The roles of multifunctional CD4 T cells in human tuberculosis are not well defined. In this study, we found that patients with tuberculosis had decreased PMA/ionomycin stimulated multifunctional CD4 T cells, and increased Mycobacterium tuberculosis antigen-specific multifunctional CD4 T cells, when compared to individuals with latent tuberculosis infection and healthy controls. PMA/ionomycin stimulated IFN-γ+IL-2+TNF-α+ CD4 T cell responses were decreased in patients with smear-positive tuberculosis compared to those with smear-negative tuberculosis. The percentage of IFN-γ+IL-2+TNF-α+ CD4 T cells in smear positive tuberculosis patients negatively correlated with the grade of sputum smear Acid-Fast Bacilli and high-resolution computed tomography score. Therefore, our findings argue against the notion that Mycobacterium tuberculosis antigen-specific multifunctional Th1 responses in peripheral blood can serve as correlates of protective immunity against tuberculosis; they suggest that the decrease in PMA/ionomycin stimulated IFN-γ+IL-2+TNF-α+ CD4 T cells may be applied for clinical diagnosis of active tuberculosis.
Purpose Platinum-based chemotherapy, consisting of etoposide and cisplatin (EP), has been the cornerstone of therapy for extensive-stage small-cell lung cancer (ES-SCLC) for decades. Despite the marked initial sensitivity of SCLC to chemotherapy, EP regimens cannot avoid the emergence of drug resistance in clinical practice. With the rise of new chemotherapy regimens in recent years and the primary resistance or insensitivity of ES-SCLC to EP regimens, it is desirable to be able to identify patients with resistant or insensitive ES-SCLC. Methods The sequencing and drug sensitivity data of SCLC cell lines were provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). The data regarding sensitivity to etoposide of 54 SCLC cell lines were analyzed, and etoposide-sensitive cell lines and etoposide-resistant cell lines were differentiated according to the IC50 values defined by the GDSC. ROC curve analysis was performed on all mutations and combinations of mutations to select the optimal panel to predict resistance to etoposide. Results ROC analysis of etoposide resistance revealed that the most significant single gene mutation indicating resistance to etoposide was CSMD3 , and the accuracy of predicting resistance to etoposide proved to be the highest when there was any mutation in CSMD3/PCLO/RYR1/EPB41L3 , area under the curve =0.804 (95% confidence interval: 0.679–0.930, P <0.001 ). Conclusion This study found that a panel with four genes ( CSMD3, EPB41L3, PCLO, and RYR1 ) can accurately predict sensitivity to etoposide. These findings provide new insights into the overall treatment for patients with ES-SCLC that is resistant or insensitive to etoposide.
Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle to successful treatment in patients with breast cancer. Besides overexpression of MDR1, the member of the ABC transporter family, glucosylceramide synthase (GCS) which allows cellular escape from ceramide-induced cellular apoptosis by mediating ceramide glycosylation was considered to be related with multidrug resistance (MDR) in breast cancer. To specifically and efficiently reverse MDR of breast carcinoma cells, two small interference RNA (siRNA) targeted multidrug resistance 1 (MDR1) and GCS mediated by plasmids were constructed and co-transfected into the MDR breast cancer cell line MCF-7/ADM. The results showed that both transient transfection and stable transfection of the two siRNA-expression plasmids could greatly decrease the relative expression of GCS mRNA and MDR1 mRNA, significantly lower than the controls (p < 0.01). Evaluation of chemosensitivity displayed a 96-fold reduction in drug resistance for Adriamycin. And the reversing effects could keep for a long period (at least 3 w). Our results demonstrated that co-inhibition of MDR1 and GCS could more effectively reverse MDR in drug resistant breast carcinoma cells in vitro.
Immune checkpoint blockade (ICB) therapy has significantly progressed the treatment of bladder cancer (BLCA). Multiple studies have suggested that specific genetic mutations may serve as immune biomarkers for ICB therapy. Additionally, the nuclear receptor corepressor 1 (NCOR1) gene is a new player in the field of immune tolerance and the development of immune cells. In the ICI-treated-cohort, NCOR1 mutations may be used as a biomarker to predict the prognosis of BLCA patients receiving ICIs. The overall survival (OS) of the NCOR1-mutant (NCOR1-MT) group was significantly longer than that of NCOR1-wild-type (NCOR1-WT) group (P = 0·031; HR [95%CI]: 0·25 [0·12–0·52]). In the TCGA-BLCA-cohort, compared with NCOR1-WT, NCOR1-MT was associated with known predictors of ICB therapy efficacy, such as higher tumor mutational burden (TMB), neoantigen load and the number of mutations in the DNA damage-repair pathway. In addition, NCOR1-MT tumors had highly infiltrating TILs, activated antitumor immunity, and a high expression of immune-related genes, suggesting that NCOR1 mutations may serve as a potential biomarker to guide ICB therapy in BLCA.
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.