Barrschwarz4627

With regards to apoptosis related proteins, ISOV increased Bax protein levels, and reduced Bcl-2 and Mcl-1 protein levels in SKSC. Importantly, there was a cooperative effect when miR-34a was overexpressed in the presence of ISOV in SK-SC, and down-regulation of miR-34a attenuated the effects of ISOV in SK-Hep-1 cells. CONCLUSION We suggest that ISOV-mediated miR-34a upregulation induces apoptosis and suppresses the stemness of SK-SC. Our data indicate that ISOV exhibits therapeutic potential for treatment of HCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.Improved understanding of the genomic and molecular landscape of acute myeloid leukemia (AML) has resulted in significant evolution of our understanding of AML biology and allows refined prognostication for those receiving standard combination chemotherapy induction. This dramatic increase in knowledge preceded, and was somewhat responsible for, at least some of eight new FDA drug approvals for AML. This review discusses the impact of genomics on clinical care of AML patients and highlights newly approved FDA drugs. Despite these recent clinical advances, however, the outcome for most patients diagnosed with AML remains dire. Thus, we describe here some of the challenges identified with treating AML including off-target toxicity, drug transporters, clonal heterogeneity, and adaptive resistance, and some of the most promising opportunities for improved therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.The genomic characterization of acute myeloid leukemia (AML) by DNA sequencing has illuminated subclasses of the disease, with distinct driver mutations, that might be responsive to targeted therapies. Approximately 15-23% of AML genomes harbor mutations in one of two isoforms of isocitrate dehydrogenase (IDH1 or IDH2). These enzymes are constitutive mediators of basic cellular metabolism, but their mutated forms in cancer synthesize an abnormal metabolite, 2-hydroxyglutarate, that in turn acts as a competitive inhibitor of multiple gene regulatory enzymes. As a result, leukemic IDH mutations cause changes in genome structure and gene activity, culminating in an arrest of normal myeloid differentiation. These discoveries have motivated the development of a new class of selective small molecules with the ability to inhibit the mutant IDH enzymes while sparing normal cellular metabolism. These agents have shown promising anti-leukemic activity in animal models and early clinical trials, and are now entering Phase 3 study. This review will focus on the growing preclinical and clinical data evaluating IDH inhibitors for the treatment of IDH-mutated AML. These data suggest that inducing cellular differentiation is central to the mechanism of clinical efficacy for IDH inhibitors, while also mediating toxicity for patients who experience IDH Differentiation Syndrome. Ongoing trials are studying the efficacy of IDH inhibitors in combination with other AML therapies, both to evaluate potential synergistic combinations as well as to identify the appropriate place for IDH inhibitors within existing standard-of-care regimens. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Increasing evidence has shown that p62 plays an important role in tumorigenesis. DW71177 price However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated. OBJECTIVE To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma. METHODS Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters. RESULTS We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal‑regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P less then 0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis. CONCLUSION Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.The mitogen-activated protein kinase (MAPK) pathwayis among the key factors in numerous cellular processes involved in tumorigenesis, suggesting it as a potential therapeutic target in gynecological cancer. MAPKs connect gene expression pathways and external stimulations. They include a network consist of Ras, Raf or MAP3K, MEK or MAP2K, ERK or MAPK. Among these,MEK is an attractive molecular target of novel cancer therapeutics as it joints upstream activators and their corresponding downstream targets.MEK inhibitors were among thefirst inhibitors of the MAPK pathway enteringinto clinical trials. Several drugs have recently been developed as MEKinhibitors. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity to treat this malignancy and captured much attention in the past decade. Here, we summarized the role of MAPK/MEK/ERK pathway in the pathogenesis of gynecological cancer, with particular emphasis on MEK inhibitors in clinical settings including PD-0325901, Selumetinib, Cobimetinib, Refametinib, Trametinib, Pimasertib, MEK162 and WX-554 in gynecologic cancers.