of progesterone receptors in solid pseudopapillary neoplasm is a possible cause of this potentially devastating event.
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[142]
TÍTULO / TITLE: - Synergistic interactions between sorafenib and everolimus in pancreatic cancer xenografts in mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-013-2117-x
AUTORES / AUTHORS: - Pawaskar DK; Straubinger RM; Fetterly GJ; Hylander BH; Repasky EA; Ma WW; Jusko WJ
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA.
RESUMEN / SUMMARY: - PURPOSE: Molecular targeting of cellular signaling pathways is a promising approach in cancer therapy, but often fails to achieve sustained benefit because of the activation of collateral cancer cell survival and proliferation pathways. We tested the hypothesis that a combination of targeted agents that inhibit compensatory pathways would be more effective than single agents in controlling pancreatic cancer cell growth. We investigated whether everolimus, an mTOR inhibitor, and sorafenib, a multi-kinase inhibitor, would together inhibit growth of low-passage, patient-derived pancreatic cancer xenografts in mice more efficaciously than either agent alone. METHODS: Tumor volume progression was measured following treatment with both drugs as single agents, in combination, and at multiple doses. Pharmacokinetics in tumors and other tissues was also assessed. Pharmacodynamic interactions were evaluated quantitatively. RESULTS: A 5-week regimen of daily oral doses of 10 mg/kg sorafenib and 0.5 mg/kg everolimus, alone and in combination, did not achieve significant tumor growth inhibition. Higher doses (20 mg/kg of sorafenib and 1 mg/kg of everolimus) inhibited tumor growth significantly when given alone and caused complete inhibition of growth when given in combination. Tumor volume progression was described by a linear growth model, and drug effects were described by Hill-type inhibition. Using population modeling approaches, dual-interaction parameter estimates indicated a highly synergistic pharmacodynamic interaction between the two drugs. CONCLUSIONS: The results indicate that combinations of mTOR and multi-kinase inhibitors may offer greater efficacy in pancreatic cancer than either drug alone. Drug effects upon tumor stromal elements may contribute to the enhanced anti-tumor efficacy.
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[143]
TÍTULO / TITLE: - The effect of gadolinium chelate contrast agent on diffusion-weighted imaging of pancreatic ductal adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Radiol. 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1177/0284185112471795
AUTORES / AUTHORS: - Liu K
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Fudan University Shanghai Cancer Center.
RESUMEN / SUMMARY: - Background:There are only two studies that discuss the effect of a gadolinium chelate contrast agent on pancreatic diffusion-weighted imaging (DWI). However, both studies only included normal pancreas and/or pancreas with pancreatitis and did not include pancreatic ductal adenocarcinoma (PDA). Purpose: To investigate the effect of gadolinium chelate contrast agent on DWI of PDA.Material and Methods:Twenty-two patients (13 men, 9 women; mean age 62 years) with histopathologically proven PDA were included in this study. DWI was acquired before and after administration of gadopentetate dimeglumine (Magnevist) with two b-values: 0 and 1000 s/mm2. The signal intensity (SI), signal-to-noise ratio (SNR), and the apparent diffusion coefficient (ADC) of the lesion were recorded for comparison.Results:The mean time interval between the initiation of contrast administration and the start of the postcontrast DWI series was 393 s (range, 350-510 s). The SIs and SNRs of lesions of b1000 and b0 images of enhanced images were significantly higher than non-enhanced images (P, 0.001, P, 0.001 for b1000 s/mm2; P ¼ 0.001, P ¼ 0.001 for b0 s/mm2). The ADC of all PDAs revealed no statistically significant difference between non-enhanced and enhanced images (P ¼ 0.709). There was also no significant difference between non-enhanced and enhanced images in subgroups based on grades of differentiation and locations of lesion.Conclusion: With increasing SI and SNR of PDA, intravenous contrast administration does not result in a significant difference in quantitative ADC measurements when comparing precontrast to postcontrast DWI when acquired approximately 6-7 min after administration.
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[144]
TÍTULO / TITLE: - CA 19-9 Nonproduction Is Associated With Poor Survival After Resection of Pancreatic Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Am J Clin Oncol. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1097/COC.0b013e318280d5f0
AUTORES / AUTHORS: - Hayman AV; Stocker SJ; Baker MS; Bentrem DJ; Prinz RA; Marsh RD; Talamonti MS
INSTITUCIÓN / INSTITUTION: - *Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago daggerDepartment of Surgery, NorthShore University HealthSystem double daggerDepartment of Medicine, Division of Hematology/Oncology, NorthShore University HealthSystem, Evanston, IL.
RESUMEN / SUMMARY: - BACKGROUND:: Carbohydrate antigen (CA) 19-9 is the most common serum biomarker used in pancreatic adenocarcinoma (PC). Elevated preoperative levels have been shown to correlate with more advanced stage, greater risk of unresectability, and overall worse survival. The prognostic value of CA 19-9 nonproduction, which is present in an estimated 5% to 15% of the population, is unclear. We sought to determine whether CA 19-9 nonproduction was associated with worse survival after PC resection. METHODS:: We retrospectively reviewed our institution’s prospective pancreatic database for all PC patients with documented preoperative CA 19-9 values who underwent resection with curative intent from March 1992 to August 2009. After excluding 10 perioperative deaths, 200 patients remained for analysis. RESULTS:: Mean and median follow-up was 23.3 and 16.1 months, respectively. Median survival in months for patients with preoperative CA 19-9 levels in U/mL by category was as follows: normal (5.1 to 36.9): 32, nonproduction (</=5): 21, mildly elevated (37 to 99.9): 35, highly elevated (100+): 16. Factors significantly associated with worse overall survival were: nonwhite race, nonproduction or highly elevated preoperative CA 19-9 (>/=100 U/mL), estimated blood loss >/=1 L, tumor size (>/=2 cm), lymph node-positivity, and advanced (3/4) histologic grade. On multivariate analysis, only CA 19-9 nonproduction or highly elevated production, estimated blood loss >/=1 L, advanced histologic grade, and node positivity remained significant in the final model. CONCLUSIONS:: CA 19-9 nonproduction is not associated with improved survival after pancreatic cancer resection, as has previously been asserted, when compared with patients with normal and elevated levels.
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[145]
TÍTULO / TITLE: - Lipocalin-2 is Associated With a Good Prognosis and Reversing Epithelial-to-Mesenchymal Transition in Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1007/s00268-013-2009-6
AUTORES / AUTHORS: - Xu B; Jin DY; Lou WH; Wang DS
INSTITUCIÓN / INSTITUTION: - Department of Hepato-biliary-pancreatic Surgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China, pfdbs1@yahoo.com.cn.
RESUMEN / SUMMARY: - BACKGROUND: Lipocalin-2 is a multifaceted modulator in cancer progression. Its clinical significance is not clear in pancreatic cancer. The purpose of this study was to investigate whether lipocalin-2 is associated with good prognosis by reversing epithelial-to-mesenchymal transition (EMT) in pancreatic cancer. METHODS: Lipocalin-2, E-cadherin, or vimentin expression was detected in 60 pancreatic adenocarcinoma specimens. Correlations between lipocalin-2 expression and EMT, the clinicopathologic characteristics, and prognosis were investigated. Whether pancreatic cancer cells’ migration and invasion (some characteristics of EMT) were affected by lipocalin-2 was also explored. RESULTS: High lipocalin-2 expression was significantly associated with a good prognosis in pancreatic cancer (p < 0.05). Overexpression of lipocalin-2 correlated with a lower extent of EMT (p < 0.05), increased E-cadherin expression (p < 0.05), decreased vimentin expression (p < 0.05), and reduced cancer cell migration and invasion in pancreatic cancer. CONCLUSIONS: Lipocalin-2 may be considered an epithelial inducer, which may reverse EMT and predict a good prognosis in pancreatic cancer.
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[146]
TÍTULO / TITLE: - Induction of pancreatic cancer cell apoptosis, invasion, migration, and enhancement of chemotherapy sensitivity of gemcitabine, 5-FU, and oxaliplatin by hnRNP A2/B1 siRNA.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Drugs. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1097/CAD.0b013e3283608bc5
AUTORES / AUTHORS: - Gu WJ; Liu HL
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, the Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
RESUMEN / SUMMARY: - We investigated the effects of inhibiting heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) expression on apoptosis, invasion, migration, and the chemotherapy sensitivity of pancreatic cancer cells to gemcitabine, 5-FU, and oxaliplatin chemotherapy using small interfering RNA (siRNA). Chemically synthesized siRNA hnRNP A2/B1 was transfected into the human pancreatic cancer cell lines SW1990 and BxPC-3. The IC50 of gemcitabine, 5-FU, and oxaliplatin was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and cycle were detected using flow cytometry. The expressions of apoptosis-related genes, p53, Bax, Bcl-2, TRAIL, Survivin, multidrug resistance 1 (MDR1), E-cadherin, and matrix metalloproteinases-2 (MMP-2) were detected using real-time PCR and western blot. Plate colony formation assay, wound scratch assay, invasion, and migration were also examined. Gemcitabine, 5-FU, and oxaliplatin inhibit the proliferation of SW1990 and BxPC-3 cells in a concentration-dependent manner. Inhibition of hnRNP A2/B1 expression significantly reduced the IC50 of gemcitabine, 5-FU, and oxaliplatin (P<0.01). hnRNP A2/B1 siRNA combined with gemcitabine, 5-FU and Oxaliplatin significantly increased (P<0.01) apoptosis of pancreatic cancer cell lines SW1990 and BxPC-3, increased the expression level of Bax mRNA, decreased Bcl-2 mRNA and MDR1 mRNA expression (P<0.01), and induced no change in p53, TRAIL, and Survivin mRNA expression in SW1990. In the western blot analysis, the expression level of Bax protein increased (P<0.01); the expression of both P-glycoprotein (Pg-p) protein and Bcl-2 protein decreased (P<0.01). Silencing hnRNP A2/B1 decreased invasion and migration in the cell line SW1990. Silencing hnRNP A2/B1 in SW1990 also correlated with an increase in E-cadherin expression and a decrease in MMP-2 expression at the same time. Inhibition of hnRNP A2/B1 expression can induce apoptosis in pancreatic cancer cells and improve chemosensitivity to gemcitabine, 5-FU, and oxaliplatin. hnRNP A2/B1 may play a role in invasion and migration in the pancreatic cancer cell line SW1990 through the regulation of E-cadherin and expression of MMP-2.
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[147]
TÍTULO / TITLE: - Role of Insulin and Igf signaling in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Mol Endocrinol. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1530/JME-12-0259
AUTORES / AUTHORS: - Trajkovic-Arsic M; Kalideris E; Siveke JT
INSTITUCIÓN / INSTITUTION: - M Trajkovic-Arsic, II Medical department, Klinikum rechts der Isar, Munich, Germany.
RESUMEN / SUMMARY: - Abstract The importance of the insulin-like growth factor system in carcinogenesis has been established for many solid cancers. It is well known that individuals with higher circulating levels of the insulin-like growth factor 1(IGF1) ligand present an increased risk of cancer. However, therapies with monoclonal antibodies targeting the IGF1 receptor (IGF1R) have been largely unsuccessful. One of the potential reasons for this failure is the existence of the highly homologous insulin receptor (IR) which appears to be at least as equally efficient as the IGF1R in the transition of mitogenic signals to the nucleus and promotion of cell growth. Furthermore, IGF1 and insulin receptors can form hybrid receptors sensitive to stimulation of all three ligands of the system: insulin, insulin-like growth factor 1 and insulin-like growth factor 2. Although the connection between insulin, diabetes and cancer has been established for years now, clear evidence that demonstrate the redundancy of insulin and insulin receptors and insulin-like growth factors and their receptors in cancer are missing. In this review, we focus on the contribution of insulin and IGFs to carcinogenesis in the insulin-producing organ, the pancreas. We give a short summary on the complexity of insulin and the IGF system in the pancreas and their potential roles in pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC). Finally, we discuss drug targeting options of this system and the rationale of simultaneous targeting of both the insulin and IGF systems.
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[148]
TÍTULO / TITLE: - Identification and impact of hepatitis B virus DNA and antigens in pancreatic cancer tissues and adjacent non-cancerous tissues.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Lett. 2013 Mar 7. pii: S0304-3835(13)00224-3. doi: 10.1016/j.canlet.2013.03.001.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canlet.2013.03.001
AUTORES / AUTHORS: - Jin Y; Gao H; Chen H; Wang J; Chen M; Li G; Wang L; Gu J; Tu H
INSTITUCIÓN / INSTITUTION: - Department of Molecular Diagnostics, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
RESUMEN / SUMMARY: - Increasing evidence suggests that a link exists between hepatitis B virus (HBV) serum markers and pancreatic cancer (PC). In this study, HBsAg and HBcAg were expressed in 21.0% (34/162) of PC and 29.0% (47/162) of non-tumor pancreatic tissues, and they were significantly associated with chronic pancreatitis (P=0.000). The HBV S, C and X genes were identified in 20% (6/30) of PC and 26.9% (7/26) of non-tumor tissues by PCR. A serological survey revealed that the prevalence of HBV DNA and anti-HBc was significantly increased in PC patients compared with healthy controls. Our data suggest that HBV infection in the pancreas may play an etiologic role in PC.
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[149]
TÍTULO / TITLE: - Contrast-Enhanced Ultrasound in the Differential Diagnosis of Exocrine Versus Neuroendocrine Pancreatic Tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827a7b01
AUTORES / AUTHORS: - Serra C; Felicani C; Mazzotta E; Piscitelli L; Cipollini ML; Tomassetti P; Pezzilli R; Casadei R; Morselli-Labate AM; Stanghellini V; Corinaldesi R; De Giorgio R
INSTITUCIÓN / INSTITUTION: - From the *Department of Medical and Surgical Sciences/Digestive Diseases and Internal Medicine, St Orsola-Malpighi Hospital; daggerDivision of Angiology and Blood Coagulation, and double daggerDepartment of Medical and Surgical Sciences, St Orsola-Malpighi Hospital; and section signCentro Interdipartimentale di Ricerca sull Alimentazione Umana (CIRAU), University of Bologna; Bologna, Italy.
RESUMEN / SUMMARY: - OBJECTIVES: Contrast-enhanced ultrasound (CEUS) has been developed to better characterize the microvasculature of solid masses in several organs, including the pancreas. In this study, we assessed CEUS accuracy in differentiating exocrine from endocrine pancreatic tumors. METHODS: A total of 127 patients with single, undetermined pancreatic masses were prospectively examined with transabdominal ultrasound and CEUS, before surgical resection or percutaneous biopsy. RESULTS: Exocrine and endocrine pancreatic tumors showed different intralesional vascularization patterns: 98.9% (90/91) of exocrine tumors were hypoenhancing, whereas 95.8 % (23/24) of endocrine tumors had a hypervascular supply. A hypoenhancing pattern, indicative of ductal adenocarcinoma, had a significant (P < 0.001) diagnostic accuracy of 91.3% with a sensitivity of 96.8%, a specificity of 85.3%, a positive predictive value and a negative predictive value of 94.7% and 90.6%, respectively. The hyperenhancing pattern, indicative of endocrine tumors, had a significant (P = 0.031) diagnostic accuracy of 73.8% with a sensitivity of 83.3%, a specificity of 60.0%, a positive predictive value and negative predictive value of 83.3% and 60.0%, respectively. CONCLUSIONS: Contrast-enhanced ultrasound has a valuable diagnostic accuracy in differentiating exocrine from endocrine pancreatic tumors, which is a fundamental step to address appropriate histological evaluation, therapeutic approach, and follow-up.
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[150]
TÍTULO / TITLE: - Virtual analysis of pancreatic cystic lesion fluid content by ultrasound acoustic radiation force impulse quantification.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Ultrasound Med. 2013 Apr;32(4):647-51.
AUTORES / AUTHORS: - D’Onofrio M; Crosara S; Canestrini S; Demozzi E; De Robertis R; Salvia R; Bassi C; Mucelli RP
INSTITUCIÓN / INSTITUTION: - Department of Radiology, University Hospital G. B. Rossi, University of Verona, Piazzale L. A. Scuro 10, 37134 Verona, Italy. mirko.donofrio@univr.it.
RESUMEN / SUMMARY: - Objectives The purpose of this study was to prospectively evaluate the application of acoustic radiation force impulse (ARFI) imaging implemented with Virtual Touch tissue quantification (Siemens AG, Erlangen, Germany) in the study of pancreatic cystic lesions by using different analysis methods compared with the final diagnosis (pathologic or by magnetic resonance imaging and endoscopic sonographic findings). Methods Thirty-eight patients with pancreatic cystic focal lesions (diameter >3 cm and located at a depth of 5.5 cm) were included in the study and underwent conventional sonography. For every patient, 5 measurements in the Virtual Touch tissue quantification region of interest were obtained. To distinguish mucinous (potentially malignant) from serous (mainly benign) cystic lesions, the result XXXX/0 was considered to mean simple liquids (comparable to water), and the accuracy of Virtual Touch tissue quantification in differentiating pancreatic cystic lesions was calculated. To consider a lesion as containing complex fluids (potentially mucinous), two different reading methods were applied: (1) at least 2 numerical values when obtaining 5 measurements; and (2) the prevalence of numerical values irrespective of the number of measurements. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for the differential diagnosis between mucinous and nonmucinous cystic lesions. Results By the first reading method, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the group of cystic lesions were 68.8%, 77.3%, 68.8%, 77.3%, and 73.7%, respectively; by the second method, the values were 37.5%, 100%, 100%, 68.8%, and 73.3%. Conclusions Acoustic radiation force impulse imaging with Virtual Touch tissue quantification can have a role in the noninvasive characterization of pancreatic cystic lesions during conventional sonographic examinations.
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[151]
TÍTULO / TITLE: - Is extended hemihepatectomy plus pancreaticoduodenectomy justified for advanced bile duct cancer and gallbladder cancer?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surgery. 2013 Feb 13. pii: S0039-6060(12)00737-4. doi: 10.1016/j.surg.2012.11.024.
●● Enlace al texto completo (gratuito o de pago) 1016/j.surg.2012.11.024
AUTORES / AUTHORS: - Sakamoto Y; Nara S; Kishi Y; Esaki M; Shimada K; Kokudo N; Kosuge T
INSTITUCIÓN / INSTITUTION: - Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: yosakamo-tky@umin.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: Major hepatopancreaticoduodenectomy (HPD) is an extensive surgical procedure offering the highest curability for patients with advanced biliary cancer. However, surgical morbidity associated with major HPD is high, and optimal indications for this procedure remain unclear. METHODS: Between 1989 and 2010, 14 patients with widespread bile duct cancer and 5 with gallbladder cancer having biliary infiltration underwent major HPD at our hospital. Preoperative portal vein embolization was performed in 17 patients undergoing right HPD. Clinicopathologic factors and survivals following HPD were compared between patients with bile duct cancer and those with gallbladder cancer. RESULTS: One patient who underwent right HPD for gallbladder cancer died of hepatic failure (5.3%) and 18 of the 19 patients (95%) developed postoperative pancreatic fistulas. The median hospital stay was 47 days. Depth of invasion was T3 in 1 patient and T4 in 2 patients with bile duct cancer and was T4 in all 5 patients with gallbladder cancer (P = .002). The clinical stage was IV in 3 patients (21%) with bile duct cancer and in all 5 patients with gallbladder cancer (P = .002). The 5-year survival rates and median survival rates of patients with bile duct cancer and gallbladder cancer were 45% vs 0 and 3.3 years vs 8 months, respectively (P < .001). CONCLUSION: HPD can be an acceptable treatment option for widespread bile duct cancer. However, the indication for HPD in advanced-stage gallbladder cancer should be considered carefully, considering the high morbidity rate and the advanced stage of the disease.
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[152]
TÍTULO / TITLE: - Histopathologic findings of multifocal pancreatic intraductal papillary mucinous neoplasms on CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - AJR Am J Roentgenol. 2013 Mar;200(3):563-9. doi: 10.2214/AJR.12.8924.
●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8924
AUTORES / AUTHORS: - Raman SP; Kawamoto S; Blackford A; Hruban RH; O’Brien-Lennon AM; Wolfgang CL; Rezaee N; Edil B; Fishman EK
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Johns Hopkins University, 601 N Caroline St, JHOC 3251, Baltimore, MD 21287, USA. srsraman3@gmail.com
RESUMEN / SUMMARY: - OBJECTIVE: The criteria for resection of solitary pancreatic side-branch intraductal papillary mucinous neoplasm (IPMN) have been well described by the Sendai consensus statement. However, the management of multiple pancreatic cystic lesions is less certain, with no clear guidelines in the literature to date. The purpose of this study was to evaluate the histopathologic findings in pancreatic IPMNs in patients with multiple (>/= 4) pancreatic cysts. MATERIALS AND METHODS: The CT scans of all patients with a pathologically proven IPMN at our institution were reviewed, and a total of 52 patients with four or more pancreatic cysts were found. Each case was reviewed for the number of cysts and the presence of signs of invasive malignancy including a coexistent solid pancreatic mass, pancreatic ductal dilatation, and mural nodularity. RESULTS: A total of 52 patients (19 men, 33 women; mean age, 71.8 years) were found to have multifocal IPMNs, defined as four or more cysts, on CT. Of these 52 patients, nine also had evidence of a solid pancreatic mass on CT. Retrospective review of the pathologic results for the remaining 43 patients (17 men, 26 women; mean age, 71.76 years) showed 18 cases of an IPMN with either high-grade dysplasia or a coexistent invasive carcinoma. Most important, 37% (7/19 patients) had no CT findings of an invasive malignancy according to the Sendai criteria (i.e., cysts >/= 3 cm in the axial plane, main pancreatic ductal dilatation >/= 6 mm, or mural nodularity within a cyst) but were found to have an IPMN with either high-grade dysplasia or invasive carcinoma. When the pancreas contained 10 or more cysts, high-grade dysplasia or invasive carcinoma tended to be more likely than low- or intermediate-grade dysplasia (odds ratio, 3.83; 95% CI, 0.87-16.8; p = 0.075). CONCLUSION: The presence of multiple pancreatic cysts should be looked on with suspicion, particularly when there are a large number of cysts, even when none of the cysts individually meet the imaging criteria for resection according to the Sendai consensus recommendations. At the very least, these patients need to be followed very closely.
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[153]
TÍTULO / TITLE: - Differences in Transcript Levels of ABC Transporters Between Pancreatic Adenocarcinoma and Nonneoplastic Tissues.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e318279b861
AUTORES / AUTHORS: - Mohelnikova-Duchonova B; Brynychova V; Oliverius M; Honsova E; Kala Z; Muckova K; Soucek P
INSTITUCIÓN / INSTITUTION: - From the *Department of Toxicogenomics, National Institute of Public Health, Prague; daggerDepartment of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc; double dagger3rd Faculty of Medicine, Charles University, Prague, Czech Republic; Departments of section signTransplantation Surgery and parallelClinical and Transplantation Pathology, Institute of Clinical and Experimental Medicine, Prague; and Departments of paragraph signSurgery and #Pathology, Masaryk University Hospital and Faculty of Medicine, Brno Bohunice.
RESUMEN / SUMMARY: - OBJECTIVES: The aim of this study was to evaluate transcript levels of all 49 human ATP-binding cassette transporters (ABCs) in one of the most drug-resistant cancers, namely, the pancreatic ductal adenocarcinoma (PDAC). Association of ABCs levels with clinical-pathologic characteristics and KRAS mutation status was followed as well. METHODS: Tumors and adjacent nonneoplastic tissues were obtained from 32 histologically verified PDAC patients. The transcript profile of ABCs was assessed using quantitative real-time polymerase chain reaction with a relative standard curve. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and sequencing. RESULTS: Most ABCs were deregulated in PDAC and 10 ABCs were associated with clinical-pathologic characteristics. KRAS mutations did not change the global expression profile of ABCs. CONCLUSIONS: The expression of ABC transporters was significantly deregulated in PDAC tumors when compared to nonmalignant tissues. The observed up-regulation of ABCB4, ABCB11, ABCC1, ABCC3, ABCC5, ABCC10, and ABCG2 in tumors may contribute to the generally poor treatment response of PDAC. The up-regulation of ABCA1, ABCA7, and ABCG1 implicates a serious impairment of cellular cholesterol homeostasis in PDAC. On the other hand, the observed down-regulation of ABCA3, ABCC6, ABCC7, and ABCC8 suggests a possible role of stem cells in the development and progression of PDAC.
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[154]
TÍTULO / TITLE: - A rare case of transient hypercortisolemia resulting from an inflammatory adrenal mass following acute pancreatitis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocrine. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s12020-013-9900-7
AUTORES / AUTHORS: - Miyata M; Yoshida M; Ueda H; Fukuoka K; Oiso Y
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology and Diabetes, Nagoya Ekisaikai Hospital, 4-66 Shounen-cho, Nakagawa-ku, Nagoya, 454-8502, Japan.
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[155]
TÍTULO / TITLE: - Pancreatic cancer-associated Cathepsin E as a drug activator.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Control Release. 2013 Feb 26;167(3):221-227. doi: 10.1016/j.jconrel.2013.02.007.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jconrel.2013.02.007
AUTORES / AUTHORS: - Abd-Elgaliel WR; Cruz-Monserrate Z; Wang H; Logsdon CD; Tung CH
INSTITUCIÓN / INSTITUTION: - Department of Translational Imaging, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, USA.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat, and better means to detect and/or treat pancreatic cancer are urgently needed to save lives. Cathepsin E (Cath E) is a proteolytic enzyme highly expressed in PDAC. In this study, a novel approach using Cath E activation of a Cath E-specific prodrug was demonstrated. Specific activation of the prodrug is expected to kill pancreatic cancer cells without harming normal pancreatic cells. A novel 5-aminolevulinic acid (5-ALA) prodrug was custom-designed to be activated selectively by endogenous Cath E within the PDAC cells. The 5-ALA prodrug was incubated with Cath E-positive and -negative tumor cells and illuminated with various doses of light. In addition, mice genetically engineered to develop PDAC were injected intravenously with the 5-ALA prodrug, and the pancreas was treated with light irradiation. One day after treatment, PDAC tissue was assessed for apoptosis. The 5-ALA prodrug was activated within the Cath E-positive tumor but not in the normal pancreatic tissue. When used in combination with light treatment, it allowed delivery of selective photodynamic therapy (PDT) to the cancerous tissues, with minimal harm to the adjacent normal tissues. With this novel Cath E activation approach, it is possible to detect pancreatic cancer cells accurately and specifically impair their viability, while sparing normal cells. This treatment could result in fewer side effects than the non-specific treatments currently in use. Cath E is a specific and effective drug activator for PDAC treatment.
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[156]
TÍTULO / TITLE: - Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Chemother Pharmacol. 2013 Mar;71(3):663-70. doi: 10.1007/s00280-012-2055-z. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1007/s00280-012-2055-z
AUTORES / AUTHORS: - Fine RL; Gulati AP; Krantz BA; Moss RA; Schreibman S; Tsushima DA; Mowatt KB; Dinnen RD; Mao Y; Stevens PD; Schrope B; Allendorf J; Lee JA; Sherman WH; Chabot JA
INSTITUCIÓN / INSTITUTION: - Division of Medical Oncology, Experimental Therapeutics Program, The Pancreas Center at Columbia, New York Presbyterian-Columbia University Medical Center, New York, NY 10032, USA. rlf20@columbia.edu
RESUMEN / SUMMARY: - PURPOSE: We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ). METHODS: A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR (100%), chemotherapy (61%), and hepatic chemoembolization (50%). Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle. RESULTS: Using RECIST parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths. CONCLUSIONS: CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.
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[157]
- CASTELLANO -
TÍTULO / TITLE:Pseudoquiste pancreatico fistulizado a cavidad pleural. Una rara causa de derrame pleural masivo.
TÍTULO / TITLE: - Pancreatic pseudocyst fistulised to pleural space: A rare cause of a massive pleural effusion.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cir Esp. 2013 Feb 26. pii: S0009-739X(13)00030-4. doi: 10.1016/j.ciresp.2012.11.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ciresp.2012.11.009
AUTORES / AUTHORS: - Caballero Rodriguez E; Hidalgo Rodriguez MA; Herrero Collantes J; Garcia Franco CE
INSTITUCIÓN / INSTITUTION: - Servicio de Cirugia Gral y del Aparato Digestivo, Hospital Universitario Nuestra Senora de Candelaria, Santa Cruz de Tenerife, España. Electronic address: eugenia0005@gmail.com.
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[158]
TÍTULO / TITLE: - The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Rep. 2013 Apr;29(4):1671-7. doi: 10.3892/or.2013.2276. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 3892/or.2013.2276
AUTORES / AUTHORS: - Thakkar A; Sutaria D; Grandhi BK; Wang J; Prabhu S
INSTITUCIÓN / INSTITUTION: - Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
RESUMEN / SUMMARY: - Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with ~37,000 deaths each year. The present study evaluated the chemopreventive potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1 mM), CUR (10 microM) and SFN (5 microM) (ACS) combination reduced cell viability by ~70% (P<0.001), and also induced cell apoptosis by ~51% (P<0.001) accompanied by activation of caspase-3 and Poly(ADP-ribose) polymerase (PARP) proteins. The NF-kappaB DNA binding activity was inhi-bited by ~45% (P<0.01) and ~75% (P<0.001) in MIA PaCa-2 and Panc-1 cells, respectively. Mechanistic studies revealed that ACS promoted increase expression of phospho extracellular signal-regulated kinase ½ (P-ERK1/2), c-Jun, p38 MAPK and p53 proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partially abolished the effect of ACS on cell viability. Data from this study demonstrate that a low-dose ACS combination inhibits cell growth by inducing cell apoptosis, and proposes sustained activation of the ERK1/2 signaling pathway as one of the possible mechanisms.
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[159]
TÍTULO / TITLE: - Tumor Necrosis Factor-alpha Levels Early in Severe Acute Pancreatitis: Is There Predictive Value Regarding Severity and Outcome?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Clin Gastroenterol. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1097/MCG.0b013e31828a6cfc
AUTORES / AUTHORS: - Surbatovic M; Radakovic S
INSTITUCIÓN / INSTITUTION: - *Clinic of Anesthesiology and Intensive Therapy, Military Medical Academy daggerFaculty of Medicine of the Military Medical Academy, University of Defense double daggerSector of Preventive Medicine, Military Medical Academy, Belgrade, Serbia.
RESUMEN / SUMMARY: - GOAL AND BACKGROUND:: One of the most important cytokines in pathogenesis of acute pancreatitis is tumor necrosis factor (TNF)-alpha. The aim of our study was to determine whether the plasma levels of TNF-alpha in patients with severe acute pancreatitis (SAP) on admission correlate with severity and outcome of SAP. STUDY:: Blood samples were obtained from 100 patients with SAP. Patients were divided into 2 groups according to severity: SAP group (n=69) and SAP-induced multiple organ dysfunction syndrome (MODS) group (n=31). Survivors were patients who were alive 90 days after taking the blood sample for cytokine measurement (53/100). Blood sample for cytokine measurement was drawn immediately after admission. TNF-alpha was measured by commercial ELISA test in plasma. RESULTS:: When comparing SAP group with SAP-induced MODS group, we found that mean values of TNF-alpha on admission were 191.5-fold lower in group with SAP-induced MODS (P<0.01). When comparing nonsurvivors with survivors, we found that mean values of TNF-alpha on admission were 63-fold higher in survivors (P<0.01). At cut-off level of 7.95 pg/mL sensitivity was 83.9% and specificity was 72.5%. Patients with TNF-alpha level lower than 7.95 pg/mL had 3.2-fold higher probability to develop SAP with MODS. At cut-off level of 10.5 pg/mL sensitivity was 83% and specificity was 77.4%. Patients with TNF-alpha level higher than 10.5 pg/mL had 4.8-fold higher probability to survive. CONCLUSIONS:: TNF-alpha is good predictor of severity and outcome. Low TNF-alpha concentration in patients with SAP predicts development of MODS and fatal outcome.
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[160]
TÍTULO / TITLE: - Pancreatic cancer and supportive care-pancreatic exocrine insufficiency negatively impacts on quality of life.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Support Care Cancer. 2013 Feb 10.
●● Enlace al texto completo (gratuito o de pago) 1007/s00520-013-1729-3
AUTORES / AUTHORS: - Gooden HM; White KJ
INSTITUCIÓN / INSTITUTION: - Cancer Nursing Research Unit, Sydney Nursing School, University of Sydney, Camperdown, Australia, helen.gooden@sydney.edu.au.
RESUMEN / SUMMARY: - PURPOSE: Pancreatic cancer is a fatal cancer with a median survival from diagnosis of around 5 months Speer et al. (Med J Aust 196(8):511-515, 2012). Given the short survival time for people with pancreatic cancer, effective supportive care is imperative to enable best quality of life. This article presents an unexpected finding from research into the psychosocial supportive care needs of people affected by pancreatic cancer that management of pancreatic exocrine insufficiency is an area of unmet need that severely impacts on quality of life and increases carer burden in people affected by pancreatic cancer. METHODS: A qualitative inquiry framework was used to explore participants’ perspectives and experience. Two groups of participants (N = 35) were recruited across Australia from people accessing the Cancer Helpline or direct referral from clinicians/nurses: patients diagnosed with pancreatic cancer (N = 12) and carers/family (N = 23) including a subgroup of bereaved participants (N = 14). Sampling continued until saturation. A thematic content analysis was conducted. RESULTS: The findings revealed that the major quality of life theme was difficulty in managing gut symptoms and complex dietary issues. Issues were related to lack of information about malabsorption and managing symptoms of pancreatic exocrine insufficiency. This was compounded by a lack of routine dietary consultation: perceived reluctance of clinicians to prescribe enzyme supplements and poor understanding of dose to diet guidelines. CONCLUSION: Participants expressed distress relating to the effects of pancreatic exocrine insufficiency. Pancreatic enzyme supplement therapy with clear dosage guidelines and associated dietary advice could resolve symptoms of malabsorption and markedly improve quality of life. For people affected by pancreatic cancer, this is an essential supportive care.
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[161]
TÍTULO / TITLE: - Pancreatic neuroendocrine tumor with cystlike changes: evaluation with MDCT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - AJR Am J Roentgenol. 2013 Mar;200(3):W283-90. doi: 10.2214/AJR.12.8941.
●● Enlace al texto completo (gratuito o de pago) 2214/AJR.12.8941
AUTORES / AUTHORS: - Kawamoto S; Johnson PT; Shi C; Singhi AD; Hruban RH; Wolfgang CL; Edil BH; Fishman EK
INSTITUCIÓN / INSTITUTION: - The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 N Caroline St, JHOC 3235A, Baltimore, MD 21287, USA. skawamo1@jhmi.edu
RESUMEN / SUMMARY: - OBJECTIVE: The objective of our study was to determine the prevalence and CT appearance of cystlike changes of pancreatic neuroendocrine tumor (NET), particularly of small (</= 3 cm) tumors. MATERIALS AND METHODS: The clinical records, images, and pathologic reports of 74 consecutive patients (average age, 55.5 years) with surgically resected pancreatic NETs who underwent preoperative CT were retrospectively reviewed. The size and location of the pancreatic NETs were recorded. The tumors were classified on the basis of CT appearance as small (</= 3 cm) or large (> 3 cm) and as solid, partially (</= 50% or > 50%) cystic, or purely ( approximately 100%) cystic. Peripheral contrast enhancement on CT was characterized, and lymph node and liver metastases found by pathologic examination were recorded. RESULTS: A total of 78 pancreatic NETs were reviewed. Five were not visualized on CT, leaving 73 pancreatic NETs in 69 patients (multiple tumors were visualized on CT of three patients) for analysis. The mean size of the 73 tumors was 3.0 +/- 2.6 (SD) cm (range, 0.7-13.1 cm); 52 tumors were 3 cm or smaller and 21 tumors were larger than 3 cm. Gross pathologic results confirmed that 13 of the 73 (17.8%) tumors were predominantly (> 50% or approximately 100%) cystic: 10 of the 52 (19.2%) tumors 3 cm or smaller and three of the 21 (14.3%) tumors larger than 3 cm. Peripheral contrast enhancement was seen in 11 of the 13 (85%) predominantly cystic pancreatic NETs. Compared with solid pancreatic NETs, predominantly cystic pancreatic NETs were less commonly associated with lymph node and liver metastases. CONCLUSION: Cystic pancreatic NETs are not rare and should be included in the differential diagnosis of a cystic pancreatic mass, particularly if the cystic mass is associated with peripheral contrast enhancement. A minority of cystic pancreatic NETs can present with no peripheral enhancement.
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[162]
TÍTULO / TITLE: - Retrospective study of gemcitabine plus S-1 versus gemcitabine alone in cases with unresectable advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatogastroenterology. 2013 Mar 11;60(127). doi: 10.5754/hge121235.
●● Enlace al texto completo (gratuito o de pago) 5754/hge121235
AUTORES / AUTHORS: - Suzuki S
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[163]
TÍTULO / TITLE: - The CT findings of pancreatic acinar cell carcinoma in five cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Imaging. 2013 Mar;37(2):302-7. doi: 10.1016/j.clinimag.2012.06.003. Epub 2012 Jul 15.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinimag.2012.06.003
AUTORES / AUTHORS: - Liu K; Peng W; Zhou Z
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
RESUMEN / SUMMARY: - OBJECTIVES: The aim of this study is to analyze the computed tomographic (CT) findings of pancreatic acinar cell carcinoma (ACC). MATERIALS AND METHODS: The CT features and clinical presentations of five patients (four men, one woman; mean age, 52 years) with pathology-proven pancreatic ACC were reviewed. The image characteristics included the lesion location and size, the exophytic nature of the tumor, intratumoral hemorrhage, calcification, the presence of cystic or necrotic components, bile or pancreatic duct dilation, attenuation on the noncontrast image, attenuation on the arterial- and venous-phase images, peripancreatic invasion, peripancreatic lymphadenopathy, and distant metastases. RESULTS: The tumors were located at the pancreatic tail in three cases and at the pancreatic head in two cases. The average lesion size was 5.3 cm. Exophytic features and cystic/necrotic components were found in 80% (4/5) and 60% (3/5) of cases, respectively. The ACC showed a mild hypodense appearance on noncontrast CT in 100% (3/3) of cases and a hypodense appearance on arterial-/venous-phase CT in 80% (4/5) of cases. The exception was one lesion that showed a significantly hyperdense appearance and a mildly hyperdense appearance on the arterial- and venous-phase images. None of the CT images showed enhancement of a capsule, calcification, intratumoral hemorrhage, bile or pancreatic duct dilation, vascular encasement, or distant metastatic disease, but three cases showed peripancreatic invasion and lymphadenopathy. CONCLUSIONS: With persistent mild enhancement, the typical ACC appears as an exophytic tumor with a focal cystic/necrotic component and the lack of ductal dilatation. The predilection for older male patients and elevated serum alpha fetoprotein are useful clinical features for confirming an ACC diagnosis.
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[164]
TÍTULO / TITLE: - Glucagonoma with necrolytic migratory erythema exhibiting responsiveness to subcutaneous octreotide injections.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - QJM. 2013 Feb 6.
●● Enlace al texto completo (gratuito o de pago) 1093/qjmed/hct027
AUTORES / AUTHORS: - Lo CH; Ho CL; Shih YL
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine.
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[165]
TÍTULO / TITLE: - Laparoscopic Partial Sleeve Duodenectomy (PSD) for Nonampullary Duodenal Neoplasms: Avoiding a Whipple by Separating the Duodenum from the Pancreatic Head.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Apr;42(3):461-6. doi: 10.1097/MPA.0b013e3182649956.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182649956
AUTORES / AUTHORS: - Stauffer JA; Raimondo M; Woodward TA; Goldberg RF; Bowers SP; Asbun HJ
INSTITUCIÓN / INSTITUTION: - From the Departments of *General Surgery, and daggerGastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL.
RESUMEN / SUMMARY: - OBJECTIVE: To learn the clinical outcome of patients undergoing laparoscopic partial sleeve duodenectomy (PSD) for lesions, which require sleeve resection of the duodenum. Traditionally, these lesions require en bloc excision of the head of the pancreas performed in an open fashion. METHODS: A retrospective review of medical records of patients with nonampullary large or circumferential duodenal lesions, which were not amenable to endoscopic or local resection for complete removal, was performed. Characteristics, complications, and technical details were analyzed. RESULTS: Ten patients (5 men and 5 women; mean age, 70 years) with duodenal lesions including adenoma (n = 5), adenocarcinoma (n = 2), lymphangiolipoma (n = 1), leiomyoma (n = 1), and neuroendocrine tumor (n = 1) were included. All patients underwent a laparoscopic approach with either a proximal PSD (n = 3) or distal PSD (n = 7) after separation of the duodenum from the pancreatic head. Reconstruction was carried out by a side-to-side duodenojejunostomy (n = 7), end-to-side duodenojejunostomy (n = 2), or gastrojejunostomy (n = 1). Mean length of stay was 5.6 days, and complications were 20%. CONCLUSIONS: Laparoscopic PSD seems to be a safe and easily applicable technique for treatment of duodenal lesions not involving the ampulla, which requires separation of the duodenum from the pancreas head with sleeve resection of the duodenum and subsequent reconstruction.
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[166]
TÍTULO / TITLE: - Pancreatic Endocrine Tumour with Disseminated Pulmonary Thromboembolism in an Owl Monkey (Aotus nancymae).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Comp Pathol. 2013 Feb 28. pii: S0021-9975(12)00423-9. doi: 10.1016/j.jcpa.2012.11.235.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jcpa.2012.11.235
AUTORES / AUTHORS: - Gozalo AS; Zerfas PM; Starost MF; Lambert LE; Elkins WR
INSTITUCIÓN / INSTITUTION: - Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: gozaloa@niaid.nih.gov.
RESUMEN / SUMMARY: - Pulmonary thromboembolism associated with pancreatic endocrine neoplasia is extremely uncommon in man and animals. Post-mortem examination of an adult owl monkey (Aotus nancymae) revealed extensive pulmonary arterial thromboembolism and a well-demarcated mass attached to the pancreas. Microscopically, the mass consisted of areas of interstitial fibrosis with loss of acini and islets and replacement by nests and sheets of polygonal cells with amphophilic cytoplasm, an eccentric round nucleus with stippled chromatin and, in some cells, with a single prominent eccentric nucleolus. Clusters of these cells were noted within vessels and adjacent lymph nodes. The cells did not express S100 or insulin, but were labelled strongly with SP-1/chromogranin. Rare individual cells expressed glucagon and somatostatin. A few cells in pulmonary thrombi/emboli and the adjacent lymph node also expressed SP-1/chromogranin. Based on cell morphology, location and immunohistochemistry the tumour was classified as pancreatic endocrine (islet cell) carcinoma with metastasis to regional lymph nodes and lung.
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[167]
TÍTULO / TITLE: - A minimally invasive and simple screening test for detection of pancreatic ductal adenocarcinoma using biomarkers in duodenal juice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar;42(2):187-92. doi: 10.1097/MPA.0b013e3182649979.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e3182649979
AUTORES / AUTHORS: - Mori Y; Ohtsuka T; Kono H; Nagayoshi Y; Ideno N; Aso T; Kozono S; Ohuchida K; Takahata S; Nakamura M; Mizumoto K; Tanaka M
INSTITUCIÓN / INSTITUTION: - From the Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - OBJECTIVES: The aim of this study was to establish a minimally invasive and simple screening test for detection of pancreatic ductal adenocarcinoma (PDAC) using duodenal juice (DJ). METHODS: Duodenal juice was collected prospectively before endoscopic retrograde cholangiopancreatography in 46 patients. A protease inhibitor was not added to the samples collected during the initial 2.5 minutes but was added in the latter 2.5 minutes. Thereafter, secretin was administered intravenously, and DJ was subsequently collected for additional 10 minutes. The sensitivities of carcinoembryonic antigen (CEA), S100 calcium-binding protein P (S100P), and interleukin 8 in DJ and pancreatic juice were assessed. RESULTS: There were 30 patients with PDAC and 16 with benign lesions. It was possible to collect an adequate amount of DJ without secretin administration. In the PDAC group, CEA concentrations in DJ were significantly higher than those in the benign group, even without the use of a protease inhibitor. S100P levels in DJ in the PDAC group were significantly higher than those in the benign group in the presence of the protease inhibitor. CONCLUSIONS: Duodenal juice collection during routine upper endoscopy and assessments of CEA and S100P in DJ might become a useful screening test for detection of PDAC.
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[168]
TÍTULO / TITLE: - Intraductal Papillary Mucinous Neoplasm Associated With Autoimmune Pancreatitis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Apr;42(3):552-554.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826cc2fc
AUTORES / AUTHORS: - Naitoh I; Nakazawa T; Notohara K; Miyabe K; Hayashi K; Shimizu S; Kondo H; Yoshida M; Yamashita H; Umemura S; Ohara H; Joh T
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya, Japan tnakazaw@med.nagoya-cu.ac.jp Department of Pathology Kurashiki Central Hospital Kurashiki, Japan Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya, Japan Department of Community-based Medical Education Nagoya City University Graduate School of Medical Sciences Nagoya, Japan Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya, Japan.
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[169]
TÍTULO / TITLE: - Branch duct intraductal papillary mucinous neoplasms of the pancreas: watch and wait is not harmless.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar;42(2):358. doi: 10.1097/MPA.0b013e31826ae338.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31826ae338
AUTORES / AUTHORS: - Fritz S; Werner J; Buchler MW
INSTITUCIÓN / INSTITUTION: - Department of General and Visceral Surgery University of Heidelberg Heidelberg, Germany Markus.Buechler@med.uni-heidelberg.de.
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[170]
TÍTULO / TITLE: - Metformin Inhibits the Growth of Human Pancreatic Cancer Xenografts.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreas. 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1097/MPA.0b013e31827aec40
AUTORES / AUTHORS: - Kisfalvi K; Moro A; Sinnett-Smith J; Eibl G; Rozengurt E
INSTITUCIÓN / INSTITUTION: - From the Departments of *Medicine, daggerSurgery, and double daggerCURE: Digestive Diseases Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA.
RESUMEN / SUMMARY: - OBJECTIVE: Pancreatic ductal adenocarcinoma is a devastating disease, with an overall 5-year survival rate of only 3% to 5%. As the current therapies offer very limited survival benefits, novel therapeutic strategies are urgently required to treat this disease. Here, we determined whether metformin administration inhibits the growth of PANC-1 and MiaPaCa-2 tumor xenografts in vivo. METHODS: Different xenograft models, including orthotopic implantation, were used to determine whether intraperitoneal or oral administration of metformin inhibits the growth of pancreatic cancer in vivo. RESULTS: We demonstrate that metformin given once daily intraperitoneally at various doses (50-250 mg/kg) to nude mice inhibited the growth of PANC-1 xenografts in a dose-dependent manner. A significant effect of metformin was obtained at 50 mg/kg and maximal effect at 200 mg/kg. Metformin administration also caused a significant reduction in the phosphorylation of ribosomal S6 protein and ERK in these xenografts. Metformin also inhibited the growth of pancreatic cancer xenografts when administered orally (2.5 mg/mL) either before or after tumor implantation. Importantly, oral administration of metformin also inhibited the growth of MiaPaCa-2 tumors xenografted orthotopically. CONCLUSIONS: The studies presented here provide further evidence indicating that metformin offers a potential novel approach for pancreatic ductal adenocarcinoma prevention and therapy.
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[171]
TÍTULO / TITLE: - Complete Pathological Remission of Locally Advanced, Unresectable Pancreatic Cancer (LAPC) after Intensified Neoadjuvant Chemotherapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onkologie. 2013;36(3):123-5. doi: 10.1159/000348527. Epub 2013 Feb 25.
●● Enlace al texto completo (gratuito o de pago) 1159/000348527
AUTORES / AUTHORS: - Hartlapp I; Muller J; Kenn W; Steger U; Isbert C; Scheurlen M; Germer CT; Einsele H; Kunzmann V
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine II, University of Wurzburg, Germany.
RESUMEN / SUMMARY: - Background: Unresectable locally advanced pancreatic cancer (LAPC) has an extremely poor prognosis. Results of neoadjuvant (radio-)chemotherapy approaches aiming at achieving resectability are currently not satisfactory. Case Report: We report the case of a 67-year-old woman with histologically confirmed pancreas carcinoma that was not resectable on first surgical exploration who achieved a well-documented complete pathological remission (pCR). The carcinoma became resectable after consecutive neoadjuvant treatment with nanoparticle albumin-bound (nab)-paclitaxel/gemcitabine and FOLFIRINOX chemotherapy regimens. Conclusion: This is the first reported LAPC case in which neoadjuvant chemotherapy alone has been shown to lead to demonstrated pCR. CA19-9 levels, but not imaging criteria, were useful for response prediction and timing of the Whipple’s procedure. The findings in this case suggest possible conceptual changes in the treatment approach for LAPC, and indicate that the new effective chemotherapy regimens should be integrated into clinical trials for LAPC.
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[172]
TÍTULO / TITLE: - Adenosquamous carcinoma of the pancreas: multidetector-row computed tomographic manifestations and tumor characteristics.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Comput Assist Tomogr. 2013 Mar;37(2):125-33. doi: 10.1097/RCT.0b013e31827bc452.
●● Enlace al texto completo (gratuito o de pago) 1097/RCT.0b013e31827bc452
AUTORES / AUTHORS: - Yin Q; Wang C; Wu Z; Wang M; Cheng K; Zhao X; Yuan F; Tang Y; Miao F
INSTITUCIÓN / INSTITUTION: - From the Departments of *Radiology, daggerGeneral Surgery, and double daggerPathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
RESUMEN / SUMMARY: - OBJECTIVE: The purpose of this article was to present the adenosquamous carcinoma (ASqC) of the pancreas: multidetector-row computed tomographic (CT) features and tumor characteristics. MATERIALS AND METHODS: The clinical data and CT studies of 12 patients with pathologically proven ASqC of the pancreas between the dates February 2001 and February 2010 were retrospectively analyzed. RESULTS: The presenting symptoms of ASqC of the pancreas were nonspecific. Elevated serum levels of carbohydrate antigen 19-9, carbohydrate antigen 12-5, and carcinoembryonic antigen were noted. The tumor was most commonly involved in the pancreatic head in 6 patients, with the dilation of the common bile duct and the upstream main pancreatic duct. All ASqCs exhibited invasive growth. No calcification and intratumoral hemorrhage were noted in ASqCs. Ten tumors showed enhancement in the early arterial phase and persistent enhancement in the portal vein phase. CONCLUSION: The typical CT appearance of ASqC was solitary oval or round without any capsule and a defined margin. The dilation of the main pancreatic duct and/or the common bile duct was always discovered. The huge infiltrative lesion outside the pancreas was detected in the tail and/or the body of the pancreas. Not only the elevation of carbohydrate antigen 19-9 is common, but also Ca12-5 and CEA, whereas human alpha fetoprotein elevation is not observed. The enhancement pattern of tumor showed persistence in the portal vein phase.
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[173]
TÍTULO / TITLE: - Hepatobiliary and Pancreatic: Cystic bile duct remnant after surgery for a choledochal cyst.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastroenterol Hepatol. 2013 Apr;28(4):754. doi: 10.1111/jgh.12126.
●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12126
AUTORES / AUTHORS: - Matsuura K; Hashimoto D; Ikuta Y; Chikamoto A; Beppu T; Baba H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
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[174]
TÍTULO / TITLE: - VEGF-C ShRNA inhibits pancreatic cancer growth and lymphangiogenesis in an orthotopic fluorescent nude mouse model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anticancer Res. 2013 Feb;33(2):409-17.
AUTORES / AUTHORS: - Shi Y; Tong M; Wu Y; Yang Z; Hoffman RM; Zhang Y; Tian Y; Qi M; Lin Y; Liu Y; Dai L; Sun Y; Wang Z
INSTITUCIÓN / INSTITUTION: - Department of Radiology, East Hospital, Tongji University School of Medicine. 150 Jimo Road, Shanghai 200120, PR China.
RESUMEN / SUMMARY: - The aim of this study was to assess the inhibitory efficacy of short hairpin RNA (ShRNA) targeting vascular endothelial growth factor C (VEGF-C) in an orthotopic pancreatic cancer mouse model. BxPC-3 human pancreatic cancer cells expressing green fluorescent protein (GFP) were orthotopically implanted onto the pancreas of nude mice. All mice were randomly divided into four groups when the average tumor size had reached 100 mm(3) and were treated with either vehicle or gemcitabine at 150 mg/kg; or intravenous VEGF-C ShRNA at 150 mg/kg; or intratumoral VEGF-C ShRNA at 150 mug/kg. In vivo fluorescence imaging was performed to monitor tumor growth and metastasis during the study. Real-time quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay (ELISA) were performed to determine the mRNA and protein level of VEGF-C in tumor tissues. Lymphatic vessel marker D2-40, blood vessel marker CD31 and proliferation marker Ki67 expression of the tumor tissues were analyzed by immunohistochemistry staining. Intravenous and intratumoral VEGF-C ShRNA treatment significantly inhibited tumor growth, downregulated the expression of VEGF-C mRNA, reduced tumor microlymphatic vessel density (MLVD), and inhibited cancer cell proliferation. Gemcitabine, as the standard treatment for pancreatic cancer, demonstrated a stronger inhibitory effect on tumor growth, with less inhibition of MLVD and more inhibition of microvessel density (MVD) and proliferation than VEGF-C ShRNA. These results indicate that different mechanisms are associated with the efficacy of gemcitabine and VEGF-C ShRNA.
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[175]
TÍTULO / TITLE: - Diabetes, insulin use, smoking, and pancreatic cancer mortality in Taiwan.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Acta Diabetol. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00592-013-0471-0
AUTORES / AUTHORS: - Tseng CH
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, National Taiwan University College of Medicine, No. 7 Chung-Shan South Road, Taipei, 100, Taiwan, ccktsh@ms6.hinet.net.
RESUMEN / SUMMARY: - The aim of the study was to evaluate the link between diabetes and pancreatic cancer (PC) mortality and the joint effect of smoking and insulin use on PC mortality. A total of 39,988 men and 46,909 women with type 2 diabetes, aged >/=25 years and recruited in 1995-1998, were followed to 2006 for PC mortality. Age-sex-specific mortality rate ratios for diabetic patients versus the general population were calculated. Cox regression was used to evaluate hazard ratios for PC mortality for covariates including age, sex, diabetes duration, body mass index, smoking, insulin use, and area of residence. The interaction and joint effect of smoking and insulin use were also evaluated. A total of 89 men and 63 women died of PC. The mortality rate ratios (95 % CI) showed a significantly higher risk in diabetic patients with a magnitude most remarkable at the youngest age: 1.51 (1.15, 1.98), 2.02 (1.35, 3.03), and 8.36 (5.39, 12.98) for >/=65, 55-64, and 25-54 years old, respectively, for men; and 1.16 (0.84, 1.59), 2.12 (1.39, 3.23) and 3.33 (1.14, 9.68), respectively, for women. In multivariable Cox regression analysis, only age was significantly predictive for PC mortality. Although smoking and insulin use might be associated with a 50 % higher risk when analyzed as individual risk factors, they did not reach statistical significance. The interaction term of smoking and insulin use was also not statistically significant in additional modeling. However, smoking and insulin use jointly increased the risk with an adjusted hazard ratio (95 % CI) of 3.04 (1.37, 6.73) when compared to patients who did not smoke and did not use insulin. Diabetic patients have a significantly higher risk of PC mortality. In patients with type 2 diabetes, smoking and insulin use may jointly increase the risk by threefold.
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[176]
TÍTULO / TITLE: - BCL10 as a useful marker for pancreatic acinar cell carcinoma, especially using endoscopic ultrasound cytology specimens.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pathol Int. 2013 Mar;63(3):176-82. doi: 10.1111/pin.12045.
●● Enlace al texto completo (gratuito o de pago) 1111/pin.12045
AUTORES / AUTHORS: - Hosoda W; Sasaki E; Murakami Y; Yamao K; Shimizu Y; Yatabe Y
INSTITUCIÓN / INSTITUTION: - Departments of Pathology and Molecular Diagnostics.
RESUMEN / SUMMARY: - Acinar cell carcinomas (ACCs) of the pancreas are characterized by the histological and immunohistochemical features of acinar cell differentiation. Recently, BCL10, originally identified as a recurrent t(1;14)(p22;q32) translocation in MALT B-cell lymphoma, was found to be immunohistochemically positive in some solid tumors, including ACC. To evaluate its diagnostic efficacy, we performed BCL10 immunohistochemistry and evaluated molecular markers correlated to pancreatic tumor lineages (neuroendocrine markers and a mutation analysis of KRAS and GNAS) using samples from 126 pancreatic tumors (17 ACCs, 24 pancreatic ductal adenocarcinomas, 4 adenosquamous carcinomas, 9 intraductal papillary mucinous neoplasms, 10 mucinous cystic neoplasms, 44 neuroendocrine tumors, 9 serous cystic tumors and 10 solid-pseudopapillary neoplasms). BCL10 was exclusively expressed in normal acini. In pancreatic tumors, 14 of 17 (82%) ACCs and 2 of 4 (50%) adenosquamous carcinomas were positive, while the other subtypes were almost negative. We subsequently examined the diagnostic utility of BCL10 in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens using 57 pancreatic tumors. BLC10 correctly identified ACCs (9/13) and adenosquamous carcinomas (2/4) but none of the other subtypes (n = 41). Therefore, we suggested that BCL10 expression is a useful marker for acinar cell differentiation, particularly in the diagnosis of EUS-FNA specimens.
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[177]
TÍTULO / TITLE: - Invaginated ampulla of Vater in synchronous malignant intraductal papillary mucinous neoplasm of the pancreas and common bile duct cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endoscopy. 2013;45 Suppl 2 UCTN:E25-6. doi: 10.1055/s-0032-1326106. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1055/s-0032-1326106
AUTORES / AUTHORS: - Han JW; Jang SI; Ma DW; Yoon SO; Lee DK
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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[178]
TÍTULO / TITLE: - A Case of Insulinoma Detected by 68Ga-DOTANOC PET/CT and Missed by 18F-Dihydroxyphenylalanine PET/CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e31825b222f
AUTORES / AUTHORS: - Treglia G; Inzani F; Campanini N; Rindi G; Agnes S; Giordano A; Rufini V
INSTITUCIÓN / INSTITUTION: - From the *Institute of Nuclear Medicine, Department of Bioimaging and Radiological Sciences and daggerInstitute of Pathology, Catholic University of the Sacred Heart, Rome; double daggerDepartment of Pathology and Laboratory Medicine, University of Parma, Parma; and section signDepartment of Surgery, Catholic University of the Sacred Heart, Rome, Italy.
RESUMEN / SUMMARY: - ABSTRACT: A 65-year-old woman with suspected insulinoma on the basis of clinical, biochemical, and conventional imaging data underwent F-dihydroxyphenylalanine (DOPA) PET/CT and Ga-DOTANOC PET/CT. F-DOPA PET/CT did not show any focal uptake in the pancreas, whereas Ga-DOTANOC PET/CT showed a focal area of intense uptake in the pancreatic tail. The patient underwent surgery and an insulinoma of about 20 mm in diameter was detected in the pancreatic tail. F-DOPA PET may fail in localizing insulin secreting tumors in adults; in these cases, the use of Ga-somatostatin analogs may lead to the correct diagnosis.
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[179]
TÍTULO / TITLE: - A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome Caused by a Metastatic Neuroendocrine Tumor of the Pancreas Detected by 68Ga-DOTANOC and 18F-FDG PET/CT.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e318279ec68
AUTORES / AUTHORS: - Treglia G; Salomone E; Petrone G; Giaccari A; Rindi G; Rufini V
INSTITUCIÓN / INSTITUTION: - From the *Institute of Nuclear Medicine, Department of Bioimaging and Radiological Sciences, daggerDivision of Endocrinology and Metabolic Diseases, and double daggerInstitute of Pathology, Catholic University of the Sacred Heart, Rome, Italy.
RESUMEN / SUMMARY: - We report a rare case of ectopic adrenocorticotropic hormone (ACTH) syndrome caused by a metastatic neuroendocrine tumor (NET) of the pancreas detected by PET/CT using different tracers. A 43-year-old female patient with Cushing syndrome (CS) by suspected ectopic ACTH secretion underwent a Ga-DOTANOC and a F-FDG PET/CT. Both these functional imaging techniques revealed increased tracer uptake in a pancreatic mass and multiple liver metastases. Histology showed the presence of a mildly differentiated pancreatic NET. Ga-DOTANOC PET/CT may be a useful functional imaging method, complementary to F-FDG PET/CT, in detecting ACTH-secreting pancreatic NETs.
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[180]
TÍTULO / TITLE: - Diagnosis and management of insulinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Feb 14;19(6):829-37. doi: 10.3748/wjg.v19.i6.829.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i6.829
AUTORES / AUTHORS: - Okabayashi T; Shima Y; Sumiyoshi T; Kozuki A; Ito S; Ogawa Y; Kobayashi M; Hanazaki K
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Kochi Health Sciences Center, Kochi 781-8555, Japan. takehiro_okabayashi@khsc.or.jp
RESUMEN / SUMMARY: - Insulinomas, the most common cause of hypoglycemia related to endogenous hyperinsulinism, occur in 1-4 people per million of the general population. Common autonomic symptoms of insulinoma include diaphroresis, tremor, and palpitations, whereas neuroglycopenenic symptoms include confusion, behavioural changes, personality changes, visual disturbances, seizure, and coma. Diagnosis of suspected cases is based on standard endocrine tests, especially the prolonged fasting test. Non-invasive imaging procedures, such as computed tomography and magnetic resonance imaging, are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion. Invasive modalities, such as endoscopic ultrasonography and arterial stimulation venous sampling, are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to non-invasive localization techniques. The range of techniques available for the localization of insulinomas means that blind resection can be avoided. Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas. A high proportion of patients with insulinomas can be cured with surgery. In patients with malignant insulinomas, an aggressive medical approach, including extended pancreatic resection, liver resection, liver transplantation, chemoembolization, or radiofrequency ablation, is recommended to improve both survival and quality of life. In patients with unresectable or uncontrollable insulinomas, such as malignant insulinoma of the pancreas, several techniques should be considered, including administration of ocreotide and/or continuous glucose monitoring, to prevent hypoglycemic episodes and to improve quality of life.
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[181]
TÍTULO / TITLE: - EUS for Pancreas Cysts: What Should We Be Sampling?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Dis Sci. 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s10620-013-2617-x
AUTORES / AUTHORS: - Sreenarasimhaiah J
INSTITUCIÓN / INSTITUTION: - University of Texas Southwestern Medical Center, Dallas, TX, USA, jayaprakash.sree@yahoo.com.
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[182]
TÍTULO / TITLE: - Tumor-positive resection margins reflect an aggressive tumor biology in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Surg Oncol. 2013 Feb 28. doi: 10.1002/jso.23299.
●● Enlace al texto completo (gratuito o de pago) 1002/jso.23299
AUTORES / AUTHORS: - Kimbrough CW; St Hill CR; Martin RC; McMasters KM; Scoggins CR
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology, The Hiram C. Polk, J.R., M.D. Department of Surgery, University of Louisville, Louisville, Kentucky.
RESUMEN / SUMMARY: - BACKGROUND: Resection margin status has been shown to impact outcomes for pancreatic adenocarcinoma (PAC), yet it remains unknown whether margin status is a reflection of tumor biology or surgical technique. METHODS: Two hundred eighty-three consecutive patients with pancreatic adenocarcinoma were identified in a prospectively maintained database. Only patients with R0 (n = 207) or R1 (n = 76) tumors were included. Each operative surgeon’s first 50 cases were excluded to control for technical inexperience. Univariable and multivariable analyses of clinicopathologic and intra-operative factors were performed. RESULTS: The median follow-up for the cohort was 30.3 months with a median overall survival (OS) of 19.0 months. The R1 group had a higher rate of lymph node ratio >0.2 (41% vs. 25%; P = 0.013), and more microvascular invasion (64% vs. 44%; P = 0.007). R0 resections had both improved overall survival (22.7 months vs. 15.0 months, P = 0.004) and disease free survival (13.5 months vs. 10.7 months, P = 0.026). Factors independently associated with overall survival were microvascular invasion (HR 2.26; P = 0.001), pre-existing pulmonary disease (HR 2.18, P = 0.043), and cardiac disease (HR 1.78, P = 0.033). CONCLUSION: Factors associated with an R1 resection reflect a biologically more aggressive tumor, with a higher likelihood of microvascular invasion and increased positive lymph node ratio. J. Surg. Oncol © 2013 Wiley Periodicals, Inc.
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[183]
TÍTULO / TITLE: - Psammoma bodies and abundant stromal amyloid in an endoscopic ultrasound guided fine needle aspirate (EUS-FNA) of a pancreatic neuroendocrine tumor: A potential pitfall.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Cytopathol. 2013 Feb 28. doi: 10.1002/dc.22975.
●● Enlace al texto completo (gratuito o de pago) 1002/dc.22975
AUTORES / AUTHORS: - Samad A; Attam R; Jessurun J; Pambuccian SE
INSTITUCIÓN / INSTITUTION: - Department of Laboratory Medicine and Pathology, and Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
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[184]
TÍTULO / TITLE: - Hepatobiliary and Pancreatic: Intrahepatic biliary cystadenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastroenterol Hepatol. 2013 Apr;28(4):753. doi: 10.1111/jgh.12127.
●● Enlace al texto completo (gratuito o de pago) 1111/jgh.12127
AUTORES / AUTHORS: - Okano K; Oshima M; Yamamoto N; Yachida S; Suzuki Y
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
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[185]
TÍTULO / TITLE: - Contemporary management of perihilar cholangiocarcinoma in a nontransplant hepatopancreatobiliary center.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Gastroenterol Hepatol. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1097/MEG.0b013e32835fba3a
AUTORES / AUTHORS: - Jegatheeswaran S; Sheen AJ; Siriwardena AK
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Regional Hepatopancreatobiliary Surgery Unit, Manchester Royal Infirmary, Manchester, UK.
RESUMEN / SUMMARY: - BACKGROUND: Perihilar cholangiocarcinoma (PHCC) is a rare tumor with a poor prognosis. Outcomes may be optimized by centralization. Recent trends suggest further improvement by localization to transplant centers. This study examines outcomes from the management of PHCC in a nontransplant hepatopancreatobiliary center. METHODS: Data were collected prospectively from patients undergoing treatment for PHCC from October 1999 to May 2011. Twenty-four patients underwent surgery. A further 54 patients had inoperable PHCC. Outcome data are reported. RESULTS: Twenty-two of 24 patients required liver resection with histological R0 status in 12 (50%). In-hospital mortality occurred in two (8%). The mean survival of patients undergoing resection was 39 (95% CI: 16-61) months. The mean survival of nonresected patients was 5 (95% CI: 3-7) months (P<0.0001; log-rank; Mantel-Cox test). CONCLUSION: Currently acceptable standards of holistic care for patients with PHCC can be provided in a nontransplant regional hepatopancreatobiliary center. Further centralization may improve resection volumes and allow more patients to benefit from extended liver resection techniques.
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[186]
TÍTULO / TITLE: - Concentrations and activities of metalloproteinases 2 and 9 and their inhibitors (TIMPS) in chronic pancreatitis and pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Physiol Pharmacol. 2012 Dec;63(6):589-99.
AUTORES / AUTHORS: - Lekstan A; Lampe P; Lewin-Kowalik J; Olakowski M; Jablonska B; Labuzek K; Jedrzejowska-Szypulka H; Olakowska E; Gorka D; Filip I; Dranka-Bojarowska D
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland. andrzejlekstan@gmail.com
RESUMEN / SUMMARY: - Pancreatic cancer (PC) and chronic pancreatitis (CP) are still significant problems. The aim of this study was a comparative analysis of the activity and concentrations of matrix metalloproteinases 2 and 9 and the concentrations of their tissue inhibitors (TIMP 1 and 2) in the PC compared to CP tissue homogenates. The study was performed in a group of 63 patients with pancreatic cancer or chronic pancreatitis selected for resection procedures. Group 1 consisted of 31 patients with CP, group 2 consisted of 32 patients with PC. There was no coincidence of pancreatic cancer in CP group. The pancreatic tumor samples have been properly prepared in order to perform electrophoresis and immunoassay testing. The activity of MMPs and the concentrations of MMPs and TIMPs were evaluated. Results: the revealed activities of gelatinases and concentrations levels of the gelatinases and their inhibitors were significantly higher in the PC tissue samples compared to CP. In both groups, higher concentrations of MMP9 compared to MMP2 and TIMP2 compared to TIMP1 were shown. High potential for tumor invasiveness demonstrated by the formation of lymph node metastases was characterized by the higher concentrations of MMP9 and TIMP2. However, in the case of infiltration of the nerve fibers, a decrease in the concentration of MMP2 was found. Conclusions: gelatinases and their inhibitors play important role in the pathogenesis of the CP as well as PC. The activity and concentration of gelatinases and the concentration of their inhibitors were all significantly higher in the PC group.
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[187]
TÍTULO / TITLE: - Intraductal growing acinar cell carcinoma of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Abdom Imaging. 2013 Mar 21.
●● Enlace al texto completo (gratuito o de pago) 1007/s00261-013-9993-8
AUTORES / AUTHORS: - Kim HJ; Kim YK; Jang KT; Lim JH
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.
RESUMEN / SUMMARY: - Acinar cell carcinoma (ACC) is a rare pancreatic exocrine neoplasm characterized by a huge, exophytic well-circumscribed hypovascular mass. There has been several reports describing intraductal and papillary variant of ACC and they showed different radiologic features from usual ACC. We present histologically confirmed cases of intraductal and papillary variant of ACC that had been found in two patients, who underwent CT and MRI. This report provides CT and MRI features of intraductal and papillary variant of ACC in pancreas with pathologic correlation after surgical excision.
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[188]
TÍTULO / TITLE: - Hypocellular pancreatic cyst aspirates—what are we missing?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Cytopathol. 2013 Mar;41(3):189-91. doi: 10.1002/dc.21797. Epub 2011 Aug 26.
●● Enlace al texto completo (gratuito o de pago) 1002/dc.21797
AUTORES / AUTHORS: - Kapur U; Staerkel GA
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USA. ukapur@lumc.edu
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[189]
TÍTULO / TITLE: - Inflammatory networks and immune surveillance of pancreatic carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Opin Immunol. 2013 Feb 16. pii: S0952-7915(13)00007-1. doi: 10.1016/j.coi.2013.01.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.coi.2013.01.006
AUTORES / AUTHORS: - Vonderheide RH; Bayne LJ
INSTITUCIÓN / INSTITUTION: - 8-121 Smilow Center for Translational Research, 3400 Civic Center Blvd, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: rhv@exchange.upenn.edu.
RESUMEN / SUMMARY: - Cancer-associated inflammation plays an important role in restraining anti-tumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA) for which a massive infiltration of immunosuppressive leukocytes into the tumor stroma is an early and consistent event in oncogenesis. Intratumoral effector T cells are rare. This pathophysiology is in contrast to many other solid tumors for which infiltration of effector T cells is often prominent, associated with improved clinical outcomes, and mechanistically contributes to tumor immunoediting that ultimately can mediate immune escape. In PDA, increasing evidence suggests that the ras oncogene drives an inflammatory program that establishes immune privilege in the tumor microenvironment. Indeed, PDA cells might remain intrinsically sensitive to T cell killing because they have never been exposed to T cell selective pressure in vivo. In support of this hypothesis, recent studies demonstrate that derailing immune suppressive pathways in the PDA microenvironment, such as tumor derived GM-CSF, facilitates T-cell mediated tumor rejection. These findings carry major implications for the development of novel, combination immunotherapies for pancreatic cancer.
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[190]
TÍTULO / TITLE: - Metachronous colonic metastasis from pancreatic cancer seven years post-pancreatoduodenectomy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Mar 14;19(10):1665-8. doi: 10.3748/wjg.v19.i10.1665.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i10.1665
AUTORES / AUTHORS: - Inada K; Shida D; Noda K; Inoue S; Warabi M; Umekita N
INSTITUCIÓN / INSTITUTION: - Kentaro Inada, Dai Shida, Kazumasa Noda, Satoru Inoue, Nobutaka Umekita, Department of Surgery, Tokyo Metropolitan Bokutoh Hospital, Sumida-ku, Tokyo 1308575, Japan.
RESUMEN / SUMMARY: - Colonic metastasis from other organs is very rare. Here we report the case of a 62-year-old man with a history of pancreatoduodenectomy for stage IIB pancreatic head cancer performed seven years back. He presented with abdominal distension and pain. Under the preoperative diagnosis of bowel obstruction, surgical treatment was performed, and a circumferential lesion causing bowel obstruction of the ascending colon was detected. A right hemicolectomy with lymph node dissection was performed. The specimen showed a 5-cm wall thickening with a cobble-stone like appearance of the ascending colon, which morphologically appeared scirrhous. Histological examination revealed cancer nests invading from the subserosa to the muscular and submucosal layers of the colon. Immunohistochemical analysis of the tumor cells demonstrated positive staining for cytokeratin 7, but negative for cytokeratin 20, which was the same as the previous pancreatic cancer specimen. These pathological and immunohistochemical features strongly supported the diagnosis of colonic metastasis from the pancreas. Thereafter, the patient received systemic chemotherapy, but unfortunately, he died 14 mo after the surgery.
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[191]
TÍTULO / TITLE: - Middle segmental pancreatectomy: A safe and organ-preserving option for benign and low-grade malignant lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastroenterol. 2013 Mar 7;19(9):1458-65. doi: 10.3748/wjg.v19.i9.1458.
●● Enlace al texto completo (gratuito o de pago) 3748/wjg.v19.i9.1458
AUTORES / AUTHORS: - Du ZY; Chen S; Han BS; Shen BY; Liu YB; Peng CH
INSTITUCIÓN / INSTITUTION: - Zhi-Yong Du, Ying-Bing Liu, Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
RESUMEN / SUMMARY: - AIM: To study the feasibility and safety of middle segmental pancreatectomy (MSP) compared with pancreaticoduodenectomy (PD) and extended distal pancreatectomy (EDP). METHODS: We studied retrospectively 36 cases that underwent MSP, 44 patients who underwent PD, and 26 who underwent EDP with benign or low-grade malignant lesions in the mid-portion of the pancreas, between April 2003 and December 2009 in Ruijin Hospital. The perioperative outcomes and long-term outcomes of MSP were compared with those of EDP and PD. Perioperative outcomes included operative time, intraoperative hemorrhage, transfusion, pancreatic fistula, intra-abdominal abscess/infection, postoperative bleeding, reoperation, mortality, and postoperative hospital time. Long-term outcomes, including tumor recurrence, new-onset diabetes mellitus (DM), and pancreatic exocrine insufficiency, were evaluated. RESULTS: Intraoperative hemorrhage was 316.1 +/- 309.6, 852.2 +/- 877.8 and 526.9 +/- 414.5 mL for the MSP, PD and EDP groups, respectively (P < 0.05). The mean postoperative daily fasting blood glucose level was significantly lower in the MSP group than in the EDP group (6.3 +/- 1.5 mmol/L vs 7.3 +/- 1.5 mmol/L, P < 0.05). The rate of pancreatic fistula was higher in the MSP group than in the PD group (42% vs 20.5%, P = 0.039), all of the fistulas after MSP corresponded to grade A (9/15) or B (6/15) and were sealed following conservative treatment. There was no significant difference in the mean postoperative hospital stay between the MSP group and the other two groups. After a mean follow-up of 44 mo, no tumor recurrences were found, only one patient (2.8%) in the MSP group vs five (21.7%) in the EDP group developed new-onset insulin-dependent DM postoperatively (P = 0.029). Moreover, significantly fewer patients in the MSP group than in the PD (0% vs 33.3%, P < 0.001) and EDP (0% vs 21.7%, P = 0.007) required enzyme substitution. CONCLUSION: MSP is a safe and organ-preserving option for benign or low-grade malignant lesions in the neck and proximal body of the pancreas.
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[192]
TÍTULO / TITLE: - Limited Efficacy of 18F-FDG PET/CT for Differentiation Between Metastasis-Free Pancreatic Cancer and Mass-Forming Pancreatitis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Nucl Med. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1097/RLU.0b013e3182817d9d
AUTORES / AUTHORS: - Kato K; Nihashi T; Ikeda M; Abe S; Iwano S; Itoh S; Shimamoto K; Naganawa S
INSTITUCIÓN / INSTITUTION: - From the *Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine; daggerDepartment of Radiology, Nagoya University Hospital; double daggerDepartment of Radiology, Nagoya University Graduate School of Medicine; and section signDepartment of Radiology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
RESUMEN / SUMMARY: - OBJECTIVE: Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is important to avoid unnecessary operative procedures. This study was aimed at evaluating the efficacy of PET/CT with F-FDG (FDG PET/CT) for the differential diagnosis between them. PATIENTS AND METHODS: FDG-PET/CT was performed in 47 study patients with pancreatic masses and without any detectable metastases, 33 of which cases were finally diagnosed as pancreatic cancer and the other 14 as pancreatitis, and the corresponding imaging data were evaluated retrospectively. The maximal SUV (SUVmax) within the masses were determined at 1 hour and mostly at 2 hours after intravenous injection of FDG. RESULTS: SUVmax at 1 hour in pancreatic cancer was significantly higher than that in mass-forming pancreatitis, and the change in SUVmax from 1- to 2-hour time points was more consistent with pancreatic cancer than with mass-forming pancreatitis. However, there remained considerable overlapping between the SUVmax values of both diseases except either at the higher range for pancreatic cancer (>7.7 at 1 hour or >9.98 at 2 hours) or at the lower range for mass-forming pancreatitis (<3.37 at 1 hour or <3.53 at 2 hours). No obvious difference was found in the FDG uptake patterns of the mass areas between both diseases. CONCLUSIONS: Differentiation between metastasis-free pancreatic cancer and mass-forming pancreatitis is difficult by FDG-PET/CT due to considerable overlapping between the SUVmax values of the two diseases, although the differential diagnosis may be possible either at the higher range of SUVmax (> 7.7 at 1 hour or >9.98 at 2 hours) for pancreatic cancer or at the lower range of SUVmax (<3.37 at 1 hour or <3.53 at 2 hours) for mass-forming pancreatitis.
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[193]
TÍTULO / TITLE: - Enhancing sorafenib-mediated sensitization to gemcitabine in Experimental Pancreatic Cancer through EMAP II.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Exp Clin Cancer Res. 2013 Mar 6;32(1):12.
●● Enlace al texto completo (gratuito o de pago) 1186/1756-9966-32-12
AUTORES / AUTHORS: - Awasthi N; Zhang C; Hinz S; Schwarz MA; Schwarz RE
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies and tends to be relatively resistant to conventional therapies. Activated Ras oncogene mutations are found in up to 90% of PDAC, leading to activation of the Ras/Raf/MEK/ERK signaling pathway. Sorafenib is a multikinase inhibitor of the Ras/Raf/MEK/ERK pathway and of tumor angiogenesis. Endothelial monocyte activating polypeptide II (EMAP) enhances gemcitabine effects in PDAC. Antitumor activity of sorafenib was evaluated in combination with gemcitabine (Gem) and the antiangiogenic agent EMAP in experimental PDAC. METHODS: Cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. Animal survival studies were performed in murine PDAC xenografts. RESULTS: Sorafenib decreased phospho-MEK, phospho-ERK1/2, phospho-p70S6K and phospho-4EBP-1 expression in PDAC cells. Sorafenib inhibited in vitro proliferation of all four PDAC cell lines tested. Additive effects on cell proliferation inhibition were observed in the gemcitabine-sorafenib combination in PDAC cells, and in combinations of sorafenib or EMAP with gemcitabine in endothelial (HUVEC) and fibroblast (WI-38) cells. Sorafenib, alone or in combination with gemcitabine and EMAP, induced apoptosis in HUVECs and WI-38 cells as observed via increased expression of cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and caspase-3 proteins. Compared to controls (median survival: 22 days), animal survival increased after Gem therapy (29 days) but not in sorafenib (23 days) or EMAP therapy alone (both 25 days). Further increases in survival occurred in combination therapy groups Gem+sorafenib (30 days, p=0.004), Gem+EMAP (33 days, p=0.002), and Gem+sorafenib+EMAP (36 days, p=0.004), but not after the sorafenib+EMAP combination (24 days). CONCLUSIONS: These findings demonstrate that the addition of a polymechanistic antiangiogenic agent such as EMAP can enhance the combination treatment effects of sorafenib and cytotoxic PDAC therapy.
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[194]
TÍTULO / TITLE: - Misleading features of neuroimaging and electroencephalography: insulinoma misdiagnosed as temporal lobe epilepsy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Epileptic Disord. 2013 Mar 25.
●● Enlace al texto completo (gratuito o de pago) 1684/epd.2013.0556
AUTORES / AUTHORS: - Aupy J; Benoilid A; Sarhan M; Dalvit C; Valenti MP; Hirsch E
INSTITUCIÓN / INSTITUTION: - Departement de Neurologie, Hopital Universitaire de Strasbourg, Strasbourg, Departement de Neurologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux.
RESUMEN / SUMMARY: - Epilepsy is a common disorder but diagnosis remains largely clinical. Although MRI and EEG significantly aid the diagnosis of epilepsy, these techniques may also be misleading and indicate abnormalities not related to phenomenology. Consequences of erroneous diagnosis of epilepsy may lead to aggressive and escalating pharmacotherapy with potentially serious side effects. Metabolic disorders, which may mimic epilepsy, should always be considered as they are potentially curable and may be fatal if untreated. We report a case of an insulinoma, misdiagnosed as temporal lobe epilepsy. We highlight the risks associated with misinterpretation of neuroimaging and EEG and outline an approach to differentiate between symptoms of insulinoma or neuroglycopenia and temporal epileptic seizures.
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[195]
TÍTULO / TITLE: - A Patient With Pancreas Divisum, Recurrent Acute Pancreatitis, and Homozygosity for the Cystic Fibrosis Transmembrane Regulator-Associated Protein 5T Allele.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Gastroenterol Hepatol. 2013 Feb 13. pii: S1542-3565(13)00189-4. doi: 10.1016/j.cgh.2013.02.012.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2013.02.012
AUTORES / AUTHORS: - Montagnani M; Cazzato S; Mutignani M; Cevenini M; Guidetti E; Zvi IB; Aldini R; Saraceni G; Cavoli C; Garagnani P; Ferrari S; Mantovani V
INSTITUCIÓN / INSTITUTION: - Dipartimento di Scienze Mediche e Chirurgiche, Policlinico S Orsola-Malpighi-Universita di Bologna, Bologna, Italy; Centro unificato di Ricerca Biomedica Applicata, Policlinico S Orsola-Malpighi-Universita di Bologna, Bologna, Italy. Electronic address: marco.montagnani@unibo.it.
RESUMEN / SUMMARY: - Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) have been reported to increase the risk of recurrent acute pancreatitis in patients with pancreas divisum. We assessed the CFTR gene in a young male patient with pancreas divisum and recurrent acute pancreatitis. Magnetic resonance cholangiopancreatography and computed tomography revealed that the patient had pancreas divisum, with an enlarged and tortuous pancreatic duct; he also had positive results from the cystic fibrosis sweat test. Genetic analysis did not identify any common CFTR mutations, but did show that he was homozygous for the 5T allele in intron 8 IVS8 5T-12TG (which affects splicing at intron 8). Endoscopic sphincterotomy and stenting of papilla minor was performed. The IVS8 5T-12TG variant has been associated with abnormal organ development, therefore it is possible that CFTR has an important role in the development of the pancreatic duct. We propose this patient has recurrent acute pancreatitis resulting from a developmental defect associated with a suboptimal CFTR function.
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[196]
TÍTULO / TITLE: - Prediction of invasive candidal infection in critically ill patients with severe acute pancreatitis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Crit Care. 2013 Mar 18;17(2):R49.
●● Enlace al texto completo (gratuito o de pago) 1186/cc12569
AUTORES / AUTHORS: - Hall A; Poole L; Renton B; Wozniak A; Fisher M; Neal T; Halloran CM; Cox T; Hampshire PA
RESUMEN / SUMMARY: - INTRODUCTION: Patients with severe acute pancreatitis are at risk of candidal infections carrying the potential risk of an increase in mortality. Since early diagnosis is problematic, several clinical risk scores have been developed to identify patients at risk. Such patients may benefit from prophylactic antifungal therapy while those patients who have a low risk of infection may not benefit and may be harmed. The aim of this study was to assess the validity and discrimination of existing risk scores for invasive candidal infections in patients with severe acute pancreatitis. METHODS: Patients admitted with severe acute pancreatitis to the intensive care unit were analysed. Outcomes and risk factors of admissions with and without candidal infection were compared. Accuracy and discrimination of three existing risk scores for the development of invasive candidal infection (Candida score, Candida Colonisation Index Score and the Invasive Candidiasis Score) were assessed. RESULTS: 101 patients were identified from 2003 - 2011. 18 (17.8%) patients developed candidal infection. 30 patients died, giving an overall hospital mortality of 29.7%. Hospital mortality was significantly higher in patients with candidal infection (55.6% compared to 24.1%, p=0.02). Candida colonisation was associated with subsequent candidal infection on multivariate analysis. The Candida Colonisation Index Score was the most accurate test, with specificity of 0.79 (0.68-0.88), sensitivity of 0.67 (0.41-0.87), negative predictive value of 0.91 (0.82-0.97) and a positive likelihood ratio of 3.2 (1.9-5.5). The Candida Colonisation Index Score showed the best discrimination with area under the receiver operating characteristic curve of 0.79 (0.69-0.87). CONCLUSIONS: In this study the Candida Colonisation Index Score was the most accurate and discriminative test at identifying which patients with severe acute pancreatitis are at risk of developing candidal infection. However its low sensitivity may limit its clinical usefulness.
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[197]
TÍTULO / TITLE: - Frequency and characterization of gastro-entero-pancreatic neuroendocrine tumor patients with high-grade of uptake at somatostatin receptor scintigraphy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocr Relat Cancer. 2013 Mar 22;20(2):229-39. doi: 10.1530/ERC-12-0169. Print 2013.
●● Enlace al texto completo (gratuito o de pago) 1530/ERC-12-0169
AUTORES / AUTHORS: - Chougnet CN; Leboulleux S; Caramella C; Lumbroso J; Borget I; Deandreis D; Duvillard P; Elias D; de Baere T; Velayoudom-Cephise FL; Guigay J; Ducreux M; Schlumberger M; Baudin E
INSTITUCIÓN / INSTITUTION: - Departments of Nuclear Medicine and Endocrine Tumors Medical Imaging, Biostatistics and Epidemiology, Pathology, Oncologic Surgery, Institut Gustave Roussy, University Paris-Sud, 114 Rue Edouard Vaillant, 94805 Villejuif Cedex, France Department of Endocrinology, University Hospital of Pointe-a-Pitre, Pointe-a-Pitre, Guadeloupe, France Departments of Medical Oncology, Digestive Oncology, Institut Gustave Roussy, University Paris-Sud, 114 Rue Edouard Vaillant, 94805 Villejuif Cedex, France.
RESUMEN / SUMMARY: - Recent studies suggest that the somatostatin receptor scintigraphy (SRS) grade of uptake is a predictor of response to peptide receptor radionuclide therapy (PRRT). To identify and characterize patients with well-differentiated (WD) neuroendocrine neoplasm (NEN) displaying a high-grade uptake at SRS. Patients with WD-NEN, whose SRS films were available for review, were retrospectively included. SRS was reviewed by three independent readers and classified into four subgroups based on a modified Krenning’s scale (mKS): no uptake (group-0), homogeneous grade 1-2 uptake (group-1), homogeneous grade 3-4 (group-2), and heterogeneous grade 1-4 (group-3). A simplified scale (sS) of SRS was also used to look for characteristics of patients with high-grade uptake. One hundred and six WD-NEN patients were enrolled. Group-0, group-1, group-2, and group-3 were found in 17, 8, 33, and 42% of cases respectively. High-grade uptake at sS (75% of cases) was correlated with older age, functioning NEN, high chromogranin-A level, and grade 1 (G1) NEN based on mitotic count. Based on the mKS or sS scales, no difference on survival was found. Thirty-three to seventy-five percent of metastatic NEN patients can be considered candidates for PRRT based on homogeneous or heterogeneous high-grade uptake. Functioning G1 NEN patients could be the best candidates for PRRT. Randomized trials are expected to confirm this result.
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[198]
TÍTULO / TITLE: - Efficacy of Everolimus in Patients with Metastatic Insulinoma and Refractory Hypoglycemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Endocrinol. 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1530/EJE-12-1101
AUTORES / AUTHORS: - Bernard V; Lombard-Bohas C; Taquet MC; Caroli-Bosc FX; Ruszniewski P; Niccoli-Sire P; Guimbaud R; Chougnet CN; Goichot B; Rohmer V; Borson-Chazot F; Baudin E
INSTITUCIÓN / INSTITUTION: - V Bernard, Nuclear Medicine and Endocrine Oncology, Gustave Roussy Institute, Villejuif, 94800, France.
RESUMEN / SUMMARY: - BACKGROUND: Refractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option. METHODS: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded. RESULTS: Twelve patients with metastatic insulinoma and refractory hypoglycemia treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/d, except in 1 patient, 5 mg/d) was given after a median of 4 previous therapeutic lines. Clinical benefit was observed in 11 patients, allowing withdrawal of hyperglycemic therapy in 6 patients. After a median duration of 6.5 months (range, 1 to 35+ months), median time to first recurrence of symptomatic hypoglycemia was 6.5 months (range, 0 to 35+ months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to 2 deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia. CONCLUSION: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.
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[199]
TÍTULO / TITLE: - CA 19-9 Concentration in Peripheral and Portal Blood of Patients Operated on for Pancreatic Tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pol Przegl Chir. 2013 Jan 1;85(1):20-8. doi: 10.2478/pjs-2013-0004.
●● Enlace al texto completo (gratuito o de pago) 2478/pjs-2013-0004
AUTORES / AUTHORS: - Szwedziak K; Strzelczyk J
RESUMEN / SUMMARY: - Pancreatic cancer is one of the most common malignant diseases in the world. Morbidity rate increases and now reaches around 200 000 new cases yearly. Poor prognosis mainly results from usually late diagnosis and non-specific symptoms. Despite of advances in radiological diagnosis of pancreatic diseases, differentiation between malignant and inflammatory pancreatic tumors still remains difficult. The aim of the studywas the assessment of clinical utility of CA 19-9 in peripheral and portal blood of patients with pancreatic tumor. Material and methods.66 patients were hospitalized at the Department of General and Transplant Surgery between October 2010 nad July 2012 due to pancreatic tumor. Blood samples were collected from peripheral vein before surgery and intraoperatively from the portal vein to measure CA 19-9 concentration. 57 patients were diagnosed with malignant tumor and 9 with inflammatory lesion. Metastases to the liver were present in 7 of all patients. Radical surgery (Whipple’s procedure in 27 cases) were performed in 34 patients. Results.Significantly higher CA 19-9 concentration in the peripheral blood and in the portal blood as well was found in the pancreatic cancer group than in the inflammatory lesions group (51.2 vs <3 and 52.1 vs 6.3 respectively). Marker concentration in case of malignant lesions was significantly higher in the portal blood than in the peripheral blood (52.1 vs 51.2; p<0.05). CA 19-9 concentration of patients with malignant pancreatic tumors but without metastases to the liver was significanlty higher in the portal blood than in the peripheral blood (19.32 vs 18.65; p<0.01). Conclusions.Determination of the CA 19-9 concentration not only in the peripheral blood but in the portal blood as well might be a useful diagnostic tool in order to differentiate between the malignant and inflammatory pancreatic tumors. We did not see any statistically significant dependency between the CA 19-9 concentrations in the peripheral blood and portal blood and if the surgery was radical or not, but significantly higher concentrations of CA 19-9 in the portal blood than the peripheral blood among the patients suffering from the malignant pancreatic tumor without metastases to the liver might be useful tool when decisions on performing pancreatoduodenectomy are being made since this surgery is forborne from when metastases are present.
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[200]
TÍTULO / TITLE: - The angiotensin II type I receptor blocker olmesartan inhibits the growth of pancreatic cancer by targeting stellate cell activities in mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Scand J Gastroenterol. 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 3109/00365521.2013.777776
AUTORES / AUTHORS: - Masamune A; Hamada S; Kikuta K; Takikawa T; Miura S; Nakano E; Shimosegawa T
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai , Japan.
RESUMEN / SUMMARY: - Abstract There is accumulating evidence that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, promote the progression of pancreatic cancer. The interactions between PSCs and pancreatic cancer have attracted substantial attention as a novel therapeutic target for the treatment of pancreatic cancer. We examined here the effects of olmesartan, an angiotensin II type I receptor blocker, on pancreatic cancer-associated fibrosis using a subcutaneous tumor model developed by co-injection of pancreatic cancer cells with PSCs in nude mice. Co-injection of pancreatic cancer cells AsPC-1 with PSCs increased the size of tumors compared with AsPC-1 cells alone. Olmesartan administrated at 10 mg/kg in drinking water inhibited the growth of subcutaneous tumors derived from the co-injection, but not those derived from mono-injection. This effect was accompanied by decreased expression of alpha-smooth muscle actin (a marker of activated PSCs) and collagen deposition. The inhibitory effect of olmesartan was also observed even if it was administrated after significant development of subcutaneous tumors. In addition, olmesartan decreased cell growth and type I collagen production in PSCs in vitro. These results suggest that olmesartan inhibited the growth of tumors by targeting stellate cell activities, and that olmesartan might be useful as an anti-fibrosis therapy in pancreatic cancer.
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[201]
TÍTULO / TITLE: - Surgical outcomes of pancreaticoduodenectomy for periampullary tumors in elderly patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Langenbecks Arch Surg. 2013 Feb 15.
●● Enlace al texto completo (gratuito o de pago) 1007/s00423-013-1061-x
AUTORES / AUTHORS: - Yamashita YI; Shirabe K; Tsujita E; Takeishi K; Ikeda T; Yoshizumi T; Furukawa Y; Ishida T; Maehara Y
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, 1-9-6 Senda-machi, Naka-ku, Hiroshima, 730-8619, Japan, yamashi@surg2.med.kyushu-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUNDS: Pancreaticoduodenectomy (PD) is an aggressive surgery with considerable operative risks, but offers the only chance for cure in patients with periampullary tumors. A growing number of elderly patients are being offered PD because of the aging of populations in developed countries. We examined surgical outcomes of PD in patients aged 75 years and older (>/=75 years). METHODS: A retrospective cohort study was performed in 65 consecutive patients who underwent PD for periampullary tumors at a single medical center during the 5 years from 2006 to 2010. We analyzed surgical outcomes such as mortality and morbidity after PD in patients aged >/=75 years (n = 21) compared to those in patients aged <75 years (n = 44). RESULTS: The positive rate of comorbidities such as hypertension was significantly higher in patients aged >/=75 years than in patients aged <75 years (76 vs. 48 %; p = 0.03). The incidence of wound infection was significantly higher in patients aged >/=75 years than in patients aged <75 years (19 vs. 0 %; p < 0.01). However, there was no significant difference in the mortality rate (0 vs. 2 %; p = 0.49) or the overall morbidity rate (33 vs. 32 %; p = 0.90). There was no significant difference in changes in body weight or serum albumin levels during the 3 months after PD between the two groups, but the recovery of serum prealbumin levels from 1 to 3 months after PD in patients aged >/=75 years was significantly delayed compared to that in patients aged <75 years (p = 0.04). There was no statistically significant difference in long-term survival between the two groups. CONCLUSIONS: Advanced age alone should not discourage surgeons from offering PD, although nutritional supports after PD for elderly patients aged >/=75 years are needed.
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[202]
TÍTULO / TITLE: - Inhibition of the Growth of Patient-Derived Pancreatic Cancer Xenografts with the MEK Inhibitor Trametinib Is Augmented by Combined Treatment with the Epidermal Growth Factor Receptor/HER2 Inhibitor Lapatinib.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neoplasia. 2013 Feb;15(2):143-55.
AUTORES / AUTHORS: - Walters DM; Lindberg JM; Adair SJ; Newhook TE; Cowan CR; Stokes JB; Borgman CA; Stelow EB; Lowrey BT; Chopivsky ME; Gilmer TM; Parsons JT; Bauer TW
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Virginia Health System, Charlottesville, VA.
RESUMEN / SUMMARY: - Mutations of the oncogene KRAS are important drivers of pancreatic cancer progression. Activation of epidermal growth factor receptor (EGFR) and human EGFR2 (HER2) is observed frequent in pancreatic adenocarcinomas. Because of co-activation of these two signaling pathways, we assessed the efficacy of inhibition of EGFR/HER2 receptors and the downstream KRAS effector, mitogen-activated protein kinase/extracellular-signal regulated kinase (ERK) kinase 1 and 2 (MEK1/2), on pancreatic cancer proliferation in vitro and in a murine orthotopic xenograft model. Treatment of established and patient-derived pancreatic cancer cell lines with the MEK1/2 inhibitor trametinib (GSK1120212) inhibited proliferation, and addition of the EGFR/HER2 inhibitor lapatinib enhanced the inhibition elicited by trametinib in three of eight cell lines. Importantly, in the orthotopic xenograft model, treatment with lapatinib and trametinib resulted in significantly enhanced inhibition of tumor growth relative to trametinib treatment alone in four of five patient-derived tumors tested and was, in all cases, significantly more effective in reducing the size of established tumors than treatment with lapatinib or trametinib alone. Acute treatment of established tumors with trametinib resulted in an increase in AKT2 phosphorylation that was blunted in mice treated with both trametinib and lapatinib. These data indicate that inhibition of the EGFR family receptor signaling may contribute to the effectiveness of MEK1/2 inhibition of tumor growth possibly through the inhibition of feedback activation of receptor tyrosine kinases in response to inhibition of the RAS-RAF-MEK-ERK pathway. These studies provide a rationale for assessing the co-inhibition of these pathways in the treatment of pancreatic cancer patients.
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[203]
TÍTULO / TITLE: - Targeting gemcitabine containing liposomes to CD44 expressing pancreatic adenocarcinoma cells causes an increase in the antitumoral activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biochim Biophys Acta. 2013 May;1828(5):1396-404. doi: 10.1016/j.bbamem.2013.01.020. Epub 2013 Feb 4.
●● Enlace al texto completo (gratuito o de pago) 1016/j.bbamem.2013.01.020
AUTORES / AUTHORS: - Dalla Pozza E; Lerda C; Costanzo C; Donadelli M; Dando I; Zoratti E; Scupoli MT; Beghelli S; Scarpa A; Fattal E; Arpicco S; Palmieri M
INSTITUCIÓN / INSTITUTION: - Department of Life and Reproduction Sciences, Biochemistry Section, University of Verona, Verona, Italy.
RESUMEN / SUMMARY: - Pancreatic adenocarcinoma is often diagnosed when metastatic events have occurred. The early spread of circulating cancer cells expressing the CD44 receptor may play a crucial role in this process. In this study, we have investigated the cellular delivery ability and both in vitro and in vivo anti-tumoral activity of liposomes conjugated with two different low molecular weight hyaluronic acids (HA 4.8kDa and HA 12kDa), the primary ligand of CD44, and containing a lipophilic gemcitabine (GEM) pro-drug. By confocal microscopy and flow cytometry analyses, we demonstrate that the cellular uptake into a highly CD44-expressing pancreatic adenocarcinoma cell line is higher with HA-conjugated (12kDa>4.8kDa) than non-conjugated liposomes. Consistently, in vitro cytotoxic assays display an increased sensitivity towards GEM containing HA-liposomes, compared to non-conjugated liposomes. Conversely, CD44 non-expressing normal cells show a similar uptake and in vitro cytotoxicity with both HA-conjugated and non-conjugated liposomes. Furthermore, we demonstrate that the HA-liposomes are taken up into the cells via lipid raft-mediated endocytosis. All the liposome formulations containing GEM show a higher antitumoral activity than free GEM in a mouse xenograft tumor model of human pancreatic adenocarcinoma. The 12kDa HA-liposomes have the strongest efficiency, while non-conjugated liposomes and the 4.8kDa HA-liposomes are similarly active. Taken together, our results provide a strong rationale for further development of HA-conjugated liposomes to treat pancreatic adenocarcinoma.
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[204]
TÍTULO / TITLE: - Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Clin Oncol. 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1007/s10147-013-0529-6
AUTORES / AUTHORS: - Ikemoto T; Shimada M; Iwahashi S; Saito Y; Kanamoto M; Mori H; Morine Y; Imura S; Utsunomiya T
INSTITUCIÓN / INSTITUTION: - Department of Digestive and Transplant Surgery, Institute of Health Bioscience, Graduate School of Medicine, The University of Tokushima, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan, tikemoto@clin.med.tokushima-u.ac.jp.
RESUMEN / SUMMARY: - BACKGROUND: The prognosis of pancreatic cancer is extremely poor regardless of various combination therapies. Immunoaugumentation against tumor cells was recently A focus. We reported that the population of Foxp3(+)CD25(+)CD4(+) regulatory T cells (Foxp3(+)Treg) was the new parameter for the estimation of host immunity and had correlation with tumor aggressiveness. Here we show the immunoaugumentation effects of Japanese Kampo medicine, Juzen-Taihoto/TJ-48, empirically considered as an immunoaugumentation drug, with investigation of Treg and other immunological parameters. PATIENTS AND METHOD: Peripheral Foxp3(+) Treg populations, CD4/CD8 ratio, and CD57(+) cells (NK cells) populations in advanced pancreatic cancer patients (n = 30, stage VI A and B according to TNM classification) were estimated after TJ-48 administration for 14 days before the anti-cancer therapy. RESULTS: Treg populations were significantly increased compared to healthy donors (Mann-Whitney U test, P < 0.001). Administration of Juzen-Taihoto/TJ-48 significantly decreased Treg populations (Mann-Whitney U test, P < 0.001) and increased the CD4/CD8 ratio (Mann-Whitney U test, P < 0.01), even though CD57(+) cell populations did not change significantly. CONCLUSIONS: Juzen-Taihoto/TJ-48 increased regulatory activities in T cells through decreasing Foxp3(+) Treg populations in advanced pancreatic cancer patients. This effect can lead to immunoaugumentation for various combination therapies.
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[205]
TÍTULO / TITLE: - Mass spectrometric analysis reveals O-methylation of pyruvate kinase from pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anal Bioanal Chem. 2013 Mar 19.
●● Enlace al texto completo (gratuito o de pago) 1007/s00216-013-6880-7
AUTORES / AUTHORS: - Zhou W; Capello M; Fredolini C; Racanicchi L; Dugnani E; Piemonti L; Liotta LA; Novelli F; Petricoin EF
INSTITUCIÓN / INSTITUTION: - Center for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Blvd, MS 1A9, Manassas, VA, 20110, USA, wzhou@gmu.edu.
RESUMEN / SUMMARY: - Pyruvate kinase (PK) is an important glycolytic enzyme that catalyzes the dephosphorylation of phosphoenolpyruvate to pyruvate. Human PK isozyme M2 (PKM2), a splice variant of M1, is overexpressed in many cancer cells, and PKM2 has been investigated as a potential tumor marker for diagnostic assays and as a target for cancer therapy. To facilitate identification and characterization of PK, we studied the enzyme from pancreatic cancer cells and normal pancreatic duct cells by electrophoresis and mass spectrometry, and identified multiple O-methylated residues from PK. These findings advance our knowledge of the biochemical properties of PK and will be important in understanding its biological function in cells.
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[206]
TÍTULO / TITLE: - Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: a Meta-Analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Gastroenterol Hepatol. 2013 Feb 12. pii: S1542-3565(13)00187-0. doi: 10.1016/j.cgh.2013.02.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.cgh.2013.02.010
AUTORES / AUTHORS: - Anand N; Sampath K; Wu BU
INSTITUCIÓN / INSTITUTION: - Center for Pancreatic Care, Southern California Permanente Medical Group; Division of Gastroenterology, Kaiser Permanente Los Angeles Medical Center; Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center.
RESUMEN / SUMMARY: - BACKGROUND & AIMS: International guidelines for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of those with specific characteristics. We performed a meta-analysis to evaluate risk of malignancy associated with each of these features of IPMNs. METHODS: We performed a comprehensive search of MEDLINE from January 1, 1996 to November 11, 2011 for studies that included any of the features mentioned in the consensus guidelines for surgical resection of main duct and branch duct IPMNs. Data were analyzed from 41 studies for the following features: cyst size >3 cm, the presence of mural nodules, dilated main pancreatic duct, symptoms, and main duct vs branch duct IPMNs. Malignant IPMNs were defined as those with carcinoma in situ or more advanced histology. A separate meta-analysis was performed for each risk factor to calculate pooled odds ratios (ORs). A random-effects model was used, based on the assumption of variation among study populations. RESULTS: The risks of malignancy associated with individual cyst features were: cyst size >3 cm (OR, 62.4; 95% confidence interval [CI], 30.8-126.3), presence of a mural nodule (OR, 9.3; 95% CI, 5.3-16.1), dilatation of the main pancreatic duct (OR, 7.27; 95% CI, 3.0-17.4), and main vs branch duct IPMN (OR, 4.7; 95% CI, 3.3-6.9]. There was a moderate level of heterogeneity among studies (I(2) range, 34-67). CONCLUSIONS: Based on a meta-analysis, cyst features proposed by the international guidelines for resection of IPMN were highly associated with malignancy. However, based on our findings, not all cyst features should be weighted equally when considering risk of malignancy; cyst size >3 cm was most strongly associated with malignant IPMN.
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[207]
TÍTULO / TITLE: - Microenvironment generated during EGFR targeted killing of pancreatic tumor cells by ATC inhibits myeloid-derived suppressor cells through COX2 and PGE2 dependent pathway.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Transl Med. 2013 Feb 9;11:35. doi: 10.1186/1479-5876-11-35.
●● Enlace al texto completo (gratuito o de pago) 1186/1479-5876-11-35
AUTORES / AUTHORS: - Thakur A; Schalk D; Tomaszewski E; Kondadasula SV; Yano H; Sarkar FH; Lum LG
INSTITUCIÓN / INSTITUTION: - Departments of Oncology and Medicine, Wayne State University and Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA. thakur@karmanos.org.
RESUMEN / SUMMARY: - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th1 enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th1 microenvironment. METHODS: We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] and gemcitabine resistant MiaPaCa-GR [MiaM] cells to generate MDSC in the presence or absence of Th1 cytokines and EGFRBi armed ATC (aATC). RESULTS: We show significantly decreased differentiation of MDSC (MiaE, p<0.005; MiaM, p<0.05) in the presence of aATC with or without Th1 cytokines. MDSC recovered from control cultures (without aATC) showed potent ability to suppress T cell functions compared to those recovered from aATC containing co-cultures. Reduced accumulation of MDSC was accompanied by significantly lower levels of COX2 (p<0.0048), PGE2 (p<0.03), and their downstream effector molecule Arginase-1 (p<0.01), and significantly higher levels of TNF-alpha, IL-12 and chemokines CCL3, CCL4, CCL5, CXCL9 and CXCL10 under aATC induced Th1 cytokine enriched microenvironment. CONCLUSIONS: These data suggest aATC can suppress MDSC differentiation and attenuation of their suppressive activity through down regulation of COX2, PGE2 and ARG1 pathway that is potentiated in presence of Th1 cytokines, suggesting that Th1 enriching immunotherapy may be beneficial in pancreatic cancer treatment.
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[208]
TÍTULO / TITLE: - Excess glucose induces hypoxia-inducible factor-1alpha in pancreatic cancer cells and stimulates glucose metabolism and cell migration.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Biol Ther. 2013 Feb 1;14(5).
AUTORES / AUTHORS: - Liu Z; Jia X; Duan Y; Xiao H; Sundqvist KG; Permert J; Wang F
INSTITUCIÓN / INSTITUTION: - Department of Clinical Immunology; Karolinska University Hospital; Huddinge, Sweden.
RESUMEN / SUMMARY: - Pancreatic cancer patients frequently show hyperglycemia, but it is uncertain whether hyperglycemia stimulates pancreatic cancer cells. We have investigated whether excess glucose induces hypoxia-inducible factor-1alpha (HIF-1alpha) and stimulates glucose metabolism and cell migration in pancreatic cancer cells. We studied wild-type (wt) MiaPaCa2 pancreatic cancer cells and a MiaPaCa2 subline (namely si-MiaPaCa2) that had HIF-1alpha-specific small interfering RNA. Wt-MiaPaCa2 cells are known to be HIF-1alpha-positive in hypoxia and HIF-1alpha-negative in normoxia, whereas si-MiaPaCa2 cells are devoid of HIF-1alpha in both normoxia and hypoxia. We incubated these cells with different amounts of glucose and determined HIF-1alpha mRNA and protein by real-time polymerase chain reaction and western blotting. We determined glucose consumption, lactate production and intracellular hexokinase-II and ATP to assess glucose metabolisms and determined pyruvate dehydrogenase kinase-1, reactive oxygen species and fumarate to assess mitochondrial activities. Further, we studied cell migration using a Boyden chamber. Excess glucose (16.7-22.2 mM) increased HIF-1alpha in hypoxic wt-MiaPaCa2 cells. HIF-1alpha expression increased ATP contents and inhibited mitochondrial activities. Extracellular glucose and hypoxia stimulated glucose metabolisms independent of HIF-1alpha. Excess glucose stimulated the migration of wt- and si-MiaPaCa2 cells in both normoxia and hypoxia. Thus, glucose stimulated cell migration independent of HIF-1alpha. Nevertheless, hypoxic wt-MiaPaCa2 cells showed greater migrating ability than their si-MiaPaCa2 counterparts. We conclude that (1) excess glucose increases HIF-1alpha and ATP in hypoxic wt-MiaPaCa2 cells, (2) extracellular glucose and hypoxia regulate glucose metabolisms independent of HIF-1alpha and (3) glucose stimulates cell migration by mechanisms that are both dependent on HIF-1alpha and independent of it.
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[209]
TÍTULO / TITLE: - Genetic testing for hereditary melanoma and pancreatic cancer: a longitudinal study of psychological outcome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Psychooncology. 2013 Feb;22(2):276-89. doi: 10.1002/pon.2080. Epub 2011 Oct 7.
●● Enlace al texto completo (gratuito o de pago) 1002/pon.2080
AUTORES / AUTHORS: - Aspinwall LG; Taber JM; Leaf SL; Kohlmann W; Leachman SA
INSTITUCIÓN / INSTITUTION: - Department of Psychology, University of Utah, Salt Lake City, UT, USA. lisa.aspinwall@utah.edu
RESUMEN / SUMMARY: - OBJECTIVE: CDKN2A/p16 mutations confer 76% lifetime risk of melanoma and up to 17% lifetime risk of pancreatic cancer. Our objective was to determine the short- and long-term impact of CDKN2A/p16 genetic counseling and test reporting on psychological distress, cancer worry, and perceived costs and benefits of testing. METHODS: Prospective changes in anxiety, depression, and cancer worry following CDKN2A/p16 counseling and test reporting were evaluated at multiple assessments over 2 years among 60 adult members of melanoma-prone families; 37 participants completed the 2-year follow-up. Quantitative and qualitative assessments of the costs and benefits of testing were carried out. Outcomes were evaluated among unaffected noncarriers (n = 27), unaffected carriers (n = 15), and affected carriers (n = 18). RESULTS: Reported anxiety and depression were low. For carriers and noncarriers, anxiety decreased significantly throughout the 2-year period, whereas depression and melanoma worry showed short-term decreases. Worry about pancreatic cancer was low and decreased significantly. In all groups, test-related distress and uncertainty were low, regret was absent, and positive experiences were high. All participants (>93% at each assessment) reported at least one perceived benefit of genetic testing; only 15.9% listed any negative aspect. Carriers reported increased knowledge about melanoma risk and prevention (78.3%) and increased prevention and screening behaviors for self and family (65.2%). Noncarriers reported increased knowledge (95.2%) and emotional benefits (71.4%). CONCLUSION: Among US participants familiar with their hereditary melanoma risk through prior epidemiological research participation, CDKN2A/p16 genetic testing provides multiple perceived benefits to both carriers and noncarriers without inducing distress in general or worry about melanoma or pancreatic cancer.
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[210]
TÍTULO / TITLE: - Dynamin 2 Potentiates Invasive Migration of Pancreatic Tumor Cells through Stabilization of the Rac1 GEF Vav1.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dev Cell. 2013 Mar 25;24(6):573-85. doi: 10.1016/j.devcel.2013.02.010.
●● Enlace al texto completo (gratuito o de pago) 1016/j.devcel.2013.02.010
AUTORES / AUTHORS: - Razidlo GL; Wang Y; Chen J; Krueger EW; Billadeau DD; McNiven MA
INSTITUCIÓN / INSTITUTION: - Center for Basic Research in Digestive Diseases, Mayo Clinic, Rochester, MN 55905, USA.
RESUMEN / SUMMARY: - The large GTPase Dynamin 2 (Dyn2) is markedly upregulated in pancreatic cancer, is a potent activator of metastatic migration, and is required for Rac1-mediated formation of lamellipodia. Here we demonstrate an unexpected mechanism of Dyn2 action in these contexts via direct binding to the Rac1 guanine nucleotide exchange factor (GEF) Vav1. Surprisingly, disruption of the Dyn2-Vav1 interaction targets Vav1 to the lysosome for degradation via an interaction with the cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein stability. Importantly, a specific mutation in Vav1 near its Dyn2-binding C-terminal Src homology 3 (SH3) domain prevents Hsc70 binding, resulting in a stabilization of Vav1 levels. Dyn2 binding regulates the interaction of Vav1 with Hsc70 to control the stability and subsequent activity of this oncogenic GEF. These findings elucidate how Dyn2 activates Rac1, lamellipod protrusion, and invasive cellular migration and provide insight into how this specific Vav is ectopically expressed in pancreatic tumors.
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[211]
TÍTULO / TITLE: - Clinical usefulness of portal venous stent in hepatobiliary pancreatic cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ANZ J Surg. 2013 Feb 20. doi: 10.1111/ans.12046.
●● Enlace al texto completo (gratuito o de pago) 1111/ans.12046
AUTORES / AUTHORS: - Zhou ZQ; Lee JH; Song KB; Hwang JW; Kim SC; Lee YJ; Park KM
INSTITUCIÓN / INSTITUTION: - Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUND: Treatment options for patients with portal vein (PV) stenosis or occlusion after surgery are limited. The purpose of this study was to investigate the efficacy and safety of PV stent placement in patients with portal vein occlusion or stenosis after radical operation for hepatobiliary pancreatic malignant tumour. METHODS: We retrospectively reviewed the records of 59 patients who underwent portal venous stent placement at the Asan Medical Center, Seoul, Korea, for PV stenosis or occlusion between February 2008 and February 2012. RESULTS: Stents were placed in the portal venous system across stenotic (n = 47) and occlusive (n = 12) lesions after percutaneous transhepatic portography. Reasons for stent placement were tumour recurrence (n = 30), portal vein resection and anastomosis (n = 18) and post-operative inflammatory changes (n = 11). Pressure gradients (superior mesenteric vein, main PV) decreased immediately after stent placement, from 10.5 mm Hg +/- 4.4 (standard deviation) to 2.5 mm Hg +/- 2.6 (P < 0.0001). Liver function was improved post-stenting (P < 0.05). The median time between the original surgery and stent placement was 16 (1-137) days in the vascular-orientated group and 306 (13-3703) days in the tumour recurrence group (P < 0.0001). Transient fever developed in 11 patients, but resolved in 2-5 days. Stents were occluded in 15 of the 59 patients (25.4%). CONCLUSION: PV stent placement is a safe choice, has an acceptable success rate and provides marked relief from portal hypertension due to portal vein occlusion or stenosis after hepatobiliary pancreatic surgery. Liver function data are also improved after portal venous stent placement.
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[212]
TÍTULO / TITLE: - Treatment of experimental pancreatic cancer by doxorubicin-, mitoxantrone-, and irinotecan-drug eluting beads.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreatology. 2013 Jan-Feb;13(1):79-87. doi: 10.1016/j.pan.2012.11.305. Epub 2012 Nov 16.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pan.2012.11.305
AUTORES / AUTHORS: - Yagublu V; Caliskan N; Lewis AL; Jesenofsky R; Gasimova L; Lohr JM; Keese M
INSTITUCIÓN / INSTITUTION: - Surgical Clinic, University Medicine Mannheim, Mannheim, Germany.
RESUMEN / SUMMARY: - BACKGROUND AND AIMS: Peritoneal carcinomatosis is a common cause of death in pancreatic cancer patients. In this metastatic stage of the disease, few patients show a sustained response to therapy. In the palliative situation, targeted and compartment restricted delivery of drugs offers the opportunity to focus drugs directly to the tumor site, which is a prerequisite for avoiding toxic side effects. Here, we demonstrate the therapeutic efficiency of biocompatible polyvinyl-alcohol hydrogel drug eluting beads (DEBs) containing doxorubicin, mitoxantrone and irinotecan in vitro and in vivo in a syngenic model of experimental pancreatic cancer. METHODS: Panc02 murine pancreatic carcinoma cells were exposed to doxorubicin, mitoxantrone and irinotecan DEBs and free compounds. The effect on cell proliferation and apoptosis induction was compared. Using this cell line, peritoneal carcinomatosis was induced in C57 black6 mice. Mortality, tumor load and therapy-associated weight loss were compared after treatment of tumor-bearing mice with DEBs or free compounds. RESULTS: In vitro treatment with DEBs decreases tumor cell proliferation and induces apoptosis. The effect is less pronounced than with corresponding doses of the free drug. Repeated applications of the free drugs in vivo, however, induce significantly higher lethality and weight loss than corresponding doses of DEBs. No relevant differences in antitumoral activity were observed. Using computer tomography and HE-histology after subcutaneous and intraperitoneal injection of radiopaque beads no systemic spread of the beads could be found. CONCLUSION: DEBs show the advantage of delivering potent cytotoxic activity to the intraperitoneal tumor manifestation while maintaining a low systemic toxicity.
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[213]
TÍTULO / TITLE: - Sunitinib malate for the treatment of pancreas malignancies - where does it fit?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Pharmacother. 2013 Apr;14(6):783-92. doi: 10.1517/14656566.2013.776540. Epub 2013 Mar 4.
●● Enlace al texto completo (gratuito o de pago) 1517/14656566.2013.776540
AUTORES / AUTHORS: - Mankal P; O’Reilly E
INSTITUCIÓN / INSTITUTION: - Columbia University College of Physicians and Surgeons, St. Luke’s-Roosevelt Hospital Center, Department of Medicine , New York , USA.
RESUMEN / SUMMARY: - Introduction: Sunitinib , a broad-spectrum multikinase inhibitor, was recently approved for use in progressive, well-differentiated pancreatic neuroendocrine tumors (pNETs). Its mechanism of action affects various signaling cascades involving antiangiogenesis and tumor proliferation, including vascular endothelial growth factors and platelet-derived growth factors. Areas covered: In this article, we review sunitinib’s mechanism of action at a molecular level and review key preclinical and clinical studies for pNETs and more limited data regarding sunitinib’s evaluation in pancreas adenocarcinoma. The data for sunitinib in pNETs are placed in the context of the changing landscape of therapeutic options for this cancer, and relevant ongoing clinical trials and future directions are highlighted. Expert opinion: Sunitinib malate has become integrated into routine clinical management for pNETs; however, its role in pancreas adenocarcinoma is not established.
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[214]
TÍTULO / TITLE: - CXCR2: a target for pancreatic cancer treatment?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Ther Targets. 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1517/14728222.2013.772137
AUTORES / AUTHORS: - Hertzer KM; Donald GW; Hines OJ
INSTITUCIÓN / INSTITUTION: - Hirshberg Translational Pancreatic Cancer Research Laboratory, David Geffen School of Medicine at UCLA, Department of Surgery , 675 Charles E Young Drive, MRL 2535, Los Angeles, CA 90095 , USA +1 310 206 0441 ; +1 310 206 2472 ; joehines@mednet.ucla.edu.
RESUMEN / SUMMARY: - Introduction: Pancreatic cancer, a leading cause of cancer deaths worldwide, is very aggressive and has minimally effective treatment options. For those who have no surgical options, medical treatments are limited. The chemokine receptor CXCR2 has become the subject of much interest recently because of multiple studies indicating its involvement in cancer and inflammatory conditions. Research now indicates that CXCR2 and its ligands are intimately involved in tumor regulation and growth and that inhibition of its function shows promising results in multiple cancer types, including pancreatic cancer. Areas covered: In this study, the authors review basic molecular and structural details of CXCR2, as well as the known functions of CXCR2 and several of its ligands in inflammation and cancer biology with specific attention to pancreatic cancer. Then the future possibilities and questions remaining for pharmacological intervention against CXCR2 in pancreatic cancer are explored. Expert opinion: Many current inhibitory strategies already exist for targeting CXCR2 in vitro as well as in vivo. Clinically speaking, CXCR2 is an exciting potential target for pancreatic cancer; however, CXCR2 is functionally important for multiple processes and therapeutic options would benefit from further work toward understanding of these roles as well as structural and target specificity.
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[215]
TÍTULO / TITLE: - Novel aspects of preoperative chemoradiation therapy improving anti-tumor immunity in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Sci. 2013 Jan 31. doi: 10.1111/cas.12119.
●● Enlace al texto completo (gratuito o de pago) 1111/cas.12119
AUTORES / AUTHORS: - Tsuchikawa T; Hirano S; Tanaka E; Matsumoto J; Kato K; Nakamura T; Ebihara Y; Shichinohe T
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
RESUMEN / SUMMARY: - Pancreatic cancer is an aggressive cancer with poor prognosis. Little is known about the immune response in the tumor microenvironment after chemotherapy for initially unresectable tumor. The purpose of this study was to investigate the immunological effects of chemoradiation therapy in the tumor microenvironment of pancreatic adenocarcinoma. Seventeen patients with pancreatic adenocarcinoma with and without preoperative chemoradiation therapy were retrospectively analyzed using immunohistochemical methods for HLA class I heavy chain, CD4+ , CD8+ , CD45RO+ and Foxp3+ T cell infiltrations. Seven of the 17 study patients received preoperative chemoradiation therapy. There were no statistically significant differences in the number of CD4+ and CD8+ T cell infiltrations in the tumor microenvironment. However, the number of Foxp3+ T cell infiltrations was significantly lower in the neoadjuvant chemoradiation therapy group. The HLA class I expression status was the same between the two groups. In conclusion, preoperative chemoradiation therapy in pancreatic adenocarcinoma is useful for reducing regulatory T cell levels in combination with its direct cytotoxic effects.
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[216]
TÍTULO / TITLE: - Therapeutic Perspectives on Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Curr Cancer Drug Targets. 2013 Mar 18.
AUTORES / AUTHORS: - Sheahan AV; Phillips PA; Khachigian LM
INSTITUCIÓN / INSTITUTION: - Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052, Australia. l.khachigian@unsw.edu.au.
RESUMEN / SUMMARY: - : Pancreatic cancer has a poor prognosis, with only 10% survival one year following diagnosis. Despite significant advances in conventional therapies (chemotherapy and radiotherapy), little improvement in patient survival has occurred in the last decade. Therefore, there is a critical need for novel and effective therapeutic approaches for this cancer. This article reviews current concepts in the pathogenesis and treatment of pancreatic cancer, the latter including tumor resection approaches and the current standard of care. We further describe recent advances in new and combination therapies, which result only in modest increases in survival, and discuss challenges in drug delivery and limiting toxicity.
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[217]
TÍTULO / TITLE: - Comparison of abdominal MRI with diffusion-weighted imaging to Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur J Nucl Med Mol Imaging. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1007/s00259-013-2371-5
AUTORES / AUTHORS: - Schmid-Tannwald C; Schmid-Tannwald CM; Morelli JN; Neumann R; Haug AR; Jansen N; Nikolaou K; Schramm N; Reiser MF; Rist C
INSTITUCIÓN / INSTITUTION: - Institute for Clinical Radiology, Ludwig Maximilians University Hospital Munich, Marchioninistr. 15, 81377, Munich, Germany.
RESUMEN / SUMMARY: - PURPOSE: The aim of the study was to evaluate contrast-enhanced MRI, diffusion-weighted MRI (DW MRI), and 68Ga-DOTATATE positron emission tomography (PET)/CT in the detection of intermediate to well-differentiated neuroendocrine tumors (NET) of the pancreas. METHODS: Eighteen patients with pathologically proven pancreatic NET who underwent MRI including DW MRI and PET/CT within 6 weeks of each other were included in this retrospective study. Two radiologists evaluated T2-weighted (T2w), T2w + DW MRI, T2w + contrast-enhanced T1-weighted (CE T1w) MR images, and PET/CT for NET detection. The sensitivity and level of diagnostic confidence were compared among modalities using McNemar’s test and a Wilcoxon signed rank test. Apparent diffusion coefficients (ADC) of pancreatic NETs and normal pancreatic tissue were compared with Student’s t test. RESULTS: Of the NETs, 8/23 (34.8 %) and 9/23 (39.1 %) were detected on T2w images by observers 1 and 2, respectively. Detection rates improved significantly by combining T2w images with DW MRI (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05) or CE T1w images (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05). Detection rates of pancreatic NET with PET/CT (both observers: 23/23 = 100 %) were statistically significantly higher than with MRI (p < 0.05). The mean ADC value of NET (1.02 +/- 0.26 x 10-3 mm2/s) was statistically significantly lower than that of normal pancreatic tissue (1.48 +/- 0.39 x 10-3 mm2/s). CONCLUSION: DW MRI is a valuable adjunct to T2w imaging and comparable to CE T1w imaging in pancreatic NET detection, quantitatively differentiating between NET and normal pancreatic tissue with ADC measurements. 68Ga-DOTATATE PET/CT is more sensitive than MRI in the detection of pancreatic NET.
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[218]
TÍTULO / TITLE: - European proficiency study with control serum for the tumor marker CA 19-9 measured on different test systems.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Lab. 2013;59(1-2):185-92.
AUTORES / AUTHORS: - Bertsch T; Aschenneller C; Bewarder N; Beyrau R; Herrmann BL; Jansen E; Klapdor R; Klemm M; Meissner J; Pfeiffer S; Schauer I; Stratmann MM; Theimer C; van de Loo HM; Wildbredt DA; Wolff C; Wollenberg P
INSTITUCIÓN / INSTITUTION: - Klinikum Nurnberg, Institut fur Klinische Chemie, Labormedizin und Transfusionsmedizin, Nurnberg, Germany. thomas.bertsch@klinikum-nuernberg.de
RESUMEN / SUMMARY: - BACKGROUND: Reliable and precise CA 19-9 testing is required for the long-term follow-up of patients with pancreatic carcinoma during therapy. The aim of this longitudinal proficiency study was to evaluate the comparability, linearity, and precision of CA 19-9 determinations performed in different laboratories using currently available test systems under routine conditions. METHODS: During the one year study period, 15 laboratories applied 7 different tests and included a liquid BIOREF control serum with pancreatic carcinoma derived CA 19-9 in their routine testing and quality control procedures. The results were collected centrally and evaluated statistically. RESULTS: The comparability of CA 19-9 results is limited especially when different tests are used, albeit, some tests show a good correlation: The CA 19-9 values obtained by different laboratories using different test systems vary up to a factor of 2. The precision of CA 19-9 determinations was acceptable in most laboratories with coefficients of variation ranging between very low 3.2% and high 17.8%. The imprecision was slightly increased when automatic dilution procedures of the analysers were used. CONCLUSIONS: The comparability of CA 19-9 test results must be improved. The precision is acceptable in most cases. In order to monitor key performance parameters, every laboratory should participate in external quality assessment schemes and should perform a routine internal quality control with a control serum independent from the test kit manufacturer.
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[219]
TÍTULO / TITLE: - Unresectable pancreatic tumour? The issue is tissue.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neth J Med. 2013 Mar;71(2):81-3.
AUTORES / AUTHORS: - du Perron LJ; Westerman M; Issa A; Smorenburg CH
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Medical Centre Alkmaar, the Netherlands.
RESUMEN / SUMMARY: - The majority of tumours in the pancreas are adenocarcinomas for which therapeutic options are limited and which are associated with an unsatisfactory prognosis. However, alternative diagnoses may result in other therapeutic approaches with often a more favourable outcome. Hence, it is crucial to obtain a histological diagnosis before a definitive therapeutic plan can be devised. In this manuscript, a small series of pancreatic tumours other than adenocarcinoma are described.
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[220]
TÍTULO / TITLE: - Expression profiles analysis of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Rev Med Pharmacol Sci. 2013 Feb;17(3):311-7.
AUTORES / AUTHORS: - Yang D; Zhu Z; Wang W; Shen P; Wei Z; Wang C; Cai Q
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Surgery, Shanghai Changzheng Hospital affiliated to the Second Military Medical University, Shanghai, China. caiqingpingasdf@hotmail.com.
RESUMEN / SUMMARY: - BACKGROUN: Pancreatic cancer is the fourth most common cause of cancer-related deaths across the globe and has a poor prognosis. AIM: To investigate the characteristics of genomic expression profiles of pancreatic cancer and screen differentially expressed genes. MATERIALS AND METHODS: Using GSE16515 dataset downloaded from GEO (Gene Expression Omnibus) database, we first screened the differentially expressed genes (DEGs) in pancreatic cancer by packages in R language. The key functions of DEGs were investigated by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. The potential functionally important SNP (Single Nucleotide Polymorphism) was selected from the dbSNP database. RESULTS: A total of 1270 DEGs were identified. Most of them were predicted to be involved in pancreatic cancer development by sequence variant. Six genes (CDC42, STAT1, RALA, BCL2L1, TGFA, and EGF) were enriched in the known pancreatic cancer pathway. All these six genes had SNP, usually mutation at A/G and C/T point. CONCLUSIONS: Our results provide some underlying biomarkers for early diagnosis of pancreatic cancer.
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[221]
TÍTULO / TITLE: - Activation of the IL-6R/Jak/Stat Pathway is Associated with a Poor Outcome in Resected Pancreatic Ductal Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointest Surg. 2013 Feb 23.
●● Enlace al texto completo (gratuito o de pago) 1007/s11605-013-2168-7
AUTORES / AUTHORS: - Denley SM; Jamieson NB; McCall P; Oien KA; Morton JP; Carter CR; Edwards J; McKay CJ
INSTITUCIÓN / INSTITUTION: - West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Level 4 Walton Building, Alexandra Parade, Glasgow, G31 2ER, UK.
RESUMEN / SUMMARY: - BACKGROUND AND OBJECTIVE: Chronic localized pancreatic inflammation in the form of chronic pancreatitis is an established risk factor for human pancreatic ductal adenocarcinoma (PDAC) development. Constitutive activation of inflammation-related signal transducer and activator of transcription (Stat)3 signaling has been implicated in the development and progression a number of malignancies, including PDAC. Although, the Janus Kinase (Jak)/Stat pathway is a potential drug target, clinicopathological, molecular, and prognostic features of Stat3-activated PDAC remain uncertain. Our aim was to determine the clinicopathological impact of this inflammatory pathway in resectable PDAC. METHODS: Using a tissue microarray-based cohort of PDAC from 86 patients undergoing pancreaticoduodenectomy with curative intent and complete clinicopathological data available, we evaluated expression of the interleukin-6 receptor (IL-6R)/Jak/Stat pathway by immunohistochemistry. IL-6R, Jak, phospho (p)-Jak, Stat3, pStat3(Tyr705), and pStat3(Ser727) were assessed in PDAC and pancreatic intraepithelial neoplasia. A Cox regression multivariate analysis model was used to determine factors influencing survival. Activation of the IL-6R/Jak/Stat3 pathway was compared with the systemic inflammatory response as measured by serum C-reactive protein levels. RESULTS: High pJak was associated with reduced overall survival in multivariate analysis when compared with those with moderate or low expression (p = 0.036; hazard ratio (HR) = 1.68) as was pStat3(Tyr705) (p < 0.001; HR = 2.66) independent of lymph node status and tumor grade. Patients with a combination of pJak(high)/pStat3(Tyr705) (high) expression had an especially poor prognosis (median survival of 8.8 months; 95 % CI, 4.4-13.2). While the IL-6R/Jak/Stat pathway did not correlate with serum C-reactive protein levels, high pStat3 expression was associated with a reduction in the density of the local tumoral immune response. CONCLUSION: Activation of the Jak/Stat3 pathway via phosphorylation was associated with adverse outcome following resection of PDAC with curative intent supporting potential roles for pJak and pStat3 as prognostic biomarkers markers and therapeutic targets.
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[222]
TÍTULO / TITLE: - Bcl-2/Bcl-xL Inhibition Increases the Efficacy of Mek Inhibition Alone and in Combination with PI3 Kinase Inhibition in Lung and Pancreatic Tumor Models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 8.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0949
AUTORES / AUTHORS: - Tan N; Wong M; Nannini MA; Hong R; Lee LB; Price S; Williams K; Savy PP; Yue P; Sampath D; Settleman J; Fairbrother WJ; Belmont LD
INSTITUCIÓN / INSTITUTION: - 1Molecular Diagnostics and Cancer Cell Biology, Genentech, Inc.
RESUMEN / SUMMARY: - Although MEK inhibition is predicted to cause cell death by stabilization of the pro-apoptotic BH3-only protein, BIM, the induction of apoptosis is often modest. To determine if addition of a Bcl-2 family inhibitor could increase the efficacy of a MEK inhibitor, we evaluated a panel of 53 non-small cell lung cancer and pancreatic cancer cell lines with the combination of navitoclax (ABT-263), a Bcl-2/Bcl-xL (BCL2/BCL2L1) antagonist, and a novel mitogen-activated protein kinase (MEK) inhibitor, G-963. The combination is synergistic in the majority of lines, with an enrichment of cell lines harboring KRAS mutations in the high synergy group. Cells exposed to G-963 arrest in G1 and a small fraction undergo apoptosis. The addition of navitoclax to G-963 does not alter the kinetics of cell cycle arrest, but greatly increases the percentage of cells that undergo apoptosis. The G-963/navitoclax combination was more effective than either single-agent in the KRAS mutant H2122 xenograft model; BIM stabilization and PARP cleavage were observed in tumors, consistent with the mechanism of action observed in cell culture. Addition of the phosphatidylinositol 3-kinase (PI3K, PIK3CA) inhibitor, GDC-0941, to this treatment combination increases cell killing compared to double or single-agent treatment. Taken together, these data suggest the efficacy of agents that target the MAPK and PI3K pathways can be improved by combination with a Bcl-2 family inhibitor.
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[223]
TÍTULO / TITLE: - Combining hedgehog signaling inhibition with focal irradiation on reduction of pancreatic cancer metastasis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-1030
AUTORES / AUTHORS: - Gu D; Liu H; Su GH; Zhang X; Chin-Sinex H; Hanenberg H; Mendonca MS; Shannon HE; Chiorean EG; Xie J
INSTITUCIÓN / INSTITUTION: - 1wells Center for pediatric research, IU School of Medicine.
RESUMEN / SUMMARY: - Pancreatic cancer often presents in advanced stages and is unresponsive to conventional treatments. Thus, the need to develop novel treatment strategies for pancreatic cancer has never been greater. Here we report that combination of focal irradiation with hedgehog (Hh) signaling inhibition exerts better than additive effects on reducing metastases. In an orthotopic model, we found that focal irradiation alone effectively reduced primary tumor growth but did not significantly affect metastasis. We hypothesized that cancer stem cells (CSC) of pancreatic cancer are responsible for the residual tumors following irradiation, which may be regulated by Hh signaling. To test our hypothesis, we showed that tumor metastasis in our model was accompanied by increased expression of CSC cell surface markers as well as Hh target genes. We generated tumor spheres from orthotopic pancreatic and metastatic tumors, which have elevated levels of CSC markers relative to the parental cells and elevated expression of Hh target genes. Irradiation of tumor spheres further elevated CSC cell surface markers and increased Hh target gene expression. Combination of Hh signaling inhibition with radiation had more than additive effects on tumor sphere regeneration in vitro. This phenotype was observed in two independent cell lines. In our orthotopic animal model, focal radiation plus Hh inhibition had more than additive effects on reducing lymph node metastasis. We identified several potential molecules in mediating Hh signaling effects. Taken together, our data provide a rationale for combined use of Hh inhibition with irradiation for clinical treatment of pancreatic cancer patients.
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[224]
TÍTULO / TITLE: - Selective Requirement of PI3K/PDK1 Signaling for Kras Oncogene-Driven Pancreatic Cell Plasticity and Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell. 2013 Mar 18;23(3):406-20. doi: 10.1016/j.ccr.2013.01.023. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2013.01.023
AUTORES / AUTHORS: - Eser S; Reiff N; Messer M; Seidler B; Gottschalk K; Dobler M; Hieber M; Arbeiter A; Klein S; Kong B; Michalski CW; Schlitter AM; Esposito I; Kind AJ; Rad L; Schnieke AE; Baccarini M; Alessi DR; Rad R; Schmid RM; Schneider G; Saur D
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine 2, Technische Universitat Munchen, Ismaningerstr. 22, 81675 Munchen, Germany.
RESUMEN / SUMMARY: - Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia (ADM), and pancreatic ductal adenocarcinoma (PDAC) formation. This contrasts with Kras-driven non-small cell lung cancer, where signaling via Craf, but not PDK1, is an essential tumor-initiating event. These in vivo genetic studies together with pharmacologic treatment studies in models of human ADM and PDAC demonstrate tissue-specific differences of oncogenic Kras signaling and define PI3K/PDK1 as a suitable target for therapeutic intervention specifically in PDAC.
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[225]
TÍTULO / TITLE: - Mechanism of action of salinomycin on growth and migration in pancreatic cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreatology. 2013 Jan-Feb;13(1):72-8. doi: 10.1016/j.pan.2012.11.314. Epub 2012 Dec 10.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pan.2012.11.314
AUTORES / AUTHORS: - He L; Wang F; Dai WQ; Wu D; Lin CL; Wu SM; Cheng P; Zhang Y; Shen M; Wang CF; Lu J; Zhou YQ; Xu XF; Xu L; Guo CY
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University of Medicine, Shanghai 200072, PR China.
RESUMEN / SUMMARY: - OBJECTIVES: Pancreatic cancer is one of the most aggressive and lethal cancers worldwide and there are few effective treatments. Recently, salinomycin (Sal) was reported to alter proliferation and apoptosis in various tumors. This prompted us to investigate the effect of Sal on pancreatic cancer cells and to explore the possible molecular mechanism in vitro. METHODS: After treatment with Sal, pancreatic cancer cell viability and apoptosis were analyzed by Hoechst 33342 staining and flow cytometry, respectively. Invasion and metastasis of pancreatic cancer cells were assayed by a Transwell migration assay. Flow cytometry was also used to assessed the fraction of CD133(+) cell subpopulations. The expression of proliferating cell nuclear antigen (PCNA), Bcl-2, E-cadherin, and Wnt/beta-catenin signaling-related proteins were detected by RT-PCR and western blot. RESULTS: Sal inhibited the growth and migration of pancreatic cancer cells in vitro in a dose- and time-dependent manner. We found that the proportion of CD133(+) cell subpopulations decreased after treatment with Sal in pancreatic cancer cell lines at the same time. The percentage of apoptotic cells was increased after Sal treatment. Compared with control groups, Bax and E-cadherin were significantly upregulated, and Bcl-2 and PCNA were significantly downregulated in Sal-treated cells. The expression of Wnt/beta-catenin signaling-related proteins (beta-catenin and p-GSK-3beta) was inhibited. CONCLUSIONS: These results indicate that Sal could influence the cell growth and migration in pancreatic cancer cells in vitro, which may occur by inhibition of Wnt/beta-catenin signaling.
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[226]
TÍTULO / TITLE: - Endoscopic Ultrasonography - A Sensitive Tool in the Preoperative Localization of Insulinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Endocr Pract. 2013 Feb 20:1-16.
●● Enlace al texto completo (gratuito o de pago) 4158/EP12122.OR
AUTORES / AUTHORS: - Joseph AJ; Kapoor N; Simon EG; Chacko A; Thomas EM; Eapen A; Abraham DT; Jacob PM; Paul T; Rajaratnam S; Thomas N
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
RESUMEN / SUMMARY: - Objective: A number of imaging modalities have been used in the preoperative localization of insulinomas. CT is the modality that is in widespread use. Endoscopic ultrasound (EUS) allows the transducer to be placed in close proximity to the pancreas, thereby yielding images of higher quality, leading to accurate localization. An accurate preoperative localization results in minimal invasive surgery and a lower occurrence of residual tumours translating into a better clinical outcome.Methods: We analyzed the hospital records of all adult patients (age > 18 yrs), who were diagnosed to have insulinoma, over a period of 6 yrs, from Oct 2004 to Sept 2010. The diagnosis was based on the clinical practice guidelines of the American Endocrine Society. The sensitivity of EUS was compared with MDCT in localization of the lesion.Results: Eighteen patients were seen over a period of 6 years, from 2004 to 2010. EUS was conducted in all 18 patients. Multi-detector CT scans were carried out in 17 patients. EUS had greater sensitivity (89%)in localizing insulinomas in comparison to CT (69%). In this series, the lesions which were missed on CT, but were picked up on EUS were smaller (less than 12 mm, p = <0.001). Lesions which were close to the mesenteric vessels and those located in the head of the pancreas were more likely to be missed on CT.Conclusions: EUS has a greater sensitivity in identifying and localizing insulinomas preoperatively. With increasing availability, the EUS should be part of a preoperative insulinoma workup.
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[227]
TÍTULO / TITLE: - Laparoscopic drainage of a large pancreatic pseudocyst.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JSLS. 2012 Oct-Dec;16(4):675-7. doi: 10.4293/108680812X13517013316870.
●● Enlace al texto completo (gratuito o de pago) 4293/108680812X13517013316870
AUTORES / AUTHORS: - Sharma D; Kataria S; Pathak R; Barua B; Lal R
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Lady Hardinge Medical College, New Delhi, India. deborshi_sh@yahoo.com
RESUMEN / SUMMARY: - Laparoscopic cystogastrostomy is an established procedure for the drainage of pancreatic pseudocysts. Cysts are mainly present in the lesser sac (retro-gastric), which is completely amenable to cystogastrostomy. We discuss the problems faced and simple solutions to the problems in managing a huge pancreatic pseudocyst of 22 cmx18 cm in a young boy 18 y of age.
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[228]
TÍTULO / TITLE: - Role of laparoscopic distal pancreatectomy for solid pseudopapillary tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JSLS. 2012 Oct-Dec;16(4):552-8. doi: 10.4293/108680812X13462882736970.
●● Enlace al texto completo (gratuito o de pago) 4293/108680812X13462882736970
AUTORES / AUTHORS: - Jarry J; Bodin R; Peycru T; Nunez M; Collet D; Cunha AS
INSTITUCIÓN / INSTITUTION: - Department of Digestive Surgery, Robert Picque Hospital, Villenave d’Ornon, France. julienjarry@hotmail.com
RESUMEN / SUMMARY: - BACKGROUND: Since the first case report regarding laparoscopic distal pancreatectomy (DP) for solid pseudopapillary tumor (SPT), few additional articles have been published. The objective of this study was to evaluate the feasibility, safety, and long-term outcome of the laparoscopic DP based on a series of adult SPT patients. METHODS: In a single-center study, we screened all adult patients undergoing a laparoscopic DP for SPT. Preoperative, operative, and postoperative data were retrospectively analysed and compared to the results of open DP for SPT published in the medical literature. RESULTS: From April 2000 to June 2010, 5 adult female patients (median age 34 y) underwent a laparoscopic DP for an SPT. No conversion to open surgery was required. The median size of the tumor was 45 mm. The postoperative mortality rate was 0%, and serious complications (Dindo IV) occurred in 2 patients. The postoperative quality of life was not significantly altered by the laparoscopic procedure. At a median follow-up of 60 mo, all patients were alive and without evidence of local recurrence, distant metastasis, diabetes, or exocrine insufficiency. CONCLUSION: Laparoscopy may offer an alternative to open surgery in the treatment of SPT of the distal pancreas in adult female patients. The laparoscopic procedure impacts neither the oncologic outcome nor the quality of life. However, due to the risk of postoperative complications, this procedure should be reserved for specialized centers.
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[229]
TÍTULO / TITLE: - The HSP70 and Autophagy Inhibitor Pifithrin-mu Enhances the Antitumor Effects of TRAIL on Human Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Ther. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1158/1535-7163.MCT-12-0954
AUTORES / AUTHORS: - Monma H; Harashima N; Inao T; Okano S; Tajima Y; Harada M
INSTITUCIÓN / INSTITUTION: - Authors’ Affiliations: Departments of 1Immunology and 2Surgery, Shimane University Faculty of Medicine, Shimane; and 3Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - TRAIL and agonistic death receptor-specific antibodies can induce apoptosis in cancer cells with little cytotoxicity to normal cells. To improve TRAIL-induced antitumor effects, we tested its effectiveness in combination with pifithrin (PFT)-mu, which has the potential to inhibit HSP70 function and autophagy, both of which participate in TRAIL resistance in cancer cells. Among the four human pancreatic cancer cell lines tested, MiaPaca-2, Panc-1, and BxPC-3 cells showed varying sensitivities to TRAIL. In MiaPaca-2 and Panc-1 cells, knockdown of HSP70 or beclin-1, the latter an autophagy-related molecule, by RNA interference augmented TRAIL-induced antitumor effects, decreasing cell viability, and increasing apoptosis. On the basis of these findings, we next determined whether the TRAIL-induced antitumor effects could be augmented by its combination with PFT-mu. The combination of TRAIL plus PFT-mu significantly decreased the viability and colony-forming ability of MiaPaca-2 and Panc-1 cells compared with cells treated with either agent alone. When applied alone, PFT-mu increased Annexin V+ cells in both caspase-dependent and -independent manners. It also promoted TRAIL-induced apoptosis and arrested cancer cell growth. Furthermore, PFT-mu antagonized TRAIL-associated NF-kappaB activation in cancer cells. In a xenograft mouse model, combination therapy significantly inhibited MiaPaca-2 tumor growth compared with treatment with either agent alone. The results of this study suggest protective roles for HSP70 and autophagy in TRAIL resistance in pancreatic cancer cells and suggest that PFT-mu is a promising agent for use in therapies intended to enhance the antitumor effects of TRAIL. Mol Cancer Ther; 12(4); 1-11. ©2013 AACR.
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[230]
TÍTULO / TITLE: - SnapShot: Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell. 2013 Mar 18;23(3):424-424.e1. doi: 10.1016/j.ccr.2013.03.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2013.03.008
AUTORES / AUTHORS: - Han H; Von Hoff DD
INSTITUCIÓN / INSTITUTION: - Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
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[231]
TÍTULO / TITLE: - Multidisciplinary Management of Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Surg Oncol Clin N Am. 2013 Apr;22(2):265-87. doi: 10.1016/j.soc.2012.12.003. Epub 2013 Jan 5.
●● Enlace al texto completo (gratuito o de pago) 1016/j.soc.2012.12.003
AUTORES / AUTHORS: - Kumar R; Herman JM; Wolfgang CL; Zheng L
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology & Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
RESUMEN / SUMMARY: - Pancreatic cancer (pancreatic adenocarcinoma) remains one of the deadliest malignancies in the western hemisphere despite improved surgical technique, chemotherapy, and radiation therapy. The appropriate management of this malignancy should incorporate multiple treatment modalities for optimal opportunity for cure. Recent trials with a variety of treatment techniques confer improved survival of patients with pancreatic cancer, even in the metastatic setting. In this review, the importance of multidisciplinary management of pancreatic cancer based on disease stage is discussed.
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[232]
TÍTULO / TITLE: - Evolution of pancreatoduodenectomy in a tertiary cancer center in India: improved results from service reconfiguration.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreatology. 2013 Jan-Feb;13(1):63-71. doi: 10.1016/j.pan.2012.11.302. Epub 2012 Nov 10.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pan.2012.11.302
AUTORES / AUTHORS: - Shrikhande SV; Barreto SG; Somashekar BA; Suradkar K; Shetty GS; Talole S; Sirohi B; Goel M; Shukla PJ
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai, India. shailushrikhande@hotmail.com
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic cancer incidence in India is low. Over the years, refinements in technique of pancreatoduodenectomy (PD) may have improved outcomes. No data is available from India, South-Central, or South West Asia to assess the impact of these refinements. PURPOSE: To assess the impact of service reconfiguration and standardized protocols on outcomes of PD in a tertiary cancer center in India. METHODS: Three specific time periods marking major shifts in practice and performance of PD were identified, viz. periods A (1992-2001; pancreaticogastrostomy predominantly performed), B (2003-July 2009; standardization of pancreaticojejunal anastomosis), and C (August 2009-December 2011; introduction of neoadjuvant chemo-radiotherapy and increased surgical volume). RESULTS: 500 PDs were performed with a morbidity and mortality rate of 33% and 5.4%, respectively. Over the three periods, volume of cases/year significantly increased from 16 to 60 (p < 0.0001). Overall incidence of post-operative pancreatic anastomotic leak/fistula (POPF), hemorrhage, delayed gastric emptying (DGE), and bile leak was 11%, 6%, 3.4%, and 3.2%, respectively. The overall morbidity rates, as well as, the above individual complications significantly reduced from period A to B (p < 0.01) with no statistical difference between periods B and C. CONCLUSION: Evolution of practice and perioperative management of PD for pancreatic cancer at our center improved perioperative outcomes and helped sustain the improvements despite increasing surgical volume. By adopting standardized practices and gradually improving experience, countries with low incidence of pancreatic cancer and resource constraints can achieve outcomes comparable to high-incidence, developed nations. SYNOPSIS: The manuscript represents the largest series on perioperative outcomes for pancreatoduodenectomy from South West and South-Central Asia - a region with a low incidence of pancreatic cancer and a disproportionate distribution of resources highlighting the impact of high volumes, standardization and service reconfiguration.
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[233]
TÍTULO / TITLE: - First report of primary pancreatic natural killer/T-cell nasal type lymphoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Rev Med Pharmacol Sci. 2013 Feb;17(3):318-22.
AUTORES / AUTHORS: - Liu W; Hua R; Zhang JF; Huo YM; Liu DJ; Sun YW
INSTITUCIÓN / INSTITUTION: - Depatment of Surgery, Shanghai Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. syw0616@126.com.
RESUMEN / SUMMARY: - BACKGROUND: Primary pancreatic lymphoma (PPL) is an extremely rare form of extranodal malignant lymphoma and pancreatic tumour. Natural killer/T-cell lymphoma is an aggressive rare form extranodal lymphoma with a predilection for the nasal cavity/nasopharynx, it can arise in other organs such as skin, testicles, spleen, adrenal, or GI tract, but the initial presentation of our patient in the pancreas is unreported. CASE PRESENTATION: We present a case of primary pancreatic natural killer/T-cell nasal type lymphoma in a 62-year-old man. The presenting symptoms were non-specific only for upper abdominal pain and weight loss. Imaging techniques showed the lesion was located in the head of pancreas. Computed tomography (CT) scanning and otorhinolaryngology examination were negative for nasopharyngeal lymphoma. The initial concern was for pancreatic tumor and the patient underwent pancreaticoduodenectomy. The diagnosis of primary pancreatic natural killer/T-cell nasal type lymphoma was established as the combination of NK-lineage antigens (TIA-1, granzyme B, CD56) with EBV-expression. CONCLUSIONS: This is the first case of primary pancreatic natural killer (NK)/T-cell nasal type lymphoma. PPL, although a rare pathologic entity, should be considered in the differential diagnosis for a large homogeneous mass with extrapancreatic extension in the head especially in those of normal serum CA 19-9 level.
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[234]
TÍTULO / TITLE: - Tumor-stromal interactions in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreatology. 2013 Jan-Feb;13(1):1-7. doi: 10.1016/j.pan.2012.11.311. Epub 2012 Nov 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.pan.2012.11.311
AUTORES / AUTHORS: - Tod J; Jenei V; Thomas G; Fine D
INSTITUCIÓN / INSTITUTION: - Cancer Sciences Unit, Somers Building, University of Southampton School of Medicine, Tremona Rd., Southampton SO16 6YD, UK. jotod@hotmail.co.uk
RESUMEN / SUMMARY: - Pancreatic adenocarcinoma has one of the worse prognoses of any cancer with a 5-year survival of only 3%. Pancreatic cancer displays one of the most prominent stromal reactions of all tumors and it is evident that this is a key contributing factor to disease outcome. The tumor microenvironment of pancreatic cancer harbors a wide spectrum of cell types and a complex network of mechanisms which all serve to promote tumor progression. It is clear that the symbiotic relationship between pancreatic cancer cells and stellate cells is the chief factor creating this unique tumor milieu. Pancreatic stellate cells play critical roles in evasion of cancer cell apoptosis, invasion and metastases, angiogenesis, and promotion of an immunosuppressive environment, all key hallmarks of malignancy. Existing treatments for pancreatic cancer focus on targeting the cancer cells rather than the whole tumor, of which cancer cells represent a small proportion. It is now increasingly evident that research targeted towards the interactions between these cell types, ideally at an early stage of tumor development, is imperative in order to propel the way forward to more effective treatments.
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[235]
TÍTULO / TITLE: - Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell. 2013 Mar 19. pii: S1535-6108(13)00068-8. doi: 10.1016/j.ccr.2013.02.005.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ccr.2013.02.005
AUTORES / AUTHORS: - Zhao D; Zou SW; Liu Y; Zhou X; Mo Y; Wang P; Xu YH; Dong B; Xiong Y; Lei QY; Guan KL
INSTITUCIÓN / INSTITUTION: - Ministry of Education Key Laboratory of Molecular Medicine, Shanghai Medical College and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200032, China; Laboratory of Molecular Cell Biology, Institute of Biomedical Science, Fudan University, Shanghai 200032, China; School of Life Sciences, Fudan University, Shanghai 200032, China.
RESUMEN / SUMMARY: - Tumor cells commonly have increased glucose uptake and lactate accumulation. Lactate is produced from pyruvate by lactate dehydrogenase A (LDH-A), which is frequently overexpressed in tumor cells and is important for cell growth. Elevated transcription by c-Myc or HIF1alpha may contribute to increased LDH-A in some cancer types. Here, we show that LDH-A is acetylated at lysine 5 (K5) and that this acetylation inhibits LDH-A activity. Furthermore, the K5-acetylated LDH-A is recognized by the HSC70 chaperone and delivered to lysosomes for degradation. Replacement of endogenous LDH-A with an acetylation mimetic mutant decreases cell proliferation and migration. Importantly, K5 acetylation of LDH-A is reduced in human pancreatic cancers. Our study reveals a mechanism of LDH-A upregulation in pancreatic cancers.
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[236]
TÍTULO / TITLE: - Effects of the silencing of hypoxia-inducible Factor-1 alpha on metastasis of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):436-46.
AUTORES / AUTHORS: - Wei H; Li F; Fu P; Liu X
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, First Affiliated Hospital, and Zhejiang University School of Medicine, Zhejiang Province, China. whycherry77@hotmail.com.
RESUMEN / SUMMARY: - BACKGROUND: Hypoxia plays a crucial role in the development of solid tumors. Hypoxia-inducible factor-1alpha (HIF-1alpha) is essential for this process, and has been suggested to be a target for cancer therapy. New therapeutic approaches for pancreatic cancer are needed owing to the extremely poor prognosis, in large part as a consequence of high rates of metastasis. The mechanism remains to be explored. AIM: To illustrate the role of hypoxia-inducible factor-1alpha in pancreatic cancer metastasis and the value of the molecule as a target for pancreatic cancer therapy. MATERIALS AND METHODS: To address this shortcoming, we used both in vitro and in vivo approaches to evaluate the overall effects of HIF-1alpha on pancreatic cancer. We used a plasmid encoding small interfering RNAs (SiRNAs) to silence HIF-1alpha expression in the Panc-1 pancreatic cancer cell line, and used a series of assays to detect changes in gene expression at the protein and mRNA levels, cell proliferation, cell apoptosis, and the abilities of cells to migrate under both hypoxia and normoxia conditions. RESULTS: Both in vitro and in vivo analysis suggested that hypoxia significantly promotes cell proliferation and migration, resulting in metastasis. Pancreatic cancer cells in which HIF-1alpha expression was inhibited were less invasive, with reduced resistance to hypoxia, impaired migration, and reduced capacity to cause metastasis. CONCLUSIONS: HIF-1alpha may be a dominant factor driving the metastatic progression of pancreatic cancer and can be a potent therapeutic target for the disease.
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[237]
TÍTULO / TITLE: - A case of pancreatic invasive ductal adenocarcinoma with malignant peritoneal cystic components.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Clin Oncol. 2013 Feb;43(2):217. doi: 10.1093/jjco/hyt009.
●● Enlace al texto completo (gratuito o de pago) 1093/jjco/hyt009
AUTORES / AUTHORS: - Zhang L; Shibamoto K
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[238]
TÍTULO / TITLE: - Pancreatic cancer causing acute pancreatitis: a comparative study with cancer patients without pancreatitis and pancreatitis patients without cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Hepatobiliary Pancreat Sci. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s00534-013-0598-y
AUTORES / AUTHORS: - Minato Y; Kamisawa T; Tabata T; Hara S; Kuruma S; Chiba K; Kuwata G; Fujiwara T; Egashira H; Koizumi K; Saito I; Endo Y; Koizumi S; Fujiwara J; Arakawa T; Momma K; Kurata M; Honda G
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
RESUMEN / SUMMARY: - BACKGROUND/PURPOSE: Although pancreatic cancer produces upstream obstructive pancreatitis, acute pancreatitis is a less common manifestation of pancreatic cancer. This study aimed to clarify the subgroup of pancreatic cancer patients who present with an episode of acute pancreatitis (Group I) in comparison with a matched group of pancreatic cancer patients without pancreatitis (Group II) and another group of acute pancreatitis patients without pancreatic cancer (Group III). METHODS: This was a retrospective comparative study of 18 patients in Group I, 300 patients in Group II and 141 patients in Group III. RESULTS: The mean age of Group I was 63.7 years and the male to female ration was 1:0.3. Serum CA 19-9 levels were elevated in 80 %. The main pancreatic duct was incompletely obstructed in 7 patients. There were no significant differences in location of tumor, clinical stage, resection rate and survival months between Group I and II. Acute pancreatitis secondary to pancreatic cancer was more likely to be mild (94 vs. 72 %, p < 0.05) and relapsed (39 vs. 16 %, p < 0.05) compared with Group III. CONCLUSIONS: Anatomic evaluation of the pancreas should be performed in patients with acute pancreatitis with no obvious etiology, even if the pancreatitis is mild, to search for underlying malignancy.
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[239]
TÍTULO / TITLE: - Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Mar 1;8:44. doi: 10.1186/1748-717X-8-44.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-44
AUTORES / AUTHORS: - Gurka MK; Collins SP; Slack R; Tse G; Charabaty A; Ley L; Berzcel L; Lei S; Suy S; Haddad N; Jha R; Johnson CD; Jackson P; Marshall JL; Pishvaian MJ
INSTITUCIÓN / INSTITUTION: - Lombardi Comprehensive Cancer Center, Georgetown University, Podium B 3800 Reservoir Road, NW, 20007, Washington, DC, USA. pishvaim@georgetown.edu.
RESUMEN / SUMMARY: - BACKGROUND: Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. METHODS: Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. RESULTS: Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. CONCLUSIONS: SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.
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[240]
TÍTULO / TITLE: - Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastrointest Oncol. 2012 Oct 15;4(10):207-15. doi: 10.4251/wjgo.v4.i10.207.
●● Enlace al texto completo (gratuito o de pago) 4251/wjgo.v4.i10.207
AUTORES / AUTHORS: - Wentz SC; Zhao ZG; Shyr Y; Shi CJ; Merchant NB; Washington K; Xia F; Chakravarthy AB
INSTITUCIÓN / INSTITUTION: - Sabrina C Wentz, Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD 21201, United States.
RESUMEN / SUMMARY: - AIM: Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.
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[241]
TÍTULO / TITLE: - Reduction in circulating pro-angiogenic and pro-inflammatory factors is related to improved outcomes in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega-3 fish oil.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2012 Nov 22. doi: 10.1111/hpb.12002.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12002
AUTORES / AUTHORS: - Arshad A; Chung WY; Steward W; Metcalfe MS; Dennison AR
INSTITUCIÓN / INSTITUTION: - Department of Hepatobiliary and Department of Pancreatic Surgery, University Hospitals of Leicester, Leicester, UK.
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic cancer is a rapidly progressive disease which is often only amenable to palliative treatment. Few patients respond to palliative chemotherapy, so surrogate markers indicating which patients are likely to respond to treatment are required. There is a well-established link between pro-inflammatory circulating cytokines and growth factors (CAF), and the development of neoplasia. Agents that may modulate these factors are of interest in developing potential novel therapeutic applications. METHODS: As part of a single-arm phase II trial in patients with advanced pancreatic cancer (APC) treated with gemcitabine and intravenous (i.v.) omega-3 rich lipid emulsion (n-3FA), serum samples were analysed for 14 CAF using a multiplex cytokine array. Baseline serum concentrations were correlated with overall (OS) and progression-free survival (PFS), and changes in concentration correlated with time and outcomes for CAF responders were analysed. RESULTS: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) concentrations reduced significantly with treatment over time. Low baseline interleukin (IL)-6 and -8 were correlated with improved OS. PDGF responders showed a tendency towards improved OS and FGF responders a significantly improved PFS. DISCUSSION: Treatment with gemcitabine plus i.v. n-3FA may reduce concentrations of CAF which may be associated with an improved outcome. Baseline IL-6 and -8 may be surrogate markers for outcome in patients with APC treated with this regimen.
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[242]
TÍTULO / TITLE: - Endoscopic ultrasound-guided fine-needle aspiration diagnosis of pancreatic schwannoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dig Liver Dis. 2013 Feb 11. pii: S1590-8658(13)00010-8. doi: 10.1016/j.dld.2013.01.008.
●● Enlace al texto completo (gratuito o de pago) 1016/j.dld.2013.01.008
AUTORES / AUTHORS: - Barresi L; Tarantino I; Granata A; Traina M
INSTITUCIÓN / INSTITUTION: - Gastroenterology and Endoscopy Unit, ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy. Electronic address: lbarresi@ismett.edu.
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[243]
TÍTULO / TITLE: - Molecular guided therapy for advanced pancreatic cancer patients with PI3K activated mutation: vision or illusion?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onco Targets Ther. 2013;6:95-7. doi: 10.2147/OTT.S38520. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S38520
AUTORES / AUTHORS: - Gazzah A; Gonzales DB; Levy A; Bahleda R; Ducreux M; Lacroix L; Soria JC
INSTITUCIÓN / INSTITUTION: - SITEP (Service des Innovations Therapeutiques Precoces), Department of Medicine, Institut Gustave Roussy, Paris XI University, Villejuif, France.
RESUMEN / SUMMARY: - Despite a modern validated regimen of chemotherapy, advanced pancreatic adenocarcinoma remains the fourth most common cause of cancer-related death worldwide. The phosphoinositide 3-kinase pathway (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a major signaling pathway that may be activated in advanced pancreatic cancer. To highlight the potential interest of this targetable pathway in selected advanced pancreatic cancer patients, we report herein a patient with an activated PI3K mutation who was treated in a phase I trial evaluating a treatment combination including an mTOR inhibitor.
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[244]
TÍTULO / TITLE: - Adenoviral insulinoma-associated protein 1 promoter-driven suicide gene therapy with enhanced selectivity for treatment of neuroendocrine cancers.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ochsner J. 2013 Spring;13(1):91-9.
AUTORES / AUTHORS: - Akerstrom V; Chen C; Lan MS; Breslin MB
INSTITUCIÓN / INSTITUTION: - Research Institute for Children, Children’s Hospital New Orleans, LA ; Diana Helis Henry Medical Research Foundation, New Orleans, LA.
RESUMEN / SUMMARY: - BACKGROUND: Insulinoma-associated protein 1 (INSM1) is a zinc finger transcriptional repressor with a limited spatial and temporal embryonic expression pattern in neuronal and neuroendocrine tissues. Interestingly, INSM1 activity is reactivated in neuroendocrine tumors such as small-cell lung cancer (SCLC), neuroblastoma, medulloblastoma, and retinoblastoma. Adenoviral constructs with the 1.7-kilobase pair INSM1 promoter-driven herpes simplex virus thymidine kinase (HSV-tk) gene could effectively suppress D283 Med subcutaneous xenograft tumor growth. Undesirably, sequences in the adenoviral backbone overrode promoter specificity in vivo. Incorporation of both the chicken beta-globin HS4 insulator sequence and 2 copies of the mouse nicotinic acetylcholine receptor (nAchR) neuronal restrictive silencer element abolished the nonspecific activation of the INSM1 promoter in vivo. METHODS: The luciferase reporter gene was replaced with the HSV-tk suicide gene to generate the Ad-K5 virus. Both in vitro cell viability assays and in vivo tumor regression studies were used to determine the efficacy of the improved configuration INSM1 promoter adenoviral construct against a panel of neuroendocrine cell lines. RESULTS: In vitro cell viability assays with the Ad-K5 HSV-tk-expressing construct further reinforced that the Ad-K5 virus could eradicate SCLC, insulinoma, medulloblastoma, and neuroblastoma cells. Further, Ad-K5 virus treatment of a D283 Med subcutaneous xenograft tumor showed a superior antitumor effect over the control Ad-RSV (Rous sarcoma virus)-HSV-tk. CONCLUSIONS: Improvements to the INSM1 promoter resulted in a stronger and more selective adenovirus. Treatment of a panel of neuroendocrine carcinomas with the Ad-K5 virus revealed enhanced antitumor activity over the RSV control, demonstrating its usefulness for the treatment of a variety of neuroendocrine tumors.
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[245]
TÍTULO / TITLE: - Clinically meaningful responses to sequential gemcitabine-based chemotherapy regimens in a patient with metastatic pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Oncol. 2013 Jan;6(1):72-7. doi: 10.1159/000346836. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1159/000346836
AUTORES / AUTHORS: - Klimant E; Markman M; Albu DM
INSTITUCIÓN / INSTITUTION: - Cancer Treatment Centers of America, Philadelphia, Pa., USA.
RESUMEN / SUMMARY: - Pancreatic cancer exhibits profound chemoresistance resulting either from pre-existing (intrinsic) mechanisms, or from anticancer drug treatment itself (acquired chemoresistance). We present the case of a patient with pancreatic adenocarcinoma metastatic to the liver who experienced clinical, radiographic and tumor marker response to three lines of gemcitabine-based chemotherapy. The regimens included: 8 cycles of gemcitabine and oxaliplatin (GEMOX), 8 cycles of gemcitabine, docetaxel and capecitabine (GTX) and more than 3 cycles of gemcitabine and nab-paclitaxel, with an exceptional response 2 years from the initiation of chemotherapy for metastatic pancreatic cancer.
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[246]
TÍTULO / TITLE: - Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Mar;126(5):937-41.
AUTORES / AUTHORS: - Chen ZF; Li YB; Han JY; Yin JJ; Wang Y; Zhu LB; Xie GY
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
RESUMEN / SUMMARY: - BACKGROUND: The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells). METHODS: INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation. RESULTS: The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone. CONCLUSIONS: Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.
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[247]
TÍTULO / TITLE: - Expression of the ZEB2 gene in pancreatic stromal cells in pancreatic ductal adenocarcinoma, pancreatitis, and normal state.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Dokl Biol Sci. 2013 Jan-Feb;448(1):61-4. doi: 10.1134/S001249661301016X. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1134/S001249661301016X
AUTORES / AUTHORS: - Usova EV; Kopantseva MR; Kostina MB; Van’kovich AN; Egorov VI; Kopantsev EP
INSTITUCIÓN / INSTITUTION: - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 15/10, Moscow, 117871, Russia.
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[248]
TÍTULO / TITLE: - Response evaluation following neoadjuvant treatment of pancreatic cancer patients.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastrointest Surg. 2013 Feb 27;5(2):12-5. doi: 10.4240/wjgs.v5.i2.12.
●● Enlace al texto completo (gratuito o de pago) 4240/wjgs.v5.i2.12
AUTORES / AUTHORS: - Tosolini C; Michalski CW; Kleeff J
INSTITUCIÓN / INSTITUTION: - Chiara Tosolini, Christoph W Michalski, Jorg Kleeff, Department of Surgery, Technische Universitat Munchen, 81675 Munchen, Germany.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplastic entities, with a very poor prognosis characterized by a high mortality rate and short survival. This is due both to its aggressive biological behaviour and the high incidence of locally advanced stages at the time of the initial diagnosis. The limits of resectability and the role of neoadjuvant (radio) chemotherapy for PDAC management are still unclear. A recently published article by Kats et al compared the radiological, surgical and histopathological results of 129 patients with borderline resectable tumors undergoing neoadjuvant treatment followed by surgery. Although post-neoadjuvant treatment imaging implied a low response rate, a high rate of complete resections was achieved. This seems to confirm that, though radiology has made a significant progress in defining locally advanced PDAC, there is place for further improvement. In particular, the differentiation between radiotherapy-induced scarring/fibrosis and cancer-associated desmoplasia remains a clinical/radiological challenge. Though selection of patients with occult systemic disease is possible with neoadjuvant treatment, downstaging does not seem to occur frequently. Thus, development of novel, more aggressive (radio) chemotherapy regimens is required to improve prognosis of patients with locally unresectable but not systemically micro-metastasized tumors.
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[249]
TÍTULO / TITLE: - Chemoradiation in patients with isolated recurrent pancreatic cancer - therapeutical efficacy and probability of re-resection.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Jan 31;8:27. doi: 10.1186/1748-717X-8-27.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-27
AUTORES / AUTHORS: - Habermehl D; Brecht IC; Bergmann F; Welzel T; Rieken S; Werner J; Schirmacher P; Buchler MW; Debus J; Combs SE
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, Heidelberg, 69120, Germany. daniel.habermehl@med.uni-heidelberg.de
RESUMEN / SUMMARY: - BACKGROUND: In the present retrospective analysis we analysed the therapeutic outcome of a set of patients, who were treated with chemoradiation (CRT) for recurrent pancreatic cancer (RPC) in a single institution. PATIENTS AND METHODS: Forty-one patients had a history of primary resection for pancreatic cancer. In case of an unresectable recurrency patients were treated with CRT at our institution between 2002 and 2010 with a median dose of 48.4 Gy (range 39.6-54 Gy). Concurrent chemotherapy regimes included Gemcitabine (GEM) in 37/41 patients (90%) and Fluorouracil (FU) or Capecitabine (CAP) in 4/41 patients (10%). Patients were re-evaluated after CRT with computed tomography and/or explorative laparotomy. During re-resection or laparotomy 15 patients received an additional intraoperative radiotherapy (IORT) with a median dose of 15 Gy (range 12-15 Gy). Median age was 65 years (range 39-76 years) and there were 26 male and 15 female patients. RESULTS: The median overall survival (mOS), local control (LC) and progression-free survival (PFS) were 16.1, 13.8 and 6.9 months respectively for all patients after the first day of CRT. Re-resection was possible in five patients (12%) and a complete remission (CR) as defined by tumor-free biopsy was seen in 6 patients (15%). When re-resection could be achieved after CRT mOS was improved to 28.3 months (n = 5 patients, 95%-CI 10.2 - 46.3 months). Patients receiving IORT had a significantly improved mOS compared to no IORT (p = 0.034). Fifteen patients (37%) experienced a local tumour progression and main site of distant metastasis was the liver (11 patients, 27%).Overall treatment-related toxicity was mild, grade III hematologic toxicity was observed in 11 patients (27%). CONCLUSION: In summary we observed a good therapeutic response with mild to moderate toxicity levels for CRT in RPC. Overall survival and PFS were clearly improved in case of induction of a complete remission (tumor-free biopsies) or after achieving a re-resection, thus providing a curative intended therapy even in case of disease recurrence.
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[250]
TÍTULO / TITLE: - Arginase II expressed in cancer-associated fibroblasts indicates tissue hypoxia and predicts poor outcome in patients with pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55146. doi: 10.1371/journal.pone.0055146. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055146
AUTORES / AUTHORS: - Ino Y; Yamazaki-Itoh R; Oguro S; Shimada K; Kosuge T; Zavada J; Kanai Y; Hiraoka N
INSTITUCIÓN / INSTITUTION: - Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
RESUMEN / SUMMARY: - An adequate level of arginine in the tissue microenvironment is essential for T cell activity and survival. Arginine levels are regulated by the arginine-catabolizing enzyme, arginase (ARG). It has been reported that arginase II (ARG2), one of two ARGs, is aberrantly expressed in prostate cancer cells, which convert arginine into ornithine, resulting in a lack of arginine that weakens tumor-infiltrating lymphocytes and renders them dysfunctional. However, immune suppression mediated by ARG2-expressing cancer cells in lung cancer has not been observed. Here we studied the expression of ARG2 in pancreatic ductal carcinoma (PDC) tissue clinicopathologically by examining over 200 cases of PDC. In contrast to prostate cancer, ARG2 expression was rarely demonstrated in PDC cells by immunohistochemistry, and instead ARG2 was characteristically expressed in alpha-smooth muscle actin-positive cancer-associated fibroblasts (CAFs), especially those located within and around necrotic areas in PDC. The presence of ARG2-expressing CAFs was closely correlated with shorter overall survival (OS; P = 0.003) and disease-free survival (DFS; P = 0.0006). Multivariate Cox regression analysis showed that the presence of ARG2-expressing CAFs in PDC tissue was an independent predictor of poorer OS (hazard ratio [HR] = 1.582, P = 0.007) and DFS (HR = 1.715, P = 0.001) in PDC patients. In addition to the characteristic distribution of ARG2-expressing CAFs, such CAFs co-expressed carbonic anhydrase IX, SLC2A1, or HIF-1alpha, markers of hypoxia, in PDC tissue. Furthermore, in vitro experiments revealed that cultured fibroblasts extracted from PDC tissue expressed the ARG2 transcript after exposure to hypoxia, which had arginase activity. These results indicate that cancer cell-mediated immune suppression through ARG2 expression is not a general event and that the presence of ARG2-expressing CAFs is an indicator of poor prognosis, as well as hypoxia, in PDC tissue.
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[251]
TÍTULO / TITLE: - Adenovirus-mediated Interferon-gamma Gene Therapy Induced Human Pancreatic Carcinoma Capan-2 Cell Apoptosis In Vitro and In Vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Anat Rec (Hoboken). 2013 Apr;296(4):604-10. doi: 10.1002/ar.22661. Epub 2013 Feb 9.
●● Enlace al texto completo (gratuito o de pago) 1002/ar.22661
AUTORES / AUTHORS: - Xie FJ; Zhao P; Zhang YP; Liu FY; Nie XL; Zhu YH; Yu XM; Zheng QQ; Mao WM; Lu HY; Wei H; Huang W
INSTITUCIÓN / INSTITUTION: - Department of Medical Oncology, Zhejiang Cancer Hospital, HangZhou, 310022, China; Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, HangZhou, 310022, China.
RESUMEN / SUMMARY: - Pancreatic cancer is one of the most lethal human malignancies with a very low 5-year survival rate, which highlights urgent needs for more effective therapeutic strategies. In this study, we examined the potential therapeutic effects of an adenovirus encoding human interferon gamma (Ad-IFNgamma) on pancreatic carcinoma cells Capan-2 in vitro and in vivo. The results indicated that Ad-IFNgamma could significantly inhibit tumor cell growth via inducing cell apoptosis. After infection, IFNgamma expressed durably and stably in xenografts, predominantly in tumor tissue, while much less in blood and liver. Thus, adenovirus-mediated intratumoral injection of human IFNgamma gene could be an effective gene therapeutic system for the treatment of pancreatic carcinoma. Anat Rec, 296:604-610, 2013. © 2013 Wiley Periodicals, Inc.
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[252]
TÍTULO / TITLE: - Dramatic Survival Benefit Related to R0 Resection of Pancreatic Adenocarcinoma in Patients With Tumor </=25 mm in Size and </=1 Involved Lymph Nodes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Gastroenterol. 2013 Mar 21;4:e33. doi: 10.1038/ctg.2013.4.
●● Enlace al texto completo (gratuito o de pago) 1038/ctg.2013.4
AUTORES / AUTHORS: - Tummala P; Howard T; Agarwal B
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St Louis, Missouri, USA.
RESUMEN / SUMMARY: - OBJECTIVES: To evaluate i) the relative importance of R0 resection, tumor size and peripancreatic lymph node (LN) status are significant determinants of survival benefit following upfront surgery for pancreatic adenocarcinoma (PaCa), ii) whether R0 resection confers survival benefit in all patients or a patient subset with certain favorable prognostic factors. METHODS: Retrospective analysis of patients (2001-2010) who underwent planned potentially curative surgical resection without neoadjuvant therapy for PaCa. RESULTS: Among 154 patients, median survival following R0 (n=105) and R1 resections was 26.8 and 17.7 months, respectively (P=0.010). Tumor size and LN status were significant determinants of survival following R0 resection. There were no differences in survival based on tumor size and LN in patients with R1 resection. Median survival was 17.7 months following R1 resection and was 70.9 months (P<0.001) and 22.2 months (P=0.44) in patients with tumor </=25 mm in size and </=1 involved LN and in the remaining patients in the cohort respectively following R0 resection. CONCLUSIONS: R0 resection is associated with dramatic survival benefit over R1 resection in a subset of patients with tumor size </=25 mm and </=1 involved LN. These findings underscore the importance of R0 resection and careful patient selection for upfront surgery in patients with PaCa.
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[253]
TÍTULO / TITLE: - The prognostic role of time to diagnosis and presenting symptoms in patients with pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Epidemiol. 2013 Apr;37(2):186-90. doi: 10.1016/j.canep.2012.12.002. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 1016/j.canep.2012.12.002
AUTORES / AUTHORS: - Gobbi PG; Bergonzi M; Comelli M; Villano L; Pozzoli D; Vanoli A; Dionigi P
INSTITUCIÓN / INSTITUTION: - Internal Medicine and Gastroenterology, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. gobbipg@smatteo.pv.it
RESUMEN / SUMMARY: - BACKGROUND: The aim of this study was to investigate the prognostic role of diagnostic delay and clinical presentation (regarding pain, jaundice, and weight loss) in pancreatic carcinoma. METHODS: One hundred and seventy patients with pancreatic cancer were diagnosed and treated in the decade 2001-2010 (100 males and 70 females, with a mean age of 65.8 years [range, 36-91]). Patients were staged with spiral computed tomography and 75% were found to have advanced disease (28 stage III, 99 stage IV disease). Ductal adenocarcinoma was diagnosed in 147 cases, other subtypes of carcinoma in the remaining 23. Fifty patients were operated with radical intent, 19 had palliative surgery, 101 were considered inoperable because of advanced disease or heavy anesthesiologic risk; 31 of these inoperable patients underwent biliary decompression by insertion of an endoluminal or percutaneous stent. Gemcitabine-containing regimens were administered to 143 patients and radiotherapy was combined in 19. Overall and relative survival were the parameters studied. Multivariate analysis was performed by multiple regressions applied to proportional-hazards model. RESULTS: From all the clinical, pathological and therapeutical factors evaluated the statistically significant ones were time to diagnosis and surgery. Among symptoms pain was related to the shortest mean time to diagnosis, weight loss to the longest, with corresponding differences in survival. These differences of observed survival were substantially confirmed in terms of relative survival. CONCLUSIONS: The poor prognosis of pancreatic carcinoma seems to depend, in part, on diagnostic delay and this, in turn, is influenced by the type of presenting symptoms.
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[254]
TÍTULO / TITLE: - Risk of pancreatic cancer in relation to ABO blood group and hepatitis C virus infection in Korea: a case-control study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Korean Med Sci. 2013 Feb;28(2):247-51. doi: 10.3346/jkms.2013.28.2.247. Epub 2013 Jan 29.
●● Enlace al texto completo (gratuito o de pago) 3346/jkms.2013.28.2.247
AUTORES / AUTHORS: - Woo SM; Joo J; Lee WJ; Park SJ; Han SS; Kim TH; Koh YH; Kim HB; Hong EK
INSTITUCIÓN / INSTITUTION: - Center for Liver Cancer, National Cancer Center, Goyang, Korea.
RESUMEN / SUMMARY: - Several studies have reported that ABO blood group, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection contribute to the development of pancreatic cancer. The aim of this study was to evaluate the association between these factors and pancreatic cancer in the Korean population. We retrospectively recruited 753 patients with pancreatic cancer and 3,012 healthy controls, matched 4 to 1 with cancer patients for age and sex, between 2001 and 2011, at the National Cancer Center, Korea. A multivariate logistic regression analysis was employed to estimate adjusted odds ratios (AORs). The AOR for pancreatic cancer in subjects with non-O blood types (A, AB, and B), compared to blood type O, was 1.29 (95% CI, 1.05-1.58; P = 0.01). Seropositivity for hepatitis B virus surface antigen was not significantly related to pancreatic cancer, either in univariate (odds ratio 1.03; 95% CI, 0.69-1.53; P = 0.91) or multivariate analysis (AOR, 1.02; 95% CI, 0.67-1.56; P = 0.93). The AOR for pancreatic cancer in subjects displaying seropositivity for anti-HCV was 2.30 (95% CI, 1.30-4.08; P < 0.01). Our results suggest that the non-O blood types and anti-HCV seropositivity, but not HBV infection, may increase the risk of developing pancreatic cancer in Korea, where HBV is endemic.
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[255]
TÍTULO / TITLE: - CA 19-9 Tumor Marker: Is It Reliable? A Case Report in a Patient With Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Adv Hematol Oncol. 2013 Jan;11(1):53-5.
AUTORES / AUTHORS: - Wu E; Kuntz S; Bhat K; Ma Q
INSTITUCIÓN / INSTITUTION: - North Dakota State University, Fargo, North Dakota.
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[256]
TÍTULO / TITLE: - CA 19-9 Tumor Marker: Is It Reliable? A Case Report in a Patient With Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Adv Hematol Oncol. 2013 Jan;11(1):50-2.
AUTORES / AUTHORS: - Wu Z; Kuntz AI; Wadleigh RG
INSTITUCIÓN / INSTITUTION: - Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC.
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[257]
TÍTULO / TITLE: - Treatment of malignant pancreatic neuroendocrine neoplasms: middle-term (2-year) outcomes of a prospective observational multicentre study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 8. doi: 10.1111/hpb.12065.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12065
AUTORES / AUTHORS: - Zerbi A; Capitanio V; Boninsegna L; Delle Fave G; Pasquali C; Rindi G; Campana D; Falconi M
INSTITUCIÓN / INSTITUTION: - Pancreatic Surgery, Department of Surgery, Humanitas Clinical and Research Center, Milan, Italy.
RESUMEN / SUMMARY: - BACKGROUND: Information on malignant pancreatic neuroendocrine neoplasms (pNENs) is mostly from retrospective studies in highly selected patients. The aim of this prospective, multicentre study was to assess treatment and outcomes of malignant pNENs in clinical practice. PATIENTS AND METHODS: Consecutive patients with newly diagnosed, histologically-proven pNENs were included and followed-up for 2 years. Tumours were defined as malignant when nodal or distant metastases were present or invasion of extrapancreatic structures/organs was evident. RESULTS: A total of 140 patients with malignant pNENs were included. Ninety-eight patients (70.0%) underwent a surgical resection (76 radical and 22 palliative). Other non-surgical treatments were used in 101 patients (72.1%): somatostatin analogues (n = 63), chemotherapy (n = 30), ablative treatments (n = 15) and peptide-receptor radionuclide therapy (n = 14). No relationship was observed between the 2010 WHO classification and type of treatment. A surgical resection was more often performed in incidentally detected tumours located in the pancreas body tail. Two-year progression-free survival was 63.8%: 82% after a radical resection, 44% after a palliative resection and 41% without a resection. A radical resection and Ki67 proliferative index >5% and >10% were the only significant prognostic determinants in multivariate analysis. CONCLUSIONS: A radical resection is the cornerstone treatment of malignant pNENs and represents, together with Ki67 assessment, the most powerful prognostic factor for 2-year outcomes.
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[258]
TÍTULO / TITLE: - Comparison of prognosis between patients of pancreatic head cancer with and without obstructive jaundice at diagnosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Surg. 2013 Mar 5. pii: S1743-9191(13)00062-9. doi: 10.1016/j.ijsu.2013.02.023.
●● Enlace al texto completo (gratuito o de pago) 1016/j.ijsu.2013.02.023
AUTORES / AUTHORS: - Nakata B; Amano R; Kimura K; Hirakawa K
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. Electronic address: bunzo@med.osaka-cu.ac.jp.
RESUMEN / SUMMARY: - PURPOSE: The aim of this study was to elicit possible differences in prognoses and clinicopathological factors in pancreatic head cancer with and without obstructive jaundice at diagnosis. METHODS: The data from 169 patients with pancreatic head cancer were retrospectively analyzed. RESULTS: Patients were divided into two groups according to serum total bilirubin at diagnosis: >/=3 mg/dL for icteric group and <3 mg/dL for non-icteric group. In all cases, icteric group (n = 104) had a significantly worse prognosis than non-icteric group (n = 65) (median survival time (MST), 7.5 months (M) vs. 13.5 M, respectively; P = 0.049). In 84 resectable cases, icteric group had a significantly worse prognosis than non-icteric group (MST, 14.2 M vs. 20.9 M, respectively; P = 0.049) after almost equivalent treatment intensities. Icteric group had significantly larger T- and N-factors according to the UICC Classification compared to non-icteric group. The total number of lymph node metastases in icteric group was significantly larger than in non-icteric group (P = 0.008). The intrapancreatic nerve invasion in icteric group was significantly stronger than in non-icteric group (P = 0.016). There were no significant differences in the mortality and morbidity between icteric and non-icteric groups. In 85 unresectable cases, there was no significant difference between the survival periods of icteric and non-icteric groups (MST, 5.2 M vs. 5.3 M, respectively). CONCLUSIONS: The presence of obstructive jaundice at diagnosis in patients with pancreatic head cancer may predict an unfavorable survival compared to such patients without obstructive jaundice.
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[259]
TÍTULO / TITLE: - Loss of TRAIL-Receptors Is a Recurrent Feature in Pancreatic Cancer and Determines the Prognosis of Patients with No Nodal Metastasis after Surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e56760. doi: 10.1371/journal.pone.0056760. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0056760
AUTORES / AUTHORS: - Gallmeier E; Bader DC; Kriegl L; Berezowska S; Seeliger H; Goke B; Kirchner T; Bruns C; De Toni EN
INSTITUCIÓN / INSTITUTION: - Department of Medicine 2, University Hospital Grosshadern, University of Munich, Munich, Germany.
RESUMEN / SUMMARY: - INTRODUCTION: Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. AIMS AND METHODS: Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated. RESULTS: The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22-0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance. CONCLUSION: This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.
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[260]
TÍTULO / TITLE: - TRAIL-induced expression of uPA and IL-8 strongly enhanced by overexpression of TRAF2 and Bcl-xL in pancreatic ductal adenocarcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatobiliary Pancreat Dis Int. 2013 Feb;12(1):94-8.
AUTORES / AUTHORS: - Zhou DH; Yang LN; Roder C; Kalthoff H; Trauzold A
INSTITUCIÓN / INSTITUTION: - Department of Oncology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. zdh19838@hotmail.com
RESUMEN / SUMMARY: - BACKGROUND: The death ligand, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), induces apoptosis and non-apoptotic signaling in some tumor cells. The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors, TRAIL-R1 and TRAIL-R2, as well as Bcl-xL and TRAF2 in TRAIL-induced expression of the pro-inflammatory cytokine IL-8 and the invasion-promoting protein urokinase (uPA) in pancreatic ductal adenocarcinoma (PDAC) cells. METHODS: Colo357wt, Colo357/TRAF2, Colo357/Bcl-xL, Panc89 and PancTuI cells were stimulated with TRAIL and uPA and IL-8 expression was detected using real-time PCR. Antagonistic, receptor-specific antibodies were used to investigate the effects of TRAIL-R1 or TRAIL-R2 inhibition. RESULTS: Dose-dependent increases in uPA and IL-8 expression were detected following TRAIL stimulation in PDAC cells. These effects were inhibited when TRAIL-R1 but not TRAIL-R2 was blocked. Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL-mediated upregulation of uPA and IL-8. CONCLUSIONS: In PDAC cells, TRAIL strongly induced uPA and IL-8 via TRAIL-R1. This response was further enhanced in cells overexpressing TRAF2 and Bcl-xL. Therefore, inhibition of the non-apoptotic “side-effects” of TRAIL treatments by inactivation of TRAF2 and Bcl-xL might represent additional relevant strategies for the treatment of pancreatic cancer.
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[261]
TÍTULO / TITLE: - Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese Society of Pancreatic Surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Hepatobiliary Pancreat Sci. 2013 Mar 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s00534-013-0595-1
AUTORES / AUTHORS: - Kato H; Usui M; Isaji S; Nagakawa T; Wada K; Unno M; Nakao A; Miyakawa S; Ohta T
INSTITUCIÓN / INSTITUTION: - Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Optimal treatment types and prognosis for patients with borderline resectable pancreatic cancer (BRPC) remain unclear because of the lack of studies involving large series of patients. METHODS: We retrospectively analyzed various prognostic factors for 624 BRPC (pancreatic head/body) patients treated from June 2002 to May 2007, by distributing questionnaires to member institutions of the Japanese Society of Pancreatic Surgery in 2010. BRPC was defined according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2009). RESULTS: Among 624 patients, 539 (86.4 %) underwent curative-intent resection, showing an R0 resection rate of 65.9 %. The 3- and 5-year survival rates were 16.1 and 9.9 % in all patients, 22.8 and 12.5 % in the resected patients, and 4.4 and 0 % (P < 0.0001) in the unresected patients, respectively. The following factors influencing survival in all patients were selected as independent prognostic factors using multivariate analysis: major arterial involvement on imaging study; preoperative treatment; surgical resection; and postoperative chemotherapy. Among the resected cases, multivariate analysis revealed that major arterial involvement and remnant tumor status were independent prognostic factors. CONCLUSION: BRPC included two distinct categories of tumors influencing survival: those with portal vein/superior mesenteric vein invasion alone and those with major arterial invasion, which was the most exacerbating factor in the analysis.
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[262]
TÍTULO / TITLE: - Staging chest computed tomography and positron emission tomography in patients with pancreatic adenocarcinoma: utility or futility?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 15. doi: 10.1111/hpb.12074.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12074
AUTORES / AUTHORS: - Pappas SG; Christians KK; Tolat PP; Mautz AP; Lal A; McElroy L; Gamblin TC; Turaga KK; Tsai S; Erickson B; Ritch P; Evans DB
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Loyola University Medical Center, Maywood, IL, USA.
RESUMEN / SUMMARY: - OBJECTIVES: This study was conducted to determine if routine staging chest computed tomography (CT) or positron emission tomography (PET) scanning alters the clinical management of patients with newly diagnosed pancreatic adenocarcinoma. METHODS: All new pancreas cancers seen in medical oncology, radiation oncology and surgery from 1 June 2008 to 20 June 2010 were retrospectively reviewed. Patients with metastatic disease on chest CT or PET, that had been unsuspected on initial imaging, were identified. RESULTS: Pancreatic adenocarcinoma was present in 247 consecutive patients. Abdominal CT demonstrated metastases in 108 (44%) and localized disease in 139 (56%) patients. Chest CT and PET were not performed in 15 (11%) of these 139 patients. In the remaining 124 patients, CT imaging suggested resectable disease in 46, borderline resectable disease in 52 and locally advanced disease in 26 patients. Chest CT demonstrated an unsuspected lymphoma in one patient with borderline resectable disease and PET identified extrapancreatic disease in two patients with locally advanced disease. Chest CT and PET added no information in 121 (98%) of the 124 patients. CONCLUSIONS: The addition of chest CT and PET to high-quality abdominal CT is of little clinical utility; additional sites of metastasis are rarely found. As the quality of abdominal imaging declines, the yield from other imaging modalities will increase. Dedicated pancreas-specific abdominal CT remains the cornerstone of initial staging in suspected or biopsy-proven pancreatic cancer.
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[263]
TÍTULO / TITLE: - Pain palliation by endoscopic ultrasound-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointestin Liver Dis. 2013 Mar;22(1):59-64.
AUTORES / AUTHORS: - Seicean A; Cainap C; Gulei I; Tantau M; Seicean R
INSTITUCIÓN / INSTITUTION: - 3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy; Regional Institute of Gastroenterology and Hepatology, Croitorilor street 19-21, 400162 Cluj-Napoca, Romania; Email:andradaseicean@yahoo.com.
RESUMEN / SUMMARY: - BACKGROUND: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) represents an alternative approach to pain palliation in patients with advanced pancreatic cancer. AIM: to evaluate the safety and initial efficacy of EUS-CPN in patients with painful unresectable pancreatic cancer. METHODS: Patients with inoperable body-tail pancreatic adenocarcinoma without prior chemotherapy and pain requiring opioid analgesia were included prospectively in this cohort study in a tertiary medical center. Central EUS-CPN was performed and the brief pain inventory and the Functional Assessment of Cancer Therapy measurement were applied before and 2 weeks after the procedure. RESULTS: Thirty-two patients underwent the procedure in one session without complications. Follow-up revealed overall pain relief in 24 patients (75%) and significant improvement in pain scores. Ratings of pain interfering with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep improved significantly. Physical, functional, and emotional well-being improved significantly, except for acceptance of illness and enjoyment of life. CONCLUSION: Central EUS-CPN was an efficient and safe method for palliative pain management in our patients with inoperable pancreatic body-tail adenocarcinoma. The pain alleviation improved the patients’ functional status, sleep, and quality of life, although other variables could also be involved, but acceptance of the illness and enjoyment of life did not change after treatment.
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[264]
TÍTULO / TITLE: - LY294002 enhances inhibitory effect of gemcitabine on proliferation of human pancreatic carcinoma PANC-1 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Huazhong Univ Sci Technolog Med Sci. 2013 Feb;33(1):57-62. doi: 10.1007/s11596-013-1071-5. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1007/s11596-013-1071-5
AUTORES / AUTHORS: - Ke XY; Wang Y; Xie ZQ; Liu ZQ; Zhang CF; Zhao Q; Yang DL
INSTITUCIÓN / INSTITUTION: - Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China, jessicawarm@hotmail.com.
RESUMEN / SUMMARY: - Phosphatidylinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) pathway plays a major role in proliferation and survival of many types of cells. The inhibitory effect of LY294002, widely applied as an inhibitor of PI3K, in combination with gemcitabine on proliferation of PANC-1 cells was investigated. The expression of PI3K, phosphorylated Akt (p-Akt) and multidrug-resistance like protein (MRP) in normal pancreas tissues, chronic pancreatitis tissues and pancreatic carcinoma tissues was detected. The effects of LY294002 combined with gemcitabine on proliferation of PANC-1 cells and protein levels of p-Akt and MRP were detected. The results showed that the positive expression rate of PI3K, p-Akt and MRP in pancreatic carcinoma tissues was significantly higher than that in normal pancreas tissues and chronic pancreatitis tissues (P<0.01 and P<0.05 respectively). LY294002 could effectively enhance the inhibitory effect of gemcitabine on proliferation of PANC-1 cells. Furthermore, Western blotting revealed that LY294002 combined with gemcitabine reduced the protein levels of p-Akt and MRP, which contributed to the inhibition of proliferation. It is concluded that LY294002 in combination with gemcitabine may represent an alternative therapy for pancreatic carcinoma.
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[265]
TÍTULO / TITLE: - Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Onco Targets Ther. 2013;6:29-40. doi: 10.2147/OTT.S37916. Epub 2013 Jan 22.
●● Enlace al texto completo (gratuito o de pago) 2147/OTT.S37916
AUTORES / AUTHORS: - Andoh Y; Makino N; Yamakawa M
INSTITUCIÓN / INSTITUTION: - Department of Pathological Diagnostics ; Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.
RESUMEN / SUMMARY: - BACKGROUND: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL) and CD4(+)CD25(high) regulatory T-cells (Tregs) among dendritic cells (DCs) fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines. METHODS: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs), were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated. RESULTS: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1) was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines. CONCLUSION: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs.
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[266]
TÍTULO / TITLE: - Triple approach strategy for patients with locally advanced pancreatic carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2012 Dec 6. doi: 10.1111/hpb.12027.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12027
AUTORES / AUTHORS: - Giardino A; Girelli R; Frigerio I; Regi P; Cantore M; Alessandra A; Lusenti A; Salvia R; Bassi C; Pederzoli P
INSTITUCIÓN / INSTITUTION: - Pancreatic Unit, Casa di Cura Pederzoli, Peschiera del Garda (VR), Italy.
RESUMEN / SUMMARY: - BACKGROUND: Radiofrequency ablation (RFA) is a relatively new technique, applied to metastatic solid tumours which, in recent studies, has been shown to be feasible and safe on locally advanced pancreatic carcinoma (LAPC). RFA can be combined with radio-chemotherapy (RCT) and intra-arterial plus systemic chemotherapy (IASC). The aim of this study was to investigate the impact on the prognosis of a multimodal approach to LAPC and define the best timing of RFA. METHODS: This is a retrospective observational study of patients who have consecutively undergone RFA associated with multiple adjuvant approaches. RESULTS: Between February 2007 and December 2011, 168 consecutive patients were treated by RFA, of which 107 were eligible for at least 18 months of follow-up. Forty-seven patients (group 1) underwent RFA as an up-front treatment and 60 patients as second treatment (group 2) depending on clinician choice. The median overall survival (OS) of the whole series was 25.6 months: 14.7 months in the group 1 and 25.6 months in the group 2 (P = 0.004). Those patients who received the multimodal treatment (RFA, RCT and IASC-triple approach strategy) had an OS of 34.0 months. CONCLUSIONS: The multimodal approach seems to be feasible and associated with an improved longer survival rate.
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[267]
TÍTULO / TITLE: - Cystic replacement of pancreas in patient with von hippel-lindau syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastrointest Cancer Res. 2013 Jan;6(1):25-6.
AUTORES / AUTHORS: - Kapur V; Brower ST
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology Section of HPB Surgery Department of Surgery Beth Israel Medical Center and Continuum Cancer Centers of New York New York, NY.
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[268]
TÍTULO / TITLE: - Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Jan 31;13:41. doi: 10.1186/1471-2407-13-41.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-41
AUTORES / AUTHORS: - Ioannou N; Seddon AM; Dalgleish A; Mackintosh D; Modjtahedi H
INSTITUCIÓN / INSTITUTION: - School of Life Sciences, Kingston University London, Kingston-upon-Thames, Surrey KT1 2EE, UK. H.Modjtahedi@kingston.ac.uk.
RESUMEN / SUMMARY: - BACKGROUND: Aberrant expression and activation of the IGF-IR have been reported in a variety of human cancers and have been associated with resistance to HER targeted therapy. In this study, we investigated the effect of simultaneous targeting of IGF-IR and HER (erbB) family, with NVP-AEW541 and afatinib, on proliferation of pancreatic cancer cells. METHODS: The sensitivity of a panel of human pancreatic cancer cell lines to treatment with NVP-AEW541 used alone or in combination with afatinib, anti-EGFR antibody ICR62, and cytotoxic agents was determined using the Sulforhodamine B colorimetric assay. Growth factor receptor expression, cell-cycle distribution and cell signalling were determined using flow cytometry and western blot analysis. RESULTS: All pancreatic cancer cell lines were found to be IGF-IR positive and NVP-AEW541 treatment inhibited the growth of the pancreatic cancer cell lines with IC50 values ranging from 342 nM (FA6) to 2.73 muM (PT45). Interestingly, of the various combinations examined, treatment with a combination of NVP-AEW541 and afatinib was superior in inducing synergistic growth inhibition of the majority of pancreatic cancer cells. CONCLUSION: Our results indicate that co-targeting of the erbB (HER) family and IGF-IR, with a combination of afatinib and NVP-AEW541, is superior to treatment with a single agent and encourages further investigation in vivo on their therapeutic potential in IGF-IR and HER positive pancreatic cancers.
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[269]
TÍTULO / TITLE: - Paraoxonase-1 (PON1) status in pancreatic cancer: relation to clinical parameters.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Folia Biol (Praha). 2012;58(6):231-7.
AUTORES / AUTHORS: - Vecka M; Jachymova M; Vavrova L; Kodydkova J; Macasek J; Urbanek M; Krechler T; Slaby A; Duskova J; Muravska A; Zak A
INSTITUCIÓN / INSTITUTION: - 4th Department of Internal Medicine, First Faculty of Medicine, General University Hospital, Charles University, Prague, Czech Republic. marek.vecka@lf1.cuni.cz
RESUMEN / SUMMARY: - Human paraoxonase 1 (PON1) has been shown to decrease the level of systemic oxidative stress, which is thought to contribute to cancer development. The aim of this study was to examine the interrelationships between PON1 status and some clinical characteristics in patients with pancreatic cancer (PC). A group of 73 consecutive patients with PC (stage II-IV) and 73 control subjects were examined. Laboratory studies included five polymorphisms of the PON1 gene (L55M, Q192R, -108C/T, -126C/T, and -162A/G), PON1 arylesterase (PON1-A) and lactonase (PON1-L) activities, as well as some markers of protein metabolism, insulin resistance, and oxidative stress. In comparison with the control group, no difference in the distribution of the PON1 polymorphisms was found in cancer patients, both arylesterase and lactonase activities being significantly lower (-33, -47 %, respectively, both P < 0.001). There was neither statistically significant association of PON1 polymorphisms with tumour stages nor with diabetes mellitus connected with PC. The genotype distribution of L55M and 108C/T differed only in a subgroup of patients presenting clinically relevant malnutrition (chi(2) = 6.50, 6.25, respectively, both P < 0.05). In the PC group, PON1-A and PON1-L activities correlated with Nutritional Risk Index (r = 0.351, 0.409, respectively, both P < 0.01), PON1-L with mid-arm muscle circumference (r = 0.328, P < 0.05), and PON1-A and PON1-L with serum albumin (r = 0.352, 0.391 respectively, both < 0.01). Our results suggest that PON1 plays an important role in PC, especially in cancer-associated malnutrition.
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[270]
TÍTULO / TITLE: - Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e57522. doi: 10.1371/journal.pone.0057522. Epub 2013 Mar 6.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057522
AUTORES / AUTHORS: - Kudgus RA; Szabolcs A; Khan JA; Walden CA; Reid JM; Robertson JD; Bhattacharya R; Mukherjee P
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America.
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic cancer is one of the deadliest of all human malignancies with limited options for therapy. Here, we report the development of an optimized targeted drug delivery system to inhibit advanced stage pancreatic tumor growth in an orthotopic mouse model. METHODPRINCIPAL FINDINGS: Targeting specificity in vitro was confirmed by preincubation of the pancreatic cancer cells with C225 as well as Nitrobenzylthioinosine (NBMPR - nucleoside transporter (NT) inhibitor). Upon nanoconjugation functional activity of gemcitabine was retained as tested using a thymidine incorporation assay. Significant stability of the nanoconjugates was maintained, with only 12% release of gemcitabine over a 24-hour period in mouse plasma. Finally, an in vivo study demonstrated the inhibition of tumor growth through targeted delivery of a low dose of gemcitabine in an orthotopic model of pancreatic cancer, mimicking an advanced stage of the disease. CONCLUSION: We demonstrated in this study that the gold nanoparticle-based therapeutic containing gemcitabine inhibited tumor growth in an advanced stage of the disease in an orthotopic model of pancreatic cancer. Future work would focus on understanding the pharmacokinetics and combining active targeting with passive targeting to further improve the therapeutic efficacy and increase survival.
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[271]
TÍTULO / TITLE: - Glucagonlike Peptide 1-Based Drugs and Pancreatitis: Clarity at Last, but What About Pancreatic Cancer?: Comment on “Glucagonlike Peptide 1-Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus”
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JAMA. Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista jama.ama-assn.org/search.dtl
●● Cita: JAMA: <> Intern Med. 2013 Mar 5:1-3. doi: 10.1001/jamainternmed.2013.3374.
●● Enlace al texto completo (gratuito o de pago) 1001/jamainternmed.2013.3374
AUTORES / AUTHORS: - Gier B; Butler PC
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[272]
TÍTULO / TITLE: - Pancreatic cyst development: insights from von Hippel-Lindau disease.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cilia. 2013 Feb 5;2(1):3. doi: 10.1186/2046-2530-2-3.
●● Enlace al texto completo (gratuito o de pago) 1186/2046-2530-2-3
AUTORES / AUTHORS: - van Asselt SJ; de Vries EG; van Dullemen HM; Brouwers AH; Walenkamp AM; Giles RH; Links TP
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology, University of Groningen, University Medical Center Groningen, PO Box 30,001, 9700 RB, Groningen, The Netherlands. t.p.links@umcg.nl.
RESUMEN / SUMMARY: - Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL) disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL). VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.
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[273]
TÍTULO / TITLE: - Von Hippel Lindau disease with metastatic pancreatic neuroendocrine tumor causing ectopic Cushing’s syndrome.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Neuro Endocrinol Lett. 2013 Feb 25;34(4):9-13.
AUTORES / AUTHORS: - Hatipoglu E; Kepicoglu H; Rusen E; Kabasakal L; Gundogdu S; Kadioglu P
INSTITUCIÓN / INSTITUTION: - Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. kadioglup@yahoo.com.
RESUMEN / SUMMARY: - We present a 39-year-old woman who was previously diagnosed with Von Hippel Lindau Disease (VHLD). She had surgery and radiotherapy for cranial hemangioblastoma (HA) 11 years ago and had unilateral adrenalectomy for pheochromocytoma in another hospital 6 month prior to her admission to our center. Moon face, buffalo hump, central obesity, progressive weight gain and menstrual irregularities persisted after adrenalectomy. Her laboratory results were consistent with ectopic Cushing’s syndrome (ECS). A pancreatic solid mass with a nodule on the left lung were revealed upon computed tomography. In addition, Gallium-68 Somatostatin Receptor PET confirmed the pancreatic involvement and demonstrated additional lesions on the left lung and in the aortocaval lymphatic system on the right side, suggesting metastatic pancreatic neuroendocrine tumor (PNET). Peptide receptor radionuclide therapy (PRRT) with [177Lutetium-DOTA0,Tyr3] octreotate was performed on the patient, with no side effects observed. She was discharged from the hospital 10 days after the first cycle.
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[274]
TÍTULO / TITLE: - Expression of Recipient CD47 on Rat Insulinoma Cell Xenografts Prevents Macrophage-Mediated Rejection through SIRPalpha Inhibitory Signaling in Mice.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58359. doi: 10.1371/journal.pone.0058359. Epub 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058359
AUTORES / AUTHORS: - Teraoka Y; Ide K; Morimoto H; Tahara H; Ohdan H
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
RESUMEN / SUMMARY: - We have previously proven that the interspecies incompatibility of CD47 is responsible for in vitro phagocytosis of xenogeneic cells by host macrophages. Utilizing an in vivo model in the present study, we investigated whether genetically engineered expression of mouse CD47 in rat insulinoma cells (INS-1E) could inhibit macrophage-mediated xenograft rejection. INS-1E cells transfected with the pRc/CMV-mouse CD47 vector (mCD47-INS-1E) induced SIRPalpha-tyrosine phosphorylation in mouse macrophages in vitro, whereas cells transfected with the control vector (cont-INS-1E) did not. When these cells were injected into the peritoneal cavity of streptozotocin-induced diabetic Rag2(-/-)gamma chain (-/-) mice, which lack T, B, and NK cells, the expression of mouse CD47 on the INS-1E cells markedly reduced the susceptibility of these cells to phagocytosis by macrophages. Moreover, these mice became normoglycemic after receiving mCD47-INS-1E, whereas the mice that received cont-INS-1E failed to achieve normoglycemia. Furthermore, injection of an anti-mouse SIRPalpha blocking monoclonal antibody into the mouse recipients of mCD47-INS-1E cells prevented achievement of normoglycemia. These results demonstrate that interspecies incompatibility of CD47 significantly contributes to in vivo rejection of xenogeneic cells by macrophages. Thus, genetic induction of the expression of recipient CD47 on xenogeneic donor cells could provide inhibitory signals to recipient macrophages via SIPRalpha; this constitutes a novel approach for preventing macrophage-mediated xenograft rejection.
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[275]
TÍTULO / TITLE: - Vanadium compounds modulate PPARgamma activity primarily by increasing PPARgamma protein levels in mouse insulinoma NIT-1 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Metallomics. 2013 Mar 1.
●● Enlace al texto completo (gratuito o de pago) 1039/c3mt20249f
AUTORES / AUTHORS: - Zhao P; Yang X
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China. xyang@bjmu.edu.cn.
RESUMEN / SUMMARY: - Vanadium compounds are promising agents in the therapeutic treatment of diabetes; however, their mechanism of action has not been clearly elucidated. The current study investigated the effects of vanadium compounds, vanadyl acetylacetonate [VIVO(acac)2] and sodium metavanadate (NaVVO3), on peroxisome proliferator-activated receptors (PPARs), especially PPARgamma, which are important targets of anti-diabetic drugs. Our experimental results revealed that treatment of NIT-1 beta-pancreas cells with vanadium compounds resulted in PPARgamma activation and elevation of PPARgamma protein levels. Vanadium compounds did not increase PPARgamma transcription but ameliorated PPARgamma degradation induced by inflammatory stimulators TNF-alpha/IL-6. Vanadium compounds induced binding of PPARgamma to heat shock protein (Hsp60). This PPARgamma-Hsp60 interaction might cause inhibition of PPARgamma degradation, thus elevating the PPARgamma level. In addition, modulation of PPARgamma phosphorylation was also observed upon vanadium treatment. The present work demonstrated for the first time that vanadium compounds are novel PPARgamma modulators. The results may provide new insights for the mechanism of anti-diabetic action of vanadium compounds.
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[276]
TÍTULO / TITLE: - RNA interferencemediated inhibition of survivin and VEGF in pancreatic cancer cells in vitro.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Mar 6. doi: 10.3892/mmr.2013.1361.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1361
AUTORES / AUTHORS: - Song J; Cao L; Li Y
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
RESUMEN / SUMMARY: - The aim of the present study was to investigate the effects of simultaneous short hairpin RNA (shRNA)targeted survivin and vascular endothelial growth factor (VEGF) inhibition on the proliferation, apoptosis and angiogenesis of human pancreatic cancer cells (Panc1). Targeted small interfering RNA (siRNA) expression vectors of survivin and VEGF were constructed and transfected into Panc1 cells. The downregulation of survivin and VEGF expression was evaluated by realtime PCR and western blot analysis. The effects of targeted shRNA on the proliferation and apoptosis of Panc1 cells were analyzed by MTT assay and flow cytometry (FCM). The culture medium from Panc1 cells transfected with siRNA was collected and human umbilical vein endothelial cells (HUVECs) were seeded in this media. The proliferation and apoptosis of the HUVECs were also investigated by MTT assay and FCM. A transfected cell line (Panc1/survivinshRNA and Panc1/VEGFshRNA) was established in which the expression of survivin and VEGF was downregulated. The cell viabilities of Panc1 cells and HUVECs in the combined inhibition groups were markedly decreased compared with the controls. The cell apoptosis rates of Panc1 cells and HUVECs in the combined inhibition groups were observed to be significantly increased compared with the controls. The simultaneous RNA interferencemediated downregulation of survivin and VEGF expression inhibited proliferation and induced the apoptosis of Panc1 cells and HUVECs, indicating that combined therapy with survivin and VEGF inhibition may serve as a potential strategy for the treatment of pancreatic cancer.
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[277]
TÍTULO / TITLE: - Biodegradable Nanocapsules as siRNA Carriers for Mutant K-Ras Gene Silencing of Human Pancreatic Carcinoma Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Small. 2013 Feb 20. doi: 10.1002/smll.201201716.
●● Enlace al texto completo (gratuito o de pago) 1002/smll.201201716
AUTORES / AUTHORS: - Lin G; Hu R; Law WC; Chen CK; Wang Y; Li Chin H; Nguyen QT; Lai CK; Yoon HS; Wang X; Xu G; Ye L; Cheng C; Yong KT
INSTITUCIÓN / INSTITUTION: - School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore; The key lab of Biomedical Engineering and Research, Institute of Uropoiesis and Reproduction, School of Medical Sciences, Shenzhen University, Shenzhen, 518060, China.
RESUMEN / SUMMARY: - The application of small interfering RNA (siRNA)-based RNA interference (RNAi) for cancer gene therapy has attracted great attention. Gene therapy is a promising strategy for cancer treatment because it is relatively non-invasive and has a higher therapeutic specificity than chemotherapy. However, without the use of safe and efficient carriers, siRNAs cannot effectively penetrate the cell membranes and RNAi is impeded. In this work, cationic poly(lactic acid) (CPLA)-based degradable nanocapsules (NCs) are utilized as novel carriers of siRNA for effective gene silencing of pancreatic cancer cells. These CPLA-NCs can readily form nanoplexes with K-Ras siRNA and over 90% transfection efficiency is achieved using the nanoplexes. Cell viability studies show that the nanoparticles are highly biocompatible and non-toxic, indicating that CPLA-NC is a promising potential candidate for gene therapy in a clinical setting.
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[278]
TÍTULO / TITLE: - Racial and Social Economic Factors Impact on the Cause Specific Survival of Pancreatic Cancer: A SEER Survey.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):159-63.
AUTORES / AUTHORS: - Cheung R
INSTITUCIÓN / INSTITUTION: - 275 S Bryn Mawr Ave, K43, Bryn Mawr, PA 19010 E-mail : cheung.r100@gmail.com.
RESUMEN / SUMMARY: - Background: This study used Surveillance, Epidemiology and End Results (SEER) pancreatic cancer data to identify predictive models and potential socio-economic disparities in pancreatic cancer outcome. Materials and Methods: For risk modeling, Kaplan Meier method was used for cause specific survival analysis. The Kolmogorov-Smirnov’s test was used to compare survival curves. The Cox proportional hazard method was applied for multivariate analysis. The area under the ROC curve was computed for predictors of absolute risk of death, optimized to improve efficiency. Results: This study included 58,747 patients. The mean follow up time (S.D.) was 7.6 (10.6) months. SEER stage and grade were strongly predictive univariates. Sex, race, and three socio-economic factors (county level family income, rural-urban residence status, and county level education attainment) were independent multivariate predictors. Racial and socio-economic factors were associated with about 2% difference in absolute cause specific survival. Conclusions: This study s found significant effects of socio-economic factors on pancreas cancer outcome. These data may generate hypotheses for trials to eliminate these outcome disparities.
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[279]
TÍTULO / TITLE: - Diagnosis and treatment of an insulinoma in a guinea pig (Cavia porcellus).
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Am Vet Med Assoc. 2013 Feb 15;242(4):522-6. doi: 10.2460/javma.242.4.522.
●● Enlace al texto completo (gratuito o de pago) 2460/javma.242.4.522
AUTORES / AUTHORS: - Hess LR; Ravich ML; Reavill DR
INSTITUCIÓN / INSTITUTION: - Veterinary Center for Birds and Exotics, 709 Bedford Rd, Bedford Hills, NY 10507, USA.
RESUMEN / SUMMARY: - CASE DESCRIPTION: A 5-year-old male guinea pig (Cavia porcellus) was examined because of lethargy, weight loss, and episodic neurologic signs, including paddling in lateral recumbency, head tilt, and circling. Prior to initial examination, the animal was treated with corn syrup whenever it appeared lethargic, plus an unknown dosage of sulfadimethoxazole. CLINICAL FINDINGS: The animal was thin, with abdominal distention and subtle torticollis. Chemistry panel results documented hypoglycemia (45 mg/dL). Corn syrup was discontinued in favor of a high-fiber formula fed via a syringe. Measurement of blood insulin concentration demonstrated hyperinsulinemia (> 1,440 pmol/L [> 201 muU/L]), with concurrent hypoglycemia (0.6 mmol/L [11 mg/dL]). TREATMENT AND OUTCOME: Diazoxide treatment for presumptive insulinoma was started at a dosage of 5 mg/kg (2.3 mg/lb), p.o., every 12 hours. A blood glucose curve demonstrated persistent hypoglycemia, and the diazoxide dosage was gradually increased to 25 mg/kg (11.4 mg/lb), p.o., every 12 hours. A second glucose curve measurement 12 days later confirmed adequate euglycemic control. Three weeks after the initial diazoxide dosage increase, the animal was reexamined for constipation and abdominal distension and died the following day. Histologic analysis confirmed a pancreatic beta-cell tumor (insulinoma). CLINICAL RELEVANCE: To the authors’ knowledge, this is the first report of premortem diagnosis and treatment of an insulinoma in a guinea pig. This case demonstrates that diazoxide treatment can help achieve euglycemia in hypoglycemic guinea pigs and is a potential treatment option for guinea pigs with insulinoma.
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[280]
TÍTULO / TITLE: - Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg Oncol. 2013 Feb 6;11:38. doi: 10.1186/1477-7819-11-38.
●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-38
AUTORES / AUTHORS: - Wang XG; Ni QF; Fei JG; Zhong ZX; Yu PF
INSTITUCIÓN / INSTITUTION: - Department of Surgery, the Second Affiliated Hospital of JiaXing Medical College, JiaXing 314000, China.
RESUMEN / SUMMARY: - BACKGROUND: We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs). METHODS: We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. RESULTS: All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years). The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm). All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months). There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. CONCLUSIONS: The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.
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[281]
TÍTULO / TITLE: - Solid Pseudopapillary Tumor of the Pancreas in a Child: Imaging Findings with Diffusion-Weighted MR Imaging.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):195-8. doi: 10.6092/1590-8577/1185.
AUTORES / AUTHORS: - Rodrigues-Duarte H; Torrao H; Coelho P; Noruegas M; Sanches M
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Portuguese Institute of Oncology of Oporto, “Francisco Gentil”, EPE. Oporto, Portugal. halioduarte@gmail.com.
RESUMEN / SUMMARY: - CONTEXT: Solid pseudopapillary tumor of the pancreas is a rare tumor more common in young girls and rare in males. CASE REPORT: We present a case of a solid pseudopapillary tumor of the pancreas in a 13-year-old boy, with typical imaging features. CONCLUSIONS: Our case report specifically illustrates the potential of diffusion-weighted imaging findings on solid pseudopapillary tumor in pediatric patients.
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[282]
TÍTULO / TITLE: - Clinical significance of pituitary tumor transforming gene 1 and transgelin-2 in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Immunopathol Pharmacol. 2013 Jan-Mar;26(1):147-56.
AUTORES / AUTHORS: - Lin H; Chen QL; Wang XY; Han W; He TY; Yan D; Chen K; Su LD
INSTITUCIÓN / INSTITUTION: - Department of Pancreatic Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
RESUMEN / SUMMARY: - Human pituitary tumor transforming gene 1 (PTTG1) is an oncogenic transcription factor that is overexpressed in many malignancies, especially cancers with metastatic potential, while transgelin-2 (TAGLN2) is an actin-binding protein shown to be a tumor suppressor. However, the expression and clinical significance of PTTG1 and TAGLN2 in pancreatic cancer remain unclear. The present study aimed to investigate the expression and clinical significance of PTTG1 and TAGLN2 in human primary pancreatic cancer. Seventy-five cases of human pancreatic cancer tissues were collected. The expression of PTTG1 and TAGLN2 protein was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of PTTG1 and TAGLN2 in cancerous tissues showed the positive staining mainly in the cytoplasm, and they were found in cancerous tissues with higher strong reactivity rate compared with the adjacent non-cancer tissues (ANCT) (56.0 percent vs 22.7 percent, P less than 0.001; 100 percent vs 84 percent, P=0.002), elevating with the ascending order of tumor malignancy. Furthermore, the positive expression of PTTG1 was associated with the gender of pancreatic cancer patients, but did not correlate with their age, pathological styles, tumor size, tumor sites, TNM staging, perineural infiltration and distant metastasis (each P greater than 0.05). In addition, Spearman rank correlation analysis showed the positive correlation of PTTG1 with TAGLN2 (r=0.624, P less than 0.001). Taken together, PTTG1 and TAGLN2 are highly expressed in human pancreatic cancer, and the positive expression of PTTG1 is associated with the gender of cancer patients, suggesting that it may represent a potential therapeutic target for the treatment of pancreatic cancer.
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[283]
TÍTULO / TITLE: - Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Microenviron. 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1007/s12307-013-0130-6
AUTORES / AUTHORS: - Heinrich EL; Arrington AK; Ko ME; Luu C; Lee W; Lu J; Kim J
INSTITUCIÓN / INSTITUTION: - Division of Surgical Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center, 1500 East Duarte Rd, Duarte, CA, 91010, USA.
RESUMEN / SUMMARY: - Chemokine receptors mediate cancer progression and metastasis. We have previously examined chemokine receptor CCR9 expression in pancreatic cancer. Here, our objective was to evaluate pancreatic stellate cells (PSCs) as a source of CCL25, the CCR9 ligand, and as an activator of CCL25-CCR9 signaling in pancreatic cancer cells. CCL25 and CCR9 expression levels in human pancreatic cancer tissues and normal human pancreas were assessed by immunohistochemsitry. In vitro secretion of CCL25 in PSCs and PANC-1 cells was verified by enzyme-linked immunosorbent assay. Pancreatic cancer cell invasion was measured using a modified Boyden chamber assay with CCL25, PSC secreted proteins, and PANC-1 secreted proteins as the chemoattractant. There was immunostaining for CCR9 expression in human pancreatic tumor tissues, but not in normal pancreatic tissue. CCL25 expression was absent in the normal pancreatic tissue sample, but was observed in cancer cells and in the stromal cells surrounding the tumor. In vitro, both PANC-1 cells and PSCs secreted CCL25. In an invasion assay, exposure to CCL25, PSC- and PANC-1-conditioned media significantly increased the invasiveness of PANC-1 cells. Inclusion of a CCR9-neutralizing antibody in the invasion assay blocked the increase in invading cells elicited by the chemoattractants. Our studies show that pancreatic cancer invasiveness is enhanced by autocrine and paracrine stimulation of CCR9. PSCs in the tumor microenvironment appear to contribute to paracrine activation of CCR9. Investigations into CCR9 as a potential therapeutic target in pancreatic cancer must consider cancer cell autocrine signaling and also paracrine signaling from interactions in the tumor microenvironment.
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[284]
TÍTULO / TITLE: - Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointest Oncol. 2013 Mar;4(1):20-9. doi: 10.3978/j.issn.2078-6891.2012.012.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.012
AUTORES / AUTHORS: - Weiss GA; Rossi MR; Khushalani NI; Lo K; Gibbs JF; Bharthuar A; Cowell JK; Iyer R
INSTITUCIÓN / INSTITUTION: - Department of Medicine, University at Buffalo, Buffalo, New York, USA;
RESUMEN / SUMMARY: - BACKGROUND: Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy. METHODS: Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted. RESULTS: No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2% and 10.5% in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6% and 11.7% of pancreatic and biliary tract carcinomas, respectively. CONCLUSIONS: A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5%), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.
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[285]
TÍTULO / TITLE: - Six1 Promotes Proliferation of Pancreatic Cancer Cells via Upregulation of Cyclin D1 Expression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e59203. doi: 10.1371/journal.pone.0059203. Epub 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0059203
AUTORES / AUTHORS: - Li Z; Tian T; Lv F; Chang Y; Wang X; Zhang L; Li X; Li L; Ma W; Wu J; Zhang M
INSTITUCIÓN / INSTITUTION: - Department of Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China.
RESUMEN / SUMMARY: - Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.
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[286]
TÍTULO / TITLE: - Theranostic nanoparticles with controlled release of gemcitabine for targeted therapy and MRI of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ACS Nano. 2013 Mar 26;7(3):2078-89. doi: 10.1021/nn3043463. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1021/nn3043463
AUTORES / AUTHORS: - Lee GY; Qian WP; Wang L; Wang YA; Staley CA; Satpathy M; Nie S; Mao H; Yang L
INSTITUCIÓN / INSTITUTION: - Departments of Surgery, double daggerRadiology and Imaging Sciences, and section signBiomedical Engineering, Emory University School of Medicine , Atlanta, Georgia 30322, United States.
RESUMEN / SUMMARY: - The tumor stroma in human cancers significantly limits the delivery of therapeutic agents into cancer cells. To develop an effective therapeutic approach overcoming the physical barrier of the stroma, we engineered urokinase plasminogen activator receptor (uPAR)-targeted magnetic iron oxide nanoparticles (IONPs) carrying chemotherapy drug gemcitabine (Gem) for targeted delivery into uPAR-expressing tumor and stromal cells. The uPAR-targeted nanoparticle construct, ATF-IONP-Gem, was prepared by conjugating IONPs with the amino-terminal fragment (ATF) peptide of the receptor-binding domain of uPA, a natural ligand of uPAR, and Gem via a lysosomally cleavable tetrapeptide linker. These theranostic nanoparticles enable intracellular release of Gem following receptor-mediated endocytosis of ATF-IONP-Gem into tumor cells and also provide contrast enhancement in magnetic resonance imaging (MRI) of tumors. Our results demonstrated the pH- and lysosomal enzyme-dependent release of gemcitabine, preventing the drug from enzymatic degradation. Systemic administrations of ATF-IONP-Gem significantly inhibited the growth of orthotopic human pancreatic cancer xenografts in nude mice. With MRI contrast enhancement by IONPs, we detected the presence of IONPs in the residual tumors following the treatment, suggesting the possibility of monitoring drug delivery and assessing drug-resistant tumors by MRI. The theranostic ATF-IONP-Gem nanoparticle has great potential for the development of targeted therapeutic and imaging approaches that are capable of overcoming the tumor stromal barrier, thus enhancing the therapeutic effect of nanoparticle drugs on pancreatic cancers.
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[287]
TÍTULO / TITLE: - Novel agents in the treatment of pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):138-40. doi: 10.6092/1590-8577/1474.
AUTORES / AUTHORS: - Dimou A; Syrigos KN; Saif MW
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Albert Einstein Medical Center. Philadelphia, PA, USA. dimouana@einstein.edu.
RESUMEN / SUMMARY: - The development of new agents and treatment strategies against pancreatic adenocarcinoma is vital, given the poor prognosis of the patients with this particular type of cancer. Three novel compounds were tested at different phases of clinical research and the results were presented in the recent ASCO Gastrointestinal Cancers Symposium. FG-3019 inhibits the connective tissue growth factor which is important in the biology of pancreatic cancer and was shown to be relatively safe in a phase I study (Abstract #213). In addition, ASG-5ME, an antibody specific for SLC44A4 that is universally expressed in pancreatic cancer and also carries a conjugate chemotherapy particle was safe at the appropriate dosing in a phase I trial (Abstract #176). Last but not least, tanespimycin, a molecule that inhibits heat shock protein 90 was not effective in the first line treatment of patients with pancreatic cancer in a phase II study (Abstract #245). Further studying of FG-3019 and ASG-5ME will show the potential activity if any of these compounds in patients with pancreatic cancer.
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[288]
TÍTULO / TITLE: - Net Expression Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Cell PL45 In Vitro and In Vivo.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57818. doi: 10.1371/journal.pone.0057818. Epub 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057818
AUTORES / AUTHORS: - Li B; Wan X; Zhu Q; Li L; Zeng Y; Hu D; Qian Y; Lu L; Wang X; Meng X
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.
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[289]
TÍTULO / TITLE: - Palliation of jaundice in pancreatic cancer: stent or surgery?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Indian J Gastroenterol. 2013 Mar 17.
●● Enlace al texto completo (gratuito o de pago) 1007/s12664-013-0317-2
AUTORES / AUTHORS: - Ramesh H
INSTITUCIÓN / INSTITUTION: - Department of Surgical Gastroenterology and Liver Transplantation, Lakeshore Hospital and Research Center, Cochin, 682 024, India, hramesh@vsnl.com.
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[290]
TÍTULO / TITLE: - The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e55513. doi: 10.1371/journal.pone.0055513. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055513
AUTORES / AUTHORS: - Delpu Y; Lulka H; Sicard F; Saint-Laurent N; Lopez F; Hanoun N; Buscail L; Cordelier P; Torrisani J
INSTITUCIÓN / INSTITUTION: - INSERM UMR 1037-University of Toulouse III, Cancer Research Center of Toulouse (CRCT), Toulouse, France.
RESUMEN / SUMMARY: - MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool.
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[291]
TÍTULO / TITLE: - Prognostic impact of cyclin d1, cyclin e and p53 on gastroenteropancreatic neuroendocrine tumours.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Asian Pac J Cancer Prev. 2013;14(1):419-22.
AUTORES / AUTHORS: - Liu SZ; Zhang F; Chang YX; Ma J; Li X; Li XH; Fan JH; Duan GC; Sun XB
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology, College of Public Health of Zhengzhou University, Zhengzhou, China E-mail : gcduan@zzu.edu.cn, xbsun21@sina.com.
RESUMEN / SUMMARY: - Conventional classifications of gastroenteropancreatic neuroendocrine tumours (GEP- NETs) are rather unsatisfactory because of the variation in survival within each subgroup. Molecular markers are being found able to predict patient outcome in more and more tumours. The aim of this study was to characterize the expression of the proteins cyclin D1, cyclin E and P53 in GEP- NETs and assess any prognostic impact. Tumor specimens from 68 patients with a complete follow-up were studied immunohistochemically for cyclin D1, cyclin E and P53 expression. High cyclin D1 and cyclin E immunostaining (>/= 5% positive nuclei) was found in 48 (71%) and 24 (35%) cases, and high P53 staining (>/= 10% positive nuclei) in 33 (49%) . High expression of P53 was more common in gastric neuroendocrine tumors and related to malignant behavior, being associate with a worse prognosis on univariate analysis (RR=1.9, 95%CI=1.1-3.2). High expression of cyclin E was significantly associated with shorter survival in the univariate analysis (RR=2.0, 95%CI=1.2-3.6) and multivariate analysis (RR=2.1, 95%CI=1.1-4.0). We found no significant correlation between the expression of cyclin D1 and any clinicopathological variables. Our study indicated a prognostic relevance for cyclin E and P53 immunoreactivity. Cyclin E may be an independent prognostic factor from the 2010 WHO Classification which should be evaluated in further studies.
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[292]
TÍTULO / TITLE: - Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 7. doi: 10.1111/hpb.12061.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12061
AUTORES / AUTHORS: - Delpero JR; Bachellier P; Regenet N; Le Treut YP; Paye F; Carrere N; Sauvanet A; Autret A; Turrini O; Monges-Ranchin G; Boher JM
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Institute Paoli Calmettes.
RESUMEN / SUMMARY: - OBJECTIVES: This study aimed to determine the impact of a standardized pathological protocol on resection margin status after pancreaticoduodenectomy (PD) for ductal adenocarcinoma. METHODS: A total of 150 patients operated during 2008-2010 were included in a prospective multicentre study using a ‘quality protocol’. Multicolour inking by the surgeon identified three resection margins: the portal vein-superior mesenteric vein margin (PV-SMVm) or mesenterico-portal vein groove; the superior mesenteric artery margin (SMAm), and the posterior margin. Resection margins were stratified by 0.5-mm increments (range: 0-2.0 mm). Pancreatic neck, bile duct and intestinal margins were also analysed. Correlations between histopathological factors and survival in the 0-mm resection margin group were analysed. RESULTS: Thirty-six patients (24%) had a PV-SMV resection (PV-SMVR). An analysis of resections categorized according to margin distances of 0 mm, <1.0 mm, <1.5 mm and <2.0 mm confirmed R1 resections in 35 (23%), 91 (61%), 94 (63%) and 107 (71%) patients, respectively. The most frequently invaded resection margin was the PV-SMVm (35% of all patients) and PV-SMVR was the only factor correlated with a higher risk for at least one 0-mm positive resection margin on multivariate analysis (P < 0.001). Two-year progression-free survival (PFS) and median PFS time in patients with R0 and R1 resections (at 0 mm), respectively, were 42.0% and 26.5%, and 19.5 months and 10.5 months, respectively (P = 0.02). A positive PV-SMVm and SMAm had significant impact on PFS, whereas a positive posterior margin had no impact. CONCLUSIONS: Pancreaticoduodenectomy requiring PV-SMVR was associated with a higher risk for R1 resection. The standardization of histopathological analysis has a clinically relevant impact on PFS data.
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[293]
TÍTULO / TITLE: - Use of panitumumab in the treatment of acinar cell carcinoma of the pancreas: A case report.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):969-971. Epub 2012 Dec 18.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1083
AUTORES / AUTHORS: - Morales M; Cabrera MA; Maeso MD; Ferrer-Lopez N
INSTITUCIÓN / INSTITUTION: - Service of Medical Oncology, University Hospital Nuestra Senora de Candelaria, Santa Cruz de Tenerife, Canary Islands 38010, España.
RESUMEN / SUMMARY: - Two cases of stage IV acinar carcinoma of the pancreas are presented. The two patients were treated with several lines of chemotherapies active against colon cancer. At last-line, both patients received panitumumab monotherapy. We describe the tumour response to the different therapies. Our findings demonstrate that panitumumab produces objective responses when used as third-line treatment in the therapy of patients with acinar cell carcinoma of the pancreas. Thus, we propose the consideration of the use of panitumumab in early lines of treatment.
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[294]
TÍTULO / TITLE: - A Diagnostic Pitfall: Pancreatic Tuberculosis, not Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Coll Physicians Surg Pak. 2013 Mar;23(3):211-3. doi: 03.2013/JCPSP.211213.
AUTORES / AUTHORS: - Samuel DO; Majid Mukhtar AA; Philip IO
INSTITUCIÓN / INSTITUTION: - Department of Medicine, Ahmadu Bello University Teaching Hospital, Shika, Kaduna State, Nigeria.
RESUMEN / SUMMARY: - Abdominal tuberculosis (TB) is one of the most common forms of extra-pulmonary tuberculosis and is responsible for considerable morbidity and mortality globally. Tuberculosis can involve any part of the gastrointestinal tract from mouth to anus, the peritoneum, liver, spleen and the pancreatobiliary system. The occurrence of abdominal TB is independent of pulmonary disease in most patients, with a reported incidence of co-existing pulmonary disease varying from 6 to 38% worldwide. We report a case of pancreatic tuberculosis also involving the vertebrae, which was initially treated as a case of pancreatic cancer.
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[295]
TÍTULO / TITLE: - Combined Serum CA19-9 and miR-27a-3p in Peripheral Blood Mononuclear Cells to Diagnose Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Prev Res (Phila). 2013 Apr;6(4):331-8. doi: 10.1158/1940-6207.CAPR-12-0307. Epub 2013 Feb 19.
●● Enlace al texto completo (gratuito o de pago) 1158/1940-6207.CAPR-12-0307
AUTORES / AUTHORS: - Wang WS; Liu LX; Li GP; Chen Y; Li CY; Jin DY; Wang XL
INSTITUCIÓN / INSTITUTION: - Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, PR China. wwsdj2002@163.com.
RESUMEN / SUMMARY: - MicroRNAs are potentially very useful biomarkers in the diagnosis of cancer. We sought to identify specific microRNAs in peripheral blood mononuclear cells (PBMCs) whose levels might facilitate diagnosis of pancreatic cancer. We investigated PBMC microRNA expression in three independent cohorts [healthy, benign pancreatic/peripancreatic diseases (BPD), and pancreatic cancer], comprising a total of 352 participants. First, we used sequencing technology to identify differentially expressed microRNAs in PBMC of pancreatic cancer, BPD, and healthy controls (n = 20 in each group). Then the selected microRNAs were analyzed using the quantitative reverse transcriptase PCR assays in the remaining 292 samples. The predictive value of the microRNAs was evaluated by logistic regression models and the receiver operating characteristic curve (AUC). We found that miR-27a-3p level in PBMCs could discriminate pancreatic cancer from BPD with a sensitivity of 82.2% and specificity of 76.7% (AUC = 0.840; 95% CI, 0.787-0.885%). Combination of PBMC miR-27a-3p and serum CA19-9 levels provided a higher diagnostic accuracy with a sensitivity of 85.3% and specificity of 81.6% (AUC = 0.886; 95% CI, 0.837-0.923%). The satisfactory diagnostic performance of the panel persisted regardless of disease status (AUCs for tumor-node-metastasis stages I-III were 0.881, 0.884, and 0.893, respectively). PBMC miR-27a-3p level represents a potential marker for pancreatic cancer screening. A panel combining serum CA19-9 and PBMC miR-27a-3p level could have considerable clinical value in diagnosing pancreatic cancer. Cancer Prev Res; 6(4); 331-8. ©2013 AACR.
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[296]
TÍTULO / TITLE: - Neoadjuvant chemoradiation therapy for borderline pancreatic adenocarcinoma: report of two cases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Surg Oncol. 2013 Feb 5;11:37. doi: 10.1186/1477-7819-11-37.
●● Enlace al texto completo (gratuito o de pago) 1186/1477-7819-11-37
AUTORES / AUTHORS: - Galindo J; Gabrielli M; Guerra JF; Cassina JC; Garrido M; Jarufe N; Borghero Y; Madrid J; Zoroquiain P; Roa JC; Martinez J
INSTITUCIÓN / INSTITUTION: - Department of Digestive Surgery, Hospital Clinico Pontificia Universidad Catolica de Chile, Marcoleta 350, Santiago, Chile. jamartin@med.puc.cl.
RESUMEN / SUMMARY: - Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery.
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[297]
TÍTULO / TITLE: - Time trends in the treatment and prognosis of resectable pancreatic cancer in a large tertiary referral centre.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 12. doi: 10.1111/hpb.12073.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12073
AUTORES / AUTHORS: - Barugola G; Partelli S; Crippa S; Butturini G; Salvia R; Sartori N; Bassi C; Falconi M; Pederzoli P
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Verona, Verona, Italy.
RESUMEN / SUMMARY: - OBJECTIVES: Mortality in pancreatic cancer has remained unchanged over the last 20-30 years. The aim of the present study was to analyse survival trends in a selected population of patients submitted to resection for pancreatic cancer at a single institution. METHODS: Included were 544 patients who underwent pancreatectomy for pancreatic cancer between 1990 and 2009. Patients were categorized into two subgroups according to the decade in which resection was performed (1990-1999 and 2000-2009). Predictors of survival were analysed using univariate and multivariate analyses. RESULTS: Totals of 114 (21%) and 430 (79%) resections were carried out during the periods 1990-1999 and 2000-2009, respectively (P < 0.0001). Hospital length of stay (16 days versus 10 days; P < 0.001) and postoperative mortality (3% versus 1%; P = 0.160) decreased over time. Median disease-specific survival significantly increased from 16 months in the first period to 29 months in the second period (P < 0.001). Following multivariate analysis, poorly differentiated tumour [hazard ratio (HR) 3.1, P < 0.001], lymph node metastases (HR = 1.9, P < 0.001), macroscopically positive margin (R2) resection (HR = 3.2, P < 0.0001), no adjuvant therapy (HR = 1.6, P < 0.001) and resection performed in the period 1990-1999 (HR = 2.18, P < 0.001) were significant independent predictors of a poor outcome. CONCLUSIONS: Longterm survival after surgery for pancreatic cancer significantly improved over the period under study. Better patient selection and the routine use of adjuvant therapy may account for this improvement.
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[298]
TÍTULO / TITLE: - Gene expression profiling of primary canine insulinomas and their metastases.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Vet J. 2013 Feb 18. pii: S1090-0233(13)00044-0. doi: 10.1016/j.tvjl.2013.01.021.
●● Enlace al texto completo (gratuito o de pago) 1016/j.tvjl.2013.01.021
AUTORES / AUTHORS: - Buishand FO; Kirpensteijn J; Jaarsma AA; Speel EJ; Kik M; Mol JA
INSTITUCIÓN / INSTITUTION: - Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands. Electronic address: F.O.Buishand@uu.nl.
RESUMEN / SUMMARY: - The gene expression profile of 10 primary canine insulinomas was compared with that of their accompanying metastases using microarray analysis and quantitative real time-PCR. Analysis of microarray data revealed 84 genes that were differentially expressed between primary insulinomas and their metastases, along with 243 genes differentially expressed between a low-metastatic and a high-metastatic subset of primary insulinomas. The genes differently expressed between primary insulinomas and their metastases clustered together in nine signalling pathways. Comparing the low-metastatic to the high-metastatic subset of primary insulinomas, 26 pathways appeared to be significantly influenced. The acinar enzymes pancreatic lipase (PNLIP) and chymotrypsinogen B1 (CTRB1) were amongst the most down-regulated genes in the malignant group of primary insulinomas and in metastases. Immunofluorescence demonstrated co-localisation of insulin and PNLIP in tumour cells. Different subsets of canine insulinomas can be identified on the basis of their gene expression profile. Canine insulinomas appear to contain amphicrine cells, which exhibit both endocrine and exocrine cell features.
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[299]
TÍTULO / TITLE: - Differential expression of RBM5 and KRAS in pancreatic ductal adenocarcinoma and their association with clinicopathological features.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):1000-1004. Epub 2012 Dec 17.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1080
AUTORES / AUTHORS: - Peng J; Valeshabad AK; Li Q; Wang Y
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China ;
RESUMEN / SUMMARY: - RNA binding motif 5 (RBM5) is a tumor suppressor gene that regulates cell proliferation, differentiation and apoptosis through pre-mRNA splicing of related genes. This study aimed to detect RBM5 and KRAS expression in pancreatic ductal adenocarcinoma and their association with clinicopathological features. Detection of RBM5 and KRAS expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting was performed at mRNA and protein levels, respectively, in pancreatic cancer and non-tumor tissues. In addition, the association of RBM5 and KRAS expression with clinicopathological parameters and tumor recurrence was analyzed. The expression of RBM5 was significantly downregulated in pancreatic cancer tissues compared to peritumoral tissues at the mRNA and protein levels. Contrastingly, KRAS was significantly overexpressed in pancreatic cancerous tissues compared to peritumoral tissues. Analysis revealed that RBM5 expression was negatively correlated with KRAS expression in pancreatic cancer. Furthermore, reduced RBM5 expression has a close association with lymph node metastasis, distant metastasis, Union for International Cancer Control (UICC) stage and nerve and venous invasion, while overexpression of KRAS proteins was significantly correlated with tumor size, lymph node metastasis, UICC stage and nerve and venous invasion of pancreatic cancer. Significant RBM5 underexpression and KRAS overexpression were observed in pancreatic cancer compared to non-tumor tissues. There is a close association of differential RBM5 and KRAS with poor clinicopathological features, suggesting their potential roles in the progression and metastasis of pancreatic cancer.
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[300]
TÍTULO / TITLE: - Interaction between cAMP, volumeregulated anion channels and the Na+HCO3cotransporter, NBCe1, in the regulation of nutrient and hypotonicityinduced insulin release from isolated rat pancreatic islets and tumoral insulinproducing BRINBD11 cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Feb 28. doi: 10.3892/mmr.2013.1346.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1346
AUTORES / AUTHORS: - Bulur N; Crutzen R; Malaisse WJ; Sener A; Beauwens R; Golstein P
INSTITUCIÓN / INSTITUTION: - Laboratory of Experimental Hormonology, Universite Libre de Bruxelles, Brussels B1070, Belgium.
RESUMEN / SUMMARY: - Soluble adenylyl cyclase (sAC) has been hypothesized to play a role in insulin secretion. The present study aimed to investigate the interaction between adenosine 3’,5’cyclic monophosphate (cAMP), volumeregulated anion channels (VRACs) and the electrogenic sodium bicarbonate (Na+HCO3) cotransporter, NBCe1, in the regulation of nutrient and hypotonicityinduced insulin release from rat pancreatic islets and tumoral insulinproducing BRINBD11 cells. In the islets, 5nitro2(3phenylpropylamino)benzoic acid (NPPB) and 5chloro2hydroxy3(thiophene2carbonyl)indole1carboxamide (tenidap) reduced glucosestimulated insulin release, however, only NPPB suppressed the enhancing action of cAMP analogs upon such a release. Insulin output from the BRINBD11 cells was stimulated by 2ketoisocaproate (KIC) or extracellular hypoosmolarity. cAMP analogs and 3isobutyl1methylxanthine increased the insulin output recorded in the isotonic medium to a greater relative extent than that in the hypotonic medium. The secretory response to KIC or hypotonicity was inhibited by NPPB or tenidap, which both also opposed the enhancing action of cAMP analogs. Inhibitors of mitogenactivated protein (MAP) kinase decreased insulin output in isotonic and hypotonic media. The inhibitor of sAC, 2hydroxyestriol, caused only a modest inhibition of insulin release, whether in the isotonic or hypotonic medium, even when tested at a concentration of 100 microM. The omission of NaHCO3 markedly decreased the secretory response to KIC or extracellular hypotonicity. The omission of Na+ suppressed the secretory response to extracellular hypotonicity. The observations of the present study do not support the hypothesis of a major role for sAC in the regulation of insulin release.
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[301]
TÍTULO / TITLE: - Vitamin E delta-tocotrienol induces p27(Kip1)-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e52526. doi: 10.1371/journal.pone.0052526. Epub 2013 Feb 5.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0052526
AUTORES / AUTHORS: - Hodul PJ; Dong Y; Husain K; Pimiento JM; Chen J; Zhang A; Francois R; Pledger WJ; Coppola D; Sebti SM; Chen DT; Malafa MP
INSTITUCIÓN / INSTITUTION: - Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America.
RESUMEN / SUMMARY: - Vitamin E delta-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that delta-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA) cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that delta-tocotrienol-induced growth inhibition occurred concomitantly with G(1) cell-cycle arrest and increased p27(Kip1) nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1) expression is a well-established adverse prognostic factor in PDCA. Furthermore, delta-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1) expression. To determine whether p27(Kip1) induction is required for delta-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1), in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1) silencing suppressed cell-cycle arrest induced by delta-tocotrienol. Furthermore, delta-tocotrienol induced p27(Kip1) mRNA expression but not its protein degradation. p27(Kip1) gene promoter activity was induced by delta-tocotrienol through the promoter’s E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1) expression by delta-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1) induction, by which delta-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1) as a biomarker for delta-tocotrienol efficacy in pancreatic cancer prevention and therapy.
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[302]
TÍTULO / TITLE: - Beclin1 inhibition promotes autophagy and decreases gemcitabine-induced apoptosis in Miapaca2 pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cell Int. 2013 Mar 13;13(1):26. doi: 10.1186/1475-2867-13-26.
●● Enlace al texto completo (gratuito o de pago) 1186/1475-2867-13-26
AUTORES / AUTHORS: - Li X; Yan J; Wang L; Xiao F; Yang Y; Guo X; Wang H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Shenyang General Hospital of PLA, 83 Wenhua Road, Shenyang, 110016, P,R, China. guoxiaozhong1962@163.com.
RESUMEN / SUMMARY: - BACKGROUND: Beclin1 is a well-known key regulator of autophagy, which is also a haploinsufficient tumor suppressor. Current studies revealed that down-regulation or monoallelic deletions of Beclin1 were frequently found in various cancers. The purpose of this study was to investigate the effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of pancreatic cancer cells. METHODS: Beclin1 expression was inhibited by siRNA transduction and gene expression was determined by Real-time PCR and Western blot. The effects of Beclin1 inhibition on autophagy and Gemcitabine-induced apoptosis of Miapaca2 cells were analyed through LC3 expression, cell viability, cell cycle and apoptosis by using Western blot. RESULTS: We observed that Beclin1 silence promoted microtubule-associated protein 1 light chain 3-II (LC3-II) protein formation and increased punctate fluorescent signals in Miapaca2 cells transfected with green fluorescent protein (GFP)-tagged LC3. Beclin1 inhibition showed a greater suppressive effect on Gemcitabine-induced apoptosis of Miapaca2 cells. CONCLUSION: Our data suggested that Beclin1 silence not only up-adjusted autophagy process, but also played an important role in the regulation of apoptosis. Beclin1 inhibition could inhibit apoptosis signaling induced by Gemcitabine in Miapaca2 cells.
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[303]
TÍTULO / TITLE: - Inhibition of human pancreatic tumor growth by cytokine-induced killer cells in nude mouse xenograft model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Immune Netw. 2012 Dec;12(6):247-52. doi: 10.4110/in.2012.12.6.247. Epub 2012 Dec 31.
●● Enlace al texto completo (gratuito o de pago) 4110/in.2012.12.6.247
AUTORES / AUTHORS: - Kim JS; Park YS; Kim JY; Kim YG; Kim YJ; Lee HK; Kim HS; Hong JT; Kim Y; Han SB
INSTITUCIÓN / INSTITUTION: - College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
RESUMEN / SUMMARY: - Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14 days. The resulting populations of CIK cells comprised 94% CD3(+), 4% CD3(-)CD56(+), 41% CD3(+)CD56(+), 11% CD4(+), and 73% CD8(+). This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100:1, CIK cells destroyed 51% of AsPC-1 human pancreatic cancer cells, as measured by the (51)Cr-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.
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[304]
TÍTULO / TITLE: - Matrix metalloproteinase-9, transforming growth factor-beta1, and tumor necrosis factor-alpha plasma levels in chronic pancreatitis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Indian J Gastroenterol. 2013 Feb 14.
●● Enlace al texto completo (gratuito o de pago) 1007/s12664-012-0299-5
AUTORES / AUTHORS: - Manjari KS; Jyothy A; Vidyasagar A; Prabhakar B; Nallari P; Venkateshwari A
INSTITUCIÓN / INSTITUTION: - Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016, India.
RESUMEN / SUMMARY: - OBJECTIVE: The aim of the study was to investigate the plasma levels of matrix metalloproteinase-9 (MMP-9), transforming growth factor-beta 1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha) in chronic pancreatitis (CP). METHODS: Blood samples were obtained from 71 patients with CP and 100 control subjects, and plasma levels of MMP-9, TGF-beta1, and TNF-alpha were determined by enzyme-linked immunosorbent assay. RESULTS: The plasma levels of MMP-9 (18.3 +/- 3.0 ng/mL, p < 0.0001), TGF-beta1 (215.4 +/- 178.1 ng/mL, p = 0.0301), and TNF-alpha (111.2 +/- 69.3 ng/mL, p < 0.001) were significantly elevated in CP compared to the control group. CONCLUSION: The role of elevated plasma MMP-9, TGF-beta1, and TNF-alpha in CP requires further evaluation.
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[305]
TÍTULO / TITLE: - Aberrant glycogen synthase kinase 3beta is involved in pancreatic cancer cell invasion and resistance to therapy.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55289. doi: 10.1371/journal.pone.0055289. Epub 2013 Feb 8.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055289
AUTORES / AUTHORS: - Kitano A; Shimasaki T; Chikano Y; Nakada M; Hirose M; Higashi T; Ishigaki Y; Endo Y; Takino T; Sato H; Sai Y; Miyamoto K; Motoo Y; Kawakami K; Minamoto T
INSTITUCIÓN / INSTITUTION: - Division of Translational and Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3beta (GSK3beta) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3beta in the invasive and treatment resistant phenotype of pancreatic cancer. METHODS: Pancreatic cancer cells were examined for GSK3beta expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3beta inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3beta inhibition on cancer cell xenografts were also examined. RESULTS: Pancreatic cancer cells showed higher expression and activity of GSK3beta than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3beta significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3beta also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3beta inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts. CONCLUSION: The targeting of GSK3beta represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.
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[306]
TÍTULO / TITLE: - Endoscopic ultrasound-guided oncologic therapy for pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Ther Endosc. 2013;2013:157581. doi: 10.1155/2013/157581. Epub 2013 Feb 24.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/157581
AUTORES / AUTHORS: - Suzuki R; Irisawa A; Bhutani MS
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Unit 1466, 1515 Holcombe Bovlevard, Houston, TX 77030-4009, USA.
RESUMEN / SUMMARY: - Since the development of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the early 1990s, its application has been extended to various diseases. For pancreatic cancer, EUS-FNA can obtain specimens from the tumor itself with fewer complications than other methods. Interventional EUS enables various therapeutic options: local ablation, brachytherapy, placement of fiducial markers for radiotherapy, and direct injection of antitumor agents into cancer. This paper will focus on EUS-guided oncologic therapy for pancreatic cancer.
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[307]
TÍTULO / TITLE: - RNA interference-mediated silencing of VEGF and bFGF suppresses endostatin secretion in pancreatic carcinoma cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):1031-1035. Epub 2013 Jan 2.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1102
AUTORES / AUTHORS: - Yan C; Wang C; Dong M; Liu S; Qi C; Zhao Y
INSTITUCIÓN / INSTITUTION: - Department of Heptobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000;
RESUMEN / SUMMARY: - Pro-angiogenic factors [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)] and anti-angiogenic factors (endostatin) play important roles in the progression of pancreatic cancer. The purpose of the present study was to investigate the knockdown effect by either VEGF or bFGF siRNA on the expression and secretion of endostatin in pancreatic carcinoma cells. Pancreatic carcinoma cell lines (sw1990, Panc-1 and PCT-3) were treated with VEGF and bFGF siRNA. The expression of VEGF, bFGF and endostatin in pancreatic carcinoma cell lines was determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Secretion of endostatin was measured by enzyme-linked immunosorbent assay (ELISA). bFGF and VEGF siRNA significantly reduced the expression of bFGF and VEGF mRNA, respectively, but did not affect mRNA and protein expression of endostatin in pancreatic carcinoma cell lines. However, secretion of endostatin in PCT-3, Panc-1 and sw1990 cells was significantly inhibited by bFGF and VEGF siRNA. This study demonstrated that pro-angiogenic factors (VEGF and bFGF) differentially modulate expression and secretion of anti-angiogenic factors (endostatin). This result may have important implications in the anti-angiogenesis therapy in pancreatic cancer.
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[308]
TÍTULO / TITLE: - Pancreatic fistula after a pancreaticoduodenectomy for ductal adenocarcinoma and its association with morbidity: a multicentre study of the French Surgical Association.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 6. doi: 10.1111/hpb.12063.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12063
AUTORES / AUTHORS: - Addeo P; Delpero JR; Paye F; Oussoultzoglou E; Fuchshuber PR; Sauvanet A; Sa Cuhna A; Le Treut YP; Adham M; Mabrut JY; Chiche L; Bachellier P
INSTITUCIÓN / INSTITUTION: - Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Hopital de Hautpierre, Universite de Strasbourg, Strasbourg.
RESUMEN / SUMMARY: - BACKGROUNDS: A pancreatic fistula (PF) is the most relevant complication after a pancreaticoduodenectomy (PD). This retrospective multicentric study attempts to elucidate the risk factors and complications of a PF in a large cohort of patients undergoing a PD for ductal adenocarcinoma. METHODS: Using a survey tool, clinical data of 1325 patients undergoing a PD for ductal adenocarcinoma at 37 institutions, between January 2004 and December 2009, were collected. Peri-operative risk factors associated with PF and its association with morbidity and mortality were assessed. Morbidity and PF were graded according to the ISGPF (International Study group for pancreatic fistula) definition and the Dindo-Clavien classification. RESULTS: Overall PF, mortality, morbidity and relaparotomy rates were 14.3%, 3.8%, 54.4% and 11.7%, respectively. PF occurred more frequently after a pancreaticojejunostomy (PJ) compared with a pancreaticogastrostomy (PG) (16.8% vs. 10.4%; P = 0.0012). Independent risk factors for PF by multivariate analysis were absence of pre-operative diabetes (P = 0.0014), PJ reconstruction (P = 0.0035), soft pancreatic parenchyma (P < 0.0001) and low-volume centre (P = 0.0286). Clinically relevant PF (grade B and C) and severe complications (Dindo-Clavien grade IIIB, IV, V) were significantly more frequent after PJ than PG (71.6% vs. 28.3%; P = 0.030 and 24.8% vs. 19.1%; P = 0.015, respectively). Overall mortality and relaparotomy rates were similar after PG and PJ. CONCLUSIONS: A soft pancreatic parenchyma, the absence of pre-operative diabetes, PJ and low-volume centre are independent risk factors for PF after PD for ductal adenocarcinoma. A significantly higher incidence and clinical severity of PF are associated with PJ.
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[309]
TÍTULO / TITLE: - Burkitt’s Lymphoma Presenting as Late-Onset Posttransplant Lymphoproliferative Disorder following Kidney and Pancreas Transplantation: Case Report and Review of the Literature.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Oncol. 2013 Jan;6(1):6-14. doi: 10.1159/000346346. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 1159/000346346
AUTORES / AUTHORS: - Naik S; Tayapongsak K; Robbins K; Manavi CK; Pettenati MJ; Grier DD
INSTITUCIÓN / INSTITUTION: - Blood and Marrow Transplantation, Division of Hematology and Oncology, University School of Medicine, Winston-Salem, N.C., USA.
RESUMEN / SUMMARY: - Posttransplant lymphoproliferative disorders (PTLD) are a rare, but serious complication following transplantation. Late-onset PTLD are often associated with more monoclonal lesions and consequently have a worse prognosis. There are only isolated case reports of Burkitt’s lymphoma presenting as PTLD. We present an extremely rare, aggressive Burkitt’s lymphoma years after kidney and pancreas transplantation which was successfully treated with combination chemotherapy along with withdrawal of immunosuppression. The patient remains in complete remission more than 2 years after his diagnosis. We also provide a succinct review of treatment of various PTLD and discuss the role of Epstein-Barr virus infection in the pathogenesis of PTLD.
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[310]
TÍTULO / TITLE: - Suppression of AKT Phosphorylation Restores Rapamycin-based Synthetic Lethality in SMAD4-defective Pancreatic Cancer Cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Cancer Res. 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 1158/1541-7786.MCR-12-0679
AUTORES / AUTHORS: - Le Gendre O; Sookdeo A; Duliepre SA; Utter M; Frias M; Foster DA
INSTITUCIÓN / INSTITUTION: - The Hunter College of the City University of New York.
RESUMEN / SUMMARY: - mTOR - the mammalian target of rapamycin - has been implicated in survival signals for many human cancers. Rapamycin and TGF-b synergistically induce G1 cell cycle arrest in several cell lines with intact TGF-b signaling pathway, which protects cells from the apoptotic effects rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-b and cytotoxic in the absence of serum. However, if TGF-b signaling is defective, rapamycin induced apoptosis in both the presence and absence of serum/TGF-b in colon and breast cancer cell lines. Since genetic dysregulation of TGF-b signaling is commonly observed in pancreatic cancers - with defects in the Smad4 gene being most prevalent, we hypothesized that pancreatic cancers would display a synthetic lethality to rapamycin in the presence of serum/TGF-b. We report here that Smad4-deficient pancreatic cancer cells are killed by rapamycin in the absence of serum; however, in the presence of serum we did not observe the predicted synthetic lethality with rapamycin. Rapamycin also induced elevated phosphorylation of the survival kinase Akt at Ser473. Suppression of rapamycin-induced Akt phosphorylation restored rapamycin sensitivity in Smad4 null, but not Smad4 wild type pancreatic cancer cells. This study demonstrates that the synthetic lethality to rapamycin in pancreatic cancers with defective TGF-b signaling is masked by rapamycin-induced increases in Akt phosphorylation. The implication is that a combination of approaches that suppress both Akt phosphorylation and mTOR could be effective in targeting pancreatic cancers with defective TGF-b signaling.
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[311]
TÍTULO / TITLE: - A Resectable Pancreatic Metastasis from Pulmonary Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Ann Thorac Cardiovasc Surg. 2013 Jan 31.
AUTORES / AUTHORS: - Igai H; Kamiyoshihara M; Nagashima T; Ohtaki Y; Shimizu K
INSTITUCIÓN / INSTITUTION: - Department of General Thoracic Surgery, Maebashi Red Cross Hospital, Gunma, Japan.
RESUMEN / SUMMARY: - A 67-year-old man, diagnosed as primary pulmonary adenocarcinoma by intraoperative fine-needle aspiration biopsy cytology, underwent right lower lobectomy with radical lymphadenectomy. The pathological stage was Stage IIA (pT1bN1M0, N-reason: 12Lpositive). After surgery, nodular shadows without intrathoracic lymph node or distant metastasis were demonstrated metachronously three times by follow-up CT. Wedge resection was performed for each of the tumors, and the pathological diagnosis in each case was primary pulmonary adenocarcinoma, Stage IA (T1b), IA (T1a) and IA (T1a), respectively.Five years after the initial pulmonary resection, a follow-up abdominal CT revealed a20-mm nodular shadow. We suspected that this pancreatic tumor might be a primary rather than metastatic one, therefore, pancreatoduodenectomy was performed. Pathological examination revealed adenocarcinoma that was positive for thyroid transcription factor (TTF)-1, allowing a final diagnosis of metastatic pulmonary adenocarcinoma.This case is very rare, because most cases of pancreatic metastasis from lung cancer have already widespread disease at the time of diagnosis.This case illustrates that pancreatic metastasis from pulmonary adenocarcinoma should be borne in mind, even if the pancreatic tumor is a solitary lesion without additional organ metastasis.
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[312]
TÍTULO / TITLE: - Pancreatic head region lymph node tuberculosis mimicking pancreatic solid pseudopapillary tumor.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Chin Med J (Engl). 2013 Mar;126(5):976-7.
AUTORES / AUTHORS: - Xu Q; Liu H; Tian YT
INSTITUCIÓN / INSTITUTION: - Department of Abdominal Surgery, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China.
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[313]
TÍTULO / TITLE: - Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Jan 14. doi: 10.1111/hpb.12019.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12019
AUTORES / AUTHORS: - John BJ; Naik P; Ironside A; Davidson BR; Fusai G; Gillmore R; Watkins J; Rahman SH
INSTITUCIÓN / INSTITUTION: - Centre for HPB Surgery and Liver Transplantation, The Royal Free London NHS Foundation Trust, London, UK.
RESUMEN / SUMMARY: - INTRODUCTION: The presence of positive nodal disease (LND) and the number of lymph nodes involved (LNB) are known to be significant prognostic markers for resected adenocarcinoma of the pancreas. In addition, the ratio of the number of involved nodes to the number of nodes resected known as the lymph node ratio (LNR) is emerging as an important prognostic marker. The role of the resection margin (RM) as presently defined (R1 </= 1 mm) is unclear as results differ based on the dataset. The aim of this study was to assess the impact of nodal disease and a redefined RM on outcome. MATERIAL AND METHODS: Retrospective analysis of pancreatic head resections for adenocarcinomas from 2003-2009. The RM was re-analysed based on tumour clearance and categorized into: histopathological evidence of a tumour; </=0.5 mm, </=1 mm, </=1.5 mm, or </=2.0 mm of the actual surgical resection margin. The impact of histopathological variables on cancer-specific survival (CSS) and disease-free survival (DFS) was analysed. RESULTS: LND, LNB and LNR were independent prognostic markers for CSS (P = 0.048, 0.003, 0.016) but, did not influence DFS. A LNR < 0.143 was associated with a higher CSS [38.16 +/- 4.69 versus 20.59 +/- 2.20 months, P = 0.0042, hazard ratio (HR) 3.74 (95% confidence interval (CI) 1.52-9.23)]. An R1 RM was not associated with CSS or DFS on multivariate analysis, irrespective of the distance. LNB and LNR maintained independent significance irrespective of the size of the RM. CONCLUSION: LNB and LNR are the only prognostic factors for CSS in patients with pancreatic head adenocarcinoma, but do not predict recurrence. Microscopic RMs does not seem to influence the outcome even when redefined. Further prospective studies are indicated to substantiate these findings.
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[314]
TÍTULO / TITLE: - Hepatic portal venous gas in pancreatic solitary metastasis from an esophageal squamous cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hepatobiliary Pancreat Dis Int. 2013 Feb;12(1):103-5.
AUTORES / AUTHORS: - Sawada T; Adachi Y; Noda M; Akino K; Kikuchi T; Mita H; Ishii Y; Endo T
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology, Sapporo Shirakaba-dai Hospital, Sapporo, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Hepatic portal venous gas (HPVG) is a rare entity commonly associated with intestinal necrosis and fatal outcome, and various underlying diseases have been reported. Pancreatic solitary metastasis without local extension is also rare in esophageal squamous cell carcinoma. METHODS: This report describes an interesting and unusual case of HPVG arising from pancreatic tumor. Autopsy revealed pathogenesis of HPVG and synchronous tumors of the esophagus and pancreas. RESULTS: A 73-year-old man developed synchronous double tumor in the esophagus and pancreas several months before acute abdomen and his death, which were generated by HPVG. Autopsy revealed that HPVG was caused by gastric wall infarction owing to expansion of an isolated pancreatic metastasis from esophageal squamous cell carcinoma. CONCLUSIONS: This is the first case of HPVG that was derived from pancreatic tumor infiltration. If he had been diagnosed with solitary pancreatic metastasis from esophageal squamous cell carcinoma in the first time, he might have an option for chemotherapy, which could let him live longer.
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[315]
TÍTULO / TITLE: - Intraductal papillary mucinous neoplasms of the pancreas: is the puzzle solved?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Indian J Gastroenterol. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s12664-013-0327-0
AUTORES / AUTHORS: - Balsarkar D; Takahata S; Tanaka M
INSTITUCIÓN / INSTITUTION: - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
RESUMEN / SUMMARY: - Intraductal papillary mucinous neoplasms (IPMN) are drawing more attention and being detected more frequently. This review focuses on current understanding of the management of IPMN, regarding morphological classification, subclassification by cell lineage features, molecular abnormalities, radiological and imaging evaluation, progression to cancer, incidence and risk factors for malignancy, risk of distinct pancreatic adenocarcinoma and extrapancreatic malignancies, treatment strategy, and types of surgical resection. In particular, missing links in solving the IPMN puzzles are described with regard to differential diagnosis, role of cyst fluid analysis, multifocal IPMN, histological evaluation of the surgical specimen, observation without resection, follow up of patients after resection, role of adjuvant therapy for invasive carcinoma, screening for other neoplasms in patients with IPMN on follow up, prognostic factors influencing long-term outcomes, and role of endoscopic therapy.
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[316]
TÍTULO / TITLE: - Lipid-rich variant of pancreatic endocrine tumour with inhibin positivity and microscopic foci of microcystic adenoma-like areas: emphasis on histopathology.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Singapore Med J. 2013 Feb;54(2):e31-4.
AUTORES / AUTHORS: - Rao AC; Monappa V; Shetty P
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka 576104, India. anuchenna@yahoo.com.
RESUMEN / SUMMARY: - Pancreatic endocrine tumours (PETs) are uncommon tumours with typical morphology characterised by relatively uniform cuboidal cells arranged in nests and festoons, with distinctive nuclear salt-and-pepper chromatin. A lipid-rich variant poses diagnostic difficulties in the midst of other pancreatic tumours and metastatic goblet cell carcinoid. A 22-year-old man presented with symptoms of abdominal pain and jaundice. His liver function test and blood glucose level were normal, but computed tomography of the abdomen suggested the presence of a tumour in the head of the pancreas. Specimen obtained by pancreaticoduodenectomy revealed an infiltrating yellow-tan tumour composed of nests and a cribriform arrangement of polygonal vacuolated cells with pyknotic nuclei, along with focal classical areas of PET. Two foci of early serous microcystic adenoma were seen. Immunohistochemistry contributed to the arrival of a conclusive diagnosis. Von Hippel-Lindau disease was excluded in our patient, as other supportive classical features of the syndrome were absent.
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[317]
TÍTULO / TITLE: - Inhibitory effect of ARHI on pancreatic cancer cells and NFkappaB activity.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Med Rep. 2013 Apr;7(4):1180-4. doi: 10.3892/mmr.2013.1342. Epub 2013 Feb 26.
●● Enlace al texto completo (gratuito o de pago) 3892/mmr.2013.1342
AUTORES / AUTHORS: - Hu YQ; Si LJ; Ye ZS; Lin ZH; Zhou JP
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian 361004, P.R. China.
RESUMEN / SUMMARY: - The aim of this study was to investigate the effect of aplasia ras homolog member I (ARHI) on proliferation, apoptosis and the cell cycle in the pancreatic cancer cell line PANC1. The study also aimed to examine the effect of ARHI on the activity of the nuclear factor (NF)kappaB and to determine whether ARHI acts as a tumor suppressor in the development of pancreatic cancer by inhibiting the activity of NFkappaB. A pIRES2EGFPARHI vector, constructed by reverse transcrition (RT)PCR, was transiently transfected into the PANC1 cells and analyzed for the expression of the ARHI protein by western blotting. A MTT assay was used to quantify cell proliferation, and apoptosis was analyzed by flow cytometry. The NFkappaB signaling pathway, specifically the pathway using the nuclear phosphorylated p65 isoform, was analyzed by western blotting. Expression of the ARHI protein was detected by western blotting subsequent to the PANC1 cells being transiently transfected with the pIRES2EGFPARHI construct. Cell proliferation was strongly inhibited in the PANC1 cells transfected with pIRES2EGFPARHI. The cell cycle assays indicated an increase in the number of cells at the G0/G1 phase and a decrease in the cells at the S phase, but the difference was not significant (P>0.05). Time course studies also indicated a marked increase in the apoptotic index following transient transfection, as well as a gradual decrease in the expression of the nuclear phosphorylated p65 protein. ARHI acts as a tumor suppressor by downregulating the NFkappaB signaling pathway, which results in the inhibition of cell proliferation, apoptosis and the cell cycle in the pancreatic tumor PANC1 cell line.
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[318]
TÍTULO / TITLE: - Efemp1 and p27Kip1 modulate responsiveness of pancreatic cancer cells towards a dual PI3K/mTOR inhibitor in preclinical models.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncotarget. 2013 Feb;4(2):277-88.
AUTORES / AUTHORS: - Diersch S; Wenzel P; Szameitat M; Eser P; Paul MC; Seidler B; Eser S; Messer M; Reichert M; Pagel P; Esposito I; Schmid RM; Saur D; Schneider G
INSTITUCIÓN / INSTITUTION: - II. Medizinische Klinik, Technische Universitat Munchen, Munchen, Germany.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease with a poor prognosis and targeted therapies have failed in the clinic so far. Several evidences point to the phosphatidylinositol 3-kinase (PI3K)-mTOR pathway as a promising signaling node for targeted therapeutic intervention. Markers, which predict responsiveness of PDAC cells towards PI3K inhibitors are unknown. However, such markers are needed and critical to better stratify patients in clinical trials. We used a large murine KrasG12D- and PI3K (p110alphaH1047R)-driven PDAC cell line platform to unbiased define modulators of responsiveness towards the dual PI3K-mTOR inhibitor Bez235. In contrast to other tumor models, we show that KrasG12D- and PI3K (p110alphaH1047R)-driven PDAC cell lines are equally sensitive towards Bez235. In an unbiased approach we found that the extracellular matrix protein Efemp1 controls sensitivity of murine PDAC cells towards Bez235. We show that Efemp1 expression is connected to the cyclin-dependent kinase inhibitor p27Kip1. In a murine KrasG12D-driven PDAC model, p27Kip1 haploinsufficiency accelerates cancer development in vivo. Furthermore, p27Kip1 controls Bez235 sensitivity in a gene dose-dependent fashion in murine PDAC cells and lowering of p27Kip1 decreases Bez235 responsiveness in murine PDAC models. Together, we define the Efemp1-p27Kip1 axis as a potential marker module of PDAC cell sensitivity towards dual PI3K-mTOR inhibitors, which might help to better stratify patients in clinical trials.
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[319]
TÍTULO / TITLE: - Different patterns of Akt and ERK feedback activation in response to rapamycin, active-site mTOR inhibitors and metformin in pancreatic cancer cells.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e57289. doi: 10.1371/journal.pone.0057289. Epub 2013 Feb 21.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0057289
AUTORES / AUTHORS: - Soares HP; Ni Y; Kisfalvi K; Sinnett-Smith J; Rozengurt E
INSTITUCIÓN / INSTITUTION: - Division of Digestive Diseases, Department of Medicine; CURE: Digestive Diseases Research Center David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, United States of America.
RESUMEN / SUMMARY: - The mTOR pathway is aberrantly stimulated in many cancer cells, including pancreatic ductal adenocarcinoma (PDAC), and thus it is a potential target for therapy. However, the mTORC1/S6K axis also mediates negative feedback loops that attenuate signaling via insulin/IGF receptor and other tyrosine kinase receptors. Suppression of these feed-back loops unleashes over-activation of upstream pathways that potentially counterbalance the antiproliferative effects of mTOR inhibitors. Here, we demonstrate that treatment of PANC-1 or MiaPaCa-2 pancreatic cancer cells with either rapamycin or active-site mTOR inhibitors suppressed S6K and S6 phosphorylation induced by insulin and the GPCR agonist neurotensin. Rapamycin caused a striking increase in Akt phosphorylation at Ser(473) while the active-site inhibitors of mTOR (KU63794 and PP242) completely abrogated Akt phosphorylation at this site. Conversely, active-site inhibitors of mTOR cause a marked increase in ERK activation whereas rapamycin did not have any stimulatory effect on ERK activation. The results imply that first and second generation of mTOR inhibitors promote over-activation of different pro-oncogenic pathways in PDAC cells, suggesting that suppression of feed-back loops should be a major consideration in the use of these inhibitors for PDAC therapy. In contrast, metformin abolished mTORC1 activation without over-stimulating Akt phosphorylation on Ser(473) and prevented mitogen-stimulated ERK activation in PDAC cells. Metformin induced a more pronounced inhibition of proliferation than either KU63794 or rapamycin while, the active-site mTOR inhibitor was more effective than rapamycin. Thus, the effects of metformin on Akt and ERK activation are strikingly different from allosteric or active-site mTOR inhibitors in PDAC cells, though all these agents potently inhibited the mTORC1/S6K axis.
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[320]
TÍTULO / TITLE: - Contribution of bone marrow derived cells to the pancreatic tumor microenvironment.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Front Physiol. 2013;4:56. doi: 10.3389/fphys.2013.00056. Epub 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 3389/fphys.2013.00056
AUTORES / AUTHORS: - Scarlett CJ
INSTITUCIÓN / INSTITUTION: - Food Bioactives and Pancreatic Cancer Biology Group, School of Environmental and Life Sciences, University of Newcastle Ourimbah, NSW, Australia ; Cancer Research Program, Garvan Institute of Medical Research Darlinghurst, Sydney, NSW, Australia.
RESUMEN / SUMMARY: - Pancreatic cancer is a complex, aggressive, and heterogeneous malignancy driven by the multifaceted interactions within the tumor microenvironment. While it is known that the tumor microenvironment accommodates many cell types, each playing a key role in tumorigenesis, the major source of these stromal cells is not well-understood. This review examines the contribution of bone marrow-derived cells (BMDC) to pancreatic carcinogenesis, with respect to their role in constituting the tumor microenvironment. In particular, their role in supporting fibrosis, immunosuppression, and neovascularization will be discussed.
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[321]
TÍTULO / TITLE: - Inhibition of Telomerase Activity by Oleanane Triterpenoid CDDO-Me in Pancreatic Cancer Cells is ROS-Dependent.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Molecules. 2013 Mar 13;18(3):3250-65. doi: 10.3390/molecules18033250.
●● Enlace al texto completo (gratuito o de pago) 3390/molecules18033250
AUTORES / AUTHORS: - Deeb D; Gao X; Liu Y; Varma NR; Arbab AS; Gautam SC
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Henry Ford Health System, Detroit, MI 48202, USA. sgautam1@hfhs.org.
RESUMEN / SUMMARY: - Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a synthetic derivative of oleanolic acid, a triterpene, with apoptosis-inducing activity in a wide range of cancer cells. Induction of apoptosis by CDDO-Me is associated with the generation of reactive oxygen species (ROS) and inhibition of telomerase activity. In the present study, we investigated the role of ROS in inhibition of telomerase by CDDO-me. Treatment of MiaPaCa-2 and Panc-1 pancreatic cancer cell lines with CDDO-Me induced the production of hydrogen peroxide and superoxide anions and inhibited the telomerase activity. Pretreatment of cells with N-acetylcycsteine, a general purpose antioxidant or overexpression of glutathione peroxidase (GPx) or superoxide dismutase-1 (SOD-1) blocked the telomerase inhibitory activity of CDDO-Me. Furthermore, blocking ROS generation also prevented the inhibition of hTERT gene expression, hTERT protein production and expression of a number of hTERT-regulatory proteins by CDDO-Me (e.g., c-Myc, Sp1, NF-kappaB and p-Akt). Data also showed that Akt plays an important role in the activation of telomerase activity. Together, these data suggest that inhibition of telomerase activity by CDDO-Me is mediated through a ROS-dependent mechanism; however, more work is needed to fully understand the role of ROS in down-regulation of hTERT gene and hTERT-regulatory proteins by CDDO-Me.
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[322]
TÍTULO / TITLE: - Increased radiosensitivity and radiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma cell lines treated with the novel Hsp90 inhibitor NVP-HSP990.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Radiat Oncol. 2013 Feb 28;8(1):42. doi: 10.1186/1748-717X-8-42.
●● Enlace al texto completo (gratuito o de pago) 1186/1748-717X-8-42
AUTORES / AUTHORS: - Milanovic D; Firat E; Grosu AL; Niedermann G
INSTITUCIÓN / INSTITUTION: - Department of Radiation Oncology, University Hospital Freiburg, Freiburg 79106, Germany. dusan.milanovic@uniklinik-freiburg.de.
RESUMEN / SUMMARY: - BACKGROUND AND PURPOSE: Heat shock Protein 90 (Hsp90) is a molecular chaperone that folds, stabilizes, and functionally regulates many cellular proteins involved in oncogenic signaling and in the regulation of radiosensitivity. It is upregulated in response to stress such a heat. Hyperthermia is a potent radiosensitizer, but induction of Hsp90 may potentially limit its efficacy. Our aim was to investigate whether the new Hsp90 inhibitor NVP-HSP990 increases radiosensitivity, thermosensitivity and radiothermosensitivity of human tumor cell lines. MATERIAL AND METHODS: U251 glioblastoma and MIA PaCa-2 pancreatic carcinoma cells were used. To determine clonogenic survival, colony forming assays were performed. Cell viability and proliferation were assesed by Trypan blue staining. Cell cycle and apoptosis analyses were performed by flow cytometry. DAPI staining was used to detect mitotic catastrophe. RESULTS: NVP-HSP990 increased the thermosensitivity, radiosensitivity and radio-thermosensitivity of both cell lines in clonogenic assays. 72 hours after irradiation with 4 Gy, a significant reduction in cell number associated with considerable G2/M acumulation and mitotic catastrophe as well as cell death by apoptosis/necrosis was observed. CONCLUSIONS: Treatment with NVP-HSP990 strongly sensitized U251 and MIA PaCa-2 cells to hyperthermia and ionizing radiation or combination thereof through augmentation of G2/M arrest, mitotic catastrophe and associated apoptosis.
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[323]
TÍTULO / TITLE: - Laparoscopic staging and surgical treatment of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - N Am J Med Sci. 2013 Jan;5(1):1-9. doi: 10.4103/1947-2714.106183.
●● Enlace al texto completo (gratuito o de pago) 4103/1947-2714.106183
AUTORES / AUTHORS: - Muniraj T; Barve P
INSTITUCIÓN / INSTITUTION: - Section of Digestive Diseases, Yale University School of Medicine, CT, USA ; Department of Medicine, Griffin Hospital, CT, USA.
RESUMEN / SUMMARY: - Pancreatic cancer is the tenth most common cancer and the fourth leading cause of cancer deaths in the United States. Surgery remains a cornerstone in the treatment of pancreatic cancer. Unfortunately, the percentage of patients presenting at the resectable stage is minimal. Although computed tomography (CT) scan remains the best modality to stage the tumor for resectability, laparoscopy and laparoscopic ultrasound offers its own advantages. Extended lymphadenectomy, portal vein resection, and arterial reconstruction have also been explored in multiple studies to enhance staging. The traditional pancreaticoduodenectomy (Whipple’s procedure) with regional lymphadenectomy is still the standard of care in the surgical treatment of pancreatic cancer.
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[324]
TÍTULO / TITLE: - Surgical treatment of pancreatic insulinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arq Bras Cir Dig. 2012 Apr-Jun;25(2):101-4.
AUTORES / AUTHORS: - Bonato FT; Coelho JC; Petruzzielo A; Matias JE; Ferreira GA
INSTITUCIÓN / INSTITUTION: - Hospital de Clinicas, Universidade Federal do Parana, Curitiba, PR, Brasil. flatb_@hotmail.com
RESUMEN / SUMMARY: - BACKGROUND: Insulinoma is a pancreatic neuroendocrine tumor originated from pancreatic islet beta cells. Although rare, is the most common pancreatic endocrine tumor, with about four cases per million people. The preferential treatment of insulinoma is surgical. AIM: To analyze the epidemiological, pathological, clinical and surgical patients treated in the last decade in two surgical services. METHODS: Were retrospectively reviewed the medical records of patients undergoing surgical treatment of insulinoma in the period of 1999 to 2011. Demographic data, type and duration of symptoms, associated or not with endocrine syndrome and diagnostic tests were obtained from medical records. Were analyzed the method of surgery, intraoperative findings and immediate and late complications. RESULTS: Sixteen patients with insulinoma underwent surgical treatment, 68,7% were women. The age ranged from 20 to 60 years, with a mean age of 39 years. Only one case was associated with multiple endocrine neoplasia type 1. Neuropsychiatric manifestations, mainly syncope, were the most prevalent. The average duration of clinical manifestations until the diagnosis was one year and a half. Imaging tests were used in all patients with 68.7% of preoperative tumor localization. All operations were performed in a conventional (open) manner, without use of laparoscopy. The lesions were identified in all portions of the pancreas with the majority in the pancreatic head. Relief of symptoms was not obtained only in one patient. There were no deaths among the patients. CONCLUSION: The diagnosis of insulinoma is often established after several months of the onset of clinical manifestations and surgical treatment is curative in almost all patients.
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[325]
TÍTULO / TITLE: - First-line treatment for advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):129-32. doi: 10.6092/1590-8577/1477.
AUTORES / AUTHORS: - Kothari N; Saif MW; Kim R
INSTITUCIÓN / INSTITUTION: - H. Lee Moffitt Cancer Center. Tampa, FL, USA. richard.kim@moffitt.org.
RESUMEN / SUMMARY: - Metastatic pancreatic cancer is a rapidly fatal disease with few therapeutic options. The authors summarize four abstracts (#148, #233, #158, #291) presented at the 2013 ASCO Gastrointestinal Cancers Symposium which were focused on novel agents for metastatic pancreatic cancer.
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[326]
TÍTULO / TITLE: - Oxaliplatin and Bolus-Modulated 5-Fluorouracil as a Second-Line Treatment for Advanced Pancreatic Cancer: Can Bolus Regimens Replace FOLFOX When Considered for Second Line?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - ISRN Oncol. 2013;2013:358538. doi: 10.1155/2013/358538. Epub 2013 Feb 24.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/358538
AUTORES / AUTHORS: - Azmy A; Abdelwahab S; Yassen M
INSTITUCIÓN / INSTITUTION: - GIT and Gynecological Oncology Unit, Ain Shams University, Cairo 11539, Egypt.
RESUMEN / SUMMARY: - Objective. Comparing activity of 2 regimens combining oxaliplatin to bolus modulated fluorouracil as second line treatment in advanced pancreatic adenocarcinoma pretreated with gemcitabine-containing schedule. Methods. Forty eight patients with advanced pancreatic adenocarcinoma were randomly assigned to receive either FU 500 mg/m(2) IV bolus weekly x6 weeks plus leucovorin 500 mg/m(2) IV weekly for 6 weeks during each 8-week cycle plus oxaliplatin 85 mg/m(2) IV on weeks 1, 3, and 5 of each 8-week (FLOX) OR receive weekly intravenous infusions of oxaliplatin 40 mg/m(2), 5-FU 500 mg/m(2), and leucovorin 250 mg/m(2) (3 weeks on, 1 week off). Results. Non progression(PR+SD) was found in 33.5% for first regimen and 29% for second regimen, and 37.5% had clinical benefit (FLOX regimen) compared to 50% in 3-weeks regimen. The median TTP was 3.9,4 months respectively. Median OS was 8, 9 months for both regimens. Only one case in 3-weeks arm suffered from grade IV diarrhea. Two cases > grade 2 neutropenia were observed; one in each treatment groups. Grade 3 anemia was recorded in 3 patients (2 in FLOX arm, one in 3-weeks arm). Conclusions. Both regimens showed encouraging efficacy, acceptable toxicity, and clinical benefit.
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[327]
TÍTULO / TITLE: - Lymph nodes metastasis and recurrences justify an aggressive treatment of gastrinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Updates Surg. 2013 Mar;65(1):19-24. doi: 10.1007/s13304-013-0201-8. Epub 2013 Feb 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s13304-013-0201-8
AUTORES / AUTHORS: - Giovinazzo F; Butturini G; Monsellato D; Malleo G; Marchegiani G; Bassi C
INSTITUCIÓN / INSTITUTION: - Surgical Department, Pancreas Institute, Hospital of ‘G.B.Rossi’, University of Verona School of Medicine, Piazzale ‘LA. Scuro’, 37134, Verona, Italy.
RESUMEN / SUMMARY: - In the current study, short- and long-term outcomes after aggressive surgical treatment for gastrinoma were evaluated. From August 1990 to August 2009, 20 patients diagnosed with Zollinger Ellison syndrome were reviewed. Eleven pancreaticoduodenectomies, three total pancreatectomies, four lymph node dissections, four enucleations and two palliative procedures were performed. Four (27.8 %) patients had disease associated with MEN1 syndrome, 13 (72.2 %) had sporadic gastrinomas (SG) and 3 had disease of unknown primary origin. No in-hospital mortality was observed. After radical resection, lymph node metastasis was present in 82 % of the cases. Eight percent of patients who underwent radical resection developed recurrence compared with 100 % of those who underwent enucleoresection (p = 0.03). Average time to recurrence in patients with sporadic gastrinoma was 66.7 months (confidence interval (CI) 62.9-70.5) in those treated with enucloeresection compared to 181.1 months (CI 124.3-237.8) in the radical resection group (p = 0.007). One recurrence was observed in the MEN1 group. Based on post-operative mortality, recurrence and lymph node metastasis, our data suggest that patients with gastrinoma should undergo abdominal exploration with aggressive resection of the primary tumour and regional lymph nodes in place of conservative treatment.
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[328]
TÍTULO / TITLE: - Serine protease inhibitor Kazal type 1 and epidermal growth factor receptor are expressed in pancreatic tubular adenocarcinoma, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Hepatobiliary Pancreat Sci. 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1007/s00534-012-0587-6
AUTORES / AUTHORS: - Ozaki N; Ohmuraya M; Ida S; Hashimoto D; Ikuta Y; Chikamoto A; Hirota M; Baba H
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
RESUMEN / SUMMARY: - BACKGROUND: Serine protease inhibitor Kazal type 1 (SPINK1) is expressed in normal human pancreatic acinar cells and in a variety of tumors, and binds to the epidermal growth factor receptor (EGFR), mediating cell proliferation through the mitogen-activated protein kinase cascade in pancreatic cancer cell lines. Here, we aimed to assess SPINK1 and EGFR expression in various neoplastic lesions, including tissues demonstrating precancerous changes. METHODS: Surgical specimens of pancreatic ductal adenocarcinoma (n = 23), intraductal papillary mucinous neoplasm (IPMN; n = 21), pancreatic neoplasms other than ductal adenocarcinoma (n = 8), chronic pancreatitis (n = 11), and pancreatic intraepithelial neoplasia (PanIN) lesions within the resected specimens were analyzed immunohistochemically for SPINK1 and EGFR expression. RESULTS: Sixty-five PanIN-1A, 32 PanIN-1B, 17 PanIN-2, and 6 PanIN-3 were identified. Both SPINK1 and EGFR were expressed in almost all PanIN lesions. All tubular ductal adenocarcinoma, IPMN, and mucinous cystadenocarcinoma samples (neoplasms of ductal origin) expressed SPINK1, whereas acinar cell carcinoma, anaplastic carcinoma, adenosquamous carcinoma, insulinoma, and islet cell carcinoma did not. EGFR was expressed in 87 % of tubular adenocarcinoma and 48 % of IPMN lesions. Among IPMN lesions, malignant lesions (IPMC) expressed EGFR more often than benign lesions (IPMA) did. Scattered expression of EGFR was observed in normal pancreatic ducts and within the tubular complex within chronic pancreatitis lesions. CONCLUSIONS: These results indicate that SPINK1 plays a role as a growth factor, signaling through the EGFR pathway in pancreatic ductal adenocarcinoma and neoplasms, and that the EGFR is involved in the malignant transformation of IPMN.
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[329]
TÍTULO / TITLE: - Second-line therapy in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):133-4. doi: 10.6092/1590-8577/1463.
AUTORES / AUTHORS: - Skoura E; Syrigos KN; Saif MW
INSTITUCIÓN / INSTITUTION: - Oncology Unit, Third Department of Medicine, University of Athens, Sotiria General Hospital; Nuclear Medicine Department, Evangelismos General Hospital. Athens, Greece. lskoura@yahoo.gr.
RESUMEN / SUMMARY: - At the time of diagnosis most of patients present with advanced or metastatic pancreatic cancer, thereby precluding surgical resection. While the standard of care in the first line setting is established, there are limited data to support a standard second-line chemotherapy regimen. The authors summarize two interesting studies (Abstract #263 and Abstract #287) presented at the 2013 ASCO Gastrointestinal Cancers Symposium. These studies concern two phase II trials about second-line chemotherapy in pancreatic cancer. The first one evaluated the role of fluoropyrimidine as monotherapy versus fluoropyrimidine in combination with irinotecan (Abstract #263) and the second one compared the fluoropyrimidine treatment with the continuation of gemcitabine as monotherapy (Abstract #287).
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[330]
TÍTULO / TITLE: - Adjuvant therapy of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):119-22. doi: 10.6092/1590-8577/1461.
AUTORES / AUTHORS: - Chaulagain CP; Ng J; Goodman MD; Saif MW
INSTITUCIÓN / INSTITUTION: - Division of Hematology and Oncology, Tufts Medical Center and Tufts University School of Medicine. Boston, MA, USA. cchaulagain@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This review is an update from the 2013 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium held in San Francisco, CA, USA. We present the summary of the findings from Abstracts #145 and #269 and discuss the potential impact on our clinical practice on this highly lethal cancer.
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[331]
TÍTULO / TITLE: - Impact of preoperative therapy on patterns of recurrence in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Feb 20. doi: 10.1111/hpb.12058.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12058
AUTORES / AUTHORS: - Papavasiliou P; Hoffman JP; Cohen SJ; Meyer JE; Watson JC; Chun YS
INSTITUCIÓN / INSTITUTION: - Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
RESUMEN / SUMMARY: - BACKGROUND: A theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence. METHODS: Medical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan-Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis. RESULTS: Preoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis. CONCLUSIONS: Preoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection.
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[332]
TÍTULO / TITLE: - Pancreatic cancer and predictors of survival: comparing the CA 19-9/bilirubin ratio with the McGill Brisbane Symptom Score.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 22. doi: 10.1111/hpb.12085.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12085
AUTORES / AUTHORS: - Dumitra S; Jamal MH; Aboukhalil J; Doi SA; Chaudhury P; Hassanain M; Metrakos PP; Barkun JS
INSTITUCIÓN / INSTITUTION: - Department of Surgery, McGill University Health Center, Montreal, QC, Canada.
RESUMEN / SUMMARY: - INTRODUCTION: Few tools predict survival from pancreatic cancer (PAC). The McGill Brisbane Symptom Score (MBSS) based on symptoms at presentation (weight loss, pain, jaundice and smoking) was recently validated. The present study compares the ability of four strategies to predict 9-month survival: MBSS, carbohydrate antigen 19-9 (CA 19-9) alone, CA19-9-to-bilirubin ratio and a combination of MBSS and the CA19-9-to-bilirubin ratio. METHODOLOGY: A retrospective review of 133 patients diagnosed with PAC between 2005 and 2011 was performed. Survival was determined from the Quebec civil registry. Blood CA 19-9 and bilirubin values were collected (n = 52) at the time of diagnosis. Receiver-operating characteristic (ROC) curves were used to determine a cutoff for optimal test characteristics of CA 19-9 and CA19-9-to-total bilirubin ratio in predicting survival at 9 months. Predictive characteristics were then calculated for the four strategies. RESULTS: Of the four strategies, the one with the greatest negative predictive value was the MBSS: negative predictive value (NPV) was 90.2% (76.9-97.3%) and the positive likelihood ratio (LR) was the greatest. The ability of CA 19-9 levels alone, at baseline, to predict survival was low. For the CA19-9-to-bilirubin ratio, the test characteristics improved but remained non-significant. The best performing strategy according to likelihood ratios was the combined MBSS and CA19-9 to the bilirubin ratio. CONCLUSION: CA19-9 levels and the CA19-9-to-bilirubin ratio are poor predictors of survival for PAC, whereas the MBSS is a far better predictor, confirming its clinical value. By adding the CA19-9-to-bilirubin ratio to the MBSS the predictive characteristics improved.
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[333]
TÍTULO / TITLE: - 53BP1 expression is a modifier of the prognostic value of lymph node ratio and CA 19--9 in pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 26;13(1):155.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-155
AUTORES / AUTHORS: - Ausborn NL; Wang T; Wentz SC; Washington MK; Merchant NB; Zhao Z; Shyr Y; Chakravarthy AB; Xia F
RESUMEN / SUMMARY: - BACKGROUND: 53BP1 binds to the tumor suppressor p53 and has a key role in DNA damage response and repair. Low 53BP1 expression has been associated with decreased survival in breast cancer and has been shown to interact with several prognostic factors in non-small cell lung cancer. The role of 53BP1 in pancreatic ductal adenocarcinoma (PDAC) has yet to be determined. We aimed to investigate whether 53BP1 levels interact with established prognostic factors in PDAC. METHODS: 106 patients for whom there was tissue available at time of surgical resection for PDAC were included. A tissue microarray was constructed using surgical specimens, stained with antibodies to 53BP1, and scored for expression intensity. Univariate and multivariate statistical analyses were performed to investigate the association between 53BP1 and patient survival with known prognostic factors for survival. RESULTS: The association of 53BP1 with several established prognostic factors was examined, including stage, tumor grade, surgical margin, peripancreatic extension, lymph node ratio (LNR), and CA 19--9. We found that 53BP1 modified the effects of known prognostic variables including LNR and CA 19--9 on survival outcomes. When 53BP1 intensity was low, increased LNR was associated with decreased OS (HR 4.84, 95% CI (2.26, 10.37), p<0.001) and high CA19-9 was associated with decreased OS (HR 1.72, 95% CI (1.18, 2.51), p=0.005). When 53BP1 intensity was high, LNR and CA19-9 were no longer associated with OS (p=0.958 and p=0.606, respectively). CONCLUSIONS: In this study, 53BP1, a key player in DNA damage response and repair, was found to modify the prognostic value of two established prognostic factors, LNR and CA 19--9, suggesting 53BP1 may alter tumor behavior and ultimately impact how we interpret the value of other prognostic factors.
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[334]
TÍTULO / TITLE: - Glutathione ethyl ester supplementation during pancreatic islet isolation improves viability and transplant outcomes in a murine marginal islet mass model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55288. doi: 10.1371/journal.pone.0055288. Epub 2013 Feb 12.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055288
AUTORES / AUTHORS: - do Amaral AS; Pawlick RL; Rodrigues E; Costal F; Pepper A; Galvao FH; Correa-Giannella ML; Shapiro AM
INSTITUCIÓN / INSTITUTION: - Alberta Diabetes Institute, University of Alberta, Edmonton AB, Canada.
RESUMEN / SUMMARY: - BACKGROUND: The success of pancreatic islet transplantation still faces many challenges, mainly related to cell damage during islet isolation and early post-transplant. The increased generation of reactive oxygen species (ROS) during islet isolation and the consumption of antioxidant defenses appear to be an important pathway related to islet damage. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we evaluated whether supplementation of glutathione-ethyl-ester (GEE) during islet isolation could improve islet viability and transplant outcomes in a murine marginal islet mass model. We also cultured human islets for 24 hours in standard CMRL media with or without GEE supplementation. Supplementation of GEE decreased the content of ROS in isolated islets, leading to a decrease in apoptosis and maintenance of islet viability. A higher percentage of mice transplanted with a marginal mass of GEE treated islets became euglycemic after transplant. The supplementation of 20 mM GEE in cultured human islets significantly reduced the apoptosis rate in comparison to untreated islets. CONCLUSIONS/SIGNIFICANCE: GEE supplementation was able to decrease the apoptosis rate and intracellular content of ROS in isolated islets and might be considered a potential intervention to improve islet viability during the isolation process and maintenance in culture before islet transplantation.
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[335]
TÍTULO / TITLE: - Genetically engineered mouse models of pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Mol Oncol. 2013 Apr;7(2):232-47. doi: 10.1016/j.molonc.2013.02.002. Epub 2013 Feb 11.
●● Enlace al texto completo (gratuito o de pago) 1016/j.molonc.2013.02.002
AUTORES / AUTHORS: - Guerra C; Barbacid M
INSTITUCIÓN / INSTITUTION: - Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas (CNIO), Melchor Fernandez Almagro 3, E-28029 Madrid, España. Electronic address: mcguerra@cnio.es.
RESUMEN / SUMMARY: - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer for which there are no effective therapies. Deep sequencing of PDAC tumors has revealed the presence of a high number of mutations (>50) that affect at least a dozen key signaling pathways. This scenario highlights the urgent need to develop experimental models that faithfully reproduce the natural history of these human tumors in order to understand their biology and to design therapeutic approaches that might effectively interfere with their multiple mutated pathways. Over the last decade, several models, primarily based on the genetic activation of resident KRas oncogenes knocked-in within the endogenous KRas locus have been generated. These models faithfully reproduce the histological lesions that characterize human pancreatic tumors. Decoration of these models with additional mutations, primarily involving tumor suppressor loci known to be also mutated in human PDAC tumors, results in accelerated tumor progression and in the induction of invasive and metastatic malignancies. Mouse PDACs also display a desmoplastic stroma and inflammatory responses that closely resemble those observed in human patients. Interestingly, adult mice appear to be resistant to PDAC development unless the animals undergo pancreatic damage, mainly in the form of acute, chronic or even temporary pancreatitis. In this review, we describe the most representative models available to date and how their detailed characterization is allowing us to understand their cellular origin as well as the events involved in tumor progression. Moreover, their molecular dissection is starting to unveil novel therapeutic strategies that could be translated to the clinic in the very near future.
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[336]
TÍTULO / TITLE: - Detection of pancreatic cancer using serum protein profiling.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2012 Nov 30. doi: 10.1111/hpb.12017.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12017
AUTORES / AUTHORS: - Velstra B; Bonsing BA; Mertens BJ; van der Burgt YE; Huijbers A; Vasen H; Mesker WE; Deelder AM; Tollenaar RA
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Biolomolecular Mass Spectometry Unit.
RESUMEN / SUMMARY: - BACKGROUND: Currently, no suitable biomarkers for the early detection of pancreatic cancer (PC) are available. Proteins present in the serum could reflect a state of the disease. In this study, these profiles as a diagnostic marker for PC were evaluated. METHODS: Serum samples were obtained from PC patients (n = 50 calibration set, n = 39 validation set) and healthy volunteers (n = 110 and n = 75 respectively) according to a uniform standardized collection and processing protocol. For peptide and protein isolation, automated solid-phase extraction (SPE) with Weak Cation Exchange (WCX) magnetic beads (MB) was performed using a 96-channel liquid handling platform. Protein profiles were obtained by mass spectrometry (MS) and evaluated by linear discriminant analysis with double cross-validation. RESULTS: A discriminating profile for PC has been identified, with a sensitivity of 78% and a specificity of 89% in the calibration set with an area under the curve (AUC) of 90%. These results were validated with a sensitivity of 74% and a specificity of 91% (AUC 90%). CONCLUSION: Serum profiles of healthy controls and PC can be discrimated between. Further research is warranted to evaluate specificity and whether this biosignature can be used for early detection in a high risk population.
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[337]
TÍTULO / TITLE: - Gallbladder bed resection or hepatectomy of segments 4a and 5 for pT2 gallbladder carcinoma: analysis of Japanese registration cases by the study group for biliary surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Hepatobiliary Pancreat Sci. 2013 Feb 22.
●● Enlace al texto completo (gratuito o de pago) 1007/s00534-012-0584-9
AUTORES / AUTHORS: - Horiguchi A; Miyakawa S; Ishihara S; Miyazaki M; Ohtsuka M; Shimizu H; Sano K; Miura F; Ohta T; Kayahara M; Nagino M; Igami T; Hirano S; Yamaue H; Tani M; Yamamoto M; Ota T; Shimada M; Morine Y; Kinoshita H; Yasunaga M; Takada T
INSTITUCIÓN / INSTITUTION: - Department of Biliary-Pancreatic Surgery, Fujita Health University, Toyoake, Aichi, Japan, akihori@fujita-hu.ac.jp.
RESUMEN / SUMMARY: - PURPOSE: Hepatectomy of segments 4a and 5 (S4a+5) is the recommended treatment for pT2 gallbladder cancer. However, gallbladder bed resection is also occasionally used. Using nationwide data from the Japanese Biliary Tract Cancer Registry and a questionnaire survey, we retrospectively compared these 2 methods of treatment. METHOD: The study involved 85 patients with pT2, pN0 gallbladder cancer (55 treated with gallbladder bed resection, and 30, with S4a+5 hepatectomy). The prognosis and mode of tumor recurrence following treatment were analyzed retrospectively, with overall survival as the endpoint. RESULTS: The 5-year survival rate did not differ significantly between the 2 groups. Univariate analysis showed that bile duct resection and perineural tumor invasion were significant prognostic factors, but the extent of hepatectomy, location of the major intramural tumor, regional lymph node excision, and histological type were not. Multivariate analysis identified perineural tumor invasion as a significant prognostic factor. Recurrence occurred most frequently in both lobes than S4a+5 of the liver following gallbladder bed resection. CONCLUSION: In the present study of cases of Japanese Biliary Tract Cancer Registry, it was not possible to conclude that S4a+5 hepatectomy was superior to gallbladder bed resection.
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[338]
TÍTULO / TITLE: - Longterm survival after pancreaticoduodenectomy for periampullary adenocarcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 8. doi: 10.1111/hpb.12071.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12071
AUTORES / AUTHORS: - Chen SC; Shyr YM; Wang SE
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Taipei Veterans General Hospital, National Yang Ming University, Taipei, Taiwan.
RESUMEN / SUMMARY: - OBJECTIVES: The aim of this study was to identify predictors for longterm survival following pancreaticoduodenectomy (PD) for pancreatic and other periampullary adenocarcinomas. METHODS: Clinicopathological factors were compared between short-term (<5 years) and longterm (>/=5 years) survival groups. Rates of actual 5-year and actuarial 10-year survival were determined. RESULTS: There were 109 (21.8%) longterm survivors among a sample of 501 patients. Patients with ampullary adenocarcinoma represented 76.1% of the longterm survivors. Favourable factors for longterm survival included female gender, lack of jaundice, lower blood loss, classical PD, absence of postoperative bleeding or intra-abdominal abscess, non-pancreatic primary cancer, earlier tumour stage, smaller tumour size (</=2 cm), curative resection, negative lymph node involvement, well-differentiated tumours, and absence of perineural invasion. Independent factors associated with longterm survival were diagnosis of primary tumour, jaundice, intra-abdominal abscess, tumour stage, tumour size, radicality, lymph node status and cell differentiation. The prognosis was best for ampullary adenocarcinoma, for which the rate of actual 5-year survival was 32.8%, and poorest for pancreatic head adenocarcinoma, for which actual 5-year survival was only 6.5%. CONCLUSIONS: The majority of longterm survivors after PD for periampullary adenocarcinomas are patients with ampullary adenocarcinoma. The longterm prognosis in pancreatic head adenocarcinoma remains dismal.
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[339]
TÍTULO / TITLE: - Neoadjuvant interferon-based chemoradiation for borderline resectable and locally advanced pancreas cancer: a Phase II pilot study.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar 19. doi: 10.1111/hpb.12086.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12086
AUTORES / AUTHORS: - Jensen EH; Armstrong L; Lee C; Tuttle TM; Vickers SM; Sielaff T; Greeno EW
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN, USA.
RESUMEN / SUMMARY: - OBJECTIVES: Neoadjuvant chemoradiotherapy (CRT) is a viable treatment strategy for patients with pancreatic cancer. This study was conducted to evaluate the Virginia Mason Protocol (5-fluorouracil, cisplatin, interferon-alpha and radiation) given in the neoadjuvant setting for the treatment of locally advanced pancreatic cancer. METHODS: A Phase II pilot study evaluating interferon-based neoadjuvant CRT in patients with locally advanced pancreatic cancer was performed. RESULTS: A total of 23 patients were enrolled. The mean age of the patients was 58.6 years. Of the 23 patients, seven (30.4%) completed all treatments. In the remaining 16 (69.6%) patients, treatment was interrupted as a result of toxicity. The most commonly reported effects of toxicity were leucopoenia/cytopoenia (n = 19, 82.6%) and gastrointestinal effects (n = 19, 82.6%). Surgical resection was successful in seven (30.4%) patients. Margins were negative in six (85.7%) of these seven patients. Positive lymph nodes were identified in three (42.9%) of seven patients. Overall survival was 11.5 months. Surgery provided improved survival (22.6 months) compared with CRT alone (8.8 months). Disease-free survival in resected patients was 17.2 months. CONCLUSIONS: Interferon-based neoadjuvant CRT may allow for resection of locally advanced pancreatic cancer, but with significant toxicity. In the absence of surgical resection, survival remains dismal.
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[340]
TÍTULO / TITLE: - A case of serous cystadenoma of the pancreas communicating with the main pancreatic duct synchronously diagnosed with pancreatic ductal carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nihon Shokakibyo Gakkai Zasshi. 2013 Mar;110(3):449-55.
AUTORES / AUTHORS: - Takahashi M; Senmaru N; Kawase H; Takahashi R; Kuroda H; Maeda M; Fujita M; Hirano S
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Steel Memorial Muroran Hospital.
RESUMEN / SUMMARY: - A 65-year-old woman who had been followed up for a cystic lesion of the tail of the pancreas was found to have cancer of the body of the pancreas. ERP showed stenosis of the main pancreatic duct (MPD) with dilatation of the distal side of the duct, and communication between the cystic lesion and MPD. She underwent distal pancreatectomy under a diagnosis of intraductal papillary-mucinous neoplasm associated with cancer of the body of the pancreas. Clinicopathologic investigation revealed that the diagnosis of the cystic lesion was serous cystadenoma having the communication with MPD. It was also indicated by the histopathologic findings that inflammatory changes of MPD caused by stenosis might contribute to the development of serous cystadenoma.
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[341]
TÍTULO / TITLE: - MR features of primary and secondary malignant lymphoma of the pancreas: a pictorial review.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Insights Imaging. 2013 Mar 20.
●● Enlace al texto completo (gratuito o de pago) 1007/s13244-013-0242-z
AUTORES / AUTHORS: - Fujinaga Y; Lall C; Patel A; Matsushita T; Sanyal R; Kadoya M
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan, fujinaga@shinshu-u.ac.jp.
RESUMEN / SUMMARY: - OBJECTIVE: To describe the imaging findings of primary and secondary pancreatic malignant lymphoma on magnetic resonance imaging (MRI), to help differentiate lymphoma of the pancreas from primary adenocarcinoma and autoimmune pancreatitis among others, and to discuss a few atypical presentations of pancreatitis mimicking lymphoma. CONCLUSION: Knowledge of these imaging manifestations of lymphoma may be helpful to arrive at an accurate diagnosis and avoid unnecessary morbidity and mortality from inadvertent surgery. MAIN MESSAGES: * Pancreatic malignant lymphoma is shown as a nodular low-density area with mild enhancement on CT. * It sometimes shows variable manifestations mimicking other tumours and inflammatory conditions. * MRI provides useful information for differentiating malignant lymphoma from other mimickers.
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[342]
TÍTULO / TITLE: - Chemopreventive Effects of 4-Methylthio-3-butenyl Isothiocyanate (Raphasatin) but Not Curcumin against Pancreatic Carcinogenesis in Hamsters.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Agric Food Chem. 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1021/jf3003174
AUTORES / AUTHORS: - Okamura T; Umemura T; Inoue T; Tasaki M; Ishii Y; Nakamura Y; Park EY; Sato K; Matsuo T; Okamoto S; Nishikawa A; Ogawa K
INSTITUCIÓN / INSTITUTION: - Division of Pathology and double daggerBiological Safety Research Center, National Institute of Health Sciences , Tokyo 158-8501, Japan.
RESUMEN / SUMMARY: - The modifying effects of 4-methylthio-3-butenyl isothiocyanate (MTBITC) and curcumin were investigated in N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamsters. Male 6-week-old Syrian hamsters were subcutaneously injected with 10 mg/kg body weight (b.w.) of BOP four times a week, and fed a diet supplemented with 80 mg/kg diet of MTBITC, equivalent to 4.6 mg/kg b.w./day for the initiation stage or 3.8 mg/kg b.w./day for the postinitiation stage administration, respectively, or 2000 mg/kg diet of curcumin, equivalent to 118.8 mg/kg b.w./day for the initiation stage or 100.8 mg/kg b.w./day for the postinitiation stage administration, respectively. The incidence of combined pancreatic lesions, including atypical hyperplasias and adenocarcinomas, was significantly decreased to 55% (P < 0.05) by the 80 mg/kg diet MTBITC given during the initiation stage as compared to the BOP alone group (85%) but not by the curcumin administration at 16 weeks after the BOP-treatment. In the second study, the multiplicity of combined pancreatic lesions was also significantly decreased to 0.50 +/- 0.51 (P < 0.05) by 700 mg/kg diet MTBITC given in the initiation stage (equivalent to 59.0 mg/kg b.w./day) as compared to the BOP alone group (1.10 +/- 1.02). Our results indicate that the naturally occurring isothiocyanate MTBITC may exert preventive effects against BOP-initiation of hamster pancreatic carcinogenesis.
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[343]
TÍTULO / TITLE: - Histological percutaneous diagnosis of stage IV microcystic serous cystadenocarcinoma of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - British Medical J (BMJ). Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista bmj.com/search.dtl
●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Jan 30;2013. pii: bcr2012007924. doi: 10.1136/bcr-2012-007924.
●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-007924
AUTORES / AUTHORS: - Wasel BA; Keough V; Huang WY; Molinari M
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Dalhousie University, Halifax, Canada.
RESUMEN / SUMMARY: - Malignant serous cystic neoplasms (SCN) of the pancreas are exceptionally rare, and only a few cases have been reported. As a result, SCN have been unanimously classified as benign tumours. Contrary to this conviction, in 1989, George et al published the very first case of a patient found to have a malignant pancreatic SCN. Up to the time of the submission of this paper, 27 cases of serous cystoadenocarcinomas have been published. In all the previously published cases of malignant SCN, the correct diagnosis was made postoperatively or at the time of autopsy. The authors present a case of a 68-year-old patient who was incidentally found to have a large liver mass on transthoracic echocardiogram ordered for suspected coronary artery insufficiency. Subsequent investigations revealed an additional large mass in the pancreas and percutaneous biopsies of both lesions revealed histological features consistent with malignant SCN metastasised to the left hepatic lobe.
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[344]
TÍTULO / TITLE: - Novel agents in gastroenteropancreatic neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):152-4. doi: 10.6092/1590-8577/1470.
AUTORES / AUTHORS: - Stevenson R; Libutti SK; Saif MW
INSTITUCIÓN / INSTITUTION: - Tufts University School of Medicine. Boston, MA, USA. rstevenson@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Neuroendocrine tumors (NET) are a diverse group of tumors that derive from epithelial cells with neuroendocrine differentiation. Gastroenteropancreatic neuroendocrine tumors are a subset of NET that arises in the gastrointestinal tract. Clinical symptoms and presentations vary depending on the location and hormones produced by the tumor. Treatment of advanced and metastatic gastroenteropancreatic NETs has traditionally been difficult with few systemic treatment options. In 2011, two new targeted therapies, everolimus and sunitinib were approved for treatment of pancreatic NET leading to increased interest in novel agents active in gastroenteropancreatic NETs. At the 2013 ASCO Gastrointestinal Cancers Symposium two abstracts presented new data regarding novel therapies. Lombard-Bohas et al. (Abstract #224) presented new data from the RADIANT-3 trial and Shen et al. (Abstract #322) looked at the use of octreotide in elderly patients with carcinoid syndrome.
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[345]
TÍTULO / TITLE: - Does pre-operative chemoradiation for initially unresectable or borderline resectable pancreatic adenocarcinoma increase post-operative morbidity? A case-matched analysis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Jan 10. doi: 10.1111/hpb.12033.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12033
AUTORES / AUTHORS: - Araujo RL; Gaujoux S; Huguet F; Gonen M; D’Angelica MI; Dematteo RP; Fong Y; Kingham TP; Jarnagin WR; Goodman KA; Allen PJ
INSTITUCIÓN / INSTITUTION: - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
RESUMEN / SUMMARY: - BACKGROUND: Neoadjuvant chemoradiation therapy for locally unresectable and borderline resectable pancreatic cancer may allow some patients to a undergo a resection, but whether or not this increases post-operative morbidity remains unclear. METHODS: The post-operative morbidity of 29 patients with initially locally unresectable/borderline pancreatic cancer who underwent a resection were compared with 29 patients with initially resectable tumours matched for age, gender, the presence of comorbidities (yes/no), American Society of Anesthesiology (ASA) score, tumour location (head/body-tail), procedure (pancreaticoduodenectomy/distal pancreatectomy) and vascular resection (yes /no). Wilcoxon’s signed ranks test was used for continuous variables and McNemar’s chi-square test for categorical variables. RESULTS: Compared with patients with initially resectable tumours, patients who underwent a resection after pre-operative chemoradiation therapy had similar rates of overall post-operative complications (55% versus 41%, P = 0.42), major complications (21% versus 21%, P = 1), pancreatic leaks and fistulae (7% versus 10%, P = 1) and mortality (0% versus 1.7%, P = 1). CONCLUSION: Although some previous studies have suggested differences in post-operative morbidity after chemoradiation, our case-matched analysis did not find statistical differences in surgical morbidity and mortality associated with pre-operative chemoradiation therapy.
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[346]
TÍTULO / TITLE: - Endoscopic Ultrasound-Guided Celiac Plexus Neurolysis in Pancreatic Cancer: A Prospective Pilot Study of Safety Using 10 mL versus 20 mL Alcohol.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Ther Endosc. 2013;2013:327036. doi: 10.1155/2013/327036. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/327036
AUTORES / AUTHORS: - Leblanc JK; Rawl S; Juan M; Johnson C; Kroenke K; McHenry L; Sherman S; McGreevy K; Al-Haddad M; Dewitt J
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology and Hepatology, Indiana University Medical Center, 550 North University Boulevard, UH 4100, Indianapolis, IN 46202, USA.
RESUMEN / SUMMARY: - Background. The dose of alcohol used in EUS-CPN is not standardized. The objective was to compare the safety of 20 mL alcohol versus 10 mL alcohol during EUS-CPN for patients with pancreatic cancer-related pain. Methods. 20 patients were selected to receive 10 mL or 20 mL of alcohol during EUS-CPN. Followup was done at baseline, 24 hours, and weekly. Health-related quality of life (HRQoL) was assessed at baseline, week 2, week 4, and every 4 weeks thereafter until pain returned. Results. There were no major complications in both groups. Minor self-limited adverse effects were seen in 6 (30%) subjects and included lightheadedness in 1 (5%), transient diarrhea in 2 (10%), and transient nausea and vomiting in 3. Pain relief was similar in both groups: 80% in the 10 mL group and 100% in the 20 mL group (P = 0.21). The mean (+/- SD) duration of pain relief in the 10 mL and 20 mL groups was 7.9 +/- 10.8 and 8.4 +/- 9.2 weeks, respectively. 30% of patients in each group had complete pain relief. Conclusions. EUS-CPN using 20 mL of alcohol is safe. Similar clinical outcomes were seen in both groups. Further investigations to confirm these findings are warranted.
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[347]
TÍTULO / TITLE: - Primary pulmonary primitive neuroectodermal tumor metastasis to the pancreas: a rare case with seven-year follow-up.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Mar 27;8(1):51.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-51
AUTORES / AUTHORS: - Shi L; Guo Z; Wu X
RESUMEN / SUMMARY: - There are only nine primitive neuroectodermal tumor (PNET) cases that have arisen in lung parenchyma without pleural or chest wall involvement in the literature. Here, we present a long-term survival case of pulmonary PNET. A pulmonary mass was detected in a 19-yearold man on a chest radiograph and computed tomography image. At the three-year follow-up, the mass had enlarged in diameter by two-fold. The lesion was resected via lower left lobectomy. Histologically, the tumor was composed of uniform cells with round nuclei and scanty cytoplasm arranged in lobules with rosettes and pseudorosettes formation. Immunohistochemically, the tumor was positive for CD99, vimentin, neuron specific enolase and chromogranin A, and negative for cytokeratins, CD3, desmin, and leukocyte common antigen. Pancreatic metastasis occurred sixteen months after the first surgery, which was managed by pancreatectomy. The patient has survived seven years after the mass was initially detected, and four years after the first lobectomy. Virtual slides The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/1500847644913244.
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[348]
TÍTULO / TITLE: - Isolated pancreatic tuberculosis: A case report and radiological comparison with cystic pancreatic lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Radiol Case Rep. 2013 Jan;7(1):1-11. doi: 10.3941/jrcr.v7i1.1292. Epub 2013 Jan 1.
●● Enlace al texto completo (gratuito o de pago) 3941/jrcr.v7i1.1292
AUTORES / AUTHORS: - Falkowski AL; Graber J; Haack HG; Tarr PE; Rasch H
INSTITUCIÓN / INSTITUTION: - Department of Radiology and Nuclear Medicine, Kantonsspital Baselland, Bruderholz, Switzerland.
RESUMEN / SUMMARY: - Pancreatic tuberculosis is rare and can occur in the absence of evidence of tuberculosis elsewhere in the body. Here we review the radiological appearance of pancreatic tuberculosis and compare it with other cystic pancreatic lesions, including common lesions (pseudocysts, serous or mucinous cystadenomas, intraductal papillary mucinous neoplasm) and rare lesions such as solid pseudopapillary tumors, etc. Their typical localizations within the pancreas and their malignant potential are presented. Knowledge of these can assist radiologists and clinicians in selecting the best approach towards making the correct diagnosis.
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[349]
TÍTULO / TITLE: - Pancreatic carcinosarcoma: case report of a rare type of pancreatic neoplasia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):212-5. doi: 10.6092/1590-8577/1309.
AUTORES / AUTHORS: - Oymaci E; Argon A; Coskun A; Ucar AD; Carti E; Erkan N; Yildirim M
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Izmir Bozyaka Training and Research Hospital. Izmir, Turkey. erkan.oymaci@hotmail.com.
RESUMEN / SUMMARY: - CONTEXT: Carcinosarcoma of the pancreas is a rare entity comprising a small subset of all pancreatic neoplasms. Diagnosis is usually established by immunohistochemical examination of the resected specimen. Prognosis is limited to several months after resection. CASE REPORT: We review the current literature on this rare type of neoplasia, considering histopathological and clinical features. The pathologic findings revealed areas of both adenocarcinoma and sarcoma of the pancreas. The adenocarcinomatous areas localized to the tumor within the head of the pancreas whereas the sarcomatous areas localized to regions of the intraductal component. DISCUSSION: Carcinosarcoma of the pancreas is a rare disease having a dismal prognosis. To our knowledge, this carcinosarcoma is the very rare reported case of a primary pancreatic neoplasm with mixed carcinomatous and sarcomatous components.
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[350]
TÍTULO / TITLE: - Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Target Oncol. 2013 Mar 26.
●● Enlace al texto completo (gratuito o de pago) 1007/s11523-013-0273-x
AUTORES / AUTHORS: - Ota S; Geschwind JF; Buijs M; Wijlemans JW; Kwak BK; Ganapathy-Kanniappan S
INSTITUCIÓN / INSTITUTION: - Division of Vascular and Interventional Radiology, Russell H. Morgan Department of Radiology and Radiological Sciences, School of Medicine, Johns Hopkins University, 600 North Wolfe Street, Blalock 545, Baltimore, MD, 21287, USA.
RESUMEN / SUMMARY: - Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.
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[351]
TÍTULO / TITLE: - Endoscopic ultrasound in the diagnosis of pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Expert Opin Med Diagn. 2013 Jan;7(1):25-35. doi: 10.1517/17530059.2012.711313. Epub 2012 Aug 6.
●● Enlace al texto completo (gratuito o de pago) 1517/17530059.2012.711313
AUTORES / AUTHORS: - Munroe CA; Fehmi SM; Savides TJ
INSTITUCIÓN / INSTITUTION: - University of California, Division of Gastroenterology , San Diego, CA , USA.
RESUMEN / SUMMARY: - Introduction: Cross sectional imaging is important for initial evaluation of pancreatic cancer, whereas endoscopic ultrasound (EUS) will often help better visualize, differentiate and make final tissue diagnosis. It plays an important role in the multi-disciplinary evaluation and staging of pancreatic cancer as accurate staging has significant impact on treatment decisions. Areas covered: This review will cover the yield and utility of EUS and EUS FNA for diagnosis of pancreas cancer. In addition, this article reviews the utility and diagnostic yield of the non-invasive imaging modalities, including surface ultrasound, CT scan, PET CT scan and MRI. Tumor size, histology and disease processes that mimic pancreatic cancers will also be reviewed. Expert opinion: The accurate diagnosis and staging of pancreatic neoplasms is essential for optimal patient management. Abdominal imaging with multidetector CT or MRI is the most important initial step in the evaluation of pancreatic cancer because they are widely available and can detect most masses and/or demonstrate dilated bile or pancreatic ducts indicative of obstruction. Endoscopic ultrasound will remain important for detecting small tumors, ruling out diseases that mimic adenocarcinoma and for obtaining tissue diagnosis with fine needle aspiration.
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[352]
TÍTULO / TITLE: - Intraductal Papillary Mucinous Neoplasms of the Pancreas (IPMNs): Epidemiology, Diagnosis and Future Aspects.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):141-4. doi: 10.6092/1590-8577/1467.
AUTORES / AUTHORS: - Konstantinou F; Syrigos KN; Saif MW
INSTITUCIÓN / INSTITUTION: - Department of Medicine and Cancer Center, Tufts Medical Center. Boston, MA, USA. wsaif@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are potentially malignant intraductal epithelial neoplasms which consist of columnar, mucin-containing cells and arise from the epithelium of the main pancreatic duct or its branches. IPMNs as well as pancreatic intraepithelial neoplasias (PanINs) and mucinous cystic neoplasms represent noninvasive precursors of invasive ductal adenocarcinoma of the pancreas. The diagnosis of IPMNs includes radiographic (CT scanning, MRI, MRCP) and endoscopic evaluation (ERCP, EUS), PET, as well as serum tumor markers and molecular markers. The Sendai Consensus Guidelines help guide surgical resection for patients with IPMN. The follow-up of these patients, as well as of those who do not undergo surgical resection, is of great importance, since patients with IPMN appear to be at risk for other malignancies. Herein, the authors summarize the data presented at the 2013 ASCO Gastrointestinal Cancers Symposium regarding incidence and clinicopathological characteristics of IPMN (Abstracts #324, #187 and #179).
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[353]
TÍTULO / TITLE: - Prognostic and predictive biomarkers in gastroenteropancreatic neuroendocrine tumors.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):155-7. doi: 10.6092/1590-8577/1472.
AUTORES / AUTHORS: - Stevenson R; Libutti SK; Saif MW
INSTITUCIÓN / INSTITUTION: - Tufts University School of Medicine. Boston, MA, USA. rstevenson@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Neuroendocrine tumors (NET) are a diverse group of tumors that derive from epithelial cells with neuroendocrine differentiation. Gastroenteropancreatic NETs are a subset of NET that arise from the gastrointestinal tract. The natural history and prognosis varies widely between different gastroenteropancreatic NETs, highlighting the importance of identifying accurate prognostic and predictive biomarkers. At the 2013 ASCO Gastrointestinal Cancers Symposium, De Braud et al. (Abstract #186) and Bellister et al. (Abstract #163) present data on two new possible biomarkers.
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[354]
TÍTULO / TITLE: - X-Ray Phase-Contrast CT of a Pancreatic Ductal Adenocarcinoma Mouse Model.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(3):e58439. doi: 10.1371/journal.pone.0058439. Epub 2013 Mar 11.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0058439
AUTORES / AUTHORS: - Tapfer A; Braren R; Bech M; Willner M; Zanette I; Weitkamp T; Trajkovic-Arsic M; Siveke JT; Settles M; Aichler M; Walch A; Pfeiffer F
INSTITUCIÓN / INSTITUTION: - Department of Physics and Institute of Medical Engineering, Technische Universitat Munchen, Garching, Germany.
RESUMEN / SUMMARY: - To explore the potential of grating-based x-ray phase-contrast computed tomography (CT) for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i) high-resolution synchrotron radiation (SR) imaging and ii) dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i) high-performance imaging for virtual microscopy applications and ii) biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI) were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR) of selected regions of interest (ROI) in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications.
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[355]
TÍTULO / TITLE: - Type IV collagen stimulates pancreatic cancer cell proliferation, migration, and inhibits apoptosis through an autocrine loop.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 26;13(1):154.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-154
AUTORES / AUTHORS: - Ohlund D; Franklin O; Lundberg E; Lundin C; Sund M
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic cancer shows a highly aggressive and infiltrative growth pattern and is characterized by an abundant tumor stroma known to interact with the cancer cells, and to influence tumor growth and drug resistance. Cancer cells actively take part in the production of extracellular matrix proteins, which then become deposited into the tumor stroma. Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. In this study, the cellular effects of type IV collagen produced by the cancer cells were characterized. METHODS: The expression of type IV collagen and its integrin receptors were examined in vivo in human pancreatic cancer tissue. The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule. RESULTS: We show that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. Furthermore, the interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis. CONCLUSION: We show that type IV collagen provides essential cell survival signals to the pancreatic cancer cells through an autocrine loop.
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[356]
TÍTULO / TITLE: - Anatomical localization of insulinomas: still a need to combine a set of diagnostic procedures.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Hormones (Athens). 2012 Oct;11(4):483-7.
AUTORES / AUTHORS: - Tamagno G; O’Shea D
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology & Diabetes Mellitus, St Vincent’s University Hospital - University College Dublin, Ireland.
RESUMEN / SUMMARY: - The diagnosis of insulinoma is based on universally defined clinical and laboratory parameters (Whipple triad and fasting test). Pre-operative tumor localization is the main challenge in the diagnostic management of insulinomas. The pre-operative and/or intra-operative localization of the tumor is required for the optimal surgical approach. We describe two cases of insulinoma characterized by a typical clinical presentation, a positive diagnosis on fasting test, and computerized tomography failure in localizing the tumor. In the first patient, angiography with hepatic venous sampling after calcium stimulation correctly localized pre-operatively the region of the pancreas where the tumor was and, following intra-operative investigations, the lesion was successfully enucleated. In the second patient, angiography with hepatic venous sampling after calcium stimulation failed to identify the region of the insulinoma, which was detected by intra-operative ultrasound and successfully enucleated. Invasive pre-operative procedures for tumor regionalization and/or localization (angiography with hepatic venous sampling after calcium stimulation, endoscopic ultrasound) should be performed in cases where the tumor cannot be localized with enough certainty by non-invasive imaging. However, a careful intra-operative study should be performed in all patients undergoing surgery to complete the information obtained pre-operatively and to exclude the presence of other smaller lesions.
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[357]
TÍTULO / TITLE: - Cystic and ductal tumors of the pancreas: Diagnosis and management.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Visc Surg. 2013 Mar 18. pii: S1878-7886(13)00013-1. doi: 10.1016/j.jviscsurg.2013.02.003.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jviscsurg.2013.02.003
AUTORES / AUTHORS: - Scoazec JY; Vullierme MP; Barthet M; Gonzalez JM; Sauvanet A
INSTITUCIÓN / INSTITUTION: - Anatomie pathologique et centre de recherche en cancerologie de Lyon, Inserm U1052/CNRS UMR5286, hospices civils de Lyon, hopital Edouard-Herriot, 69437 Lyon cedex 03, France.
RESUMEN / SUMMARY: - Incidentally discovered cystic tumors of the pancreas (CTP) are an increasingly frequent entity. It is essential to differentiate lesions whose malignant potential is either nil or negligible (pseudocyst, serous cystadenoma, simple cysts) from lesions with intermediate malignant potential (intraductal papillary mucinous tumor of the pancreas [IPMN] involving the secondary ducts, cystic endocrine tumor) or those with high malignant potential (mucinous cystadenoma, solid pseudopapillary tumors and IPMN involving the main pancreatic duct). The approach to defining malignant potential is based on diagnostic CT scan, magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), often complemented by EUS-guided cyst puncture for biochemical and cytological analysis of cyst fluid. Surgery for diagnostic purposes should be avoided because of its significant morbidity. For pseudocysts, simple cysts and serous cystadenomas, abstention is the general rule. Resection, preserving as much pancreatic parenchyma as possible, is the rule for IPMN involving the main pancreatic duct, mucinous cystadenomas, solid and pseudopapillary tumors, and cystic endocrine tumors. Resection is rarely indicated at the outset for IPMN involving secondary pancreatic ducts; morphologic observation is the general rule and preventive excision may be indicated secondarily. Good collaboration between surgeons, radiologists and endosonographists is necessary for optimal management of CTP.
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[358]
TÍTULO / TITLE: - Pancreatic cyst fluid analysis for differential diagnosis between benign and malignant lesions.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Feb;5(2):613-616. Epub 2012 Dec 12.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2012.1071
AUTORES / AUTHORS: - Talar-Wojnarowska R; Pazurek M; Durko L; Degowska M; Rydzewska G; Smigielski J; Janiak A; Olakowski M; Lampe P; Grzelak P; Stefanczyk L; Malecka-Panas E
INSTITUCIÓN / INSTITUTION: - Department of Digestive Tract Diseases, Medical University, Lodz 90-153;
RESUMEN / SUMMARY: - The majority of pancreatic cysts are detected incidentally when abdominal imaging is performed during unrelated procedures. The aim of the present study was to assess the diagnostic utility and clinical value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and amylase analysis in pancreatic cyst fluid. The study included 52 patients with pancreatic cystic lesions, who underwent fine-needle aspiration biopsy to collect cystic fluid for cytological and biochemical analysis. Cysts were classified as benign (simple cysts, pseudocysts and serous cystadenomas) in 36 patients or premalignant/malignant (mucinous cyst-adenomas, intraductal papillary mucinous neoplasm and cystadenocarcinomas) in 16 patients. CEA and CA 19-9 were elevated in patients with malignant cysts (238+/-12.5 ng/ml and 222+/-31.5 U/ml, respectively) compared with benign lesions (34.5+/-3.7 ng/ml and 18.5+/-1.9 U/ml, respectively; P<0.001). Based on these results, the sensitivity and specificity of CEA were 91.8 and 63.9% and of CA 19-9 were 81.3 and 69.4%, respectively. Mean amylase levels in benign lesions (27825.7+/-91.9 U/l) were higher compared with malignant pancreatic cysts (8359.2+/-32.7 U/l; P<0.05). Cyst fluid analysis may prove a safe and useful adjunct for the differential diagnosis of pancreatic cystic lesions. In the present study, promising results for CEA and CA 19-9 have been demonstrated, however, the clinical value of these molecules must be confirmed.
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[359]
TÍTULO / TITLE: - Pancreatic cancer: FDG-PET is not useful in early pancreatic cancer diagnosis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Gastroenterol Hepatol. 2013 Apr;10(4):203-5. doi: 10.1038/nrgastro.2013.42. Epub 2013 Mar 12.
●● Enlace al texto completo (gratuito o de pago) 1038/nrgastro.2013.42
AUTORES / AUTHORS: - Strobel O; Buchler MW
INSTITUCIÓN / INSTITUTION: - Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
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[360]
TÍTULO / TITLE: - Potentials of plasma NGAL and MIC-1 as biomarker(s) in the diagnosis of lethal pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55171. doi: 10.1371/journal.pone.0055171. Epub 2013 Feb 1.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055171
AUTORES / AUTHORS: - Kaur S; Chakraborty S; Baine MJ; Mallya K; Smith LM; Sasson A; Brand R; Guha S; Jain M; Wittel U; Singh SK; Batra SK
INSTITUCIÓN / INSTITUTION: - Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
RESUMEN / SUMMARY: - Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-beta family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91) and compared it with those in healthy control (HC) individuals (n = 24) and patients with chronic pancreatitis (CP, n = 23). The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (+/- standard deviation, SD) plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2), 219.2 U/mL (7.8) and 4.5 ng/mL (4.1), respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81%) but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively). For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively). CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage ½) pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml). Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029). Overall, MIC-1 in combination with CA19-9 improved the diagnostic accuracy of differentiating PC from CP and HCs.
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[361]
TÍTULO / TITLE: - Silencing of B7-H3 increases gemcitabine sensitivity by promoting apoptosis in pancreatic carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncol Lett. 2013 Mar;5(3):805-812. Epub 2013 Jan 8.
●● Enlace al texto completo (gratuito o de pago) 3892/ol.2013.1118
AUTORES / AUTHORS: - Zhao X; Zhang GB; Gan WJ; Xiong F; Li Z; Zhao H; Zhu DM; Zhang B; Zhang XG; Li DC
INSTITUCIÓN / INSTITUTION: - Departments of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
RESUMEN / SUMMARY: - In numerous types of cancer, the expression of a novel member of the B7 ligand family, the B7-H3 immunoregulatory protein, has been correlated with a poor prognosis. In the present study, we investigated the role of B7-H3 in chemoresistance in pancreatic carcinoma. Silencing of B7-H3, through lentivirus-mediated delivery of stable short hairpin RNA, was observed to increase the sensitivity of the human pancreatic carcinoma cell line Patu8988 to gemcitabine as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 caused the cancer cells to be more resistant to the drug. Subsequently, we investigated the underlying mechanisms of B7-H3-mediated gemcitabine resistance, and found that the levels of survivin decreased in cells in which B7-H3 had been knocked down. In vivo animal experiments demonstrated that tumors in which B7-H3 had been knocked down displayed a slower growth rate compared with the control xenografts. Notably, gemcitabine treatment led to a strong antitumor activity in mice with tumors in which B7-H3 had been knocked down; however, this effect was only marginal in the control group. Furthermore, survivin expression was weak in gemcitabine-treated tumors in which B7-H3 had been knocked down and apoptosis was increased, as revealed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining. In summary, the present study demonstrated that B7-H3 induces gemcitabine resistance in pancreatic carcinoma cells, at least partially by downregulating survivin expression. These results provide novel insights into the function of B7-H3 and encourage the design and investigation of approaches targeting this protein in treating pancreatic carcinoma.
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[362]
TÍTULO / TITLE: - Bilateral thoracic splanchnic nerve radiofrequency thermocoagulation for the management of end-stage pancreatic abdominal cancer pain.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pain Physician. 2013 Mar;16(2):125-33.
AUTORES / AUTHORS: - Papadopoulos D; Kostopanagiotou G; Batistaki C
INSTITUCIÓN / INSTITUTION: - 2nd Department of Anesthesiology, School of Medicine, University of Athens, “Attikon” Hospital, Athens, Greece.
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic cancer pain is often severe and refractory to conservative therapies. Several interventional techniques have been described for the management of end-stage pancreatic cancer pain, with variable results and complications. OBJECTIVES: The aim of this study was to assess the efficacy of bilateral radiofrequency thermocoagulation of splanchnic nerves for pain relief, the consumption of opioids, and the quality of life in patients suffering from severe pain due to pancreatic malignancies. STUDY DESIGN: A retrospective observational design. SETTING: The study includes patients with end-stage pancreatic abdominal cancer pain, which is refractory to conservative treatment. METHODS: Thirty-five patients were studied. They were evaluated prior to and after the radiofrequency thermocoagulation of both splanchnic nerves under fluoroscopic guidance. The assessment included the pain intensity (Numeric Rating Scale 0 - 10), quality of life (self-reported quality of life score 0 - 10), and 24-hour consumption of opioids with monthly follow-up visits until the end of life. RESULTS: Follow-up was completed 6 months after the intervention. The pain scores, quality of life, and consumption of opioids were significantly improved during the entire follow-up period. A slight deterioration was noticed during the fifth month because of malignancy progression. No complications that could be attributed to the technique were observed. LIMITATIONS: The study was not prospective and does not have a control group with a different intervention for comparisons. CONCLUSION: Radiofrequency thermocoagulation of both splanchnic nerves may offer a safe and effective technique for pain management and quality of life improvement in patients with end-stage pancreatic cancer towards the end of life.
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[363]
TÍTULO / TITLE: - Obstructive jaundice caused by pancreatic head malignancies are there predictive factors for successful endoscopic biliary stenting?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Prilozi. 2012 Dec;33(2):59-71.
AUTORES / AUTHORS: - Deriban G; Andreevski B; Mishevski J; Krstevski M; Trajkovska M; Popova R; Joksimovic N; Serafimoski V
INSTITUCIÓN / INSTITUTION: - University Gastroenterohepatology Clinic, Medical Faculty, Skopje, R. Macedonia.
RESUMEN / SUMMARY: - (Full text is available at manu.edu.mk/prilozi). Endoscopic retrograde cholangiopancreatography provides precise imaging of malignant biliopancreatic strictures and allows palliative treatment with endoscopic stenting. Initial successful biliary stenting can be achieved in about 69-100% of patients with pancreatic head malignancies. Preliminary data from our Clinic reported a much lower success rate of endoscopic biliary stenting in obstructive jaundice caused by pancreatic head malignancies. These findings may be because patients are referred at more advanced stages, which could contribute to the lower success rate of biliary stenting. We aimed to determine the success rate of endoscopic biliary stenting prospectively in 50 patients with pancreatic head malignancies and to asses if clinical, laboratory and ultrasound findings can be predictive of success and safety in biliary stenting. Initial successful biliary stenting was achieved in 70% of our patients. No major complications (perforation, severe pancreatitis, massive bleeding, death) were noted. We were able to identify factors predictive of a lower success rate which were associated with a more advanced disease and a longer delay before treatment. Based on our results, we conclude that ERCP should be offered without delay as a primary treatment option for all patients with unresectable pancreatic head malignancy and as a possible treatment option in patients with resectable malignancy who are poor candidates for surgery. Key words: Pancreatic head malignancy, obstructive jaundice, endoscopic biliary stenting.
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[364]
TÍTULO / TITLE: - Molecular analysis of precursor lesions in familial pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54830. doi: 10.1371/journal.pone.0054830. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054830
AUTORES / AUTHORS: - Crnogorac-Jurcevic T; Chelala C; Barry S; Harada T; Bhakta V; Lattimore S; Jurcevic S; Bronner M; Lemoine NR; Brentnall TA
INSTITUCIÓN / INSTITUTION: - Molecular Oncology Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom. T.C.Jurcevic@qmul.ac.uk
RESUMEN / SUMMARY: - BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC) is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic pancreatic adenocarcinoma.
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[365]
TÍTULO / TITLE: - Signaling via MYD88 in the pancreatic tumor microenvironment: A double-edged sword.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Oncoimmunology. 2013 Jan 1;2(1):e22567.
●● Enlace al texto completo (gratuito o de pago) 4161/onci.22567
AUTORES / AUTHORS: - Zambirinis CP; Miller G
INSTITUCIÓN / INSTITUTION: - Department of Surgery; S. Arthur Localio Laboratory; New York University School of Medicine; New York, NY USA.
RESUMEN / SUMMARY: - We have recently shown that Toll-like receptor (TLR) signaling exacerbates pancreatic fibro-inflammation and promotes carcinogenesis in mice. Paradoxically, inhibition of the TLR-MYD88 signaling pathway is pro-tumorigenic owing to the dendritic cell-mediated TH2-polarization of CD4+ T cells. TLR signaling appears to be central in pancreatic cancer-associated inflammation.
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[366]
TÍTULO / TITLE: - 3D pancreatic carcinoma spheroids induce a matrix-rich, chemoresistant phenotype offering a better model for drug testing.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Feb 27;13:95. doi: 10.1186/1471-2407-13-95.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-95
AUTORES / AUTHORS: - Longati P; Jia X; Eimer J; Wagman A; Witt MR; Rehnmark S; Verbeke C; Toftgard R; Lohr M; Heuchel RL
INSTITUCIÓN / INSTITUTION: - CLINTEC, Karolinska Institutet, Stockholm 14186, Sweden. matthias.lohr@ki.se.
RESUMEN / SUMMARY: - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer related death. It is lethal in nearly all patients, due to an almost complete chemoresistance. Most if not all drugs that pass preclinical tests successfully, fail miserably in the patient. This raises the question whether traditional 2D cell culture is the correct tool for drug screening. The objective of this study is to develop a simple, high-throughput 3D model of human PDAC cell lines, and to explore mechanisms underlying the transition from 2D to 3D that might be responsible for chemoresistance. METHODS: Several established human PDAC and a KPC mouse cell lines were tested, whereby Panc-1 was studied in more detail. 3D spheroid formation was facilitated with methylcellulose. Spheroids were studied morphologically, electron microscopically and by qRT-PCR for selected matrix genes, related factors and miRNA. Metabolic studies were performed, and a panel of novel drugs was tested against gemcitabine. RESULTS: Comparing 3D to 2D cell culture, matrix proteins were significantly increased as were lumican, SNED1, DARP32, and miR-146a. Cell metabolism in 3D was shifted towards glycolysis. All drugs tested were less effective in 3D, except for allicin, MT100 and AX, which demonstrated effect. CONCLUSIONS: We developed a high-throughput 3D cell culture drug screening system for pancreatic cancer, which displays a strongly increased chemoresistance. Features associated to the 3D cell model are increased expression of matrix proteins and miRNA as well as stromal markers such as PPP1R1B and SNED1. This is supporting the concept of cell adhesion mediated drug resistance.
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[367]
TÍTULO / TITLE: - Solid pseudopapillary tumor of the pancreas and concomitant urogenital malformations in a young woman.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Diagn Pathol. 2013 Feb 27;8:35. doi: 10.1186/1746-1596-8-35.
●● Enlace al texto completo (gratuito o de pago) 1186/1746-1596-8-35
AUTORES / AUTHORS: - Guan ZW; Sun L; Wang YQ; Xu BX
INSTITUCIÓN / INSTITUTION: - Department of Nuclear Medicine, Chinese PLA General Hospital, Ruxing road 28, Beijing 100853, China. xbx301@yahoo.com.
RESUMEN / SUMMARY: - Solid pseudopapillary tumor (SPT) of the pancreas is a rare pancreatic tumor with low malignant potential. It occurs characteristically more often in young women. SPT associated with extra- and pancreatic anomalies are occasionally reported. Here we report a case of pancreatic SPT with concomitant urogenital malformations including solitary kidney and uterus didelphys in a 25-year-old woman. The patient underwent central pancreatectomy, and SPT was confirmed with pathological results. Recurrence or metastasis was not found after 14 months of follow-up. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: diagnosticpathology.diagnomx.eu/vs/4264758678755142.
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[368]
TÍTULO / TITLE: - An insulinoma presenting as hypoglycaemia associated with exercise stress testing.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - British Medical J (BMJ). Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista bmj.com/search.dtl
●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Feb 18;2013. pii: bcr2012008436. doi: 10.1136/bcr-2012-008436.
●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008436
AUTORES / AUTHORS: - Lainis F; Fahy E; Murphy M
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology, South Infirmary Victoria University Hospital, Cork, Ireland.
RESUMEN / SUMMARY: - A 68-year-old man presented to the accident and emergency department with a history of central chest pain associated with exertion. He was admitted for assessment and when an acute coronary syndrome was excluded, he underwent exercise stress testing. His exercise stress testing was discontinued due to lightheadedness. His capillary glucose was checked and it showed hypoglycaemia (2.2 mmol/l). In light of this, a 72 h supervised fast was performed and it became positive within 24 h with low plasma glucose, inappropriately high insulin and C peptide levels. Sulfonylurea screen was negative. CT, MRI and endoscopic ultrasound revealed a 2 cm pancreatic tail insulinoma. He underwent successful surgical enucleation of this lesion.
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[369]
TÍTULO / TITLE: - The ace of spades: reverse takotsubo cardiomyopathy in the context of angiographic embolization of recurrent metastatic serotonin-positive neuroendocrine tumour of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Med. 2013;2013:793193. doi: 10.1155/2013/793193. Epub 2013 Feb 7.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/793193
AUTORES / AUTHORS: - Mazzetti IA; Marcaccio MJ; Boutross-Tadross O; Salehian O; Demers C
INSTITUCIÓN / INSTITUTION: - McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1.
RESUMEN / SUMMARY: - A 62-year-old woman undergoing embolization of recurrent neuroendocrine tumor, positive for serotonin, developed chest pain and bradycardia with lateral ST-segment depression. Cardiac biomarkers were elevated, and echocardiography revealed akinesis of all basal segments with a normally contracting apex. The absence of flow-limiting coronary disease on angiography confirmed the presence of reverse Takotsubo cardiomyopathy. After optimal medical therapy for six weeks, left ventricular function returned to normal. Takotsubo cardiomyopathy has been described across a wide variety of hyperadrenergic states; the description of the reverse-type Takotsubo cardiomyopathy in the setting of embolization of recurrent neuroendocrine with serotonergic positivity tumour is novel.
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[370]
TÍTULO / TITLE: - Isolated fat-containing pancreatic metastasis from hepatocellular carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Jpn J Radiol. 2013 Mar 29.
●● Enlace al texto completo (gratuito o de pago) 1007/s11604-013-0193-9
AUTORES / AUTHORS: - Nishiofuku H; Marugami N; Tanaka T; Anai H; Maeda S; Masada T; Takano M; Mitoro A; Kichikawa K
INSTITUCIÓN / INSTITUTION: - Department of Radiology, Nara Medical University, 840 Shijo-cho, Nara, Kashihara, 634-8522, Japan, nishiofukuhideyuki@yahoo.co.jp.
RESUMEN / SUMMARY: - We report a case of a 50-year-old male with isolated pancreatic metastasis from hepatocellular carcinoma (HCC), in which chemical shift magnetic resonance imaging detected the presence of fat, and which mimicked fatty replacement. A solitary metastatic pancreatic tumor originating from HCC is very rare. Furthermore, we believe that this is the first report of fat-containing pancreatic metastasis from HCC.
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[371]
TÍTULO / TITLE: - Enzyme inhibition of dopamine metabolism alters 6-[18 F]FDOPA uptake in orthotopic pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - EJNMMI Res. 2013 Mar 14;3(1):18.
●● Enlace al texto completo (gratuito o de pago) 1186/2191-219X-3-18
AUTORES / AUTHORS: - Tuomela J; Forsback S; Haavisto L; Vahlberg T; Gronroos TJ; Solin O; Haaparanta-Solin M
RESUMEN / SUMMARY: - BACKGROUND: An unknown location hampers removal of pancreatic tumours. We studied the effects of enzyme inhibitors on the uptake of 6-[18F]fluoro-l-3,4-dihydroxyphenylalanine ([18F]FDOPA) in the pancreas, aiming at improved imaging of pancreatic adenocarcinoma. METHODS: Mice bearing orthotopic BxPC3 pancreatic adenocarcinoma were injected with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and scanned with positron emission tomography/computed tomography (PET/CT). For [18F]FDOPA studies, tumour-bearing mice and sham-operated controls were pretreated with enzyme inhibitors of aromatic amino acid decarboxylase (AADC), catechol-O-methyl transferase (COMT), monoamine oxidase A (MAO-A) or a combination of COMT and MAO-A. Mice were injected with [18F]FDOPA and scanned with PET/CT. The absolute [18F]FDOPA uptake was determined from selected tissues using a gamma counter. The intratumoural biodistribution of [18F]FDOPA was recorded by autoradiography. The main [18F]FDOPA metabolites present in the pancreata were determined with radio-high-performance liquid chromatography. RESULTS: [18F]FDG uptake was high in pancreatic tumours, while [18F]FDOPA uptake was highest in the healthy pancreas and significantly lower in tumours. [18F]FDOPA uptake in the pancreas was lowest with vehicle pretreatment and highest with pretreatment with the inhibitor of AADC. When mice received COMT + MAO-A inhibitors, the uptake was high in the healthy pancreas but low in the tumour-bearing pancreas. CONCLUSIONS: Combined use of [18F]FDG and [18F]FDOPA is suitable for imaging pancreatic tumours. Unequal pancreatic uptake after the employed enzyme inhibitors is due to the blockade of metabolism and therefore increased availability of [18F]FDOPA metabolites, in which uptake differs from that of [18F]FDOPA. Pretreatment with COMT + MAO-A inhibitors improved the differentiation of pancreas from the surrounding tissue and healthy pancreas from tumour. Similar advantage was not achieved using carbidopa.
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[372]
TÍTULO / TITLE: - Laparoscopic resection of pancreatic cystadenomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Arq Bras Cir Dig. 2012 Jul-Sep;25(3):165-8.
AUTORES / AUTHORS: - Farah JF; Lupinacci RM; Apodaca-Torres FR
INSTITUCIÓN / INSTITUTION: - Departamento de Cirurgia Geral e Oncologica, Hospital do Servidor Publico Estadual de Sao Paulo, SP, Brasil. jose.farah@einstein.br
RESUMEN / SUMMARY: - BACKGROUND: Laparoscopic pancreatic resections have become increasingly frequent with good results reported by several centers. However, few studies have focused on laparoscopic treatment of pancreatic cystic lesions. AIM: To analyze the results of minimally invasive treatment of pancreatic cystic lesions. METHODS: Were included all laparoscopic pancreatic resections performed at three centers. Surgical procedures included resection of the pancreas and left enucleations (with or without splenectomy). The post-operative complications were classified according to the classification proposed by Clavien and Dindo6. The diagnosis of pancreatic fistula was confirmed if the amylase dosage of the drainage liquid in the third postoperative day was more than three times the amount of serum amylase. RESULTS: Were performed 44 laparoscopic pancreatic resections. Fifteen patients underwent surgery for suspected pancreatic cystadenoma and 13 had this diagnosis confirmed. There were 12 women (92%), and the average age of patients was 50 years. Six patients had minor postoperative complications. There were five (38%) pancreatic fistulas, neither considered as severe ©, and only one patient required hospital readmission and radiological drainage. In this series, there were no conversions, reoperations, or mortality. CONCLUSIONS: The laparoscopic approach is a safe and effective option for the treatment of pancreatic cystic lesions. The incidence of pancreatic fistula has good evolution and not diminishes the benefits of minimally invasive surgery.
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[373]
TÍTULO / TITLE: - Extensive multiarterial resection attending total duodenopancreatectomy and adrenalectomy for MEN-1-associated neuroendocrine carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - World J Gastrointest Surg. 2012 Oct 27;4(10):238-45. doi: 10.4240/wjgs.v4.i10.238.
●● Enlace al texto completo (gratuito o de pago) 4240/wjgs.v4.i10.238
AUTORES / AUTHORS: - Egorov VI; Kharazov AF; Pavlovskaya AI; Petrov RV; Starostina NS; Kondratiev EV; Filippova EM
INSTITUCIÓN / INSTITUTION: - Vyacheslav Ivanovich Egorov, Sechenov First State Medical University, Ostroumov 14th City Hospital, Department of Surgical Oncology, 117997 Moscow, Russia.
RESUMEN / SUMMARY: - Pancreatic neuroendocrine tumors (PNTs) are relatively uncommon although these neoplasms have been noted to grow in occurrence in recent decades. Surgical removal of locally advanced PNTs involving major vessels and adjacent organs is warranted by reason of an appreciably more favorable prognosis as compared to exocrine pancreas cancer. We are reporting a case of successful multi-organ resection combined with a wide excision of the superior mesenteric, common, proper, left and right hepatic arteries (in the presence of the hepatomesenteric trunk variant of aberrant arterial anatomy) for multifocal PNTs in the setting of multiple neuroendocrine neoplasia type 1 syndrome. The procedure resulted in pain abolition, a significant improvement in the patient’s life quality and allowed her to return to work. Follow-up computed tomography at 15 mo post-surgery showed no evidence of disease recurrence.
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[374]
TÍTULO / TITLE: - New developments in the management of borderline resectable pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):123-5. doi: 10.6092/1590-8577/1473.
AUTORES / AUTHORS: - Sharma J; Ng J; Goodman MD; Saif MW
INSTITUCIÓN / INSTITUTION: - Division of Hematology Oncology, Department of Medicine, Tufts Medical Center. Boston, MA, USA. jsharma@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - The optimal management of borderline resectable pancreatic cancer remains unclear. Neoadjuvant chemoradiation remains the most common approach in the United States, while neoadjuvant chemotherapy alone is also widely utilized and has demonstrated efficacy but there has been no clear consensus about a regimen that would be most beneficial in this setting. We will discuss three abstracts that were presented in the 2013 ASCO Gastrointestinal Cancers Symposium in which various regimens were evaluated in the neoadjuvant setting.
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[375]
TÍTULO / TITLE: - Impact of tumour associated macrophages in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMB Rep. 2013 Mar;46(3):131-8.
AUTORES / AUTHORS: - Mielgo A; Schmid MC
INSTITUCIÓN / INSTITUTION: - Liverpool Cancer Research UK Centre; The National Institute for Health Research Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Prescot Street, Liverpool L7 8XP, UK mschmid@liv.ac.uk.
RESUMEN / SUMMARY: - During cancer progression, bone marrow derived myeloid cells, including immature myeloid cells and macrophages, progressively accumulate at the primary tumour site where they contribute to the establishment of a tumour promoting microenvironment. A marked infiltration of macrophages into the stromal compartment and the generation of a desmoplastic stromal reaction is a particular characteristic of pancreatic ductal adenocarcinoma (PDA) and is thought to play a key role in disease progression and its response to therapy. Tumour associated macrophages (TAMs) foster PDA tumour progression by promoting angiogenesis, metastasis, and by suppressing an anti-tumourigenic immune response. Recent work also suggests that TAMs contribute to resistance to chemotherapy and to the emergence of cancer stem-like cells. Here we will review the current understanding of the biology and the pro-tumourigenic functions of TAMs in cancer and specifically in PDA, and highlight potential therapeutic strategies to target TAMs and to improve current therapies for pancreatic cancer. [BMB Reports 2013; 46(3): 131-138].
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[376]
TÍTULO / TITLE: - Natural history of asymptomatic pancreatic cystic neoplasms.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Mar;15(3):175-81. doi: 10.1111/j.1477-2574.2012.00522.x. Epub 2012 Jul 23.
●● Enlace al texto completo (gratuito o de pago) 1111/j.1477-2574.2012.00522.x
AUTORES / AUTHORS: - Morris-Stiff G; Falk GA; Chalikonda S; Walsh RM
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Section of Surgical Oncology and Hepatopancreatobiliary Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
RESUMEN / SUMMARY: - BACKGROUND: The management of asymptomatic pancreatic cysts is controversial and indications for excision are based on pathology and natural history. OBJECTIVES: This study aimed to examine outcomes of asymptomatic lesions using a protocol based on size and cyst fluid analysis. METHODS: Asymptomatic cysts were identified from a prospectively maintained database. Sequential cross-sectional imaging studies were assessed, and results of endoscopic ultrasound-guided aspiration were co-analysed. RESULTS: A total of 338 asymptomatic patients underwent evaluation. Overall, 84 cysts were <1.5 cm and 254 were >/=1.5 cm in diameter. Median patient follow-up was 5.1 years [interquartile range (IQR): 4.1-6.9 years]. In the group in which cysts measured <1.5 cm in diameter, median cyst size was 1.0 cm (IQR: 0.6-1.2 cm) at presentation and increased to 1.2 cm (IQR: 0.7-1.6 cm) during follow-up. Five (6.0%) patients underwent resection, all within 2 months of presentation. In the group in which cysts measured >/=1.5 cm in diameter, median cyst size was 2.5 cm (IQR: 2.0-3.4 cm) at presentation and increased to 2.7 cm (IQR: 3.0-4.2 cm). A total of 63 (24.8%) patients underwent resection. Surgery was performed with 2 months in 53 (84.1%) patients, within 12 months in four (6.3%) patients and at >12 months post-presentation in six (9.5%) patients. A total of 70.6% of resected specimens were identified as malignancies or mucinous lesions. CONCLUSIONS: Asymptomatic cysts of <1.5 cm in diameter can safely be followed by imaging and are expected to undergo little change. A quarter of all asymptomatic cysts measuring >/=1.5 cm are appropriately resected based on imaging and cyst fluid analysis.
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[377]
TÍTULO / TITLE: - Interest of intraoperative ultrasonography during pancreatectomy for metastatic renal cell carcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Res Hepatol Gastroenterol. 2013 Mar 13. pii: S2210-7401(13)00033-8. doi: 10.1016/j.clinre.2013.01.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.clinre.2013.01.006
AUTORES / AUTHORS: - Facy O; Angot C; Guiu B; Al Samman S; Matte A; Rat P; Ortega-Deballon P
INSTITUCIÓN / INSTITUTION: - Department of Digestive Surgical Oncology, University hospital, 14, rue Gaffarel, 21079 Dijon cedex, France; Inserm 866, Equipe Avenir, Locoregional Therapy in Surgical Oncology, Dijon, France. Electronic address: olivier.facy@chu-dijon.fr.
RESUMEN / SUMMARY: - BACKGROUND: Isolated pancreatic metastases from renal cell carcinoma may be treated by surgical resection in a curative intent. As they are frequently multiple, a good imaging workup is mandatory to plan the appropriate resection. The aim of this study was to define the imaging workup that should be performed in this setting. METHODS: We reviewed all patients who underwent pancreatic resection for metastasis of renal cell carcinoma in a single centre during a 20-year period. The results of the intraoperative ultrasonography were compared to those of the preoperative imaging and the final pathology results. RESULTS: Thirteen patients were studied. A CT scan was always performed whereas only three patients had a MRI (only one revealed another tumor). Intraoperative ultrasonography found new tumors in 50% of patients when it was performed (4/8) and modified the management in 40% of them, while preoperative PET scan was useless. CONCLUSIONS: Intraoperative ultrasonography is a low-cost and non-invasive technique that should be routinely included in the surgical exploration of pancreatic metastases from renal carcinoma.
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[378]
TÍTULO / TITLE: - Comparative Effectiveness of Minimally Invasive and Open Distal Pancreatectomy for Ductal Adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JAMA. Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista jama.ama-assn.org/search.dtl
●● Cita: JAMA: <> Surg. 2013 Feb 20:1-7. doi: 10.1001/jamasurg.2013.1673.
●● Enlace al texto completo (gratuito o de pago) 1001/jamasurg.2013.1673
AUTORES / AUTHORS: - Magge D; Gooding W; Choudry H; Steve J; Steel J; Zureikat A; Krasinskas A; Daouadi M; Lee KK; Hughes SJ; Zeh HJ; Moser AJ
RESUMEN / SUMMARY: - IMPORTANCE Multicenter studies indicate that outcomes of open (ODP) and minimally invasive distal pancreatectomy (MIDP) are equivalent for benign lesions. However, data for pancreatic carcinoma are limited. OBJECTIVE To compare outcomes of ODP and MIDP for early-stage pancreatic ductal carcinoma to determine relative safety and oncologic efficacy. DESIGN Retrospective analysis of 62 consecutive patients undergoing ODP or MIDP for pancreatic ductal carcinoma by intention to treat with propensity scoring to correct for selection bias. SETTING A high-volume university center for pancreatic surgery. PARTICIPANTS Sixty-two patients at a single institution. INTERVENTIONS Patients underwent ODP or MIDP. MAIN OUTCOME MEASURES Perioperative mortality, morbidity, readmission, postoperative complications, disease progression, and overall survival. RESULTS Thirty-four patients underwent ODP, and 28 underwent MIDP with 5 conversions to ODP. No significant differences in age, body mass index, performance status, tumor size, or radiographic stage were identified. High rates of margin-negative resection (ODP, 88%; MIDP, 86%) and median lymph node clearance (ODP, 12; MIDP, 11) were achieved in both groups with equal rates and severity of postoperative complications (ODP, 50%; MIDP, 39%) and pancreatic fistula (ODP, 29%; MIDP, 21%). Despite conversions, intended MIDP was associated with reduced blood loss (P = .006) and length of stay (P = .04). Conversion was associated with a poor histologic grade and positive nodes. Median overall survival for the entire cohort was 19 (95% CI, 14-47) months. Minimally invasive distal pancreatectomy was performed increasingly in later study years and for patients with a higher Charlson-Age Comorbidity Index. Overall survival after ODP or intended MIDP was equivalent after adjusting for comorbidity and year of surgery (relative hazard, 1.11 [95% CI, 0.47-2.62]). CONCLUSIONS AND RELEVANCE We detected no evidence that MIDP was inferior to ODP based on postoperative outcomes or overall survival. This conclusion was verified by propensity score analysis with adjustment for factors affecting selection of operative technique.
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[379]
TÍTULO / TITLE: - Re-occurrence of pancreatic insulinoma: an usual cause of hypoglycaemia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - British Medical J (BMJ). Acceso gratuito al texto completo.
●● Enlace a la Editora de la Revista bmj.com/search.dtl
●● Cita: British Medical J. (BMJ): <> Case Rep. 2013 Feb 1;2013. pii: bcr2012008287. doi: 10.1136/bcr-2012-008287.
●● Enlace al texto completo (gratuito o de pago) 1136/bcr-2012-008287
AUTORES / AUTHORS: - Anwuzia-Iwegbu C; Nadarasa K; Drake W
INSTITUCIÓN / INSTITUTION: - Department of Specialist Endocrine, Barts & The Royal London, UK. c.anwuzia-iwegbu@uea.ac.uk
RESUMEN / SUMMARY: - A 42-year-old woman presented to her general practitioner (GP) with episodes of feeling ‘shaky’ exacerbated by physical exercise and prolonged fast. She was previously diagnosed with an insulinoma in 2006 (serum glucose 1.6 mmol/l, serum insulin 3.1 mIU/l and serum C peptide <165 pmol/l). CT abdomen/transabdominal ultrasound revealed a 1 cm insulinoma in the uncinate process of the pancreas and the patient later underwent pancreatic enucleation in 2006. Postpancreatic enucleation, 72 h fast was negative. The patient remained asymptomatic postoperation and re-presented to a locum GP 6 years later with initial symptoms. She was reviewed during her annual follow-up and, owing to concerns relating to her background, she was admitted to the specialist endocrine department for further investigations. A 72 h fast was positive for hypoglycaemia with serum glucose level 1.8 mmol/l, serum insulin 8.6 mIU/l and serum C peptide 443 pmol/l.
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[380]
TÍTULO / TITLE: - Pancreatic cancer: updates on translational research and future applications.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):145-8. doi: 10.6092/1590-8577/1466.
AUTORES / AUTHORS: - Sarris EG; Syrigos KN; Saif MW
INSTITUCIÓN / INSTITUTION: - Department of Medicine and Cancer Center, Tufts Medical Center. Boston, MA, USA. wsaif@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Pancreatic cancer is one of the most lethal malignancies with a mortality rate almost equal to its incidence. It is ranked as the fourth leading cause of cancer-related deaths in the United States, and despite intensive basic and clinical research over the last few years, the survival benefit for the majority of patients with pancreatic cancer is still disappointing. Due to the absence of specific symptoms and the lack of early detection tests, pancreatic cancer is usually diagnosed at an advanced inoperrable stage and palliative chemotherapy with the purine analogue gemcitabine in combination with the targeted agent erlotinib, remains the mainstay method in the management of these patients. Therefore, there is an imperative need for new findings in the translational research field with prognostic, predictive and therapeutic value. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #141 which investigates the interaction between liver and pancreatic organ damage in patients with pancreatic cancer and the potential contribution of the patatin-like phospholipase domain containing 3 (PNPLA3) gene variation in pancreatic cancer development and on Abstract #149, in which, the prognostic and predictive role of SWI/SNF complex, a chromatin-remodeling complex, is examined. The key role of pharmacogenomics, in terms of predicting response and resistance to chemotherapy in pancreatic cancer patients, is analyzed in Abstract #142 and the contribution of circulating tumor cell detection in the early diagnosis of pancreatic cancer, allowing the avoidance of more invasive procedures like EUS-FNA, is discussed in Abstract #157. Lastly, in Abstract #164, the diagnostic utility of YKL-40 and IL-6 in pancreatic cancer patients is investigated.
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[381]
TÍTULO / TITLE: - Bmi1 enhances tumorigenicity and cancer stem cell function in pancreatic adenocarcinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(2):e55820. doi: 10.1371/journal.pone.0055820. Epub 2013 Feb 20.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0055820
AUTORES / AUTHORS: - Proctor E; Waghray M; Lee CJ; Heidt DG; Yalamanchili M; Li C; Bednar F; Simeone DM
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
RESUMEN / SUMMARY: - BACKGROUND: Bmi1 is an integral component of the Polycomb Repressive Complex 1 (PRC1) and is involved in the pathogenesis of multiple cancers. It also plays a key role in the functioning of endogenous stem cells and cancer stem cells. Previous work implicated a role for cancer stem cells in the pathogenesis of pancreatic cancer. We hypothesized that Bmi1 plays an integral role in enhancing pancreatic tumorigenicity and the function of cancer stem cells in pancreatic ductal adenocarcinoma. METHODS: We measured endogenous Bmi1 levels in primary human pancreatic ductal adenocarcinomas, pancreatic intraepithelial neoplasias (PanINs) and normal pancreas by immunohistochemistry and Western blotting. The function of Bmi1 in pancreatic cancer was assessed by alteration of Bmi1 expression in several cell model systems by measuring cell proliferation, cell apoptosis, in vitro invasion, chemotherapy resistance, and in vivo growth and metastasis in an orthotopic model of pancreatic cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human pancreatic cancer xenografts after Bmi1 silencing. RESULTS: Bmi1 was overexpressed in human PanINs, pancreatic cancers, and in several pancreatic cancer cell lines. Overexpression of Bmi1 in MiaPaCa2 cells resulted in increased proliferation, in vitro invasion, larger in vivo tumors, more metastases, and gemcitabine resistance while opposite results were seen when Bmi1 was silenced in Panc-1 cells. Bmi1 was overexpressed in the cancer stem cell compartment of primary human pancreatic cancer xenografts. Pancreatic tumorspheres also demonstrated high levels of Bmi1. Silencing of Bmi1 inhibited secondary and tertiary tumorsphere formation, decreased primary pancreatic xenograft growth, and lowered the proportion of cancer stem cells in the xenograft tissue. CONCLUSIONS: Our results implicate Bmi1 in the invasiveness and growth of pancreatic cancer and demonstrate its key role in the regulation of pancreatic cancer stem cells.
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[382]
TÍTULO / TITLE: - Primary monophasic synovial sarcoma of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Visc Surg. 2013 Mar 11. pii: S1878-7886(13)00007-6. doi: 10.1016/j.jviscsurg.2013.01.006.
●● Enlace al texto completo (gratuito o de pago) 1016/j.jviscsurg.2013.01.006
AUTORES / AUTHORS: - Luc G; Collet D; Reich S; Stanislas S; Sa-Cunha A
INSTITUCIÓN / INSTITUTION: - Service de chirurgie digestive et coelioscopique, avenue de Magellan, 33604 Pessac cedex, France. Electronic address: guillaume.luc33@yahoo.fr.
RESUMEN / SUMMARY: - We report a case of synovial sarcoma of the pancreas in a 44-year-old male who presented with multiple episodes of retroperitoneal hemorrhage; the diagnosis was confirmed by histology. The patient underwent distal pancreatectomy without complication, and the hospital stay was nine days. No adjuvant treatment was administered. The patient is alive at 1 year.
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[383]
TÍTULO / TITLE: - Basic equations and computing procedures for frailty modeling of carcinogenesis: application to pancreatic cancer data.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Inform. 2013;12:67-81. doi: 10.4137/CIN.S8063. Epub 2013 Feb 18.
●● Enlace al texto completo (gratuito o de pago) 4137/CIN.S8063
AUTORES / AUTHORS: - Mdzinarishvili T; Sherman S
INSTITUCIÓN / INSTITUTION: - Eppley Cancer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
RESUMEN / SUMMARY: - Modeling of cancer hazards at age t deals with a dichotomous population, a small part of which (the fraction at risk) will get cancer, while the other part will not. Therefore, we conditioned the hazard function, h(t), the probability density function (pdf), f(t), and the survival function, S(t), on frailty alpha in individuals. Assuming alpha has the Bernoulli distribution, we obtained equations relating the unconditional (population level) hazard function, hU (t), cumulative hazard function, HU (t), and overall cumulative hazard, H0, with the h(t), f(t), and S(t) for individuals from the fraction at risk. Computing procedures for estimating h(t), f(t), and S(t) were developed and used to fit the pancreatic cancer data collected by SEER9 registries from 1975 through 2004 with the Weibull pdf suggested by the Armitage-Doll model. The parameters of the obtained excellent fit suggest that age of pancreatic cancer presentation has a time shift about 17 years and five mutations are needed for pancreatic cells to become malignant.
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[384]
TÍTULO / TITLE: - Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer rarely leads to radiological evidence of tumour regression.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2012 Dec 2. doi: 10.1111/hpb.12015.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12015
AUTORES / AUTHORS: - Dudeja V; Greeno EW; Walker SP; Jensen EH
INSTITUCIÓN / INSTITUTION: - Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
RESUMEN / SUMMARY: - BACKGROUND: Neo-adjuvant chemo-radiotherapy has been proposed to improve resectability of locally-advanced pancreatic cancer (LAPC). However, the ability of neo-adjuvant therapy to induce radiological tumour regression has not been reported. METHODS: Pre- and post-treatment computed tomography (CT) scans of patients undergoing neo-adjuvant chemo-radiotherapy for LAPC were reviewed. LAPC was sub-classified into borderline resectable disease [</=180 degrees involvement of the superior mesenteric artery (SMA); short-segment encasement/abutment of the common hepatic artery; or tumour-associated deformity, abutment or short-segment occlusion of the superior mesenteric vein (SMV)/ portal vein (PV) that was amenable to vascular resection and reconstruction] and locally advanced un-resectable pancreatic cancer (vascular involvement more than that described for borderline resectable pancreatic cancer). The radiological response and surgical resection rates were assessed. RESULTS: Sixteen patients received neo-adjuvant therapy for LAPC during 2005-2008. Regression of major vascular involvement, i.e. un-encasement or regression of abutment of any involved vessels was not observed in any patient. Pre- and post-treatment tumour densities were not statistically different. Fifty per cent of patients with borderline resectable disease and none of the patients with locally advanced un-resectable pancreatic cancer eventually underwent surgical resection. CONCLUSION: Neo-adjuvant treatment does not induce radiological tumour regression of LAPC with major vascular involvement. Patient selection for neo-adjuvant trial enrolment should remain focused on borderline disease which may have a potential for surgical resection.
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[385]
TÍTULO / TITLE: - Pancreaticoduodenectomy following chemoradiotherapy for locally advanced adenocarcinoma of the pancreatic head.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Jan 10. doi: 10.1111/hpb.12039.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12039
AUTORES / AUTHORS: - Denost Q; Laurent C; Adam JP; Capdepont M; Vendrely V; Collet D; Sa Cunha A
INSTITUCIÓN / INSTITUTION: - University Hospital Centre (CHU) Bordeaux, Haut-Leveque Hospital, Digestive Surgery, Bordeaux, France; CHU Bordeaux, Saint-Andre Hospital, Digestive Surgery, Bordeaux, France.
RESUMEN / SUMMARY: - OBJECTIVES: The aim of this study was to assess oncological outcomes in patients treated with pancreaticoduodenectomy for advanced pancreatic head adenocarcinoma after preoperative chemoradiotherapy and to compare these with outcomes in patients treated with surgery alone. METHODS: From 2004 to 2009, patients treated with pancreaticoduodenectomy for pancreatic head adenocarcinoma were included in a retrospective comparative study. Patients with locally advanced adenocarcinoma were treated with preoperative chemoradiotherapy (CRT group) and were compared with those treated with surgery alone (SURG group). RESULTS: A total of 111 patients were included; these comprised 72 patients in the SURG group and 39 patients in the CRT group. The median follow-up was 21 months. Patients in the CRT group presented with a more advanced tumoral status. Microscopic resection rates were similar in both groups, but nodal status and vascular or lymphatic emboli were lower in the CRT group. At 3 years, the SURG and CRT groups exhibited similar overall (36% and 51%, respectively) and disease-free (35% and 37%, respectively) survival (P = 0.10). CONCLUSIONS: In patients with advanced pancreatic head adenocarcinoma, a good response after preoperative chemoradiotherapy results in a survival rate similar to that in patients treated with surgery alone in whom the initial prognosis is better.
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[386]
TÍTULO / TITLE: - Nestin and its emerging role in tumor progression and carcinogenesis in systemic tumors besides pancreatic carcinomas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Med Mol Morphol. 2013 Mar;46(1):56-7. doi: 10.1007/s00795-013-0022-3. Epub 2013 Feb 16.
●● Enlace al texto completo (gratuito o de pago) 1007/s00795-013-0022-3
AUTORES / AUTHORS: - Kapoor S
INSTITUCIÓN / INSTITUTION: - , Mechanicsville, VA, USA, shailendrakapoor@yahoo.com.
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[387]
TÍTULO / TITLE: - Microinvasion of high-grade pancreatic intraepithelial neoplasia.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Case Rep Gastroenterol. 2013 Jan;7(1):30-6. doi: 10.1159/000346693. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1159/000346693
AUTORES / AUTHORS: - Kawada N; Uehara H; Takada R; Yamai T; Fukutake N; Katayama K; Takenaka A; Nagata S; Tomita Y
INSTITUCIÓN / INSTITUTION: - Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
RESUMEN / SUMMARY: - High-grade pancreatic intraepithelial neoplasia (PanIN-3) is recognized as a precursor lesion of invasive ductal carcinoma (IDC). However, histological evidence that PanIN-3 invades beyond the basement membrane of pancreatic ductal epithelium, that is, the moment PanIN-3 becomes IDC, has not been captured yet. This may be because PanINs which are microscopic papillary or flat lesion rarely develop clinical symptoms and are not detectable on imaging examination. On the other hand, most IDCs were found in the advanced stage with massive invasion. In this report, PanIN-3 obstructed several branch pancreatic ducts and subsequently caused pancreatitis which developed clinical symptom and was detectable as a pancreatic mass in imaging studies. A 65-year-old woman was referred to our institution for further examination of her repeated pancreatitis. Abdominal ultrasound revealed a low echoic mass of 13 mm in diameter in the pancreatic body without upstream dilatation of the main pancreatic duct (MPD). Endoscopic retrograde pancreatography showed a strictured segment of 2 mm in length in the MPD at the pancreatic body. Cytological examination of pancreatic juice revealed adenocarcinoma and distal pancreatectomy was performed. A resected specimen revealed a whitish mass of 15 mm in diameter in the pancreatic body, which was identified as pancreatitis by histological examination. Papillary growth of PanIN-3 was seen mainly in the branch ducts. Each PanIN-3 was located separately in the branch ducts with normal epithelia in the MPD between them. In three adjacent branch ducts, PanIN-3 was observed to be invading microscopically beyond the basement membrane.
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[388]
TÍTULO / TITLE: - Giant serous microcystic pancreas adenoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Rare Tumors. 2012 Oct 10;4(4):e56. doi: 10.4081/rt.2012.e56. Epub 2012 Dec 10.
●● Enlace al texto completo (gratuito o de pago) 4081/rt.2012.e56
AUTORES / AUTHORS: - Dikmen K; Bostanci H; Yildirim AC; Sakrak O; Kerem M
INSTITUCIÓN / INSTITUTION: - Turkish Ministry of Health, Dr. Nafiz Korez Sincan State Hospital General Surgery Clinic, Ankara;
RESUMEN / SUMMARY: - Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11x9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12x11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient’s symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.
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[389]
TÍTULO / TITLE: - What is recent in pancreatic cancer immunotherapy?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Biomed Res Int. 2013;2013:492372. doi: 10.1155/2013/492372. Epub 2012 Dec 26.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/492372
AUTORES / AUTHORS: - Niccolai E; Prisco D; D’Elios MM; Amedei A
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, University of Florence and Patologia Medica Unit Department of Biomedicine, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, Italy.
RESUMEN / SUMMARY: - Pancreatic cancer (PC) represents an unresolved therapeutic challenge, due to the poor prognosis and the reduced response to currently available treatments. Pancreatic cancer is the most lethal type of digestive cancers, with a median survival of 4-6 months. Only a small proportion of PC patients is curative by surgical resection, whilst standard chemotherapy for patients in advanced disease generates only modest effects with considerable toxic damages. Thus, new therapeutic approaches, specially specific treatments such as immunotherapy, are needed. In this paper we analyze recent preclinical and clinical efforts towards immunotherapy of pancreatic cancer, including passive and active immunotherapy approaches, designed to target pancreatic-cancer-associated antigens and to elicit an antitumor response in vivo.
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[390]
TÍTULO / TITLE: - A PK2/Bv8/PROK2 antagonist suppresses tumorigenic processes by inhibiting angiogenesis in glioma and blocking myeloid cell infiltration in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - PLoS One. 2013;8(1):e54916. doi: 10.1371/journal.pone.0054916. Epub 2013 Jan 23.
●● Enlace al texto completo (gratuito o de pago) 1371/journal.pone.0054916
AUTORES / AUTHORS: - Curtis VF; Wang H; Yang P; McLendon RE; Li X; Zhou QY; Wang XF
INSTITUCIÓN / INSTITUTION: - Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.
RESUMEN / SUMMARY: - Infiltration of myeloid cells in the tumor microenvironment is often associated with enhanced angiogenesis and tumor progression, resulting in poor prognosis in many types of cancer. The polypeptide chemokine PK2 (Bv8, PROK2) has been shown to regulate myeloid cell mobilization from the bone marrow, leading to activation of the angiogenic process, as well as accumulation of macrophages and neutrophils in the tumor site. Neutralizing antibodies against PK2 were shown to display potent anti-tumor efficacy, illustrating the potential of PK2-antagonists as therapeutic agents for the treatment of cancer. In this study we demonstrate the anti-tumor activity of a small molecule PK2 antagonist, PKRA7, in the context of glioblastoma and pancreatic cancer xenograft tumor models. For the highly vascularized glioblastoma, PKRA7 was associated with decreased blood vessel density and increased necrotic areas in the tumor mass. Consistent with the anti-angiogenic activity of PKRA7 in vivo, this compound effectively reduced PK2-induced microvascular endothelial cell branching in vitro. For the poorly vascularized pancreatic cancer, the primary anti-tumor effect of PKRA7 appears to be mediated by the blockage of myeloid cell migration/infiltration. At the molecular level, PKRA7 inhibits PK2-induced expression of certain pro-migratory chemokines and chemokine receptors in macrophages. Combining PKRA7 treatment with standard chemotherapeutic agents resulted in enhanced effects in xenograft models for both types of tumor. Taken together, our results indicate that the anti-tumor activity of PKRA7 can be mediated by two distinct mechanisms that are relevant to the pathological features of the specific type of cancer. This small molecule PK2 antagonist holds the promise to be further developed as an effective agent for combinational cancer therapy.
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[391]
TÍTULO / TITLE: - Thromboembolism and anticoagulation in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):135-7. doi: 10.6092/1590-8577/1480.
AUTORES / AUTHORS: - Habib M; Saif MW
INSTITUCIÓN / INSTITUTION: - Tufts Medical Center. Boston, MA, USA. wsaif@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Pancreatic cancer is a hypercoagulable condition, and venous thromboembolism affects up to 17% to 57% of pancreatic cancer patients. Initiating chemotherapy further increases the risk. For cancer patients initiating chemotherapy, there is currently no approved treatment for the primary prevention of venous thromboembolism risk. The authors summarize the two abstracts (#151 and #284) presented at the 2013 ASCO Gastrointestinal Cancers Symposium which were focused newer treatment options and the incidence of thromboembolism in pancreatic cancer patients especially in East Asian patients. Additionally the authors review the risk of thrombosis associated with the chemotherapy and erythropoiesis stimulating agents and its prognostic implications and possible managements.
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[392]
TÍTULO / TITLE: - Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cell Cycle. 2013 Mar 7;12(7).
AUTORES / AUTHORS: - Sun X; Liu M; Hao J; Li D; Luo Y; Wang X; Yang Y; Li F; Shui W; Chen Q; Zhou J
INSTITUCIÓN / INSTITUTION: - Key Laboratory of Protein Science and Department of Genetics and Cell Biology; College of Life Sciences; Nankai University; Tianjin, China.
RESUMEN / SUMMARY: - Parkin, an E3 ubiquitin ligase well known for its role in the pathogenesis of juvenile Parkinson disease, has been considered as a candidate tumor suppressor in certain types of cancer. It remains unknown whether parkin is involved in the development of pancreatic cancer, the fourth leading cause of cancer-related deaths worldwide. Herein, we demonstrate the downregulation and copy number loss of the parkin gene in human pancreatic cancer specimens. The expression of parkin negatively correlates with clinicopathological parameters indicating the malignancy of pancreatic cancer. In addition, knockdown of parkin expression promotes the proliferation and tumorigenic properties of pancreatic cancer cells both in vitro and in mice. We further find that parkin deficiency increases the proportion of cells with spindle multipolarity and multinucleation. Parkin-depleted cells also show a significant increase in spindle misorientation. These findings indicate crucial involvement of parkin deficiency in the pathogenesis of pancreatic cancer.
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[393]
TÍTULO / TITLE: - Pancreatic cancer deaths creep up.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Discov. 2013 Mar;3(3):OF3. doi: 10.1158/2159-8290.CD-NB2013-017. Epub 2013 Jan 31.
●● Enlace al texto completo (gratuito o de pago) 1158/2159-8290.CD-NB2013-017
RESUMEN / SUMMARY: - U.S. pancreatic cancer death rates crept up between 2000 and 2009, with an annual increase of 0.4%, according to the American Cancer Society 2013 Cancer Facts and Figures report. The incidence of the disease also inched up during that time.
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[394]
TÍTULO / TITLE: - Cytomorphologic and immunophenotypical features of acinar cell neoplasms of the pancreas.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Cancer Cytopathol. 2013 Feb 13. doi: 10.1002/cncy.21279.
●● Enlace al texto completo (gratuito o de pago) 1002/cncy.21279
AUTORES / AUTHORS: - Sigel CS; Klimstra DS
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.
RESUMEN / SUMMARY: - BACKGROUND: Acinar cell neoplasms of the pancreas are rare but when encountered, the diagnosis is often established based on cytology specimens. Diagnostic accuracy is important because acinar cell carcinomas are aggressive yet may mimic tumors with different outcomes and management. METHODS: The authors identified all patients with a diagnosis of acinar cell neoplasm in the institutional database; assessed cytomorphology and immunocytochemistry for trypsin, chymotrypsin, synaptophysin, chromogranin A, and MIB-1; and compared all cytology and final histological diagnoses for diagnostic discrepancies. RESULTS: Cytological features were described for 16 histologically proven malignant acinar cell neoplasms: acinar cell carcinoma (8 cases), mixed acinar-neuroendocrine carcinoma (6 cases), mixed acinar-ductal carcinoma (1 case), and pancreatoblastoma (1 case).The majority of aspirates from acinar cell cystadenomas were nondiagnostic or negative (5 of 6 cases; 83%). Acinar and neuroendocrine differentiation that was detected by immunocytochemistry in >20% of tumor cells was found to be correlated with mixed acinar-neuroendocrine carcinoma histology. Cytohistological correlation included 32 patients with 17 discordant diagnoses (53%). The following preoperative cytology diagnoses proved to be acinar cell neoplasms on resection: neuroendocrine tumor (5 cases), adenocarcinoma (5 cases), atypical ductal cells (2 cases), solid pseudopapillary neoplasm, and hepatocellular carcinoma. Three aspirates diagnosed as acinar cell carcinoma by cytology proved to be chronic pancreatitis (2 cases) and ductal adenocarcinoma (1 case). CONCLUSIONS: Acinar cell carcinoma has a distinctive cytological appearance but is frequently misdiagnosed on cytology. Immunocytochemistry is useful for identifying acinar differentiation. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
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[395]
TÍTULO / TITLE: - Response of Human Pancreatic Cancer Cell Xenografts to Tetraiodothyroacetic Acid Nanoparticles.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Horm Cancer. 2013 Feb 28.
●● Enlace al texto completo (gratuito o de pago) 1007/s12672-013-0137-y
AUTORES / AUTHORS: - Yalcin M; Lin HY; Sudha T; Bharali DJ; Meng R; Tang HY; Davis FB; Stain SC; Davis PJ; Mousa SA
INSTITUCIÓN / INSTITUTION: - Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, Albany, NY, 12208, USA.
RESUMEN / SUMMARY: - Tetraiodothyroacetic acid (tetrac) and its nanoparticle formulation (Tetrac NP) act at an integrin cell surface receptor to inhibit tumor cell proliferation and tumor-related angiogenesis. Human pancreatic cancer cell (PANC-1 and MPanc96) xenografts were established in nude mice, and the effects of tetrac versus Tetrac NP on tumor growth and tumor angiogenesis were determined. The in vitro effects of tetrac and Tetrac NP were also determined by reverse transcription polymerase chain reaction or immunoblot on gene expression or gene products relevant to cell cycle arrest, apoptosis, or angiogenesis. Tetrac and Tetrac NP reduced both PANC-1 tumor mass by 45-55 % and PANC-1 tumor hemoglobin content, a marker of angiogenesis, by 50-60 % (*P < 0.05) in treated groups vs. controls by treatment day 15. Comparable results were obtained with tetrac and Tetrac NP in suppressing tumor growth and tumor angiogenesis in MPanc96 xenografts. In vitro studies showed that tetrac and Tetrac NP caused accumulation of pro-apoptotic protein BcLx-s. Tetrac NP was more effective than tetrac in increasing cellular abundance of mRNAs of pro-apoptotic p53 and p21 and anti-angiogenesis thrombospondin 1 protein in PANC-1 and MPanc96 cancer cell lines. Tetrac NP noticeably decreased expression of EGFR and of anti-apoptosis gene XIAP; tetrac did not affect EGFR and increased XIAP mRNA in both MPanc96 and PANC-1. In conclusion, tetrac or Tetrac NP effectively inhibited human pancreatic xenograft growth and tumor angiogenesis via a plasma membrane receptor that downstream modulated cellular abundance of proteins or mRNAs relevant to apoptosis and angiogenesis.
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[396]
TÍTULO / TITLE: - Gastrointestinal hemorrhage after concurrent chemoradiotherapy in locally advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gut Liver. 2013 Jan;7(1):106-11. doi: 10.5009/gnl.2013.7.1.106. Epub 2012 Dec 5.
●● Enlace al texto completo (gratuito o de pago) 5009/gnl.2013.7.1.106
AUTORES / AUTHORS: - Lee KJ; Kim HM; Jung JW; Chung MJ; Park JY; Bang S; Park SW; Lee WJ; Seong JS; Song SY
INSTITUCIÓN / INSTITUTION: - Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
RESUMEN / SUMMARY: - BACKGROUND/AIMS: While chemoradiotherapy (CRT) is considered to be a reasonable treatment for locally advanced pancreatic cancer (LAPC), there is little information about the associated risk of gastrointestinal (GI) hemorrhage. We investigated the clinical features of GI toxicity after CRT in patients with LAPC and examined the effect of GI hemorrhage on survival. METHODS: Patients enrolled in this study had received CRT for pathologically proven LAPC. Their medical records were retrospectively reviewed. RESULTS: A total of 156 patients with LAPC (median age, 65 years; range, 39 to 90 years) who received treatment between August 2005 and March 2009 were included in this study. The most common GI toxicities were ulcer formation (25.6%) and hemorrhage (25.6%), and the most common grade 3 to grade 5 GI toxicity was hemorrhage (65%). The origins of GI hemorrhage were gastric ulcer (37.5%), duodenal ulcer (37.5%), and radiation gastritis (15.0%). The independent risk factor for GI hemorrhage was tumor location in the pancreatic body. The median overall survival of the patients with a GI hemorrhage was 13.8 months (range, 2.8 to 50.8 months) and was not significantly different from that of patients without GI hemorrhage. CONCLUSIONS: GI hemorrhage was common in patients with LAPC after CRT. Although GI hemorrhage was controlled with endoscopic hemostasis, preventive measures should be investigated to reduce needless suffering.
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[397]
TÍTULO / TITLE: - Combined EUS-Guided Abdominal Cavity Drainage and Cystogastrostomy for the Ruptured Pancreatic Pseudocyst.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Gastroenterol Res Pract. 2013;2013:785483. doi: 10.1155/2013/785483. Epub 2013 Mar 3.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/785483
AUTORES / AUTHORS: - Nan G; Siyu S; Xiang L; Sheng W; Guoxin W
INSTITUCIÓN / INSTITUTION: - Shengjing Hospital, China Medical University, No. 36 Sanhao Street, Shenyang, Liaoning Province 110004, China.
RESUMEN / SUMMARY: - Background. Endoscopic-Ultrasonography- (EUS-) guided puncture and drainage of pancreatic pseudocyst is currently one of the most widely accepted nonsurgical treatments. To date, this technique has only been used for pancreatic pseudocysts adhesive to the gastric wall. This study introduces the technique of EUS-guided pseudocyst drainage and additional EUS-guided peritoneal drainage for the ruptured pseudocyst. Methods. Transmural puncture and drainage of the cyst were performed with a 19 G needle, cystotome, and 10 Fr endoprosthesis. Intraperitoneal drainage was performed with a nasobiliary catheter when rupture of pseudocyst occurred. The entire procedure was guided by the echoendoscope. Results. A total of 21 patients, 8 men and 13 women, with a mean age of 36 years, were included in this prospective study. All of the pseudocysts were successfully drained by EUS. Peritoneal drainage was uneventfully performed in 4 patients. There were no severe complications. Complete pseudocyst resolution was established in all patients. Conclusion. The technique of EUS-guided transmural puncture and drainage, when combined with abdominal cavity drainage by a nasobiliary catheter, allows successful endoscopic management of pancreatic pseudocysts without adherence to gastric wall.
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[398]
TÍTULO / TITLE: - Locally advanced pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):126-8. doi: 10.6092/1590-8577/1469.
AUTORES / AUTHORS: - Oikonomopoulos GM; Huber KE; Syrigos KN; Saif MW
INSTITUCIÓN / INSTITUTION: - Second Oncology Clinic, St. Savvas Anticancer Hospital. Athens, Greece. goik77@yahoo.com.
RESUMEN / SUMMARY: - Treatment of locally advanced pancreatic cancer is palliative, based on chemotherapy and according to response, chemoradiotherapy can be applied. The authors summarize three abstracts (#LBA146, #256 and #303) presented on the 2013 ASCO Gastrointestinal Cancers Symposium, which were focused on treatment of locally advanced pancreatic cancer. A discussion is presented about the different chemotherapy or chemoradiotherapy regimens, that move away from gemcitabine-based treatment, and the effort to find less toxic, but efficient therapeutic combinations.
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[399]
TÍTULO / TITLE: - Quercetin Preserves beta -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Evid Based Complement Alternat Med. 2013;2013:303902. doi: 10.1155/2013/303902. Epub 2013 Feb 27.
●● Enlace al texto completo (gratuito o de pago) 1155/2013/303902
AUTORES / AUTHORS: - Li JM; Wang W; Fan CY; Wang MX; Zhang X; Hu QH; Kong LD
INSTITUCIÓN / INSTITUTION: - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
RESUMEN / SUMMARY: - Fructose-induced hyperinsulinemia is associated with insulin compensative secretion and predicts the onset of type 2 diabetes. In this study, we investigated the preservation of dietary flavonoid quercetin on pancreatic beta -cell mass and function in fructose-treated rats and INS-1 beta -cells. Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. It also prevented fructose-induced beta -cell proliferation and insulin hypersecretion in INS-1 beta -cells. High fructose increased forkhead box protein O1 (FoxO1) expressions in vivo and in vitro, which were reversed by quercetin. Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1 beta -cells. The elevated Akt phosphorylation in fructose-treated INS-1 beta -cells was also restored by quercetin. Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. In fructose-treated INS-1 beta -cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. These results demonstrate that quercetin protects beta -cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation.
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[400]
TÍTULO / TITLE: - Management of malignant insulinoma.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Clin Transl Oncol. 2013 Mar 5.
●● Enlace al texto completo (gratuito o de pago) 1007/s12094-012-0996-7
AUTORES / AUTHORS: - Ferrer-Garcia JC; Iranzo Gonzalez-Cruz V; Navas-Desolis S; Civera-Andres M; Morillas-Arino C; Merchante-Alfaro A; Caballero-Diaz C; Sanchez-Juan C; Camps Herrero C
INSTITUCIÓN / INSTITUTION: - Department of Endocrinology and Nutrition, Consorcio Hospital General Universitario de Valencia, Valencia, España.
RESUMEN / SUMMARY: - AIM: Malignant insulinoma is an infrequent functional endocrine tumor of the pancreas. Adequate therapy is a demanding challenge for oncologists and endocrinologists. OBJECTIVE: To evaluate the results of multidisciplinary management of malignant insulinoma. MATERIALS AND METHODS: Retrospective review of patients with malignant insulinoma treated from 1995 to 2011. RESULTS: Seven patients with malignant insulinoma were included: four males and three females; median age was 61.8 years (range 37-78). Six tumors were sporadic and one was diagnosed in a patient with a type 1 multiple endocrine neoplasia (MEN-1). Surgery was performed in six cases and one patient was considered unresectable. Hypoglycemias persisted in all cases and somatostatin analogs, glucocorticoids and diazoxide were used. Two patients received everolimus. Other techniques were chemoembolization and internal radiation therapy with yttrium-90. Successful liver transplant was done in the patient with MEN-1. CONCLUSION: Hypoglycemia management is complex and requires multiple therapies. Further evaluations will be necessary to determine the best treatment.
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[401]
TÍTULO / TITLE: - AnvirzelTM in combination with cisplatin in breast, colon, lung, prostate, melanoma and pancreatic cancer cell lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Pharmacol Toxicol. 2013 Mar 25;14(1):18.
●● Enlace al texto completo (gratuito o de pago) 1186/2050-6511-14-18
AUTORES / AUTHORS: - Apostolou P; Toloudi M; Chatziioannou M; Ioannou E; Knocke DR; Nester J; Komiotis D; Papasotiriou I
RESUMEN / SUMMARY: - BACKGROUND: Platinum derivatives are used widely for the treatment of many cancers. However, the toxicity that is observed makes imperative the need for new drugs, or new combinations. AnvirzelTM is an extract which has been demonstrated with experimental data that displays anticancer activity. The aim of the present study is to determine whether the combination of Cisplatin and AnvirzelTM has a synergistic effect against different types of cancer.Materials and methods: To measure the efficacy of treatment with Cisplatin and AnvirzelTM, methyl-tetrazolium dye (MTT) chemosensitivity assays were used incorporating established human cancer cell lines. Measurements were performed in triplicates, three times, using different incubation times and different concentrations of the two formulations in combination or on their own. t-test was used for statistical analysis. RESULTS: In the majority of the cell lines tested, lower concentrations of AnvirzelTM induced a synergistic effect when combined with low concentrations of Cisplatin after an incubation period of 48 to 72 h. The combination of AnvirzelTM/Cisplatin showed anti-proliferative effects against a wide range of tumours. CONCLUSION: The results showed that the combination of AnvirzelTM and Cisplatin is more effective than monotherapy, even when administered at low concentrations; thus, undesirable toxic effects can be avoided.
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[402]
TÍTULO / TITLE: - Brain metastasis in pancreatic cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Int J Mol Sci. 2013 Feb 19;14(2):4163-73. doi: 10.3390/ijms14024163.
●● Enlace al texto completo (gratuito o de pago) 3390/ijms14024163
AUTORES / AUTHORS: - Lemke J; Scheele J; Kapapa T; Wirtz CR; Henne-Bruns D; Kornmann M
INSTITUCIÓN / INSTITUTION: - Clinic of General and Visceral Surgery, University Hospital Ulm, Albert-Einstein-Allee 23, Ulm 89071, Germany. marko.kornmann@uniklinik-ulm.de.
RESUMEN / SUMMARY: - Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreatic cancer were identified. In three patients brain metastases were the first manifestation of pancreatic cancer. All other patients developed brain metastases during their clinical course. In most cases, the disease progressed rapidly and the patients died within weeks or months. However, two patients showed long-term survival. Of note, both patients received resection of the pancreatic cancer as well as curative resection of the metachronous brain metastases. Brain metastases in pancreatic cancer are a rare condition and usually predict a very poor prognosis. However, there is evidence that resection of brain metastases of pancreatic cancer can be immensely beneficial to patient’s survival, even with the chance for cure. Therefore, a surgical approach in metastatic pancreatic cancer should be considered in selective cases.
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[403]
TÍTULO / TITLE: - Advancements in the management of pancreatic cancer: 2013.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):112-8. doi: 10.6092/1590-8577/1481.
AUTORES / AUTHORS: - Saif MW
INSTITUCIÓN / INSTITUTION: - Tufts Medical Center. Boston, MA, USA. wsaif@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Pancreatic cancer still remains a significant, unresolved therapeutic challenge and is the most lethal type of gastrointestinal cancer with a 5-year survival rate of 5%. Adjuvant chemotherapy remains to be gemcitabine alone, though fluorouracil offers the same survival and role of radiation remains controversial. Nevertheless, only a few patients survive for at least 5 years after R0 resection and adjuvant therapy. Borderline resectable pancreatic cancer remains an area that requires multi-disciplinary approach. Neo-adjuvant therapy very likely plays a role to downstage to a resectable state in these subgroup patients. There are different treatment approaches to locally advanced pancreatic cancer management, including single or multi-agent chemotherapy, chemotherapy followed by chemoradiation, or immediate concurrent chemoradiation. Most patients need palliative treatment. Once pancreatic cancer becomes metastatic, it is uniformly fatal with an overall survival of generally 6 months from time of diagnosis. Gemcitabine has been the standard since 1997. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, leucovorin) has already shown superiority over gemcitabine in both progression-free survival and overall survival, but this regimen is suitable only for selected patients in ECOG performance status 0-1. FOLFIRINOX has already trickled down to the clinic in various modifications and in different patient groups, both locally advanced and metastatic. Many targeted agents, including bevacizumab, cetuximab showed negative results, except mild benefit with addition of erlotinib with gemcitabine, which was not considered clinically significant. There is no consensus regarding treatment in the second-line setting. It will be true to say that there was a real medical breakthrough with regards to improving the prognosis of pancreatic cancer as of 2013 with the results of MPACT study. In this study, patients who received nab-paclitaxel plus gemcitabine lived a median of 8.5 months, compared with 6.7 months for those who received gemcitabine alone. At the end of one year, 35% of those getting nab-paclitaxel were alive, compared with 22% of those getting only gemcitabine. After two years, the figures were 9% for those getting nab-paclitaxel and 4% for those who received gemcitabine.
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[404]
TÍTULO / TITLE: - Mass Spectrometry-based Quantitative Proteomic Profiling of Human Pancreatic and Hepatic Stellate Cell Lines.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Genomics Proteomics Bioinformatics. 2013 Mar 22. pii: S1672-0229(13)00032-6. doi: 10.1016/j.gpb.2013.01.009.
●● Enlace al texto completo (gratuito o de pago) 1016/j.gpb.2013.01.009
AUTORES / AUTHORS: - Paulo JA; Kadiyala V; Banks PA; Conwell DL; Steen H
INSTITUCIÓN / INSTITUTION: - Department of Pathology, Boston Children’s Hospital, Boston, MA 02115, USA; Proteomics Center at Boston Children’s Hospital, Boston, MA 02115, USA; Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: joao_paulo@post.harvard.edu.
RESUMEN / SUMMARY: - The functions of the liver and the pancreas differ; however, chronic inflammation in both organs is associated with fibrosis, which evidence suggests is partially regulated by organ-specific stellate cells. We explore the proteome of human hepatic stellate cells (hHSC) and human pancreatic stellate cells (hPaSC) using mass spectrometry (MS)-based quantitative proteomics to investigate pathophysiologic mechanisms. Proteins were isolated from whole cell lysates of immortalized hHSC and hPaSC. These proteins were tryptically digested, labeled with tandem mass tags (TMT), fractionated by OFFGEL, and subjected to MS. Proteins significantly different in abundance (P < 0.05) were classified via gene ontology (GO) analysis. We identified 1223 proteins and among them, 1222 proteins were quantifiable. Statistical analysis determined that 177 proteins were of higher abundance in hHSC, while 157 were of higher abundance in hPaSC. GO classification revealed that proteins of relatively higher abundance in hHSC were associated with protein production, while those of relatively higher abundance in hPaSC were involved in cell structure. Future studies using the methodologies established herein, but with further upstream fractionation and/or use of enhanced MS instrumentation will allow greater proteome coverage, achieving a comprehensive proteomic analysis of hHSC and hPaSC.
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[405]
TÍTULO / TITLE: - Pancreatic cancer clusters and arsenic-contaminated drinking water wells in Florida.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - BMC Cancer. 2013 Mar 12;13:111. doi: 10.1186/1471-2407-13-111.
●● Enlace al texto completo (gratuito o de pago) 1186/1471-2407-13-111
AUTORES / AUTHORS: - Liu-Mares W; Mackinnon JA; Sherman R; Fleming LE; Rocha-Lima C; Hu JJ; Lee DJ
INSTITUCIÓN / INSTITUTION: - Department of Epidemiology and Public Health, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th St,, CRB 1512, Miami, FL, 33136, USA. wliu@med.miami.edu.
RESUMEN / SUMMARY: - BACKGROUND: We sought to identify high-risk areas of pancreatic cancer incidence, and determine if clusters of persons diagnosed with pancreatic cancer were more likely to be located near arsenic-contaminated drinking water wells. METHODS: A total of 5,707 arsenic samples were collected from December 2000 to May 2008 by the Florida Department of Health, representing more than 5,000 individual privately owned wells. During that period, 0.010 ppm (10 ppb) or greater arsenic levels in private well water were considered as the threshold based on standard of United States Environmental Protection Agency (EPA). Spatial modeling was applied to pancreatic cancer cases diagnosed between 1998-2002 in Florida (n = 11,405). Multivariable logistic regression was used to determine if sociodemographic indicators, smoking history, and proximity to arsenic-contaminated well sites were associated with residence at the time of pancreatic cancer diagnosis occurring within versus outside a cluster. RESULTS: Spatial modeling identified 16 clusters in which 22.6% of all pancreatic cancer cases were located. Cases living within 1 mile of known arsenic-contaminated wells were significantly more likely to be diagnosed within a cluster of pancreatic cancers relative to cases living more than 3 miles from known sites (odds ratio = 2.1 [95% CI = 1.9, 2.4]). CONCLUSIONS: Exposure to arsenic-contaminated drinking water wells may be associated with an increased risk of pancreatic cancer. However, case-control studies are needed in order to confirm the findings of this ecological analysis. These cluster areas may be appropriate to evaluate pancreatic cancer risk factors, and to perform targeted screening and prevention studies.
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[406]
TÍTULO / TITLE: - New insights into pancreatic cancer-induced paraneoplastic diabetes.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Nat Rev Gastroenterol Hepatol. 2013 Mar 26. doi: 10.1038/nrgastro.2013.49.
●● Enlace al texto completo (gratuito o de pago) 1038/nrgastro.2013.49
AUTORES / AUTHORS: - Sah RP; Nagpal SJ; Mukhopadhyay D; Chari ST
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Mayo Clinic, 200 First Street South West, Rochester, MN 55905, USA.
RESUMEN / SUMMARY: - Up to 85% of patients with pancreatic cancer have diabetes or hyperglycaemia, which frequently manifests as early as 2-3 years before a diagnosis of pancreatic cancer. Conversely, patients with new-onset diabetes have a 5-8-fold increased risk of being diagnosed with pancreatic cancer within 1-3 years of developing diabetes. Emerging evidence now indicates that pancreatic cancer causes diabetes. As in type 2 diabetes, beta-cell dysfunction and peripheral insulin resistance are seen in pancreatic cancer-induced diabetes. However, unlike in patients with type 2 diabetes, glucose control worsens in patients with pancreatic cancer in the face of ongoing, often profound, weight loss. Diabetes and weight loss, which precede cachexia onset by several months, are paraneoplastic phenomena induced by pancreatic cancer. Although the pathogenesis of these pancreatic cancer-induced metabolic alterations is only beginning to be understood, these are likely mechanisms to promote the survival and growth of pancreatic cancer in a hostile and highly desmoplastic microenvironment. Interestingly, these metabolic changes could enable early diagnosis of pancreatic cancer, if they can be distinguished from the ones that occur in patients with type 2 diabetes. One such possible biomarker is adrenomedullin, which is a potential mediator of beta-cell dysfunction in pancreatic cancer-induced diabetes.
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[407]
TÍTULO / TITLE: - Masquerade without a mass: an unusual cause of severe acute pancreatitis.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - J Gastrointest Oncol. 2013 Mar;4(1):114-7. doi: 10.3978/j.issn.2078-6891.2012.050.
●● Enlace al texto completo (gratuito o de pago) 3978/j.issn.2078-6891.2012.050
AUTORES / AUTHORS: - To CA; Quigley MM; Saven A; Nicholson L
INSTITUCIÓN / INSTITUTION: - Department of Internal Medicine, Department of Medicine, Scripps Clinic/Green Hospital, La Jolla, CA, USA.
RESUMEN / SUMMARY: - After excluding the typical causes, the underlying etiology of severe acute pancreatitis is often elusive; tumors are on the differential but may be difficult to prove in the absence of a discrete mass on imaging. In this report, we describe the case of an elderly woman with diffuse large B-cell lymphoma masquerading as acute pancreatitis. To our knowledge, only twelve other cases of pancreatic B-cell lymphoma presenting as acute pancreatitis have been described. However, while other cases involved well-circumscribed tumors of the pancreas, this is the first known case of pancreatic lymphoma of a diffusely infiltrating pattern presenting as acute pancreatitis.
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[408]
TÍTULO / TITLE: - BRCA-Associated Pancreatic Cancer: The Evolving Management.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - JOP. 2013 Mar 10;14(2):149-51. doi: 10.6092/1590-8577/1462.
AUTORES / AUTHORS: - Leung K; Saif MW
INSTITUCIÓN / INSTITUTION: - Division of Hematology/Oncology, Department of Medicine and Cancer Center, Tufts Medical Center. Boston, MA, USA. wsaif@tuftsmedicalcenter.org.
RESUMEN / SUMMARY: - Pancreatic cancer is one of the deadliest cancers. While BRCA-associated pancreatic cancers are uncommon, the distinctive phenotype of this malignancy may offer unique therapeutic targets. At the 2013 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, a review of the characteristics and outcomes of one large case series (Abstract #278), however, did not reveal a benefit to first-line platinum chemotherapy in the treatment of advanced pancreatic cancer. In another study (Abstract #147), substantial responses were observed in both patients with BRCA2-associated pancreatic cancer treated with the poly-(ADP-ribose) polymerase (PARP) inhibitor ABT-888 (veliparib). We will review these abstracts and our current knowledge of the treatment for patients with BRCA-associated pancreatic cancer. In this group of patients, these new results continue to shape our understanding of this disease.
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[409]
TÍTULO / TITLE: - Is tumour size an underestimated feature in the current TNM system for malignancies of the pancreatic head?
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - HPB (Oxford). 2013 Jan 29. doi: 10.1111/hpb.12052.
●● Enlace al texto completo (gratuito o de pago) 1111/hpb.12052
AUTORES / AUTHORS: - Petermann D; Demartines N; Schafer M
INSTITUCIÓN / INSTITUTION: - Department of Visceral Surgery, University Hospital CHUV, Lausanne, Switzerland.
RESUMEN / SUMMARY: - BACKGROUND: As the long-term survival of pancreatic head malignancies remains dismal, efforts have been made for a better patient selection and a tailored treatment. Tumour size could also be used for patient stratification. METHODS: One hundred and fourteen patients underwent a pancreaticoduodenectomy for pancreatic adenocarcinoma, peri-ampullary and biliary cancer stratified according to: </=20 mm, 21-34 mm, 35-45 mm and >45 mm tumour size. RESULTS: Patients with tumour sizes of </=20 mm had a N1 rate of 41% and a R1/2 rate of 7%. The median survival was 3.4 years. N1 and R1/2 rates increased to 84% and 31% for tumour sizes of 21-34 mm (P = 0.0002 for N, P = 0.02 for R). The median survival decreased to 1.6 years (P = 0.0003). A further increase in tumour size of 35-45 mm revealed a further increase of N1 and R1/2 rates of 93% (P < 0.0001) and 33%, respectively. The median survival was 1.2 years (P = 0.004). Tumour sizes >45 mm were related to a further decreased median survival of 1.1 years (P = 0.2), whereas N1 and R1/2 rates were 87% and 20%, respectively. DISCUSSION: Tumour size is an important feature of pancreatic head malignancies. A tumour diameter of 20 mm seems to be the cut-off above which an increased rate of incomplete resections and metastatic lymph nodes must be encountered and the median survival is reduced.
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[410]
TÍTULO / TITLE: - Identifying Biomarkers and Drug Targets Using Systems Biology Approaches for Pancreatic Cancer.
RESUMEN / SUMMARY: - Enlace al Resumen / Link to its Summary
REVISTA / JOURNAL: - Pancreat Disord Ther. 2012 Dec 6;2(4):1000e128.
AUTORES / AUTHORS: - Tan Y; Miele L; Sarkar FH; Wang Z
INSTITUCIÓN / INSTITUTION: - Department of General Surgery, Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, PR China, 233004.
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