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ABSTRACT: Background : At present plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) is undergoing validation as a biological marker in colorectal cancer (CRC). The clinical implementation of plasma TIMP-1 in prognosis, prediction, screening and monitoring CRC requires robust information as to the influence of preanalytical factors, including inter- and intrapersonal biological variations. The aim of the present study was to evaluate the possible effects of smoking on the level of TIMP-1 in plasma from healthy subjects. Materials and methods : Forty-six never-smokers and 48 daily smokers participated in the 13-week study. Smokers were randomized into 3 groups of 16 subjects each: one group continued to smoke, a second group refrained from smoking and used a transdermal nicotine patch, and a third group refrained from smoking and used placebo patches. Plasma TIMP-1 levels were determined using ELISA. Results : No significant differences in TIMP-1 levels could be shown between the smoking group, the 2 different abstinent smoking groups and the never-smoking group. Conclusion : Smoking does not appear to have any influence on TIMP-1 levels in plasma collected from healthy subjects.
The International journal of biological markers 04/2013; · 1.48 Impact Factor
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Scandinavian journal of gastroenterology 12/2011; 47(3):256-7. · 2.08 Impact Factor
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ABSTRACT: Complement activation may play a prominent role in acute pancreatitis (AP). Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) participate in complement activation. The objective of the present study was to evaluate the role of MBL and MASP-2 as markers in AP with regard to etiology, inflammatory activity, severity, and development of multiorgan failure.
Sixty patients with AP were included. All patients were diagnosed and treated according to a standardized regimen. Blood samples were obtained immediately on admission and again on days 1, 2, and 14.
Both MBL (P < 0.001) and MASP-2 (P = 0.002) levels changed significantly over time, but without any significant relation to severity, multiorgan failure, or mortality. We found significantly higher levels of MBL (P = 0.04) in alcohol- than in gallstone-induced AP, but no significant difference in MASP-2 levels.
The MBL and MASP-2 acted as acute-phase reactants, but overall, they were not markers for severity, multiorgan failure, nor for mortality in AP. Our results suggest that MBL and MASP-2 play only a minor role in the inflammatory response in AP.
Pancreas 10/2011; 40(7):1097-102. · 2.39 Impact Factor
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ABSTRACT: Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities are available, an international consensus on screening procedures is still not established. The rather limited compliance in present screening procedures is a significant drawback. Furthermore, some of the procedures are costly and, therefore, selection methods for these procedures are needed. Current research into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among the screening populations, and thereby improve the compliances. Furthermore, the involvement of the media, including social media, may add even more individuals to the screening programs. Implementation of validated RAE and progressively improved screening methods may reform the cost/benefit of screening procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest.
Scandinavian journal of gastroenterology 08/2011; 46(11):1283-94. · 2.08 Impact Factor
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ABSTRACT: Transfusion of blood components may increase the risk of complications in relation to surgery. During storage, red blood cells (RBCs) undergo structural and functional changes that may reduce function and viability after transfusion. The aim of the study was to evaluate the quality of buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days.
Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35, respectively. The samples were analysed for various biomarkers expressing the oxidative stress and inflammation, including malondialdehyde (MDA), α-tocopherol (AT), dehydroascorbic acid (DHA), ascorbate (ASC), YKL-40 and interleukin-6 (IL-6).
The levels ofMDA, ASC, DHA, IL-6 and YKL-40 changed significantly during the storage period (p < 0.001, p < 0.001, p < 0.001, p = 0.004 and p < 0.001 respectively). A significant change in AT levels could not be shown (p = 0.087).
RBCs displayed significant changes in all measured indices of oxidative and inflammatory stress during a storage period of 35 days except for AT. The data suggest a possible rationale behind the observation that aging blood products may increase the risk of complications following surgery and blood transfusion.
Scandinavian journal of clinical and laboratory investigation 03/2011; 71(4):299-303. · 1.38 Impact Factor
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Hans J Nielsen,
Nils Brünner,
Lars N Jorgensen,
Jesper Olsen,
Hans B Rahr,
Knud Thygesen,
Ute Hoyer,
Søren Laurberg,
Petra Stieber,
Marinus A Blankenstein,
Gerard Davis,
Barry L Dowell,
Ib J Christensen
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ABSTRACT: The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis.
Individuals (n = 4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals.
Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) = 1.8 (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR = 1.6, 1.3-1.9, or ≥ 5 ng/ml, OR = 2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR = 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR = 1.4, 95% CI: 1.1-1.8, and CEA ≥ 5 ng/ml, OR = 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained.
This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.
Scandinavian journal of gastroenterology 01/2011; 46(1):60-9. · 2.08 Impact Factor
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ABSTRACT: Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC.
During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms.
High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels.
This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.
European journal of cancer (Oxford, England: 1990) 12/2010; 46(18):3323-31. · 4.12 Impact Factor
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ABSTRACT: Vascular Endothelial Growth Factor (VEGF) plays a prominent role in tumor angiogenesis and plasma VEGF concentration may carry prognostic information in colorectal cancer. The VEGF receptor 1 (VEGFR-1) is a regulatory receptor which is shredded into plasma of patients with colorectal cancer. For both molecules, large biological variation and lack of standardization of assay procedures are major challenges.
We investigated pre-analytical, analytical, as well as short term and long term biological variation of plasma VEGF and VEGFR-1 in volunteers. In addition, we evaluated plasma VEGF and VEGFR-1 as markers of colorectal disease in a case-control study on four groups of 77 individuals undergoing bowel endoscopy. Groups were categorized as 'no findings', 'non-malignant findings', 'adenoma', or 'colorectal cancer'.
In the studies on variation, temperature and delay before centrifugation significantly influenced plasma VEGF and, to a minor extent, plasma VEGFR-1 concentrations. In addition, we found large biological variations with CV up to 69.2% for VEGF and CV up to 35.9% for VEGFR-1. For both molecules the intra-subject variation exceeded the inter-subject variation. In the case control study neither plasma VEGF nor VEGFR-1 was able to differentiate between the four groups of individuals although plasma VEGFR-1 was significantly lower in patients with 'no findings'.
There was no difference in plasma VEGF or VEGFR-1 between patients with no findings, benign disease, pre-malignant findings, and malignant findings after endoscopy. The poor discrimination between patients may be explained by the large inter- and intra-subject variations found for both molecules in volunteers.
Scandinavian journal of clinical and laboratory investigation 11/2010; 70(7):503-11. · 1.38 Impact Factor
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ABSTRACT: Preoperative biomarkers serum CEA and plasma TIMP-1 have been shown to have prognostic and predictive value in patients with colorectal cancer. The aim of the present study was to evaluate the possible impact of chemoradiotherapy (CRT) on preoperative biomarker levels in patients with rectal cancer.
Thirty-three patients with rectal cancer were prospectively included. The patients received CRT for 6-8 weeks. Blood samples were collected before CRT (pre-CRT) and preoperatively (post-CRT).
Median CEA was 3.5 (range 0.6-36.1) μg/l and 2.4 (range 0.0-10.2) μg/l (p=0.002) and median plasma TIMP-1 was 132.1 (range 77.8-342.7) μg/l and 140.0 (range 82.6-440.9) μg/l (p=0.04) in the pre- and post-CRT measurements, respectively.
CRT induced a significant decrease in serum CEA and increase in plasma TIMP-1 levels. Therefore, the preoperative biomarker levels may be affected by treatments received before blood sample collection. Translation of results of preoperative biomarkers needs to take such facts into consideration.
Anticancer research 11/2010; 30(11):4755-9. · 1.73 Impact Factor
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ABSTRACT: The liberated domain I of the urokinase plasminogen activator receptor [uPAR(I)] is a significant prognostic marker in lung and ovarian cancer, although the uPAR(I) concentration is below the limit of quantification (LOQ) in a substantial proportion of patient samples (Lung Cancer 2005;48:349-55; Clin Cancer Res 2008;14:5785-93; APMIS 2009;117:755-61). This study was undertaken to design an immunoassay with improved functional sensitivity for measuring uPAR(I) and to evaluate the prognostic value of uPAR(I) for colorectal cancer (CRC) patients.
Surface plasmon resonance analysis identified 2 monoclonal antibodies, R3 and R20, that simultaneously bind to the liberated uPAR(I) but not to intact uPAR. We used R3 for capture and Eu-labeled R20 for detection in designing a 2-site sandwich time-resolved fluorescence immunoassay (TR-FIA 4) for measuring liberated uPAR(I). TR-FIA 4 was validated for use with citrated plasma. The prognostic value of the uPAR(I) concentration was evaluated in 298 CRC patients. The Cox proportional hazards model was used for the uni- and multivariate survival analyses.
The LOQ was 0.65 pmol/L. Liberated uPAR(I) was measurable in all patient samples with TR-FIA 4. In the multivariate analysis that included sex, age, tumor stage, tumor localization, and adjuvant treatment, the uPAR(I) concentration measured with TR-FIA 4 (hazard ratio, 1.72; 95% CI, 1.15-2.57; P = 0.009), as well as the concentration of intact soluble uPAR plus the cleaved uPAR fragment containing domains II and III, tumor stage, and age were independent predictors of prognosis.
TR-FIA 4 has a functional sensitivity improved 4-fold over that of the previous uPAR(I) assay. The uPAR(I) concentration measured with TR-FIA 4 is an independent predictor of prognosis in CRC patients.
Clinical Chemistry 10/2010; 56(10):1636-40. · 7.91 Impact Factor
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ABSTRACT: The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance.
The different suPAR forms were measured in serum preoperatively collected from 518 patients. Patients were followed up to nine years (median 7.9 years) and the primary endpoint was overall survival. The different suPAR forms were measured using Time Resolved Fluorescence Immunoassays(TR-FIAs): Intact, suPAR(I-III) by TR-FIA 1; intact and cleaved, suPAR(I-III)+(II-III) by TR-FIA 2; and liberated uPAR(I) by TR-FIA 3.
All three uPAR variants demonstrated prognostic significance when evaluated individually. In a multivariable analysis suPAR(I-III)+(II-III) and the liberated uPAR(I) were shown to be independent markers of prognosis (HR=1.74, CI:1.33-2.26; p <0.0001 and HR=1.32; CI:1.02-1.71; p=0.036 respectively), and independent of the clinical baseline variables: age, gender, tumor stage and localization.
This study demonstrated that suPAR(I-III)+(II-III) and the liberated uPAR(I) in serum are independent prognostic markers in CRC.
Acta oncologica (Stockholm, Sweden) 08/2010; 49(6):805-11. · 2.27 Impact Factor
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ABSTRACT: The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue inhibitor of metalloproteinases (TIMP)-1 as a prognostic index in patients with primary, curatively resected CRC.
Blood samples were collected before surgery from 422 patients with CRC stage I-III (Dukes' stage A-C). CEA was determined in serum by a routine analysis and TIMP-1 was determined in plasma using a validated in-house enzyme-linked immunosorbent assay. Disease-free survival (DFS) was registered and its associations with serum CEA and plasma TIMP-1 levels were studied using a Cox multivariate model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for DFS were calculated.
An event was recorded in 186 patients: 75 had local recurrence, 75 had distant metastases, 28 had both local recurrence and distant metastases, and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale, serum CEA and plasma TIMP-1 were statistically significant in a multivariate analysis with HR = 1.1 (95% CI 1.0-1.2) and HR = 1.5 (95% CI 1.1-2.0), respectively. The two serological markers could be combined to form a prognostic index adjusted for baseline variables. This index showed a 51% increase in HR for a given CEA level if the TIMP-1 level was doubled.
Preoperative serum CEA and plasma TIMP-1 levels are independent predictors of DFS in patients with primary resectable CRC. In combination these two proteins could form an index for the assessment of risk of disease recurrence in early-stage CRC.
Scandinavian journal of gastroenterology 01/2010; 45(2):200-7. · 2.08 Impact Factor
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ABSTRACT: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been suggested to be a valuable marker in colorectal cancer (CRC), but the effects of chemotherapy on TIMP-1 levels are unknown. The present study evaluated the effect of chemotherapy on TIMP-1 levels in comparison with carcinoembryonic antigen (CEA) levels in patients with stage III colon cancer.
Thirty patients who had been curatively resected for stage III colon cancer were included. The patients received 10-12 cycles of modified FOLFOX6 regimen. Blood samples were collected before and after the first and the second cycle and three months later.
No significant change could be detected in CEA levels while TIMP-1 raised significantly after the second cycle but returned to normal 3 months later.
Plasma CEA levels are stable during adjuvant chemotherapy while the plasma level of TIMP-1 might be directly affected by chemotherapy represented by a transient rise about 2 weeks following the initiation of treatment.
Anticancer research 01/2010; 30(1):233-7. · 1.73 Impact Factor
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ABSTRACT: The three human ficolins, H-ficolin, L-ficolin and M-ficolin, are pattern recognition molecules of the innate immune system. All three ficolins can activate the lectin pathway of the complement system after binding to pathogens. H- and L-ficolin are serum proteins with an average concentration of 18 and 3 microg/ml, respectively. M-ficolin has been described as a membrane-associated pattern recognition receptor of monocytes, being also present in granulocytes; recently, minuscule amounts of M-ficolin have been found in serum, too. No assay specific for M-ficolin has yet been described and biological variations are unknown. We have raised specific monoclonal anti-human M-ficolin antibodies and have developed a quantitative assay for M-ficolin. M-ficolin elutes as a large, 900-kDa protein upon gel permeation chromatography of serum. Analysis of M-ficolin levels in serum samples of 350 blood donors reveals a mean concentration of 1.07 microg/ml, ranging from 0.28 to 4.05 microg/ml. Analyses of consecutive acute phase serum samples from major surgery patients indicated a complex response. Ontogeny was investigated through cord blood samples from healthy full-term babies, which showed adult levels, with sequential samples showing no increase from birth to 1 year of age. We suggest that M-ficolin should also be considered as a humoral pattern recognition molecule.
Journal of Innate Immunity 01/2010; 2(2):167-80. · 4.21 Impact Factor
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ABSTRACT: To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and overall survival.
Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The first response evaluation was performed after 8 weeks of chemotherapy.
Median plasma TIMP-1 and serum CEA levels did not change significantly during 6 weeks of treatment. High plasma TIMP-1 and high serum CEA levels before treatment and at weeks 2, 4 and 6 were related to poor objective response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP-1 before and during treatment were significantly associated with poor overall survival; p < 0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment.
Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for mCRC. The results indicate that plasma TIMP-1 in particular and serum CEA may be valuable biomarkers even in samples collected during treatment with chemotherapy.
Oncology 01/2010; 79(1-2):144-9. · 2.27 Impact Factor
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ABSTRACT: INTRODUCTION. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. MATERIAL AND METHODS. Plasma and serum samples were collected prior to vaccination and continuously during treatment. GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 instrument. CEA and TIMP-1 were analysed on ELISA platforms. RESULTS. Patients achieving stable disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. CONCLUSION. The increased levels of key pro-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine.
Acta oncologica (Stockholm, Sweden) 01/2009; 48(8):1157-64. · 2.27 Impact Factor
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ABSTRACT: Interleukin (IL)-6, a key player in the inflammatory response, may be a useful biomarker in rheumatoid arthritis (RA). The aim was to determine analytical variability, a reference interval in healthy subjects, and long- and short-term variation in serum and plasma IL-6 in healthy subjects and RA patients. An enzyme-linked immunosorbent assay from R&D was used for determination of serum and plasma IL-6. The IL-6 concentration did not depend on the type of anticoagulant used or the 3-h time delay between sampling and processing or repeated freeze-thaw cycles. The median plasma and serum IL-6 in 318 healthy subjects were 1.3 pg ml(-1) (range 0.33-26) and 1.4 pg ml(-1) (range 0.25-23), respectively. The median coefficient of variation in plasma IL-6 in 27 healthy subjects during 1 month, and repeated after 6 and 12 months were 27%, 31% and 26%, respectively. No significant long-term changes were observed in serum IL-6 over a 3-year period (14%, p = 0.33). Exercise (cycling) increased serum IL-6 in healthy subjects but not in RA patients. In conclusion, circulating IL-6 is stable regarding sample handling and shows little variation over time. Changes in IL-6 concentrations > 60% (2 times the biological variation) are likely to reflect changes in disease activity and not only pre-analytical or normal biological variability.
Biomarkers 02/2008; 13(1):59-78. · 2.21 Impact Factor
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ABSTRACT: Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) may be a valuable biological marker in Colorectal Cancer (CRC). However, prospective validation of TIMP-1 as a biological marker should include a series of pre-analytical considerations. TIMP-1 is stored in platelets, which may degranulate during collection and storage. The aim of this study was to evaluate the influence of platelet TIMP-1 contamination on plasma TIMP-1 levels in healthy volunteers.
All four parts of this study were done on EDTA-plasma. 1: The effect of stasis was evaluated in plasma collected with and without tourniquet. The collected whole blood was centrifuged at three different g-values. The effect of cellular contamination was evaluated 2: by adding plasma from just above the buffy-coat to one of four tubes containing plasma from the same sample and 3: by separating the plasma into three layers: upper, middle and lower. 4: The effect of temperature was studied by collection and handling of corresponding samples on ice and at room temperature. Prior to analysis samples were stored at -80 degrees C. TIMP-1 was determined using a validated in-house ELISA.
1: TIMP-1 levels in plasma collected with or without stasis were not significantly different. Similarly TIMP-1 levels were not affected by the studied differences in centrifugation force. 2: TIMP-1 levels were significantly increased in plasma potentially contaminated with platelets (p<0.0001). 3: Separation of plasma into an upper, middle and lower layer did not affect the levels of plasma TIMP-1. 4: Samples kept at room temperature following collection showed significantly higher plasma TIMP-1 levels than samples kept on ice (p<0.0001).
Contamination with platelets during handling and storage of plasma may have significant effect on TIMP-1 levels. The results can define a standard operating procedure for sample collection and handling, which is important in obtaining uniform, comparable and reproducible plasma TIMP-1 levels.
Clinica Chimica Acta 05/2007; 380(1-2):128-32. · 2.54 Impact Factor
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ABSTRACT: The urokinase-type plasminogen activation (uPA) system and the mannan-binding lectin (MBL) complement activation pathway are involved in regulation of immune responses. The blood concentrations of these molecules in the individual patient thus could be related to the risk of postoperative infectious complications. The aim of this retrospective study was to determine the association between the soluble uPA receptor (suPAR) and MBL concentrations and the development of postoperative bacterial infectious complications.
Blood samples were drawn preoperatively from 544 patients scheduled to undergo primary resection for colorectal cancer. Plasma suPAR was determined by enzyme-linked immunosorbent assay and serum MBL by time-resolved immunofluorescent assay. The following infectious events were recorded during the first month after surgery: surgical site or perineal infection or both, intra-abdominal abscess, anastomotic leakage, pneumonia, and blood stream infection. Data on perioperative blood transfusions in addition to clinical baseline characteristics were included as well.
The numbers of surgical site infections, intra-abdominal abscesses, anastomotic leakages, pneumonias, and blood stream infections were 51, 20, 32, 78, and 19, respectively. Univariate analysis showed that elevated concentrations of suPAR (p = 0.01; odds ratio [OR] 2.2; 95% confidence interval [CI] 1.2, 3.9), low concentrations of MBL (p = 0.047; OR 0.9; 95% CI 0.8, 1.0), and perioperative blood transfusion (p = 0.006; OR 1.5; 95% CI 1.1, 2.0) were associated with the development of pneumonia. Significant associations with other bacterial infections could not be demonstrated. Multivariate analysis including disease stage, sex, and age showed that suPAR, MBL, and perioperative blood transfusion were significantly and independently associated with postoperative pneumonia.
Concentrations of suPAR and MBL, in addition to perioperative blood transfusion, were significantly associated with the development of postoperative pneumonia. No other statistically significant relationships could be demonstrated. Thus, further research should be directed to clarifying the biological role of these two molecules in the development of postoperative pneumonia.
Surgical Infections 11/2006; 7(5):463-71. · 1.80 Impact Factor
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ABSTRACT: Increased plasma concentrations of vascular endothelial growth factor (sVEGF) are associated with poor prognosis of colorectal cancer patients. The aim was to investigate the contribution of the tumor to plasma concentrations of VEGF and VEGF receptor 1 (VEGFR1). Preoperative blood samples from a peripheral vein and intraoperative blood samples from a tumor artery, a tumor vein, and from a peripheral vein were drawn from 28 patients undergoing elective surgical resection of primary rectal cancer. Plasma concentrations of VEGF and VEGFR1 were determined by ELISA. Counts of white blood cells and platelets were performed in all samples. No significant difference between plasma VEGF levels in the obtained blood samples was found (0.35 < P < 0.86). Plasma sVEGFR1 concentrations were significantly increased in tumor veins compared with tumor arteries. In addition, a significant reduction in plasma sVEGFR1 concentrations from preoperative to intraoperative samples was observed. There was a significant efflux of neutrophils to the tumor, but none of the observed changes in plasma VEGF or VEGFR1 levels correlated to changes in counts of white blood cells or platelets (sVEGF: 0.33 < P < 0.73 and sVEGFR1: 0.32 < P < 0.98). No changes in sVEGF plasma concentrations from tumor arteries to tumor veins were demonstrated, whereas there was a significant increase in sVEGFR1 from tumor arteries to tumor veins. Changes in sVEGF or sVEGFR1 from tumor arteries to tumor veins were not associated with changes in counts of white blood cells or platelets.
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 02/2004; 14(11-12):611-5. · 1.30 Impact Factor
