Biomedical subjects

G Jakse

Publications and source records attributed to G Jakse.

252 records · Page 14Linked to original sources

PubMedDate not supplied

Experimental and clinical efficacy of 2', 2'-difluorodeoxycytidine (gemcitabine) against renal cell carcinoma.

Preclinical and clinical studies have been performed to evaluate the efficacy of gemcitabine (2',2'-difluorodeoxycytidine; dFdC) in human renal cell carcinoma. Experimental data corroborated dFdC as an effective drug against cell lines from renal cell carcinomas (ACHN, A-498, SN12C) at concentrations much below clinically achievable doses. ACHN-bearing nude mice showed an overall response rate of 27% to dFdC (3 mice with complete response, 1 with partial response, 3 with stable and 8 with progressive disease). Objective response from 37 evaluable patients was 8.1% (1 patient with complete response and 2 patients with partial response). Gemcitabine was well tolerated thus, although gemcitabine at the dosage and schedule chosen had only small activity, the observed toxicity may permit further dose escalation or a more frequent administration of the drug.

Adolescent↗

PubMedDate not supplied

Treatment of renal cancer patients with gemcitabine (2',2'-difluorodeoxycytidine) and interferons: antitumor activity and toxicity.

Combined therapy of gemcitabine with interferons on patients with histologically confirmed metastatic renal cell carcinoma is reported. Patients had an unfavourable disease due to documented tumor progression after various interferon-alpha-based immunotherapy (26 weeks on average). The median number of metastatic sites was 6.1 per patient and 78% of the patients exhibited >/= 4 lesions. Nine evaluable patients received at least 6 doses of gemcitabine and 8 doses of interferon-gamma. Overall, therapy resulted in a remission rate of 15% (4 x partial response; 4 x minor response) for single measurable lesions (n=53). Remissions were more often found for lesions, that did not progress at baseline evaluation (n=30; OR: 20%), compared to 8.7% for sites in progression (n=23). However, as a result of therapy, 43.5% of the progressive lesions did not continue to progress. Although only one of nine patients finally overall achieved a minor remission and one patient a stable disease, the median time to tumor progression (6.1 months) and the median survival (13.5 months) was favourable. In conclusion, the combination of gemcitabine and interferon demonstrated cytotoxic and cytostatic effects on metastases of renal cell carcinoma at a tolerable toxicity, thus controlled clinical studies for first line therapy with gemcitabine and interferon are in progress.

Adult↗

PubMedDate not supplied

Immunohistochemical analysis of prostate-specific antigen does not correlate to other prognostic factors in breast cancer.

BACKGROUND: Prostate-specific antigen (PSA) is found in 30-40% of female breast tumors, as recently described. Diamandis and co-workers could demonstrate that PSA correlate significantly to a relapse-free survival and lower tumor stages in patients with breast cancer using a time-resolved immunofluorometric analysis. The presence of PSA in these tumors seems to reflect a favourable prognostic marker for that disease. The aim of our study was to evaluate the role of PSA as a prognostic factor in breast cancer using an immunohistochemical technique. MATERIALS AND METHODS: The PSA immunoreactivity of tissues from one-hundred women with malignant breast tumors was correlated to tumor staging, histomorphological tumor type, and biochemical estrogen and progesterone receptor content. Additionally, survival analysis was performed according to Kaplan and Meier. RESULTS: 49% of the tumors revealed positive staining for PSA. No significant correlation between PSA and the other parameters, or the mean survival time (PSA pos.: 5.3 years, PSA neg.: 5.4 years) could be demonstrated. CONCLUSIONS: As there were no significant correlations between PSA and other prognostic markers, PSA detected by immunohistochemistry seems not to be helpful in prognostic evaluation of breast cancer.

Biomarkers, Tumor↗

PubMedDate not supplied

Age related changes of free and total prostate specific antigen in serum.

UNLABELLED: PSA in serum exists in several molecular forms. The amount of free and total PSA and ratio are discussed to be useful to increase the ability of PSA to distinguish prostate cancer from benign prostatic hyperplasia. Therefore, we tried to characterize the age related changes of free and total PSA in a German rural population. METHODS: Serum samples were obtained from 697 men. All study participants were between 20 and 79 years old and had no clinical evidence of prostate cancer by serum PSA, digital rectal examination and transrectal ultrasonography. The sera were kept frozen at -20 degrees C until analysis and were assayed within 3 months after sampling. Free and total PSA values were determined employing a chemiluminescent enzyme immunoassay (Immulite PSA and Freies PSA, DPC Biermann). RESULTS: Free PSA, total PSA and the free-to-total PSA ratio (f-/t-ratio) demonstrated a correlation with patient age (r = 0.855, p = 0.0141; r = 0.857, p = 0.0137; r = -0.788, p = 0.0352). Employing the median and the 95% percentile the age-specific reference ranges for free and total PSA were calculated. For the f-/t-ratio the median and the interquartile range (i.e. 25th-75th percentile) were calculated. CONCLUSION: In confirmation of a recent report, we found a direct correlation of free PSA, total PSA and the f-/t-ratio with age, whereas free and total PSA increases, the f-/t-ratio decreased with advancing age.

Adult↗

PubMedDate not supplied

Critical aspects related to the interpretation of the free-to-total PSA-ratio.

INTRODUCTION: The number of assays available for the measurement of total and free PSA is increasing. As different methods can determine different PSA concentrations as well as different free-to-total PSA ratios in identical serum samples, the cut-offvalue for the ratio still needs to be determined. METHODS: 114 sera from patients with histologically confirmed benign prostatic hyperplasia (BPH; n = 58) and cancer of the prostate (CaP; n = 56) were analyzed with two different assays. Free PSA (free), total PSA (total) and the free-to-total- PSA ratio (ratio) were determined employing Enzym-Test PSA und freies PSA (Boehringer Mannheim, Germany) and Immulite PSA und freies PSA (DPC Biermann, Bad Nauheim, Germany) RESULTS: The statistical results are tabulated below: [table: see text] CONCLUSION: Direct comparison of the two assays revealed a high statistical correlation (r = 0.94-0.99) for free and total PSA. In contrast, the ratio of the two assays was not as reproducible (r = 0.81-0.83). This result indicates that the reference range for the ratio is dependent on the assay employed and an that uncritical use of an applied reference range can be counter-productive.

Aged↗

PubMedDate not supplied

Cytokeratin markers in patients with prostatic diseases.

OBJECTIVES: Recently tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). Cyfra 8/18, a marker which recognizes both cytokeratin 8 and 18 fragments, is thought to improve sensitivity and specificity of TPS. In our study we investigated the ability of the TPS and cyfra 8/18 serum concentration to discriminate between patients with clinically localized CaP and BPH. METHODS: Serum levels of TPS and Cyfra 8/18 were determined in patients with untreated CaP (pT1-3pNoMo: n = 11) and BPH (n = 22). The TPS and the Cyfra 8/18 concentrations were correlated to the prostate specific antigen (PSA) serum concentration. RESULTS: Median TPS concentration was 45.3 U/L in CaP-patients and 54.8 U/L in BPH-patients. This difference is statistically not significant (p = 0.2). Median Cyfra 8/18 level was 0.64 ng/mL in CaP-patients and 0.57 ng/mL in BPH-patients. This difference is statistically not significant (p = 0.91). Furthermore no correlation with PSA levels could be established (TPS: r = -0.13; Cyfra 8/18: r = 0.17). CONCLUSION: In contrast to recent reports we found both cytokeratin markers, TPS as well as Cyfra 8/18, to be non-discriminative parameters in CaP and BPH.

Aged↗

PubMedDate not supplied

Metastatic workup of patients with prostate cancer employing alkaline phosphatase and skeletal alkaline phosphatase.

PURPOSE: To compare the efficacy of two tests, alkaline phosphatase (AP) and skeletal alkaline phosphatase (SAP) as staging markers to discriminate patients with cancer of the prostate (CaP) with bone metastases (M+) from those without bone metastases (Mo). MATERIALS AND METHODS: Patients with previously untreated CaP were entered in the retrospective analysis. Serum concentrations of AP (n = 215) and SAP (n = 73) were available. After staging the patients could be divided into 2 groups: Group I: patients with CaP and bone metastases (cT2-4 NxMoss AP: n = 40; SAP: n = 21) Group II: patients with CaP without bone metastases (cT3-4 Nx Mo; pT1-3 No Mo; AP: n = 175; SAP: n = 52). RESULTS: None of the Mo patients but 71% of the M+ patients exhibited a SAP value above the reference range (< 19 ng/ml). This difference is statistically significant (p < 0.001) and resulted in a sensitivity and specificity of 71% and 100%, respectively. The Youden-index is 0.7. In contrast 7% of the Mo patients and only 13% of the M+ patients exhibited a AP value above the reference range (< 170 U/l). This difference is statistically not significant (p = 0.71) and resulted in a sensitivity and specificity of 13% and 93%, respectively. The Youden-index is 0.06. CONCLUSION: SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it provides more information than AP concerning the skeletal status of these patients.

Adult↗

PubMedDate not supplied

Serum concentrations of transforming growth factor-beta 1 in patients with benign and malignant prostatic diseases.

INTRODUCTION: Transforming growth factor-beta 1 (TGF-beta 1) is found to be most markedly elevated in prostate cancer tissue. We determined the concentration of serum TGF-beta 1 in patients with cancer of the prostate (CaP), and correlated them to tumour stage and serum PSA. METHODS: Serum TFG-beta 1 levels and serum PSA levels were determined in 80 patients with untreated CaP (Group I: pT1-3pNoMo: n = 58; Group II: T1-3pN + Mo: n = 6; Group III: T1-4NxM+: n = 16). Patients with histologically confirmed BPH (n = 50) served as controls. RESULTS: Median TGF-beta 1 levels were not different in CaP- and in BPH-patients (32.86 ng/ml and 35.15 ng/ml respectively; p > 0.05). Furthermore there was no increase in TGF-beta 1 concentrations with advancing tumour stage (Group I: 32.86 ng/ml; Group II: 34.3 ng/ml; Group III: 33.44 (ng/ml; p > 0.05). No correlation with PSA levels could be established (Spearman r = -0.19; p = 0.05). CONCLUSION: TGF-beta 1 was found to be non-discriminative between BPH and CaP. Furthermore no TGF-beta 1 increase could be observed with advancing tumour stage in patients with CaP.

Aged↗

PubMedDate not supplied

Differential expression of the drug resistance markers DNA topoisomerase II alpha and glutathione S-transferase-pi in the histological compartments of Wilms' tumors.

More than 80% of the patients presenting with Wilms' tumor can be cured today. Some patients, however, fail to respond to chemotherapy. The objective of this study was to analyze the immunohistochemical distribution of two markers of cytostatic drug resistance, e.g. DNA topoisomerase II alpha (Topo II alpha) and glutathione S-transferase-pi (GST-pi) in 23 Wilms' tumor patients who had undergone an operation between 1984 and 1997. Eight patients had stage I disease, seven stage II, three stage III, four stage IV, and one stage V disease. Five tumors showed high malignancy histology. Investigations were carried out on formalin-fixed and paraffin-embedded tissue sections using the indirect immunoperoxidase method. Topo II alpha was predominantly present in the epithelial components of the specimens. It was more frequently found in anaplastic tumors. There was no difference in the presence of Topo II alpha in the epithelial components between specimens derived from treated and untreated patients. Topo II alpha was, however, less expressed in the blastemal and stromal elements of specimens after preoperative treatment. If GST-pi was present, it was confined to the epithelial components except for one case. While no expression of GST-pi was found in preoperatively untreated Wilms' tumors, it was present in epithelial compartments in 57% of tumors after chemotherapy. In conclusion, preoperative chemotherapy led to compartment-specific alterations in the expression levels of both markers indicating a contribution to treatment response of Wilms' tumors.

Antigens, Neoplasm↗

PubMedDate not supplied

Altered prostate specific antigen reference range after transurethral resection of the prostate.

OBJECTIVES: We investigated how transurethral resection of the prostate (TURP) affected the serum concentration of prostate specific antigen (PSA) and whether the reference range for PSA has to be altered in these patients following TURP. METHODS: 55 patients were retrospectively analysed. All had undergone TURP for bladder outlet obstruction due to benign prostatic hyperplasia which was confirmed by histopathological amination. PSA was determined pre-operatively and postoperatively every 6 months for 48 months. These patients were compared to 12 patients who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP). In the latter group, in all patients a TURP had been performed up to 7 years before CaP was diagnosed. RESULTS: The median PSA concentration was 4.9 ng/ml before TURP and was subsequently reduced to 0.6 ng/ml after 48 months. There was a steady decrease of the PSA concentration during the observation period. In contrast in patients who subsequently developed a CaP, the median PSA concentration before TURP was 6.8 ng/ml and was reduced to only 2.2 ng/ml after 48 months. PSA levels started to rise before CaP was diagnosed. CONCLUSION: After a TURP with a benign histopathologic specimer) PSA levels decrease steadily to values below 2 ng/ml. In case these patients demonstrate a rising PSA in the follow-up after partial prostatectomy, a CaP should be ruled out.

Aged↗

PubMedDate not supplied

Are age-specific reference ranges for prostate specific antigen population specific?

INTRODUCTION: At present PSA is Considered to be the leading screening test for prostate cancer. We determined whether in men 60 to 79 year old with a serum prostate specific antigen (PSA) within age specific PSA reference ranges prostate biopsy could be safely eliminated. METHODS: We retrospectively analysed all 60-79 year old men who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP) at our institution. All patients had undergone prostate biopsy following an abnormal rectal examination and/or PSA greater than 4.0 ng/ml. We compared our results using the standard reference range of 0 to 4.0 ng/ml with those we had obtained using the age specific PSA reference ranges of Oesterling et al. RESULTS: 204 men between 60-69 years and 67 men between 70-76 years had undergone RPP for CaP. Applying age specific PSA reference ranges 56 CaP would have been overlooked. Of those 46% had a favourable histology. Taken together 54% of the cancers overlooked had an unfavourable histology. CONCLUSION: In contrast to previous reports of unfavourable histological characteristics in only 5-24% of missed cancers, applying age specific PSA reference ranges, 54% of missed cancers in our patients exhibited an unfavourable histology. We therefore conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population.

Age Factors↗

PubMedDate not supplied

Tissue polypeptide specific antigen serum concentrations in patients with newly diagnosed prostatic diseases.

UNLABELLED: Recently, tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). In our study we investigated the ability of the TPS serum concentration as a staging marker in patients with newly diagnosed CaP. METHODS: Serum levels of TPS and PSA were determined in patients with newly diagnosed, untreated CaP (pT1-3pNoMo: n = 71; T1-4NxM+: n = 39) and BPH (n = 30). The TPS serum concentration was correlated to the PSA serum concentration. RESULTS: Median TPS concentration was 33.6 U/L in the pT1-3pNoMo-group; 113.5 U/L in the Tl-4NxM(+)-group and 59.7 U/L in the BPH-group. Although the TPS concentration failed to discriminate between patients with localized CaP and BPH, it discriminated very well between patients with (M+) and without (Mo) bone metastases (p < 0.001). Furthermore no correlation with PSA levels could be established. CONCLUSION: The TPS serum concentration seems to provide additional information in the initial staging of patients with newly diagnosed untreated CaP.

Aged↗

PubMedDate not supplied

Serum levels of prostate specific antigen in men on hemodialysis.

UNLABELLED: The measurement of prostate specific antigen (PSA) is widely used for the early detection of prostate cancer. However the influence of renal failure on the serum levels of the PSA molecular forms is still a matter of investigation. We therefore examined the serum concentration of total and free PSA in patients undergoing hemodialysis and discuss the influence of renal failure on both types. MATERIALS AND METHODS: Serum concentrations of total PSA, free PSA and the free-to-total PSA ratio were measured in 48 men undergoing hemodialysis. Total and free PSA levels were measured employing a chemiluminescent enzyme immunoassay. RESULTS: Serum levels of total PSA, free PSA as well as the free-to-total PSA ratio did not change significantly in uremic patients after hemodialysis. Median total PSA concentration was 1.1 ng/mL before and 1.15 ng/mL after hemodialysis (p = 0.24); median free PSA concentration was 0.29 ng/mL before and 0.32 ng/mL after hemodialysis (p = 0.14). Median free-to-total PSA ratio was 0.29 ng/mL before and 0.31 ng/mL after hemodialysis (p = 0.66). CONCLUSION: Serum free PSA as well as total PSA is not eliminated by hemodialysis and the slightly elevated levels of free PSA and the free-to-total PSA ratio in uremic patients after hemodialysis may be caused by the concomitant decrease in binding proteins. We therefore conclude that the reference ranges for total PSA, free PSA and the f-/t-PSA ratio are applicable undergoing chronic hemodialysis.

Adult↗

PubMedDate not supplied

Differential expression of the heat shock protein 70 in the histological compartments of nephroblastomas.

Nephroblastomas (Wilms' tumors) are curable with survival rates above 80%. Nevertheless, some tumors fail to respond to therapy and those patients have a poor prognosis. Prognostic factors for nephroblastomas have still not been satisfactorily explored. In an effort to unravel molecular markers for non-responding nephroblastomas, we investigated by means of immunohistochemistty the expression of heat-shock protein 70 (HSP70) in formalin-fixed and paraffin-embedded tissue samples from 32 children afflicted with nephroblastoma. The results were validated using real-time RT-PCR. HSP70 expression was confined to blastemal and epithelial components, while the tumor stroma was negative. HSP70 expression was greater, if the tumors had been chemotherapeutically treated prior to operation, indicating that cytostatic drugs induce HSP70. Furthermore, high HSP70 expression was confined to tumors from children who survived, whereas tumors from dead patients were negative or weakly-positive for HSP70. Though the number of cases analyzed was small, they provide an indication that HSP70 expression may be of prognostic value.

Adolescent↗

PubMedDate not supplied

Expression of glucose transporter 1 (Glut-1) in cell lines and clinical specimens from human prostate adenocarcinoma.

BACKGROUND: Increased uptake and metabolism of glucose is a characteristic of malignant transformation. Overexpression of glucose transporters, especially Glut-1, is a common event in human malignancies. To date, little is known about the role of Glut-1 in human prostate cancer (PC). The aim of this study was to investigate the expression of Glut-1 both in PC cell lines and clinical specimens of primary PC. MATERIALS AND METHODS: The PC cell lines DU145, PC3 and LNCaP were assessed for Glut-1 mRNA expression by Northern blot analysis. In a total of 45 primary PC specimens, radioactive (35S) in situ hybridizations (RISH) for Glut-1 mRNA expression were performed on frozen sections. Quantification of Glut-1 expression was obtained by use of an image analysis system. RESULTS: Glut-1 expression was detected in all 3 cell lines. Expression in the more poorly-differentiated cell lines DU145 and PC3 was even higher than in the hormone-responsive LNCaP cell line. In situ hybridizations in primary PC revealed Glut-1 expression just above the detection limit in well-differentiated tumors. Significantly increased Glut-1 expression was detected in moderately- to poorly-differentiated PC. CONCLUSION: Glut-1 is expressed in PC cell lines and primary PC. The level of expression increases with advancing grade of malignancy. These findings support a role for Glut-1 in PC proliferation.

Adenocarcinoma↗

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Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.

The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.

Aged↗

PubMedDate not supplied

Increased discrimination between benign prostatic hyperplasia and prostate cancer through measurement of percentage free PSA.

OBJECTIVE: The value of Prostate-Specific Antigen (PSA) for the early detection of Prostate Cancer (CaP) is controversial due to an appreciable false positive rate causing unnecessary biopsies. As PSA exits in both free and bound forms the percentage of free PSA was found to be lower in CaP than in Benign Prostatic Hyperplasia (BPH). We investigated whether the percentage of free PSA offers better discrimination on the detection of CaP. MATERIAL AND METHODS: In a retrospective analysis the percentage of free PSA was determined in the sera of 50 consecutive patients with histologically proven BPH (n = 30) and clinically localised CaP without metastases (n = 20; pT1-3 No Mo). Serum levels of free PSA and total PSA were determined employing a chemiluminescent enzyme immunoassay. RESULTS: Patients with CaP demonstrated a lower percentage of free PSA (median: 8.5, range: 2.7-24.5) than patients with BPH (median: 22.35, range: 8.9-66.7). (p < 0.001). CONCLUSION: Determination of percentage of free PSA enhances the discrimination between BPH and CaP and may reduce the number of unnecessary biopsies in patients with elevated PSA.

Diagnosis, Differential↗

PubMedDate not supplied

Metastatic workup of patients with prostate cancer employing skeletal alkaline phosphatase.

PURPOSE: To compare the efficacy of two tests, prostate-specific antigen (PSA) and skeletal alkaline phosphatase (SAP) as staging markers to discriminate patients with cancer of the prostate (CaP) with bony metastases (M1) from those without bony metastases (Mo). MATERIAL AND METHODS: Forty-seven untreated patients with Mo (n = 26) and M1 (n = 21) CaP were entered in this study. Serum concentrations for SAP and PSA were determined using two immunoassays. RESULTS: None of the Mo patients but 65% of the M1 patients exhibited a SAP value above the reference range (< 19 ng/ml). A corresponding cut-offpoint of 100 ng/ml for PSA showed that 27% of Mo patients and only 65% of the M1 patients exhibited a value > 100 ng/ml. This resulted in a sensitivity and specificity of 65% and 100% for SAP and 65% and 73% for PSA. CONCLUSION: Our findings suggest that SAP could become a useful marker in the evaluation of patients with newly diagnosed CaP as it seems to provide additional information concerning the skeletal status of these patients.

Adult↗