Mutations in the gene ELOVL4 have been shown to cause stargardt-like macular dystrophy. ELOVL4 is part of a family of fatty acid elongases and is yet to have a specific elongase activity assigned to it. We generated Elovl4 Y270X mutant mice and characterized the homozygous mutant as well as homozygous Elovl4 knockout mice in order to better understand the function or role of Elovl4. We found that mice lacking a functional Elovl4 protein died perinatally. The cause of death appears to be from dehydration due to faulty permeability barrier formation in the skin. Further biochemical analysis revealed a significant reduction in free fatty acids longer than C26 in homozygous mutant and knockout mouse skin. These results implicate the importance of these long chain fatty acids in skin barrier development. Furthermore, we suggest that Elovl4 is likely involved in the elongation of C26 and longer fatty acids.
Background: Current treatment options for human epidermal growth factor receptor 2 (HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit. Further, there is no specific treatment for HER2 immunohistochemistry (IHC) 2+ and fluorescence in-situ hybridization-negative patients. Here, we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing, advanced gastric or gastroesophageal junction cancer.Methods: Patients with HER2-overexpressing (IHC 2+ or 3+), locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC48 2.5 mg/kg alone every 2 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee. Secondary endpoints included progressionfree survival (PFS), overall survival (OS), duration of response, time to progression, disease control rate, and safety.
Programmed cell death-1 (PD-1) is an oncogene associated with suppressing proliferation and cytokine production of T cells in the progression of liver cancer. microRNAs (miRs) regulate gene expression via specific binding to the target 3′untranslated region of mRNA. In the present study, miR-374b was indicated to interact with PD-1 and affect the tumor-targeting capacity of cytokine-induced killer (CIK) cells. miR-374b inhibitor significantly increased PD-1 expression in CIK cells. A synthetic small interfering (si)RNA targeting PD-1 was employed to silence the expression level of PD-1 in CIK cells. Then, the antitumor effect of siPD-1 in CIK cells was investigated. In vitro study demonstrated that IFN-γ secretion and the concentration of lactate dehydrogenase were significantly increased in the PD-1 knockdown group; however, the viability of HepG2 cells in the PD-1 knockdown group had significantly decreased, compared with the HepG2 cells in the negative control group. In vivo study indicated that mice inoculated with HepG2 cells and CIK cells with PD-1 knocked down had a significantly smaller tumor volume, compared with the control group. To conclude, human CIK cells transfected with siPD-1 can target liver cancer cells and enhance immunotherapy efficacy, and therefore they have potential in the immunotherapy of liver cancer.
Recently, mutations in transmembrane protein 240 (TMEM240) were identified as the cause of spinocerebellar ataxia type 21 (SCA21) in several French families. Clinically, SCA21 is characterized as an early-onset, slowly progressive cerebellar syndrome typically associated with cognitive impairment. To date, molecular screening of SCA21 has not been reported among patients of other ethnic origins or in other areas. Here we used Sanger sequencing to detect mutations in exons of TMEM240 in 340 unrelated probands with spinocerebellar ataxia for whom commonly known causative mutations have been excluded (96 probands of autosomal dominant spinocerebellar ataxia families and 244 patients with sporadic spinocerebellar ataxia). As a result, a de novo missense mutation (c.509C > T/p.P170L) was identified in one sporadic SCA patient. The condition manifested as early-onset (30 years old), slowly progressive cerebellar ataxia accompanied by mild early evidenced mental retardation, mild frontal behavior disorders and intentional hand tremors. Although rare, a SCA21 case was identified and described in mainland China, thus broadening the ethnic distribution of SCA21 beyond French families.
We explored that lncRNA FUNDC2P4 down-regulation promoted EMT leading to tumour proliferation, invasion and migration by reducing E-cadherin expression in residual HCC after insufficient RFA in vitro. These results suggest that FUNDC2P4 may have potentially therapeutic value for prevention and treatment of HCC recurrence after RFA in the future.
Metronomic chemotherapy with prednisone, etoposide, and cyclophosphamide resulted in higher ORR and DCR, fewer adverse effects, and longer PFS in patients with relapsed or refractory NHL, with significant reduction in serum CECs and VEGF levels.
Cisplatin resistance remains a major obstacle to effective chemotherapies for non-small cell lung cancer (NSCLC). Chaperonin containing TCP1 subunit 3 (CCT3) has been extensively investigated in various cancers, but not in the context of drug resistance. In the present study, we aimed to investigate the role of CCT3 in cisplatin resistance of lung adenocarcinoma (LUAD) cells. By surveying the Gene Expression Profiling Interactive Analysis (GEPIA) website, we found CCT3 expression to be up-regulated in NSCLCs, which correlated with the poor prognosis of LUAD patients. Furthermore, both mRNA and protein levels of CCT3 were upregulated in the cisplatinresistant A549/DDP cells compared to the cisplatin-sensitive A549 cells. Importantly, upon cisplatin treatment, short hairpin RNA (shRNA)-mediated CCT3 knockdown significantly inhibited the proliferation, invasion and migration of A549/DDP cells, and induced significant G2/M cell cycle arrest and apoptosis in A549/DDP cells. Moreover, CCT3 knockdown significantly weakened the tumorigenicity of the cisplatin-treated A549/DDP cells in vitro and in vivo. Finally, CCT3 knockdown re-sensitized A549/DDP cells to cisplatin through inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. In conclusion, our results demonstrated that CCT3 could promote cisplatin resistance of LUAD cells via activating the JAK2/ STAT3 pathway, indicating that CCT3 may be a novel molecular target for overcoming cisplatin resistance in LUAD patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.