Deubiquitylases in Tumors / 中国生物化学与分子生物学报

Dynamic ubiquitination in eukaryotes either enters proteins into the 26S proteasome degradation pathway or functions in signal transduction, and therefore regulates protein stability, localization and activity, thus participates in transcription, cell cycle, inflammation, tumor, immunity and other functions.Ubiquitination modification is a reversible process, which is regulated by ubiquitin ligases (E3s) and deubiquitylases (I)lJBs).DUBs mediate the deubiquitination of substrate proteins, regulate protein functions, and participate in various cellular processes.The protein abundance, localization and catalytic activity of deubiquitylases are strictly regulated.During the occurrence and development of tumors, many important tumor-related proteins are regulated by deubiquitylases, and dysfunction of deubiquitylases also affect DNA damage repair, apoptosis, autophagy, molecular signaling pathways and chromatin remodeling, which modulate the process of cell growth, invasion and metastasis in tumors.Therefore, DUB is an important protein family involved in tumorigenesis, and is potential drug targets.Many small molecule inhibitors have been used in the research of anti-tumor treatments.This article mainly summarizes the regulation mechanism of ubiquitin molecules, ubiquitin chain specificity, and deubiquitinating enzyme system in tumors, and provides basis for the design of clinical drug targets and diagnostic indicators.

Relation between c-erbB1, c-erbB2, MAPK expression and resistance to tamoxifen in breast cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the growth regulation pathway and the mechanism of acquired resistance to tamoxifen (TAM) in breast cancer cells.</p><p><b>METHODS</b>TAM was used to induce wild-type MCF-7 human breast cancer cell line and establish a tamoxifen-resistant (TAM-R) cell line. RT-PCR, Western blot and immuocytochemical techniques were used to detect and compare mRNA and protein of c-erbB1, cerbB2, c-erbB3, c-erbB4 in wild-type MCF-7 and TAM-R MCF-7 cell lines.</p><p><b>RESULTS</b>Compared with wild-type MCF-7 cells, the mRNA of c-erbB1 increased 6 times (P < 0.05) and the protein 3 times higher (P < 0.05), and the mRNA of c-erbB2 increased 3 times (P < 0.05) and the protein 1.5 times higher (P < 0.05) in TAM-R MCF-7 cells. However, comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. c-erbB4 could not be detected. Under basic conditions, phosphorylated c-erbB1/c-erbB2 and c-erbB1/c-erbB3 heterodimers but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased level of phosphorylated MAPK.</p><p><b>CONCLUSION</b>Our findings demonstrated that the development of TAM-resistance in MCF-7 cells is related with the autocrine release and action of an c-erbB1-specific ligand inducing preferential c-erbB1/c-erbB2 dimerization and downstream activation of the MAPK pathway.</p>

Relationship between hepatic insulin resistance and the expression of genes involved in hepatic glucose output / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the relationship between hepatic insulin resistance induced by high fat diet and the expression of genes involving hepatic glucose output.</p><p><b>METHODS</b>Normal 8-week-old male SD rats were randomly divided into two groups, i.e, normal chow group (NC, n = 10) and high fat diet group (HF, n = 10). They were fed for 28 weeks. Body weight and fasting blood glucose (FBG) were measured. At the end of the experiment, the rats were sacrificed and their fasting insulin (INS) and triglycerides (TG) were measured. Hepatic insulin sensitivity was measured by tissue uptake of 3H-2-deoxyglucose and the content of hepatic glycogen was measured using the anthrone method. Gene expression was investigated by using the semi-quantitative RT-PCR method.</p><p><b>RESULTS</b>As compared with NC group, CF group rats developed visceral obesity which was accompanied by higher plasma TG. FBG in CF group increased starting from the 18th week (NC 4.77+/-63 mmol/L vs HF 5.45+/-87 mmol/L, P < 0.05). The rate of uptake of 3H-2-deoxyglucose in livers decreased by 51% in the HF group. The content of hepatic glycogen increased by 92.4% (P < 0.01). The level of phosphoenolpyruvate carboxykinase (PEPCK) and PGC-1a mRNA increased by 41.5% and 30.8%, respectively (P < 0.05).</p><p><b>CONCLUSION</b>A high fat diet induced expressions of PGC-1a and PEPCK. It suggests that gluconeogenesis may play a role in the increase of hepatic glucose output and FBG.</p>

Effect on late-stage mammary cancer treated by endocrinotherapy or chemotherapy combined with pingxiao capsule / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the action of pingxiao capsules (PXC) and its significance in the treatment of late stage mammary cancer (LSMC).</p><p><b>METHODS</b>One hundred and forty-two LSMC patients were randomized into four groups: the two single treated groups treated by endocrinotherapy (ET) alone (n = 27) and by chemotherapy alone (n=44) respectively, and the two PXC combined treated groups treated with PXC plus endocrinotherapy (n=27) or chemotherapy (n=44). The remission rate and progression time (TTP) of disease, the survival time and quality of life (QOL) of patients, and the adverse reaction were compared between the single treated groups and the combined treated groups.</p><p><b>RESULTS</b>The median progression time was obviously prolonged, and QOL improved in the combined treated groups than those in the single treated groups (P < 0.05), but no significant difference was found in the remission rate or adverse reaction between them.</p><p><b>CONCLUSION</b>PXC can improve QOL, prolong the progression time in patients of LSMC, and with less adverse reaction. It is worth spreading combination of PXC with chemo- or endocrino-therapy in clinical application for treatment of LSMC patients.</p>