PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8+ T cell suppression.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by metabolic dysregulation. Tumor cell immune escape plays an indispensable role in the development of TNBC tumors. Furthermore, in the abstract, we explicitly mention the techniques used and enhance the clarity and impact of our findings. "Based on bioinformatics analysis results, we utilized CRISPR/Cas9 technology to knockout the target gene and established a mouse model of breast cancer. Through experiments such as CCK8, scratch assay, and Transwell assay, we further investigated the impact of target gene knockout on the malignant behavior of tumor cells. Subsequently, we conducted immunohistochemistry and Western Blot experiments to study the expression of macrophage polarization and infiltration-related markers and evaluate the effect of the target gene on macrophage polarization. Next, through co-culture experiments, we simulated the tumor microenvironment and used immunohistochemistry staining to observe and analyze the distribution and activation status of M2 macrophages and CD8+ T cells in the co-culture system. We validated in vivo experiments the molecular mechanism by which the target gene regulates immune cell impact on TNBC progression.

Prognostic impact of neutrophil-to-lymphocyte ratio in gliomas: a systematic review and meta-analysis.

BACKGROUND: In some malignant tumors, a high neutrophil-to-lymphocyte ratio (NLR) is connected with unfavorable prognosis. Nevertheless, the prognostic value of the NLR in gliomas remains disputed. The clinical significance of the NLR in gliomas was investigated in our study. METHODS: The databases, PubMed, Embase, and the Cochrane Library, were searched using words like "glioma," "glioblastoma," "neutrophil-to-lymphocyte ratio," and others through May 2019. We evaluated the significance of NLR on overall survival (OS) of patients with gliomas in our study. RESULTS: Finally, 16 cohorts with 2275 patients were analyzed. The pooled analysis revealed that an elevated NLR was connected with unfavorable OS (hazards ratio (HR): 1.43, 95% confidence interval (CI): 1.27-1.62) outcomes of patients with gliomas. CONCLUSION: A high NLR can be considered a high-risk prognostic factor in gliomas, and more adjuvant chemotherapy should be recommended for high-risk patients.

Prognosis of Patients With Brainstem Glioblastoma Based on "age, surgery and radiotherapy": A SEER Database Analysis.

Introduction: Primary brainstem glioma is a rare tumor with a dismal prognosis that poses significant treatment challenges. The purpose of the current study is to identify and determine prognostic factors associated with survival in high-grade brainstem glioma patients. Methods: We gathered the data from the SEER database for the duration of years from 1973 to 2016 to examine the survival of patients particularly reported with the high-grade brainstem glioma and subsequently ascertained the potential impact of demographic features, tumor, and clinical characteristics on the overall survival of these patients. The survival patterns were assessed using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) analysis was performed between patients with or without radiation therapy based on age and surgical resection to investigate the effect of radiotherapy on overall survival (OS). Results: A total 232 patient's data were obtained from the SEER database and included in this study. The median overall survival was 8 months. Kaplan-Meier survival analysis delineated that the patients who were in younger age (P = .001) and underwent surgery (P = .001) exhibited typically a better prognosis. Among 232 patients, a total of 204 patients were categorized as radiotherapy group (RG) received radiation therapy whereas 28 patients were considered as nonradiotherapy group (NRG), who were not receiving radiotherapy. Radiotherapy was associated with an improvement in the overall survival without statistical significance (P = .104). PSM was performed between RG and NRG based on age and surgical resection. After the PSM, 56 patients were included. Overall Survival was significantly different between both groups (P = .038). Conclusion: Furthermore, the patients with high-grade brain glioma who received "both radiotherapy and chemotherapy" exhibited significantly longer survival compared to the patients who received chemotherapy alone. Multivariate analysis showed that treatment with surgery and radiotherapy were considered as the independent prognostic factors (P < .05).

Clinical Application of Iodine-125 Seed Brachytherapy Combined with Anti-PD-1 Antibodies in the Treatment of Lung Cancer.

PURPOSE: The purpose of this case report was to investigate the clinical efficacy and tolerability of anti-programmed cell death protein (PD)-1 antibody combined with iodine (I)-125 seed brachytherapy in lung cancer treatment. METHODS: Three patients with advanced PD-L1-positive non-small-cell lung cancer were treated first with I-125 seed brachytherapy and then with anti-PD-1 antibody. Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. FINDINGS: All 3 patients had complete response or partial response. None of the 3 patients had reported obvious adverse events. IMPLICATIONS: Encouraging preliminary results provide important support for further clinical treatment of lung cancer using anti-PD-1 antibody combined with I-125 seed brachytherapy.

The pharmacological role of histone demethylase JMJD3 inhibitor GSK-J4 on glioma cells.

Glioma is regarded as the most prevalent malignant carcinoma of the central nervous system, and lack of effective treatment. Thus, the development of new therapeutic strategies targeting glioma is of significant clinical importance. In the present study, histone H3K27 demethylase jumonji domain-containing protein 3 (JMJD3) was investigated as target for glioma treatment. The mRNA of JMJD3 was overexpressed in glioblastoma tissues compared to normal brain tissues (P<0.05). The content of JMJD3 was also higher in glioma cells than in human brain microvascular endothelial cell (hCMEC), and the corresponding level of H3K27me3 was decreased (P<0.05). The treatment with JMJD3 specific inhibitor GSK-J4 can increase the content of H3K27me3 in glioma cells, which means the activity of JMJD3 was inhibited. GSK-J4 can inhibit glioma cell proliferation in a concentration dependent and time-dependent manner (P<0.05). GSK-J4 also induced glioma cell apoptosis and inhibited cell migration (P<0.05). But there was no obvious effect of GSK-J4 on hCMEC cells. All together, these data suggest that GSK-J4 has important potential in the gliomas treatment.

Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis.

AIM: To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 µg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ. CONCLUSION: Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.