Biology subjects

Tsamchoe, M.

Publications and source records attributed to Tsamchoe, M..

3 recordsLinked to original sources

bioRxiv2025

Extracellular Vesicles of Salivary Mesenchymal Stem Cells Mitigate Acute Irradiation Injury: Use of an ex-vivo organotypic human slice tissue culture as a disease model

AbstractIonizing radiation (IR) therapy for cancer patients can damage surrounding healthy tissues, particularly the salivary glands (SGs), leading to oral and systemic health issues reducing the quality of life of the patients. The mechanisms behind IR damage in SGs are not fully understood, and current therapies often fail to meet patient needs adequately. Therefore, identifying targeted pathways and alternative treatments is essential. To address this, we developed an ex vivo model of SG damage using human salivary glands obtained from patients. Healthy submandibular glands were harvested, cultured, and exposed to IR. RNA sequencing revealed elevated markers for DNA damage, inflammation, and ferroptosis, with four specific genes--FDXR, MDM2, H2AX, and p21--showing increases in expression that correlated with the IR dose. Using them, we developed a high-throughput genetic screening method to evaluate stem cell therapies aimed at mitigating IR injury. Conditioned media from mesenchymal stem/stromal cells (MSC-CM) were found to reduce the expression of all four markers, maintain tissue viability, promote cell proliferation, and decrease oxidative stress. Further analysis involved separating MSC-CM into two fractions: Extracellular Vesicles (EV)-rich and EV-depleted. The EV-depleted fractions retained elevated levels of DNA damage response markers, indicating that EVs play a crucial role in mediating tissue repair. In contrast, the EV-rich fractions reduced the markers of DNA damage response and were readily absorbed by the tissue slices. In conclusion, we have developed a genetic screening method to evaluate treatments for acute IR injury, emphasizing the significant role that EVs play in the repair process.

molecular biology↗

bioRxiv2025

EGFR Mutation Subtypes Modulate Distinct Metabolic Profiles and Clinical Outcomes in Lung Cancer: A Retrospective Analysis

Lung cancer continues to be a leading contributor of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) as most prevalent cases. Identification of epidermal growth factor receptor (EGFR) mutations has profoundly enhanced our understanding and treatment of NSCLC, leading to the development of precision therapies, including EGFR tyrosine kinase inhibitors (TKIs). This retrospective study analyzed EGFR mutation distributions and their effect on overall survival (OS) using data accessed from TCGA. Our analysis revealed that EGFR mutations are most prevalent in lung cancer, with L858R appearing as the most frequent mutation, followed by E746_A750del and T790M. Remarkably, OS analysis exhibited that C797S mutations were linked with the least OS, with T790M, G719S, L861Q, and G719A also displaying significantly decreased OS compared to L858R mutations. Gene set enrichment analysis (GSEA) of T790M versus L858R cases revealed significant metabolic reprogramming in T790M mutants, noticeable by upregulation of oxidative phosphorylation (CPT1A, NDUFS1), lipid metabolism (HMGCR), and mTORC1 signaling. Metabolic adaptation observed in T790M indicates elevated bioenergetic flexibility and detoxification efficiency, possibly leading to therapeutic resistance. The work underscores EGFR mutation subtypes as distinct biological entities with distinctive metabolic needs, suggesting HMGCR (statin-targetable) and PPAR agonists as probable therapeutic paths for T790M-driven resistance. These understandings support for mutation-specific treatment approach and highlight the necessity to combine metabolic pathway targeting with EGFR blockade to augment responses in lung cancer.

cancer biology↗

bioRxiv2021

Cancer cells induce hepatocytes apoptosis in co-opted colorectal cancer liver metastatic lesions

Vessel co-option in colorectal cancer liver metastases (CRCLM) has been recognized as one of the mechanistic pathways that contribute to resistance against anti-angiogenic therapy. In vessel co-opted CRCLM lesions, the cancer cells are highly motile that move toward and along the pre-existing sinusoidal vessels and hijack them to gain access to nutrient. The movement of cancer cells is accompanied by replacement of the hepatocytes. However, the molecular mechanisms by which this replacement occurs are unclear yet. To examine the involvement of apoptosis in hepatocytes replacement by cancer cells in co-opted lesions, we conducted immunohistochemical staining for chemonaive CRCLM specimens using pro-apoptotic markers antibody, such as cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1). The results suggested overexpression of pro-apoptotic markers in liver parenchyma of co-opted lesions compared to angiogenic lesions, specifically the hepatocytes that are in close proximity to the cancer cells. Importantly, co-culturing hepatocytes with colorectal cancer cells induced overexpression of pro-apoptotic markers in the hepatocytes. Altogether, these results propose that cancer cells could exploit apoptosis to replace the hepatocytes and establish vessel co-option in CRCLM.

cancer biology↗