Astragalus polysaccharides sensitize ovarian cancer stem cells to PARPi by inhibiting mitophagy via PINK1/Parkin signaling.

Ovarian cancer (OC) remains the most lethal gynecological malignant tumor. PARP inhibitors (PARPi) have significantly improved survival, particularly in patients with OC with BRCA1/2 mutations. However, the majority of patients eventually develop resistance to PARPi.

Extracellular cancer‑associated fibroblasts: A novel subgroup in the cervical cancer microenvironment that exhibits tumor‑promoting roles and prognosis biomarker functions.

Tumor invasion and metastasis are the processes that primarily cause adverse outcomes in patients with cervical cancer. Cancer-associated fibroblasts (CAFs), which participate in cancer progression and metastasis, are novel targets for the treatment of tumors. The present study aimed to assess the heterogeneity of CAFs in the cervical cancer microenvironment through single-cell RNA sequencing.

Fatty acid metabolism-related lncRNA prognostic signature for serous ovarian carcinoma.

To explore the role of fatty acid metabolism (FAM)-related lncRNAs in the prognosis and antitumor immunity of serous ovarian cancer (SOC). A SOC FAM-related lncRNA risk model was developed and evaluated by a series of analyses. Additional immune-related analyses were performed to further assess the associations between immune state, tumor microenvironment and the prognostic risk model.

Effects of lysate/tissue storage at -80°C on subsequently extracted EVs of epithelial ovarian cancer tissue origins.

Small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs), play vital roles in intercellular communication. We optimized a method that extracts EVs from epithelial ovarian cancer (EOC) tissues for the purpose of investigating whether cryopreservation of EOC tissues affects the phenotypes, contents, and biological functions of extracted EVs. EV morphology, the number and size distribution of EVs, and EV-related markers were analyzed.

Long non-coding RNA SLC25A21-AS1 inhibits the development of epithelial ovarian cancer by specifically inducing PTBP3 degradation.

Background: Epithelial ovarian cancer (EOC) is a highly prevalent disease that rapidly metastasizes and has poor prognosis. Most women are in the middle or late stages when diagnosed and have low survival rates. Recently, long non-coding RNAs (lncRNAs) were recognized to play pivotal roles in the development of EOC.

PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells.

Background: Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague.

Methods: Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant ovarian cancer cell line SKOV3-TR30, as compared to its parental cell line SKOV3.

PLAA suppresses ovarian cancer metastasis via METTL3-mediated mA modification of TRPC3 mRNA.

Wide metastasis contributes to a high death rate in ovarian cancer, and understanding of the molecular mechanism helps to find effective targets for metastatic ovarian cancer therapy. It has been found that phospholipase A2-activating protein (PLAA) is inactivated in some cancers, but its role in cancer metastasis remains unknown. Here, we found that PLAA was significantly downregulated in ovarian cancer highly metastatic cell lines and patients, and the low expression of PLAA was associated with poorer prognosis and high-risk clinicopathological features of patients.

Msuite2: All-in-one DNA methylation data analysis toolkit with enhanced usability and performance.

DNA methylation is an important epigenetic regulator that plays crucial roles in various biological processes. Recent developments in experimental approaches and dramatic expansion of sequencing capacities have imposed new challenges in the analysis of large-scale, cross-species DNA methylation data. Hence, user-friendly toolkits with high usability and performance are in urgent need.

Antibody-Peptide Epitope Conjugates for Personalized Cancer Therapy.

Unlabelled: Antibody-peptide epitope conjugates (APEC) are a new class of modified antibody-drug conjugates that redirect T-cell viral immunity against tumor cells. APECs contain a tumor-specific protease cleavage site linked to a patient-specific viral epitope, resulting in presentation of viral epitopes on cancer cells and subsequent recruitment and killing by CD8+ T cells. Here we developed an experimental pipeline to create patient-specific APECs and identified new preclinical therapies for ovarian carcinoma.

Lymphocyte and macrophage infiltration in omental metastases indicates poor prognosis in advance stage epithelial ovarian cancer.

Objective: To investigate the prognostic value of immune cells within omental metastases originating from advanced epithelial ovarian cancer (EOC).

Methods: We performed immunohistochemical analysis to determine the levels of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and CD68+ tumor-associated microphages (TAMs) in omental specimens from 100 patients with advanced EOC. Significant prognostic factors, including immune cells and clinical parameters, were assessed by Kaplan-Meier survival analysis and Cox models.

PD-L1 Expression in Endometrial Serous Carcinoma and Its Prognostic Significance.

Purpose: Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC.

Materials And Methods: A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis.

Chemokines and Innate Lymphoid Cells in Skin Inflammation.

As the outermost barrier, skin plays an important role in protecting our bodies against outside invasion. Under stable conditions or during inflammation, leukocytes migration is essential for restoring homeostasis in the skin. Immune cells trafficking is orchestrated by chemokines; leukocytes express receptors that bind to chemokines and trigger migration.

Single-cell imaging of T cell immunotherapy responses in vivo.

T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell-based immunotherapies in vivo.

Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy.

Several cancer immunotherapy approaches, such as immune checkpoint blockade and adoptive T-cell therapy, boost T-cell activity against the tumor, but these strategies are not effective in the absence of T cells specific for displayed tumor antigens. Here we outline an immunotherapy in which endogenous T cells specific for a noncancer antigen are retargeted to attack tumors. The approach relies on the use of antibody-peptide epitope conjugates (APECs) to deliver suitable antigens to the tumor surface for presention by HLA-I.

High-Risk Human Papillomavirus E7 Maintains Stemness Via APH1B In Cervical Cancer Stem-Cell Like Cells.

Purpose: To determine whether early proteins from high-risk human papillomavirus (HPV) have the capacity to maintain cellular stemness.

Patients And Methods: First, we isolated cancer stem cell like cells from two cervical cancer cell lines, SiHa and CaSki, using non-adhesive culture with serum-free medium. Second, we knocked down HPV16 E7 in SiHa sphere cells and overexpressed HPV16 E7 in U2OS sphere cells.

STON2 negatively modulates stem-like properties in ovarian cancer cells via DNMT1/MUC1 pathway.

Background: Cancer stem cells (CSCs) possess abilities of self-renewal and differentiation, have oncogenic potential and are regarded to be the source of cancer recurrence. However, the mechanism by which CSCs maintain their stemness remains largely unclear.

Methods: In this study, the cell line-derived ovarian CSCs (OCSCs), 3AO and Caov3, were enriched in serum-free medium (SFM).

The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A pathway contribute to paclitaxel resistance in ovarian cancer.

Paclitaxel is widely used as a first-line chemotherapeutic drug for patients with ovarian cancer and other solid cancers, but drug resistance occurs frequently, resulting in ovarian cancer still presenting as the highest lethality among all gynecological tumors. Here, using DIGE quantitative proteomics, we identified UBC13 as down-regulated in paclitaxel-resistant ovarian cancer cells, and it was further revealed by immunohistochemical staining that UBC13 low-expression was associated with poorer prognosis and shorter survival of the patients. Through gene function experiments, we found that paclitaxel exposure induced UBC13 down-regulation, and the enforced change in UBC13 expression altered the sensitivity to paclitaxel.

Autophagy maintains the stemness of ovarian cancer stem cells by FOXA2.

Background: Cancer stem cells (CSCs) are regarded as the main cell type responsible for the initiation, metastasis, drug resistance, and recurrence of cancer. But the mechanism by which cancer stem cells maintain their stemness remains unclear.

Methods And Results: In the present study, ovarian cancer stem cells (OCSCs) were revealed to have an enhanced autophagic flux.

TXNDC17 promotes paclitaxel resistance via inducing autophagy in ovarian cancer.

Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Here, we showed that TXNDC17 screened from 356 differentially expressed proteins by LC-MS/MS label-free quantitative proteomics was more highly expressed in paclitaxel-resistant ovarian cancer cells and tissues, and the high expression of TXNDC17 was associated with poorer prognostic factors and exhibited shortened survival in 157 ovarian cancer patients.

OPCML gene promoter methylation and gene expression in tumor and stroma cells of invasive cervical carcinoma.

To investigate the CpG island methylation and the mRNA expression of OPCML gene in patients with cervical carcinoma, we collected tumor and stroma cells from 36 invasive cervical carcinoma samples and 16 normal cervical tissues as well as Hela cells. Methylation specific PCR was used to detect promoter CpG island methylation status, and fluorescence quantitative RT-PCR was used to detection of OPCML gene expression. Our data showed that OPCML gene promoter methylation may play an important role in the carcinogenesis of cervical carcinoma and OPCML gene may be a cervical carcinoma-associated candidate TSG (tumor suppressor gene).

[Protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats].

Aim: To determine the protective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia induced by endothelin-1 in rats.

Methods: Slow microinjection of endothelin-1 (120 pmol in 6 microL, for > 6 min) into the region near the middle cerebral artery was used to induce focal cerebral ischemia. ONO-1078 (0.