Xinyu Wang

Secondary cytoreductive surgery in platinum-sensitive relapsed ovarian cancer: a meta-analysis of randomized controlled trials

To evaluate the role of secondary cytoreduction in patients with platinum-sensitive recurrent ovarian cancer. The PubMed, Medline, Embase, Cochrane Library and Web of Science databases were searched. Randomized controlled trials (RCTs) that compare secondary cytoreduction plus chemotherapy with chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer were selected. Pooled hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. There was no difference in overall survival (OS) between the surgery group and no surgery group (HR = 0.89; 95% CI 0.77, 1.04; p = 0.14), but secondary cytoreduction showed a significant improvement in progression-free survival (PFS) (HR = 0.67; 95% CI 0.54, 0.76; p < 0.00001). A subgroup analysis comparing the complete gross resection subpopulation with the no surgery group achieved a significant longer OS (HR = 0.70, 95% CI 0.58-0.85; p = 0.0003) and a greater PFS benefit (HR = 0.56, 95% CI 0.48-0.66; p < 0.00001). In addition, as compared with incomplete resection, the OS benefit of complete gross resection was more evident (HR = 0.51, 95% CI 0.37-0.69; p < 0.0001). In women with platinum-sensitive recurrent ovarian cancer, although secondary cytoreduction followed by chemotherapy resulted in longer PFS than chemotherapy alone, it did not lead to significant benefit in OS. However, when complete gross resection was achieved, it significantly prolonged OS and provided a greater PFS benefit.

Molecular profile-based recommendations for postoperative adjuvant therapy in early endometrial cancer with high-intermediate or intermediate risk: a Chinese randomized phase III trial (PROBEAT)

The use of molecular categorisation is shifting paradigm towards the use of molecular information to refine risk stratification in endometrial cancer (EC). To date, evidence to support molecular-guided therapies is limited to retrospective studies and secondary molecular analyses of patients receiving standard treatment. The PROBEAT study is the first randomized phase III trial to evaluate tailored adjuvant treatment based on WHO-endorsed molecular classification in Chinese EC patients. It is expected to provide a clinical decision-making tool for adjuvant treatment of patients with high-intermediate risk (HIR) or intermediate risk (IR) EC to better optimise and personalise patient care and increase relapse-free survival. The PROBEAT trial is a prospective, multicentre study led by Women's Hospital of Zhejiang University Gynaecologic Oncology Group. Recruitment started on January 24, 2022, and 590 patients with HIR or IR endometrioid EC are expected to be recruited from 13 clinical centres in China. All tumor tissues will be classified into four molecular subtypes ( ClinicalTrials.gov Identifier: NCT05179447.

SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells

As cancer stem cells (CSCs) are considered as the origin of tumor development, recurrence, and drug resistance, we aimed to explore the mechanism related to modulating stemness in CSCs, thus facilitating to search for new therapeutic strategy for ovarian cancer. In this study, ovarian cancer stem cells (OCSCs) induced from cell line 3AO and A2780 were enriched in serum-free medium (SFM). The effect of SURF4 on CSC-like properties was evaluated by sphere-forming assays, re-differentiation assays, quantitative real-time polymerase chain reaction, flow cytometry, Western blotting, cell viability assays and in vivo xenograft experiments. The downstream molecule participating in SURF4 maintaining stemness was screened by RNA-sequencing and identified by the experiments of gene function. SURF4 was upregulated expressed in OCSCs. Knockdown of SURF4 reduced the expression of the related stem markers (SOX2 and c-MYC), inhibited self-renewal ability, and improved the sensitivity to chemotherapeutic drugs (paclitaxel and cisplatin) in OCSCs. SURF4 knockdown also inhibited tumorigenesis in nonobese diabetic/severe combined immunodeficiency mice. BIRC3 expression was controlled by SURF4, and BIRC3 showed the similar effect as SURF4 did, and BIRC3 overexpression partially recovered stem-like properties abolished by SURF4 knockdown. Our findings suggest that SURF4 possesses the ability to maintain stemness of OCSCs via BIRC3, and may serve as a potential target in stem cell-targeted therapy for ovarian cancer.

Moderate Static Magnet Fields Suppress Ovarian Cancer Metastasis via ROS‐Mediated Oxidative Stress

Metastasis is the leading cause of cancer patient death, which is closely correlated with reactive oxygen species (ROS) levels. It is well known that the effects of ROS on tumors are diverse, depending on ROS concentration and cell type. We found that ovarian cancer cells have significantly lower levels of ROS than normal ovarian cells. Moreover, increased ROS levels in ovarian cancer cells can substantially inhibit their migration and invasion ability. Furthermore, the results show that moderate static magnetic field (SMF) can inhibit ovarian cancer cell migration, invasion, and stemness in a ROS‐dependent manner. RNA sequencing results confirm that SMFs increased the oxidative stress level and reduced the stemness of ovarian cancer cells. Consistently, the expressions of stemness‐related genes were significantly decreased, including hyaluronan receptor (CD44), SRY‐box transcription factor 2 (Sox2), and cell myc proto‐oncogene protein (C‐myc). Furthermore, moderate SMFs provided by a superconducting magnet and permanent magnet have good biosafety and can both inhibit ovarian cancer metastasis in mice. Therefore, our study demonstrates the effects of SMFs on oxidative stress and metastasis in the ovarian cancer cells, which reveals the potential of applying SMF as a physical method in cancer therapy in the future.

Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer

AbstractCircular RNAs (circRNAs) are critical regulators in the occurrence and development of numerous cancers, in which abnormal autophagy plays a key role. However, the potential involvement of circRNAs in autophagy is largely unknown. Here, we identified the overexpression of circTICRR, a circular RNA, in cervical cancer. In vitro experiments showed that knockdown of circTICRR activated autophagy, and consequently promoted apoptosis and inhibited proliferation in cervical cancer cells, and vice versa. CircTICRR interacted with HuR protein via binding to F287/F289 in the RRM3 domain of HuR, stabilizing GLUD1 mRNA and elevating the level of GLUD1 protein. In vivo experiments revealed that knockdown of circTICRR suppressed the growth of transplanted tumors. An inhibitory peptide specific to the binding site between circTICRR and HuR protein promoted autophagy, induced apoptosis, suppressed proliferation in cervical cancer cells, and inhibited the growth of xenografts. Our findings suggest that circTICRR acts as an oncogene in cervical cancer and the interaction between circTICRR and HuR protein may be a potential target in cervical cancer therapeutics.

Head-to-Head Comparison of DH3 HPV Test and HC2 Assay for Detection of High-Risk HPV Infection in Residual Cytology Samples from Cervical Cancer Screening Setting: Baseline and 3-Year Longitudinal Data

The benefits of testing for high-risk human papillomavirus (hrHPV) in cervical cancer screening have already been demonstrated. Hybrid Capture 2 (HC2) is the best validated HPV assay and has been considered the gold standard for hrHPV testing.