Childhood, Youth, and Identity: A Roundtable Conversation from the Global South

This roundtable session initially took place as part of the international conference “Childhood, Youth, and Identity in South Asia,” organized by the Department of History, Shiv Nadar University, Greater Noida, and the Centre for Publishing, Ambedkar University Delhi, India, on January 6–7, 2020

Clinical impact of epithelial–mesenchymal transition for cancer therapy

Abstract The epithelial–mesenchymal transition (EMT) represents a pivotal frontier in oncology, playing a central role in the metastatic cascade of cancer—a leading global health challenge. This comprehensive review delves into the complexities of EMT, a process where cancer cells gain exceptional mobility, facilitating their invasion into distant organs and the establishment of secondary malignancies. We thoroughly examine the myriad of factors influencing EMT, encompassing transcription factors, signalling pathways, metabolic alterations, microRNAs, long non‐coding RNAs, epigenetic changes, exosomal interactions and the intricate dynamics of the tumour microenvironment. Particularly, the review emphasises the advanced stages of EMT, crucial for the development of highly aggressive cancer phenotypes. During this phase, cancer cells penetrate the vascular barrier and exploit the bloodstream to propagate life‐threatening metastases through the mesenchymal–epithelial transition. We also explore EMT's significant role in fostering tumour dormancy, senescence, the emergence of cancer stem cells and the formidable challenge of therapeutic resistance. Our review transcends a mere inventory of EMT‐inducing elements; it critically assesses the current state of EMT‐focused clinical trials, revealing both the hurdles and significant breakthroughs. Highlighting the potential of EMT research, we project its transformative impact on the future of cancer therapy. This exploration is aimed at paving the way towards an era of effectively managing this relentless disease, positioning EMT at the forefront of innovative cancer research strategies

Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Technique

BackgroundHuman cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts.Methods and resultsWe used the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells. Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared with unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging, and positron emission tomography. Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function 2 weeks after cell delivery, as assessed by echocardiography (P=0.002) and MRI (P=0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated human endothelial cells, which enhanced hind limb perfusion (P<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging.ConclusionsThe phiC31 integrase genomic modification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types

Clinical impact of epithelial–mesenchymal transition for cancer therapy

The epithelial–mesenchymal transition (EMT) represents a pivotal frontier in oncology, playing a central role in the metastatic cascade of cancer—a leading global health challenge. This comprehensive review delves into the complexities of EMT, a process where cancer cells gain exceptional mobility, facilitating their invasion into distant organs and the establishment of secondary malignancies. We thoroughly examine the myriad of factors influencing EMT, encompassing transcription factors, signalling pathways, metabolic alterations, microRNAs, long non-coding RNAs, epigenetic changes, exosomal interactions and the intricate dynamics of the tumour microenvironment. Particularly, the review emphasises the advanced stages of EMT, crucial for the development of highly aggressive cancer phenotypes. During this phase, cancer cells penetrate the vascular barrier and exploit the bloodstream to propagate life-threatening metas-tases through the mesenchymal–epithelial transition. We also explore EM significant role in fostering tumour dormancy, senescence, the emergence of cancer stem cells and the formidable challenge of therapeutic resistance. Our review transcends a mere inventory of EMT-inducing elements; it critically assesses the current state of EMT-focused clinical trials, revealing both the hurdles and significant breakthroughs. Highlighting the potential of EMT research, we project its transformative impact on the future of cancer therapy. This exploration is aimed at paving the way towards an era of effectively managing this relentless disease, positioning EMT at the forefront of innovative cancer research strategies.</p

Role of exosomes in epithelial−mesenchymal transition

Epithelial−mesenchymal transition (EMT) is a fundamental process driving cancer metastasis, transforming non?motile cells into a motile population that migrates to distant organs and forms secondary tumors. In recent years, cancer research has revealed a strong connection between exosomes and the EMT. Exosomes, a subpopulation of extracellular vesicles, facilitate cellular communication and dynamically regulate various aspects of cancer metastasis, including immune cell suppression, extracellular matrix remodeling, metastasis initiation, EMT initiation, and organ-specific metastasis. Tumor-derived exosomes (TEXs) and their molecular cargo, comprising proteins, lipids, nucleic acids, and carbohydrates, are essential components that promote EMT in cancer. TEXs miRNAs play a crucial role in reprogramming the tumor microenvironment, while TEX surface integrins contribute to organ-specific metastasis. Exosome-based cancer metastasis research offers a deeper understanding about cancer and an effective theranostic platform development. Additionally, various therapeutic sources of exosomes are paving the way for innovative cancer treatment development. In this Review, we spotlight the role of exosomes in EMT and their theranostic impact, aiming to inspire cancer researchers worldwide to explore this fascinating field in more innovative ways.</p