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Biomedical subjects

G Sufrin

Publications and source records attributed to G Sufrin.

At least 37 records · Page 2Linked to original sources

Effect of unilateral nephrectomy on tumor growth of the murine renal cell adenocarcinoma and neuroblastoma.

Compensatory renal growth has been observed following contralateral nephrectomy in man and in certain animals. In a recent study of murine Wilms' tumor, tumor growth was observed to be affected by contralateral nephrectomy; therefore, a murine renal cell adenocarcinoma and neuroblastoma were evaluated. Comparison of tumors in sham-nephrectomized animals to tumors in mice who had undergone unilateral nephrectomy showed no significant increase in tumor weights. However, the contralateral kidney in the uninephrectomized animals had increased in weight as compared to that in tumor-bearing intact mice and the kidneys removed at uninephrectomy. This study demonstrates that factors influencing compensatory renal growth do not affect all renal tumors or other solid tumors.

Animals↗

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling.

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium (p less than 0.05), and the mean stromal TLI was also increased (0.16 per cent, p less than 0.1). The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium (p less than 0.001) or epithelium of nodular hyperplasia (p less than 0.05). Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium (mean TLI 0.02 per cent) may account for the rarity of seminal vesicular carcinomas.

Adenocarcinoma↗

Heterotransplantation of human transitional cell carcinoma in athymic mice.

Human bladder tumors were obtained and transplanted into nude mice or other control animals. Tumor measurements, growth rate and selected histological studies were completed. No correlation between the growth of the tumor in the nude mouse and the clinical course of histologic tumor appearance in the host was detected. Metastases were not found. This feature has been noted generally to be uncommon in the nude mice model with some other human tumors. Despite careful technique tumor growth was achieved in only 40% of the appropriate experiments. The factors responsible for this variability and different growth rate in the nude mouse require further assessment before the results of other experimental treatments can be evaluated.

Animals↗

Prostatitis in the rat.

A high incidence of spontaneous, non-acute, age-dependent prostatitis was observed in the lateral prostate of Copenhagen rats and Wistar rats. The lumen of infected acini was filled with polymorphonuclear leucocytes, shed epithelial cells and cell residues. Epithelial cells lining such acini showed degenerative changes. Lymphocytes and macrophages were seen in the stroma. A histochemically observed increase in acid phosphatase and beta-glucuronidase activity in affected epithelial cells may indicate an increased lysosomal activity. Some bacteriological cultures of infected lateral prostates were positive for Proteus vulgaris and diphtheroids. It is suggested that this spontaneous rat prostatitis may be a useful model for the study of the pathogenesis and treatment of human non-acute prostatitis.

Acid Phosphatase↗

Adenosine deaminase activity in a transplantable murine renal adenocarcinoma.

Adenosine deaminase (ADA) activity was studied in tumor tissue, spleen, and bone marrow of animals bearing a transplantable murine renal carcinoma. Tumor tissue and splenic ADA specific activities were elevated in these animals when compared to controls although splenic specific activity subsequently declined with increasing tumor burden. Marrow ADA specific activity was the same in tumor bearing animals as in controls regardless of variations in tumor size. Studies of this enzyme may offer insight into salvage pathways of purine biosynthesis thereby suggesting exploitable targets for chemotherapy.

Adenocarcinoma↗

Studies of renin-aldosterone axis in stable normotensive and hypertensive renal allograft recipients.

Functional aspects of the renin-aldosterone axis were investigated in long-term normotensive and hypertensive renal allograft recipients. Unstimulated plasma renin and aldosterone levels were within control range in all patients and rose significantly in response to sodium depletion. However, no difference in the stimulated renin and aldosterone values between normotensive and hypertensive patients was noted. Baseline aldosterone secretory rates were elevated in all patients, but were higher in hypertensive patients than in normotensive patients. In both groups sodium depletion failed to augment this already elevated aldosterone secretion rate. Possibly, changes in the body pool and/or metabolic clearance rate of aldosterone account for elevations in plasma levels despite a relatively fixed secretory rate, though the role played by the lack of normal innervation of the kidneys cannot be ignored. It is unknown whether these observations may be causal or affected by other presently unknown or unmonitored factors. This in part may reflect unfolding problems in the understanding of nonrenal transplant hypertension.

Adult↗

Adenosine deaminase activity in patients with carcinoma of the bladder.

Adenosine deaminase is an important enzyme in purine metabolism, and patients with abnormal lymphocyte and erythrocyte adenosine deaminase levels have been shown to have impaired immune competence. Since immune factors have been shown to be important in patients with transitional cell carcinoma of the bladder we studied adenosine deaminase activity in the hemic cells of 48 patients with this tumor. Lymphocyte adenosine deaminase levels were elevated in patients with transitional cell carcinoma and correlated with stage, activity, clinical course and tumor resection but not with tumor grade. Erythrocyte adenosine deaminase levels also were elevated in patients with transitional cell carcinoma but did not correlate with other disease parameters. Lymphocyte adenosine deaminase activity in patients with transitional cell carcinoma may be a sensitive indicator of disease activity and further studies may provide insight into the host-tumor relationship at the enzyme level.

Adenosine Deaminase↗

Coagulation factors in renal adenocarcinoma.

Coagulation factors, including plasma fibrinogen, serum fibrinogen-fibrin degradation products, platelet counts and prothrombin times, were studied in patients with renal adenocarcinoma. Plasma fibrinogen levels were elevated and correlated with tumor stage, disease activity and therapy. Fibrinogen-fibrin degradation product levels also were elevated, although such elevations did not correlate with other parameters. Platelet count and prothrombin times were normal. Fibrinogen may be a valuable marker of disease activity in patients with renal carcinoma. In addition, since significant intratumoral fibrin deposits have been demonstrated anticoagulants or fibrinolytic agents may enhance cytotoxic therapy and should be considered in adjunctive chemotherapeutic protocols.

Adenocarcinoma↗

Studies of lymphocyte adenosine deaminase activity in patients with renal and transitional cell carcinoma.

Adenosine deaminase (ADA) is a critical enzyme in purine metabolism and lymphocyte ADA activity is specifically related to immunocompetence in man. Since immunologic factors are relevant in patients with renal and transitional cell carcinoma, we studied lymphocyte ADA activity in these patients. In renal adenocarcinoma patients lymphocyte ADA activity was reduced. Such reductions were most marked in low-as compared to high-stage lesions. Nephrectomy resulted in a rise and disease progression in a decline in ADA activity. In contrast, bladder, carcinoma patients showed elevated lymphocyte ADA activity most marked in high-stage lesions. Disease progression was associated with a rise and tumor resection with a decline in lymphocyte ADA activity. Discordance in patterns of lymphocyte ADA activity when patients with renal and transitional cell carcinoma are compared suggests unique host-tumor interactions at the enzyme level. Studies of ADA may offer insight into molecular aspects of immune mechanisms.

Adenocarcinoma↗

Adenosine deaminase activity in patients with renal adenocarcinoma.

Erythrocyte and lymphocyte adenosine deaminase (ADA) levels were studied in 31 patients with renal cell carcinoma (RCC). Decreased lymphocyte ADA levels occurred in patients with RCC. Erythrocyte ADA levels were reduced only in blood type B and O patients. Nephrectomy resulted in a rise in lymphocyte and erythrocyte ADA levels. Progression of clinical disease was associated with a fall in lymphocyte ADA values in all patients and with a rise in erythrocyte levels only in blood type A patients. Our results suggest that changes in erythrocyte and lymphocyte ADA levels in RCC patients are acquired and may offer insight into host-tumor interactions.

ABO Blood-Group System↗

Secondary involvement of the bladder in malignant lymphoma.

A study of 599 patients who had died of malignant lymphoma between 1952 and 1972 revealed involvement of the bladder in 13 per cent. Bladder involvement was always a secondary event, occurred in association with disseminated disease and was more common in non-Hodgkin's lymphoma than in Hodgkin's disease. Direct infiltration from adjacent pelvic foci as well as discrete apparent metastatic foci was noted. Involvement was usually microscopic although the presence of gross disease was invariably clinically manifest. Cystoscopy and cystography were valuable in the diagnosis of gross lesions. In contrast to primary vesical lymphoma the treatment of secondary vesical lymphoma was symptomatic and an operation was indicated rarely. Local radiotherapy was effective in treating the symptoms of secondary vesical lymphoma.

Adult↗

Hormones in renal cancer.

Plasma renin, erythropoietin and chorionic gonadotropin levels were evaluated in 57 patients with renal adenocarcinoma. Renin elevation, found in 37 per cent, was unrelated to blood pressure levels but was associated with high grade, high stage lesions of mixed histologic cell type and predicted a poor prognosis. Erythropoietin was raised in 63 per cent of patients and was more sensitive than renin in indicating the presence of renal adenocarcinoma. However, it was less specific and did not correlate directly with tumor grade, stage, histologic type, prognosis or hematocrit and hemoglobin levels. None of the patients had elevated chorionic gonadotropin levels. Therefore, we believe that renin and erythropoietin determinations may be of value as biochemical tumor markers in renal adenocarcinoma.

Adenocarcinoma↗

Pharmacokinetic studies of a transplantable murine renal adenocarcinoma.

An animal model to investigate new therapeutic approaches for the treatment of renal adenocarcinoma has been further studied. This model is based on a transplantable murine renal adenocarcinoma whose growth follows Gompertzian kinetics, relates to tumor RNA and DNA content, and also correlates with the rate of tumor DNA synthesis. This model in the current study was also evaluated for the ability of various therapeutic agents to inhibit tumor DNA synthesis. Such tests may be valuable for the preclinical screening of potentially useful drugs and may provide insight into fundamental aspects of tumor control. In this study, CCNU, BCNU, and adriamycin were potent inhibitors of tumor DNA synthesis whereas cytosine arabinoside, bleomycin, and cyclophosphamide were not. These observations were confirmed by autoradiography and correlated with other experimental end points of tumor therapy such as tumor weight and animal survival. This preclinical screening model is an effective and helpful means whereby new drugs and drug combinations can be tested for potential use in human renal cell carcinoma.

Adenocarcinoma↗

Pharmacokinetic studies in the chemotherapy of neuroblastoma using the C1300 murine system.

The transplantable C1300 murine neuroblastoma has been characterized biochemically and an in vivo model for the screening of new therapeutic approaches to the treatment of neuroblastoma developed. Subcutaneous inoculation of A/J mice with 10)6) C1300 cells results in predictable tumor growth and animal death in 25 +/- 4 days. Tumor growth is Gompertzian, correlates with increases in tumor RNA and DNA content and with the rate of tumor DNA synthesis as measured by [3H] thymidine incorporation. The model proposed is based on the degree to which various therapeutic options are able to inhibit tumor DNA synthesis, and these observations have been confirmed autoradiographically. A single course of either cyclophosphamide (25, 50, 100 or 200 mg/kg), BCNU (2, 7.5, 15, or 30 mg/kg) or cytosine arabinoside (15, 30, 60, 90 mg/kg) resulted in dose-related inhibition of tumor DNA synthesis. The maximum decline in DNA synthesis that was produced by the highest dose of each agent was by 81%, 77% and 68% of untreated tumor values respectively. Adriamycin, however, even at lethal levels (10 mg/kg), did not elicit significant inhibition of tumor DNA synthesis. Radiotherapy (200 R, 500 R or 1000 R) also produced graded inhibition of tumor DNA synthesis. This model is potentially useful for the preclinical screening of therapuetic options in the treatment of neuroblastoma. Thus, single agent therapy, combination chemotherapy and combined radiotherapy and chemotherapy may be rapidly evaluated for possible clinical use.

Animals↗