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Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

500 records · Page 28Linked to original sources

Ultrasonography versus clinical examination in evaluation of testicular tumors.

The diagnostic results of clinical examination and gray-scale ultrasonography for scrotal pathology were compared in 411 patients. Sensitivity and specificity of the clinical diagnosis of a testis tumor improved significantly with the use of ultrasonography. Criteria for the ultrasonographic diagnosis of a testicular tumor were evaluated. We had no false-negative ultrasonographic diagnoses, and they have rarely been reported in the literature. With ultrasonography, the number of false-positive clinical diagnoses was reduced from 11 to 5.

Follow-Up Studies↗

Critical review of the models to study the biologic progression of bladder cancer.

For transitional cell carcinoma of the bladder, clinical data indicate that invasive, metastatic tumors can arise through at least two different progression pathways. The majority of invasive, metastatic bladder neoplasms clinically present de novo, i.e., the patients have no history of malignant bladder disease. This implies that the highly malignant tumor cells either arise de novo or have undergone a rapid progression. Alternatively, a considerable fraction of patients with superficial bladder cancer process to invasive disease after a history of relatively benign superficial TCC. The molecular and cell biological basis of tumor progression is only poorly understood. Clearly, a better understanding of this progress could have profound clinical implications, since patients with superficial TCC with a high risk for progression would have to be treated more aggressively. We discuss the problems that are associated with tumor biological studies on early steps in the progression of TCC, especially from a "model system point of view."

Animals↗

Immunohistochemical analysis of tumor antigen saturation following injection of monoclonal antibody G250.

Clinical tumor targeting studies with monoclonal antibody (mAb) G250 showed excellent targeting of primary renal cell carcinomas (RCC). However, tumor uptake decreased at higher mAb G250 doses, suggesting saturation of the G250 antigenic determinants. In this immunohistochemical study we investigated the saturability of G250 antigen sites after i.v. administration of mAb G250 at various protein doses in nude mice with RCC xenografts. Five groups of mice received five different protein doses (1, 3, 10, 30 or 100 micrograms) of murine mAb G250. Three days post injection mice were killed and the tumors were removed. Free G250 antigen sites, i.e., not targeted by the i.v. injected murine mAb G250 were determined by immunohistochemical staining with chimeric mAb G250. Distinct staining of the G250 antigen was observed only at the 1 and 3 micrograms dose whereas G250 antigen staining at higher doses was virtually negative. The results of this study indicate that saturation of antigen occurs at relatively low doses of i.v. administered mAb G250. Apparently, all antigenic determinants present on the RCC tumor cells were targeted, while previous preclinical studies suggested that i.v. administration of mAb G250 only saturated the accessible antigen sites.

Animals↗

Leukocytes and cytokines in the urine of superficial bladder cancer patients after intravesical immunotherapy with bacillus Calmette-Guerin.

The urine of superficial bladder cancer patients treated intravesically with BCG was examined for the presence of leukocytes and cytokines. The number of leukocytes was markedly increased 24h and 48h after five or more BCG instillations. Flow cytofluorometric analysis revealed that, in addition to large numbers of granulocytes, monocytes/macrophages and T-lymphocytes were clearly detectable. The T cells were predominantly CD4+ and probably activated, since they expressed IL2 receptors and HLA-DR. The cytokines IL1, IL2, IL6 and TNF alpha were also increased after BCG instillations. These cytokines and leukocytes may play a role in the antitumor activity of BCG.

Administration, Intravesical↗

Intravesical Bacillus Calmette-Guérin treatment for superficial bladder cancer: results after 15 years of experience.

Superficial bladder cancer has a high recurrence rate and considerable progression rate. The treatment currently consists of resection and adjuvant intravesical chemotherapy or immunotherapy. Intravesical instillation of Bacillus Calmette-Guérin (B.C.G.) is considered to be one of the most successful immunotherapies in man. Durable response rates of 60-70% are achieved. Toxicity is more pronounced in comparison with intravesical chemotherapy. In this article we describe the experience with B.C.G. during the last 15 years. No consensus has been reached yet about the ideal treatment scheme, appropriate strain and optimal dosage. The mechanisms of action are complicated and still not completely understood.

Humans↗

Combined effects of tumor necrosis factor alpha and radiation in the treatment of renal cell carcinoma grown as radia spheroids.

We have investigated the antiproliferative effects of Tumor Necrosis Factor Alpha (TNF) and radiation on a recently described rat renal cell tumor line grown as multicellular tumor spheroids (MTS). Treatment commenced when the spheroids had reached a diameter of 250 microns. TNF was diluted in the tissue culture medium in different concentrations, ranging from 250-1000 ng/ml. TNF monotherapy had a dose-dependent inhibiting effect on spheroid growth. Single-dose irradiation with 2, 4 or 6 Gy also retarded spheroids significantly in their growth. In the combination treatment the highest dose of TNF (1000 ng/ml) was added 4 hours prior to radiation. TNF could not induce a potentiation of the radiation injury at 2 Gy. The combination with 4 Gy, however, had additive and the combination with 6 Gy synergistic antiproliferative effects; in these treatment regimens respectively 2 and 5 out of 24 spheroids were controlled, i.e. cured. These experiments suggest that TNF in combination with radiotherapy may be beneficial for the treatment of renal cell carcinoma or cancer in general.

Animals↗

Multiparameter analysis of four human renal cell carcinoma xenografts in nude mice.

Four human renal cell carcinoma xenografts (RC2, RC14, RC43, NC65), maintained in nude mice for several years, were investigated in a multi - disciplinary study, using (immuno) histochemical, biochemical and ultrastructural techniques. Histological, cellular, nuclear and biological characteristics were investigated. All tumors showed histologically recognizable features of human renal cell carcinomas, although marked differences between the four tumors were seen, both at the histological and ultrastructural level. Flowcytometric analysis of tumor cell suspensions allowed DNA quantification as well as the detection of subpopulations. Immunohistochemical staining procedures using tissue specific antibodies against intermediate filament proteins revealed two populations of tumor cells. Most tumor cells in three of the xenografts coexpressed cytokeratins and vimentin, while in RC43 most of the tumor cells expressed only vimentin. Northern blot analysis showed a higher expression of vimentin mRNA in all tumors as compared to normal kidney tissue. RC43 showed a three-fold higher level of vimentin mRNA than the other xenografts. Growth potential in the human tumor cloning system was evaluated by temporal growth pattern analysis. These experiments showed that the xenografts resemble human primary renal cell tumors in different ways, and reflect different characteristics that can be present in human renal cell carcinoma.

Aneuploidy↗

Multidisciplinary evaluation of rat renal cell carcinoma.

The rat renal cell carcinoma system as described by deVere White and Olsson in 1980 is used widely as a model for its human counterpart. The tumor arose spontaneously in a male Wistar Lewis rat and its behaviour has been shown to be stable during multiple passages. We have compared this tumor with the human renal cell carcinoma using a multidisciplinary approach. Light microscopy and electron microscopy showed a great resemblance of this rat tumor to a human renal cell carcinoma of the clear cell type with the ultrastructural presence of desmosomes. With the use of tissue specific antibodies against intermediate filament proteins, it could be shown that their expression is comparable to human renal cell carcinoma, i.e. coexpression of vimentin and different cytokeratins in the tumor cells. The cells could also be shown to contain cytokeratin 18. An aneuploid cell population in the tumor, expressing both vimentin and keratin, could be characterized by DNA flow cytometry in double labeling experiments. Comparison of normal and malignant rat kidney tissue by Northern blot analysis revealed increased levels of vimentin mRNA. In conclusion, this tumor model seems to have several histological and biological properties in common with the human renal tumor.

Actins↗

[The place of surgery in the treatment of testicular tumors other than seminoma (author's transl)].

Surgery plays an important part in the treatment of non seminomatous testicular tumors. An oncologically correct technique of orchidectomy is the first essential if the better prognosis of these tumors, noted in the past decade, is to be further improved. The testis should be removed through an inguinal approach. Radical retroperitoneal lymphadenectomy is gaining more favour at the present time. This operation, routinely performed in the US. is being performed more frequently in Europe. The justification for this major operation with a definite morbidity is to be found in the better survival rate achieved in patients undergoing surgery as compared to that achieved using other treatment modalities. A description of the operative technique delineates the magnitude of the surgery but also shows that, working methodically the operation is feasible.

Humans↗

Role of mycoplasmas in chronic prostatitis.

In 17 out of 102 patients with clinically diagnosed chronic prostatitis the disease could be attributed to known urogenital tract pathogens. Of the remaining 85 patients, Ureaplasma urealyticum was isolated from 38, Chlamydia trachomatis from five, and both organisms together from two. The results of antimicrobial treatment of the patients suggest an etiological relationship between Ureaplasma urealyticum and certain cases of chronic prostatitis. In these cases urethritis seems to be an accompanying symptom (urethro-prostatitis). No relation could be demonstrated between a favorable outcome of therapy and particular serotypes of ureaplasma. Our study could not establish any pathogenic role for Mycoplasma hominis.

Adolescent↗

Enhanced pharmacological testing in patients with erectile dysfunction.

This study was designed to evaluate the practical use of the combination of a low-dose intracavernous injection test (ICI) and visual erotic stimulation (VES) in the assessment of patients with erectile dysfunction. Additionally, a postinvestigation questionnaire (PIQ) was used to rate the erection following the investigation when the patient had left the office. It was hypothesized that the combination (ICIVES) and the PIQ would yield a higher erectile response rate than ICI or VES alone and would minimize the occurrence of prolonged erection. Of the 90 patients studied, 17 (19%) showed adequate erections to VES, 10 (11%) to ICI, and 60 (67%) to ICIVES. Of the 30 non-responders, 7 (23%) reported adequate erections on the PIQ. Overall, in 75% of the patients adequate erections were achieved. No prolonged erections were encountered. It is concluded that the combination of a low-dose ICI and VES, and the application of a postinvestigation questionnaire, is a powerful and safe test to select patients for autoinjection therapy.

Adult↗

Increased expression of a 68-kDa protein in the corpus cavernosum of some men with erectile dysfunction.

Erectile dysfunction (ED) may be caused by abnormalities of intracavernous penile structures. In order to investigate whether specific proteins could be identified that might be related to ED, the composition of structural proteins in cavernous tissues of patients with ED was compared to that of normal cavernous tissues by gel electrophoresis. Increased expression of a 68-kDa nonionic detergent extraction-resistant protein was demonstrated in tissues of more than half of the patients with vasculogenic ED, whereas only one out of nine normal cavernous tissues showed the same phenomenon. Increased expression was not related to a specific type of vascular insufficiency, aging, or diabetic constituency. Histochemical and immunochemical studies revealed that the increased amount of the 68-kDa protein is not merely the result of a surplus of nervous, smooth muscle, or elastic tissues. Furthermore, antibodies specific for 68-kDa neurofilament and 62- to 67.5-kDa tropoelastin did not recognize the 68-kDa protein on Western blots. The possibility that the 68-kDa protein may help us understand the etiology of certain cases of erectile dysfunction is discussed.

Antibodies, Monoclonal↗

Value of urine cytology in screening patients with prostatitis syndromes.

We reviewed the results of urine cytology examination of 206 patients with a diagnosis of prostatitis syndromes in the period 1985-1991. The urine samples showed an incidence of 20.4% for slight to moderate atypia and 6.3% for severe atypia. In these patients, cystoscopy, bladder biopsies and intravenous urography were performed to exclude malignancies. In only 6 of the 13 patients with severe atypia of the urine cytology were malignancies found. In cases of malignancy, the ages of the patients ranged from 51 to 64 years (mean, 58.6), and they complained most frequently of irritative bladder symptoms. In these patients, urinalysis frequently showed leukocyturia, and in all the samples, erythrocyturia was found.

Adult↗

Tenascin-C expression in prostatic intraepithelial neoplasia (PIN): a marker of progression?

BACKGROUND: Tenascin (tenascin-C) has been suggested to be associated with active epithelial-stromal interactions. We evaluated tenascin expression in tissue remodelling processes presumably associated with PIN and prostate carcinoma (PCa). MATERIALS AND METHODS: Tenascin immunoreactivity was evaluated in 38 PIN lesions (low-grade = 5, high-grade = 33) from 27 paraffin-embedded PCa specimens, and compared with expression in pre-existent (normal) prostate, benign prostatic hyperplasia (BPH), and PCa. RESULTS: Periepithelial stromal tenascin expression was low in low-grade PIN, and similar to normal glands and BPH, whereas expression in high-grade PIN was high and partly overlapped that of well-/moderately differentiated PCa. High-grade PCa usually expressed little, if any tenascin. CONCLUSIONS: The variable periglandular tenascin expression in high-grade PIN may reflect the biologic behaviour of this lesion, and may be indicative of variable levels of tissue remodelling. In well/moderately differentiated PCa tenascin expression levels may be an indicator of tumour progression.

Biomarkers, Tumor↗