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1.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36835258

RESUMO

Oxaliplatin is successfully used to eradicate micro-metastasis and improve survival, whereas the benefit of adjuvant chemotherapy in the early stages of colorectal cancer remains controversial. Inflammation plays a crucial role in colorectal cancer tumorigenesis. Inflammatory mechanisms are mediated by different immune cells through different cytokines, chemokines, and other proinflammatory molecules that trigger cell progression, an increase of cancer stem cell population, hyperplasia, and metastasis. This study focuses on the analysis of the oxaliplatin effect on tumourspheres formation efficiency, cell viability, cancer stem cells and stemness marker mRNA expression, as well as inflammation-related signature profile expression and its prognosis in primary- and metastatic-derived colorectal tumourspheres derived from colorectal cell lines isolated from the same patient 1 year apart. The results indicate that primary-derived colorectal tumourspheres respond to oxaliplatin, adapting to the adverse conditions through the modulation of CSCs and the stemness properties of tumourspheres. However, metastatic-derived colorectal tumourspheres response led to the release of cytokines and chemokines, promoting an inflammatory process. In addition, the expression of inflammatory markers showing greater difference between primary and metastatic tumours after oxaliplatin treatment correlates with poor prognosis in KM survival studies and is associated with a metastatic phenotype. Our data demonstrated that oxaliplatin triggers an inflammation-related signature profile expression in primary-derived colorectal tumourspheres, related with poor prognosis and a metastatic phenotype, which allow the tumour cells to adapt to the adverse condition. These data highlight the need for of drug testing and personalized medicine in the early stages of colorectal cancer.


Assuntos
Neoplasias Colorretais , Humanos , Oxaliplatina/uso terapêutico , Neoplasias Colorretais/patologia , Citocinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
2.
Cancers (Basel) ; 14(3)2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35159084

RESUMO

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection.

3.
Antioxidants (Basel) ; 10(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34573003

RESUMO

Obesity, a physiological situation where different proinflammatory cytokines and hormones are secreted, is a major risk factor for breast cancer. Mitochondrial functionality exhibits a relevant role in the tumorigenic potential of a cancer cell. In the present study, it has been examined the influence of an obesity-related inflammation ELIT treatment (17ß-estradiol, leptin, IL-6, and TNFα), which aims to stimulate the hormonal conditions of a postmenopausal obese woman on the mitochondrial functionality and invasiveness of MCF7 and T47D breast cancer cell lines, which display a different ratio of both estrogen receptor isoforms, ERα and ERß. The results showed a decrease in mitochondrial functionality, with an increase in oxidative stress and invasiveness and motility, in the MCF7 cell line (high ERα/ERß ratio) compared to a maintained status in the T47D cell line (low ERα/ERß ratio) after ELIT treatment. In addition, breast cancer biopsies were analyzed, showing that breast tumors of obese patients present a high positive correlation between IL-6 receptor and ERß and have an increased expression of cytokines, antioxidant enzymes, and mitochondrial biogenesis and dynamics genes. Altogether, giving special importance to ERß in the pathology of obese patients with breast cancer is necessary, approaching to personalized medicine.

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