Differences in plasma TIMP-1 levels between healthy people and patients with rectal cancer stage II or III

Oblak, Irena; Anderluh, Franc; Velenik, Vaneja; Možina, Barbara; Ocvirk, Janja; Ciric, Eva; Podvrsnik, N.H.

doi:10.2478/v10019-011-0027-2

Cited by 4 publications

(2 citation statements)

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“…TIMP-1 is suggested to inhibit the proteolytic activity of MMPs [ 11 , 12 ], and the observed association between overweight and TIMP-1 may imply a protecting mechanism by overweight in COPD. We also confirmed, as previously shown [ 29 , 30 ], that serum TIMP-1 is associated with age. The MMP-9/TIMP-1 ratio was analysed in order to evaluate the protease-antiprotease imbalance of possible importance in the pathogenesis of COPD and, besides increasing pack years, decreasing FEV 1 % predicted was close to significantly related to the ratio.…”

Section: Discussionsupporting

confidence: 92%

Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

et al. 2015

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BackgroundChronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.MethodsSpirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.ResultsMedian serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).ConclusionProductive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.

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Section: Discussionsupporting

confidence: 92%

Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

et al. 2015

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“…colorectal, breast, lung, ovarian, bladder carcinoma6,9, but, also in a variety of nonmalignant conditions: asthma, diabetes, cardiovascular and autoimmune diseases 9. Increased TIMP-1 plasma levels were found in patients with colorectal cancer compared to healthy controls, and were associated with advanced disease stage and poor prognosis 6,8–12. In metastatic colorectal cancer, elevated level of the inhibitor in plasma was predictive for low probability of response to chemotherapy 13.…”

Section: Introductionmentioning

confidence: 99%

The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperative radiochemotherapy in patients with rectal cancer

Oblak¹,

Velenik²,

Anderluh³

et al. 2013

Radiology and Oncology

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BackgroundThe aim of this study was to analyse whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients.Patients and methods.Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I– III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA).ResultsMedian follow-up time was 68 months (range: 3–93 months) while in survivors it was 80 months (range: 68–93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22–523 ng/mL) and the mean level (±standard deviation) was 192 (±87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2–3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage.ConclusionsAlthough we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative radiochemotherapy in our cohort of patients with rectal cancer, TIMP-1 levels were recognized as an independent prognostic factor for OS in these patients.

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Extracellular Matrix and Colorectal Cancer: How Surrounding Microenvironment Affects Cancer Cell Behavior?

Crotti

Piccoli

Rizzolio

et al. 2016

Journal Cellular Physiology

113

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Colorectal cancer (CRC) whit more than a million of new cases per year is one of the most common registered cancers worldwide with few treatment options especially for advanced and metastatic patients.The tumor microenvironment is composed by extracellular matrix (ECM), cells, and interstitial fluids. Among all these constituents, in the last years an increased interest around the ECM and its potential role in cancer tumorigenesis is arisen. During cancer progression the ECM structure and composition became disorganized, allowing cellular transformation and metastasis. Up to now, the focus has mainly been on the characterization of CRC microenvironment analyzing separately structural ECM components or cell secretome modifications. A more extensive view that interconnects these aspects should be addressed. In this review, biochemical (secretome) and biomechanical (structure and architecture) changes of tumor microenvironment will be discussed, giving suggestions on how these changes can affect cancer cell behavior. J. Cell. Physiol. 232: 967-975, 2017. © 2016 Wiley Periodicals, Inc.

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Differences in plasma TIMP-1 levels between healthy people and patients with rectal cancer stage II or III

Cited by 4 publications

References 10 publications

Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperative radiochemotherapy in patients with rectal cancer

Extracellular Matrix and Colorectal Cancer: How Surrounding Microenvironment Affects Cancer Cell Behavior?

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