Exploring the multifaceted effects of Interleukin-1 in lung cancer: From tumor development to immune modulation.

Lung cancer, acknowledged as one of the most fatal cancers globally, faces limited treatment options on an international scale. The success of clinical treatment is impeded by challenges such as late diagnosis, restricted treatment alternatives, relapse, and the emergence of drug resistance. This predicament has led to a saturation point in lung cancer treatment, prompting a rapid shift in focus towards the tumor microenvironment (TME) as a pivotal area in cancer research. Within the TME, Interleukin-1 (IL-1) is abundantly present, originating from immune cells, tissue stromal cells, and tumor cells. IL-1's induction of pro-inflammatory mediators and chemokines establishes an inflammatory milieu influencing tumor occurrence, development, and the interaction between tumors and the host immune system. Notably, IL-1 expression in the TME exhibits characteristics such as staging, tissue specificity, and functional pluripotency. This comprehensive review aims to delve into the impact of IL-1 on lung cancer, encompassing aspects of occurrence, invasion, metastasis, immunosuppression, and immune surveillance. The ultimate goal is to propose a novel treatment approach, considering the intricate dynamics of IL-1 within the TME.

γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies. In addition to αß T cells and natural killer (NK) cells, γδ T cells represent an immune cell population with significant therapeutic potential against both hematologic and solid tumours. To evaluate the efficacy of γδ T cells in cervical cancer treatment, we generated patient-derived healthy and cancer ectocervical organoids. Furthermore, we examined transformed healthy organoids, expressing HPV16 oncogenes E6 and E7. We analysed the effector function of in vitro expanded γδ T cells upon co-culture with organoids. Our findings demonstrated that healthy cervical organoids were less susceptible to γδ T cell-mediated cytotoxicity compared to HPV-transformed organoids and cancerous organoids. To identify the underlying pathways involved in this observed cytotoxicity, we performed bulk-RNA sequencing on the organoid lines, revealing differences in DNA-damage and cell cycle checkpoint pathways, as well as transcription of potential γδ T cell ligands. We validated these results using immunoblotting and flow cytometry. We also demonstrated the involvement of BTN3A1 and BTN2A1, crucial molecules for γδ T cell activation, as well as differential expression of PDL1/CD274 in cancer, E6/E7+ and healthy organoids. Interestingly, we observed a significant reduction in cytotoxicity upon blocking MSH2, a protein involved in DNA mismatch-repair. In summary, we established a co-culture system of γδ T cells with cervical cancer organoids, providing a novel in vitro model to optimize innovative patient-specific immunotherapies for cervical cancer.

Risk factors for postoperative myasthenia gravis in patients with thymoma without myasthenia gravis: A systematic review and meta-analysis.

Introduction: According to the principle, thymomas combined with myasthenia gravis (MG) require surgical treatment. However, patients with non-MG thymoma rarely develop MG and early- or late-onset MG after surgery is called postoperative MG (PMG). Our study used a meta-analysis to examine the incidence of PMG and risk factors. Methods: Relevant studies were searched for in the PubMed, EMBASE, Web of Science, CNKI,and Wanfang databases. Investigations that directly or indirectly analyzed the risk factors for PMG development in patients with non-MG thymoma were included in this study. Furthermore, risk ratios (RR) with 95% confidence intervals (CI) were pooled using meta-analysis, and fixed-effects or random-effects models were used depending on the heterogeneity of the included studies. Results: Thirteen cohorts containing 2,448 patients that met the inclusion criteria were included. Metaanalysis revealed that the incidence of PMG in preoperative patients with non-MG thymoma was 8%. Preoperative seropositive acetylcholine receptor antibody (AChR-Ab) (RR = 5.53, 95% CI 2.36 - 12.96, P<0.001), open thymectomy (RR =1.84, 95% CI 1.39 - 2.43, P<0.001), non-R0 resection (RR = 1.87, 95% CI 1.36 - 2.54, P<0.001), world health organization (WHO) type B (RR =1.80, 95% CI 1.07 - 3.04, P= 0.028), and postoperative inflammation (RR = 1.63, 95% CI 1.26 - 2.12, P<0.001) were the risk factors for PMG in patients with thymoma. Masaoka stage (P = 0.151) and sex (P = 0.777) were not significantly associated with PMG. Discussion: Patients with thymoma but without MG had a high probability of developing PMG. Although the incidence of PMG was very low, thymectomy could not completely prevent the occurrence of MG. Preoperative seropositive AChR-Ab level, open thymectomy, non-R0 resection, WHO type B, and postoperative inflammation were risk factors for PMG. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022360002.

UM-6 induces autophagy and apoptosis via the Hippo-YAP signaling pathway in cervical cancer.

Melittin's non-specific cytotoxicity and hemolytic activity restrict its clinical use, but polypeptide modification is thoµght to be highly selective and well-tolerated. Here, we synthesized a novel antineoplastic peptide UM-6 based on melittin and explored the mechanism related to its anti-proliferation and metastasis on cervical cancer (CC). In the present study, we demonstrated that UM-6 inhibits viability of CC cell lines Caski and Hela in vitro by inducing apoptosis and autophagy with low toxicity to normal epithelial cells. UM-6 also triggers the Hippo signaling pathway, promoting cytoplasmic retention and phosphorylation-dependent degradation of YAP, as well as inhibiting YAP-TEAD binding and reducing transcriptional activity, suppressing downstream target gene expression. Injection of UM-6 in mice can significantly inhibit the growth of xenograft tumors, and greatly reduce the number, volume, and burden of abdominal tumors in the metastasis models without significant toxicity. These current results suggest that UM-6 has the potential to serve as a new anticancer drug candidate.

Neutrophil-Lymphocyte Ratio as a Prognostic Parameter in NSCLC Patients Receiving EGFR-TKIs: A Systematic Review and Meta-Analysis.

OBJECTIVE: To research the impact of neutrophil-lymphocyte ratio (NLR) as a prognostic parameter in non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). METHODS: We searched the databases such as the American Society of Clinical Oncology (ASCO), EMBASE, PubMed, the European Society of Medical Oncology (ESMO), Wanfang, and CNKI for articles illustrating the impact of pretreatment NLR on survival data in NSCLC patients undergoing EGFR-TKIs treatment. We did a meta-analysis for overall survival (OS) and progression-free survival (PFS). RESULTS: We recruited 10 studies in our meta-analysis. Our study suggested that patients with low NLR had better PFS (hazard ratio (HR) = 1.67, 95% confidence interval (CI) = (1.16-2.39), and P value = 0.005) and OS (HR = 1.66, 95% CI = (1.08-2.55), and P value = 0.02) in comparison to patients with high NLR. CONCLUSION: In conclusion, our meta-analysis revealed that lower NLR predicted a better survival (PFS and OS) in patients receiving the treatment of EGFR-TKIs.

The HIPPO pathway in gynecological malignancies.

The Hippo pathway has been initially discovered by screening genes that regulate organ size in Drosophila. Recent studies have highlighted the role of the Hippo pathway in controlling organ size, tissue homeostasis and regeneration, and signaling dysregulation, especially the overactivation of the transcriptional coactivator YAP/TAZ, which leads to uncontrolled cell growth and malignant transformation. The core components of the Hippo pathway may initiate tumorigenesis by inducing tumor stem cells and proliferation, ultimately leading to metastasis and drug resistance, which occurs extensively in gynecological malignancies, including cervical cancer, ovarian cancer, and endometrial cancer. In this review, we attempt to systematically summarize recent progress in our understanding of the mechanism of Hippo pathway regulation in tumorigenesis and the mechanisms that underlie alterations during gynecological malignancies, as well as new therapeutic strategies.

Primary malignant melanomas of the female lower genital tract: clinicopathological characteristics and management.

The female lower genital tract melanomas mainly include vulvar, vaginal and cervical melanoma. There is little clinical data on the melanomas thus making them highly lethal with their prognosis being worse than for cutaneous melanoma and other gynecological malignancies. Surgery is still the primary treatment for gynecological melanomas with wide local resection (WLE) of tumors with adequate margins being preferred for early-stage vulvar melanoma while complete resection of the primary tumor is the standard treatment for early-stage cervical and vaginal melanoma. Sentinel lymph node biopsy seems to avoid unnecessary complete regional lymphadenectomy. However, it should be chosen cautiously. Recently discovered molecular changes have provided new hopes for effective systemic treatment of female genital tract melanomas. In this review, we summarize the pathogenesis and clinicopathological characteristics of these rare melanomas with particular emphasis on new therapies and clinical management methods that may affect prognosis. The review aims to provide a viable direction for clinicians to diagnose and treat female lower genital tract melanomas.

The Progress of Methylation Regulation in Gene Expression of Cervical Cancer.

Cervical cancer is one of the most common gynecological tumors in females, which is closely related to high-rate HPV infection. Methylation alteration is a type of epigenetic decoration that regulates the expression of genes without changing the DNA sequence, and it is essential for the progression of cervical cancer in pathogenesis while reflecting the prognosis and therapeutic sensitivity in clinical practice. Hydroxymethylation has been discovered in recent years, thus making 5-hmC, the more stable marker, attract more attention in the field of methylation research. As markers of methylation, 5-hmC and 5-mC together with 5-foC and 5-caC draw the outline of the reversible cycle, and 6-mA takes part in the methylation of RNA, especially mRNA. Furthermore, methylation modification participates in ncRNA regulation and histone decoration. In this review, we focus on recent advances in the understanding of methylation regulation in the process of cervical cancer, as well as HPV and CIN, to identify the significant impact on the prospect of overcoming cervical cancer.

Long non-coding RNAs on the stage of cervical cancer (Review).

Cervical cancer is one of most malignant gynecological tumors. However, effective means for diagnosing and treating cervical cancer have yet to be identified. A few decades ago, long non-coding RNAs (lncRNAs) were regarded as useless parts of the genome, however, increasing data have demonstrated the importance of lncRNAs in the diagnosis and treatment of cervical cancers. The aim of the present study is to summarize the role(s) of HOTAIR, MALAT1, CCAT2, SPRY4-IT1, RSU1P2, CCHE1, lncRNA-EBIC and PVT1. Approximately 14 lncRNAs are involved in cervical cancer and several important proteins, miRNAs and other molecules and play crucial roles in a few traditional signaling pathways that have been proven to be related to those lncRNAs. In conclusion, lncRNAs may be useful as exact treatment targets and diagnostic biomarkers for improving therapies in cervical cancer patients and lncRNAs may contribute to effective diagnosis and treatment methods for cervical cancer.