Imbalance of desmoplastic stromal cell numbers drives aggressive cancer processes.

Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66-0.83), accompanied by change in expression of key molecules such as E-cadherin and ß-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell-cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer-stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.

Chronic pancreatitis.

INTRODUCTION: Chronic pancreatitis affects 3-9 people in 100,000; 70% of cases are alcohol-induced. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of lifestyle interventions in people with chronic pancreatitis? What are the effects of dietary supplements in people with chronic pancreatitis? What are the effects of drug interventions in people with chronic pancreatitis? What are the effects of nerve blocks for pain relief in people with chronic pancreatitis? What are the effects of different invasive treatments for specific complications of chronic pancreatitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: avoiding alcohol consumption, biliary decompression, calcium supplements, ductal decompression (endoscopic or surgical), low-fat diet, nerve blocks, opioid analgesics, pancreatic enzyme supplements, pseudocyst decompression (endoscopic or surgical), resection using distal pancreatectomy, resection using pancreaticoduodenectomy (Kausch-Whipple or pylorus-preserving), and vitamin/antioxidant supplements.