Several lines of evidence suggest that endothelial dysfunction and damage present early steps in the pathophysiology of vascular complications in diabetes mellitus [1±3]. Several studies using cultured endothelial cells clearly show that incubation of these cells with high concentrations of glucose leads to severe changes in the proliferation, the adhesive and synthetic properties [1]. Consequently, regulation of vascular relaxation by endothelium becomes disturbed in diabetes [2,3]. In addition to glucose, high concentrations of proinsulin have been shown to promote the synthesis of the plasminogen activator inhibitor type-1 (PAI-1) [4]. This observation indicates that endothelial function can be directly influenced not only by glucose, but also by proinsulin. Thus, high proinsulin levels may contribute to the development of vascular complications in diabetes, if secreted excessively. In line with this assumption proinsulin is increased in the late pre-insulin-dependent diabetes mellitus [5] and especially in non-insulin-dependent diabetic patients with abnormal prohormone convertase PC2 and PC3 activity [6] or with a point mutation in the Diabetologia (1998)

Abstract. The aim of this study was to investigate the correlation between H-ras mutation and primary hepatocellular carcinoma (HCC) and to describe the role of H-ras mutation in carcinogenesis. Clinical samples of 69 patients were collected and the expression levels of H-ras in HCC and the surrounding normal tissues were examined using HotStarTaq PCR. H-ras mutation was further analyzed using the PCR direct sequencing method. The results showed that H-ras mutation was present in 49 samples (49/69, 71.01%), of which 19 had codon 40 mutated from CTA to CTG and 30 had codon 61 mutated from GGC to AGC. By contrast, only 2 mutations were found in the normal tumor-adjacent tissues. The H-ras mutation rate in the high-risk of metastatic recurrence group was markedly higher than that in the low-risk group (P<0.01). The H-ras mutation rate in patients with metastatic recurrence during postoperative follow-up was also significantly higher than that in patients without metastatic recurrence (P<0.01). Based on the above results, the H-ras mutation frequency in cancer tissues is markedly higher compared with that in normal tissues. H-ras mutation may play an important role in the genesis and development of HCC and may serve as a reliable marker for individual comprehensive therapy in HCC.

BackgroundProtein kinase C (PKC), interleukin (IL)-13, prostaglandin E2 (PGE2), and prostacyclin 2 (PGI2) can all play crucial roles in pulmonary fibrosis. However, their functions remain unclear in hepatic fibrosis mediated by hepatic stellate cells (HSCs), which has been demonstrated to be related to transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF).Material/MethodsAll the experiments were based on LX-2 Hepatic stellate cells. The expression of TGF-β1 and PDGF were assessed by ELISA, RT-PCR, and Western blotting in human HSCs treated by IL-13, PGE2, and PGI2, respectively. At the same time, bridge assay and CCK8 assay were used to detect the cell proliferation and activity, PKC activity assay was used to test the activity of PKC, and PKC agonist and antagonist were used to verify the results obtained previously.ResultsWe found that IL-13, PGE2, and PGI2 significantly enhanced the expression of TGF-β1 and PDGF in human HSCs, which also clearly improved the proliferation and cell activity of HSCs. Moreover, PKC activity was significantly increased following IL-13, PGE2, and PGI2 treatments. We also found that the expression of TGF-β1 and PDGF, as well as the proliferation and cell activity of HSCs, were significantly enhanced by the PKC agonist phorbol 12-myristate 13-acetate (PMA), but suppressed by the PKC antagonist calphostin C.ConclusionsWe found that IL-13, PGE2, and PGI2 stimulated HSCs proliferation and secretion of TGF-β1 and PDGF by activating PKC, which predicted their potential roles in hepatic fibrosis.