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Results for “Biomarker variability”

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PubMed1996

Prognostic factors for response to chemotherapy containing platinum derivatives in patients with unresectable non-small cell lung cancer. (NSCLC).

PURPOSE: To identify pretreatment variables predicting response to platinum derivatives containing chemotherapy in patients with unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients included in one of the 7 consecutive clinical trials conducted by the European Lung Cancer Working Party between December 1980 and August 1991. All patients received a cisplatin or carboplatin containing chemotherapy. We analyzed 22 potential prognostic factors including sex, age, histology, performance status, weight loss, type of lesions, extent of disease, main metastatic sites and several biological parameters, namely white blood cell count (WBC), neutrophil count, platelet count, hemoglobinemia, creatininemia, serum alkaline phosphatases and LDH. RESULTS: On 1052 eligible patients. 107 were not assessable for response. The objective response rate was 26% (95% C.I.: 23, 29%). Univariate analysis identified as statistically significantly associated with a higher objective antitumoral response rate the following characteristics: a normal platelet count, the absence of skin metastasis, the absence of adrenal metastasis, a higher creatininemia, a normal hemoglobinemia, an older age and a normal WBC count. On a restricted set of variables including data from 777 patients, a multivariate logistic regression model disclosed age and platelet count as significantly and independently related to response rate. CONCLUSION: Clinical and demographic characteristics of patients with unresectable NSCLC, as well as routine laboratory parameters, could not accurately predict response to chemotherapy in a population of patients selected for a clinical trial. Future studies on this subject should include more sophisticated variables as new biomolecular makers.

Adult↗

PubMed2001

Chemical fingerprinting applied to the evaluation of marine oil pollution in the coasts of Canary Islands (Spain).

Chemical fingerprinting approach to environmental assessment is illustrated in the evaluation of marine oil pollution in the coasts using two limpet species as bioindicator organisms, and based on profiles and concentrations of n-alkanes and aromatic hydrocarbons in their tissues. Accidental and chronic releases of hydrocarbons can contaminate the marine environment of the Canary Islands not only because of their geographical situation but also because of the very dense tanker traffic around. This situation affects coastal areas, fishing activities, tourism resort, etc. Concentrations of n-alkanes and aromatic hydrocarbons (polycyclic aromatic hydrocarbons and methyl-polycyclic aromatic hydrocarbons) in the soft tissues of the marine intertidal and subtidal limpets, Patella crenata and Patella ullysiponensis aspera, were evaluated. Limpet samples were collected at monthly intervals, at three locations on the southeast coast of Tenerife over a 3-year period (1991-93). Levels of hydrocarbons found in limpets are similar to concentrations found in unpolluted areas around the world. From application of principal component analysis, the interpretation of variable loading plots gives information on variable correlation and can be used to distinguish among potential sources of pollution and the ability of studied molluscs to be used as bioindicator organisms.

Alkanes↗

PubMed2001

Relationship of the functional recovery after hip arthroplasty to the neuroendocrine and inflammatory responses.

We studied the relationship between the neuroendocrine and inflammatory responses to hip arthroplasty and functional recovery in 102 patients undergoing elective arthroplasty for osteoarthritis. Blood samples were collected for up to 7 days after surgery and analysed for concentrations of norepinephrine, epinephrine, cortisol, interleukin-6 and C-reactive protein. The primary outcome measures were milestones in hospital, times to walk 10 and 25 m, pain on discharge from hospital, and function 1 and 6 months after surgery. Walking distances in hospital were significantly delayed in patients with greater interleukin 6 and C-reactive protein concentrations, but few neuroendocrine measures had significant correlations with functional recovery in hospital. Multivariate analysis showed that the interleukin 6 concentration on day 1 was the unique predictor of time to walk 10 and 25 m, and that the day 2 concentration of C-reactive protein was the unique predictor of pain on discharge from hospital. No significant correlations were found between the inflammatory and neuroendocrine variables and recovery at 1 and 6 months. We conclude that the inflammatory response affects immediate functional recovery after hip arthroplasty.

Adult↗

PubMed2000

Preoperative UFT administration for patients with advanced colorectal cancer--increased uptake of 5-fluorouracil by tumor tissue is a prognostic factor.

The aim of this study was to clarify whether increased 5-fluorouracil (5-FU) uptake by tumor tissue following preoperative UFT administration is a prognostic factor after surgery in colorectal cancer patients. We examined the concentrations of 5-FU in tumor or normal tissue of 96 colorectal cancer patients who received UFT (400 mg/day) orally for 7 days prior to surgery. Patients were divided into two groups with high or low 5-FU concentrations in tumor tissue (defined as higher or lower than the cut-off value, respectively). The cut-off value of 5-FU was established based on the upper limit of the 95% confidence interval of the median of the concentration found in normal tissue (0.106 microg/g). Of the 96 patients, 62 (64.6%) were in the low-5-FU group and 34 (35.4%) in the high-5-FU group. The latter had a more favorable clinical outcome (p=0.0465). Cox regression analysis revealed that two independent variables, stage and 5-FU status in tumor tissue, were significant for prediction of survival. These findings suggest that increased uptake of 5-FU by tumor tissue following preoperative oral administration of UFT is an independent prognostic factor in colorectal cancer patients. This variable needs to be considered in the design of future therapeutic trials.

Administration, Oral↗

PubMed2003

Collagen turnover in bone diseases.

PURPOSE OF REVIEW: The primary aim of this review is to highlight recent advances in techniques available for assessing collagen turnover, particularly in relation to the diagnosis and management of bone disorders. As collagen is the major protein constituent of bone, its metabolites form the basis of most of the biochemical markers, but their efficacy needs to be viewed in the context of other non-collagenous markers, for which methodology is also advancing rapidly. RECENT FINDINGS: New markers of bone metabolism have been developed utilising the age-dependent isomerisation and racemisation of aspartyl residues at the C-terminal end of collagen. These methods allow measurement of the ratio between newly synthesised and mature collagen: this ratio appears to provide a novel indicator of the fracture risk for osteoporosis. Other studies have led to an improved understanding of biological variability, particularly in relation to the effects of feeding. Bone resorption assays have been applied to a wide range of diseases and have been especially useful in monitoring the efficacy of novel therapies. SUMMARY: New assays have been developed to facilitate better monitoring of collagen metabolism in bone diseases. A more complete understanding of biological variability, particularly the effects of feeding, have led to improved clinical applicability of these assays in detecting disease and monitoring therapy. Part of the future challenge, however, is to ensure that commercial assay developments keep pace with clinical expectations.

Biomarkers↗

PubMed2006

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients.

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO(x)) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO(x)/Cr ratio and number of NO(x) peaks was significantly greater in the migraine group compared with controls (P = 0.01 and P = 0.007, respectively). In the second approach, high NO(x) values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO(x) persisted being pulsatile, and migraineurs had more peaks compared with controls (P = 0.01). In seven patients, NO(x) peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16-7.77; no overlap of 95% CI). In four patients, NO(x) peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO(x) excretion between control and migraine populations, the variable temporal association of NO(x) peaks and headaches suggests a complex role of NO in this condition.

Biomarkers↗

PubMed1998

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract.

BACKGROUND/AIMS: Uncontrolled complement activation may be of immunopathological importance in inflammatory diseases of the gastrointestinal tract. Expression of membrane bound factors that regulate complement activation was therefore studied in situ. METHODS: Frozen tissue specimens were obtained from patients with Helicobacter pylori gastritis, coeliac disease, Crohn's disease, or ulcerative colitis, and from histologically normal controls. Sections were examined by immunofluorescence with monoclonal antibodies to protectin (CD59), decay accelerating factor (DAF), and membrane cofactor protein (MCP). RESULTS: Protectin and MCP were widely expressed in normal and diseased mucosae. MCP was generally observed basolaterally on all epithelial cells, whereas apical protectin expression was more intense on the epithelium of normal colonic mucosa than in the normal duodenum (p = 0.001). Epithelial DAF and to some extent protectin were upregulated in gastritis, coeliac disease, and inflammatory bowel disease. Areas of the stomach with intestinal metaplasia expressed DAF, unlike the adjacent gastric epithelium. Parietal cells of the gastric body expressed neither protectin nor DAF. CONCLUSION: Epithelial complement inhibitory molecules were expressed differently at various normal gastrointestinal sites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.

Adult↗

PubMed1990

Biochemical predictors for osteoporotic fractures in elderly Chinese--a longitudinal study.

In a longitudinal study of 283 elderly subjects aged 60 years or over living in the community, 9 subjects (7 women and 2 men) developed osteoporosis-related fractures in 30 months. These subjects initially had higher random urinary hydroxyproline/creatinine and calcium/creatinine ratios, and lower plasma 25-hydroxyvitamin D concentrations. These biochemical variables may be useful predictors of osteoporosis-related fractures and may provide a suitable community screening method to identify those most at risk.

25-Hydroxyvitamin D 2↗

PubMedDate not supplied

Evaluation of critical differences of CEA and CA 15.3 levels in serial samples from patients operated for breast cancer.

In the present investigation we evaluated the variability of tumor marker levels in the follow-up of patients without evidence of disease after resection of primary breast cancer. CEA and CA15.3 were measured using commercially available methods in serial blood samples collected from 170 patients. The coefficient of variation among all samples from each patient, which accounts for the total variability (analytical variability+biological variability), was widely scattered (from 4 to 99% for CEA; from 4 to 52% for CA15.3). The critical difference was calculated using the formula designed by Fraser [CD = 2.77. (CVa2 + CVb2)1/2]. It ranged from 11 to 276 for CEA and from 11 to 144 for CA15.3. From the present findings we conclude that: 1) it is possible to identify individually tailored decision criteria to evaluate tumor marker variations in the follow-up of breast cancer patients; 2) in a considerable number of cases the non-tumor-related variability is too high to allow the early identification of minor tumor marker variations that are of clinical relevance.

Analysis of Variance↗

PubMed2005

MRI as a marker for disease heterogeneity in multiple sclerosis.

BACKGROUND: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient. OBJECTIVE: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/tissue loss and to assess if such MS subgroups retain their intergroup differences long term. METHODS: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients. RESULTS: By consecutive employment of MRI measures reflective of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in selected MRI measures for 8 years. CONCLUSIONS: The inflammatory activity and destructiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients.

Adult↗

PubMed2001

Markers of the acute phase response in cardiovascular disease: an update.

There is now widespread agreement that inflammation is a key component in the progression of atheromatous lesions. Inflammatory cells are present at all stages in the development of the atheromatous plaque, and gene knockout experiments in mice show that atheroma is largely prevented in the absence of the normal inflammatory mediators. In humans reduction of inflammation accompanies successful treatment strategies for atheroma. An increasing number of studies suggest that the acute phase protein, C-reactive protein, provides increased prognostic information over and above existing markers of atheroma severity or progression in healthy individuals and in the acute coronary syndromes. Recent advances in our knowledge of the normal variability of C-reactive protein levels and in precise and sensitive measurements strengthen the arguments for adding this marker to the repertoire of the routine laboratory assessment of cardiovascular disease.

Acute-Phase Reaction↗

PubMed1993

Pre-operative plasma tetranectin as a prognostic marker in ovarian cancer patients.

Plasma tetranectin (TN) was tested as a biochemical prognostic marker in ovarian cancer on 39 patients. In stage I + II the 5-year survival was 33% (2/6) if plasma TN was < or = 6.7 mg l-1 and 100% (15/15) with plasma TN > 6.7 mg l-1. For stage III + IV the survival was 0% (0/11) at 26 months for patients with plasma TN < or = 6.7 mg l-1 and 29% (2/7) after 5 years with plasma TN > 6.7 mg l-1. By multivariate testing the relative hazard (RH) of death was found to be 73 times higher in patients with plasma TN < or = 6.7 mg l-1 compared to patients with values above 6.7 mg l-1 (p < 0.001). For comparison, the maximal RH for the other tested variables were: 15 for advanced stage, 2.5 for grade, four for residual tumour and 2.5 for younger age.

Adult↗

PubMed2004

Minimal residual disease in neuroblastoma: to GAGE or not to GAGE.

We assessed the utility of GAGE gene expression as a marker of minimal residual disease (MRD) in neuroblastoma. The GAGE gene family shows a high degree of homology (>90%), clustering into two subgroups. GAGE-1, -2, and -8 form one subset, almost identical among themselves, while GAGE-3 to -7 constitute the other subset. The entire GAGE family (GAGE-1-8) was studied by RT-PCR followed by Southern blotting to increase both the sensitivity and specificity of the technique. Surprisingly, expression of GAGE was detected in 59% of peripheral blood samples from normal controls (20/35) as well as in a similar proportion from neuroblastoma patients with localized disease (stages 1 and 2). The study of GAGE-1, -2, and -8 with specific primers lowered this percentage to 28% (10/35), of which only two (6%) showed a high level of expression (directly visualized after RT-PCR). We conclude that GAGE genes can show a variable, usually low level of illegitimate expression in normal blood cells, and therefore their use as MRD markers should be taken with caution.

Antigens, Neoplasm↗

PubMed2006

[The effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma patients].

OBJECTIVE: To investigate the effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma (HCC) patients. METHODS: Serum samples were collected from 112 HCC patients, Special serum protein or peptide spectra was determined by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after treating the sample onto weak cation exchange (WCX2) protein chip for each case. The serum protein profiles were compared by BioMarker Wizard Software among the patients stratified according to gender, AFP, presence of portal vein tumor thrombus (PVTT), tumor size, tumor number, presence of cirrhosis, respectively. RESULTS: According to serum protein fingerprints of 112 HCC patients, a total of 100 protein peaks were identified at the m/z value ranging from 1100 to 30,000. (1) Sixteen significant differential proteins were found between the groups of HCC with single tumor and those with multiple tumors (P < 0.01). (2) Only one significant differential protein was found between the groups of HCC with tumor size > 3 cm and those with tumor size 5 cm and those with tumor size 10 cm and those with tumor size <or= 10 cm (P < 0.01). (3) Sixteen significant differential proteins were found between the groups of macroscopic portal vein tumor thrombus (Ma-PVTT) and those without PVTT (N-PVTT); Only 2 significant differential protein were found between the groups of microscopic portal vein tumor thrombus (Mi-PVTT) and N-PVTT (P < 0.01); eight significant differential proteins were found between the groups of Ma-PVTT and Mi-PVTT (P < 0.01). (4) No significant differential protein was found when patients stratified according to gender, presence of cirrhosis and AFP. CONCLUSIONS: PVTT, tumor number and tumor size had significant effects on serum protein fingerprint, while no significant effect on serum protein from gender, presence of cirrhosis and AFP. The most profound impact on the serum protein was attained when cutoff was chosen to be presence of Ma-PVTT compared to less effect from Mi-PVTT and 5cm for tumor size.

Adult↗

PubMed1993

Facilitated method for measurement of biliary secretion rates in healthy humans.

We have developed a facilitated method for determining secretion of constituents into bile. The ratio of constituent/bilirubin was measured in gallbladder bile and multiplied by bilirubin secretion rate, estimated by measuring endogenous production of carbon monoxide (VCO) by breath sampling. Accuracy of this method was assessed by measuring secretion rate of 99mTechnetium-labeled disofenin during steady-state constant intravenous infusion. In nine subjects, mean (+/- SEM) secretion of disofenin by the CO method was 104.2 +/- 7.2% of expected and by standard marker perfusion was 97.8 +/- 13.1% of expected. In ten subjects, secretion rate of cholesterol by the CO method averaged 103 mumol/h by the CO method compared to 113 by marker perfusion (NS). Compared to marker perfusion (which is believed to reflect 24-h secretion rate), the CO method significantly underestimated secretion rate of bile acid (1110 vs. 1332 mumol/h, P = 0.076) and lecithin (295 vs. 413 mumol/h, P = 0.01), probably because gallbladder bile contained a disproportionate amount of fasting versus postprandial bile. Thus, this new method provides an accurate secretion rate for biliary constituents secreted at a relatively constant rate, including cholesterol, with less variability than marker perfusion. However, it can be used to estimate secretion of bile acid and lecithin only when a 20-30% underestimation of 24-h secretion is acceptable.

Adult↗

PubMed1997

Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis.

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.

Adenocarcinoma↗

PubMed1997

Comparison of analytical performance and biological variability of three bone resorption assays.

We have compared the analytical performance and biological variability of three commercially available bone resorption assays: Pyrilinks-D, Osteomark, and CrossLaps, for the measurement of urinary free deoxypyridinoline (Dpd), cross-linked N-telopeptides of type I collagen (NTx), and linear C-telopeptides of type I collagen (CTx), respectively. The intraassay and interassay CVs for precision of the Dpd and NTx assays were < 10% for analyte concentrations greater than the second calibrator (i.e., 3 nmol/L Dpd or 30 nmol bone collagen equivalents/L NTx). The CTx assay demonstrated poor precision for analyte concentration lower than the third calibrator (i.e., 200 micrograms/L). The NTx assay exhibited nonlinear recovery for sample dilutions prepared in buffer; however, this nonlinear recovery could be corrected for sample dilutions made in urine at a low analyte concentration. Supplement recoveries of each of the three assays were within 100% +/- 10% on average. All three analytes showed stability through five freeze-thaw cycles. The mean day-to-day variations were 16% for Dpd, and 23% for both NTx and CTx. Similar diurnal rhythm was observed for all three assays on average, with the peak in the early morning and the nadir in the afternoon. Mean amplitude of the diurnal variation was 37% for Dpd and NTx, and 57% for CTx. Variations within the reference intervals for a healthy premenopausal population were 28% for Dpd, 57% for NTx, and 56% for CTx. Pyrilinks-D has demonstrated analytical precision and accuracy equal or superior to Osteomark and CrossLaps in all areas. Dpd exhibits the least biological variability day-to-day, within individuals across the diurnal cycle, and within a healthy premenopausal population.

Adult↗

PubMedDate not supplied

Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras point mutations in colorectal liver metastases.

Paired colorectal liver metastases (CLM) and normal tissue samples from a consecutive series of 36 patients were studied prospectively. MIB-1 expression was studied by immunohistochemistry on paraffin-embedded sections. DNA ploidy and S-phase fraction (SPF) measurements were performed by flow cytometry on frozen tissues. Mutations within the p53 (exons 5-8) and c-Ki-ras (codons 12 and 13) genes were detected by PCR single-strand conformation polymorphism analysis followed by sequencing. A high correlation was observed between the MIB-1 LI and SPF value (rho=0.81; P<0.01). Moreover, p53 gene mutations were associated with either high MIB-1 LI and high SPF. In univariate analysis, SPF and MIB-1 levels were related to risk of death. The association between overall survival and DNA-ploidy or p53 mutations did not reach statistical significance, but a slightly better survival was observed for patients either with DNA-diploid tumours or without mutations (P=0.05 and P=0.06, respectively). SPF was shown by multivariate Cox model analysis to be an independent prognostic variable and thus it might be a useful prognostic factor in patients with CLM.

Adult↗