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Biomedical subjects

M Lein

Publications and source records attributed to M Lein.

At least 37 records · Page 2Linked to original sources
PubMed2001

Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis.

OBJECTIVE: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha-1- antichymotrypsin-bound PSA (PSA-ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: A total of 166 white men (age: 65-88 years) with a tPSA between 2 and 20 microg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA-ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA-ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). RESULTS: For statistical analysis only patients with tPSA between 2 and 20 microg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 microg/l, BPH 4.03 microg/l; Roche: PCa 7.75, BPH 4.13), PSA-ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA-ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2-20 microg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA-ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA-ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were not significantly different. CONCLUSION: The determination of PSA-ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA-ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

Aged↗
PubMed2000

Intense-field double ionization of helium: identifying the mechanism

We present quantum mechanical calculations of the electron and ion momentum distributions following double ionization of a one-dimensional helium atom by ultrashort laser pulses (780 nm) at various intensities. The two-electron momentum distributions exhibit a clear transition from nonsequential to sequential double ionization. We provide strong evidence that rescattering is responsible for nonsequential ionization by calculating the momentum spectrum of the He2+ recoil ions-which we find in excellent agreement with recent experiments-and by analyzing the electronic center-of-mass motion via Wigner transforms.

Journal Article↗
PubMed2000

Search for a parity-violating energy difference between enantiomers of a chiral iron complex

Mossbauer spectra for l and d enantiomers of the Fe(phen)3Sb2(C4H2O6)(2);8H(2)O complex are reported. Four independent experiments show a small but reproducible energy shift of the Fe-Mossbauer spectra for the two enantiomers of 0.004+/-0. 002 mm/sec ( 1.9x10(-10) eV). This exceedingly small energy difference is comparable to that predicted by the parity-violating energy difference (PVED) using a Z6.2 scaling law applied to low Z ( Z = 6) molecules. Theoretical calculations suggest that the PVED for the Fe(phen)2+3 moiety should be smaller than this estimate, however, PVED effects of the chiral antimony tartrates are not taken into account.

Journal Article↗
PubMed2000

Synthetic inhibitor of matrix metalloproteinases (batimastat) reduces prostate cancer growth in an orthotopic rat model.

BACKGROUND: Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of the study was to determine the potential of a synthetic metalloproteinase inhibitor, batimastat, to show its in vitro effect on MatLyLu cancer cells and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats. METHODS: In vitro, a dose response curve of batimastat was generated over 4 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg/kg body weight) or vehicle administered once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation. RESULTS: Significant inhibition of tumor cell proliferation in vitro occurred at 400 and 4,000 ng/ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 g in the control group without treatment, to 22.3 g in the vehicle group, and to 11.1 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat. CONCLUSIONS: Batimastat is able to reduce tumor growth in the standard prostate cancer model. Using this model, activity against cancer progression of future inhibitory agents can be reliably assessed.

Animals↗
PubMed2000

Matrix-metalloproteinases and their inhibitors in plasma and tumor tissue of patients with renal cell carcinoma.

Matrix-metalloproteinases (MMPs) are associated with invasive and metastatic behavior of several human malignant tumors. We have determined MMP-2 and MMP-9 and tissue inhibitors of MMPs (TIMP-1 and TIMP-2) in blood plasma and in renal tissue samples of patients with renal cell carcinoma (RCC) from cancerous and non-cancerous parts of the same kidney. In tumor tissue, MMP-9 and TIMP-1 were significantly higher than in normal counterparts. MMP-2 was not different between tumor tissue and normal counterparts. TIMP-2 values could not be measured. In plasma, MMP-9 concentrations were significantly higher in RCC patients than in healthy controls, MMP-2 and TIMP-2 concentrations were higher in healthy controls and TIMP-1 concentrations were not different.

Adult↗
PubMed2000

[Molecular forms of prostate-specific antigen and human kallikrein 2 as possible indicators in prostatic carcinoma diagnosis].

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and in the monitoring of patients with this diagnosis. Molecular forms of PSA and human kallikrein 2 (hK2) have been used to discriminate between benign prostatic hyperplasia and prostate cancer, as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha 1-antichymotrypsin (ACT-PSA), and complexed PSA (cPSA) is given together with our own results. The ratio of fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate cancer diagnosis based on tPSA measurements. The number of biopsies can be reduced in the total PSA range of 4-10 micrograms/l. Furthermore, carcinomas can be detected in patients with PSA values less than 4 micrograms/l. ACT-PSA or cPSA alone and the calculated derivatives are not superior in their discriminatory power compared with tPSA and the fPSA% value. The other molecular PSA forms and hK2 are still objects of research and their diagnostic significance needs to be evaluated in more extensive clinical trials.

Biomarkers, Tumor↗
PubMed2000

Laser-induced hyperthermia in rat prostate cancer: role of site of tumor implantation.

OBJECTIVES: To investigate the importance of the site of tumor implantation on the treatment response to laser-induced hyperthermia (LIH) of rat prostate cancer (PCa), because interventional manipulations of PCa have been reported to increase metastatic dissemination. METHODS: Seven to nine days after either subcutaneous or orthotopic implantation of MatLyLu cells, LIH (46.5 degrees C) was induced using pulsed irradiations of a neodymium:yttrium-aluminum-garnet laser. Both local control and distant metastases were evaluated. Plasma metalloproteinase 9 (MMP-9) was tested as a possible marker of PCa progression and LIH response. RESULTS: Twelve days after LIH treatment of subcutaneous tumors, the volumes were reduced by 64% after 8 minutes of irradiation, 73% after 10 minutes, 81% after 15 minutes, and 91.1% after 20 minutes. In the orthotopic model, the corresponding tumor reductions were 44% after 10 minutes, 61% after 20 minutes, and 65% after 30 minutes. Lung metastases were observed in only 1 animal with subcutaneous tumors. In contrast, 86% of the orthotopic tumor-bearing animals treated for 30 minutes had lung metastases compared with 23% of the untreated tumor-bearing rats. MMP-9 expression was detected in both orthotopic and subcutaneous tumor tissue and in the plasma of tumor-bearing rats. The prostate tissue of healthy rats and subcutaneous tumor-bearing rats was devoid of MMP-9. The plasma levels of MMP-9 showed a trend toward direct correlation with local tumor control but no correlation with the incidence of metastasis. CONCLUSIONS: These data emphasize the importance of the site of tumor implantation for evaluation of the efficacy of therapeutic interventions and may warrant further studies before widespread clinical application of LIH as monotherapy.

Animals↗
PubMed2000

ACT-PSA and complexed PSA elimination kinetics in serum after radical retropubic prostatectomy: proof of new complex forming of PSA after release into circulation.

OBJECTIVES: To study the elimination kinetics of alpha(1)-antichymotrypsin (ACT)-prostate-specific antigen (PSA) and complexed PSA (cPSA) in comparison to the biexponential decrease of total PSA and free PSA after radical prostatectomy. METHODS: Serum total PSA, free PSA, ACT-PSA, and cPSA values and the corresponding ratios were determined in venous blood from 12 patients with prostate cancer. The samples were taken before surgery, immediately after surgery, 1, 2, 3, 4, 5, and 6 hours after surgery, and then once daily for the next 10 days. Total PSA and cPSA were analyzed by using Immuno 1 PSA assays (Bayer Corporation); free PSA was measured using the AxSym test kit (Abbott Diagnostics). For ACT-PSA, the ES analyzer system was used (Roche Diagnostics). Statistical calculations were performed with the analysis of variance and Wilcoxon tests. RESULTS: During the first 6 hours after radical retropubic prostatectomy, we found nearly constant levels of ACT-PSA and cPSA, in contrast to the rapid elimination of free PSA and significant decrease in total PSA. From days 1 to 10, a continuous and nearly identical decrease of ACT-PSA and cPSA occurred compared with total PSA; free PSA was eliminated more rapidly. CONCLUSIONS: In addition to the opinion that the first PSA decrease might be an effect of the operation itself or caused by renal elimination alone, our findings indicate that the initial rapid decrease of free PSA immediately after surgery could be caused by new complex forming of PSA with ACT and other serum protease inhibitors.

Aged↗
PubMed2000

Elimination of serum complexed prostate-specific antigen after radical retropubic prostatectomy.

Total prostate-specific antigen (PSA) and complexed PSA were determined in venous blood from 12 patients with prostate cancer before and after radical prostatectomy by using Immuno 1 PSA assays. The elimination kinetics of complexed PSA were compared with that of total PSA. Nearly constant concentrations of complexed PSA were found during the first six hours after surgery, in contrast to the rapid elimination of free PSA and the significant decrease of total PSA. From day one to ten there was a continuous and nearly identical decrease of complexed PSA compared to total PSA. Our findings suggest that the initial rapid decrease of free PSA immediately after operation could be caused by formation of new PSA-complex.

Humans↗
PubMed2000

Different stability of free and complexed prostate-specific antigen in serum in relation to specimen handling and storage conditions.

The effect of sample collection, storage conditions (time and temperature), and freeze-thaw cycles on the stability of free prostate-specific antigen (fPSA), PSA complexed with alpha1-antichymotrypsin (ACT-PSA), and total PSA (tPSA) in serum was studied. The analytes were quantified using immunoassays for tPSA and fPSA on the Elecsys system 2010 and a research assay for ACT-PSA on the ES system (Roche Diagnostics). The stability of the analytes was calculated as percentages of the values measured in samples 1 h after blood collection. When the samples were stored at 37 degrees C, at room temperature or at 4 degrees C, the stability of ACT-PSA was less impaired than that of fPSA. To avoid erroneous results in the determination of PSA isoforms and their corresponding ratios, serum samples should be preserved at 4 degrees C when the analysis is performed within 8 h after blood collection, or they should be stored at -80 degrees C if the analysis is not feasible during that period.

Blood Chemical Analysis↗
PubMed2000

Molecular forms of prostate-specific antigen in malignant and benign prostatic tissue: biochemical and diagnostic implications.

BACKGROUND: Patients with prostate cancer (PCa) show a lower ratio of free prostate-specific antigen (fPSA) to total PSA (tPSA) in serum than patients with benign prostatic hyperplasia (BPH). The patterns of the intracellular PSA isoforms in malignant and benign prostatic tissue have been studied as potential molecular reasons for this phenomenon. METHODS: Prostatic tissue samples were obtained after cystoprostatectomy from patients with bladder cancer (n = 10), from BPH patients (transurethral resection of the prostate, n = 10; adenomectomy, n = 10), and from the cancerous and noncancerous parts of the same prostates removed surgically by prostatectomy because of PCa (n = 20). PSA pattern was characterized by gel filtration, immunoblotting, and immunoassays for tPSA, fPSA, alpha(1)-antichymotrypsin-PSA (ACT-PSA), and complexed PSA (Bayer Immuno 1 assay). Comparisons were made with the PSA concentrations in serum. RESULTS: The major portion of tPSA in all tissue samples was fPSA; complexed PSA forms were <2%. Samples from cystoprostatectomy patients had the lowest and those from adenomectomy patients the highest values of tPSA and fPSA. PSA concentrations were lower in cancerous than in the noncancerous parts of the prostate. No significant correlations were found between tumor stage or grade and the amounts of tPSA, fPSA, and ACT-PSA in tissue. Tissue PSA values were not correlated with the serum PSA concentrations nor with the ratios fPSA/tPSA and ACT-PSA/tPSA in sera. CONCLUSIONS: The amounts of tPSA and the PSA isoforms in prostatic tissue explain neither the concentrations of tPSA and PSA isoforms in serum nor the behavior of the ratio fPSA/tPSA in patients with BPH and PCa.

Adult↗
PubMed2000

Ratio of free or complexed prostate-specific antigen (PSA) to total PSA: which ratio improves differentiation between benign prostatic hyperplasia and prostate cancer?

BACKGROUND: The aim of this study was to compare the diagnostic utility of a new assay that measures all forms of prostate-specific antigen complexed (cPSA) to serum proteins except alpha(2)-macroglobulin with the assay of free PSA (fPSA) and the corresponding ratios to total PSA (tPSA) to improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa). METHODS: Serum samples were collected from 91 men without prostate disease and with normal digital rectal examination (controls), 144 untreated patients with PCa, and 89 patients with BPH. tPSA and cPSA were measured using the Bayer Immuno 1 system; fPSA and the additional tPSA were measured with the Roche Elecsys system. RESULTS: The median cPSA/tPSA, fPSA/tPSA, and fPSA/cPSA ratios were significantly different between patients with BPH and PCa (78.7% vs 90.7%, 25.5% vs 12.1%, and 36.8% vs 14.3%, respectively; P <0.001). No correlations of cPSA and its ratios to tumor stage and grade were found. ROC analysis showed that cPSA was not different from tPSA (areas under the curve, 0.632 vs 0.568), whereas the cPSA/tPSA ratio was similar to the fPSA/tPSA ratio in increasing discrimination between BPH and PCa patients with tPSA concentrations in the tPSA gray zone between 2 and 10 microg/L (areas under the curve, 0.851 vs 0.838). CONCLUSIONS: Compared with tPSA, the fPSA/tPSA and cPSA/tPSA ratios both improve the differentiation between BPH and PCa comparably and are similarly effective in reducing the rate of unnecessary biopsies, whereas cPSA alone does not have any effect.

Adult↗
PubMed2000

Molecular forms of prostate-specific antigen and human kallikrein 2 as promising tools for early diagnosis of prostate cancer.

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and for the monitoring of patients with this diagnosis. Molecular forms of PSA and also human kallikrein 2 have been used to discriminate between benign prostatic hyperplasia and prostate cancer as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha1-antichymotrypsin (ACT-PSA), and complexed PSA is given together with our results. The ratio of fPSA:tPSA has been shown to improve the specificity of prostate cancer diagnosis on the basis of tPSA measurements. Unnecessary biopsies can be reduced by about 19-64% in the total PSA range of 4-10 microg/liter while only missing 5-10% of cancers. Furthermore, carcinomas in patients with PSA values <4 microg/liter can be detected, indicating an improved sensitivity because of the percent fPSA at low PSA values. ACT-PSA or complexed PSA alone and the calculated derivatives are not superior in their discriminatory power compared with the percent fPSA. The diagnostic significance of the other molecular PSA forms and human kallikrein 2 needs to be evaluated in more extensive clinical trials.

Biomarkers, Tumor↗