Jing Zheng

Tirzepatide for fertility-sparing treatment in obese/overweight patients with endometrial cancer and atypical hyperplasia: a phase II single-arm clinical trial protocol

Introduction Approximately 3–5% of patients with endometrial cancer (EC) are diagnosed under the age of 40 years, with 70% of these individuals being nulliparous. Consequently, fertility-sparing treatment for eligible young patients with endometrial lesions is increasingly being accepted. Obesity is a well-known factor closely associated with the incidence and prognosis of endometrial lesions. As obesity rates rise, weight loss interventions become particularly important in the treatment of these patients. Tirzepatide is currently the most effective glucagon-like peptide-1 receptor agonist for weight control. This trial aims to explore the synergistic effects and safety of tirzepatide combined with standard fertility-preserving treatment for endometrial lesions. Methods and analysis This single-arm, phase II clinical trial aims to evaluate the efficacy and safety profile of tirzepatide as an adjunctive therapy to standard fertility-sparing treatment in obese or overweight patients with atypical hyperplasia (AH) or EC. The study will enrol a total of 45 patients, each receiving a combination of standard fertility-sparing treatment for EC and AH alongside tirzepatide. The primary outcomes include the reversal rate and time to remission (in months) of endometrial lesions, which are determined through endometrial pathology sampling every 3 months, as well as the percentage of weight reduction. Secondary objectives include evaluating changes in body morphology and composition, alterations in metabolic parameters during the study, as well as reproductive outcomes and the rate of tumour recurrence during follow-up. Ethics and dissemination This study has received approval from the Ethics Committee of Peking Union Medical College Hospital (I-25PJ1055). Written informed consent will be obtained from all participants. The trial results will be disseminated through peer-reviewed medical journals and presented at an academic conference. Trial registration number ChiCTR2500102009.

Combined single cell and spatial transcriptome analysis reveals hedgehog pathway-related genes as potential therapeutic targets for cervical cancer

Cervical cancer (CC) remains one of the most common and deadly malignancies among women worldwide, with exceptionally high morbidity and mortality rates. The aberrant activation of the hedgehog pathway is intimately associated with tumor development and progression. Nevertheless, the potential therapeutic targets within the hedgehog pathway in CC have yet to be clearly identified. In this study, we conducted an in-depth investigation of hedgehog pathway-related genes in CC, integrating single-cell sequencing data and spatial transcriptomics. Utilizing a comprehensive scoring algorithm, we identified that myofibroblasts within CC tissue exhibit a highly enriched hedgehog pathway. Our analysis of the myofibroblast development process revealed that MYH9 plays a crucial role. Further exploration using spatial transcriptome data allowed us to delve into the role of MYH9 in myofibroblasts. We discovered that MYH9-negative and MYH9-positive myofibroblasts display distinct profiles. Validation using extensive transcriptome data demonstrated that a high infiltration of MYH9-positive myofibroblasts is a risk factor for CC patients, significantly impacting prognosis and immunotherapeutic efficacy. Our study provides unique insights into the relationship between CC and the hedgehog pathway, offering new directions for cancer treatment strategies.

Long-term survival outcomes of female genital tract rhabdomyosarcoma in children, adolescents and young adults at a national rare disease diagnosis and treatment center in China

Rhabdomyosarcoma (RMS) is a rare soft-tissue sarcoma mainly affecting children and adolescents. The genitourinary tract is the second common site involved by RMS. We report the therapeutic effects and long-term survival outcomes of female genital tract RMS. Patients diagnosed with female genital RMS and younger than 25 years old from Peking Union Medical College Hospital between January 1996 and December 2023 were identified. Clinical features, treatment modalities, and survival outcomes were documented. Patient prognosis evaluation was re-evaluated according to the Children's Oncology Group (COG) risk stratification system. A total of 26 patients were included, with a mean age of 8.1 years. The median follow-up duration was 59.3 months. Primary tumor sites were distributed as follows: vagina (n=12), cervix (n=8), vulva (n=2), pelvic region (n=2), uterus (n=1), and subcutaneous perineum (n=1). The COG Risk Stratification System classified 15 patients as low-risk subset 1, 8 as low-risk subset 2, 2 as intermediate-risk, and 1 as high-risk. Nine patients (34.62%) experienced disease recurrence with a median progression free survival of 15.3 months. The disease-specific mortality rate was 26.92% (7/26). Six patients (66.7% of recurrent cases) succumbed to the disease following recurrence, while one stage 4 patient died during initial treatment. Patients diagnosed as RMS in female genital tract in early stage can have relatively good prognosis. Advanced stage and nonstandard primary treatment were related with increased risk of recurrence. Patients with disease recurrence tend to have poor prognoses and higher mortality rates.