Background: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and oxaliplatin) as first-line treatment.
Patients And Methods: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome.
Results: No significant associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1.17-2.78]. Furthermore, increase in TIMP-1 levels from baseline to immediately before the second cycle of chemotherapy had a significant negative effect on survival (P = 0.03, HR = 1.30, 95% CI: 1.02-1.65) while a decrease in TIMP-1 was significantly associated with a higher objective response rate (P = 0.03).
Conclusions: Both high baseline and subsequent increase in TIMP-1 levels were associated with shorter OS in patients with mCRC receiving XELOX as first-line treatment, whereas baseline TIMP-1 levels were not associated with response or PFS following XELOX treatment.
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http://dx.doi.org/10.1093/annonc/mdq354 | DOI Listing |
Int J Rheum Dis
January 2025
Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Disease, Minda Hospital of Hubei Minzu University, Enshi, China.
Osteoarthritis is a systemic disease that primarily damages articular cartilage and also affects the synovium, ligaments, and bone tissues. The key mechanisms involved are chondrocyte death and degradation of the extracellular matrix. This study aims to identify differentially expressed genes (DEGs) associated with ferroptosis and investigate their roles in the development of osteoarthritis.
View Article and Find Full Text PDFJ Orthop Surg Res
January 2025
Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University of China, Gongti South Rd, No. 8, Beijing, 100020, China.
Objective: This study aims to investigate changes in matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) levels in the intervertebral discs of New Zealand white rabbits under simulated overload and microgravity conditions, focusing on the expression of MMP1, MMP3, and TIMP1. The findings aim to provide a theoretical foundation for preventing and delaying lumbar disc degeneration in these environments.
Methods: Overload was simulated using an animal centrifuge, and microgravity was mimicked through tail suspension.
Am J Cancer Res
December 2024
Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health Bethesda, MD 20892, USA.
Anaplastic thyroid cancer (ATC) is a lethal endocrine malignancy. It has been shown that tumor-associated macrophages (TAMs) contribute to the aggressiveness of ATC. However, stimulatory factors that could facilitate the induction and infiltration of TAMs in the ATC tumor microenvironment (TME) are not fully elucidated.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Research Department, Royal College of Surgeons of Ireland, Adliya 15503, Bahrain.
Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS.
View Article and Find Full Text PDFRespir Res
January 2025
Department of Public Health and Clinical Medicine, Section of Medicine, Umeå University, 901 87, Umeå, Sweden.
Background: In COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regulated, but to what extent this regulation occurs through epigenetic mechanisms remains unknown.
Methods: To explore the interplay between MMPs, TIMPs, and DNA methylation (DNAm) we (1) analysed MMP-9, -12, and TIMP-1 concentrations in BAL fluid, and profiled DNAm in BAL cells from 18 COPD and 30 control subjects, (2) estimated protein-COPD relationships using multivariable regression, (3) identified protein quantitative trait methylation loci (pQTMs) with COPD as a potential modifier in a separate interaction model, and (4) integrated significant interactions with a previous COPD GWAS meta-analysis.
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