Danbo Wang

Research Protocol for the Phase I Clinical Study of the Recombinant Fully Human Anti-PD-L1 Monoclonal Antibody Socazolimab

Anti-Tumor Efficacy Assessment using iRECIST criteria by IRC Evaluation

Lymph node metastasis is a key driver of poor outcomes in cervical cancer. However, the molecular mechanisms of circular RNAs (circRNAs) driving cervical cancer lymph node metastasis remain unclear. We identified circZFR, fatty acid synthase (FASN) and YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) protein expression in the cervical cancer patients with long and short disease-free survival (DFS). Functional experiments were performed to investigate the function of circZFR, FASN and YTHDF3 on cell migration and invasion. MeRIP-qPCR, RNA pulldown, RNA Immunoprecipitation (RIP), and Co-Immunoprecipitation (Co-IP) assays were executed to investigate the mechanism of circZFR regulating FASN protein expression. Our study reveals that elevated FASN protein is closely linked to metastasis and reduced survival, and identified a regulatory mechanism involving circular RNAs. We identified circZFR as a crucial regulator, significantly enhancing FASN protein expression. CircZFR overexpression was significantly correlated with accelerated lymph node metastasis and shortened DFS. Mechanistically, circZFR binds to the m6A reader protein YTHDF3, facilitating m6A recognition on FASN mRNA and recruiting the translation initiator eIF4A3, thereby boosting FASN translation. These findings establish circZFR as a pivotal driver of cervical cancer progression and highlight its inhibition as a promising therapeutic strategy.

Background: Coexistent cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VaIN) is problematic, posing challenges for patient management. This study focused on the clinical characteristics of coexistent CIN 2/3 and VaIN (all degrees), evaluating the proclivity for disease recurrence/persistence at 6 months after treatment.Methods: A retrospective case–control study of women treated for coexistent CIN 2/3 and VaIN (CE group) was undertaken between January 2018 and December 2020. During the same period, women with CIN 2/3 only were selected chronologically (1:2 ratio) for comparison (sCIN group). A loop electrosurgical excision procedure (LEEP) was the standard treatment for CIN 2/3, performing electrofulguration of VaIN in tandem. First follow-up visits at 6 months thereafter entailed testing for human papillomavirus (HPV). Univariate and multivariate analyses served to assess pertinent risk factors.Results: There were 91 CE group members, each treated for coexistent CIN 2/3 and VaIN (VaIN 1, 35; VaIN 2/3, 56). Age ≥50 years (OR = 3.362, 95% CI: 1.421–7.954) emerged as an independent risk factor for coexistent disease. Positive margins and persistent high-risk HPV (HR-HPV) infection after treatment were more common in the CE (vs. sCIN) group (p = 0.012 and p < 0.001, respectively), as was recurrent/persistent high-grade disease (17.6% vs. 2.2%; p < 0.001). In the CE group, persistent HR-HPV infection 6 months after treatment (OR = 21.320, 95% CI: 2.509–181.188) was the sole independent risk factor for disease recurrence/persistence at 6 months.Conclusions: Comprehensive vaginal wall examinations are warranted for women with CIN 2/3, particularly those >50 years old. Close follow-up by HPV test is also indicated if CIN 2/3 and VaIN coexist, given a heightened incidence of recurrent/persistent disease.

Ovarian cancer (OC) is the most lethal gynecological malignancy worldwide, characterized by heterogeneity at the molecular, cellular and anatomical levels. Most patients are diagnosed at an advanced stage, characterized by widespread peritoneal metastasis. Despite optimal cytoreductive surgery and platinum-based chemotherapy, peritoneal spread and recurrence of OC are common, resulting in poor prognoses. The overall survival of patients with OC has not substantially improved over the past few decades, highlighting the urgent necessity of new treatment options. Unlike the classical lymphatic and hematogenous metastasis observed in other malignancies, OC primarily metastasizes through widespread peritoneal seeding. Tumor cells (the “seeds”) exhibit specific affinities for certain organ microenvironments (the “soil”), and metastatic foci can only form when there is compatibility between the “seeds” and “soil.” Recent studies have highlighted the tumor microenvironment (TME) as a critical factor influencing the interactions between the “seeds” and “soil,” with ascites and the local peritoneal microenvironment playing pivotal roles in the initiation and progression of OC. Prior to metastasis, the interplay among tumor cells, immunosuppressive cells, and stromal cells leads to the formation of an immunosuppressive pre-metastatic niche in specific sites. This includes characteristic alterations in tumor cells, recruitment and functional anomalies of immune cells, and dysregulation of stromal cell distribution and function. TME-mediated crosstalk between cancer and stromal cells drives tumor progression, therapy resistance, and metastasis. In this review, we summarize the current knowledge on the onset and metastatic progression of OC. We provide a comprehensive discussion of the characteristics and functions of TME related to OC metastasis, as well as its association with peritoneal spread. We also outline ongoing relevant clinical trials, aiming to offer new insights for identifying potential effective biomarkers and therapeutic targets in future clinical practice.

Background The “Healthy China” initiative, along with advancements in technology for cancer diagnosis and treatment, has significantly enhanced outcomes for patients with gynecologic tumors. The trends of late marriage and delayed childbirth have led to an increasing number of women diagnosed with gynecologic cancers who are seeking fertility preservation in China. This issue is critical yet often overlooked in clinical practice. This review aims to synthesize the existing research on fertility preservation within the field of gynecologic oncology, emphasizing both clinical explorations and expert guidelines. Methods We conducted a comprehensive literature review on fertility preservation in the context of gynecologic tumors, examining treatment approaches, commonly employed tumor management technologies, and specific techniques for preserving fertility. Results This extensive review highlights the importance of integrating fertility preservation strategies into treatment plans for gynecologic tumors. It explores various methods to safeguard fertility during chemotherapy, radiation therapy, and surgical interventions. For patients with early-stage cervical cancer, surgical options are available; however, these may result in obstetric complications. Neoadjuvant chemotherapy is currently under investigation as an alternative approach. Endometrial cancer can be managed through hysteroscopic resection combined with hormonal therapy. The feasibility of fertility preservation in ovarian cancer varies based on tumor type and patient age. In cases of vulvar and vaginal cancers, partial excision may be considered following a thorough evaluation. Chemotherapy for gestational trophoblastic tumors has proven effective and typically preserves fertility despite potential decreases in AMH levels. Conclusion This review provides a comprehensive and current synthesis of the latest evidence and clinical practice guidelines regarding fertility preservation in gynecologic cancers. Its aim is to assist clinicians and researchers in addressing the urgent and increasing demand for effective fertility preservation strategies for their patients. Graphical Abstract