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Biomedical subjects

M F Sarosdy

Publications and source records attributed to M F Sarosdy.

65 records · Page 4Linked to original sources

Tumor-specific immunotherapy of murine bladder cancer with butanol-extracted antigens and ethylchlorformate polymerized tumor protein.

Successful treatment of superficial bladder cancer using nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) has been well documented. Investigation of two potential tumor-specific immunotherapeutic agents using a murine transitional-cell carcinoma model (MBT-2) is reported. The survival of mice immunized with tumor proteins obtained by treating tumor cells with either 1-butanol or ethylchlorformate was compared to the survival of animals immunized with BCG. Long-term immunity conferred by each of these agents was also assessed. Significant protection by both agents was noted in all treatment groups compared to controls. Long-term immunity was also found to result from treatment with both investigational agents as well as with BCG. Butanol-extracted antigens and ethylchlorformate polymerized tumor protein may be useful as immunotherapeutic alternatives to BCG.

Animals↗

A new technique for continent urinary diversion.

Canine experimental surgery was used to investigate the feasibility of creating a new continent urinary reservoir. Remodelled ileum was used to fashion this reservoir like the Kock pouch, but without either of the intussuscepted nipple valves which it uses. Ureters were implanted directly into the wall of the reservoir using a nonrefluxing technique. Continence was obtained by plication of a short limb of intact ileum exiting from the reservoir through which intermittent catheterization was performed. Three of four animals which remained infection-free had good to excellent results. Reservoir infection in four additional animals was associated with failure due to ureteral obstruction. The advantages of this reservoir include the use of ileum to achieve a low-pressure reservoir, the absence of the complex nipple valves of the Kock pouch, and the absence of foreign bodies such as staples and artificial sphincters. While the followup in this study is recognized as relatively short-term, the successes seen in this difficult-to-use animal model suggest that further evaluation of this simplified procedure is warranted.

Animals↗

In vitro chemosensitivity testing of human neuroblastoma cell lines in soft agar: a tumor-specific drug screening model.

Tumor-specific screening of investigational anticancer drugs is a new approach to cytotoxic drug screening. A tumor-specific drug screening model has been designed using established human neuroblastoma cell lines. In vitro drug sensitivity was studied using a modification of the human tumor stem cell assay. Eleven cell lines were tested initially for colony formation in soft agar. Four cell lines formed only small cell clusters, while three cell lines formed colonies at a very low rate. The four remaining lines formed colonies with satisfactory efficiency. These cell lines were exposed to three concentrations each of cis-platinum, vincristine, doxorubicin, L-phenylalanine mustard, and ethidium chloride and suspended in soft agar. Colony formation was tabulated and sensitivities determined for each cell line. A heterogeneous pattern of in vitro sensitivity was observed. Limitations and pitfalls as well as potential advantages of using such a tumor-specific drug screening system are discussed.

Agar↗

Upper gastrointestinal bleeding following renal transplantation.

Upper gastrointestinal bleeding has been shown to be a common complication of renal transplantation and one which carries a significant risk of mortality. In a retrospective review of 200 consecutive renal transplants in 194 patients, we found an incidence of only 6 per cent and a mortality rate of 8.3 per cent. Allograft survival in this group of patients was 58 per cent. These results are the product of careful preoperative evaluation, close attention to the patients for early signs of bleeding, and aggressive diagnostic and therapeutic intervention at the first evidence of bleeding. We also report an association of hypercalcemia with post-transplant upper gastrointestinal bleeding, with cessation of bleeding after parathyroidectomy.

Antacids↗

Hypercalcemia-induced upper gastrointestinal bleeding after renal transplantation.

Hypercalcemia is common in patients after renal transplantation and may stimulate gastrin hypersecretion with associated peptic disease. We report on 2 patients with hypercalcemia and life-threatening gastrointestinal hemorrhage controlled by subtotal parathyroidectomy. Retrospective review of our last 10 patients with gastrointestinal hemorrhage revealed that all of those with normal renal function had elevated serum calcium levels. Because of the increased mortality associated with gastrointestinal hemorrhage in renal transplant patients (43%), patients prone to development of hypercalcemia may benefit from early subtotal parathyroidectomy.

Adult↗

Prediction of response to cancer chemotherapy.

Cytotoxic chemotherapy plays a key role in the treatment of carcinoma for thousands of patients annually who either present with metastatic disease or relapse after surgical excision of apparently localised disease. Unfortunately, there is such a wide range of responsiveness to drug therapy within individual tumour types that response of an individual patient's tumour to cytotoxic therapy cannot be accurately predicted. Intensive efforts to increase the accuracy of selection of effective chemotherapy have recently culminated in an in vitro system which employs soft agar and standard laboratory tissue culture techniques to predict drug sensitivity and resistance for an individual patient's tumour with reasonable accuracy. Research in this system is being actively pursued at several centres and further modifications and refinements may well make cancer chemotherapy more precise than previously possible. This review surveys methods of studying in vitro drug sensitivity which have been tested and for which clinical correlations are available. The technique and results of the more recently developed human tumour stem cell assay and the potential applications of this system are also discussed.

Agar↗

Prospective clinical trial of a human tumor cloning system.

A prospective clinical trial was performed to evaluate the usefulness of a human tumor cloning system for selecting single-agent chemotherapy for patients with advanced cancers. Six hundred four single-agent trials were performed in the 470 patients whose tumors were submitted for drug sensitivity testing. Only 246 of these 604 trials (41%) could be directed by the cloning system results because of inadequate tumor growth and other difficulties. In these 246 prospective trials, there was a 60% true positive and an 85% true negative rate for predicting for response or lack of response of an individual patient's tumor to the single agent. There was also a relationship between the percentage of decrease in survival of tumor colony-forming units and the probability of a clinical response of the patient's tumor to the same drug used in vivo. Despite these encouraging findings, work to improve tumor growth and additional prospective clinical trials of the system are needed before the system can be recommended for routine clinical use.

Breast Neoplasms↗

Clonogenic assay and in vitro chemosensitivity testing of human urologic malignancies.

Over the past year, we have attempted to grow both primary and metastatic urologic malignancies using a recently developed human tumor cloning system. Formation of colonies in vitro occurred in 125 of 164 primary tumors (76%), including 34 of 47 uroepithelial cancer specimens, 45 of 50 renal cell cancer specimens, 24 of 33 prostatic cancer specimens, and 22 of 34 testicular cancer specimens. A large percentage of metastatic cancers have also been successfully cultured. Growth sufficient for chemosensitivity testing ranged from 43% of the uroepithelial cancers cultured to 64% of the renal cell cancer specimens cultured. When in vitro chemosensitivity testing was performed, the in vitro chemosensitivity results show a striking similarity to clinical response rates for the same agents used for these tumors. Overall the human tumor cloning system appears to be a reasonable model for the study of human urologic malignancies.

Acid Phosphatase↗

Serum and bone marrow radioimmunoassay of acid phosphatase in prostatic cancer.

Use of radioimmunoassay (RIA) for determinations of prostatic acid phosphatase has recently received considerable attention because of reported higher sensitivity and specificity than previous enzymatic assays. We have compared the sensitivity and specificity of a commercially available RIA to a highly specific enzymatic assay (thymolphthalein monophosphate) using 37 patients with prostatic cancer and 34 patients with surgically proved benign prostatic hyperplasia. Seventeen of the cancer patients and all 34 of the BPH patients were studied prospectively. We further evaluated specificity by performing the RIA on 25 specimens of bone marrow from patients with nonprostatic disease. Our results indicate the radioimmunoassay is not, at this time, an adequate screening tool, and we question its accuracy in staging patients anymore reliably than by enzymatic assay.

Acid Phosphatase↗

Application of the mixed cell agglutination test for cell surface antigens to renal cell carcinoma.

The mixed cell agglutination test is used to demonstrate the presence or absence of the A, B and H(O) blood group antigens on the surface of superficial bladder tumors. Absence of these antigens has been shown to correlate well with invasive disease. Therefore, the test has an important prognostic value in bladder cancer. To determine its clinical value in patients with renal cell carcinoma the mixed cell agglutination test was done on unstained sections of tumor from 42 patients for whom followup was available. Red cell adherence was determined independently by each of us and without knowledge of the clinical status of the patients. Only 3 tumors were graded negative, while 14 were each 2 and 3 plus, and 11 were 4 plus. Tumor stage and patient blood type did not correlate with the degree of agglutination. Over-all survival did correlate significantly with 4 plus agglutination (p less than 0.041) as did 1 and 5-year survival (p less than 0.049 and 0.046, respectively). All 11 patients whose tumors had 4 plus reactions are alive, with a median followup of 5.0 years. Currently, there is little to offer the patient who has metastatic disease or is at high risk for its development after nephrectomy. Our preliminary report suggests some degree of accuracy in predicting the latter group by excluding those at low risk. Further studies would seem warranted so that the mixed cell agglutination test might be applied when better adjuvant therapy is discovered.

ABO Blood-Group System↗