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Biomedical subjects

H Wolter

Publications and source records attributed to H Wolter.

17 recordsLinked to original sources

Genetic changes in stage pT2N0 prostate cancer studied by comparative genomic hybridization.

OBJECTIVE: To identify chromosomal regions important for progression in clinically organ-confined prostate cancer, as the genetic changes underlying the development and progression of prostate cancer are poorly understood. MATERIALS AND METHODS: Comparative genomic hybridization (CGH) was used to search for DNA sequence copy-number changes in a series of 50 primary organ-confined prostate adenocarcinomas (pT2N0) removed by radical prostatectomy. RESULTS: CGH analysis indicated that 23 (46%) of the primary prostate adenocarcinomas showed chromosome alterations. The percentage of tumours with losses (38%) was higher than with gains (28%). Losses of 13q (24%), 8p (18%), 6q (10%), 16q (8%), 18q (6%) and 5q (6%) and gains of 17q (12%), 20q (12%), 9q (10%), 17p (8%) and 8q (6%) were the most frequent alterations. Amplifications were found at 8q24-qter. Minimal overlapping regions of loss, indicative of the presence of tumour-suppressor genes, were mapped to 13q21.1-q21.3 and 8p21.2, and minimal overlapping regions of gain, indicative of the presence of oncogenes, were found at 9q34.4-qter, 17q25-qter and 20q13.3-qter. There was a significant association between Gleason score and losses and gains (P = 0.003), and an association between chromosomal imbalance and high histological grade (P = 0.008). CONCLUSION: These results suggest that losses or gains of DNA in these regions are important for prostate cancer progression, and document the spectrum of chromosomal alterations in stage pT2N0 of clinically organ-confined prostate cancer.

Adenocarcinoma↗

Cluster analysis of comparative genomic hybridization (CGH) data using self-organizing maps: application to prostate carcinomas.

Comparative genomic hybridization (CGH) is a modern genetic method which enables a genome-wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that region. Usually it is not possible to evaluate all 46 chromosomes of a metaphase, therefore several (up to 20 or more) metaphases are analyzed per individual, and expressed as average. Mostly one does not study one individual alone but groups of 20-30 individuals. Therefore, large amounts of data quickly accumulate which must be put into a logical order. In this paper we present the application of a self-organizing map (Genecluster) as a tool for cluster analysis of data from pT2N0 prostate cancer cases studied by CGH. Self-organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule, i.e., in our examples it gets the CGH data as only information (no clinical data). We studied a group of 40 recent cases without follow-up, an older group of 20 cases with follow-up, and the data set obtained by pooling both groups. In all groups good clusterings were found in the sense that clinically similar cases were placed into the same clusters on the basis of the genetic information only. The data indicate that losses on chromosome arms 6q, 8p and 13q are all frequent in pT2N0 prostatic cancer, but the loss on 8p has probably the largest prognostic importance.

Carcinoma↗

Detailed marker chromosome analysis in cell line U-BLC1, established from transitional-cell carcinoma of the bladder.

A permanent cell line, U-BLC1, was established from a primary transitional-cell carcinoma, TCC, of the urinary bladder. Karyotype analysis showed the line to be highly aberrant, with a near-triploid chromosome number of 68 to 73. Comparative genomic hybridization revealed some distinct differences between the primary tumor and the established cell line. Karyotype analysis showed 3 marker chromosomes with homogeneously staining regions, HSRs, in the cell line. The HSRs were isolated by microdissection and the microdissection probes were hybridized to normal metaphase chromosomes. The HSRs contain sequences known to be frequently involved in amplification in transitional-cell carcinoma of the bladder, 6p22, 7p11-p12, 9p23-pter, and one region not yet reported to be amplified in primary TCC of the bladder, 1p31-p32. A candidate-gene approach showed that in the region 7p11-p12 the EGFR locus is amplified and highly expressed.

Aged↗

Fluorodeoxyglucose whole-body positron emission tomography in colorectal cancer patients studied in routine daily practice.

PURPOSE: To evaluate the routine clinical value of attenuation-corrected whole-body fluorodeoxyglucose positron emission tomography in colorectal cancer, a total of 59 patients who were referred for evaluation of suspected or proven colorectal cancers were studied. METHODS: Positron emission tomography scans were recorded using a Siemens ECAT Exact 921/47. RESULTS: Median follow-up after the positron emission tomography study was 11 (mean, 12.3; range, 1-21) months. According to computed tomography, coloscopy, and ultrasound, we recorded eight apparently false-positive results. During later follow-up, however, three of those cases, which were negative with computed tomography, magnetic resonance imaging, sonography, or laparoscopy, turned out to be true-positive instead. In 3 patients, a primary colorectal cancer was suspected; in 26 patients, a recurrence of colorectal cancer was suspected. Eight patients were studied for follow-up after the history of colorectal cancer with no suspicion of recurrence. In 12 patients, the rise of serum tumor marker concentrations was the reason for the positron emission tomography study; 12 patients with known metastatic disease were also included ("restaging"). With regard to the entire patient population, we found an overall sensitivity of 100 percent, a specificity of 67 percent, and positive and negative predictive values of 92 and 100 percent, respectively. Being merely confirmative with respect to tumor recurrence or distant metastases in the majority of patients, positron emission tomography revealed a primary tumor in one patient and confirmed metastatic foci in several patients that had not been delineated by other imaging modalities. CONCLUSION: A whole-body positron emission tomography scan provides optimum conditions to locate metastatic lesions that might not be seen otherwise. There is a trend showing that positron emission tomography diagnostics as a consequence of early increased tumor markers is a highly sensitive combination, because computed tomography and magnetic resonance imaging were not as sensitive in early recurrences. Positron emission tomography, as performed in daily clinical practice, proved to be a powerful diagnostic tool in our subset of colorectal cancer patients.

Adult↗

Alternatives to CYVADIC combination therapy of soft tissue sarcomas.

The CYVADIC combination has been the preferred treatment for soft tissue sarcomas for the last 10 years. Other combination therapies are necessary, because the remission rate achieved with CYVADIC is only 30%. Alternative therapies for these tumors are combinations including cis-platinum, ifosfamide, epipodophyllin, and high-dose methotrexate. Our therapeutic results with combinations of cis-platinum and ifosfamide are comparable to those achieved with CYVADIC. However, the side-effects, such as nausea, vomiting and fatigue, of cis-platinum used in the palliative treatment of these tumors are intolerable for many patients. A combination of adriamycin and ifosfamide, which leads to a higher remission rate of 44% and has lower toxicity than CYVADIC, is giving encouraging results.

Adult↗

Alternatives to CYVADIC-combination therapy of soft tissue sarcomas.

The CYVADIC combination has been the preferred treatment for soft tissue sarcomas for the last 10 years. Other combinations of therapy are necessary because the remission rate achieved with CYVADIC is only thirty per cent. Alternative therapies for these tumours are combinations including cis-platinum, ifosfamide, epipodophyllin and high-dose methotrexate. Our therapeutic results with combinations of cis-platinum and ifosfamide are comparable to CYVADIC. However, side-effects such as nausea, vomiting and fatigue due to cis-platinum in the palliative treatment of these tumours are intolerable for many patients. A combination of adriamycin and ifosfamide, which exhibits a higher remission rate of 44% and lower toxicity than CYVADIC, is giving encouraging results.

Adult↗

[Aspects of practical oncology. Oncologic dietetics--treatment of anorexia and cachexia].

Tumor- and/or therapy-related malnutrition can be a crucial factor in the success of treatment of neoplastic diseases. The aetiology of anorexia in many patients is still unknown. Impaired survival rates and the outcome of therapy are related to the nutritional status, although this has not been investigated in well controlled clinical studies. However, it is generally accepted that it is possible to improve therapy by balancing the diet. It is not known whether additional parenteral nutrition improves survival rates. Therefore, the individually adjusted diet which considers the patient's tastes and disease-related abnormalities (i.e. stomatitis or therapy-related mucosal dryness) should be preferred. Balanced formulas allow an additional caloric intake. In advanced disease status, a difficulty in swallowing or tumors which obstruct the oesophagus or the cardia may make tube feeding necessary. Total parenteral nutrition is possible via venous catheters for weeks or even months if antiseptic principles are followed very carefully. If a dietary concept is included early in cancer therapy, the quality of life is improved and surgical, radio- and/or chemotherapy, when performed, is made easier and more successful.

Anorexia↗

[The influence of doxepin on the efficiancy of the human heart (author's transl)].

This work was aimed at clarifying whether the anti-depressant doxepin had a cardiodepressant action, or favoured or initiated arrhythmias and/or ventricular conduction disorders, when administered orally for 14 days at a daily dosage of 75 mg. Under doxepin therapy there was a slight increase in mean heart rate on effort in comparison to the placebo. This increase, which amounted to 2 to 6 beats per minute, was most marked among the younger patients, but had neither clinical nor statistical significance (cocaine-like effect of tricyclic psychotropic drugs). No significant changes of ECG, blood-pressure, x-ray determination of heart volume (by the method of Klepzig and Frisch), and maximum performance on the cycle ergometer were stated under doxepin therapy in comparison to the placebo. On the basis of these results it appears justified to state that administering oral doses of about 75 mg doxepin per day for moderately long periods produces no cardiotoxic side-effects.

Age Factors↗

[Experimental comparison of the tuberculostatic activities of INH, INHG and INHG-Na (author's transl)].

In a comparative experimental study the glucuronic acid derivatives of isonicotinoylhydrazone (INH), isonicotinoyl-hydrazone d-glucuronic acid lactone (INHG, Gluronazid) and INH-sodium glucuronid (INHG-N-A, Gluronazid pro infusione) were shown to have the same tuberculostatic activity as INH both in vitro and in vivo. As judged by the serum inhibitory activity the serum level shows a different temporal pattern. After the administration of INHG or INHG-Na, the inhibitory activity reaches its peak later than does INH but remains in the active range essentially longer. The most substantial and, with regard to therapy, most significant difference between INHG or INHG-Na and INH lies in the varying toxicological properties. Both the oral and intravenous LD50 increase in the sequence INH, INHG and INHG-Na. The i.v. LD50 of INHG-Na exceeds the oral LD50. As compared to INH the lower toxicity permits a higher dosage of gluronazide. Thus a continuously higher serum inhibitory activity can be achieved than with a corresponding INH therapy.

Administration, Oral↗

[Not Available].

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Education, Medical↗