Studies on androgen receptor mutations and amplification in human prostate cancer.
Explore the source record for details and available documents.
Chloramphenicol O-Acetyltransferase↗
Biomedical subjects
Helmut Klocker
Publications and source records attributed to Helmut Klocker.
Screening with low PSA cutoff values results in low rates of positive surgical margins in radical prostatectomy specimens.
BACKGROUND: In the literature, positive margins in radical prostatectomy specimens, the rate of which ranges between 7% and 46%, are associated with adverse patient survival. The aim of the present study was to determine the predictive value of preoperative serum prostate specific antigen (PSA) values for the rate of positive margins in radical retropubic prostatectomy. METHODS: The study included a cohort of 845 patients who underwent radical retropubic prostatectomy between October of 1993 and December of 1999. All patients were stratified in groups on the basis of their preoperative PSA values: PSA group I, 0-1.99 ng/ml; PSA group II, 2-3.99 ng/ml; PSA group III, 4-5.99 ng/ml; PSA group IV, 6-7.99 ng/ml; PSA group V, 8-9.99 ng/ml; and PSA group VI, >10 ng/ml. For each group, the pathologic stage, Gleason score, and the incidence of positive margins were analyzed. For statistical analysis, the Mann Whitney U-test was used. RESULTS: Our data show a significantly higher rate of organ-confined prostate cancers and a significantly lower rate of positive surgical margins in patients with preoperative total PSA values of less than 4 ng/ml compared with patients with higher preoperative total PSA levels. CONCLUSION: As tumor stage and surgical margin status after radical prostatectomy are important predictors of the likelihood of PSA recurrence, which necessitates additional therapy, these findings support the concept of PSA screening by using low PSA cutoff levels.
Adult↗
Microsatellite alterations in human bladder cancer: detection of tumor cells in urine sediment and tumor tissue.
OBJECTIVES: Bladder cancer is the result of clonal expansion of cancer cells in which multiple genetic alterations have occurred. Loss of heterozygosity (LOH) studies have demonstrated that alterations in microsatellite regions are common in bladder cancer. This observation offers the possibility of early tumor detection by examining the DNA of urinary sediment. METHODS: We investigated alterations of 17 microsatellite loci in urinary bladder carcinomas of different stages and grades. Per locus, 19-30 specimens were evaluated. DNA was isolated from tumor specimens, urinary sediment and peripheral blood lymphocytes. DNA fragments of 17 microsatellite loci were amplified by PCR and analyzed for genomic alterations. RESULTS: Microsatellite alterations were detected in tumor tissue and urine sediment from 27 out of 31 patients (87%). Urine sediment analysis alone proved positive in 24 out of 31 patients (77%). The type of lesions most frequently detected was LOH (74% of all alterations), followed by length alteration (24%) and additional alleles (2%). On average, the alteration frequency was 22% per locus. The loci at chromosomes 9 and 18 proved most informative. No alterations were found in grade I tumors. The study revealed a correlation between microsatellite alterations and the respective grades and stages of the tumors. Average alteration frequencies per locus were: 27.4% in grade III versus 19.3% in grade II tumors, 26.5% in invasive versus 12.3% in superficial tumors. CONCLUSIONS: Our results demonstrate that microsatellite alterations are common in bladder cancer and that analysis of genomic instabilities in urine samples should be further evaluated as a method for bladder cancer screening in a high-risk group. Especially, when a set of microsatellites is used that shows a high probability of detecting alterations and allows easy handling, this could be an alternative or a completion to currently available methods.
Carcinoma, Transitional Cell↗
Inhibition of LNCaP prostate tumor growth in vivo by an antisense oligonucleotide directed against the human androgen receptor.
We have shown recently that a 15-mer phosphorothioate oligodeoxynucleotide (ODNas750/15) that hybridizes to the (CAG)n polyglutamine region of mRNA encoding human androgen receptor (AR) inhibits the expression of AR in LNCaP prostate cancer cells in vitro. This AR downregulation was accompanied by significant cell growth inhibition and reduced PSA secretion. In the present study we investigated the effects of this antisense AR ODN on prostate tumor growth in vivo using a mouse xenograft model. Via subcutaneously implanted diffusion pumps, either ODNas750/15 or a scrambled control sequence ODNsr750/15 was continuously administered into LNCaP tumor-bearing male nude mice for 7 weeks. Compared with untreated control animals, treatment with ODNas750/15 resulted in significant tumor growth inhibition. Retardation of tumor growth was also significant in castrated mice, whereas the scrambled control ODN did not exert any effects. No side effects such as loss of body weight were observed at any time of treatment. ODN treatment was well tolerated and, in contrast to castration, did not induce shrinkage of mouse prostates. Both AR expression in the tumor and PSA levels in mouse serum correlated with tumor size. However, we failed to demonstrate a correlation between tumor retardation and Ki-67 antigen expression and the number of apoptotic cells, respectively. Testing of antisense-treated LNCaP cells revealed that expression levels of other proteins that contain shorter polyglutamine sequence stretches such as HDAC2, TFIID, and c-jun were not affected. The present study demonstrates that downregulation of AR with antisense ODNas750/15 causes prostate tumor growth inhibition. These results further point out the important role of the AR in prostate tumors and support further testing of AR downregulation for treatment of prostate cancer.
Animals↗
Curbing tobacco's toll starts with the professionals: World No Tobacco Day.
Explore the source record for details and available documents.
Health Facilities↗
Derivatized cellulose combined with MALDI-TOF MS: a new tool for serum protein profiling.
Providing a rapid and sensitive protein profiling method for biomarker discovery from a variety of biological samples is crucial for the introduction of new markers that improve cancer patient diagnosis at early tumor stages, thus increasing the chances of curative treatment. We report here the development and application of derivatized cellulose particles for selective serum protein profiling. For immobilized metal ion affinity chromatography (IMAC), cellulose was derivatized with glycidyl methacrylate (GMA) and subsequently with iminodiacetic acid (IDA). To investigate the application of this material for generating protein profiles of human serum samples, the serum samples were agitated with the derivatized cellulose particles to a suspension and incubated for 2 h at 30 degrees C. After washing, 1 microL of the IDA-Cu(2+)-cellulose suspension was applied directly onto a MALDI-target, mixed with sinapinic acid (SA) and analyzed with MALDI-TOF MS. Consistent serum specific data were obtained from aliquoted samples analyzed several times, indicating the reliability of the method. However, the serum fingerprints obtained proved to be specific for any given serum. The technique presented allows a high enrichment of sample on the developed target leading to a high sensitivity and reproducibility without depletion of albumin and immunoglobulin, and sample elution prior to MS-analysis. The study demonstrates for the first time that derivatized cellulose particles combined with MALDI-TOF MS represent a simple, economical, and rapid approach to generate serum protein profiles for biomarker identification.
Biomarkers↗