Factors Impacting Return to Work/School among Hematopoietic Cell Transplantation Survivors in India.

Introduction: While there are data about return to work after hematopoietic cell transplantation (HCT) in survivors from resource-rich regions, similar data from resource-challenged settings are scarce. This study assessed the incidence of and factors affecting return to work/school (RTW) among HCT survivors in India. Methods: This single-center cross-sectional study was conducted at the long-term follow-up (LTFU) clinic of a large-volume HCT center during 2022-2023. HCT survivors surviving beyond four months were included after obtaining informed consent. Patients' sociodemographic, disease, HCT, and work details were recorded. The factors affecting RTW were evaluated using univariate (ANOVA) and logistic regression analyses. Results: A total of 126 HCT survivors participated in the study. Of these, 34 (27%) did not RTW, 47 (37%) returned to part-time work, and 45 (36%) returned to full-time work at a median of more than three years post-HCT. The three groups did not significantly differ in age, sex, or marital status. The univariate analysis revealed that education, pre-HCT job status, income, and conditioning intensity were significantly associated with RTW. Logistic regression analysis revealed that survivors with a higher (taxable) income were more likely to RTW than those with a lower (non-taxable) income (OR 3.5; CI 1.2-10.2, p=0.01). Survivors with a desk job were more likely to RTW than those who were unemployed/retired or students (OR 4.5; CI 1.1-18.0, p=0.03). Conclusion: Socioeconomic factors, like pre-HCT job status and income, were significantly associated with post-HCT RTW. Therefore, there is a need to integrate multidisciplinary RTW programs for HCT survivors in India.

Knockdown of E-cadherin induces cancer stem-cell-like phenotype and drug resistance in cervical cancer cells.

Cervical cancer is one of the leading causes of mortality amongst women in developing countries, and resistance to therapy is the main reason for treatment failure. Recent advances suggest that cancer stem cells (CSCs) are critically involved in regulating the chemo-resistant behavior of cervical cancer cells. In our study, cells with the CSC phenotype were isolated, and we examined the expression levels of stem cell markers and genes associated with epithelial-mesenchymal transition (EMT) using different assays. However, the cells with the CSC phenotype could not be cultured for further cytotoxicity studies, so we established a model of CSC in cervical cancer cells. We performed siRNA-mediated knockdown of E-cadherin in these cells, and studied them for EMT-associated stem-cell-like properties. We also performed dose-dependent cell viability assays using clinically relevant drugs such as cisplatin, cyclopamine, and GANT58 to analyze the drug resistant behavior of these cancer cells. We found that knockdown of E-cadherin induces EMT in cervical cancer cells, imparting stem-cell like characteristics along with enhanced tumorsphere formation, cell migration, invasiveness, and drug resistance. This is the first study to establish a CSC model in cervical cancer cells by knockdown of E-cadherin, which can be used to develop anti-cancer therapies.

Sonic hedgehog pathway activation regulates cervical cancer stem cell characteristics during epithelial to mesenchymal transition.

Resistance to therapy and metastasis remains one of the leading causes of mortality due to cervical cancer despite advances in detection and treatment. The mechanism of epithelial to mesenchymal transition (EMT) provides conceptual explanation to the invasiveness and metastatic spread of cancer but it has not been fully understood in cervical cancer. This study aims to investigate the mechanism by which silencing of E-cadherin gene regulates EMT leading to proliferation, invasion, and chemoresistance of cervical cancer cells through the Hedgehog (Hh) signaling pathway. We developed an in vitro EMT model by the knockdown of E-cadherin expression in cervical cancer cell lines. To understand the role of developmental pathway like Hh in the progression of cervical cancer, we investigated the expression of Hh pathway mediators by array in E-cadherin low cervical cancer cells and observed upregulation of Hh pathway. This was further validated on low passage patient-derived cell lines and cervical carcinoma tissue sections from cervical cancer patients. Further, we evaluated the role of two inhibitors (cyclopamine and GANT58) of the Hh pathway on invasiveness and apoptosis in E-cadherin low cervical cancer cells. In conclusion, we observed that inhibition of Hh pathway with GANT58 along with current therapeutic procedures could be more effective in targeting drug-resistant EMT cells and bulk tumor cells in cervical cancer.