Exosomes are small membrane vesicles that are secreted by a multitude of cell types. The exosomes derived from dendritic cells (Dex), tumor cells (Tex), and malignant effusions demonstrate immunomodulatory functions, and are even under clinical trial for cancer treatments. In this study we report the phase I clinical trial of the ascites-derived exosomes (Aex) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) in the immunotherapy of colorectal cancer (CRC). The Aex isolated by sucrose/D(2)O density gradient ultracentrifugation are 60-90-nm vesicles that contain the diverse immunomodulatory markers of exosomes and tumor-associated carcinoembryonic antigen (CEA). Totally 40 patients (HLA-A0201(+)CEA(+)) with advanced CRC were enrolled in the study, and randomly assigned to treatments with Aex alone or Aex plus GM-CSF. Patients in both groups received a total of four subcutaneous immunizations at weekly intervals. We found that both therapies were safe and well tolerated, and that Aex plus GM-CSF but not Aex alone can induce beneficial tumor-specific antitumor cytotoxic T lymphocyte (CTL) response. Therefore, our study suggests that the immunotherapy of CRC with Aex in combination with GM-CSF is feasible and safe, and thus can serve as an alternative choice in the immunotherapy of advanced CRC.
This study aims to comprehensively analyze the diagnosis and prognosis of lncRNAs in hepatocellular carcinoma (HCC). From the Gene Expression Omnibus database, we screened out and analyzed the differently expressed lncRNAs and related mRNAs using bioinformatics methods. The expressions of lncRNAs were validated in tumor tissues, cell lines and the Cancer Genome Atlas database. At the same time, we also conducted an exploratory analysis on the diagnostic and prognostic ability of lncRNAs in HCC. In this study, we found that most of the targeted mRNAs promote the biological process of cell division, cellular component of nucleoplasm, molecular function of protein binding, which were significantly associated with 12 KEGG pathways. LncRNA CRNDE and LINC01419 also had significant diagnostic value in HCC. In particular, the sensitivity, specificity and area under the curve of CRNDE were 71.0%, 87.1% and 0.701 (95% CI: 0.543-0.860), respectively. In addition, the high expression of CRNDE and GBAP1 predicated poor prognosis, while the high expression of LINC01093 suggested the opposite outcome. Through the comprehensive analysis of lncRNAs, it provided an important reference for the early diagnosis, prognosis evaluation, pathogenesis and targeted therapy of HCC.
Osteoporosis, a systemic bone disorder, is prevalent in postmenopausal woman. Bone mesenchymal stem cells (BMSCs), precursors of osteogenic cells, may contribute to prevention or treatment of bone frustrate in osteoporosis. Recently, two studies suggested a role of calcitonin gene-related peptide (CGRP) in promoting osteogenesis of BMSCs under physiological conditions. However, the role of CGRP on BMSCs, which are derived from osteoporotic tissues, is unclear. Here, we investigated the role of CGRP on BMSCs isolated from female osteoporotic rats. Data showed that CGRP stimulated cell proliferation and inhibited cell apoptosis for short-term culture of BMSCs. Instead, CGRP induced BMSCs differentiation into the osteoblasts and promoted formation of calcified nodules after long-term culture. Moreover, CGRP gradually up-regulated expression levels of osteoporotic differentiation-related genes including alkaline phosphatase, Collagen type I, Bmp2, Osteonectin, and Runx2 during osteogenic differentiation. In conclusion, CGRP promoted proliferation and induced osteogenic differentiation and mineralization during female osteoporotic rat-derived BMSC differentiation. These findings support a potential role of CGRP on the prevention or treatment of osteoporotic fracture.
Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities.
Members of tumour necrosis factor (TNF) family usually trigger both survival and apoptotic signals in various cell types. Heat shock proteins (HSPs) are conserved proteins implicated in protection of cells from stress stimuli. However, the mechanisms of HSPs in TNFα-induced signalling pathway have not been fully elucidated. We report here that HSP70 over-expression in human colon cancer cells can inhibit TNFα-induced NFκB activation but promote TNFα-induced activation of c-Jun N-terminal kinase (JNK) through interaction with TNF receptor (TNFR)-associated factor 2 (TRAF2). We provide evidence that HSP70 over-expression can sequester TRAF2 in detergent-soluble fractions possibly through interacting with TRAF2, leading to reduced recruitment of receptor-interacting protein (RIP1) and IκBα kinase (IKK) signalosome to the TNFR1–TRADD complex and inhibited NFκB activation after TNFα stimuli. In addition, we found that HSP70–TRAF2 interaction can promote TNFα-induced JNK activation. Therefore, our study suggests that HSP70 may differentially regulate TNFα-induced activation of NFκB and JNK through interaction with TRAF2, contributing to the pro-apoptotic roles of HSP70 in TNFα-induced apoptosis of human colon cancer cells.
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.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.