Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PI3K/AKT constitutes an important pathway regulating the signaling of multiple biological processes and plays a critical role in carcinogenesis. PIK3CA gene missense mutations have been reported in many human cancer types. The mutation of it in hepatocellular carcinoma cases varies with different races and regions. In this study, we investigated PIK3CA mutation in Chinese hepatocellular carcinoma patients. A total 90 Chinese patients of hepatocellular carcinoma were recruited in this study. Exons 9 and 20 hotspots mutations of PIK3CA gene were detected by PCR-based DNA sequencing. Two point mutations (E542K and D549H) in exon 9 were found in only one patient (1/90; 1.11%), no mutation was found in exon 20 in any cases. 57 patients are associated with HBV infection (57/90; 63.3%), and 8 patients with HCV infection (8/90; 8.9%). The frequency of the PIK3CA mutations in hepatocellular carcinoma seems to be lower in Chinese hepatocellular carcinoma patients. These findings suggest that PI3K mutations may not play a major role in hepatic carcinogenesis in Chinese. HBV infection has close relationship with HCC in Chinese.
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PMID:Low frequency of PIK3CA gene mutations in hepatocellular carcinoma in Chinese population. 2166 6

Primary liver cancer (hepatocellular carcinoma, HCC) is a leading cause of cancer-related deaths, and alternative ways to treat this disease are urgently needed. In recent years, novel approaches to cancer treatment have been based on microRNAs, small non-coding RNA molecules that play a crucial role in cancer progression by regulating gene expression. Overexpression of some microRNAs has shown therapeutic potential, but whether or not this was the case for microRNA-203 (miR-203) in liver cancer was unknown. Therefore, the aim of this study was to investigate the effect of miR-203 overexpression in liver cancer and explore the related mechanisms. Liver cancer cells from the HepG2 and Hep3B cell lines were transfected with either miR-203 mimics or negative control RNA, and then the cells were subjected to cell viability, cell proliferation, and Western blotting assays. As a result of microRNA-203 overexpression, HepG2 and Hep3B cell viability and cell proliferation significantly declined. Furthermore, microRNA-203 overexpression led to inhibited expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3)/protein kinase B (Akt), c-Jun, and p38 mitogen-activated protein kinases (p38 MAPK), and restored glycogen synthase kinase 3 (GSK 3) activity in HepG2 cells. Our results suggest that c-Jun, p38 MAPK, PIK3CA/Akt, and GSK3 signaling involved in the effect of miR-203 on the proliferation of HCC cells.
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PMID:MicroRNA-203 suppresses proliferation in liver cancer associated with PIK3CA, p38 MAPK, c-Jun, and GSK3 signaling. 2888 44

The proviral integration of Moloney virus (PIM) family of protein kinases are overexpressed in many haematological and solid tumours. PIM kinase expression is elevated in PI3K inhibitor-treated breast cancer samples, suggesting a major resistance pathway for PI3K inhibitors in breast cancer, potentially limiting their clinical utility. IBL-302 is a novel molecule that inhibits both PIM and PI3K/AKT/mTOR signalling. We thus evaluated the preclinical activity of IBL-302, in a range of breast cancer models. Our results demonstrate in vitro efficacy of IBL-302 in a range of breast cancer cell lines, including lines with acquired resistance to trastuzumab and lapatinib. IBL-302 demonstrated single-agent, anti-tumour efficacy in suppression of pAKT, pmTOR and pBAD in the SKBR-3, BT-474 and HCC-1954 HER2+/PIK3CA-mutated cell lines. We have also shown the in vivo single-agent efficacy of IBL-302 in the subcutaneous BT-474 and HCC-1954 xenograft model in BALB/c nude mice. The combination of trastuzumab and IBL-302 significantly increased the anti-proliferative effect in HER2+ breast cancer cell line, and matched trastuzumab-resistant line, relative to testing either drug alone. We thus believe that the novel PIM and PI3K/mTOR inhibitor, IBL-302, represents an exciting new potential treatment option for breast cancer, and that it should be considered for clinical investigation.
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PMID:Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer. 3204 15