Pancreatic Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Pancreatic Cancer, including details on symptoms, causes, treatment, information.

CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.

Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL, Torigian DA, O'Dwyer PJ, Vonderheide RH

Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.

Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer.

Published 25 March 2011 in Science, 331(6024): 1612-6.
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Articles on Pancreatic Cancer published 25 March 2011:

CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.   Science, 331(6024): 1612-6.

Immunosuppressive tumor microenvironments can restrain antitumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA). Because CD40 activation can reverse immune suppression and drive antitumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable PDA and observed tumor regressions in some patients. We reproduced this treatment effect in a genetically engineered mouse model of PDA ... [Abstract] [Full-text]

Articles on Pancreatic Cancer published 22 March 2011:

Peptide receptor radioligand therapy is an effective treatment for the long-term stabilization of malignant gastrinomas.   Cancer, 117(7): 1377-85.

[Abstract] [Full-text]

Articles on Pancreatic Cancer published 17 March 2011:

Celiac plexus block for pancreatic cancer pain in adults.   Cochrane Database Syst Rev, 3: CD007519.

[Abstract] [Full-text]

Celiac plexus block for pancreatic cancer pain in adults.   Cochrane Database Syst Rev, 3: CD007519.

[Abstract] [Full-text]

Visualization of CD44 and CD133 in normal pancreas and pancreatic ductal adenocarcinomas: non-overlapping membrane expression in cell populations positive for both markers.   J Histochem Cytochem, 59(4): 441-55.

Tumor-initiating cells of pancreatic ductal adenocarcinoma (PDAC) have been isolated based on expression of either CD133 or CD44. The authors aimed to visualize pancreatic cells simultaneously expressing both these cell surface markers by employing the same antibodies commonly used in cell-sorting studies. Normal and diseased pancreatic tissue, including 51 PDAC cases, were analyzed. CD44 and CD133 expression was determined by immunohistochemical double staining on formalin-fixed material and ... [Abstract] [Full-text]

Articles on Pancreatic Cancer published 9 March 2011:

DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.   Science, 331(6021): 1199-203.

Pancreatic neuroendocrine tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1, which encodes menin, a component of a histone methyltransferase ... [Abstract] [Full-text]

Articles on Pancreatic Cancer published 7 March 2011:

Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas.   Gut, 60(4): 509-16.

[Abstract] [Full-text]

Articles on Pancreatic Cancer published 4 March 2011:

A novel in vitro pancreatic carcinogenesis model.   Toxicol Lett, 202(1): 15-22.

Environmental factors (e.g., BaP) have been pointed out as one of the etiologies of pancreatic cancer. However, very limited experimental assays are available to identify pancreatic specific environmental mutagens or susceptibility genes. In this study, we have developed a simple in vitro cell culture model system that can be used to study the molecular and biochemical aspects of carcinogenesis in a near-normal immortalized pancreatic ductal epithelial cell lines. In order to demonstrate that ... [Abstract] [Full-text]

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