The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling.

Endometrial cancer (ECa) is the most common female gynecologic cancer. When comparing the two histological subtypes of endometrial cancer, Type II tumors are biologically more aggressive and have a worse prognosis than Type I tumors. Current treatments for Type II tumors are ineffective, and new targeted therapies are urgently needed. LIFR and its ligand, LIF, have been shown to play a critical role in the progression of multiple solid cancers and therapy resistance. The role of LIF/LIFR in the progression of Type II ECa, on the other hand, is unknown. We investigated the role of LIF/LIFR signaling in Type II ECa and tested the efficacy of EC359, a novel small-molecule LIFR inhibitor, against Type II ECa. The analysis of tumor databases has uncovered a correlation between diminished survival rates and increased expression of leukemia inhibitory factor (LIF), suggesting a potential connection between altered LIF expression and unfavorable overall survival in Type II ECa. The results obtained from cell viability and colony formation assays demonstrated a significant decrease in the growth of Type II ECa LIFR knockdown cells in comparison to vector control cells. Furthermore, in both primary and established Type II ECa cells, pharmacological inhibition of the LIF/LIFR axis with EC359 markedly decreased cell viability, long-term cell survival, and invasion, and promoted apoptosis. Additionally, EC359 treatment reduced the activation of pathways driven by LIF/LIFR, such as AKT, mTOR, and STAT3. Tumor progression was markedly inhibited by EC359 treatment in two different patient-derived xenograft models in vivo and patient-derived organoids ex vivo. Collectively, these results suggest LIFR inhibitor EC359 as a possible new small-molecule therapeutics for the management of Type II ECa.

The Effect of the COVID-19 Pandemic on the Family and Community Medicine Residency Training Program: The Philippine Experience.

Background: The COVID-19 pandemic had a profound impact on medical education, particularly in Family and Community Medicine training programs. This study aimed to assess the impact in the Philippines by comparing the number of cases and procedures before and during the pandemic, as well as the adaptations made by these programs. Objective: The objective of this study was to determine the effect of the COVID-19 pandemic on Family and Community Medicine training in the Philippines by comparing the average number of cases and procedures done before and during the pandemic and the changes implemented by the different accredited training programs. Methods: A cross-sectional study utilizing an explanatory sequential mixed methods approach was undertaken. The quantitative portion collected data on cases and procedures from the participating institutions' residents using the standardized checklist of the Philippine Academy of Family Physicians. The qualitative portion was done through a focused group discussion (FGD) following a prepared set of FGD questions. Analysis of variation (ANOVA) was used to compare the average cases seen and procedures across the four years and content analysis for the qualitative data. Results: There was a significant decrease in the average number of adult and pediatric cases during the pandemic years (2020-2021) compared to before (2018-2019). Various organ systems cases such as neurology, ophthalmology, dermatology, and gastrointestinal, showed significant differences (p-value <0.05) in the average number of pediatric cases. For adult cases, significant differences (p-value <0.05) were found for several organ system cases when comparing the years before (2018-2019) and during the pandemic (2020-2021), including neurology, ophthalmology, ENT, dermatology, cardiology, gastrointestinal, genitourinary, reproductive health, musculoskeletal, and endocrinology cases. The trainers adjusted training activities to support the hospital's COVID-19 response and that prompted an abrupt shift to online strategies for patient consultations, teaching sessions, and examinations. Conclusion: The COVID-19 pandemic led to a reduction in the variety of cases and procedures in Family and Community Medicine training, impacting the fulfillment of specialty training requirements. However, it also drove innovation through the integration of technology, including online teaching methods. These experiences underscore the importance of resilience and adaptability in medical education and offer valuable lessons for future training programs, potentially leading to improvements in training and patient care through innovative methodologies.