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K H Kurth

Publications and source records attributed to K H Kurth.

At least 73 records · Page 4Linked to original sources
PubMed1994

Proteoglycans and glycosaminoglycans in tumor growth and migration: first experience with tumors of bladder and prostate origin.

Proteoglycans (PGs), macromolecules that contain bound glycosaminoglycans (GAGs), are an abundant and ubiquitously distributed group of proteins with a large variety of heterogeneous structures. In recent years a whole range of functions, varying from structural/mechanical support to involvement in the regulation of cell proliferation and cell mobility, cell-cell interactions, and angiogenesis and modulation of the extracellular matrix, have been attributed to these compounds. In this communication an overview is presented dealing with the available knowledge of the (regulatory) properties of PGs and GAGs as participants in tumor growth and metastasis. Acquaintance with the biochemical, biophysical, and biological characteristics of PGs and GAGs may provide a rational basis of the therapeutic use of GAGs in the prevention of tumor growth and invasion. The scarcely available information related to the role of PGs and GAGs in uro-oncology and the potential application of GAGs in the treatment of urological tumors are discussed.

Animals↗
PubMed1994

The effects of intravesical pretreatment with pentosan polysulfate on the bacillus Calmette-Guérin induced immune reaction of the guinea pig.

Immunotherapy with intravesical instillation of bacillus Calmette-Guérin (BCG) is an effective treatment for superficial bladder carcinoma. In the present study the BCG-induced immunological reaction in the guinea pig (PPD skin test, bladder wall infiltrates and number of cells in the iliac lymph nodes) was investigated after intravesical pretreatment with pentosan polysulphate (PPS), which modulated BCG attachment to the bladder wall. Pentosan polysulfate is a molecule comparable to the naturally occurring glycosaminoglycans (GAGs) of the bladder mucosa. The data obtained after six weekly instillations of BCG-RIVM (5 x 10(6) - 5 x 10(7) cfu) with or without preinstillation with PPS (10 mg. in 1 ml. for 0.5 hour) suggested an elevation of the immunological reaction to intravesical BCG. A strong binding capacity of PPS to the mammalian bladder wall was observed. In addition, and in contrast to bacteria commonly causing cystitis, a significant binding of PPS to mycobacteria was found: 3.5, 3.6 and 3.1 micrograms./ml. dry weight of BCG Connaught, RIVM and Pasteur, compared with 0.2, 0.3, 0.7 and 0.0 microgram./mg. dry weight of Escherichia coli, Streptococcus faecalis, Klebsiella pneumoniae and Proteus. The results suggest that PPS enhances the attachment of BCG to the bladder wall, resulting in an increased BCG-induced immunological reaction in the guinea pig. It may be speculated that pretreatment with PPS may increase the efficacy of BCG therapy in man, especially in those patients not exhibiting an immunological reaction.

Administration, Intravesical↗
PubMed1993

The detection of prostatic carcinoma. 4- or 7-MHz transrectal ultrasonography?

In this prospective study a comparison of 4-versus 7-MHz transrectal ultrasonography for the detection of prostatic carcinoma is reported. A total of 150 prostates were biopsied due to suspicion of malignancy arising at either digital rectal examination, 4- and/or 7-MHz transrectal ultrasonography, or elevated serum prostate-specific antigen levels. Malignancies of the prostate were detected in 68 of the 147 eligible biopsy core specimens. The results show only marginal differences in the sensitivity, specificity, and predictive values for the two transducers.

Adult↗
PubMed1993

Cytokine production by the human bladder carcinoma cell line T24 in the presence of bacillus Calmette-Guerin (BCG).

The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T24 treated with BCG was investigated. A 24-h treatment of T24 cells with BCG resulted in a tenfold higher secretion of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) when compared with T24 cells treated with Escherichia coli, Streptococcus faecalis or a cell wall preparation of Nocardia rubra (N-CWS). No secretion of IL-1 beta and IL-2 was detected. Pre-exposing T24 cells to BCG for various periods of time indicated that a minimum exposure time of 0.5-1 h was required to upregulate IL-6 and TNF alpha production. Extending the BCG pre-exposure time to 2 and 3 h further increased the rate of cytokine production. No significant difference was found, however, between the rate of secretion initiated after a 2-h or 3-h pre-exposure period. The amounts of these cytokines secreted in the presence of BCG-conditioned medium did not differ significantly from the constitutively secreted amounts, excluding an effect of products possibly secreted by BCG on the upregulation of IL-6 and TNF alpha. In addition, upregulation of cytokine production appeared to be dependent on the concentration of BCG. The results suggest that cytokines may be produced by urothelial tumor cells after intravesical instillation in patients with superficial bladder cancer, which may play a role in the mode of action of BCG.

BCG Vaccine↗
PubMed1993

Increased urinary albumin indicating urothelial leakage following intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer.

This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL)1 beta, IL2, IL6, and tumor necrosis factor alpha (TNF alpha) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24 h thereafter. The mean concentration of albumin in pre-therapy specimens was 112 +/- 118 (range 2-432) micrograms albumin/ml urine, approximating 14 +/- 14 micrograms/mumol creatinine (creat) (n = 15), which was comparable to the mean pre-instillation value of 16 +/- 32 micrograms/mumol creat (n = 96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P < 0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3-6. A significant correlation between albumin and concentration of the cytokines IL1 beta, IL2, IL6, and TNF alpha was found (P < 0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n = 418), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1993

Deoxyribonucleic acid ploidy of core biopsies and metastatic lymph nodes of prostate cancer patients: impact on time to progression. The European Organization for Research and Treatment of Cancer Genitourinary Group.

We studied 98 patients with locally confined but lymph node positive prostatic cancer (1 stage T1, 29 stage T2, 55 stage T3 and 2 stage T4) who were not treated by radical prostatectomy. A retrospective analysis was done of deoxyribonucleic acid (DNA) ploidy of pretreatment core biopsies of the primary tumor and lymph node metastases. While DNA ploidy has been shown to be an important prognostic factor if applied to radical prostatectomy specimens, core biopsy specimens and nodal metastases have rarely been studied. Of the 98 patients 87 were evaluable for DNA ploidy: 45 (52%) had diploid, 13 (15%) had tetraploid and 29 (33%) had aneuploid tumors. The ploidy of the primary tumor and of the lymph node metastases correlated significantly with the rate of progression and interval to progression. Also, significant correlations were noted between the percentages of cells in the S phase or S plus G2 phases of the cell cycle and interval to progression. Most patients in this study are part of the European Organization for Research and Treatment of Cancer protocol 30846, a prospective randomized study of early versus delayed treatment in lymph node positive, otherwise locally confined prostate cancer. This study is ongoing. Early endocrine treatment was associated with a significantly longer interval to progression. In a Cox regression analysis of the prognostic factors involved in this study, early endocrine treatment was more important than ploidy or proliferation patterns. Stage (T category) and histopathological grade did not show a correlation with progression. Followup is still too short and the numbers of patients are too small for relevant subgroup analysis. DNA ploidy measurement by flow cytometry on archival (paraffin embedded) core biopsy and lymph node material is possible, and produces meaningful results in predicting the prognosis of prostatic cancer. Since this information can be made available before treatment decisions, its exact value in the management of locally confined prostate cancer can be determined.

Aged↗
PubMed1993

Mitomycin C versus estramustine in the treatment of hormone resistant metastatic prostate cancer: the final analysis of the European Organization for Research and Treatment of Cancer, genitourinary group prospective randomized phase III study (30865).

A total of 171 patients with progressive metastatic prostate cancer following hormonal therapy was randomized to receive either 560 to 700 mg. estramustine orally per day or 15 mg./m.2 mitomycin C by intravenous infusion every 6 weeks. The patients were recruited during a 2.5-year period, and 70% had undergone more than 1 previous therapy for prostate cancer, with some having received as many as 5 different previous treatments. The overall results were disappointing. The median time to progression was 5 months and 50% of the patients died within 10 months. There was no difference in efficacy between the 2 treatment arms. Toxicity was severe in both arms but appeared earlier in those patients receiving estramustine, leading to a tendency for earlier deterioration in performance status. In this group of heavily pretreated patients there appears to be no justification for the use of either of these agents at the present time.

Aged↗
PubMed1993

A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder.

A total of 431 eligible patients with solitary, primary or recurrent stages Ta and T1 transitional cell carcinoma of the bladder was included in a randomized multicenter trial to compare a single intravesical instillation of 80 mg. epirubicin with water given immediately after resection, with respect to the disease-free interval and recurrence rate. The interval to initial recurrence was significantly better in favor of the epirubicin group. After a mean followup of 2 years it became evident that the recurrence rate after a single epirubicin instillation was decreased by nearly half with the same trend being found in all subgroups examined. Toxicity was mainly restricted to bladder irritation in plus or minus 10% of the cases. Pathology review brought considerable changes in T category from stages T1 to Ta (53%). Changes in grade were less pronounced but nevertheless important.

Administration, Intravesical↗
PubMed1993

Analysis of biopsy findings and implant quality following ultrasonically-guided 125I implantation for localised prostatic carcinoma.

Transperineal ultrasound-guided 125I implantation was undertaken in 52 patients with localised prostate cancer. After implantation, ultrasound-guided biopsies were taken from the previous malignant areas every 6 months in all patients. The percentage of negative biopsies increased from 22% at 6 months to 50% at 48 months. Implant quality was analysed in 37 patients. The difference between isodose levels encompassing the prostate and the aimed levels of 160 Gy was taken as a measure of implant quality. A good quality implant (< 10% underdosage) was found in 43% of patients, a moderate quality (10-25% underdosage) in 35%, and a poor quality implant (> 25% underdosage) in 22%. A statistically significant correlation was found between the quality of the implant and resulting negative biopsy at the original tumour site. Determination of prostate specific antigen (PSA) was not possible from the beginning of the study but an analysis with biopsy findings, implant quality and prostate volume reduction during follow-up has been performed since 1989. A significant correlation was observed between implant quality and serum PSA, and also between volume reduction and serum PSA.

Aged↗
PubMed1993

A plea for cold biopsy, fulguration and immediate bladder instillation with Epirubicin in small superficial bladder tumors. Data from the EORTC GU Group Study 30863.

The sensitivity of cystoscopy to distinguish infiltrating from superficial bladder tumors is very high. Only 28 (5.6%) of 501 single tumors, which were considered to be superficial by the urologist at visual inspection, were found to be infiltrating on pathological examination. If the size of the tumor and/or the cytological grade are considered, one can further reduce the number of infiltrating tumors missed, but it was impossible to identify them all. The recurrence rate of tumors at the resection site 4 weeks after TUR suggests the importance of trauma of the bladder mucosa in promoting recurrence. A single instillation of Epirubicin immediately after TUR prevents implantation of tumor cells and reduces the recurrence rate to nearly 50%. A combination of cold forceps biopsy and fulguration may be the most reasonable treatment for small bladder tumors.

Administration, Intravesical↗
PubMed1992

Prognostic factors in bladder carcinoma: histologic parameters and expression of a cell cycle-related nuclear antigen (Ki-67).

A total of 316 biopsies from patients with bladder carcinoma who entered a trial of the genito-urinary group of the European Organization for Research and Treatment of Cancer (EORTC) were reviewed. The histological data were subsequently correlated with the clinical course. A strong correlation between the number of mitoses and the time of first recurrence, muscle invasion, and death was noted. Next the expression of Ki-67 in frozen sections from 49 transitional cell carcinomas (TCCs) and the DNA content of the tumour cells were determined. The frequency of Ki-67-positive tumour cells increased with tumour grade and stage. Grade II TCCs and superficially infiltrating TCCs showed a wide range of Ki-67 scores. There was a significant difference in Ki-67 score between non-infiltrating (Ta) and superficially infiltrating (T1) grade II TCCs. All DNA-aneuploid carcinomas but also 15 out of 36 DNA-diploid tumours contained more than 10 per cent Ki-67-positive cells. Only some of these tumours were DNA-aneuploid or -tetraploid. The results indicate that the number of Ki-67-positive cells in grade II tumours may be a useful aid in separating grade II TCCs with a favourable prognosis from those with a poor clinical outcome.

Antigens, Neoplasm↗
PubMed1992

BCG treatment and the importance of an inflammatory response.

A prospective study was performed on patients with superficial bladder tumour treated with bacillus Calmette-Guérin (BCG). The kinetics of interleukin-6 (IL-6) titres were monitored in urine collected at regular intervals for 24 h during 14 BCG treatments, each consisting of six weekly intravesical instillations. IL-6 titres were quantified with an ELISA system and compared with a bioassay (biologically active IL-6) system. After instillation, urinary IL-6 titres transiently increased, reaching maximum levels between 2 and 6 h after instillation. IL-6 titres appeared to be significantly correlated with an increase of total cells retrieved by bladder washout 3 h after instillation. The kinetics of the weekly maximum biologically active IL-6 titres indicate that three types of BCG-induced response occur: an "early" response starting at the first instillation; a "late" response after the third instillation; or no IL-6 response. The "early" response appeared to be associated, but not strictly correlated, with an IL-2 response. The results suggest that the effectiveness of BCG treatment is determined by two processes, an inflammatory one, followed by a delayed type of hypersensitivity response.

BCG Vaccine↗
PubMed1992

Intravesical therapy with adriamycin and 4-epirubicin for superficial bladder cancer: the experience of the EORTC GU Group.

The anthracycline derivatives Adriamycin and 4-epirubicin are used to prevent recurrent tumors after transurethral resection of superficial bladder tumors. Both drugs are instilled intravesically. The present report describes the results of two multicenter, prospective, randomized phase III studies carried out by the EORTC GU Group. In protocol 30,790, after a mean follow-up period of 26.6 months, the recurrence rate for 165 patients treated with Adriamycin was 0.29 and the tumor rate was 0.74. For 156 patients treated with Epodyl, the recurrence rate was 0.29 and the tumor rate was 0.57. This difference was not statistically significant. For 70 patients who received transurethral resection alone, the recurrence rate was 0.65 and the tumor rate, 2.04. In protocol 30,763, patients with good prognostic factors were treated with one single instillation of 4-epirubicin versus sterile water. After a mean follow-up period of 16 months, in 190 patients treated with 4-epirubicin the recurrence rate was 0.20 and the tumor rate was 0.35; in 196 patients treated with sterile water, the recurrence rate was 0.37 and the tumor rate was 0.65 (P = 0.0001). Adriamycin and 4-epirubicin were efficacious, and severe side effects were not encountered. The superiority of Adriamycin over Epodyl could not be proven.

Administration, Intravesical↗
PubMed1992

Treatment of localized prostatic carcinoma using the transrectal ultrasound guided transperineal implantation technique.

Treatment of localized prostate cancer by ultrasonically guided transperineal 125I implantation, in contrast to open 125I implantation, may allow for ideal distribution of the seeds and may therefore lead to better treatment results. 46 patients with localized prostatic carcinoma (T1-T2, G1-G3, N0, M0) have been treated since 1985, using this new technique. The longest follow-up is 64 months (median 30 months). The irradiation implantation dose to the prostate was 160 Gy. Assessed by ultrasonography an average prostate volume reduction of 20% was achieved at 6 months, increasing to 24% at 12 months, 39% at 24 months and 56% at 48 months. To evaluate response of the primary tumor systematic ultrasonically guided needle biopsies from the previous malignant prostate areas were performed in all patients every 6 months during follow-up. Tumor-negative biopsies were obtained in 33% of patients at 12 months, 40% at 24 months, progressively increasing to 50% at 48 months. Three patients developed distant metastases, and 6 died, of whom 1 patient due to prostate cancer. Morbidity from implantation has been low and the erectile function was preserved in all patients at 12 months postimplantation. The high percentage of tumor-positive biopsies during follow-up indicates that this technique fails to cure a significant proportion of patients.

Aged↗
PubMed1992

Mycobacterial adherence and BCG treatment of superficial bladder cancer.

The importance of adherence of BCG (Bacillus Calmette Guerin) to the bladder wall as an initiator of the processes leading to the BCG-induced antitumor activity is still controversial. A study was initiated addressing this subject by an experimental procedure modulating BCG adherence using pretreatment with pentosan polysulphate (PPS), a polysulphated polysaccharide with glycosaminoglycan (GAG)-like properties and reported bacterial antiadherence properties to the bladder mucosa. Furthermore, PPS is applied as a drug to treat chronic and radiation induced cystitis. It was reasoned that application of PPS during BCG treatment may prevent cystitis, a common side effect. However, nothing is known about a potential interaction of PPS with the effectiveness of BCG treatment. The results obtained with guinea pigs receiving prior to each of the 6 weekly instillation with BCG-RIVM (1 x E7 cfu) an intravesical pretreatment with 10 mg PPS in 1 ml for 0.5 hours indicated an enhancement of the PPD skin reaction, inflammatory response and number of iliac lymph nodes cells after instillation 6 compared to non-pretreated animals. These results, contrary to the expected, were supported by the indication of an increased binding of [3H]uracil-labeled BCG to the bladder after PPS pretreatment. To explain these results, the binding of PPS to the bladder wall and BCG were quantitated spectrophotometrically with DMB (dimethylmethylene blue). After administration of 40 g, 80 g, and 10 mg in appropriate volumes into the rat, guinea pig & human bladder 0.9 +/- 0.3, 4.3 +/- 1.1g, and 5.7 +/- 1.8 mg PPS (n > 5) were recovered respectively, showing a strong adherence.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗