c-kit (CD117) expression in human tumors and its prognostic value: an immunohistochemical analysis.

c-kit functions as a tyrosine kinase receptor and represents a target for small molecule kinase inhibitors. The expression pattern for c-kit was studied in different human tumor types to their correlation with prognosis. Paraffin-embedded tumor tissues from 282 patients were analyzed immunohistochemically for c-kit expression. Survival and follow-up data were available from 192/282 (68%) patients. c-kit immunopositivity was found in 62/282 (22%) cases. c-kit expression was found in 14/83 (17%) colorectal cancers, in 13/62 (21%) breast cancers, in 7/20 sarcomas (35%), in 5/14 (36%) renal cell carcinomas, in 2/12 ovarian cancers (17%) and in 2/12 (17%) hepatocellular carcinomas. We found no significant correlation between c-kit expression and prognosis although a trend to a worse prognosis in patients with c-kit positive tumors could be observed. Expression of c-kit was found in tumor samples with varying intensities and infrequently.

Transgenic overexpression of insulin receptor substrate 1 in hepatocytes enhances hepatocellular proliferation in young mice only.

AIM: The insulin receptor substrate-1 (IRS-1) is a multisite docking protein which plays a central role in the signal transduction of growth factors such as insulin and insulin-like growth factors (IGF-1 and IGF-2). It is found to be frequently overexpressed in human hepatocellular carcinoma (HCC). METHODS: To study IRS-1 overexpression in hepatocytes in vivo, transgenic mice overexpressing IRS-1 exclusively in hepatocytes were created, showing enhanced hepatocyte proliferation in young animals. In the present study, the phenotype of IRS-1 transgenic animals was characterized over a period of two years. The livers of transgenic and control mice were analyzed for IRS-1 expression and phosphorylation, activation of the downstream mitogen-activated protein kinase (MAPK) cascade and phosphatidylinositol 3' kinase (PI3'K) and macroscopical and histological abnormalities. RESULTS: The enhanced hepatocyte proliferation observed in young IRS-1 transgenic animals was no longer detectable in adult mice. Despite constitutive overexpression and phosphorylation of IRS-1, MAPK- and IRS-1-associated PI3'K activity were significantly reduced in older transgenic mice. Furthermore, no premalignant lesions or HCC were detected in IRS-1 transgenic animals up to the age of 24 months. CONCLUSIONS: Therefore, additional mechanisms such as enhanced growth factor expression or impaired negative feedback control mechanisms may augment IRS-1 overexpression in human hepatocarcinogenesis.

Transgenic mice replicating hepatitis B virus but lacking expression of the major HBsAg.

Hepatitis B Virus (HBV) transgenic mice replicating the viral genome at high level but lacking expression of the small envelope protein (HBsAg) have been produced using a terminally redundant viral DNA construct (HBV 1.4). The generation of viable infectious progeny was dependent on sex and age of mice. Viral mRNA was abundant in liver and kidneys and at low levels in other organs of the mice. No viral particles or HBV envelope proteins could be detected in sera of mice. Despite expression of non-secreted LHBs and MHBs proteins in the liver, there was no accumulation of viral particles in the endoplasmic reticulum of hepatocytes and no necroinflammatory hepatitis was observed. Therefore, these mice represent an excellent model for studies of the role of HBsAg in viral assembly, antiviral immune responses, the further understanding of HBV immunopathogenesis, and the development of antiviral vaccines.

Pancreatico-mediastinal fistula with a mediastinal mass lesion demonstrated by MR imaging.

Internal pancreatic fistulas are uncommon but well-recognized complications of inflammatory pancreatic disease. A case of a pancreatico-mediastinal fistula with a mediastinal mass lesion in a patient with a documented history of chronic alcohol consumption and previous episodes of acute pancreatitis is described. Since the clinical symptomatology was dominated by pulmonary complaints, magnetic resonance (MR) imaging using a breathhold coronal T2-weighted sequence with spectral fat saturation was essential in clarifying this difficult and rare pathology. Furthermore, the depiction of a fistulous tract between a mediastinal mass lesion and the retroperitoneum posterior to the pancreas, i.e., a pancreatico-mediastinal fistula by MR imaging has not been previously reported, to the best of our knowledge.

Cardiopulmonary bypass reduction of bronchial blood flow: a potential mechanism for lung injury in a neonatal pig model.

BACKGROUND: During total cardiopulmonary bypass, blood flow to the lungs is limited to flow through the bronchial arteries. We tested the hypothesis that bronchial blood flow during cardiopulmonary bypass is insufficient to prevent ischemia of the lung and that perfusion of the pulmonary arteries with oxygenated blood during bypass would reduce lung injury. METHODS: Eighteen piglets (5.0 +/- 0.5 kg) were subjected to 120 minutes of normothermic total cardiopulmonary bypass, followed by 60 minutes of postbypass perfusion. Nine of them received continuous pulmonary perfusion with oxygenated blood during bypass. Six additional piglets served as a control group and were mechanically ventilated after sternotomy for 180 minutes only. We quantitated bronchial arterial blood flow, tissue lactate content, and alveolar septal thickness and surface area. We also obtained bronchioalveolar lavage fluid samples. RESULTS: With the beginning of cardiopulmonary bypass, bronchial arterial blood flow decreased to 13% of baseline (42.1 +/- 10.4 to 5.6 +/- 1.0 mL/min). It remained decreased until the end of bypass and returned to starting levels 60 minutes after bypass. The decrease in bronchial blood flow was associated with a 3-fold increase in tissue lactate content. At the end of reperfusion there was a 2-fold increase in alveolar septal thickness and significant accumulations relative to control in the bronchoalveolar lavage fluid of albumin, lactate dehydrogenase, neutrophils, and elastase. Controlled pulmonary perfusion significantly ameliorated all the observed changes. CONCLUSION: Cardiopulmonary bypass caused a reduction in bronchial arterial blood flow, which was associated with injury of the lung. Controlled pulmonary perfusion reduced injury to the lung during bypass. The inflammatory response, as evidenced by bronchoalveolar lavage fluid, may be caused by ischemia.