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Biomedical subjects

H Ruebben

Publications and source records attributed to H Ruebben.

8 recordsLinked to original sources

[High-dose rate brachytherapy for high-risk prostate cancer].

To estimate disease-free survival it is necessary to allocate patients into tumor risk groups: locally advanced prostate carcinoma with extracapsular spread or localized prostate carcinoma of tumor stage T2c or one of the risk factors PSA >20 or Gleason > or =8 apply for the high-risk group. Intermediate-risk carcinomas are those belonging to tumor stage T2b or with PSA >10-20 or Gleason 7. Particularly for patients with intermediate and high-risk disease early PSA relapse is of major interest. This phenomenon could be a consequence of current inadequate imaging of lymph node or bone metastasis or as a consequence subclinical metastatic spread remains undetectable during radical treatment. However, tumor biology itself could lead to the progression of the disease in the high-risk group. As a consequence, risk-adapted therapy is very important in these cases. The applied radiation dose plays an important role in radiotherapy. Several publications have shown that the biochemical relapse correlates with the generally accepted risk factors and the radiation dose. Regarding this, high-quality treatment planning and HDR brachytherapy combined with EBRT (external beam radiation therapy) leads to good treatment results in selected groups. So far in our own experience, HDR brachytherapy in combination with EBRT is a successful form of treatment with few acute and late side effects in the first 42 patients examined. First results concerning to PSA relapse-free time, quality of life, miction, and erectile function are promising.

Biomarkers, Tumor↗

Single agent carboplatin for CS IIA/B testicular seminoma. A phase II study of the German Testicular Cancer Study Group (GTCSG).

BACKGROUND: The aim was to investigate the use of single agent carboplatin in patients with seminoma stage IIA/B. PATIENTS AND METHODS: In a prospective phase II trial, single agent carboplatin at a dose of AUC 7 mg.min/ml every 4 weeks for three cycles in stage IIA (n=51) or four cycles in stage IIB (n=57) was given to 108 patients with previously untreated seminoma stage IIA/B. Patients with residual masses of >or=3 cm were scheduled to receive secondary surgery. RESULTS: A complete response (CR) was achieved by 88/108 (81%) patients, 17/108 (16%) achieved a partial response (PR), two of 108 (2%) showed no change, and one patient progressed. In all patients with PR the residual disease was <or=3 cm; yet in two of 17 patients with PR, in two of two patients with NC and in one patient with disease progression residual tumor resection was performed demonstrating vital seminoma. Toxicity was acceptable with grades 3 and 4 myelosuppression, nausea and vomiting in less than 10% of patients each. After a median follow-up of 28 months (range 1-68 months) 14/108 (13%) patients relapsed, all after having achieved a CR. All relapses occurred in the retroperitoneum. One patient died from an unrelated cause. The overall failure rate was 19/108 patients (18%). The overall and disease specific survival was 99% and 100%, respectively. CONCLUSIONS: Four cycles of single agent carboplatin AUC 7 do not safely eradicate retroperitoneal metastases in patients with stage IIA/B seminoma.

Adult↗

Tumor cell motility as a novel target in cancer--experimental and clinical results.

BACKGROUND: Surgery, chemotherapy and radiotherapy are the mainstay of tumor management. However, in systemic disease cure can be achieved in yet a few tumor entities. Based on cell biological research we have characterized the process of tumor progression and metastasis and disclosed that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of a tumor. METHODS: According to this principle we derived therapeutical methods differing from hitherto existing treatments by being exclusively focused on tumor cell motility. Characterization of so-called anti-motility factors was performed biochemically as well as with motility assays by in vitro studies in established bladder carcinoma cell lines. RESULTS: We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying antimotility factors in patients with advanced bladder cancer. CONCLUSION: Both basic research as well as the results of first clinical trials confirm, that advanced carcinomas can be influenced by inhibition of tumor cell motility.

Adult↗

Detection of germ-cell tumor cells in the peripheral blood by nested reverse transcription-polymerase chain reaction for alpha-fetoprotein-messenger RNA and beta human chorionic gonadotropin-messenger RNA.

By establishing sensitive nested reverse transcription-PCRs for the detection of mRNA of alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (betahCG), we investigated the presence of circulating tumor cells in the peripheral blood of 119 patients with germ-cell tumor. A total of 336 blood samples obtained before and during therapy were examined with regard to clinical applicability. The overall ratio of positive PCR results was 26.5% and was independent of the serum concentration of AFP and hCG/betahCG. No correlation of the positivity for AFP-mRNA to serum AFP level was found. In contrast, positive results in betahCG-PCR were twice as frequent in patients with elevated serum hCG/betahCG levels as in those with normal serum hCG/betahCG levels (P = 0.012). To develop a valid correlation to tumor stage, tumor histology, and serum level of tumor markers, a subgroup of 36 patients was evaluated before definite therapy. The subgroup revealed an overall ratio of 33.3% positive PCR results. The serum level of both of the markers did not correlate with the detection of corresponding mRNA in peripheral blood samples. However, positive betahCG-PCR results were found exclusively in patients with elevated serum hCG/betahCG (6 of 18 versus 0 of 18; P = 0.019). Patients with stage IIC/III germ-cell tumor demonstrated nearly twice the frequency of positive PCR results as patients with stage I tumor [7 (41.2%) of 17 versus 4 (23.5%) of 17] in this subgroup. With regard to histology, positive PCR results were found mostly in embryonal carcinoma.

Adolescent↗

Keyhole-limpet hemocyanin immunotherapy in the bilharzial bladder: a new treatment modality? Phase II trial: superficial bladder cancer.

The efficacy of immunotherapy with keyhole-limpet hemocyanin or bacillus Calmette-Guerin for superficial bladder cancer is well known. A strong similarity has been noted between keyhole-limpet hemocyanin antigen and schistosomal antigen. In regard to this finding, we investigated the mechanisms of specific immunotherapy with keyhole-limpet hemocyanin in schistosomal associated transitional cell carcinoma. Keyhole-limpet hemocyanin was used for its ability to prevent tumor recurrence and because of its similarity to schistosomal antigen for intravesical specific immunotherapy in 13 patients with superficial transitional cell bladder tumors (Ta, Tis, T1) associated with urinary schistosomiasis. Keyhole-limpet hemocyanin immunotherapy reduced the recurrence rate of superficial bladder tumors to 15.4% compared to 76.9% before therapy.

Adjuvants, Immunologic↗

Characterization of the new bladder cancer cell line HOK-1: expression of transitional, squamous and glandular differentiation patterns.

The new continuous cell line HOK-1 derived from a grade-III transitional-cell bladder carcinoma with foci of squamous and glandular differentiation was shown to retain this phenotypical heterogeneity for more than 45 passages in vitro. Electron microscopy revealed transitional as well as a considerable proportion of squamous carcinoma and adenocarcinoma cells. PAS-positive mucus was detected in numerous cells. These features were principally maintained when grown as multicellular spheroids and in nude mice. More pronounced signs of differentiation (i.e., expression of cytokeratins 10 and 11, formation of glandular structures) were found in xenograft tumours. Independently, cytokeratins 13, 18 and 19 were detected in vitro and in vivo, reflecting the urothelial origin. The line forms distinct colonies in soft agar, expresses Lewis-x and Lewis-y antigens and reacts with monoclonal antibodies (MAbs) against CEA, beta-HCG and URO-5. Cytogenetic analysis revealed several related clones with a rearrangement at chromosome 1 and loss of one X chromosome as common karyotypic changes in all clones. DNA content, as quantified by image analysis, showed a DNA stemline close to 2c. The new cell line HOK-1 can be used as an in vitro model to study the mechanisms of heterogeneous differentiation patterns in bladder cancer.

Aged↗

Magnetic resonance imaging of acute and long-term alterations following extracorporeal shock wave lithotripsy in rats.

The kidneys of 30 rats were treated by extracorporeal shock wave lithotripsy (ESWL) with different doses of extracorporeal shock waves: 500, 1,000 and 2,000. The animals were sacrificed after 24 h, 7, 14 or 35 days. Magnetic resonance (MR) imaging at 1.5T was used to evaluate the effects of ESWL on T1- and T2-weighted (spin echo 600/22, 1,600-2,000/90) images compared to histology and macroscopy. The severity of pathologic changes correlated dose dependently with the number of shock waves given (500-2,000). The MR findings following ESWL in 50 kidneys included diffuse loss of the corticomedullary junction (n = 20), perirenal and subcapsular fluid (n = 23), intrarenal foci of increased (n = 16) or decreased (n = 8) signal intensity, and loss of distinction between renal, splenic or hepatic contours (n = 7), detected macroscopically as adhesions. Subcapsular and intrarenal findings corresponded to acute hematomas and organized fibrotic tissue morphologically. In long-term groups MR revealed fibrotic shrinkage of the renal convexity as indentation of the kidney surface (n = 12). MR imaging is a sensitive method for the detection of specific alterations following ESWL, especially intrarenal changes, which are important for possible long-term lesions after ESWL.

Animals↗