Identification of a Novel Mesenchymal Stem Cell–Related Signature for Predicting the Prognosis and Therapeutic Responses of Bladder Cancer DOI Creative Commons
Enguang Yang,

Luhua Ji,

Xinyu Zhang

и другие.

Stem Cells International, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

Background: Mesenchymal stem cells (MSCs) have been identified to a unique migratory pattern toward tumor sites across diverse cancer types, playing crucial role in progression, treatment resistance, and immunosuppression. This study aims formulate prognostic model focused on MSC‐associated markers efficiently predict the clinical outcomes responses therapy individuals with bladder (BC). Methods: Clinical transcriptome profiling data were extracted from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA‐BLCA) GSE31684 databases. Systematic quantification of MSC prevalences stromal indices was undertaken, culminating discernment genes correlated MSCs following thorough application weighted gene coexpression network analysis techniques. Subsequently, an exhaustive risk signature pertinent formulated by amalgamating methods univariate Least Absolute Shrinkage Selection Operator (LASSO) Cox regression models. Drugs targeting associated screened using molecular docking. Results: for incorporated five critical genes: ZNF165, matrix remodeling‐associated 7 (MXRA7), CEMIP, ADP‐ribosylation factor‐like 4C (ARL4C), cerebral endothelial cell adhesion molecule (CERCAM). In case BC patients, stratification performed into discrete categories, utilizing median score as criterion. It striking that those classified within high‐MSC‐risk bracket demonstrated correlations unfavorable implications. Enhanced responsiveness immunotherapy low‐MSC‐risk patients delineated compared their counterparts. A heightened receptivity noted particular chemotherapy drugs, encompassing gemcitabine, vincristine, paclitaxel, gefitinib, sorafenib, this high‐risk group. Conversely, superior reaction cisplatin distinctly evident among marked low scores. results docking kaempferol exhibited favorable quercetin MXRA7, mairin limonin diosphenol ARL4C. Conclusions: five‐gene demonstrates substantial efficacy prognosticating gauging regimens. ARL4C, CERCAM are underscored promising candidates warranting further exploration anti‐MSC therapeutic strategies, thereby offering novel insights personalized approaches BC.

Язык: Английский

Stroma-driven horizontal transfer of TCA proteins mediates metabolic plasticity and imatinib resistance in leukemia DOI Creative Commons
Katarzyna Piwocka, Piotr Chrościcki,

Nikodem Kasak

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Abstract Leukemia cells residing in the bone marrow often exhibit resistance to tyrosine kinase inhibitors. Metabolic rearrangement of cancer has recently gained particular attention as a possible cause adaptation and insensitivity drug treatment. We demonstrated here that stromal directly transferred membrane vesicles together with proteins related tricarboxylic acid (TCA/Krebs) cycle leukemic cells. This transfer was dependent on direct cell-to-cell contact led increased metabolic plasticity. In addition, co-culture activities TCA cycle, oxidative phosphorylation capacity, therefore protected from loss homeostasis stress response imatinib. As result stroma, reductions OXPHOS, mitochondria-related parameters maximal respiration observed imatinib-treated cells, were substantially less present, spare respiratory capacity parameter even higher compared control Metabolome profiling revealed co-cultured treated imatinib levels TCA-related metabolites such isocitric acid, L-malic ketoglutaric cis-aconitic well lower level stress. The rho0 analysis horizontal GFP-positive mitochondria excluded their status important for stroma-driven protection. Altogether, our data provide insight into novel mechanism marrow-mediated protection associated plasticity driver been indicated leukemia stem however indicate presence may support all conclusion, we postulate elements involved can be targeted achieve therapeutic effect overcome caused by microenvironment.

Язык: Английский

Процитировано

0
Bioengineering facets of the tumor microenvironment in 3D tumor models: insights into cellular, biophysical and biochemical interactions DOI Creative Commons

Salma T. Rafik,

Deniz Bakkalci, Alexander J. MacRobert

и другие.

FEBS Open Bio, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

The hallmarks of cancer extend beyond genetic anomalies to encompass a sophisticated tumor microenvironment, involving interactions between and non-cancer cells within dynamic biophysical setting, influencing progression. microenvironment is multifaceted, it increasingly clear that the interaction interdependence these different facets need be better understood. Tissue engineering 3D in vitro models provides an opportunity study their on Cancer metastasis still poses major challenge, accounting for 90% cancer-related deaths. This accentuates critical establish patient-specific model systems replicate complexity at all stages Herein, we outline latest advancements tools utilized analyze such models. Henceforth, multifaceted can elucidated using tools.

Язык: Английский

Процитировано

0
Identification of a Novel Mesenchymal Stem Cell–Related Signature for Predicting the Prognosis and Therapeutic Responses of Bladder Cancer DOI Creative Commons
Enguang Yang,

Luhua Ji,

Xinyu Zhang

и другие.

Stem Cells International, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

Background: Mesenchymal stem cells (MSCs) have been identified to a unique migratory pattern toward tumor sites across diverse cancer types, playing crucial role in progression, treatment resistance, and immunosuppression. This study aims formulate prognostic model focused on MSC‐associated markers efficiently predict the clinical outcomes responses therapy individuals with bladder (BC). Methods: Clinical transcriptome profiling data were extracted from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA‐BLCA) GSE31684 databases. Systematic quantification of MSC prevalences stromal indices was undertaken, culminating discernment genes correlated MSCs following thorough application weighted gene coexpression network analysis techniques. Subsequently, an exhaustive risk signature pertinent formulated by amalgamating methods univariate Least Absolute Shrinkage Selection Operator (LASSO) Cox regression models. Drugs targeting associated screened using molecular docking. Results: for incorporated five critical genes: ZNF165, matrix remodeling‐associated 7 (MXRA7), CEMIP, ADP‐ribosylation factor‐like 4C (ARL4C), cerebral endothelial cell adhesion molecule (CERCAM). In case BC patients, stratification performed into discrete categories, utilizing median score as criterion. It striking that those classified within high‐MSC‐risk bracket demonstrated correlations unfavorable implications. Enhanced responsiveness immunotherapy low‐MSC‐risk patients delineated compared their counterparts. A heightened receptivity noted particular chemotherapy drugs, encompassing gemcitabine, vincristine, paclitaxel, gefitinib, sorafenib, this high‐risk group. Conversely, superior reaction cisplatin distinctly evident among marked low scores. results docking kaempferol exhibited favorable quercetin MXRA7, mairin limonin diosphenol ARL4C. Conclusions: five‐gene demonstrates substantial efficacy prognosticating gauging regimens. ARL4C, CERCAM are underscored promising candidates warranting further exploration anti‐MSC therapeutic strategies, thereby offering novel insights personalized approaches BC.

Язык: Английский

Процитировано

0