1%).
 
  Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit-risk balance in sorafenib pretreated aHCC with MET overexpression.
 
  ClinicalTrials.gov NCT02115373.
 ClinicalTrials.gov NCT02115373.Radiotherapy is essential to the treatment of nasopharyngeal carcinoma (NPC) and acquired or innate resistance to this therapeutic modality is a major clinical problem. However, the underlying molecular mechanisms in the radiation resistance in NPC are not fully understood.  https://www.selleckchem.com/products/bms-265246.html  Here, we reanalyzed the microarray data from public databases and identified the protein tyrosine phosphatase receptor type D (PTPRD) as a candidate gene. We found that PTPRD was downregulated in clinical NPC tissues and NPC cell lines with its promoter hypermethylated. Functional assays revealed that PTPRD overexpression sensitized NPC to radiation in vitro and in vivo. Importantly, miR-454-3p directly targets PTPRD to inhibit its expression and biological effect. Interestingly, mechanistic analyses indicate that PTPRD directly dephosphorylates STAT3 to enhance Autophagy-Related 5 (ATG5) transcription, resulting in triggering radiation-induced autophagy. The immunohistochemical staining of 107 NPC revealed that low PTPRD and high p-STAT3 levels predicted poor clinical outcome. Overall, we showed that PTPRD promotes radiosensitivity by triggering radiation-induced autophagy via the dephosphorylation of STAT3, thus providing a potentially useful predictive biomarker for NPC radiosensitivity and drug target for NPC radiosensitization.Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.Therapeutic strategies to treat pancreatic ductal adenocarcinoma (PDAC) remain unsatisfying and limited. Therefore, it is imperative to fully determine the mechanisms underlying PDAC progression. In the present study, we report a novel role of regulator of calcineurin 1, isoform 4 (RCAN1.4) in regulating PDAC progression. We demonstrated that RCAN1.4 expression was decreased significantly in PDAC tissues compared with that in para-cancerous tissues, and correlated with poor prognosis of patients with pancreatic cancer. In vitro, stable high expression of RCAN1.4 could suppress the metastasis and proliferation and angiogenesis of pancreatic tumor cells. In addition, interferon alpha inducible protein 27 (IFI27) was identified as having a functional role in RCAN1.4-mediated PDAC migration and invasion, while VEGFA play a vital role in RCAN1.4-mediated PDAC angiogenesis. Analysis of mice with subcutaneously/orthotopic implanted xenograft tumors and liver metastasis model confirmed that RCAN1.4 could modulate the growth, metastasis, and angiogenesis of tumors via IFI27/VEGFA in vivo. In conclusion, our results suggested that RCAN1.4 suppresses the growth, metastasis, and angiogenesis of PDAC, functioning partly via IFI27 and VEGFA. Importantly, our results provided possible diagnostic criteria and therapeutic targets for PDAC.Emerging evidence suggests that long noncoding RNAs (lncRNAs) function as competitive endogenous RNA (ceRNA) targeting proteins and genes; however, the role of lncRNAs in hepatocellular carcinoma (HCC) is not well understood. We investigated the mechanism by which lncRNA SNHG6 promotes the development of HCC. RT-qPCR revealed upregulated lncRNA SNHG6 in the HCC setting. Elevated SNHG6 expression was indicative of poor prognosis in patients with HCC. SNHG6 overexpression resulted in increased cyclin D1, cyclin E1, and E2F1 expression both in vitro and in vivo. SNHG6 also promoted HCC cell proliferation by enhancing G1-S phase transition in vitro. Dual luciferase reporter assays, RIP, and RNA pull-down assays demonstrated SNHG6 competitively bound to miR-204-5p and inhibited its expression preventing miR-204-5p from targeting E2F1. Overexpression of miR-204-5p abolished the effect of SNHG6. Our data suggest that SNHG6 functions as a ceRNA that targets miR-204-5p resulting in an increased E2F1 expression and enhanced G1-S phase transition, thereby promoting the tumorigenesis of HCC.Chronic myeloid leukemia (CML) is an age-dependent blood malignancy. Like many other age-dependent human diseases, laboratory animal research of CML uses young mice that do not factor in the influence of aging. To understand how aging may impact animal modeling of human age-dependent diseases, we established the first aging mouse model of human CML in BALB/c mice in the advanced age defined by 75% survival. This model was developed by noncytotoxic depletion of bone marrow lineage-positive cells followed by BCR-ABL retroviral transduction and transplantation. CML developed in aging mice shared many similarities to that in young mice, but had increased incidence of anemia that is often seen in human CML. Importantly, we showed that aging of both donor hematopoietic stem cells and recipient bone marrow niche impacted BCR-ABL mediated leukemogenesis and leukemia spectrum. Optimal CML induction relied on age-matching for donors and recipients, and cross-transplantation between young and old mice produced a mixture of different leukemia.