Pathological and Molecular Evaluation of Pancreatic Neoplasms

Rishi, Arvind; Goggins, Michael; Wood, Laura D.; Hruban, Ralph H.

doi:10.1053/j.seminoncol.2014.12.004

Cited by 64 publications

(51 citation statements)

References 106 publications

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“…The development of PDA is initiated by mutations in the KRas oncogene followed by inactivating mutations and deletion of tumor suppressor genes including TRP53, CDKN2A, and SMAD4 (1). The role of these alterations in the initiation and progression of PDA has been attributed to cell-intrinsic processes that are critical for malignant transformation, including the bypass of proliferative barriers, metabolic adaptation and metastatic dissemination.…”

Section: Introductionmentioning

confidence: 99%

IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia

et al. 2016

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A salient feature of pancreatic ductal adenocarcinoma (PDA) is an abundant fibroinflammatory response characterized by the recruitment of immune and mesenchymal cells and the consequent establishment of a pro-tumorigenic microenvironment. Here we report the prominent presence of B cells in human pancreatic intraepithelial neoplasia (PanIN) and PDA lesions as well as in oncogenic K-Ras-driven pancreatic neoplasms in the mouse. The growth of orthotopic pancreatic neoplasms harboring oncogenic K-Ras was significantly compromised in B cell-deficient mice (μMT), and this growth deficiency could be rescued by the reconstitution of a CD1dhighCD5+ B cell subset. The pro-tumorigenic effect of B cells was mediated by their expression of IL-35 through a mechanism involving IL-35-mediated stimulation of tumor cell proliferation. Our results identify a previously unrecognized role for IL-35-producing CD1dhighCD5+ B cells in the pathogenesis of pancreatic cancer and underscore the potential significance of a B cell/IL-35 axis as a therapeutic target.

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Section: Introductionmentioning

confidence: 99%

IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia

et al. 2016

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“…While cancer incidence and mortality rates have been declining in the US during the past decade, pancreatic cancer incidence and mortality rates have increased (1). The majority of pancreatic cancers are pancreatic ductal adenocarcinomas (PDA) (2). Diabetes, obesity, and smoking are known risk factors for PDA (3–5).…”

Section: Introductionmentioning

confidence: 99%

Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

Nogueira

Newton

Pollak

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers. Methods We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate odds ratios (OR) and 95% confidence intervals (CI). Results Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per standard deviation OR=0.67, 95% CI 0.54, 0.84, p-interaction=0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR=0.43, 95% CI 0.23, 0.81), not associated in former smokers, and positively associated in smokers (OR=1.23, 95% CI 1.04, 1.45, p-interaction=0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers. Conclusion Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance explain associations in non-smokers. Impact Future studies of these biomarkers and PDA should examine results by smoking status.

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“…Germline mutations in BRCA2, p16, ATM, STK11, PRSS1/PRSS2, SPINK1, PALB2, and DNA mismatch repair genes are associated with varying degrees of increased risk for pancreatic carcinoma. Mutation in BRCA2 is probably the most common inherited disorder in familial pancreatic cancer [3]. Among the remaining 90%, the major risk factors are tobacco, H. pylori infection, and factors related to dietary habits [4].…”

Section: Introductionmentioning

confidence: 99%

SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)

et al. 2016

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Pancreatic cancer remains an aggressive disease with a 5 year survival rate of 5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery. Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid option in patients with positive margins. Borderline resectable pancreatic cancer is defined as the involvement of the mesenteric vasculature with a limited extension. These tumors are technically resectable, but with a high risk of positive margins. Neoadjuvant treatment represents the best option for achieving an R0 resection. In advanced disease, two new chemotherapy treatment schemes (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in overall survival compared with gemcitabine alone. Progress in pancreatic cancer treatment will require a better knowledge of the molecular biology of this disease, focusing on personalized cancer therapies in the near future.

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Pathological and Molecular Evaluation of Pancreatic Neoplasms

Cited by 64 publications

References 106 publications

IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia

IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia

Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

SEOM Clinical Guideline for the treatment of pancreatic cancer (2016)

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