Lawvest3846

Ovarian cancer is the most lethal gynecologic malignancy. Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective in treating ovarian cancer. However, cancer cell insensitivity and resistance remain challenges. Determination of the exact chemoresistance mechanisms and potential targeted therapies is urgent. CDCA8 (cell division cycle associated 8) participates in the tumorigenesis of various cancers; however, the exact biological function of CDCA8 in ovarian cancer remains obscure. Here, we found that CDCA8 was overexpressed in ovarian cancer and that high expression of CDCA8 promoted the proliferation of ovarian cancer cells in vitro and in vivo. Moreover, silencing of CDCA8 sensitized ovarian cancer cells to olaparib and cisplatin by inducing G2/M arrest, accelerating apoptosis, increasing DNA damage and interfering with RAD51 accumulation in vitro. In addition, MYBL2 (MYB proto-oncogene-like 2), identified as an upstream transcription factor of CDCA8, was positively correlated with the expression level of CDCA8 in ovarian cancer. learn more Finally, MYBL2 enhanced the aggressive characteristics of ovarian cancer cells by regulating CDCA8. In conclusion, high CDCA8 expression was involved in the tumorigenesis, aggressiveness and chemoresistance of ovarian cancer. CDCA8 silencing combined with olaparib treatment might lead to substantial progress in ovarian cancer targeted therapy.Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. β-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of β-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of β-elemene (10 μg/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated β-galactosidase (SA-β-Gal) activity, upregulation of several senescence-associated genes such as p16, p53 and NF-κB, and downregulation of Lamin B1. However, a high concentration of β-elemene induced apoptosis in glioma cells. Treatment with β-elemene caused a marked down-regulation of Yes-associated protein (YAP) expression in glioma cells, which is a key transcriptional co-activator in multiple cancers. Moreover, cyclin dependent kinase 6 (CDK6), which is a known downstream target of YAP, was decreased in glioma cells that treated with β-elemene. The overexpression of YAP and CDK6 significantly rescued β-elemene-induced senescence in glioma cells. Finally, β-elemene treatment also induced the senescence of glioma cells in glioma xenograft model through inactivation of YAP-CDK6 pathways, which might inhibit the glioma growth. Taken together, these results reveal a previously unknown role of β-elemene in glioma cell senescence in vitro and in vivo that is associated with YAP-CDK6 signaling pathway, which will enhance our understanding of glioma cell senescence, and provide novel strategies for the treatment of gliomas.In this study, in vitro cytotoxic effects of seven adamantyl isothiourea derivatives were evaluated against five human tumor cell lines using the MTT assay. Compounds 5 and 6 were found to be the most active derivatives particularly against hepatocellular carcinoma (HCC). To decipher the potential mechanisms involved, in vivo studies were conducted in rats by inducing HCC via chronic thioacetamide (TAA) administration (200 mg/kg, i.p., twice weekly) for 16 weeks. Compounds 5 and 6 were administered to HCC rats, at a dose of 10 mg/kg/day, for further 2 weeks. In vitro and in vivo antitumor activities of compounds 5 and 6 were compared to those of the anticancer drug doxorubicin (DOXO). In the HCC rat model, compounds 5 and 6 significantly reduced serum levels of ALT, AST with ALP and α-fetoprotein. H & E and Masson trichrome staining revealed that both compounds suppressed hepatocyte tumorigenesis and diminished fibrosis, inflammation and other histopathological alterations. Mechanistically, compounds 5 and 6 markedly decreased protein expression levels of α-SMA, sEH, p-NF-κB p65, TLR4, MyD88, TRAF-6, TNF-α, IL-1β and TGF-β1, whereas they increased caspase-3 expression in liver tissues of HCC rats. In most analyses, the effects of compound 6 were more comparable to DOXO than compound 5. These findings suggested that the compounds 5 and 6 displayed in vitro and in vivo cytotoxic potential against HCC, probably via inhibition of TLR4-MyD88-NF-κB signaling.Hepatocellular carcinoma (HCC) is the most frequent malignancy of the liver, which is considered the fourth leading cause of cancer-related death in the United States. Liver transplant and surgical resection are curative treatments for HCC, but only 10-15% of HCC patients are eligible candidates. The FDA-approved sorafenib is a multi-kinase inhibitor systemic therapy for advanced HCC that extends the overall survival by over 3 months when compared with placebo. Adoptive transfer of Natural Killer (NK) cells holds great promise for clinical cancer treatment. However, only limited clinical benefit has been achieved in cancer patients. Therefore, there is currently considerable interest in development of the combination of sorafenib and NK cells for the treatment of HCC patients. However, the mechanism of how sorafenib affects the function of NK cells remains to be comprehensively clarified. In this paper, we will discuss NK cell-based immunotherapies that are currently under preclinical and clinical investigation and its potential combination with sorafenib for improving the survival of HCC patients.The renin-angiotensin system (RAS) regulates physiological functions of the cardiovascular system, kidneys, and other tissues. Various in vivo and in vitro studies have shown that RAS plays a pivotal role in the development of malignant tumors, while several retrospective studies have confirmed that patients undergoing long-term RAS inhibitors (RASi) treatment have a lowered risk of cancer. Moreover, blocking RAS has been shown to inhibit tumor growth, metastasis, and angiogenesis in various experimental models of malignant tumors. Herein, we review the available RASi-related literature and provide an analysis using the scientific atlas software VOSviewer. We observed that recent studies have primarily focused on gene expression, tumor biology, and survival analysis. Through an in-depth data analysis from the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx), we identified the impact of AGTR1, an essential component of RAS, on tumors, and we discuss the underlying biological mechanism of RASi. Furthermore, we outline the research progress and potential use of RASi in tumor treatment.