Search

The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade.

Subject and Method. Plasma erythropoietin levels were determined by Keighley's method to study the changes in erythropoiesis before and after human renal homotransplantation. Results. Erythropoietin titres in pre-transplant patients were low, while they returned to normal after successful renal transplantation. In acute rejection they were significantly high. After its reversal normal levels of erythropoietin were obtained in accordance with a normalization of the graft functions. Reticulocyte counts paralleled with erythropoietin values. Conclusion. High levels of plasma erythropoietin contribute to the diagnosis of acute rejection. Normalization of the plasma erythropoietin levels after the acute rejection could be regarded as an indication for good function of the graft. The grafted kidneys seem to function in producing erythropoietin.

The clinical efficacy and safety of 3.75 or 7.5 mg leuprorelin acetate depot given subcutaneously once every 4 weeks was evaluated in a collaborative study of 81 patients with untreated prostatic cancer. Efficacy of treatment was assessed using criteria based on a meeting of the Prostatic Cancer Study Group funded by the Japanese Ministry of Health and Welfare and using National Prostatic Cancer Project criteria. Japanese criteria enabled evaluation of individual parameters, unlike the National Prostatic Cancer Project System which classified a patient as unevaluable if one evaluation parameter was unavailable. Leuprorelin acetate depot suppressed serum luteinizing hormone, follicle stimulating hormone and testosterone concentrations. Objective response rates of the prostate, bone mtastases, serum prostatic acid phosphatase and soft tissue metastases, and subjective dysuria and pain responses were comparable to those found with conventional hormone therapy. Leuprorelin acetate depot was well tolerated, with no significant differences in response to the two doses.L'efficacité clinique de l'acétate de leuproréline sous forme retard à la dose de 3,75 ou 7,5 mg administré par voie sous-cutanée une fois toutes les 4 semaines a été évaluée dans le cadre d'une étude, portant sur 81 malades souffrant d'un cancer prostatique. L'efficacité du traitement a été évaluée en faisant appel à des critères déterminés par le Prostatic Cancer Study Group (Groupe d'Etudes sur le Cancer Prostatique) fondé par le Ministère de la Santé du Japon et le National Prostatic Cancer Project (Projet National sur le Cancer Prostatique). Les critères janonais ont rendus possibles l'évaluation de paramètres individuels à l'encontre du système adopté par le Projet National sur le Cancer Prostatique qui a classé un malade comme étant non évaluable dès que l'obtention d'un paramètre d'évaluation n'était pas possible. L'acétate de leuproréline retard induit la réduction des concentrations plasmatiques en hormones lutéinisantes, en hormones de stimulation des follicules (FSH) et en testérone. Les taux objectifs d'amélioration de la prostate, des métastases des tissus mous et des taux plasmatiques de phosphatase acide prostatique, de la dysurie subjective et des degrés de douleurs étaient comparables aux hormonothérapies conventionnelles. L'acétate de leuproréline retard a été bien toléré, et n'a pas induit de différences significatives dans la réponse obtenue aux deux doses administrées.L'efficacia clínica di 3,75 o 7,5 mg di leuprorelin acetato, in preparazione “ritardo”, somministrato per via sottocutanea ogni 4 settimane è stata valutata nel corso di uno studio collaborativo condotto su 81 pazienti ammalati di cancro alla prostata. L'efficacia del trattamento è stata valutata adottando dei criteri scaturiti da una riunione del Gruppo di Studio sul Cancro della Prostata, fondato dal Ministero della Sanit à giapponese, nonchè dei criteri stabiliti dal “National Prostatic Cancer Project”. I criteri elaborad in Giappone hanno consentito la valutazione dei singoli paramtri a differenza del sistema del “National Prostatic Cancer Project”, nell'ambito del quale un paziente veniva classificato corne non valutabile nel caso che uno dei parametri necessari alla valutazione non fosse disponibile. Il leuprorelin acetato, in preparazione “ritardo”, ha soppresso le concentrazioni seriche di ormone luteinizzante, ormone follicolostimolante e testosterone. I tassi di risposta oggettivi, relativi alle metastasi prostatiche, ossee, alla concentrazione serica di fosfatasi acida prostatica ed alle metastasi dei tessuti molli, nonchè le risposte soggettive relative alla disuria ed al dolore, sono risultati comparabili a quelli ottenuti con una convenzionale terapia ormonale. Il leuprorelin acetato, in preparazione “ritardo”, è stato ben tollerato, senza significative differenze nella risposta alle due dosi.

Purpose: Evaluation of prognostic significance of nucleolar organizer regions (NORs) in renal cell carcinoma (RCC). Materials and Methods: Nuclear organizer regions were quantified in a series of 59 cases of RCC by the silver colloid method, and the NOR index was obtained from the ratio between mean NOR counts in each neoplastic nucleus and in normal nucleus. The patients were staged pathologically and divided into 2 groups by average NOR index of all cases, which was 0.76. Correlations between the NOR index and other parameters were statistically analyzed, and the prognostic value of the NOR index was also examined. Results: The NOR indices from each group were correlated with the survival curve. In low stage tumors (pT1 or 2 N0M0), the low NOR index group had a survival rate of almost 100 per cent while in those patients with higher NOR indices, there was a significantly increased mortality (p less than 0.01). In patients presenting with high stage tumors (excluding pT1 and 2 NOMO), the survival rate was significantly improved in those patients with a low NOR index (p less than 0.01). On the other hand, the patients with a low NOR index have a better prognosis than those with a high NOR index within each tumor grade (p less than 0.01). Statistical analysis by the log rank test indicated NORs to be a significant predictor of survival over the whole series within low and high pathological stages and within each tumor grade. Analysis of the data with Cox's proportional hazard model showed that NOR index had a stronger hazard ratio than grade or stage of tumor (p = 0.0005). Conclusions: Our study has demonstrated that NOR index is a new prognostic indicator for patients with RCC (p = 0.0005).

To examine the precise localization of lysosomal cysteine proteinases, cathepsins B, H, and L in rat epididymal epithelial cells, immunohistochemistry and enzyme assay were applied to the epididymal tissue. Granular immunodeposits for cathepsins B and H were detected in epididymal epithelial cells, whereas faint or no immunoreactivity for cathepsin L was found. Moreover, immunoreactivity for cathepsin B appeared mainly in principal cells and was more intense in the head of the epididymis than in the tail, whereas that for cathepsin H appeared in both principal and clear cells and was more intense in the tail than the head. By enzyme assay, activities of cathepsins B and H showed a similar distribution to that of the immunoreactivity. The cathepsin L-specific activity was distributed evenly in each part of the epididymis and was also detected in epididymal fluids obtained from the body and tail parts. By immunoblotting, proforms of cathepsins B, H, and L were present in the seminal fluid. The results suggest that cathepsins B and H are involved in the intracellular degradation system of epididymal epithelial cells, and proforms of cathepsins B, H, and L may be secreted into the epididymal duct lumen.

Nucleic acid metabolism was investigated to determine the metabolic activity of bladder carcinoma cells. Surgically obtained specimens were subjected to this investigation. Radio-active nucleic acid precursors, 14C-Formate via the de novo synthetic pathway, and 14C-Adenine via the salvage pathway, were used. Activities of bladder carcinoma cells were determined by their incorporation rates. The results were as follows: 14C-Formate incorporation was much higher in grade III bladder carcinoma cells than in the normal epithelium of the bladder; it was highest in stage B2 bladder carcinoma cells. 14C-Adenine was found to be incorporated into nucleic acid bases of bladder carcinoma cells. It was observed that as the grades and stages progressed, higher incorporation rates were observed. Comparison between the activities of de novo synthesis and salvage pathway was made. The latter was more active than the former in bladder carcinoma cells.

A new bisphosphonate, disodium dihydrogen (cycloheptylamino) methylene bisphosphonate monohydrate (YM175), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) in terms of its effect on tumour induced osteolysis using a bladder tumour in mice (MBT-2). The method consisted of inoculating tumour cells subcutaneously (SC) over the calvaria in mice, resulting in a local tumour causing fragmentation of the bone. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumour. This osteolysis was evaluated by measuring the increased area of bone resorption in reduced opacity to radiograph and histology. The results showed the following sequence of potency: YM175 > AHPrBP = HEBP. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumour. YM175 appears to be an interesting new bisphosphonate with possible clinical application.

Renal tumours, obtained after nephrectomy, were subjected to in vitro study of the incorporation rate of C 14-8-adenine into nucleic acid bases.-In 10 examples of renal cell carcinoma, the incorporation rate into adenine and guanine were 2.01x10-2 (cpm/umole base) and 1.83x10-2 for DNA, and 3.00x10-2 and 2.83x10-2 for RNA. The incorporation rate in renal pelvic tumour was rather higher than that in renal cell carcinoma. It was demonstrated that the incorporation rate in Wilms tumour was highest.-These incorporation rates provide an index of the biological activity of the tumour cells.