STING inhibitors sensitize platinum chemotherapy in ovarian cancer by inhibiting the CGAS-STING pathway in cancer-associated fibroblasts (CAFs).

Chemotherapy resistance in ovarian cancer hampers cure rates, with cancer-associated fibroblasts (CAFs) playing a pivotal role. Despite their known impact on cancer progression and chemotherapy resistance, the specific mechanism by which CAFs regulate the tumor inflammatory environment remains unclear. This study reveals that cisplatin facilitates DNA transfer from ovarian cancer cells to CAFs, activating the CGAS-STING-IFNB1 pathway in CAFs and promoting IFNB1 release. Consequently, this reinforces cancer cell resistance to platinum drugs. High STING expression in the tumor stroma was associated with a poor prognosis, while inhibiting STING expression enhanced ovarian cancer sensitivity. Understanding the relevance of the CGAS-STING pathway in CAFs for platinum resistance suggests targeting STING as a promising combination therapy for ovarian cancer, providing potential avenues for improved treatment outcomes.

The diagnostic and prognostic value of haematologic parameters in multiple myeloma patients.

OBJECTIVES: Multiple myeloma (MM) is a malignant disease characterized by a single clonal proliferation of B cell-derived plasma cells in the bone marrow. It is the second most common haematologic malignancy in adults. The objective of this retrospective study is to evaluate the diagnostic and prognostic value of haematologic parameters in MM. METHODS: The difference of NLR/ALB ratio (NAR) and NLR/HDL-C ratio (NHR) between the 151 newly diagnosed MM patients and 153 healthy controls was compared. According to NAR and NHR cutoff values obtained from the ROC curve, MM patients were divided into low group and high group. The differences in hematological parameters and survival time between the two groups were compared. Independent prognostic analysis was performed using Cox proportional hazard regression model. RESULTS: The NAR and NHR values in MM group were significantly higher than those in control group (P < 0.001). Higher NAR levels were significantly associated with lower albumin (ALB), higher ß2 microglobulin(ß2-MG), higher creatinine (Crea), and highe ISS stage (All P<0.05). High NHR group was significantly correlated with age , ß2-MG and ISS stage (All P<0.05). In high NAR or NHR groups, OS and DFS was significantly shortened and the prognosis was poor (P < 0.05). Multivariate analysis showed that PLT, ISS stage and NAR were independent prognostic indicators of OS in MM patients, while ALB, PLT and NAR were independent prognostic factors of DFS. CONCLUSION: NAR and NHR are inexpensive, readily available diagnostic indicators for MM, and NAR is an independent prognostic factor for MM.

Overexpression of RIPK4 Predicts Poor Prognosis and Promotes Metastasis in Ovarian Cancer.

This study was conducted to evaluate the prognostic value of receptor-interacting protein kinase 4 (RIPK4) in ovarian cancer (OC) and its role in tumorigenesis. RNA expression and the corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The relationship between clinical-pathological characteristics and RIPK4 expression was analyzed using the Wilcoxon signed-rank test and logistic regression. The Cox regression and the Kaplan-Meier method were used to evaluate the relationship between clinicopathological features and overall survival (OS). Gene set enrichment analysis (GSEA) was performed using Molecular Signatures Database. Scratch assay, transwell assay, and cell transfection were used to verify the function of RIPK4. Overexpression of RIPK4 was associated with the stage of OC and distant metastasis. Survival analysis revealed that patients with OC and higher expression of RIPK4 had a poorer prognosis. Univariate and multivariate analyses indicated that high expression of RIPK4 was associated with poor OS, as well as age and stage of OC. The areas under the curve (AUC) at 1, 4, and 8 years were 0.737, 0.634, and 0.669, respectively, according to the established OS prediction model. GSEA revealed that adherens junction, cadherin binding, and Wnt signaling pathway were enriched in the high RIPK4 expression group. Cell transfection confirmed RIPK4 was involved in the Wnt signaling pathway. RIPK4 can act as a potential prognostic molecular marker for poor survival in OC. Moreover, RIPK4 is associated with tumor metastasis and implicated in the regulation of the Wnt signaling pathway.

Diagnosis and survival values of neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in esophageal cancer.

BACKGROUND: Recent studies have borne out claims that inflammation has a vital role in the development and progression of many diseases, including cancers. It has been reported that neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) could act as independent prognostic factors for several malignant tumors. We evaluated the diagnosis and prognosis values of preoperative inflammatory indicators, including NLR and RDW in esophageal cancer (EC). METHODS: We retrospectively analyzed the clinical data of 354 EC patients and 220 early esophageal cancer (EEC) undergoing potentially curative esophagectomy in Shandong Provincial Hospital Affiliated to Shandong University and chose 201 age and sex-matched healthy volunteers as the control group. We compared the clinicopathological features, survival curves and prognosis of the EC patients between the high and low groups according to the cutoff values of NLR and RDW. RESULTS: Significant higher preoperative NLR and RDW values were detected in patients with EEC and EC compared to the healthy controls (P < .001). A high RDW was significantly associated with an older age (P < .05). NLR and RDW values after surgery in EC group were significantly higher than those before surgery (P < .001 and P < .001, respectively). For EEC group, a higher RDW value showed a significantly worse overall survival (OS) and disease-free survival (DFS) (P = .040 and P = .013, respectively). For EC group, an increased NLR indicated a significantly association with poor overall survival (OS) (P = .004) and DFS (P = .001). Preoperative NLR can act as an independent prognostic indicator for EC. CONCLUSION: The preoperative NLR and RDW are convenient, practical easily measured biomarkers of clinical diagnosis and prognostic assessment of patients with EC. Furthermore, NLR was more effective than RDW acting as an independent prognostic biomarker for EC.

Applying Electrospun Gelatin/Poly(lactic acid-co-glycolic acid) Bilayered Nanofibers to Fabrication of Meniscal Tissue Engineering Scaffold.

The menisci are fibrocartilaginous tissues composed primarily of an interlacing network of collagen fibers with nanoscale diameter. Electrospinning is a suitable process of producing nanoscale fibers that mimic collagen fibers. In this study, a bilayered scaffold (group B), which consists of a gelatin nanofiber mesh and a PLGA nanofiber mesh, has been fabricated through an electrospinning method. At the same time, we electrospun pure PLGA fibrous mesh (group A) and gelatin/PLGA composite fibrous mesh (group C) as control groups. In order to compare all scaffold morphologies, the scaffolds were imaged by SEM and some parameters were measured and analyzed as following: Diameters of fibrils are from the smallest of less than average 0.14 µm for group C to the biggest of nearly average 0.38 µm for group B. The scaffolds pore diameters are from average 4.9 µm for group A to average 11.2 µm for group B. Porosity rates show that the group B has the highest porosity rate at about 91%. The scaffolds' properties were compared and analyzed, including hydrophilicity property (water contact angle) and mechanical properties (tensile strength). The results of water contact angle showed the group B is the most hydrophil among the groups. The results of tensile strength showed the tensile strength of group C is the weakest among the groups. All the results showed significant differences between the groups. Finally, in vitro, the meniscal cells derived from New Zealand white rabbits menisci were seeded in the scaffolds. We observed the cells proliferation behavior in the scaffolds. All above demonstrates that a bi-layered gelatin/PLGA scaffold reveals not only concurrent effects of mechanics and cytocompatibility in a fibrous context, but also a promising scaffold for future meniscal repair strategies.