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Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokines. [ABSTRACT FROM AUTHOR]

Twenty-five patients with primary metastatic adenocarcinoma renis were treated by embolization and delayed nephrectomy. The objective of the study was to examine whether the natural history of the disease is influenced by this combined treatment. Most patients (19/25) had measurable metastatic lesions. No patient received additional therapy unless progression occurred. Embolization was mainly performed with Gelfoam and Gianturco coils. Complete remission of metastases was observed in 1 patient (still in remission after 36 months); stable disease in 6 patients (lasting between 14 and 31 months). Eighteen patients died after a median survival of 5.7 months (range 14 days to 11 months). No major complication related to the embolization procedure occurred. Angio-infarction followed by nephrectomy cannot be recommended for widespread use in patients with primary metastatic kidney carcinoma. The procedure may be tested in controlled clinical trials together with other treatment protocols, such as immunotherapy, infarction with radioactive particles, or chemoembolization. These approaches are experimental and therefore limited to institutions with sufficient experience. [ABSTRACT FROM AUTHOR]

Of 39 human kidney carcinoma transplanted to nude mice, four tumor lines were maintained on nude mice by serial transplantation. The established tumor cell lines were used to determine the assay evaluability of three different drug-testing systems: the subrenal capsule assay (SRC), the in vitro assay with labeled DNA precursor (L-DNA-P) and the stem cell assay (STC). Tumor cell lines were used because they allowed us to perform the different assays with the same tumor. Criteria for assay evaluability were measurable growth of the transplanted tumor fragment (histologically proved) in the SRC-assay, the amount of thymidine incorporation in relation to the number of cells in vitro and time of incubation in the L-DNA-P-assay, and a mean colony count for the sixfold plated cells of 50 or greater in the STC-assay. The criteria for evaluability were fulfilled when athymic or irradiated immunocompetent mice were used for the SRC-assay. However, in immunocompetent, non-irradiated mice, remarkable incursion of host cells was found. In the L-DNA-P-assay, optimal incorporation was reached after different times of culture, with different cell numbers. Therefore the technique of assaying with labeled DNA precursor lacks optimally defined assay conditions. The tumor cell lines examined in the stem cell assay demonstrated excellent growth; they therefore may be useful for pharmacological studies of drug interactions. [ABSTRACT FROM AUTHOR]

Between 1973 and 1979, 130 patients with pT noninvasive bladder carcinoma were treated either by TUR plus intravesical chemotherapy with a single dose of Epodyl on the following day (60 patients), or by TUR only (70 patients). There was no significant difference between the two treatment groups as to time until first recurrence. However, the recurrence rate with Epodyl was significantly lower than that with no adjuvant treatment ( P<0.01). The incidence of increase in T-category was lower among patients who received Epodyl ( P<0.01). Thus single dose intravesical chemotherapy following TUR appeared to be beneficial. [ABSTRACT FROM AUTHOR]

Development and progression of prostate cancer is a multistep process of cumulative genetic damage, acquired during a life-time. However, the altered genotype acts against an appropriate background of epigenetic control mechanisms. Several mechanisms of mitotically heritable, epigenetic control of differential gene transcription have been noted, such as stromal-epithelial and cell-cell interactions. In prostate cancer, an important, supporting and/or inhibiting role of stromal-epithelial interaction has been implicated in tumor growth, angiogenesis and metastasis, which includes cell proliferation, adhesion and motility. Within these processes, data mainly obtained in systems other than the prostate have shown a crucial (regulatory) role of proteoglycans (PGs) acting at the level of cell-cell and cell-pericellular matrix interactions. Although little information has been recorded from normal, benign hyperplastic and malignant prostate tissue, PGs are components of both the cell surface and the extracellular matrix (ECM) that form associations with other molecules, such as fibronectin and laminin. On the basis of cell-ECM adhesion/interaction as a prerequisite for both cell proliferation and motility, and the involvement of PGs, the purpose of this study was to investigate the possible biological relevance of (free) glycosaminoglycans (GAGs), as major functional substructures of PGs, on cell adhesion of a series of human prostatic cell lines cultured in vitro. The effects of a series of exogenously applied GAGs on cell adhesion and proliferation were studied in the human cell lines LNCaP. DU 145 and PC-3, cultured on tissue culture plastic as substratum. The applied GAGs were the natural GAGs, heparin, heparan, dermatan, chondroitin-4 and chondroitin-6 sulfate, and the semisynthetic, GAG-like pentosan polysulfate (PPS). Addition of GAGs (1–300 μg/ml) to cultures that were allowed to adhere for 24 h prior to GAG addition did not affect cell proliferation. In contrast, whereas the natural GAG added during cell adhesion had no effect. PPS strongly inhibited proliferation of LNCaP and DU145, but not the less anchorage-dependent PC-3 cells. Under the latter conditions, after 6 days of culturing the IC50 of proliferation were determined to be < 1 and 50 μg PPS/ml for LNCaP and DU145, respectively, corresponding with a profound effect on cell morphology. Direct measurements of cell adhesion confirmed that, in contrast to the natural GAGS, PPS inhibited cell adhesion. In conclusion, the interference of a nonnatural, GAG-like structure with cell adhesion may be interpreted as the involvement of PGs of the cell surface in cell adhesion, possibly affecting the various processes (proliferation, angiogenesis and metastasis) of prostate tumor progression. Although similar interferences of nonnatural GAGs with cell-adhesion-associated proliferation of anchorage-dependent cells remain to be established under in vivo conditions, this type of compounds deserves further attention as a tool with which to study the role of cell adhesion in the progression of prostate cancer and as a potential candidate for the development of a stromal-epithelial targeted therapy. [ABSTRACT FROM AUTHOR]

Clinical evaluation in oncology has typically focused on outcome indicators, while less attention has been paid to how treatment affects quality of life (QOL) of the patient. In this article some general aspects of quality of life are discussed, a short review of published data on QOL in patients with prostate cancer is given and results of a QOL study executed by the authors on patients with lymph node positive prostatic cancer are presented. The purpose of the study was to examine the impact of immediate or delayed treatment (after objective progression) in patients with prostatic carcinoma (T1-3 N1-3 M0) on quality of life parameters. To this end an extended questionnaire was constructed. Fifty-five patients participated. Assessment was performed twice, in 1994 and 1995. The comparison between patients with and patients without treatment showed in 1994 as well as in 1995 significant differences for hormonal treatment side effects such as sexual functioning and hot flushes, all of which were experienced more frequently by treated patients. In 1994 the treated patients experienced more psychological distress while in 1995 they showed worse physical function, less energy and more fatigue when compared to patients under surveillance. The premise that active treatment would improve the psychological quality of life was not sustained. In addition global health status and quality of life were identified as independent factors for progression in untreated patients with lymph node positive prostate cancer. Finally, an increase in prostate-specific antigen (PSA) in hormonally treated patients not only indicated hormonal escape but also a decrease in QOL. [ABSTRACT FROM AUTHOR]

Objectives: Twelve patients with superficial papillary transitional cell carcinoma of the bladder (pTa, pT1) were treated with six consecutive weekly intravesical instillations of Rubratin (in a dose of 1.5, 3.0, or 4.5 mg), a cell wall skeleton preparation of Nocardia rubra (NCW). The main objective of this study was to look for local immunomodulating effects of NCW and in the first four patients the effect on a marker lesion was also investigated. Methods: Local immunostimulation in all 12 patients was determined by (1) measurement of cytokine induction [interleukin 1 β (IL1 β), IL2, IL6, and tumor necrosis factor alpha (TNFα)], (2) leukocyte influx into the urine, and (3) phenotypic analysis of the lymphocyte fraction of these leukocytes. Results: Significantly elevated levels of Rubratin-induced IL1β ( P < 0.001), IL2 ( P < 0.001), IL6 ( P < 0.01), and TNFα ( P < 0.001) were found compared to control pretherapy levels. Rubratin also induced leukocyte influx into the urine. Fluorescence-activated cell sorter (FRCS) analysis of the urinary leukocytes indicated T-cell activation (IL2 receptor and HLA-DR expression), while in two out of five patients the CD4/CD8 ratios were increased. Urinary cytokine induction by Rubratin was comparable with cytokine induction observed in non-responding bacillus Calmette-Guérin (BCG) patients (recurrent tumor within 6 months), but less compared with responding BCG patients (no recurrent tumor within 6 months). Clinical results showed no response on the marker lesion and in five out of eight patients early recurrence was found after complete transurethral resection (TUR) of the bladder tumors. This biological response modifier caused no local or systemic side effects at the doses used. Conclusion: Although local immunostimulation by intravesical Rubratin administration can be induced, the amount of immunocompetent cells attracted to the bladder is not as high as observed in BCG-responding patients, resulting in lower amounts of cytokines produced. This could also explain the lack of clinical efficacy. [ABSTRACT FROM AUTHOR]

In intravesical therapy for superficial bladder carcinoma urothelial cells may, through the production of cytokines, contribute to the bacillus Calmette-Guérin (BCG)-induced local immunological reaction and associated antitumor efficacy. The aim of this study was to investigate such a role for the neutrophil-attracting cytokine interleukin-8 (IL-8). The appearance of IL-8 in patients' urine after BCG therapy was compared with BCG-induced IL-6 and IL-2 and the stability of IL-8 in urine was tested. Compared to IL-6 and IL-2, a rapid induction of IL-8 was observed, occurring after the first BCG instillation. Urinary IL-8 was highly stable, even after 24 h incubation at 37°C. The IL-8 concentration after the first instillation seemed to be associated with subsequent development of an immune response. Consequently, IL-8 seems an attractive candidate for investigation of its prognostic value for a clinical response to BCG therapy. [ABSTRACT FROM AUTHOR]

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) 1β, IL2, IL6, and tumor necrosis factor alpha (TNFα) 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 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2-432) μg albumin/ml urine, approximating 14±14 μg/ μmol creatinine (creat) ( n=15), which was comparable to the mean pre-instillation value of 16±32 μg/μmol 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 IL1β, IL2, IL6, and TNFα was found ( P<0.01), correlation coefficients ( r) being 0.56, 0.56, 0.67, and 0.71 ( n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFα→IL2→albumin→IL6→IL1β. TNF peaked most frequently after 2-4h and IL1β after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a 'leakiness' of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy. [ABSTRACT FROM AUTHOR]

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 (TNFα) 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-1β 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 TNFα 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 TNFα. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In a recent paper, we described the expression pattern of proto-oncogenes in primary human renal cell carcinoma [12]. To test the possibility of using xenografts as a useful alternative for such studies, we analyzed xenografts of a number of human renal cell carcinomas in nu/nu mice. Xenografts included RC2, RC14, RC21, RC43 and NC65. Northern blot analysis indicated that c- Ras was expressed in all these xenografts. The identify of the ras transcripts in the individual xenografts was further specified as c-Ha- ras, c-Ki- ras or N- ras. Expression of c- myc and the p53 gene was also found in a number of these tumors. Only RC21 failed to express the c- myc or the p53 gene. In all xenografts, a 3.0 kb c- fes/fps mRNA was present. In RC2, RC14, RC21 and RC43, low levels of the 4.8 kb ab 1 transcript were detectable. Transcripts of myb and sis could not be detected in any of the xenografts. The results indicated that the expression pattern of a variety of proto-oncogenes in xenografts of human renal cell carcinomas was similar to that in the primary tumors. [ABSTRACT FROM AUTHOR]

The purpose of this study was to demonstrate the ability of a new method to discriminate between benign and malignant tissue. Tissue samples from three patients with bladder tumours and one patient with bladder diverticula have been examined by histophotometry. This method, based on the correlation of nuclear volume and nucleic acid contents per cell uses thick formalin fixed samples. The results are obtained by measurements averaging more than one hundred thousand cells per sample. By this histophotometric examination a clear differentiation between malignant and benign tissue could be achieved. It was also possible to determine the degree of malignancy and to differentiate between infiltrating and noninfiltrating tumour, as well as inflamed bladder tissue. The results obtained histophotometrically were compared with the histological findings. [ABSTRACT FROM AUTHOR]

In the light of the high incidence of cardiovascular side effects with oestrogen therapy in patients with prostatic cancer, other medications altering androgen metabolism are under investigation. The influence of the anti-prolactin bromocriptine (CB154) on plasma kinetics of testosterone and on endogenous hormones was studied and compared with the effect of ethinyl oestradiol in 25 patients with prostatic carcinoma. Bromocriptine significantly suppressed both prolactin and testosterone, inhibited the transfer of androgen from the inner pool into the deep compartment and favoured its degradation. Ethinyl oestradiol decreased testosterone, LH and FSH, and prolonged the biological half-life of testosterone. The effects of bromocriptine on androgen metabolism might be of therapeutic value in patients with prostatic carcinoma. [ABSTRACT FROM AUTHOR]

In a group of ten patients, treated with cisplatin for advanced or metastatic urothelial cancer, renal function deteriorated in six. In a group of 28 patients, treated with cisplatin for tumours outside the urinary tract, renal function was impaired in 14 (50%). Renal function deterioration occurred more frequently in later life. Localization of the primary tumour in the urinary tract does not seem to predispose to renal function impairment. In contrast with reports in the literature, there was a significant decrease in serum calcium levels in spite of magnesium suppletion and normal serum magnesium levels. These calcium levels spontaneously returned to normal some months after the last treatment course with cisplatin. [ABSTRACT FROM AUTHOR]

The EORTC Urological Group is one of the 31 clinical groups and working parties within the European Organization for Research and Treatment of Cancer (EORTC). Intravesical chemotherapy has been used as chemoresection or chemoprophylaxis. Chemoresection has mainly been utilized in phase II studies to demonstrate ablation of existing disease and to study the mechanism of drug action. These studies are usually performed by individual members to obtain relevants information for the preparation of randomized trials. One example is a phase II chemoresection study with 4′-epi-doxorubicin (ERP). The EORTC GU Group extended its phase II trials to study remission in patients with primary carcinoma in situ. A new concept introduced in the prospective, randomized phase III trials includes the evaluation of chemoresection of a marker lesion as a prognostic factor in long-term prophylactic treatment. Chemoprophylaxis in the phase III trials aims to study the disease-free period, the recurrence rate and the long-term survival. So far, a series of five phase III trials, totaling more than 2,000 patients, demonstrated the efficacy of chemoprophylaxis to reduce tumor recurrence rates. The variation in the results of the different trials are due more to the prognostic factors (characteristics of the tumors) than to the related efficacy of the chemoprophylactic drugs. The selection of currently employed drugs, Mitomycin C, Epirubicin and BCG, is based on reported results, lack of toxicity, and drug availability in Europe. The data collected will be of great importance to determine the optimal clinical management of superficial bladder cancer. [ABSTRACT FROM AUTHOR]

Copyright of Oral & Maxillofacial Surgery is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An attempt was made to interpret bacterial adsorption to the lumenal surface of the urinary bladder wall under normal and pathological conditions according to the DLVO theory of lyophobic colloid stability, which describes the interaction between a bacterium and the bladder-wall surfaces as a balance of attraction and repulsion forces. Computer modeling suggested that a decrease in the surface potential of the bladder wall may well explain an increased bacterial adsorption, possibly associated with bacterial cystitis. With the intent of preventing bacterial adsorption, treatment of bacterial cystitis by intravesical instillation of pentosan polysulfate (PPS) was evaluated. PPS is a polysaccharide with high affinity (4±2 mg/bladder) to the bladder. The attachment of PPS strongly depends on the intrinsic properties of the bacterial surface. Theoretical considerations indicate that either complete coverage of the bacterium with PPS or an absence of PPS affinity is a prerequisite for obtaining steric interaction or prevention of bacterial sorption. Experimentally, an absence of PPS affinity (0-0.7 μg/mg bacteria) was found for bacteria commonly found during cystitis. Immunological treatment of superficial bladder cancer by bacillus Calmette-Guérin (BCG) depends on the interaction of BCG with the bladder wall. Improvement of the treatment may be obtained by increasing BCG adsorption. In this respect, the phenomenon of bridging in which PPS binds simultaneously to both BCG and the bladder-wall surface was investigated. Theoretical considerations and experimental results appeared to be in good agreement. It was found that BCG binds a considerable amount of PPS (3.4±0.3 μg/mg BCG). In a guinea pig model the theoretical considerations, indicating the occurrence of bridging at a low and narrow range of PPS concentrations, seemed to be confirmed. In contrast to a high PPS concentration of 10 mg/ml, at a low (0.1 mg/ml) PPS concentration a significant stimulation of the BCG-associated immune reaction(s) was observed. The results suggest that to obtain PPS-induced bridging between BCG and the bladder wall and to prevent steric interaction, PPS should be instilled prior to BCG, separated by extensive washout of free PPS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to examine whether ultrasound abnormalities of the prostate and seminal vesicles, which may be related to male accessory gland infection, are reproducible. Forty-seven men attending an infertility clinic were studied. Imaging findings of transrectal ultrasonography were recorded. Kappa (κ)-values to determine the intra-and inter-observer variation were assessed. Calcifications have good intra-observer (κ=0.77; 95% CI: 0.59–0.96) and good inter-observer reproducibility (κ=0.73; 95% CI: 0.54–0.93). Dilatation of the peri-prostatic plexus had moderate intra-observer (κ=0.57; 95% CI: 0.33–0.80) and good inter-observer reproducibility (κ=0.74; 95% CI: 0.55–0.94). Other ultrasound abnormalities of the prostate were not reproducible. None of the ultrasound abnormalities of the seminal vesicles were reproducible. In our study the prevalence of ultrasound abnormalities which may be related to male accessory gland infection was as high as 96%. However, only calcifications and dilatation of the venous plexus had good reproducibility. Other observed ultrasound abnormalities of the prostate and seminal vesicles were poorly reproducible and are therefore of no use in the diagnosis of male accessory gland infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Interest in the assessment of QoL in urological patients is growing. This is especially true for patients suffering from prostate cancer. Questionnaires have been developed to measure cancer-specific QoL, while disease specific modules are constructed to supplement these general questionnaires. However, none of these questionnaires include psychosocial measures. It has been repeatedly suggested that the assessment of QoL might be influenced by psychosocial factors such as coping style, mood, ability to express emotions, stressful life events and social support. We studied the influence of psychosocial factors on the assessed QoL in patients with BPH and PC. [ABSTRACT FROM AUTHOR]

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)