Shujie Liao

A Promising New Model: Establishment of Patient‐Derived Organoid Models Covering HPV‐Related Cervical Pre‐Cancerous Lesions and Their Cancers

AbstractThe lack of human‐derived in vitro models that recapitulate cervical pre‐cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection‐associated pre‐cancerous lesions and cancers for a long time. Here, a long‐term 3D organoid culture protocol for high‐grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human‐derived samples, a small biobank of cervical pre‐tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre‐tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus‐specific T‐cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre‐cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre‐cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV‐related cervical diseases.

A novel dual-effect bimodal chip cancer research platform: Chips system interconnected vascularized tumor organoids culture with real-time exploration and detection from bench to bedside

Nowadays, cancer researches widely employed organoids as research model. Organoids provide a realistic applicate scene but how to real-time detect and quantified the organoid status is still a bottleneck. To bridge this knowledge gap, we developed an all-in-one microfluidic platform that, for the first time, seamlessly integrates a vascularized tumor organoids-on-a-chip model (VOoC) with a real-time ELISA detection module for advanced tumor research and point of care testing (POCT). The platform features a unique integration of two cutting-edge technologies: (1) VOoC consists of a perfusable self-forming vessel network throughout the tumor organoid, emulates in vivo tumor angiogenesis, and (2) a real-time microfluidic diagnostic chip equipped with ELISA for simultaneously monitoring of tumor biomarker expression levels. We demonstrated the platform's capabilities using cervical cancer organoids and evaluated the drug efficacy of cisplatin and bevacizumab. This coupled system enables simultaneous tumor microenvironment modeling and continuous, real-time monitoring of secreted biomarkers, a capability not achievable with conventional disconnected systems. By combining these two systems, our dual-effect bimodal chip platform holds great promise for advancing personalized medicine and cancer research, offering a powerful tool for both drug screening and quick diagnosis.

Microbiome and gartynecologic cancer

In recent years more and more studies have pointed out that the microbiota plays an important role in the development of gynecological tumors. A healthy female reproductive tract microbiota is dominated by lactobacilli, which can produce lactic acid and other metabolites to protect the normal reproductive tract microenvironment. If the microflora is out of balance, the abnormally increased flora may contribute to inflammation and even cancer in the reproductive system by activating the immune response, regulating metabolites and hormone levels. In this review, we focus on the relationship between microbiota and three common gynecological cancers, namely cervical, endometrial and ovarian cancers, as well as the significance of microbes in the prevention, diagnosis, and treatment of these cancers, and we introduce the application of multi-omics techniques in microbes; finally, we analyze the common characteristics of microbes in gynecological cancers, and we propose the current challenges and future research directions.