Wei Wei

Plant-based diets and the risk of lung cancer: a large prospective cohort study

Phase II trial of efficacy, safety and biomarker analysis of sintilimab plus anlotinib for patients with recurrent or advanced endometrial cancer

Background Although co-inhibition of the angiogenesis and programmed death 1 (PD-1) pathways is proposed as an effective anticancer strategy, studies in Chinese patients with endometrial cancer are sufficient. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor affecting tumor angiogenesis and proliferation; sintilimab is an anti-PD-1 monoclonal antibody. Methods This was a phase II trial using Simon’s two-stage design. This study enrolled patients with endometrial cancer who had progressed after platinum-based chemotherapy. Sintilimab 200 mg was administered intravenously on day 1 every 3 weeks, and anlotinib 12 mg was administered on days 1–14 in a 21-day cycle. The primary endpoint was the objective response rate (ORR) using the immune-related Response Evaluation Criteria in Solid Tumors criteria. Immunohistochemistry and whole-exome sequencing were used as correlative investigations. Results Between November 2019 and September 2020, 23 eligible patients were enrolled. The ORR and disease control rates were 73.9% (95% CI, 51.6 to 89.8) and 91.3% (95% CI, 72.0 to 98.9), respectively, with 4 complete and 12 partial responses. With a median follow-up of 15.4 months (95% CI, 12.6 to 18.3), the median progression-free survival was not reached, and the probability of PFS >12 months was 57.1% (95% CI, 33.6 to 75.0). Exploratory analysis revealed that mutations in the homologous repair pathway showed a trend for higher ORR (100% vs 0%, p=0.07). Treatment-related grade 3/4 adverse events were observed in 50.0% of the patients. Conclusions Sintilimab plus anlotinib demonstrated robust therapeutic benefits with tolerable toxicity in endometrial cancer. Trial registration number NCT04157491.

IL-21 promotes the anti-tumor effect of anti-CD47 chimeric antigen receptor macrophages in ovarian cancer

Macrophages play a key role in immunity against solid tumors. However, their development and clinical applications are limited by their difficult-to-transfect nature, low proliferative capacity, and easily changing polarization states. The combination of chimeric antigen receptor (CAR) technology with macrophages to form chimeric antigen receptor macrophages (CAR-Ms) is an emerging strategy for adoptive cell therapy. In our previous study, we confirmed that anti-CD47 CAR-Ms have potential for ovarian cancer treatment. Here, we demonstrated that the introduction of IL-21 significantly increases the tumor-suppressive effect of anti-CD47 CAR-Ms against ovarian cancer. Specifically, IL-21-modified CAR-Ms with second-generation CARs targeting CD47 showed potent tumor cell-killing activity, both in vitro and in vivo, through direct and indirect pathways (direct phagocytosis and activation of cytotoxic T lymphocytes). In addition, an IL-21 modification significantly enhanced the tumor microenvironmental regulation of immunosuppression mediated by anti-CD47 CAR-Ms in vivo, thereby improving their therapeutic efficacy in a mouse model of ovarian cancer, without any obvious adverse effects. Taken together, these results suggest that anti-CD47 CAR-Ms combined with IL-21 is a promising treatment strategy for ovarian cancer.

Achieving flexible fairness metrics in federated medical imaging

The rapid adoption of Artificial Intelligence (AI) in medical imaging raises fairness and privacy concerns across demographic groups, especially in diagnosis and treatment decisions. While federated learning (FL) offers decentralized privacy preservation, current frameworks often prioritize collaboration fairness over group fairness, risking healthcare disparities. Here we present FlexFair, an innovative FL framework designed to address both fairness and privacy challenges. FlexFair incorporates a flexible regularization term to facilitate the integration of multiple fairness criteria, including equal accuracy, demographic parity, and equal opportunity. Evaluated across four clinical applications (polyp segmentation, fundus vascular segmentation, cervical cancer segmentation, and skin disease diagnosis), FlexFair outperforms state-of-the-art methods in both fairness and accuracy. Moreover, we curate a multi-center dataset for cervical cancer segmentation that includes 678 patients from four hospitals. This diverse dataset allows for a more comprehensive analysis of model performance across different population groups, ensuring the findings are applicable to a broader range of patients.

Expression and prognostic significance of NKD2 in ovarian cancer

AbstractPurposeNaked2 (NKD2) is a negative regulator of Wnt signaling pathway and associates with transforming growth factor secretion. The role of NKD2 in ovarian cancer is unknown.Patients and methodsGene expression profiles were measured and compared in nine patients by RNA sequencing. NKD2 expressions in ovarian cancer were measured by reverse transcription polymerase chain reaction and western blot. Tissue slides of 79 patients were stained and scored for NKD2 expression. In vitro experiments were conducted to explore the role of NKD2 in ovarian cancer. The prognostic role of NKD2 was evaluated by survival analysis.ResultsNKD2 was upregulated in patients with better survival by mRNA and protein expression. Patients were classified as NKD2-high group (n = 30) and NKD2-low group (n = 49) according to immunohistochemical score. High NKD2 was correlated with lower recurrence rate (P = 0.002) and higher percentage of platinum-sensitive recurrence (P = 0.006). Median progression-free survival was significantly longer for NKD2-high patients than NKD2-low patients (49.1 vs.14.1 months, P < 0.001). Accordingly, there was a significantly difference in terms of overall survival time between two groups (hazard ratio: 3.04; 95% confidence interval: 1.58–5.85, P < 0.001). Multivariate regression suggested that NKD2 was independently prognostic factors in terms of progression-free survival (hazard ratio: 2.91; 95% confidence interval: 1.61–5.27, P < 0.001) and overall survival (hazard ratio: 3.6; 95% confidence interval: 1.80–7.21, P < 0.001). In vitro studies further demonstrated that NKD2 suppressed ovarian cancer cell proliferation, colony formation and cell migration.ConclusionNKD2 is a novel prognostic marker and could suppress tumor progression in ovarian cancer.