Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity.
In this study, we reported two X-ray crystal structures of human NSDHL, which revealed a detailed description of the coenzyme-binding site and the unique conformational change upon the binding of a coenzyme. A structure-based virtual screening and biochemical evaluation were performed and identified a novel inhibitor for NSDHL harboring suppressive activity towards EGFR. In EGFR-driven human cancer cells, treatment with the potent NSDHL inhibitor enhanced the antitumor effect of an EGFR kinase inhibitor. Overall, these findings could serve as good platforms for the development of therapeutic agents against NSDHL-related diseases. PMID: 32140747 [PubMed - as supplied by publisher]
Conclusions: In SECC diagnosed as stage T2N0M0 by CT and EUS, the incidence of postoperative pathologic upstaging increases with a large TV, high TC, high TGs, high PLR, and high number of lymph nodes examined.
British Journal of Cancer, Published online: 22 September 2020; doi:10.1038/s41416-020-01085-zGenkwadaphnin inhibits growth and invasion in hepatocellular carcinoma by blocking DHCR24-mediated cholesterol biosynthesis and lipid rafts formation
In conclusion, long-term feeding of either HFHF or WDHC are reliable methods to induce NASH and diet-potentiated liver cancer in mice of both sexes; however, the choice of diet involves a trade-off between severity of metabolic syndrome and liver damage. PMID: 32924526 [PubMed - as supplied by publisher]
Background and AimsMutational profiling of patient tumors has suggested that hepatocellular carcinoma (HCC) development is mainly driven by loss-of-function mutations in tumor suppressor genes. p90 Ribosomal S6 kinase 2 (RSK2) functions as a direct downstream kinase of ERK1/2, and elevated RSK2 expression supporting oncogenic functions has been reported in some cancers. We investigated if RSK2 was also dysregulated by inactivating mutations in cancers including HCC.MethodsWe performed exome-sequencing and targeted DNA-sequencing on HBV-associated HCCs to examine recurrent RSK2 mutations.
ConclusionsOur findings indicate that the lipid metabolism ‐related signature shows prognostic significance for HCC.
Contributors : Igor Astsaturov ; Suraj PeriSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusOncogenic transformation alters the metabolism of cellular lipids to sustain tumor growth. We define a reciprocal mechanism by which cholesterol metabolism controls the formation and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of Nsdhl, or treatment with cholesterol-lowering statins caused murine pancreatic carcinomas induced by KrasG12D expression and homozygous Trp53 loss to undergo a differentiation swit...
-Hung Liu Statins, also known as HMG-CoA reductase inhibitors, are a class of cholesterol-lowering drugs and their anti-cancer effects have been studied in different types of malignant diseases. In the present study, we investigated the anti-proliferative effects of statins, including cerivastatin and simvastatin, on oral squamous cell carcinoma (OSCC) cells. Our data showed that statins inhibited the proliferation of three OSCC cell lines in a dose-dependent manner and this growth inhibition was confirmed through G0/G1 cell cycle arrest. Accordingly, we found the upregulation of p21 and downregulation of cyclin-depend...
ConclusionThe trial evidence is not sufficiently robust to confirm or refute the efficacy and safety of statins in patients with solid malignant tumours. Study and patient characteristics may explain this uncertainty. The potential role of high-dose statins in adjuvant settings deserves further research.
CONCLUSION: Whereas further testing in patients are necessary to better clarify the therapeutic potential for OC of repurposed drugs, we believe that their use, better if combined with OC targeted delivery systems, can significantly contribute to the development of novel and effective anti OC treatments. PMID: 32660396 [PubMed - as supplied by publisher]
In conclusion, these results demonstrate that the downregulation of HMGCS2 attenuates the protective effect of the KD by shifting ketone production to enhance de novo lipogenesis in HCC. Our study elucidates a new molecular mechanism underlying the crosstalk between HMGCS2 expression and the KD in cancer treatment, which provides more information for precision medicine in developing personalized treatment strategies.