Biomedical subjects

Patrik Finne

Publications and source records attributed to Patrik Finne.

23 records · Page 2Linked to original sources

PubMed2003

Dual-label immunoassay for simultaneous measurement of prostate-specific antigen (PSA)-alpha1-antichymotrypsin complex together with free or total PSA.

BACKGROUND: A major portion of prostate-specific antigen exists in circulation as a complex with alpha(1)-antichymotrypsin (PSA-ACT), whereas a minor part is free (fPSA). The proportion of PSA-ACT is increased in prostate cancer (PCa), but immunologic determination of PSA-ACT is hampered by a background produced by nonspecific adsorption of ACT to the solid phase. To reduce the nonspecific interference, we produced an antibody specific for complexed ACT and developed immunofluorometric assays (IFMAs) for simultaneous measurement of fPSA + PSA-ACT (fPSA/PSA-ACT) and PSA-ACT + total PSA (tPSA, PSA-ACT/tPSA). METHODS: Monoclonal antibodies (MAbs) were produced by immunization with PSA-ACT. The dual-label time-resolved IFMAs for fPSA/PSA-ACT and PSA-ACT/tPSA used a capture MAb to tPSA, an Eu(3+)-labeled MAb to fPSA or complexed ACT, and an Sm(3+)-labeled MAb to complexed ACT or to tPSA as tracer antibodies. The clinical utility was evaluated using serum samples from individuals with or without PCa with PSA concentrations of 2.0-20.0 micro g/L. RESULTS: One MAb (1D10) showed low cross-reactivity with free ACT and cathepsin G-ACT. A sandwich assay for PSA-ACT with 1D10 as tracer had a detection limit of 0.05 micro g/L, and with this assay, PSA-ACT was undetectable in female sera. The detection limit for fPSA was 0.004 micro g/L. Determinations of the ratio of fPSA to PSA-ACT and the proportions of fPSA/tPSA and PSA-ACT/tPSA provided the same clinical specificity for PCa and provided significantly better clinical specificity than did tPSA. CONCLUSIONS: Background problems observed in earlier PSA-ACT assays are eliminated by the use of a MAb specific for complexed ACT as a tracer. The same clinical validity can be obtained by determination of fPSA or PSA-ACT together or in combination with tPSA.

Aged↗

PubMed2002

Prostate-specific antigen and other prostate-derived proteases cleave IGFBP-3, but prostate cancer is not associated with proteolytically cleaved circulating IGFBP-3.

BACKGROUND: Proteolysis of insulin-like growth factor-binding proteins (IGFBPs) may increase IGF-mediated growth stimulation and development of cancer in the organs producing large amounts of proteases, such as the prostate. METHODS: We studied proteolysis of IGFBP-3 by three prostate-derived proteases, namely prostate specific antigen (PSA), human kallikrein 2 (hK2), and trypsin, and also by native seminal plasma. Cleavage of 125I-IGFBP-3 was studied by SDS-PAGE and autoradiography. We also used two different sandwich-type IGFBP-3 immunoassays, called "intact" and "total" IGFBP-3 assays. These assays differ in their capacity to recognize proteolytically degraded IGFBP-3. RESULTS: HK2, PSA, and trypsin all cleaved IGFBP-3 at the concentrations normally present in seminal plasma. The IGFBP-3 cleavage by seminal plasma was inhibited by ZnCl2, which strongly inhibits hK2 and PSA, but not by a specific trypsin inhibitor. The IGFBP-3 fragments resulting from proteolytic cleavage by PSA, hK2, or trypsin were undetectable in the "intact IGFBP-3 assay," whereas the "total IGFBP-3 assay" also detected the proteolytic fragments. No increased fragmentation of IGFBP-3 was found in serum of 659 men with elevated PSA concentrations, of whom 178 had a proven prostate cancer. Furthermore, the IGFBP-3 levels were not associated with the PSA concentrations. CONCLUSIONS: These results show that, while seminal plasma and prostate-derived proteases can cleave IGFBP-3, in patients with prostate cancer the circulating IGFBP-3 is not significantly proteolyzed by either PSA, hK2, or trypsin.

Cell Division↗

PubMed2002

Estimation of prostate cancer risk on the basis of total and free prostate-specific antigen, prostate volume and digital rectal examination.

BACKGROUND AND OBJECTIVE: Approximately 70% of the men with an elevated serum prostate-specific antigen (PSA) identified in prostate cancer screening do not have prostate cancer. Other available diagnostic variables may be utilized to reduce the number of false positive PSA results, but few algorithms for calculation of the combined impact of multiple variables are available. The objective of this study was to establish nomograms showing the probability of detecting prostate cancer at biopsy on the basis of total PSA, and the percentage of free PSA in serum, prostate volume and digital rectal examination (DRE) findings. METHODS: In a randomized, population-based prostate cancer screening trial 10284 men aged 55-67 years were screened during 1996 and 1997 in two metropolitan areas in Finland. Results for men (n=758) with a serum PSA of 4-20 microg/l were used to establish the risk nomograms. Of these 200 (26%) had prostate cancer at biopsy. RESULTS: Prostate cancer probability depended most strongly on the percentage of free PSA. Total PSA, prostate volume, and DRE also contributed to prostate cancer probability, whereas age and family history of prostate cancer did not. More false positive PSA results could be eliminated by using the multivariate risk model rather than the percentage of free PSA (p<0.001) or PSA density (p=0.003) alone. CONCLUSIONS: Wide variation in probability of detecting prostate cancer among screened men with a serum PSA of 4-20 microg/l was observed. The nomograms established can be used to avoid or defer biopsy in men with a low prostate cancer probability in spite of a serum PSA level exceeding 4 microg/l.

Aged↗

PubMedDate not supplied

Combination of HCGbeta, CA 19-9 and CEA with logistic regression improves accuracy in gastrointestinal malignancies.

BACKGROUND: Earlier studies suggest that the free beta-subunit of human chorionic gonadotropin (hCGbeta) may be a useful tumour marker for gastrointestinal cancers. Our aim was to investigate hCGbeta in serum in gastrointestinal diseases in comparison with CA 19-9 and carcinoembryonic antigen (CEA). PATIENTS AND METHODS: The serum concentrations of hCGbeta, CA 19-9 and CEA were measured from 142 patients with malignant and 178 with benign gastrointestinal diseases. The diagnostic accuracies of the markers were compared and a diagnostic algorithm was established with logistic regression (LR) analysis. RESULTS: The hCGbeta serum level was elevated most frequently in bile duct (56%), pancreatic (45%) and gastric cancer (41%). In benign diseases, hCGbeta concentration was elevated in 10% of the patients. In an LR model each marker provided independent diagnostic information and the probability of cancer was calculated. It was applied as a diagnostic algorithm providing better accuracy than the markers alone. In receiver operating characteristic (ROC) curve analysis the area under the curve (AUC) value of the algorithm was significantly higher than the AUC values of CA 19-9, CEA, or hCGbeta (p=0.009-0.049). CONCLUSION: Serum hCGbeta, CA 19-9 and CEA provide additive diagnostic information in gastrointestinal malignancies and the use of an algorithm established by LR analysis improves diagnostic accuracy.

Adult↗

PubMedDate not supplied

Tenascin-C expression and its prognostic significance in oral and pharyngeal squamous cell carcinoma.

BACKGROUND: Tenascin-C (Tn-C) is an extracellular matrix protein with growth-, invasion- and angiogenesis-promoting activities. It is up-regulated in tumorigenesis and has been suggested to correlate with prognosis in various carcinomas, but its significance in squamous cell carcinoma of the head and neck remains unknown. The purpose of this study was to examine the prognostic significance of Tn-C expression in oral and pharyngeal squamous cell carcinomas. PATIENTS AND METHODS: Tn-C expression was determined by immunohistochemistry in 65 consecutive tumors from patients with primary oral and pharyngeal squamous cell carcinoma. Based on staining intensity, both the stroma and invasion border were separately classified into two groups and the results correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: The tumor stroma showed strong Tn-C expression in 56 (86%) samples, and weak Tn-C expression in 9 (14%). At the invasion border, Tn-C expression was strong in 38 (58%) samples and weak in 27 (42%). Tn-C expression was not a statistically significant predictor of survival and there was no correlation between Tn-C expression and tumor or patient characteristics. CONCLUSION: Tn-C protein was overexpressed in the majority of our oral and pharyngeal squamous cell carcinoma samples. The presence of TnC did not appear to predict for OS or DFS.

Adult↗