The hedgehog (Hh) family of genes, sonic hedgehog (Shh), Indian hedgehog (Ihh), and desert hedgehog (Dhh) encode signaling molecules that regulate multiple functions during organ development and in adult tissues. Altered hedgehog signaling has been implicated in disturbed organ development as well as in different degenerative and neoplastic human diseases. Hedgehog signaling plays an important role in determination the fate of the mesoderm of the gut tube, as well as in early pancreatic development, and islet cell function. Recently, it has been shown that deregulation of hedgehog signaling molecules contributes to the pathogenesis and progression of pancreatic cancer and of chronic pancreatitis. Inhibition of hedgehog signaling using hedgehog antagonists reduces pancreatic cancer cell growth in vitro and in vivo, thus holding promise of novel agents in the treatment of this devastating disease. In this review, we discuss the role of hedgehog signaling during pancreatic development, its role in the pathogenesis of both chronic pancreatitis and pancreatic cancer, and lastly, the implications of this newly available information with regards to treatment of pancreatic cancer.
Pancreatic cancer has an abysmal prognosis. Targets for early detection, prevention and therapy are desperately needed. Inflammatory pathways have an important impact on tumour growth and progression. Expression of BLT2 (the second leukotriene B 4 receptor) was investigated by real-time RT -PCR and immunohistochemistry. Cell proliferation was studied after stable transfection with BLT2, after treatment with siRNA and Compound A as an agonist. BLT2 is expressed in all pancreatic cancer cell lines. Results from real-time RT -PCR revealed significant overexpression of BLT2 in malignant intraductal papillary mucinous neoplasias (IPMNs) and pancreatic adenocarcinoma. Intense staining was evident in IPMNs, infiltrating tumour cells and advanced pancreatic intraepithelial neoplasias (PanINs) but not in normal ductal cells. Overexpression of BLT2 as well as stimulation of Colo357, Panc-1 and AsPC1 cells with Compound A caused a significant increase in tumour cell proliferation, an effect reversed after siRNA treatment. This study demonstrates for the first time the expression of BLT2 in the pancreas and overexpression in pancreatic cancers and malignant IPMNs in particular. Upregulation of BLT2 is already evident in precursor lesions (PanINs, IPMNs). Overexpression of this receptor leads to significant growth stimulation. Therefore, we suggest BLT2 as a new target for chemoprevention and therapy for pancreatic cancer.
ObjectivesTo evaluate the incidence and risk factors for the development of flank incisional hernias or bulges following surgical flank approaches to the kidney.Patients and methodsIn all, 100 consecutive adult patients who underwent variable renal surgeries via flank approaches were included in this prospective study. The incidence and risk factors for flank hernias and bulges were studied at 1- and 6-months postoperatively.ResultsAt 6 months postoperatively, the incidence of flank bulge was 14% and for lumbar hernia was 10%. The univariate analysis showed 13 significant factors to be associated with the occurrence of a flank bulge or hernia following flank incisions. When the significant risk factors in the univariate analysis were studied by multivariate analysis, using a logistic regression analysis, four independent risk factors were identified. These were: body mass index (BMI) ≥26.3 kg/m2 (P = 0.04), the use of a self-retaining retractor during surgery (P = 0.02), not preserving or identifying the neurovascular bundle (NVB) during surgery (P = 0.028), and postoperative abdominal distention (P = 0.001). Moreover, all cases included in our study who underwent en masse wound closure, developed surgical wound infection or who had constipation developed postoperative flank bulge or hernia.ConclusionHigh BMI, the use of self-retaining retractor, not identifying or preserving the NVB, postoperative abdominal distention, en masse wound closure, surgical wound infection, and constipation are significant risk factors associated with postoperative flank hernia and bulge.
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