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Results for “Biomarker variability”

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PubMed2002

Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays.

AIMS: Using tissue microarrays, this study analysed the expression of the multidrug resistance protein, MRP2, by immunohistochemistry with two different MRP2 antibodies. This is the first study to address the expression of MRP2 in various common human neoplasms. METHODS AND RESULTS: Immunohistochemistry was performed on zinc formalin-fixed tissue to evaluate normal tissues and carcinomas using two antibodies against MRP2 (EAG5, a polyclonal antibody, and M2-lll-6, a monoclonal antibody). Immunostaining was localized in neoplastic cells mainly on the cell membrane with M2-lll-6 and cell membrane and cytoplasm with EAG5. In normal tissues MRP2 was expressed in liver, gastrointestinal tract, and kidney tubular epithelial cells with both antibodies. MRP2 was seen in nine of 22 renal cell carcinomas, eight of 13 gastric carcinomas, 25 of 49 breast carcinomas, 14 of 32 lung carcinomas, 39 of 50 colon carcinomas, and 16 of 17 ovarian carcinomas. There was < 10% variability between the two antibodies. MRP2 expression was highest in moderate to poorly differentiated tumours from colon, lung, gastric, and ovarian carcinomas and in grade 2 and 3 breast and renal carcinomas. CONCLUSION: The expression of MRP2 in many solid human tumours indicates that inherent drug resistance may play an important role as a biomarker for predictive chemotherapy treatment.

Antibodies, Monoclonal↗

PubMed1999

Evaluation of nuclear matrix protein 22 as a tumour marker in the detection of transitional cell carcinoma of the bladder.

OBJECTIVES: To evaluate the sensitivity and specificity of urinary nuclear matrix protein-22 (NMP22) in detecting bladder cancer, to compare the diagnostic performance of NMP22 alone and when corrected by urinary creatinine level, and to correlate NMP22 level with the histological and clinical characteristics of bladder cancer. PATIENTS, SUBJECTS AND METHODS: The study included 267 patients classified into five groups: group 1 comprised 111 patients with active transitional cell carcinoma (TCC) of the bladder; group 2 included 76 patients who had had bladder TCC but were being followed and were free of disease, as confirmed by cystoscopy; group 3 comprised 25 patients with benign urological diseases; group 4 included 25 patients with other malignant pathological conditions; group 5 constituted a control group of 30 healthy subjects free of urological diseases. Urinary NMP22 was measured using an enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were constructed to obtain the thresholds which gave optimal sensitivity and specificity for combinations of NMP22 alone and when corrected by urinary creatinine level. Stage, grade, tumour size, pattern of growth, focality and the presence of recurrence were recorded and their associations with NMP22 evaluated. RESULTS: The mean levels of NMP22 were 122.8, 5.1, 3.7, 2.3 and 0.3 U/mL for groups 1-5, respectively; overall, these values were significantly different (P<0.001). The mean (95% CI) optimal combination of 78.2% (69.3-85.5) sensitivity and 95.5% (87.3-99.0) specificity was obtained from the ROC analysis with a threshold value of 13.7 U/mL NMP22. When values were corrected by urinary creatinine levels, the threshold given by the best combination of sensitivity and specificity, at 73.2% (63.2-81.7) and 97.0% (89.6-99.5), respectively, was 3.0 U/mg creatinine. NMP22 level was statistically associated with stage, grade, tumour size and focality. CONCLUSIONS: Urinary NMP22 appeared to be a potential tumour marker for detecting TCC of the bladder; when corrected by urinary creatinine level, it might provide a better interpretation than when used alone. NMP22 correlated with the most relevant variables in bladder cancer. As a noninvasive adjunct, NMP22 might have a role in guiding urologists about the need for cystoscopy in such patients.

Biomarkers, Tumor↗

PubMed2003

NF-kappa B nuclear localization and its prognostic significance in prostate cancer.

OBJECTIVE: To detect the subcellular localization of NF-kappa B (p65) in human prostate cancer tissues of different histological grades, and to test whether NF-kappa B localization alone, or combined with the histological grade, can be used to predict patient outcome. PATIENTS AND METHODS: Prostate cancer tissues were obtained from radical prostatectomy specimens; the histological grade was determined using the Gleason grading system. Clinical outcomes were defined as good (5-year disease-free survival with undetectable levels of prostate specific antigen) or poor (progression to bone metastases). The subcellular localization of NF-kappa B was visualized by immunohistochemistry using an anti-p65 antibody. RESULTS: The NF-kappa B subcellular localization was initially assessed in 45 specimens; in these samples a nuclear localization of NF-kappa B was specific to cancer tissues, but did not correlate with the Gleason score (P = 0.089). NF-kappa B was then assessed as a prognostic marker to complement Gleason score in predicting cancer progression. Tumour tissues from 30 men with a known clinical outcome were included; 10 of 17 patients who had a poor outcome were positive for NF-kappa B nuclear staining, whereas only two of 13 with a good outcome were positive (P = 0.026). When NF-kappa B subcellular localization and Gleason score were combined, two risk categories of progression were defined. Eleven of 13 specimens from those with a good outcome were in the low-risk category (Gleason 2-4 or Gleason 5-7 with negative nuclear NF-kappa B) and 12 of 17 in the poor outcome group were in the high-risk category (Gleason 8-10 or Gleason 5-7 with positive nuclear NF-kappa B; P = 0.004). CONCLUSION: NF-kappa B is detectable in the nucleus in prostate cancer tissues and positivity can be used to help predict patient outcome. Multivariate analyses using other clinical and molecular variables are underway, and will validate the usefulness of NF-kappa B as a prognostic factor.

Aged↗

PubMed1990

Biologic indicators of prognosis in breast cancer.

With increasing options for adjuvant therapy in breast cancer, it is even more important to know which patients are at risk for recurrent disease. Variables such as tumor size and node status are well-established markers. Others have recently been proposed. Will these new markers improve our ability to assess prognosis and select appropriate management modalities?

Biomarkers, Tumor↗

PubMed2004

Changes in total lymphocyte count as a surrogate for changes in CD4 count following initiation of HAART: implications for monitoring in resource-limited settings.

BACKGROUND: A major obstacle to the administration of highly active antiretroviral therapy (HAART) in resource-limited settings is the high cost of CD4 count testing. The total lymphocyte count (TLC) has been proposed as a surrogate marker to monitor immune response to therapy. OBJECTIVE: To assess, in a developed country setting, the capability and clinical utility of TLC change as a surrogate marker for CD4 count change in monitoring patients on HAART. METHODS: Longitudinal co-variation between changes in TLC and concomitant changes in CD4 count following the initiation of HAART was examined using a retrospective cohort study of 126 HIV-positive patients attending The Miriam Hospital, Brown University, Providence, RI. Analyses included evaluation of the direction of TLC change as a marker for direction of CD4 change, using sensitivity and specificity; evaluation of absolute change in TLC as a marker for benchmark changes in CD4 (> or =50 over 6 months, > or =100 over 12 months), using receiver-operator characteristic (ROC) curves; and a regression model of change in TLC as a function of change in CD4, to understand within-individual variation of longitudinal TLC measures. RESULTS: In the first 24 months of HAART, the sensitivity of a TLC increase as a marker for CD4 count increase over the same time period ranged from 86-94%, and the specificity ranged from 80-85%. The median change in TLC among patients with a CD4 count rise of > or =100 cells/mm at 1 year of HAART was +766 cells/mm while that of patients with a CD4 count rise of <100 cells/m was +100 cells/mm. The area under the corresponding ROC curve was 0.89, suggesting that change in TLC discriminates well between those with 1-year CD4 change of > or =100 vs. those with change <+100. From a regression analysis, we found that mean change in TLC per 1 cell/mm change in CD4 count was 7.3 (SE 1.2, P < 0.001). The degree of this association varied from individual to individual but was positive for all individuals. CONCLUSIONS: Within the first 2 years of HAART, the direction of change in TLC appears to be a strong marker for direction of concomitant change in CD4 count (sensitivity 86-94% and specificity 80-85%, depending on length of interval). Positive and negative predictive values depend on the proportion of CD4 changes that are positive. In this cohort, that proportion is 87.9%, which yields high positive predictive value (96-98%) but lower negative predictive value (43-63%). Findings from the regression model suggest that taking multiple measurements of TLC at more frequent intervals may reduce variability and potentially improve predictive accuracy.

Adolescent↗

PubMed2003

Plasma concentrations of von Willebrand factor and intracellular adhesion molecule-1 for prediction of outcome after successful cardiopulmonary resuscitation.

OBJECTIVE: Ischemia/reoxygenation following cardiopulmonary resuscitation might cause endothelial injury/activation that could contribute to an adverse outcome after cardiopulmonary resuscitation. We studied plasma concentrations of von Willebrand factor (vWF) antigen and soluble intracellular adhesion molecule (sICAM)-1 as markers of a generalized endothelial injury/activation in relation to outcome after cardiopulmonary resuscitation. DESIGN: Retrospective study on stored plasma samples. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty-five patients who survived >24 hrs after in- or out-of-hospital cardiopulmonary resuscitation and 15 noncritically ill control patients.I NTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of vWF antigen and sICAM-1 on day 2 after cardiopulmonary resuscitation were higher in patients than in controls (p < .001 and p = .001, respectively). In-hospital cardiopulmonary resuscitation, cardiopulmonary resuscitation duration > or = 15 mins, severe cardiovascular failure, and renal dysfunction/failure at the time of blood sampling were associated with significant elevations in vWF antigen and sICAM-1 concentrations. Patients with an unfavorable outcome after cardiopulmonary resuscitation (cerebral performance category > or = 3) exhibited higher vWF antigen and sICAM-1 concentrations than patients with good outcome (cerebral performance category 1-2; p < .001 and p = .097, respectively). Renal dysfunction/failure, severe cardiovascular failure, systemic inflammatory response syndrome, and cardiopulmonary resuscitation duration > or = 15 mins were also associated with higher adverse outcome rates. Combination of these four variables into a cardiac arrest risk score (levels 0-4) showed adverse outcome rates of 100, 56, and 0% in patients with arrest scores of 4, 2-3, and 0-1, respectively. A vWF antigen concentration >166% was an independent predictor of outcome after cardiopulmonary resuscitation (p = .002) and was associated with increased adverse outcome rates in patients with cardiac arrest risk scores of 2-3. Furthermore, both vWF antigen concentrations >166% and sICAM-1 concentrations >500 ng/mL had 100% specificity for an adverse outcome in patients after out-of-hospital cardiopulmonary resuscitation but were less predictive in patients after in-hospital cardiopulmonary resuscitation. CONCLUSIONS: vWF antigen and sICAM-1 might be useful adjunctive variables for early determination of outcome in patients after successful out-of-hospital cardiopulmonary resuscitation.

Adult↗

PubMed2003

Loss of p27 expression is associated with poor prognosis in stage I-II pancreatic cancer.

OBJECTIVE: p27 is a cyclin-dependent kinase inhibitor that prevents progression of the cell cycle from G1 phase. Postranscriptional loss of p27 correlates with poor prognosis in various solid tumors. In pancreatic cancer, the loss of p27 expression has been correlated with high tumor grade and advanced clinical stage, but data on its prognostic value are lacking. METHOD: In this retrospective study, the association between immunohistochemical p27 expression and prognosis was evaluated in 147 patients with pancreatic cancer using a commercial anti-Kip1/p27 monoclonal antibody. RESULT: p27 expression was generally low; in 103 of the 147 pancreatic cancer tumors examined, no nuclear staining was observed and in only 5 specimens did more than 50% of the nuclei stain, probably reflecting the aggressive nature of the disease. Loss of p27 expression was associated with poor prognosis in stage I-II pancreatic adenocarcinoma; the 5-year survival for p27 negative patients was 3.6% compared with 20% for p27-positive patients (p = 0.03). In a multivariate survival analysis in patients with stage I-II disease, p27 (HR 1.8) was a significant prognostic factor, independent of grade (RR 2.9). There was no association between p27 and other clinical variables. In conclusion, tissue expression of p27 is a significant predictor of 5-year survival in stage I-II pancreatic adenocarcinoma.

Aged↗

PubMed2025

Exome-wide association study reveals 7 functional variants associated with ex-vivo drug response in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by poor survival outcomes. Further, due to the extreme molecular heterogeneity of the disease, drug treatment response varies from patient to patient. The variability of drug response can cause unnecessary treatment in more than half of the patients with no or partial therapy responses leading to severe side effects, monetary as well as time loss. Understanding the genetic risk factors underlying the drug response in AML can help with improved prediction of treatment responses and identification of biomarkers in addition to mechanistic insights to monitor treatment response. Here, we report the results of the first Exome-Wide Association Study (EWAS) of ex-vivo drug response performed to date with 175 AML cases and 47 drugs. We used information from 55,423 germline exonic SNPs to perform the analysis. We identified exome-wide significant (p < 9.02 × 10- 7) associations for rs113985677 in CCIN with tamoxifen response, rs115400838 in TRMT5 with idelalisib response, rs11878277 in HDGFL2 with entinostat, and rs2229092 in LTA associated with vorinostat response. Further, using multivariate genome-wide association analysis, we identified the association of rs11556165 in ATRAID, and rs11236938 in TSKU with the combined response of all 47 drugs and 29 nonchemotherapy drugs at the genome-wide significance level (p < 5 × 10- 8). Additionally, a significant association of rs35704242 in NIBAN1 was associated with the combined response for nonchemotherapy medicines (p = 2.51 × 10- 8), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the first EWAS to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients.

Humans↗

PubMed2005

Serum uric acid levels as a predictor of in-hospital death in patients hospitalized for decompensated heart failure.

OBJECTIVES: The aim of this study was to determine the value of serum uric acid levels in predicting in-hospital mortality of chronic heart failure patients hospitalized for decompensation in spite of appropriate medical therapy. METHODS AND RESULTS: This study was conducted in patients who were admitted to our clinic between January 2003 and April 2004 due to decompensated heart failure. Only patients who had a functional capacity of class IV and who already received loop diuretic and ACE inhibitor therapy before their admission were included. Patients with recurrent admissions during this period were excluded. Eighty-five patients fulfilled these criteria: group I consisted of 25 patients who died during hospitalization whereas group II consisted of 60 patients who were discharged alive after treatment. Age, sex, left ventricular ejection fraction derived from 2-D echocardiography, serum sodium (Na), gamma-glutamyl transpeptidase (GGT), creatinine, uric acid levels, white blood cell counts and drugs used on admission were the selected parameters as predictors of in-hospital mortality in these patients. When stepwise logistic regression analysis was used, female sex and serum uric acid levels at admission appear to be the only predictors of death during that hospitalization independent of other variables. CONCLUSIONS: Serum uric acid levels may be used as a predictor of death in hospitalized heart failure patients with class IV symptoms.

Aged↗

PubMed1999

[Histological characteristics and clinical significance of Japanese prostate cancer with low levels of prostate specific antigen of 4.0 ng/ml or lower].

PURPOSE: They set a normal limit of prostate specific antigen (PSA) to 4.0 ng/ml in Tandem R assay at most institutions. We investigated clinical and histological characteristics of prostate cancer based on whole mount step-section histology of radical prostatectomy specimens, and taking notice of Japanese prostate cancer whose levels of PSA are less than 4.0 ng/ml in normal levels. MATERIALS AND METHODS: One hundred and twenty-two patients underwent radical prostatectomy for clinically resectable prostate cancer at University Hospital from February 1992 to April 1997. Clinicopathological findings were stratified according to the preoperative PSA levels in 111 patients without preoperative endocrine therapy. Immunohistochemical study for PSA was conducted in 7 randomly selected patients. RESULTS: Of the patients 22 (19.8%) had normal (4.0 ng/ml or lower) preoperative serum PSA. Mean tumor volume in this PSA range was 1.5 cm3 with one pT 0 case included. Pathologically organ confined, potentially curable disease (< pT 3) was found in 17 (77.3%) patients and extracapsular extension and seminal vesicle invasion in 5 (23.8%), respectively. No patients had positive pelvic lymph nodes. Well differentiated tumors of Gleason scores 2-4 were found in 9 (40.9%) of the patients, moderately differentiated tumors (Gleason scores 5, 6) in 5 (22.7%) and poorly differentiated histology (Gleason scores 7-10) in 7 (31.8%). Sixteen (72.7%) patients had clinically significant tumors (> 0.5 cm3, Gleason score > or = 7). All 7 patients had positive staining for PSA, but its intensity did not correlate with serum PSA levels. CONCLUSIONS: Many prostate cancers found in surgical specimens were clinically significant despite the low levels of PSA and potentially curable by definitive treatment. Age, co-morbidity and other clinicopathological variables as well as PSA levels should all be taken into account when treatment options are discussed.

Aged↗

PubMed1999

Bcl-2 expression on fine-needle aspirates from primary breast carcinoma: correlation with other biologic factors.

BACKGROUND: The bcl-2 gene encodes for a protein that is involved in cell death regulation. It frequently is expressed in breast tumors, in which it is associated with favorable prognostic factors. It has been suggested that bcl-2 also may act as a modulator of response to chemotherapy and/or endocrine therapy. Because fine-needle aspiration (FNA) biopsy has been established as a reliable method for the diagnosis and biologic characterization of breast carcinoma, we assessed Bcl-2 expression on FNAs from primary breast carcinoma and evaluated its correlations with other prognostic variables. METHODS: Bcl-2, estrogen receptor (ER), progesterone receptor (PgR), p53 protein expression, and Ki-67 growth fraction were evaluated by immunocytochemistry on FNAs from 130 patients with primary breast carcinoma. Nuclear cytologic grade was assessed on FNA smears. RESULTS: Bcl-2 was expressed in 99 of 130 FNAs (76%). Bcl-2 expression was correlated with positive ER (P < 0.001) and PgR (P < 0.001) status and inversely correlated with p53 (P = 0.0036), Ki-67 (P = 0.0073), and nuclear cytologic grade (P < 0.001). CONCLUSIONS: Bcl-2 expression, evaluated by immunocytochemistry on FNAs from primary breast carcinoma, correlates with favorable prognostic features such as ER and PgR expression, p53 negativity, a low Ki-67 index, and high tumor differentiation. These results are in agreement with those found on histologic samples. As FNA biopsy is used increasingly as a primary tool in the diagnosis of breast carcinoma, Bcl-2 evaluation by immunocytochemistry on FNA may provide, in addition to other biologic variables, useful information for prognostic and predictive purposes, particularly in patients considered to be candidates for neoadjuvant treatments. Cancer (Cancer Cytopathol)

Biomarkers, Tumor↗

PubMed2004

Semi-quantitative RT-PCR assessment of molecular markers in breast large-core needle biopsies.

Large-core needle biopsies are frequently used for the preoperative evaluation of the breast lesions. In addition to initial diagnostic information, they can show the status of molecular markers with predictive and prognostic value and further contribute to an optimal selection of treatment strategy. So far, the potential use of large-core needle biopsies in assessment of marker profile of the breast lesions was studied using the immunostaining approaches. In this work, we sought to determine whether analysis of the large-core needle biopsy by semi-quantitative reverse-transcription polymerase chain reaction reveals molecular data that correspond with the marker status of the subsequently removed tumor. Five molecular markers including ER, PR, c-erbB-2/HER-2/neu, c-erbB-3/HER-3, and CD44 were assessed on mRNA isolated from 23 large-core needle biopsies and corresponding surgical breast cancer specimens using beta2- microglobulin as an internal standard. Significant or highly significant correlation between core biopsies and excised tumors was observed for each marker when the mRNA expression status was scored as positive or negative, with the concordance of the data ranging from 73.9% to 86%. Using the dichotomous scoring, majority of the biopsies (75%) displayed molecular profile that was either identical to the profile of the related tumor specimen, or with the difference in one marker. However, no significant correlation was found when the levels of the markers were expressed as continuous variables, possibly due to intratumoral cell heterogeneity. These results suggest potential usefulness and reliability of semi-quantitative RT PCR in the evaluation of large-core needle biopsies with regard to marker positivity or negativity. On the other hand, the marker-related data expressed as continuous variables cannot be accurately assessed on the large- core needle specimens using this approach, indicating the need for methodological improvements.

Adult↗

PubMed2005

Analyzing synovial tissue samples. What can we learn about early rheumatoid arthritis, the heterogeneity of the disease, and the effects of treatment?

The synovium is the key target of the disease process in rheumatoid arthritis (RA). Examination of synovial tissue samples may provide insight into the events that take place in different phases of the disease and may help to decipher the mechanism of action of antirheumatic treatment. This review describes the features of synovitis in early RA, which clearly represent chronic inflammation. There is marked interindividual variability, suggesting that RA consists of different pathogenetic subsets. Evaluation of serial synovial tissue samples has shown that effective treatment is associated with a reduction in synovial macrophages, independent of the specific mechanism of action of the compound. This suggests that these are key effector cells in the pathogenesis. In addition, it provides a biomarker that can be used in clinical trials.

Antirheumatic Agents↗

PubMed2006

[Immunologic laboratory testing in clinical practice for rheumatoid arthritis].

The recent clinical practices for rheumatoid arthritis have changed greatly. First, biologic agents such as tumor necrosis factor blocker have been developed as well as disease-modifying antirheumatic drugs, with great efficacy in intractable RA. On the other hand, the importance of early effective therapeutic intervention has been recognized since early treatment prevents the progression of joint damage. However, early diagnosis of RA is not so easy because of the lack of appropriate diagnostic criteria. New laboratory tests have appeared for the diagnosis and prognostic prediction of RA. Among them, anticyclic citrullinated peptide antibodies (anti-CCP), which bind epitopes containing citrulline, seem to be attracting the most attention. Although rheumatoid factor (RF) is the only serologic marker among the seven classification criteria of the American College of Rheumatology (ACR) for RA, variability of the RF assay within laboratories and/or between laboratories, and quality assurance has not been established. We must address the standardization of RF assay as soon as possible.

Antirheumatic Agents↗

PubMed1989

Serum hyaluronate as a marker for disease severity in the Lactobacillus casei model of arthritis in the rat.

Serum concentrations of hyaluronate may provide a clinically relevant, quantitative marker of disease in patients with active rheumatoid arthritis (RA). We studied the utility of serum hyaluronate in an animal model, with features reminiscent of human RA, in which LEW/N female rats were made arthritic by intraperitoneal injection of sonicated Lactobacillus casei. When serum hyaluronate was measured by an inhibition ELISA, a dose dependent correlation was found between the amount of L. casei injected and both joint score and serum hyaluronate in the chronic phase of the disease. A linear correlation between the chronic phase joint score and serum hyaluronate was observed (r = 0.69, p less than 0.001). Two orally administered compounds, flurbiprofen (20 mg/kg) and methotrexate (0.125 mg/kg), were effective in decreasing both variables. Thus, serum hyaluronate may have utility in evaluating the therapeutic efficacy of antirheumatic/antiinflammatory agents in vivo in the chronic phase of RA-like diseases.

Animals↗

PubMedDate not supplied

Reproducibility and variability of the rectal mucosal proliferation index using proliferating cell nuclear antigen immunohistochemistry.

Rectal mucosal proliferation has been shown to be increased in patients with neoplastic lesions of the large bowel and may serve as a marker of risk for colorectal malignancy. We conducted analyses to determine reliability and components of variability that might suggest optimal analysis strategies for studies of proliferation. Endoscopic pinch biopsies were obtained from 17 adult patients, labeled using proliferating cell nuclear antigen, scored using strict rules, and then rescored. Labeling index, defined as the proportion of labeled cells in a crypt, was calculated for each crypt, biopsy, subject, and group. There was excellent reproducibility. The technician was able to select previously scored crypts 95% of the time. The overall labeling index was identical on repeat. There was considerable variability in labeling index among crypts from a single biopsy and between biopsies of a single subject. Variance component estimates suggested that 20% of the variability of labeling index was due to subject, 30% due to the biopsy within a subject, and 50% due to crypts within a biopsy. There were substantial gains in statistical power by scoring two biopsies rather than one. There was less gain from further increases in biopsy number. There was little statistical advantage for counting more than 8 crypts/biopsy. Demonstrating a decrease of 25% in the mean labeling index with 90% power could require more than 100 subjects/group. We conclude that proliferating cell nuclear antigen is an extremely reproducible method to determine proliferation index. There is considerable variability among subjects, biopsies, and crypts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

Fibrin D-dimer as a marker of disease activity in systemic onset juvenile rheumatoid arthritis.

OBJECTIVE: To study the prevalence of coagulation abnormalities in children with systemic juvenile rheumatoid arthritis (JRA) using a sensitive marker of fibrin degradation, and to determine whether serial levels of this variable parallel disease activity or predict response to medications in this disease. METHODS: Levels of d-dimer were determined in 24 consecutive patients with systemic JRA in conjunction with complete blood counts, erythrocyte sedimentation rate, maximum fever, duration of morning stiffness, and swollen joint count. Serial levels were then obtained in 11 patients. Linear regression analyses were done to determine any correlations between d-dimer and the other variables; and paired t test was used to compare levels before and after treatment interventions. Levels of d-dimer were also compared against concurrent clinical events such as pericarditis. RESULTS: Elevated levels of d-dimer were found in 23/24 of the patients (96%). When serial levels were analyzed, there were correlations between levels of d-dimer and fever (p = 0.03) and total leukocyte count (p = 0.04), but not with other variables. There was a significant reduction in levels before and after treatment in patients deemed to be clinical responders to immunomodulatory agents (p = 0.02). Elevated levels were also indicative of severe disease over the remainder of followup; lack of d-dimer indicated a benign disease course. CONCLUSION: With the use of a sensitive and specific marker of fibrinolysis known as d-dimer, coagulation abnormalities were more prevalent in children with systemic JRA than previously reported, and are frequently found during periods of active disease. Furthermore, serial levels of d-dimer appear to parallel response to disease modifying agents, and may predict outcome over a short followup period. Fibrin d-dimer may represent a novel marker that, when used in combination with known variables, could enhance that assessment of disease activity and response to medications in children with systemic onset JRA.

Adolescent↗

PubMed2006

Evaluation of the prognostic value of cellular inhibitor of apoptosis protein in epithelial ovarian cancer using automated quantitative protein analysis.

PURPOSE: The cellular inhibitor of apoptosis protein (cIAP) is regarded as an important prognostic biomarker in cancer. Here, we sought to determine the prognostic value of cIAP protein levels in epithelial ovarian cancer using a novel method of compartmentalized in situ protein analysis. METHODS: A tissue array composed of 150 advanced-stage ovarian cancers, treated with surgical debulking followed by platinum/paclitaxel-based combination chemotherapy, was constructed. For evaluation of protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis. RESULTS: The mean follow-up time for the entire cohort was 34.4 months. Patients with tumors bearing high cIAP membranous expression had a 3-year survival rate of 31% compared with 73% for patients with low cIAP expressing tumors (P = 0.0020). In multivariable analysis, adjusting for well-characterized prognostic variables, low membranous cIAP expression level was the only significant prognostic factor for overall survival. CONCLUSIONS: Our results indicate that cIAP protein levels have prognostic value in ovarian cancer patients. Modulation of cIAP levels may improve clinical outcome in ovarian cancer.

Automation↗