SDF-1 and VEGF-C as potential circulating angiogenic biomarkers for bevacizumab in patients with metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 480-480
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Mariko Ogura ◽  
Masato Ozaka ◽  
...  

480 Background: Bevacizumab (BV) plus chemotherapy (chemo) has been shown to improve survival for metastatic colorectal cancer (mCRC). Stromal cell-derived factor-1 (SDF-1) is known as a ligand for CXCR-4. We previously reported that proportion of CXCR4-positive circulating endothelial cells at baseline was correlated with the prognosis of BV plus chemo (Matsusaka, et al. Cancer. 2011). The aim of this study was to investigate changes during treatment in serum candidate cytokines including SDF-1 as potential markers of treatment response to BV. Methods: Patients receiving first-line BV plus chemo with mCRC were enrolled in this prospective study. Serum samples were analyzed before initiation of treatment and during treatment (on days 14 and 56) and at the time of progressive disease. Correlation between tumor response and changes in serum levels of the cytokines (such as VEGF, SDF-1, Ang-1 and -2, etc.) were investigated. Differences in the means of continuous measurements were tested by the Student’s t test. A two-way repeated-measures analysis of variance was used to evaluate differences between sequential continuous variables. Results: 24 were enrolled at the first interim analysis. 14 patients were assessable; some who got conversion surgery or discontinued treatment due to toxicity in early were excluded. Tumor response was achieved in 57% of the patients. SDF-1 levels at baseline (p=0.045) and on days 14 (p=0.049) were significantly lower in tumor responder, while a trend toward higher on days 56 compared to non-responder. The results of a two-way repeated-measures analysis of variance to evaluate differences between sequential continuous variables showed significant differences in VEGF-C (p=0.043) and SDF-1 (p=0.02), influenced by tumor response. Serum levels of SDF-1 trended toward increase on days 14 and decrease on days 56, whilst VEGF-C trended toward decrease on days 14 and 56. Conclusions: Changes Serum levels of SDF-1 and VEGF-C showed correlation with tumor response to BV plus chemo, suggesting that these surrogate markers may represent anti-angiogenic condition for BV treatment. This study is currently ongoing, and further analysis will be performed in more population.

2019 ◽  
Vol 34 (3) ◽  
pp. 292-301 ◽  
Author(s):  
Michal Vočka ◽  
Daniel Langer ◽  
Vladimir Fryba ◽  
Jaromir Petrtyl ◽  
Tomas Hanus ◽  
...  

Objective: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. Methods: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. Results: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). Conclusion: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neel I. Nissen ◽  
Stephanie Kehlet ◽  
Mogens K. Boisen ◽  
Maria Liljefors ◽  
Christina Jensen ◽  
...  

AbstractA desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.


2005 ◽  
Vol 27 (3) ◽  
pp. 375-381 ◽  
Author(s):  
Gershon Tenenbaum ◽  
Betsy Becker

The current paper criticizes the concept, research methodology, data analyses, and validity of the conclusions made in Hardy, Woodman, and Carrington’s (2004) article published in this journal. In their repeated-measures analysis of data from the performances of 7 golfers, they did not examine changes in performance scores on successive holes. Instead, Hardy et al. used several ANOVA models to examine how performance varied with respect to somatic and cognitive anxiety level and self-confidence interaction. By doing so, their findings produced effects which we argue to be conceptually and empirically limited. We also address problems associated with dichotomization of continuous variables, measurement errors when splitting data, eradication of random significant effects, cell sizes in segmental quadrant analysis, and correlation between somatic and cognitive anxiety. We believe these difficulties prevent any reliable conclusions and/or generalizations from being made.


1988 ◽  
Vol 66 (1) ◽  
pp. 139-143 ◽  
Author(s):  
Erich Gott ◽  
Carl Mc Gown

The purpose of this study was to determine the effects of two putting stances (conventional versus side-saddle) and two points of aim (ball versus hole) on putting accuracy. Subjects (12 men, 4 women) were taught to putt using four methods: (a) conventional stance, eyes on the ball; (b) conventional stance, eyes on the hole; (c) side-saddle stance, eyes on the ball; and (d) side-saddle stance, eyes on the hole. Each subject practiced each method for 2 wk., after which they were tested for purring accuracy by counting putts made, determining constant error, and by calculating variable error. Accuracy was assessed at 5 and 15 ft. A 2 by 2 repeated-measures analysis of variance showed that there was no single combination of stance and point of aim that was significantly better than another at either distance. This suggests that, contrary to popular opinion, the traditional method of putting is not the best method for putting; other methods are equally as good and could be used if individually desired.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Thomas Faulkenberry

In this paper, I develop a formula for estimating Bayes factors directly from minimal summary statistics produced in repeated measures analysis of variance designs. The formula, which requires knowing only the F-statistic, the number of subjects, and the number of repeated measurements per subject, is based on the BIC approximation of the Bayes factor, a common default method for Bayesian computation with linear models. In addition to providing computational examples, I report a simulation study in which I demonstrate that the formula compares favorably to a recently developed, more complex method that accounts for correlation between repeated measurements. The minimal BIC method provides a simple way for researchers to estimate Bayes factors from a minimal set of summary statistics, giving users a powerful index for estimating the evidential value of not only their own data, but also the data reported in published studies.


Author(s):  
Rahin Sh Hamad ◽  
Bushra H. Shnawa ◽  
Shereen J. Al-Ali

Colorectal cancer (CRC) is classified as one of the most prevalent cancer types worldwide, with high morbidity and mortality rates. Patients of CRC have been shown to express a detectable cytokine in serum which contributes to cancer pathogenesis. Therefore, the serum interleukin 10 (IL-10) level in CRC patients was investigated in this study. Patients' medical records with CRC admitted to the Rizgary and Nanakali hospitals, Erbil, Iraq was analyzed as the study group compared to the healthy volunteers' control group. Seventy-one serum samples were collected, thirty-one from diagnosed CRC patients and forty from healthy controls. The concentrations of IL-10 in the sera were assessed by enzyme-linked immunosorbent assay (ELISA). The present finding showed that IL-10 Was significantly elevated in CRC patients' sera compared to the control group, suggesting confirmation of its usefulness for detecting CRC patients' prognosis. A non-significant Pearson correlation was detected between IL-10 serum levels and the CRC group's age, gender, and body mass index. Herein is the first study on the evaluation of IL-10 levels in CRC patients in Kurdistan, Iraq.


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