PubMed Health⌕ Search

Biomedical subjects

H Rübben

Publications and source records attributed to H Rübben.

At least 109 records · Page 6Linked to original sources
PubMed1999

The need for further reproductive medical advice after vasectomy reversal.

The aim of this study was to determine the motivation of patients (n = 73) who had undergone microsurgical refertilization for further treatment (assisted reproduction) and the demand for medical counseling. By an interview, 57/73 patients could be evaluated for motivation, further demand for medical counseling, and the postoperative outcome (patency rate). In all, 60% of the patients who failed the treatment and 33% with a patent anastomosis mentioned interest for further counseling, especially for assisted reproduction. The satisfaction rate after the refertilization was nearly identical in the two groups (67%/64%). Following microscopical vasovasostomies the patency was 92%, which was significantly different from that observed after macroscopical refertilization (55%). In conclusion, the standard for refertilization is the microsurgical technique. Furthermore, there is a strong need for counseling that involves urological-andrological advice given by the same work group, including advisement on the techniques of assisted reproduction that might be necessary following the operative treatment.

Counseling↗
PubMed1999

Intravesical therapy with pertussis toxin before radical cystectomy in patients with bladder cancer: a Phase I study.

OBJECTIVES: To ascertain the side effects of intravesical instillation of pertussis toxin (PTX) because it inhibits tumor cell motility in vitro and in vivo and seems to be a promising therapeutic approach against cancer. METHODS: We initiated a Phase I study and measured the effect of intravesical instillation of PTX before radical cystectomy. Study end points were PTX-related side effects. PTX was instilled at five dose levels, starting with 14 microg and continuing to 72 microg. RESULTS: Fifteen patients, with a median age of 64 years, were included in the study. Intravesical instillation of PTX was without local or systemic side effects (grade 0, according to National Cancer Institute toxicity criteria). CONCLUSIONS: Treatment with PTX was safe and well tolerated without any significant local or systemic toxicity in dosages up to 72 microg. Therefore, the influence of PTX on local tumor should be evaluated in a Phase II study.

Administration, Intravesical↗
PubMed1999

Influence of pertussis toxine on local progression and metastasis after orthotopic implantation of the human prostate cancer cell line PC3 in nude mice.

Tumor cell migration is a fundamental process of metastasis. Pertussis toxine inhibits lysophosphatidic acid related cell migration by ADP-ribosylation of G proteins. We examined the influence of pertussis toxine (PTX) on progression and metastasis of the human hormone-insensitive prostate cancer cell line PC-3 after orthotopic implantation in nude mice. In 30 athymic male nude mice (NMRI) 5x10(5) PC-3 cells were injected into the dorsal prostate. After 7 d 15 mice received a total of six intraperitoneal injections of 5 micro g PTX/100 g body weight at an interval of 4 d. The other 15 mice received phosphate buffered saline and served as control. All mice were killed at 37 d followed by macroscopical and histological evaluation of local tumor growth and metastasis. In the control group tumorigenicity was 100% (15 out of 15). Mean weight of the tumor bearing unit of prostate and seminal vesicles was 541 mg (243-763 mg). The rate of positive lymphnodes was 100% with a mean transversal diameter of 3.9 mm (1.2-5.4 mm). In the PTX group local take rate was 100% with a mean weight of 251 mg (88-478 mg) (P two sided <0.0001). The rate of positive lymphnodes was 60% (9 out of 15) (P=0.017) with a mean transversal diameter of 2.3 mm (1.0-4.5 mm). PTX following orthotopic implantation of the human hormone-insensitive PC-3 cell line significantly reduces local tumor growth as well as metastasis to locoregional lymphnodes.

Journal Article↗
PubMed1999

Therapy of superficial bladder carcinomas.

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 x weekly, 5 x monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3-6 months after initial diagnosis. There is no need - except in clinical trials - for the administration of unverified or not admitted drugs.

Carcinoma, Transitional Cell↗
PubMed1999

Tumor cell motility. A novel therapeutic target in bladder carcinoma, experimental and clinical results.

Surgery, chemotherapy and radiotherapy are the current modalities of tumor management. However, in systemic disease, predicted patients' cure can be achieved in but a few tumor diseases. Based on previous basic research we have highlighted that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of bladder tumors. Thus, we have attempted therapeutical methods differing from hitherto existing treatments by focusing on a tumor cell function we call cell motility. Characterization of so-called anti-motility drugs was performed biochemically as well analyzed by in vitro by using in established bladder carcinoma cell lines. We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying anti-motility drugs in patients which were chemotherapy-resistant and having metastatic bladder cancer. Both basic research as well as the results of first translational clinical trials confirmed, that advanced bladder carcinomas can be favorably affected by inhibition of tumor cell motility.

Adult↗
PubMed1998

Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals carrying the G protein beta3 subunit 825 T-allele.

We have recently described a C825T polymorphism in the gene encoding for the Gbeta3 subunit of heterotrimeric G proteins. The 825T allele is associated with a novel splice variant (Gbeta3-s) and enhanced signal transduction via pertussis toxin (PTX)-sensitive G proteins. fMLP-induced chemotaxis, but not O2- generation, was increased in neutrophils with the TC/TT (EC50 = 1.5 +/- 1.3 nM) genotypes compared to the CC genotype (EC50 = 5.9 +/- 1.5 nM). Maximal fMLP-induced increase in [Ca2+]i was significantly reduced in neutrophils from individuals with TC/TT genotype vs. CC genotype (212.9 +/- 10.1 nM vs. 146.4 +/- 24.2 nM). Gbeta3-s appears to be associated with enhanced immune cell function in humans.

Alleles↗
PubMed1998

[Therapy of hormone refractory prostatic carcinoma].

In patients with hormone-resistant prostate cancer primary androgen deprivation eventually fails. The begin of secondary treatment is depending on clinical symptoms; since survival cannot be prolonged in progressive disease improvement of quality of life is of paramount importance. Altering of endocrine treatment and antiandrogen withdrawal can cause a transient improvement of the sense of well being. Single agent chemotherapy with little side effects should be preferred as compared with polychemotherapy since response rates do not exceed 30%. Although 2/3 of the patients benefit from chemotherapy there is however no proof that it is superior to symptom-related pain relief. The indication for surgical management such as TURP and spinal cord decompression is depending on clinical symptoms from local progression and systemic disease.

Antineoplastic Agents, Hormonal↗
PubMed1998

Phase II trial of titanocene dichloride in advanced renal-cell carcinoma.

Titanocene dichloride was capable of inhibiting the growth of different types of human tumors in vitro. A total of 14 patients with metastatic renal-cell carcinoma (RCC) received 270 mg/m2 titanocene dichloride every 3 weeks for 6 weeks. Although the toxicities and side effects encountered were mild to moderate, no partial or complete response was detectable. In conclusion, titanocene dichloride has no advantage in the therapy of RCC.

Adult↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor and interferon-alpha 2B in patients with advanced renal cell carcinoma.

OBJECTIVE: Biological response modifiers such as interferon-alpha2B (IFN-alpha2B) have well-known clinical activities against renal cell carcinoma (RCC). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has antitumorigenic effects both in vitro and in vivo. Therefore, a phase-I/II trial of IFN-alpha2B and GM-CSF was performed in patients with metastatic RCC. METHODS: 21 patients in groups of 3 patients received GM-CSF at 7 different dose levels (15-300 microg) subcutaneously in combination with IFN-alpha2B at a fixed dose of 10 x 10(6) IU s.c. three times weekly for 12 weeks. RESULTS: Two complete remissions have been observed, both with lung metastases only. With increasing dose levels of GM-CSF a slight tendency to more toxicity was detectable. Due to grade-3 toxicities 5 patients (24%) dropped out of the treatment schedule. Increases in WBC, neutrophils, lymphocytes, and monocytes were noted but were not related to the dose levels of GM-CSF. CONCLUSIONS: Results demonstrate that simultaneous administration of GM-CSF and IFN-alpha2B is tolerated up to doses of 120-150 microg GM-CSF three times weekly. But there is no additional antitumorigenic effect of GM-CSF because the overall response rate of the combined administration of GM-CSF/IFN-alpha2B is similar to IFN-alpha2B alone and there is no obvious dose relationship between increasing doses of GM-CSF and the responses.

Adult↗
PubMed1997

Paclitaxel-based second-line therapy for patients with advanced chemotherapy-resistant bladder carcinoma (M1): a clinical Phase II study.

BACKGROUND: In a previous clinical trial, the authors disclosed that the expression of tumor cell motility factor gp78hAMFR correlates with tumor progression in patients with bladder carcinoma. This study was initiated to evaluate whether the combination of cytostatic drugs with an antimotility factor has an effect on chemotherapy-resistant bladder carcinoma. METHODS: In a Phase II trial, the authors evaluated the influence of paclitaxel, carboplatin, and an antimotility factor (acellular pertussis vaccine [APV]) in 18 patients with cisplatin- and methotrexate-resistant metastatic bladder carcinoma. Intramuscular injection of APV 3 times in the first week, on Days 1, 4, and 7, was followed by paclitaxel 135 mg/m2 and carboplatin 400 mg/m2. After an interval of 1 week APV was given again on Days 15 and 19. Each cycle lasted 3 weeks. On Day 22 the cycle was repeated. RESULTS: Four of 18 patients had objective responses (2 had complete remissions and 2 had partial remissions). After a median number of 2.5 cycles, side effects did not exceed World Health Organization Grade 4. CONCLUSIONS: The results of this clinical Phase II study demonstrate that the combination of paclitaxel-based therapy causes complete remissions previously not obtained with second-line chemotherapy, although no conclusions can be drawn as to the effectiveness of the individual substances. Further trials have to be evaluated with regard to the individual components.

Adult↗
PubMed1997

Deletion analysis at the DEL-27, APC and MTS1 loci in bladder cancer: LOH at the DEL-27 locus on 5p13-12 is a prognostic marker of tumor progression.

Inactivation of relevant tumor-suppressor genes by allelic or homozygous deletion is a characteristic event in tumor cells. Here, the prognostic value of allelic deletions on 5p13-12 at the putative del-27 tumor-suppressor locus and in the APC tumor-suppressor gene on 5q21, as well as homozygous deletions of the MTS1 (p16INK4, CDKN 2) tumor-suppressor gene on 9p21 was assessed in 87 bladder cancers using microdissection and PCR-based assays. Tumor-specific LOH was detected in 10 of 38 (26%, del-27), and 15 of 30 (50%, APC) informative specimens. Homozygous deletion of the MTS1 gene was detected in 33% of 84 tumors investigated. These deletion frequencies implicate the 3 tumor-suppressor regions in the genesis of transitional-cell carcinoma. In contrast to deletions of the APC or MTS1 genes, LOH at the del-27 locus correlated with tumor progression. This suggests that loss of the putative tumor-suppressor gene DEL-27 is involved in an aggressive behavior of the tumor cells and appears to be a prognostic marker for the clinical outcome of patients with transitional-cell carcinoma.

Carcinoma, Transitional Cell↗
PubMed1997

Orthotopic implantation of human prostate cancer cell lines: a clinically relevant animal model for metastatic prostate cancer.

BACKGROUND: To study the metastatic behavior of human prostate cancer cell lines, orthotopic injection in nude mice was performed. METHODS: Local tumor growth, metastasis formation, prostate-specific antigen, and androgen receptor expression were examined. RESULTS: Hormone-independent cell lines (PC-3, PC-3-125-IL, and TSU-Pr1) were highly tumorigenic and had a higher rate of lymph node metastasis after orthotopic than after subcutaneous implantation. PC-3 cell lines also consistently metastasized to the lungs. The androgen-sensitive LNCaP cell line showed local growth in 7 of 10, and lymph node metastasis in 4 animals. Significant serum PSA levels and strong receptor expression in primary and metastatic tumor tissues were observed. CONCLUSIONS: These results demonstrates that orthotopic implantation of human prostate cancer cell lines, including LNCaP, reproducibly leads to metastasis formation in nude mice.

Animals↗
PubMed1997

Detection of loss of heterozygosity in the APC tumor suppressor gene in nonpapillary renal cell carcinoma by microdissection and polymerase chain reaction.

The role of the APC (adenomatous polyposis coli) tumor suppressor gene in the genesis of nonpapillary renal cell carcinoma is addressed. The frequency of allelic deletion in the APC gene was analyzed using microdissection of the tumor specimens and a PCR (polymerase chain reaction)-based assay for the detection of intragenic loss of heterozygosity (LOH). Twelve of 29 carcinomas investigated were informative (41%). In five of these (42%) LOH was detected in the APC gene, LOH did not correlate with tumor grade or stage. This high frequency of intragenic LOH suggests an implication of the APC gene or a closely linked gene in the genesis of a subset of nonpapillary renal cell carcinoma. The use of a microdissection technique allows the reliable detection of tumor-specific LOH when using a PCR-based assay.

Aged↗
PubMed1997

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate.

We have quantified and characterized alpha 1-, alpha 2- and beta-adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. alpha 1-, alpha 2- and beta-adrenoceptor were identified in radioligand binding studies using [3H]prazosin, [3H]RX 821002 and [125I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance beta > alpha 2 >> alpha 1 (not detectable), with no major difference between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was beta > alpha 2 >> alpha 1 (not detectable) and beta >> alpha 1 > alpha 2, respectively. The alpha 2-adrenoceptors in all tissues were homogeneously of the alpha 2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The beta-adrenoceptors represented a mixed population with a dominance of the beta 2-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1997

Detection of vital germ cell tumor cells in short-term cell cultures of primary tumors and of retroperitoneal metastasis--clinical implications.

By establishing short-term cell cultures derived from retroperitoneal metastasis after neoadjuvant chemotherapy, our aim was to improve the diagnosis and prognosis in patients with advanced testicular germ cell tumors. The histological evaluation of surgically removed metastatic tissue by retroperitoneal lymphadenectomy (RLA) is extremely complicated after previous chemotherapy, but knowledge of persistence of vital tumor cells in residual lesions is of great prognostic value and therapeutic consequence in patients with testicular germ cell tumors. We therefore investigated whether vital tumor tissue could be detected in short-term cell cultures derived from such metastatic lesions by measuring the concentration of the tumor markers beta human chorionic gonadotropin (beta HCG) and alpha-1 fetoprotein (AFP) in cell culture supernatants. We initially demonstrated the specificity of the determination in cell cultures of human transitional-cell carcinoma cell lines, human foreskin fibroblasts and normal testicular tissue. In a group of 20 patients with untreated primary testicular germ cell tumors, detection of beta HCG and AFP was increased about threefold in cell culture supernatants in comparison to the serum concentration. Finally, we prepared primary cell cultures from surgically removed retroperitoneal metastasis of 12 patients with testicular germ cell tumors after chemotherapy. The serum concentrations of beta HCG and AFP of all patients were at normal values when RLA was performed. However, pathologically increased concentrations of beta HCG (3/3) and AFP (2/3) in cell culture supernatants were found in 3 of 12 cell cultures. Interestingly, these three patients with a pathological increase in beta HCG and AFP as determined in the supernatant of the short-term cell cultures had tumor progression within a mean follow-up of 3 +/- 1 months (P < 0.01), whereas 9 of 12 patients who had no pathological increase in beta HCG and AFP as determined in the supernatant of the short-term cell culture were in complete remission (CR) after a mean follow-up of 40 +/- 11.6 months.

Adult↗