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.

Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in the conservative treatment of malignant ovarian germ cell tumors: a multicenter and retrospective study.

OBJECTIVE: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). METHODS: A propensity score matching algorithm was performed between the BEP and PC groups. The χ² test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. RESULTS: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8-44 years), and the median follow-up period was 63 months (range, 2-191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. CONCLUSION: The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.

Posterior-only correction surgery for idiopathic scoliosis Lenke type 5c: differences of strategies and outcomes between adult patients and adolescent patients.

PURPOSE: To compare radiographic parameters, and functional and surgical outcomes between lumbar adolescent idiopathic scoliosis (AIS) and lumbar adult idiopathic scoliosis (AdIS). METHODS: A retrospective study was performed to identify Lenke 5c type AIS and AdIS patients from our scoliosis database who had undergone posterior surgical treatment for scoliosis. Preoperative and postoperative radiographic and clinical outcomes were compared between the two groups. RESULTS: A total of 22 patients were included in AdIS group, and 44 matched patients in AIS group. AdIS group had significantly larger L3 and L4 tilt and translation than AIS group (P < 0.05). AdIS group had larger T10-L2 angle and smaller T5-T12 angle (P < 0.05). AdIS group had higher VAS scores (P < 0.05) and pain domain of SRS-22 scores (P < 0.05) as compared to AIS group. Correlation analysis demonstrated positive relationship between VAS scores and T10-L2 angle (r = 0.492, P < 0.05). AdIS group was fused longer than AIS group (P < 0.05). Cobb angle of TL/L curve was larger and correction ratio was smaller at AdIS group (P < 0.05). AdIS group still had significantly larger L3 and L4 tilt and translation than AIS group (P < 0.05). CT measurements demonstrated larger postoperative vertebral body rotation at apical vertebrae and LIV at AdIS group (P < 0.05). Vertebral correction ratio was smaller at AdIS group (P < 0.05). CONCLUSION: Lenke 5c AdIS patients had greater preoperative and postoperative L3 and L4 tilt and translation, as well as less correction of major curve and vertebral body derotation than AIS patients. However, the incidence of adding-on was similar between the two groups.

Spontaneous correction of scoliosis after curettage of spinal osteoid osteoma: How and when?

BACKGROUND: Scoliosis behavior after curettage of spinal osteoid osteoma has been not clarified as most studies regarding scoliosis secondary to osteoid osteoma (OO) were case reports. The aims of this study were to investigate (1) clinical and radiographic features of scoliosis secondary to OO; (2) scoliosis behavior after Curettage of OO. METHODS: A retrospective study was performed at patients who were diagnosed as OO clinically or pathologically from July 1998 to December 2019 in a single institution. Age, gender, location of pain, location of lesion and curve pattern of scoliosis were collected preoperatively. Intraoperative blood loss, operation time and surgical complications were documented. VAS scores and curve magnitude were collected pre- and postoperatively and at last follow-up. RESULTS: The mean operation time was 124 ± 32 min and the average intraoperative blood loss was 274 ± 134 ml. The mean preoperative VAS score was 6.2 ± 2.7, and the mean postoperative VAS score was 2.1 ± 1.8. Thoracic scoliosis was improved from 22.7 ± 10.6° to 6.2 ± 4.3° after operation, and to 4.1 ± 4.3° at last follow-up. Lumbar scoliosis was improved from 18.1 ± 7.4° to 6.7 ± 5.2° after operation, and to 5.3 ± 3.9° at last follow-up. Trunk shift was improved from 34.7 ± 12.4  to 10.5 ± 7.2 mm after operation, and to 8.4 ± 5.6 mm at last follow-up. There was no significant differences as to sagittal radiographic parameters (P > 0.05). CONCLUSION: Patients with spinal OO had a significantly high incidence of scoliosis. Patients could get rapid relief of pain and scoliosis with low occurrence. Night pain, pain at the concave side of curve, normal sagittal alignment could help differentiate it from scoliosis associated with lumbar disc herniation.

Evaluation of the prognostic value of lymphadenectomy for low-grade serous ovarian cancer: A case-control multicenter retrospective study.

BACKGROUND: The prognostic value of lymphadenectomy in low-grade serous ovarian cancer (LGSOC) remains uncertain. MATERIALS AND METHODS: A retrospective analysis of 155 patients with LGSOC who underwent surgery over a ten-year period (2011-2020) was performed. The propensity score matching (PSM) algorithm was performed between the lymphadenectomy and no lymphadenectomy groups, and Kaplan-Meier analyses were conducted to evaluate clinical prognosis. Finally, univariate and multivariate Cox proportional hazards regression analyses were performed to analyze high-risk factors associated with clinical prognosis. RESULTS: In the pre-PSM cohort, 110 (71.0%) patients underwent lymphadenectomy. Of these, 54 (34.8%) experienced recurrence, and 27 (17.4%) died. There were statistical differences in disease-free survival (DFS) (P = 0.018) and overall survival (OS) (P = 0.016) in the post-PSM cohort. In the subgroup analysis, there were no statistically significant differences in DFS (P = 0.449) or OS (P = 0.167) in the FIGO I/II cohort. However, in the FIGO III/IV cohort, DFS (P = 0.011) and OS (P = 0.046) were statistically different between the two groups. Age > 50 years, FIGO stage III/IV, and suboptimal cytoreductive surgery were risk factors associated with prognosis. In the lymphadenectomy group, the histological status of pelvic lymph nodes had no significant effect on DFS (P = 0.205) or OS (P = 0.114). CONCLUSION: Lymphadenectomy was associated with DFS and OS, particularly in patients with advanced LGSOC patients. Age > 50 years, advanced FIGO stage III/IV, and suboptimal cytoreductive surgery were high-risk factors associated with clinical prognosis in patients with LGSOC.

Niraparib exhibits a synergistic anti-tumor effect with PD-L1 blockade by inducing an immune response in ovarian cancer.

BACKGROUND: Immune checkpoint blockades (ICBs) therapy showed limited efficacy in ovarian cancer management. Increasing evidence indicated that conventional and targeted therapies could affect tumor-associated immune responses and increase the effectiveness of immunotherapy. However, the effects of Niraparib, one of the poly (ADP) ribose polymerase (PARP) inhibitors, on the immune response remains unclear. Delineating the crosstalk between cytotoxic anticancer agents and cancer-associated immunity may lead to more efficient combinatorial strategies. METHODS: Programmed death ligand 1 (PD-L1) expression in human ovarian cancer cells after PARP inhibitors treatment was examined by western blotting (WB) and flow cytometry. The expression of poly ADP-ribose polymerase (PARP1), PD-L1, and CD8 in human ovarian cancer tissues was detected by immunohistochemistry(IHC). The effect of Niraparib and PD-L1 blockade in ovarian cancer progression was investigated in vivo. The changes of immune cells and cytokines in vitro and in vivo were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Changes of cGAS/STING signal pathway after Niraparib treatment were determined by WB, ELISA. RESULTS: Niraparib upregulated membrane PD-L1 and total PD-L1 expression in ovarian cancer cells and had a synergistic effect with PD-L1 blockade in vivo. In clinical patient samples, Niraparib augmented cytotoxic CD8+T cell proportion and function. In vivo and vitro, Niraparib can also increase the proportion of T cells and combined with PD-L1 blockade could further enhance the effect. Besides, Niraparib activated the cGAS-STING pathway, increasing the levels of cytokines such as CCL5 and CXCL10, which played a vital role in augmenting the infiltration and activation of cytotoxic T cells. CONCLUSIONS: Niraparib could modulate the immune response via the activation of the cGAS/STING pathway, and combination with PD-L1 blockade could further enhance the effect. These results provide a sound theoretical basis for clinical treatment.

Quantitative Analysis of Glucose Metabolic Cleavage in Glucose Transporters Overexpressed Cancer Cells by Target-Specific Fluorescent Gold Nanoclusters.

The glucose metabolism rate in cancer cells is a crucial piece of information for the cancer aggressiveness. A feasible method to monitor processes of oncogenic mutations has been demonstrated in this work. The fluorescent gold nanoclusters conjugated with glucose (glucose-AuNCs) were successfully synthesized as a cancer-targeting probe for glucose transporters (Gluts) overexpressed by U-87 MG cancer cells, which can be observed under confocal microscopy. The structural and optical characterizations of fluorescent glucose-AuNCs were confirmed by transmission electron microscope (TEM) and Fourier transform infrared spectroscopy (FTIR). The MTT assay exhibited the high biocompatibility of water-soluble glucose-AuNCs for further biomedical applications. The glucose metabolic cleavage of glucose-AuNCs by glycolytic enzymes from U-87 MG cancer cell was measured by fluorescence change of glucose-AuNCs. The fluorescence change based on the integrated area under fluorescence spectra ( A t) of glucose-AuNCs was plotted as a function of different reaction time ( t) with glycolytic enzymes. The fitted curve of A t versus t showed the first-order kinetics to explain the mechanism of glucose metabolic cleavage rate of glucose-AuNCs by glycolytic enzymes. The rate constant k could be utilized to determine the glucose metabolism rate of glucose-AuNCs for the quantitative analysis of cancer aggressiveness. Our work provides a practical application of target-specific glucose-AuNCs as a fluorescence probe to analyze the glucose metabolism in Gluts overexpressed cancer cells.