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1.
Oncol Res ; 32(1): 227-239, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38188686

RESUMEN

Transient receptor potential (TRP) channels are strongly associated with colon cancer development and progression. This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature, with further validation of signature in real world samples from our hospital treated patient samples. Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed to evaluate this gene signature's predictive accuracy and robustness in both training and testing cohorts, respectively. Additionally, the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature's immune infiltration landscape and underlying functional implications. The support vector machine algorithm was applied to evaluate the signature's potential in predicting chemotherapy outcomes. The findings unveiled a novel three TRP channels-related gene signature (MCOLN1, TRPM5, and TRPV4) in colon adenocarcinoma (COAD). The ROC and K-M survival curves in the training dataset (AUC = 0.761; p = 1.58e-05) and testing dataset (AUC = 0.699; p = 0.004) showed the signature's robust predictive capability for the overall survival of COAD patients. Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration, especially an increased presence of M2 macrophages, in high-risk group patients compared to their low-risk counterparts. High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy, evident through increased CD86 and PD-1 expression profiles. Moreover, the TRPM5 gene within the signature was highly expressed in the chemoresistance group (p = 0.00095) and associated with poor prognosis (p = 0.036) in COAD patients, highlighting its role as a hub gene of chemoresistance. Ultimately, this signature emerged as an independent prognosis factor for COAD patients (p = 6.48e-06) and expression of model gene are validated by public data and real-world patients. Overall, this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.


Asunto(s)
Adenocarcinoma , Neoplasias del Colon , Canales de Potencial de Receptor Transitorio , Humanos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Resistencia a Antineoplásicos/genética , Biología Computacional
2.
Front Oncol ; 12: 1007514, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36267978

RESUMEN

Background: Treatment options for metastatic colorectal cancer (CRC) are mostly ineffective. We present new evidence that tumor tissue collagen type X alpha 1 (COL10A1) is a relevant candidate biomarker to improve this dilemma. Methods: Several public databases had been screened to observe COL10A1 expression in transcriptome levels with cell lines and tissues. Protein interactions and alignment to changes in clinical parameters and immune cell invasion were performed, too. We also used algorithms to build a novel COL10A1-related immunomodulator signature. Various wet-lab experiments were conducted to quantify COL10A1 protein and transcript expression levels in disease and control cell models. Results: COL10A1 mRNA levels in tumor material is clinical and molecular prognostic, featuring upregulation compared to non-cancer tissue, increase with histomorphological malignancy grading of the tumor, elevation in tumors that invade perineural areas, or lymph node invasion. Transcriptomic alignment noted a strong positive correlation of COL10A1 with transcriptomic signature of cancer-associated fibroblasts (CAFs) and populations of the immune compartment, namely, B cells and macrophages. We verified those findings in functional assays showing that COL10A1 are decreased in CRC cells compared to fibroblasts, with strongest signal in the cell supernatant of the cells. Conclusion: COL10A1 abundance in CRC tissue predicts metastatic and immunogenic properties of the disease. COL10A1 transcription may mediate tumor cell interaction with its stromal microenvironment.

3.
GMS J Med Educ ; 38(1): Doc27, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33659632

RESUMEN

Background: In the summer semester 2020, a new format was introduced at the Otto-von-Guericke-University Magdeburg for first-year medical students in the subject of medical sociology with a neighborhood-related social environment analysis. Didactic approach: Due to the COVID-19 pandemic, the didactic concept had to be changed at short notice from seminar group-related fieldwork in different districts of Magdeburg to individual work at the place of study or home, supplemented by accompanying online offers. The students were asked to characterize their neighborhood in terms of quality of life, health and illness as well as medical care by means of interviews with inhabitants of their immediate living environment, a neighborhood inspection with the taking of photographs and an analysis of official secondary data. The aim was to gain initial experience in scientific work (data collection, presentation and interpretation of results, as well as reporting). An evaluation of this new course and conclusions derived from it for its further development will be reported. Evaluation: 51 percent of the students participated in an evaluation of the course. The clear majority rated the internship as "good" or "very good". As a suggestion for improvement, the desire for optional supplementary individual counseling and better formal preparation for the performance assessments were expressed several times. Two thirds of those surveyed consider the online teaching format to be useful even in post-pandemic times.


Asunto(s)
COVID-19/epidemiología , Educación Médica/organización & administración , Medio Social , Sociología Médica/educación , Estado de Salud , Humanos , Pandemias , Calidad de Vida , Investigación , Características de la Residencia , SARS-CoV-2
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