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Biomedical subjects

Z Wajsman

Publications and source records attributed to Z Wajsman.

At least 91 records · Page 5Linked to original sources
PubMed1980

Studies of tumor implants in immunologically privileged sites.

Wilms' tumor, renal cell carcinoma, and neuroblastoma in animals were transplanted from donors to recipients with strong histocompatibility differences. No strong evidence of the privileged site theory was found in this study and no obvious evidence of an immunosuppressive effect of testosterone was found. The most important factor noted in these studies was that the take of tumor transplant seems to be related more to the type of tumor itself. Further studies of transplant results of such different types of tumors are warranted and are being conducted. An interaction between the hormonal supportive concept and the privileged site seems tenable.

Adenocarcinoma↗
PubMed1980

Effects of diethylstilbestrol and estramustine phosphate on serum sex hormone binding globulin and testosterone levels in prostate cancer patients.

Serum testosterone-estradiol binding globulin and total testosterone were measured in 2 groups of male controls (less than 50 and more than 65 years old) and in 7 groups of prostatic cancer patients treated with various endocrine manipulation procedures, including orchiectomy, and estramustine phosphate and diethylstibestrol therapy. There were 133 individuals studied. Total serum testosterone levels were significantly higher in the younger versus the older control group and testosterone-estradiol binding globulin levels were significantly higher in the older men. Whereas orchiectomy reduced serum testosterone to low concentrations (72 plus or minus 11 ng. per 100 ml.) testosterone-estradiol binding globulin levels were not altered. In contrast, estramustine phosphate and diethylstilbestrol therapy, when administered to intact or castrated patients, resulted in depressed testosterone and markedly elevated testosterone-estradiol binding globulin serum levels, particularly in those patients receiving estramustine phosphate (less than 35 ng. per 100 ml. and more than 6 micrograms per 100 ml., respectively). These studies led to the conclusion that diethylstilbestrol or estramustine phosphate therapy is significantly more effective than orchiectomy in eliciting a concomitant elevation of testosterone-estradiol binding globulin and a depression of total testosterone. Even though free serum testosterone was not measured in the present study the law of mass action would indicate that in those patients with high testosterone-estradiol binding globulin (more than 5 microgram. per 100 ml.) and low total testosterone levels (less than 80 ng. per 100 ml.) the availability of biologically active (unbound steroid) testosterone would be negligible.

Adult↗
PubMed1980

Measurements of prolactin and androgens in patients with prostatic diseases.

Testosterone (T), dihydrostestosterone (DHT) and prolactin (HPr) levels were determined in normal males and females, in patients with benign prostatic hypertrophy (BPH) and in clinically stable patients with prostatic carcinoma (CAP), intact and orchiectomized. CAP patients were either untreated or on different modalities of therapy. The HPr levels were higher in prostatic cancer patients, in BPH patients, and in subjects on estrogen therapy. No significant differences were found between controls or patients treated with 5-Fu plus cytoxan. The T and DHT levels were decreased in all noncontrol subjects. The levels of DHT in intact, untreated CAP patients or those receiving 5-FU plus cytoxan were significantly higher than in BPH patients. Based on these observations, it appears that HPr could be involved with T and DHT in a feedback control role, especially in BPH. The alterations in these hormone levels in CAP treated or untreated patients are in marked contrast and must be evaluated further.

Adult↗
PubMed1980

Chemotherapy of advanced, hormonally resistant prostatic carcinoma.

9 advanced prostate cancer patients were given a dose of 1-(2-chlorethyl-3[4-methyl cyclohexyl]-1-nitrosourea) (MeCCNU) 175 mg/m2 orally every 6 weeks. All of them had previously failed on hormonal therapy. 8 patients have progressed during the chemotherapy and only 1 was considered to be stable during a period of 18 weeks. Hematologic toxicity was seen in 3 patients. 21 patients with advanced prostatic carcinoma who failed hormonal therapy were treated with a combination of estracyt (600 mg/m2/day) plus MeCCNU (175 mg/m2/6 weeks) in oral doses. 1 patient had stable disease for about 30 weeks and another one had a subjective response for 12 weeks. 11 patients had hematologic toxicity and 5 of them required dose modification. 10 patients with stage D carcinoma of the prostate were given oral estracyt at a dose of 600 mg/m2/day plus cis-diamminedichloroplatinum (DDP) at an intravenous dose of 60 mg/m2 twice a week repeated every 3 weeks plus methotrexate (MTX) at an i.v. dose of 100 mg/m2 twice a week, repeated every 3 weeks. All of the patients had failed on prior therapy. 9 patients are evaluable, 4 patients had an objective response and 2 others had a subjective response. 2 patients had hematologic toxicity (life threatening) and 2 others had a decrease in creatinine clearance to 60 mg/min and required dose modification. The combination of estracyt + DDP + MTX or a modification seems to be promising.

Antineoplastic Agents↗
PubMed1980

Hypothalamo-pituitary-adrenal axis in patients with prostatic carcinoma.

Insulin-induced pituitary growth hormone (GH), adrenocorticotrophic hormone (ACTH) and adrenal cortical response were studied in 12 patients with prostatic carcinoma. 3 patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. 5 patients showed lack of ACTH-cortisol response to insulin-induced hypoglycemia. Those patients subsequently presented clinically with rapidly progressing disease.

Adenocarcinoma↗
PubMed1980

The chemotherapy of prostatic carcinoma.

Results of the first randomized trial of the National Prostatic Cancer Project (NPCP) revealed an advantage for cytoxan and 5-FU over standard therapy in hormonally resistant stage D prostate carcinoma. A subsequent trial for patients previously irradiated, receiving the less myelosuppressive agents estracyt or streptozotocin also revealed an advantage over standard therapy. Other completed randomized trials have revealed activity for prednimustine and DTIC. Trials underway for newly diagnosed stage D disease or for stage D disease clinically stable to diethylstilbestrol (DES) show promising activity for cytoxan and DES combined. Current randomized trials in advanced disease are comparing methyl CCNU and hydroxyurea wih cytoxan, and estracyt or vincristine alone or in combination. Chemotherapy in earlier staged patients as adjuvants to definitive surgery or irradiation is underway in two trials, comparing the effects of cytoxan or estracyt as long-term therapies with no additional treatment.

Antineoplastic Agents↗
PubMed1980

Modern concepts of acid and alkaline phosphatase measurement.

Three new assay methods for prostatic acid phosphatase are described relative to results of biochemical methods. Methods for total and isozymes of alkaline phosphatase are also described. Results of a field trial for acid phosphatase tests among multiple institutions in the United States revealed a marked increase in sensitivity for one assay (CIEP) over biochemical methods. which was positive with increasing frequency as the clinical and surgical stage advanced beyond B. Only for stage D did the biochemical method approach the sensitivity of the CIEP assay. The CIEP assay has potential value as a screen for prostate cancer. Another acid phosphatase assay (RIA) proved difficult to perform for many institutions in the field trial. A new solid phase immunofluorescent assay recently introduced may on further testing be more sensitive than the CIEP assay. Total alkaline phosphatase levels studied in patients with advanced disease were markedly elevated in over one-third of the cases. Higher levels were associated with poor survival or response to chemotherapy. Alkaline phosphatase isozyme levels were of added value in locating the site of the increased alkaline phosphatase activity in soft tissue, bone, or liver. Occasionally in the face of a normal total value, increased isozyme activity in one of the aforementioned compartments preceded clinical ability to detect the metastatic foci.

Acid Phosphatase↗
PubMed1979

Chronic hematuria and localized bladder damage following combined cyclophosphamide and local radiotherapy.

A 13-year-old white male had Ewing sarcoma of the right pubic and ischial bones. Initial therapy consisted of 5,400 rads in seven weeks to the right side of the pelvis and 14 intravenous injections of cyclophosphamide (Cytoxan, CTX) at 500 mg/m2; BCNU and Adriamycin maintenance therapy continued for a total of two years. He has now been disease-free for five years. Three months following the completion of the right pelvic radiotherapy (RT), while on intravenous CTX, severe hematuria appeared, which subsided, but at present he has continuous microscopic hematuria, as well as periodic episodes of gross hematuria. Serial cystocopies initially revealed thickening and hemorrhagic and edematous changes on the right (irradiated) side of the bladder, and recent multiple telangiectatic patches have been demonstrated as a late "healing" phase. This case demonstrates the additive toxicity to the bladder of CTX and RT, illustrating that the hemorrhagic cystitis can be extremely protracted lasting five years.

Adolescent↗
PubMed1979

Two new, direct, and specific methods of acid phosphatase determination. National field trial.

A national study of the new specific assays for prostatic acid phosphatase was conducted by the National Prostatic Cancer Project. The results of the study have confirmed that the counterimmunoelectrophoretic method is easily reproducible, highly specific, and sufficiently sensitive. Based on tests as performed by different institutions, the counterimmunoelectrophoretic (CIEP) method was also shown to have high reproducibility and was found to be of much greater sensitivity than the conventional biochemical methods for the detection of earlier stages of prostatic cancer. The national study of the radioimmunoassay (RIA) has shown that although being a highly sensitive method, it could not be readily distributed at this time from one specialized center. It requires highly specific, expensive technical assistance and is not yet available nationwide. CIEP is recommended at this time to be used as the preferred method in the evaluation and diagnosis of prostatic cancer. The value of counterimmunoelectrophoresis in detecting early prostatic cancer as a screening method is promising, but still under study.

Acid Phosphatase↗
PubMed1979

Insulin-induced growth hormone responses in patients with prostatic carcinoma.

Insulin-induced pituitary growth hormone (GH) response was studied in 12 patients with prostatic carcinoma. Three patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. The patients subsequently presented clinically with rapidly progressing disease. Such observations are compatible with the viewpoint that abnormally high or low GH levels systemically present, may be associated with a particularly bad clinical prognosis. Further studies will clarify this relationship.

Adenocarcinoma↗
PubMed1979

Paradoxical increase of renal blood flow in anesthetized hypertensive dog treated with indomethacin.

To evaluate the effect of prostaglandin inhibition on the renal blood flow of the ischemic kidney, we administered indomethacin to 10 anesthetized dogs with renal artery stenosis and contralateral nephrectomy. Following the operation to produce renal ischemia, there was an increase of blood pressure associated with an increase of renin and the prostaglandins F1 (PGF1), and E (PGE). The administration of indomethacin to the intact, normotensive animals caused the anticipated decrease of prostaglandin E, renin, and renal blood flow. However, in the hypertensive dogs, indomethacin caused a paradoxical 45 per cent increase in the renal blood flow, despite a 44 per cent decrease of prostaglandin E. PGF1, PGE, renin, and erythropoietin exhibited the anticipated decreased levels. The study suggests that prostaglandins may not be the sole important factor in the regulation of renal blood flow in the presence of ischemia. Other important factors likely include the renin-sensitive angiotensin, the adrenergic, and the kallikrein-kinin systems.

Animals↗
PubMed1979

Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer.

The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.

Aged↗
PubMed1979

Steroid hormone receptors in the prostate.

Specific receptors for dihydrotestosterone and estradiol-17-beta have been identified in cytosols of the human and baboon prostate. Binding of radioactive estradiol-17-beta to the 0.4 M potassium chloride extractable component of human prostate nuclei also was demonstrated. Cyproterone acetate and diethylstilbestrol, agents of known high affinity for dihydrotestosterone and estradiol-17-beta receptors, respectively, did not bind significantly to sex hormone binding globulin and, therefore, were useful as competitors in distinguishing binding of dihydrotestosterone and estradiol-17-beta to sex hormone binding globulin and to their specific receptors. Displacement of [3H]-estradiol-17-beta binding by diethylstilbestrol in cytosols of 11 needle biopsy specimens (mean equals 16.8 mg.) from prostatic cancer patients was analyzed. These preliminary data indicated a trend towards greater competition by diethylstilbestrol for high affinity binding sites in differentiated tumor specimens from men who were not receiving estrogen therapy. Objective and subjective responses to hormone therapy were recorded in these patients, whereas the disease in those men with low displacement assay values progressed.

Aged↗
PubMed1979

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9% of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Chlorambucil↗
PubMed1979

The effect of drug schedule on mouse neuroblastoma treated with cyclophosphamide.

The potential difference in survival due to scheduling of cyclophosphamide treatment was examined in A/J mice inoculated with neuroblastoma C1-1300 cells. Treatment was started on the third day post tumor implantation. There were four groups of animals each consisting of 30 mice: Group A, a control group, was injected with 0.3 cc of normal saline for a week. Group B was injected with cyclophosphamide 50 mg/kg/day every other day for five doses. This cycle was repeated in the same fashion starting on day 17. Group C was injected with cyclophosphamide 250 mg/kg on day 3 and this was repeated on day 17. Group D was injected with cyclophosphamide 50 mg/kg/day for five consecutive days. This cycle was repeated on day 17-21. The median survival for group B was 26.2 days (the same as the control group), for group C 47.7 days (87% increased survival) and for group D 63.2 days (143% increased survival with 30% possible cures). Twenty-three percent of the mice in group B died of pneumonia and another 23% had minor evidence of lung infection. Only three mice in this group had tumor at the time of death. The study suggests that the response of murine neuroblastoma as well as the development of pneumonia in A/J mice treated with cyclophosphamide might be schedule dependent.

Animals↗
PubMed1978

Intermittent occlusion of the abdominal aorta: a conceptual approach in treating below-diaphragm tumors (a preliminary report).

A modified form of tumor strangulation as a possible treatment modality is considered. Intermittent intra-aortic occlusion by means of specially designed catheters and equipment is described. As a preliminary feasibility study, occlusion in non-tumor-bearing animals has begun, with projection for future human cases anticipated. Theoretical concepts of substances from the occlusion process resulting in cure and specific immunity in experimental animals are evaluated, and the belief in the development of modified antigens and antibodies as a consequence of restriction of a growing tumor's proliferating blood supply is discussed.

Animals↗
PubMed1978

Further study of fibrinogen degradation products in bladder cancer detection.

A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.

Cytodiagnosis↗