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Results for “Biomarker variability”

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PubMed2002

Plasma, liver and kidney folate and plasma homocysteine concentrations are poor response variables at very low dietary folate intakes, in a folate depletion/repletion rat model.

Folate depletion/repletion rat models are popular protocols for assessing the bioavailability of folate. Much of the early work carried out on folate bioavailability concentrated on foods naturally high in folate. However, foods low in folate often contribute significantly to folate intake because of their high consumption in the general population. Therefore, the assessment of the bioavailability of foods low in folate is essential to properly estimate folate intake. The present study investigated plasma, liver and kidney folate and plasma homocysteine concentrations as appropriate response variables for measuring folate bioavailability in the rat at very low dietary folate intakes. One hundred and one weanling male rats (Wistar strain) were fed a folate-deficient diet containing 1% succinyl sulfathiazole for 28 d. Following depletion, six rats were randomly assigned to each of 16 repletion diets containing folic acid, fortified white bread, unfortified wholemeal bread or unfortified rye bread calculated to provide 6.25, 12.5, 18.75 and 25 micrograms folate/kg of each diet. After a further 28 d, plasma, liver and kidney folate concentrations were determined by microbiological assay. Plasma homocysteine was measured by HPLC as a functional indicator of folate status. Only a weak correlation was found between the response variables measured and dietary folate intake, indicating that this folate depletion/repletion rat model is not suitable for testing the response of rats fed diets containing very low levels of folate.

Animals↗

PubMed2005

Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 in evaluating prognostic significance.

The objective of this study was to evaluate the expression of bcl-2 in Dukes' stage B and stage C (AJCC/UICC stage I and III) colorectal adenocarcinomas and to examine its association with clinicopathological features, p53, ki-67 and long term outcome. Paraffin embedded specimens from 61 patients with Dukes' stage B (AJCC/UICC stage I) and 39 patients with Dukes' stage C (AJCC/UICC stage III) colorectal adenocarcinoma who were treated with surgery were assessed. We used immunohistochemistry to determine the expression of bcl-2, p53 and ki-67 with a five-year follow-up. Positive bcl-2 expression was seen in 27 cases (27%). Expression of bcl-2 protein was related to tumor stage (p=0.0117). There was very strong evidence of an association between bcl-2 staining and ki-67 score (p<0.001). There was a trend towards increased survival in patients whose tumors expressed bcl-2 protein (p=0.001). When entered into a multivariate analysis model, which also included p53 and stage, bcl-2 staining emerged as a prognostic indicator variable. Expression of bcl-2 appears to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Adenocarcinoma↗

PubMedDate not supplied

Tumor necrosis factor-alpha and interferon-gamma in serum of multiple myeloma patients.

The levels of TNF-alpha and IFN-gamma were examined in serum from 32 patients with multiple myeloma and 33 healthy controls using sensitive enzyme-linked immunosorbent assays (ELISA). The detection limits for TNF-alpha and IFN-gamma were 80 pg/ml and 200 pg/ml, respectively. All samples were obtained at the time of diagnosis, before treatment. In sera from 8 of the myeloma patients the TNF-alpha concentrations were above the detection limit with a maximum value of 1.0 ng/ml. Overall, the TNF-alpha levels of the myeloma patients did not differ from the levels of the control group. Detectable amounts of IFN-gamma were found in 17 of the patient sera with 10.7 ng/ml as the top value. In contrast, the control group showed significantly lower s-IFN-gamma levels without detectable amounts in any of the samples (p less than 0.01). High IFN-alpha levels in 4 patients coincided with intercurrent infections but were not accompanied by a parallel increase of the TNF-alpha levels. The TNF-alpha and IFN-gamma values were compared with the serum levels of beta 2-microglobulin, calcium and creatinine, the M-component, the erythrocyte sedimentation rate, the degree of plasma cell infiltration of the bone marrow, the degree of skeletal destructions and with patients survival. No significant correlations could be observed between TNF-alpha or IFN-gamma and these variables of myeloma activity. We conclude that detection of serum TNF-alpha and IFN-gamma levels in multiple myeloma appears to be without any clinical value.

Aged↗

PubMed1993

Transcription and protein expression of mb-1 and B29 genes in human hematopoietic malignancies and cell lines.

The transmembrane forms of all immunoglobulin (Ig) classes are associated with two glycoproteins, mb-1 and B29, that are crucial for signal transduction following antigen binding to the Ig molecule. We have investigated the transcription and protein expression of mb-1 and B29 genes during B-cell development. Sixty human continuous cell lines (35 B-lineage, 11 T-lineage, 11 myeloid-lineage and three non-hematopoietic) and 75 hematopoietic malignancies (55 B-lineage, 12 T-lineage and eight myeloid-lineage), were tested for RNA expression by Northern blotting experiments with the mb-1 pRA3 cDNA probe, and a newly isolated B29 cDNA probe. Protein expression was analyzed by immunofluorescence microscopy of cytocentrifuge preparations, which were labeled with the anti-mb-1 HM57 monoclonal antibody (mAb) and an anti-B29 polyclonal antiserum, directed against intracellular epitopes of these polypeptides. Except for two early precursor B-cell lines, mb-1 and B29 transcripts and proteins were detected in all B-cell lines and B-cell malignancies, i.e. from immature to more mature B cells, irrespective of their Ig class expression. Transcription of mb-1 genes seems to be down-regulated at the plasma cell stage, because no mb-1 transcripts and mb-1 proteins could be detected in the four plasma cell lines and two plasma cell leukemias tested. B29 transcripts were detectable in these cell samples, but low levels of B29 proteins were only detected in one plasma cell line. The HM57 mAb gave strong labeling on fresh cytocentrifuge preparations of all B-cell samples, and this mb-1 protein expression appeared to be B-cell specific. We therefore conclude that the HM57 mAb is well suited for the detection of the mb-1 molecule as a pan-B-cell marker for the diagnosis of immature and mature B-cell malignancies. The expression pattern of the mb-1 protein is comparable to that of the CD19 and CD22 antigens, but has the advantage of being B-lineage specific. Although B29 protein expression was restricted to B-lineage cells, the anti-B29 antiserum is less suitable for diagnosis of B-cell malignancies, because of the variable and generally weak signals on cytocentrifuge preparations.

Antigens, CD↗

PubMed2006

Transepidermal water loss, serum IgE and beta-endorphin as important and independent biological markers for development of itch intensity in atopic dermatitis.

BACKGROUND: Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD. OBJECTIVES: To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD. METHODS: This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH. RESULTS: There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity. CONCLUSIONS: Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.

Adolescent↗

PubMed2005

Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome.

OBJECTIVES: Children with Hutchinson-Gilford Progeria Syndrome (HGPS) die of severe premature atherosclerosis at an average age of 13 years. Although the LMNA gene defect responsible for this "premature aging syndrome" has been identified, biological mechanisms underlying the accelerated atherosclerosis are unknown. We determined whether children with HGPS demonstrate abnormalities in known biomarkers for cardiovascular disease (CVD) risk. STUDY DESIGN: We quantified serum lipids, lipoproteins, C-reactive protein (CRP), and adiponectin in children with HGPS and age-matched control children. RESULTS: HDL cholesterol (P < .0001) and adiponectin (P < .001) concentrations decreased significantly with increasing age in HGPS but not in control children. There was a positive correlation between these variables in HGPS ( P < .0001) but not control children. Mean total cholesterol, LDL and HDL cholesterol, triglyceride, and median CRP levels were similar between HGPS and control children (all P > .05). CONCLUSIONS: Declining HDL cholesterol and adiponectin with advancing age may contribute to accelerated atherosclerotic plaque formation in HGPS. Several factors frequently associated with CVD risk in normal aging (elevated CRP, total and LDL cholesterol) showed no difference and are unlikely to influence CVD risk in HGPS. HDL and adiponectin may represent significant mediators and potential therapeutic targets for atherosclerosis in HGPS.

Adiponectin↗

PubMed2003

Primary breast cancer in elderly women: biological profile and relation with clinical outcome.

A biological characterisation carried out on 14,007 primary breast cancers provided evidence in favour of a relation between advanced age and favourable features (positivity for oestrogen/progesterone receptors, low proliferative rate, absence of p53 accumulation, bcl-2 overexpression, diploid DNA content), showed a similar pattern of association between patho-biological variables regardless of patient age, and demonstrated a relation between biological variables and disease outcome in the elderly, comparable to that already reported for younger patients. In fact, oestrogen receptor and proliferative activity provided independent prognostic information either in node-negative or in node-positive tumours treated with radical or conservative surgery plus radiotherapy, alone or followed by adjuvant hormonal therapy. It would be thus reasonable to use biomarkers as a complement to clinico-pathological features in a 'risk-factor profile system' even for elderly patients, upon their validation in prospective studies and after assessing the cost-benefit of treatments planned on the basis of biological information.

Adult↗

PubMed2002

Motivating parents of kids with asthma to quit smoking: the PAQS project.

The Parents of Asthmatics Quit Smoking (PAQS) project contrasts two theory-based smoking cessation interventions for parents of children with asthma, and compares mechanisms of behavior change within and across theoretical perspectives. We hypothesize that enhancing the perception of risk to self and child will motivate smoking cessation more than standard approaches that emphasize building self-efficacy and coping skills for quitting in a population that is largely not motivated to quit smoking. Smokers (n = 288) and their asthmatic children who receive nurse-delivered in-home asthma education (as part of the insurance carrier's standard of care) are randomized into one of two treatment conditions: (1) the Behavioral Action Model (BAM), in which nurses emphasize goal setting and skill building to enhance self-efficacy to quit smoking, or 2) the Precaution Adoption Model (PAM), in which nurses tailor the intervention to the smoker's readiness to quit and incorporate biomarker feedback [i.e. level of carbon monoxide exposure to the smoker and level of environmental tobacco smoke (ETS) exposure to the child] in order to increase risk perception in smokers. In both conditions, smokers who are ready to quit receive the nicotine patch. Analyses will examine (1) quit rates, ETS level and motivation to quit as the primary dependent variables, (2) mediators of behavior change between and within conditions, and (3) relations between parent smoking outcomes and child asthma morbidity (i.e. ER visits and asthma symptoms) post-treatment. Results will help tailor interventions to this population, and identify mechanisms of behavior change that result in adaptive health outcomes for smokers and their children who have asthma.

Adolescent↗

PubMed1995

Role of the pathologist in biomarker studies.

Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomarkers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alterations in the tissues at risk and include differentiation, genetic composition, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation of genetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumor classification as well as whether it is intraepithelial or invasive. If the process is intraepithelial, the grade and extent of the intraepithelial lesion are reported. If the neoplasm is invasive, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathologic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistochemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; results may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis and flow cytometry, can determine total DNA content. Using static image analysis, very small tumors can be studied. In addition, adjacent intraepithelial and invasive components of a tumor may be studied from a single slide. Steroid receptors, oncogenes, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthetic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach is generally not applicable with current image analysis equipment; however, cell cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerase chain reaction, and in situ PCR, can have many applications when applied to paraffin-embedded tissues, including detection of viral DNA, identification and measurement of apoptosis, and defining gene deletions.

Biomarkers, Tumor↗

PubMed2025

Chromosomal instability by low-coverage whole-genome sequencing assay predicts prognosis in bladder cancer patients underwent radical cystectomy.

PURPOSE: To investigate chromosomal instability (CIN) in tumor tissue from radical bladder resection and to evaluate whether it can be used as a biomarker for the molecular typing of (BC). METHODS: DNA was extracted from formalin-fixed paraffin-embedded samples of 50 BC patients who were followed up to March 23 2023 using the Qiagen nucleic acid kits. We analyzed CIN in tumor of bladder by low-coverage whole genome sequencing (LC-WGS). Kaplan-Meier log-rank test was used to perform survival analysis. The association between variables and overall and progression-free survival was analyzed using the Cox proportional hazards model. RESULTS: There were 44 genome segments with statistically significant changes in copy number. CIN was significantly correlated with tumor stage, lymph node metastasis, relapse and survival status. Patients with high CIN were found to have a worse survival, with a median overall survival (OS) of 15 months. In addition, patients with high CIN were more likely to relapse, with a median progression-free survival (PFS) of 7 months. Patients with low CIN showed better OS and PFS. However, there was no significant difference in OS and PFS between T2 and T3-T4 patients. Multivariate cox regression analysis showed that high CIN was an independent predictor of OS, and high CIN and muscle invasion were independent predictors of PFS. Furthermore, patients with abnormal copy number of a single chromosome also had a poor prognosis, with a median survival of 14-30 months for OS and 5-10 months for PFS, while negative patients had a better prognosis. CONCLUSION: CIN was significantly correlated with tumor stage, lymph node metastasis, relapse and survival status of BC. Patients with high CIN or abnormal copy numbers of a single chromosome have a poor prognosis. CIN might be better than T stage in predicting the prognosis of patients with BC. Molecular typing of CIN can be used as an independent prognostic factor for BC.

Humans↗

PubMed2025

Cellular Adhesion Molecules and Adverse Outcomes in Chronic Heart Failure: Findings From the DAPA-HF Randomized Clinical Trial.

IMPORTANCE: Vascular cell adhesion molecule 1 (VCAM-1) and intracellular cell adhesion molecule 1 (ICAM-1) are responsible for immune cell-cell interactions. Systemic levels of VCAM-1 are associated with incident heart failure (HF). OBJECTIVES: To determine if VCAM-1 and ICAM-1 levels are associated with progression of established HF. DESIGN, SETTING, AND PARTICIPANTS: Participants enrolled in the biomarker substudy of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) randomized clinical trial had VCAM-1 and ICAM-1 levels measured at baseline and 12 months. The DAPA-HF trial was conducted at 410 sites in 20 countries. Patients with HF and reduced ejection fraction (HFrEF) in New York Heart Association (NYHA) class II to IV with elevated natriuretic peptides were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Data were analyzed from January 2023 to January 2025. INTERVENTIONS: Dapagliflozin, 10 mg, once daily vs placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of a worsening HF event or cardiovascular death. The associations between VCAM-1 and ICAM-1 levels at baseline and the primary outcome, its components, and all-cause death were analyzed using Cox proportional hazards regression models adjusted for known prognostic variables including estimated glomerular filtration rate (eGFR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT), as well as high-sensitivity C-reactive protein. RESULTS: A total of 3051 participants (mean [SD] age, 67.2 [10.5] years; 2386 male [78.2%]) were included in this study. Mean (SD) follow-up time was 17.6 (5.2) months. The median (IQR) baseline VCAM-1 level was 997 (816.7-1218.8) ng/mL. Compared with patients with lower concentrations of VCAM-1, those with higher concentrations of VCAM-1 were older (mean [SD] age T3 vs T1, 69.7 [9.7] years vs 64.1 [10.7] years; P < .001), in worse NYHA class (T3 vs T1, NYHA class III/IV 35.6% [362 of 1017] vs 26.5% [269 of 1017]; P < .001), and had higher NT-proBNP (median [IQR] T3 vs T1, 2018 [1126-3753] pg/mL vs 1118 [693-1830] pg/mL) and hs-TnT (median [IQR] T3 vs T1, 24.7 [17.1-37.5] ng/L vs 16.6 [11.6-24.9] ng/L) concentrations, and lower eGFR (mean [SD] T3 vs T1, 58.4 [17.6] mL/min/1.73 m2 vs 71.7 [18.0] mL/min/1.73 m2). Patients in tertile 3 of VCAM-1, compared with tertile 1, had the highest risk of each outcome (eg, adjusted hazard ratio [HR] for primary outcome 1.40; 95% CI, 1.11-1.77; P = .004). ICAM-1 level was not associated with an elevated risk of any outcome. The benefit of dapagliflozin vs placebo in reducing the risk of the primary outcome was consistent across VCAM-1 tertiles: HR, 0.76 (95% CI, 0.54-1.06), 0.82 (95% CI, 0.59-1.12), and 0.77 (95% CI, 0.61-0.98) for tertiles 1, 2 and 3, respectively (P for interaction = .93). There was no significant change in VCAM-1 level with dapagliflozin at 52 weeks. CONCLUSIONS AND RELEVANCE: Results of this substudy of the DAPA-HF randomized clinical trial demonstrate that higher VCAM-1 levels, possibly reflecting a distinct inflammatory/immune pathophysiological pathway in HFrEF, were associated with worse outcomes, even after adjustment for conventional prognostic variables. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124.

Aged↗

PubMed2000

Synthetic spectra of simulated terrestrial atmospheres containing possible biomarker gases.

NASA's proposed Terrestrial Planet Finder, a space-based interferometer, will eventually allow spectroscopic analyses of the atmospheres of extrasolar planets. Such analyses would provide information about the existence of life on these planets. One strategy in the search for life is to look for evidence of O3 (and hence O2) in a planet's atmosphere; another is to look for gases that might be present in an atmosphere analogous to that of the inhabited early Earth. In order to investigate these possibilities, we have calculated synthetic spectra for several hypothetical terrestrial-type atmospheres. The model atmospheres represent four different scenarios. The first two, representing inhabited terrestrial planets, are an Earth-like atmosphere containing variable amounts of oxygen and an early Earth-type atmosphere containing methane. In addition, two cases representing Mars-like and early Venus-like atmospheres were evaluated, to provide possible "false positive" spectra. The calculated spectra suggest that ozone could be detected by an instrument like Terrestrial Planet Finder if the O2 concentration in the planet's atmosphere is > or = 200 ppm, or 10(-3) times the present atmospheric level. Methane should be observable on an early-Earth type planet if it is present in concentrations of 100 ppm or more. Methane has both biogenic and abiogenic sources, but concentrations exceeding 1000 ppm, or 0.1% by volume, would be difficult to produce from abiogenic sources alone. High methane concentrations in a planet's atmosphere are therefore another potential indicator for extraterrestrial life.

Astronomy↗

PubMed1999

Is serum bilirubin concentration the only valid prognostic marker in primary biliary cirrhosis?

From the many prognostic models for primary biliary cirrhosis (PBC) patients based on Cox's regression analysis, the Mayo model has gained the most popularity and was successfully validated in some centers. The aim of our study was to validate the Mayo survival model for Polish PBC patients and, in case of its inapplicability, to select prognostic variables and to create time-fixed and time-dependent survival models for the patients. We used database information on patients from 6 medical centers in Poland, fulfilling clinical, serological, and/or pathological criteria of PBC. The Mayo model was validated using data from 116 PBC patients. The time-fixed and time-dependent models were created using data on clinical and biochemical variables used in the Mayo model from 162 and 208 patients, respectively. The Mayo model validation was performed graphically and by one-sample log-rank tests after dividing the study sample into 3 groups of high, medium, and low risk. The survival analysis was performed using Cox's proportional hazards regression method on clinical and biochemical variables used in the Mayo model. Treatment with ursodeoxycholic acid (UDCA) was included in the time-dependent analysis. Validation showed that the Mayo model overestimated death risk in Polish PBC patients. Of the variables used in the Mayo model, serum bilirubin concentration appeared to be the only variable of prognostic importance. The analysis shows that serum bilirubin concentration holds most of the prognostic information for our PBC patients irrespective of prior treatment with UDCA.

Bilirubin↗

PubMed2004

Immunohistochemical study for O6-methylguanine-DNA methyltransferase in the non-neoplastic and neoplastic components of gliomas.

Although the expression O6-methylguanine-DNA methyltransferase (MGMT) is an important hallmark for decision of nitrosourea chemotherapy for glioma patients, no immunohistochemical method for analysis of MGMT has been standardized yet. Gliomas usually contain non-neoplastic cells even deep in the tumor. It is not known which of these components expresses MGMT. To clarify this point, we investigated MGMT expression in the non-neoplastic cells in autopsy and surgical specimens by immunohistochemistry. High grade gliomas were also studied to find a cut-off point for treatment decision. MGMT immunohistochemistry in the normal brain or brain with non-neoplastic disease revealed nuclear staining in some endothelial cells, inflammatory cells, ependymal cells, astrocytes and oligodendroglias. Some cells were double stained with CD68 (macrophages or microglias). The neurons were consistently MGMT-negative. High grade gliomas always contained an MGMT-positive non-neoplastic component. Although, the endothelial cells were easily distinguished from the neoplastic cells, other cells were often mistaken for tumor cells. The population of MGMT-positive non-neoplastic cells was usually less than 10%. We set a cut off-point at 10% between the positive and negative groups because the statistical difference in the overall survival was most distinct at this value. In 51 high grade glioma patients, who received both radiotherapy and chemotherapy with nimustine (ACNU), the median overall survival of the MGMT-negative group (23 months) was significantly longer than that of the MGMT-positive group (14 months) (P < 0.009). Multivariate analysis revealed that the negative MGMT expression was a significant prognostic variable next to the degree of surgical removal for the overall survival. In the MGMT-positive group, addition of platinum-based chemotherapy did not improve the survival.

Aged↗

PubMed2006

Role of MIB1 in predicting survival in patients with glioblastomas.

BACKGROUND: Histologic immunomarkers of cell cycle proteins have been utilized for prognosis in high-grade astrocytic tumors. One such marker, MIB1, an antibody immunoreactive throughout the cell cycle, is predictive of more aggressive disease and poorer prognosis in astrocytomas. An independent role of MIB1 analysis for survival prediction and clinical management within histologic grades has not been clearly proven. METHODS: This study retrospectively evaluated MIB1 reactivity in tissue samples from 116 patients with glioblastomas on initial medical presentation. Clinical variables considered included gender, age, Karnofsky Performance Scores (KPS), extent of surgical resection, adjuvant radiation and survival. RESULTS: Univariate and multivariate analyses were used to correlate these variables with MIB1 staining. MIB1 staining does not predict overall survival or response to adjuvant therapy as an independent risk factor. CONCLUSION: MIB1 labeling does not predict patient survival as an independent variable and does not predict response to additional therapies. Patient survival with glioblastoma was predicted by KPS, age, extent of resection and use of adjuvant radiotherapy.

Adult↗

PubMed1986

Cyclic chemotherapy with cyclophosphamide, doxorubicin, and cisplatin plus vinblastine and bleomycin in advanced germinal tumors. Results with 100 patients.

One hundred patients with advanced mixed germ-cell tumors were treated with cisplatin, cyclophosphamide, and doxorubicin alternating with vinblastine and bleomycin (cyclic CISCAII/VBIV). The chemotherapy achieved an 89 percent continuous disease-free status (85 percent with chemotherapy, 4 percent with chemotherapy plus surgery). The mean follow-up duration for patients with continuous complete remission was 132 weeks (+/- 6.2), with a median of 126 weeks. Multivariate analysis using a stepwise logistic regression of prognostic variables revealed that a high serum level of the beta subunit of human chorionic gonadotropin (more than 50,000 mIU/ml) was of prognostic significance, followed by the Samuels staging criteria and extragonadal origin of disease. Thirty-two patients underwent exploratory surgery after they had had two courses of chemotherapy beyond the establishment of a stable mass and absent serum biomarkers. No viable cancer was found at exploration, and all patients remain alive and free of disease. The acute toxicity of the cyclic chemotherapy was formidable, but only one patient had a fatal complication. Thirty-six percent of the CISCAII courses and 44 percent of the VBIV courses were associated with leukopenic fever, and 5 percent of the CISCAII courses and 8 percent of the VBIV courses were associated with culture-positive infection. Long-term toxicity was unusual: bleomycin lung toxicity 1 percent, cardiac toxicity 1 percent. CISCAII/VBIV cyclic chemotherapy is superior to cisplatin, vinblastine, and bleomycin (PVB) chemotherapy; it results in a higher complete remission rate, a lower relapse rate, and a lower incidence of long-term complications. Patients with a high risk of failure of PVB chemotherapy (Samuels stage IIIB3 to IIIB5) or with extragonadal tumors should be treated with CISCAII/VBIV.

Adolescent↗

PubMed2006

Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients.

The purposes of this study were to examine the correlations between proliferation markers and survival rate in oral squamous cell carcinoma (OSCC) patients, and to evaluate the efficacy of proliferation markers in predicting lymph node metastasis. The patients' age, gender, T score, clinical stage, PCNA and Ki-67 index were analysed. Univariate analysis showed that T score had a significant influence on survival, and stage 4 group had a significantly lower survival rate. Lymph node metastasis was also a significant predictor of survival. Using a cut-off point of 25%, those patients with lower Ki-67 scores had survival advantage over those with higher Ki-67 scores. PCNA did not show any differences in survival with a cut-off point of 50%. Ki-67 and PCNA were significantly higher in the primary tumours associated with lymph node metastasis (pN+) than in those without lymph node metastasis (pN0). Multivariate analysis showed that clinical stage and Ki-67 were independent prognostic factors for survival in OSCC patients. From this result, it can be postulated that the cancer staging based on the TNM stage was a powerful prognostic variable and Ki-67 had a significant effect on the cumulative survival rate.

Adolescent↗

PubMed2005

Natural history and predictors of disease severity in chronic hepatitis C.

Cirrhosis is the end-stage consequence of fibrosis progression in patients with chronic hepatitis C. The median time from infection to cirrhosis is 30 years, with a high inter-individual variability, which is now better understood. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male gender, alcohol consumption, HIV co-infection and low CD4 count. Metabolic conditions such as steatosis, being overweight and diabetes are emerging as independent co-factors of fibrogenesis. The recent validation of non-invasive biomarkers should facilitate the study of fibrosis progression in large populations.

Disease Progression↗