PURPOSE: To investigate the relationship between rising patterns of prostate-specific antigen (PSA) before chemotherapy and PSA flare during the early phase of chemotherapy in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: This study included 55 patients with CRPC who received chemotherapy and in whom pre-treatment or post-treatment PSA levels could be serially obtained. The baseline parameters included age, performance, Gleason score, PSA level, and disease extent. PSA doubling time was calculated using the different intervals: the conventional interval from the second hormone manipulation following the nadir until anti-androgen withdrawal (PSADT1), the interval from the initial rise after anti-androgen withdrawal to the start of chemotherapy (PSADT2), and the interval from the nadir until the start of chemotherapy (PSADT3). The PSA growth patterns were analyzed using the ratio of PSADT2 to PSADT1. RESULTS: There were two growth patterns of PSA doubling time: 22 patients (40.0%) had a steady pattern with a more prolonged PSADT2 than PSADT1, while 33 (60.0%) had an accelerating pattern with a shorter PSADT2 than PSADT1. During three cycles of chemotherapy, PSA flare occurred in 11 patients (20.0%); of these patients, 3 were among 33 (9.1%) patients with an accelerating PSA growth pattern and 8 were among 22 patients (36.4%) with a steady PSA growth pattern (p=0.019). Multivariate analysis showed that only PSA growth pattern was an independent predictor of PSA flare (p=0.034). CONCLUSION: An exponential rise in PSA during anti-androgen withdrawal is a significant predictor for PSA flare during chemotherapy in CRPC patients.
Aged ; Aged, 80 and over ; Androgen Antagonists ; Antineoplastic Agents/*therapeutic use ; Follow-Up Studies ; Humans ; Karnofsky Performance Status ; Male ; Middle Aged ; Neoplasm Grading ; Predictive Value of Tests ; Prostate-Specific Antigen/*blood ; Prostatic Neoplasms, Castration-Resistant/*blood/*drug therapy/pathology ; Taxoids/*therapeutic use ; Tumor Markers, Biological/blood

No abstract available.
Biopsy ; Blood Glucose/metabolism ; C-Peptide/blood ; Calcium Gluconate/administration & dosage/*diagnostic use ; Female ; Humans ; Immunohistochemistry ; Injections, Intra-Arterial ; Insulin/blood ; Insulinoma/blood/*blood supply/pathology/surgery ; Middle Aged ; Pancreatic Neoplasms/blood/*blood supply/pathology/surgery ; Pancreaticoduodenectomy ; Splenic Artery/*radiography ; *Tomography, X-Ray Computed ; Treatment Outcome ; Tumor Markers, Biological/blood

BACKGROUND/AIMS: alpha-Fetoprotein (AFP) is the biomarker most widely used to detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that are reportedly associated with tumorigenesis and metastasis. This study was conducted to evaluate the clinical utility of using plasma GPC3 and OPN as diagnostic biomarkers for HCC. METHODS: We measured the plasma levels of GPC3 and OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The GPC3 levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup analyses, including subgroups of HCC patients with low serum AFP and PIVKA II levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high sensitivity (62.1%) for detecting small HCC tumors. CONCLUSIONS: The plasma levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However, GPC3 may have a complementary role in diagnosing HCC in patients with nondiagnostic levels of conventional tumor markers and with small-sized tumors.
Carcinoma, Hepatocellular/*diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Glypicans ; Humans ; Liver Neoplasms/*diagnosis ; Male ; Middle Aged ; Osteopontin/*blood ; ROC Curve ; Tumor Markers, Biological/*blood

PURPOSE: To evaluate the relationship between levels of total testosterone and total prostate-specific antigen (PSA) in healthy men with PSA<4 ng/mL. MATERIALS AND METHODS: The study comprised 179 men with a mean age of 59.19+/-12 years who visited Osmaniye State Hospital, Osmaniye, Turkey, between January 2006 and January 2007 for a routine checkup. The patients were divided into two subgroups: patients with PSA<2.5 mg/ml (group I, n=160 patients) and patients with PSA of 2.5 to 4 ng/mL (group II, n=19 patients). The relationship between PSA and testosterone levels was investigated in both groups and in patients aged <60 years. The mean testosterone level was calculated for patients aged <50 years and was compared with the mean value of patients aged > or =50 years. RESULTS: In all patients, the mean values for serum PSA and total testosterone were 1.27+/-0.88 ng/mL and 404.04+/-158.86 ng/mL, respectively. No correlation was detected between serum PSA and testosterone levels in either subgroup (group I, r=0.072, p=0.363; group II, r=0.031, p=0.900) or in patients aged <60 years (r=0.032, p=0.72). The mean values of testosterone in patients aged > or =50 years and in patients aged <50 years were 417.01+/-163.35 and 344.16+/-120.21 ng/dL, respectively (p=0.02). CONCLUSIONS: No impact of testosterone was found on the PSA level in healthy men with PSA <4 ng/mL. Therefore, a high serum testosterone level may not mandate adjustment of PSA values. This serum sex hormone showed a significant increment after the age of 50 years. Further studies including a larger number of patients should be carried out to confirm these findings.
Aged ; Aging/blood ; Humans ; Kallikreins/*blood ; Male ; Middle Aged ; Prostate-Specific Antigen/*blood ; Reference Values ; Testosterone/*blood ; Tumor Markers, Biological/blood

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.
Humans ; Male ; Prostate-Specific Antigen/*blood ; Prostatectomy ; Prostatic Neoplasms/*diagnosis/pathology/surgery ; Protein Isoforms/blood ; Protein Precursors/*blood ; Sensitivity and Specificity ; Severity of Illness Index ; Tumor Markers, Biological/blood

Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-alpha and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8+/-14.4 vs. 22.2+/-6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (gamma=0.671; gamma=0.612; and gamma=0.601, P<0.001, respectively), but not with serum TNF-alpha levels. Serum LRG levels in patients with an active disease status (DAS28> or =2.6) were significantly higher than those in remission (DAS28<2.6) (36.45+/-14.36 vs. 24.63+/-8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-alpha and it may be a novel biomarker for assessing inflammatory activity in patients with RA.
Adult ; Aged ; Area Under Curve ; Arthritis, Rheumatoid/blood/*diagnosis ; Biological Markers/blood ; Blood Sedimentation ; C-Reactive Protein/analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Glycoproteins/*blood ; Humans ; Male ; Middle Aged ; ROC Curve ; *Severity of Illness Index ; Tumor Necrosis Factor-alpha/blood

Our study aimed to investigate whether serum leucine-rich alpha-2-glycoprotein (LRG) levels are elevated in patients with rheumatoid arthritis (RA). In addition, we assessed their correlation with disease activity parameters and pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Our study included 69 patients with RA and 48 age- and sex-matched healthy controls. Serum concentrations of TNF-alpha and LRG were determined by enzyme-linked immunosorbent assay. Serum LRG concentrations were significantly elevated in patients with RA compared with those in healthy controls (30.8+/-14.4 vs. 22.2+/-6.1 ng/mL; P<0.001). In patients with RA, serum LRG levels were found to be correlated with disease activity score 28 (DAS28), erythrocyte sedimentation rate, and C-reactive protein levels (gamma=0.671; gamma=0.612; and gamma=0.601, P<0.001, respectively), but not with serum TNF-alpha levels. Serum LRG levels in patients with an active disease status (DAS28> or =2.6) were significantly higher than those in remission (DAS28<2.6) (36.45+/-14.36 vs. 24.63+/-8.81 ng/mL; P<0.001). Our findings suggest that serum LRG could contribute to the inflammatory process independent of TNF-alpha and it may be a novel biomarker for assessing inflammatory activity in patients with RA.
Adult ; Aged ; Area Under Curve ; Arthritis, Rheumatoid/blood/*diagnosis ; Biological Markers/blood ; Blood Sedimentation ; C-Reactive Protein/analysis ; Enzyme-Linked Immunosorbent Assay ; Female ; Glycoproteins/*blood ; Humans ; Male ; Middle Aged ; ROC Curve ; *Severity of Illness Index ; Tumor Necrosis Factor-alpha/blood

OBJECTIVE: The purpose of this study was to evaluate the expression of epidermal growth factor-like domain 7 (EGFL7) in epithelial ovarian cancer, and to assess its relevance to clinicopathological characteristics and patients' survival. METHODS: A total of 177 patients with epithelial ovarian cancer were enrolled in the current study. For each patient, a retrospective review of medical records was conducted. Immunohistochemical staining for EGFL7 was performed using tissue microarrays made with paraffin-embedded tissue block. EGFL7 expression levels were graded on a grade of 0 to 3 based on the percentage of positive cancer cells. We analyzed the correlations between the expression of EGFL7 and various clinical parameters, and also analyzed the survival outcome according to the EGFL7 expression. RESULTS: The expression of EGFL7 in ovarian cancer tissues was observed in 98 patients (55.4%). High expression of EGFL7 (grade 2 or 3) was significantly correlated with pathologic type, differentiation, stage, residual tumor after debulking surgery, lymphovascular space involvement, lymph node metastasis, high cancer antigen 125, peritoneal cytology, and ascites. Among these clinicopathologic factors, differentiation was significantly correlated with EGFL7 expression in multivariate analysis (p<0.05). Survival analysis showed that the patients with high EGFL7 expression had a poorer disease free survival than those with low EGFL7 expression (p=0.002). CONCLUSION: Our data suggest that EGFL7 expression is a novel predictive factor for the clinical progression of epithelial ovarian cancer, and may constitute a therapeutic target for antiangiogenesis therapy in patients with epithelial ovarian cancer.
Adult ; CA-125 Antigen/blood ; Cell Differentiation/physiology ; Endothelial Growth Factors/*metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Proteins/metabolism ; Neoplasm Staging ; Neoplasm, Residual ; Neoplasms, Glandular and Epithelial/*diagnosis/pathology/surgery ; Ovarian Neoplasms/*diagnosis/pathology/surgery ; Prognosis ; Retrospective Studies ; Survival Analysis ; Tumor Markers, Biological/*metabolism

Dirofilaria immitis (heartworm) infections affect domestic dogs, cats, and various wild mammals with increasing incidence in temperate and tropical areas. More sensitive antibody detection methodologies are required to diagnose asymptomatic dirofilariasis with low worm burdens. Applying current transcriptomic technologies would be useful to discover potential diagnostic markers for D. immitis infection. A filarial homologue of the mammalian translationally controlled tumor protein (TCTP) was initially identified by screening the assembled transcriptome of D. immitis (DiTCTP). A BLAST analysis suggested that the DiTCTP gene shared the highest similarity with TCTP from Loa loa at protein level (97%). A histidine-tagged recombinant DiTCTP protein (rDiTCTP) of 40 kDa expressed in Escherichia coli BL21 (DE3) showed immunoreactivity with serum from a dog experimentally infected with heartworms. Localization studies illustrated the ubiquitous presence of rDiTCTP protein in the lateral hypodermal chords, dorsal hypodermal chord, muscle, intestine, and uterus in female adult worms. Further studies on D. immitis-derived TCTP are warranted to assess whether this filarial protein could be used for a diagnostic purpose.
Animal Structures/chemistry ; Animals ; Antibodies, Helminth/blood ; Antigens, Helminth/chemistry/*genetics/immunology/*isolation & purification ; Cloning, Molecular ; Dirofilaria immitis/chemistry/*genetics/immunology ; Disease Models, Animal ; Dogs ; Escherichia coli/genetics ; Gene Expression ; Molecular Sequence Data ; Molecular Weight ; Recombinant Fusion Proteins/chemistry/genetics/immunology/isolation & purification ; Sequence Analysis, DNA ; Tumor Markers, Biological/chemistry/*genetics/immunology/*isolation & purification

BACKGROUND/AIMS: Oxidative stress increases the risk of cardiovascular complications of metabolic syndrome (MetS). This study was conducted to examine the difference in antioxidant capacity according to the presence of MetS, and to characterize the association between antioxidant capacity and MetS-related factors. METHODS: We used the biological antioxidant potential (BAP) test to estimate antioxidant capacity. The BAP test has recently been used as an indicator of antioxidant capacity. We measured BAP levels in 45 patients with MetS (mean age, 44.6 +/- 1.1 years) and 47 age- and sex-matched controls (mean age, 42.7 +/- 1.1 years). To evaluate the association between antioxidant capacity and MetS, adiponectin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-alpha, and homeostatic model assessment for insulin resistance (HOMA-IR), linear regression and logistic analyses were performed. RESULTS: The mean BAP of the MetS group (1,937.3 +/- 36.5 micromol/L) was significantly lower than that of the non-MetS group (2,101.7 +/- 29.5 micromol/L). Also, the mean BAP was low in persons having low high density lipoprotein and high triglyceride. Reduced antioxidant capacity was significantly associated with adiponectin, HOMA-IR and hs-CRP after adjusting for age and sex. The odds ratios for MetS with BAP, log adiponectin, log HOMA-IR, and log hs-CRP were 0.63 (95% confidence interval [CI], 0.49 to 0.82), 0.22 (0.10 to 0.51), 14.24 (4.35 to 46.58), and 1.93 (1.36 to 2.75), respectively. CONCLUSIONS: Persons with MetS showed reduced antioxidant capacity. We identified relationships between antioxidant capacity measured by BAP test and MetS, as well as MetS-related factors, such as insulin resistance, hs-CRP, and adiponectin.
Adipokines/blood ; Adult ; Antioxidants/*metabolism ; Biological Markers/blood ; C-Reactive Protein/metabolism ; Case-Control Studies ; Female ; Humans ; Insulin Resistance ; Interleukin-6/blood ; Male ; Metabolic Syndrome X/*blood ; Middle Aged ; Predictive Value of Tests ; Tumor Necrosis Factor-alpha/blood