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Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 343 records · Page 19Linked to original sources

Phase I/II study of recombinant interferon alpha and gamma in advanced progressive renal-cell carcinoma.

In vitro studies have documented the synergistic antiviral and antiproliferative activity of recombinant interferon alpha (rIFN alpha) and rIFN gamma. Furthermore, rIFN gamma is a strong immunomodulator with optimal effects at a relative low dose (0.1 mg/m2). On the basis of these observations, we began a phase I/II study with the combination of rIFN gamma at 100 micrograms/m2 (2 x 10(6) IU/m2) and rIFN alpha 2c 6 micrograms/m2 (2 x 10(6) IU/m2), injected twice a week subcutaneously. In cases of stable or progressive disease we increased the dose of rIFN alpha 2c every 2 weeks by 6 micrograms/m2 until the maximum tolerated dose was reached. A total of 32 patients with proven progressive renal-cell carcinoma were included. Of the 31 eligible patients, 21 were male and 10 female, their average age was 57.2 years (range 35-72), 28 had had nephrectomy, their median Karnofsky performance status was 90% (70%-100%), and their tumors were localized predominantly to visceral tissue. In 2, response was complete and in 6 it was partial, for a response rate of 25%. The disease had stabilized in 5 patients and progressed in 16. The median duration of partial response was 14 months (8-16 months); of 2 cases of complete response, 1 persists (23+ months), and the other suffered a relapse after 22 months. The median time to response was 24 weeks (18-24 weeks). The maximum tolerated dose of rIFN alpha was 30 micrograms/m2 (range of 6-36 micrograms/m2). Side-effects included those known to be associated with interferon treatment. One patient developed septicemia during a period with grade 4 leukopenia. Our study permits no conclusion regarding the additional value of rIFN gamma.

Adult↗

Presence of interleukin-2 in urine of superficial bladder cancer patients after intravesical treatment with bacillus Calmette-Guérin.

Urine samples were obtained from patients with superficial bladder cancer after immunotherapy with bacillus Calmette-Guérin (BCG). The patients were repeatedly (once a week for 6 consecutive weeks) treated with intravesical administration of approximately 5 X 10(8) culturable particles of BCG. Some patients received more than six BCG instillations. The urine samples were investigated for the presence of interleukin-2 (IL-2) in an in vitro bioassay using a murine cytotoxic T cell line (CTTL-16) that shows IL-2-dependent growth. Preliminary experiments indicated the presence of inhibitory factors in the urine. This inhibitory activity was abolished after 24 h dialysis. In a neutralization assay with both polyvalent and monoclonal anti-(human IL-2) antibody it was demonstrated that there was indeed IL-2 in the urine samples. In 8 of 11 patients the presence of IL-2 in the urine was demonstrated. The IL-2 production was directly related to the BCG administration as samples obtained just before the BCG instillation were always negative. In IL-2-positive samples a maximum level of IL-2 was observed between 2 h and 6 h after the BCG instillation. In urine samples obtained 24 h after the BCG IL-2 was not detected. In most patients the urine became positive after the third or fourth PCG instillation.

BCG Vaccine↗

Histological analysis of ultrasonic images of the prostate: an accurate technique.

Ultrasonography of the prostate furnishes images which still cannot be fully interpreted morphologically. In a cadaver study, the ultrasound images of two groups (21 and 19) prostates, obtained in a water bath, were compared with histology slides taken at corresponding levels. In the first part of the study, using a 4 MHz probe, there was a correlation between hyperechoic lesions and stone formations in 9 out of 15 cases. A relation between hypoechoic lesions and the existence of a carcinoma could also be established in 4 out of 12 cases. In the second part of the study, using a 7 MHz probe, there was a correlation between hyperechoic lesions and stone formations in all cases. Hypoechoic lesions correlated with the presence of a carcinoma in 1 out of 8 cases. The technique used appears to be well suited for the comparative study of ultrasound images and histology. Application of the 7 MHz probe is preferable as, because of a better resolution, smaller lesions can be detected. The results of this study are not very encouraging for the use of transrectal ultrasound for the detection of small prostatic carcinomas.

Aged↗

In vivo effects of high energy shock waves on urological tumors: an evaluation of treatment modalities.

We have studied the effect of high energy shock waves (HESW) alone or in combination with cytotoxic drugs on the growth of urological tumors. The effects of HESW on kidney or prostatic tumors depend largely on the tumor line used. In the rapidly growing prostate tumor no antitumor effect was evident in vivo, but in vitro examination of the in vivo shocked cells showed that the clonogenic potential of HESW treated cells was inhibited. In the more slowly growing tumors, like human kidney xenografts, a temporary growth delay is observed in vivo. The effect on tumor growth depends not only on the number of HESW administered but also on the initial tumor volume. The smaller the tumor burden, the better the antitumor effect. Single shock wave administration may cause a growth delay, and repeated administration leads to a prolonged delay in growth. This effect is temporary and several days after stopping the HESW administration the tumor regains its original growth potential (same doubling time). Finally we could show that tumor growth was suppressed in different tumor models for a longer period by a combination of HESW and a single dose of adriamycin. The effect of combined treatment resulted in a persistent longer doubling time.

Animals↗

In vivo antiproliferative effects of gamma-interferon and tumor necrosis factor alpha in a rat renal cell carcinoma model system.

We have investigated the antiproliferative activities of recombinant rat-gamma-interferon and recombinant human tumor necrosis factor alpha in a rat renal cell carcinoma model system. The tumor was transplanted subcutaneously, the drugs were administered peritumorally. Gamma-interferon treatment starting two days after tumor implantation resulted in a dose-dependent growth inhibiting effect. Tumor necrosis factor alpha was only effective at the highest concentration. Different combinations of the drugs have additive or synergistic antiproliferative effects. The combination of both highest doses completely inhibited tumor growth without any obvious toxic effects on the rats. Rechallenge of the cured rats with a tumor piece in the contralateral flank did not result in a tumor specific immune response. Shortening of the treatment period to two weeks resulted in an increased lag-period, but finally all tumors started to grow. Furthermore, the anti-tumor effect was dependent on tumor volume at start of therapy. Monotherapy could not inhibit tumor growth of an established tumor. The combination with both highest doses, however, inhibited tumor growth even when treatment was started at a tumor volume of two to five cm3. Treatment with gamma-interferon and tumor necrosis factor is most effective at low tumor burden. These studies suggest that clinical application of these drugs is most effective in an adjuvant setting.

Animals↗

The importance of prognostic factors in the individual treatment of patients with disseminated germ cell tumours.

Following chemotherapy for disseminated testicular cancer, 55 patients underwent surgery because of residual tumour. The histological findings were viable tumour in 12 patients, mature teratoma in 12 and fibrosis and/or necrosis in 31. Retroperitoneal abdominal masses were evaluated radiographically before and after chemotherapy. The reduction in size of these masses after chemotherapy appeared to have prognostic significance. A decrease of more than 70% was always associated with fibrosis. A residual mass over 50 mm indicated viable tumour or mature teratoma. Seminoma or embryonal carcinoma was more likely to result in fibrosis/necrosis in the resected tissue. Both the Indiana and the EORTC classification models can be used for prognosis. Radiographic measurements before and after chemotherapy are of considerable prognostic significance. These objective indicators help in planning treatment and so diminish the side effects of therapy and maintain or even increase the high cure rate in disseminated testicular cancer.

Cisplatin↗

Use of intravesical bacillus Calmette-Guérin in the treatment of superficial transitional cell carcinoma of the bladder: an overview.

Since 1976 superficial bladder cancer is treated with intravesical instillations of Bacillus Calmette-Guérin (BCG). The results with BCG are superior to other intravesical chemotherapeutics, both in superficial tumors and carcinoma in situ. BCG probably acts as a nonspecific potentiator of the immune system. Comparative studies have to give information about the effectiveness and side effects of the different strains of BCG, and about the best clinical schedule. Toxicity is mild in 95% of the cases. Severe side effects and antituberculous drugs are discussed.

Administration, Intravesical↗

Extragonadal germ cell tumor invading the prostate.

To our knowledge, only 3 patients with an extragonadal germ cell tumor of the prostate have been described in the literature until now. We here present a patient with a germ cell tumor arising in the retroperitoneum, invading the prostate, which was successfully treated by a combination of chemotherapy and nonmutilating surgery.

Adult↗

A new longer-acting LHRH analog depot: preliminary results of a Dutch open phase II clinical study on a 10.8 mg Zoladex 3-monthly depot.

A new longer-acting depot formulation containing 10.8 mg Zoladex was administered subcutaneously without anesthetic to 35 patients with advanced carcinoma of the prostate. Pharmacodynamic and pharmacokinetic data show that following a transient elevation in serum LH and testosterone, the levels of both hormones decrease. Serum testosterone reaches the castrate range in all patients by week 4 and remains at this level for at least 12 weeks. The serum Zoladex profile shows that castrate serum testosterone values can be sustained by very low serum concentrations of the drug of around 0.05 ng/ml. In this preliminary report, the efficacy and safety of this new longer-acting 3-month depot formulation of 10.8 mg Zoladex has been shown to be comparable to the 1-month depot formulation of 3.6 mg Zoladex, in patients with advanced carcinoma of the prostate.

Aged↗

Use of luteinizing-hormone-releasing hormone nasal spray in the treatment of cryptorchidism: is there still an indication? A clinical study in 78 boys with 103 undescended testicles.

We treated 78 boys with 103 undescended testicles with luteinizing-hormone-releasing hormone (LHRH) nasal spray, 400 micrograms 3 times daily for 4 weeks. After one (28 testicles) or two (5 testicles) courses of LHRH, 33 testicles in 25 boys were in the normal scrotal position. The success rate is 32%. In 41 testicles (40%) the result was a better mobility and/or a further descent, facilitating the proper diagnosis or the operation. 70 testicles were operated, and anatomic abnormalities were seen 37 times. In 6 boys minor side effects were noted. Reviewing the literature there is agreement that LHRH spray sometimes is necessary to confirm the presence of a retractile testicle, and so can be used in trying to avoid an operation.

Administration, Intranasal↗

Oncogene expression in prostate cancer.

Molecular biology has proven to be instrumental in studies on the onset and progression of cancer. Reasoning that tumorigenesis can be considered as a multistep process in which a normal cell gradually escapes from its delicately regulated growth pattern, one might describe this process in terms of gene expression. The group of genes that are good candidates for investigation in this context are the proto-oncogenes. Recent progress in oncogene research, has led us to believe that the group of oncogenes is much greater in number than the fifty so far characterized, since all growth factor-, growth factor receptor-, signal transducer- and transcription regulating genes have a potency to become oncogenic. Recessive genes, such as tumor suppressor genes might be equally relevant to the onset and progression of cancer. In this paper we confine ourselves to the role of protooncogenes in urological cancers, in particular prostate cancer. The usefulness of these genes as markers of progression in prostate cancer will be discussed.

Biomarkers, Tumor↗

The in vitro effect of electromagnetically generated shock waves (Lithostar) on the Dunning R3327 PAT-2 rat prostatic cancer cell-line. A potentiating effect on the in vitro cytotoxicity of vinblastin.

High energy shock wave lithotripsy has proven to be an effective tool in the management of renal calculi. The effects of electrohydraulically generated high energy shock waves (HESW) on tumor cells were described only recently. Here we present data on the experimental design for treatment of tumor cells, using electromagnetically generated shock waves. The determination of the focal area, in which pressures are at least 50% of the maximum pressure, appeared to be essential. In vitro HESW treatment resulted in a dose dependant anti-proliferative effect on Dunning R-3327 PAT-2 rat prostate cancer subline, determined by temporal growth curve analysis after plating of treated cells in soft agar. Furthermore, it was shown that HESW treatment had a potentiating effect on Vinblastin treatment. The combination of HESW with Vinblastin appeared to have an additive in vitro anti-proliferative effect on PAT-2 prostatic cancer cells.

Animals↗