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Biomedical subjects

D L Lamm

Publications and source records attributed to D L Lamm.

At least 91 records · Page 5Linked to original sources

Rapid screening of potential human bladder carcinogens: genotoxicity in meiosis repair deficient Drosophila melanogaster.

To find a quick screen of potential bladder carcinogens, a genotoxicity test in Drosophila melanogaster stocks containing DNA repair mutations was evaluated. Meiosis repair deficient male Drosophila melanogaster mei-9, mei-41, and the double mutant mei-9-41 were allowed to mate with attached -x females on media containing the test agent. Genotoxic agents produce DNA damage which accumulates and can be lethal in mei males, whereas the attached -x females are able to repair the damage and survive. Thus, the sex ratio of the progeny is a measure of genotoxicity which can be correlated with mutagenicity and carcinogenicity. In this study, tea, coffee, and saccharin were not genotoxic (p greater than 0.3). Dose dependent toxicity was observed in bracken fern (p less than 0.001). The known mutagen and bladder carcinogen, cyclophosphamide, was highly genotoxic (p less than .001). Drosophila genotoxicity not only permits rapid screening of mutagens, but may also have advantages over other systems in the screening of potential bladder carcinogens.

Animals↗

A practical guide to the use of intravesical BCG for the management of stage Ta, T1, CIS, transitional cell cancer.

Intravesical instillations of BCG are effective in preventing tumor recurrence, eliminating existing tumor and treating CIS in a substantial number of patients. As with any type of therapy, side effects can occur. Because a live organism is being used, care must be taken in the handling and administration of the product. Patients should be informed about the common types of reactions so that these may be reported to the urologist. In turn, the urologist must decide if the treatment plan needs to be modified or the patient started on medications which can prevent or reduce the severity of the side effects. At times a decision must be made regarding withholding or delaying treatment and there are situations when BCG should be stopped.

Administration, Intravesical↗

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↗

Androgen receptors in biopsy specimens of prostate adenocarcinoma. Heterogeneity of distribution and relation to prognostic significance of receptor measurements for survival of advanced cancer patients.

Needle biopsy specimens of primary adenocarcinoma and surgical specimens of carcinomatous nodal tissue were obtained from previously untreated clinical D stage prostatic adenocarcinoma patients. Assessment of the relation between specimen androgen receptor site content and survival using either scatterplots or Kaplan-Meier analyses showed specimen receptor content was a poor prognostic P greater than 0.1, of survival subsequent to orchiectomy or diethylstilbestrol (DES) therapy. The possibility that heterogeneity of specimen androgen receptor site content contributed to this finding was evaluated by comparing receptor content of multiple small or large tissue specimens from the same prostate gland of patients with benign prostatic hyperplasia or nonmetastatic prostatic cancer. This evaluation showed significant microheterogeneity of human prostate androgen receptor site content which was substantially masked in large tissue specimens. We conclude that microheterogeneity of human prostate androgen receptor site content compromises the use of biopsy specimen androgen receptor measurements as a prognostic of patient survival subsequent to initiation of hormonal therapy.

Adenocarcinoma↗

Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide.

Recent evidence suggests a role for both immunotherapy and chemotherapy in the treatment of transitional cell carcinoma. Glucan, a derivative of the cell wall of Saccharomyces cerevisiae and a potent immunostimulant, was used in combination with cyclophosphamide for treatment of implanted murine transitional cell carcinoma (MBT 2). Cyclophosphamide prevented tumor appearance when tumor burden was low and decreased tumor growth rate in larger tumor volumes, but was unable to eradicate established tumors. Glucan did not reduce tumor incidence but decreased animal mortality. These experimental observations may correlate well with clinical evidence and suggest future clinical use of these agents.

Animals↗

Immunological assessment of renal cancer patients as evaluated by the lymphocyte adherence inhibition test.

The lymphocyte adherence inhibition test was used to evaluate tumor immunity toward 2 types of soluble renal cancer antigens extracted from 3 different renal cancer specimens. These extractions were accomplished with either 3 molar potassium chloride or 2.5 per cent butanol, and were tested in 23 patients with renal cancer, 8 with benign renal disease and 9 with bladder cancer. In 62 tests of lymphocyte adherence inhibition reactivities toward 3 molar potassium chloride in renal cancer patients the mean value of lymphocyte adherence inhibition reactivity (32.7 +/- 15.4 per cent) was significantly greater compared to that observed in 20 examinations in patients with benign renal disease (17.6 +/- 9.4 per cent, p less than 0.001) and 24 tests in bladder cancer patients (15.4 +/- 4.4 per cent, p less than 0.001). With a lymphocyte adherence inhibition index of greater than 20 per cent as a positive response, there were 50 true positive findings (81 per cent) in the renal cancer group, while the combined benign renal disease and bladder tumor groups had 34 true negative responses (77 per cent). With the butanol extract the mean lymphocyte adherence inhibition reactivity of the 62 tests done on renal cancer patients (38.9 +/- 10.8 per cent) was significantly greater than either control group (7.1 +/- 6.2 per cent, p less than 0.001 for benign renal disease and 5.9 +/- 2.6 per cent, p less than 0.001 for bladder tumor). Moreover, of 62 tests done on renal cancer patients 59 (95 per cent) had true positive responses, while 43 of the 44 tests (98 per cent) in the combined control group showed true negative findings. These results suggest that immune responses in renal cancer can be assessed with the lymphocyte adherence inhibition test, and they may be useful in the diagnosis and management of renal cancer patients.

Adult↗

Serum lymphocyte adherence inhibition test in bladder cancer patients.

In 29 patients with a history of bladder cancer cystoscopic determination of tumor status was correlated with the results of a serum modified capillary tube lymphocyte adherence inhibition test. With donor lymphocytes from 3 healthy volunteers as indicator cells, patient sera were added to a butanol extract of the T-24 tissue-cultured bladder carcinoma cell line. Lymphocyte adherence inhibition of more than 15 per cent was selected as positive. Mean values for 17 cases positive for tumor were 26.6 +/- 14.1 per cent compared to 10.0 +/- 6.8 per cent for 18 cases negative for tumor. False positive and false negative values at this cutoff averaged 19 and 14 per cent, respectively, and there was no significant difference in the individual results of the 3 donor leukocytes. Serial examinations of 6 patients had lymphocyte adherence inhibition values consistent with the changes in tumor status. These results suggest that the serum lymphocyte adherence inhibition test correlates well with clinical tumor status and, therefore, may serve as a useful tumor marker in patients with bladder cancer.

Adult↗

Complications of bacillus Calmette-Guerin immunotherapy in 1,278 patients with bladder cancer.

Our series of 195 patients, plus 134 reported on in the literature and 949 reviewed by various physicians provide 1,278 patients for review of bacillus Calmette-Guerin therapy complications. Cystitis occurred in 91 per cent of the patients. Complications identified included fever more than 103F in 50 patients (3.9 per cent), granulomatous prostatitis in 17 (1.3 per cent), bacillus Calmette-Guerin pneumonitis or hepatitis in 12 (0.9 per cent), arthritis or arthralgia in 6 (0.5 per cent), hematuria requiring catheterization or transfusion in 6 (0.5 per cent), skin rash in 5 (0.4 per cent), skin abscess in 5 (0.4 per cent), ureteral obstruction in 4 (0.3 per cent), epididymo-orchitis in 2 (0.2 per cent), bladder contracture in 2 (0.2 per cent), hypotension in 1 (0.1 per cent) and cytopenia in 1 (0.1 per cent). Most of the severe irritative side effects and subsequent systemic complications can be prevented with prophylactic isoniazid given for 3 days, beginning the morning of treatment. Patients with life-threatening systemic bacillus Calmette-Guerin infection or anaphylaxis should receive 500 mg. cycloserine twice daily for 3 days in addition to combination antituberculous therapy because the rapid action of this drug may be life-saving. Direct intralesional bacillus Calmette-Guerin immunotherapy can produce sepsis and death, and should be avoided but intravesical bacillus Calmette-Guerin generally is well tolerated and has produced no complication in more than 95 per cent of the patients treated.

Biological Products↗

A trial of bacillus Calmette-Guérin versus adriamycin in superficial bladder cancer: a South-West Oncology Group Study.

One hundred and sixty-one evaluable patients with biopsy-confirmed transitional cell carcinoma of the bladder were studied in a cooperative protocol comparing intravesical BCG and adriamycin. Patients have been followed for 2-25 months (median 15.7 months) with cystoscopy at 3-month intervals, urinary cytology, and bladder biopsy. Sixteen of 88 patients (19%) who received BCG immunotherapy developed tumor recurrence compared with 45 recurrences (54%) in the 83 patients who received adriamycin chemotherapy (p less than 0.001, chi 2). Eighty-nine of the randomized patients had documented carcinoma in situ. The complete response rate in 41 patients with carcinoma in situ who received BCG was 85%, compared with a complete response rate of only 39% in 46 patients who received adriamycin (p less than 0.001, chi 2). These data suggest that BCG immunotherapy is superior to adriamycin chemotherapy in the prevention of recurrent superficial transitional cell carcinoma and the treatment of in situ carcinoma of the urinary bladder.

Administration, Intravesical↗

Bacillus Calmette-Guerin immunotherapy for bladder cancer.

Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. While the optimal protocol for bacillus Calmette-Guerin remains to be determined, experience with 92 randomized and 30 nonrandomized (high risk) patients followed for up to 5 years provides information that may improve future protocols. Side effects of bacillus Calmette-Guerin are observed to increase with increasing frequency and duration of treatment. The protection from tumor recurrence has persisted: only 6 of 30 patients (20 per cent) treated with bacillus Calmette-Guerin have had recurrent tumor compared to 14 of 27 controls (52 per cent, p equals 0.008, chi-square test), and mean time to recurrence increased from 24 to 48 months (p less than 0.005, Savage). Skin test reactivity to purified protein derivative is particularly useful in predicting response to bacillus Calmette-Guerin immunotherapy. Currently, 60 patients have been randomized to receive bacillus Calmette-Guerin immunotherapy and only 1 of 22 patients (4.5 per cent) in whom the purified protein derivative skin test results converted from negative to positive has had recurrent tumor, compared to 12 recurrences (32 per cent) in patients whose skin tests were positive before treatment or failed to convert following treatment (p equals 0.014, chi-square). Seven recurrences (33 per cent) developed in 21 patients whose skin tests remained negative (p equals 0.015) and 5 recurrences (29 per cent) developed in 17 patients whose tests previously were positive (p equals 0.068, Fisher's test, not significant). The benefit of percutaneous bacillus Calmette-Guerin is suggested by the observations that the recurrence rate in patients treated with intravesical bacillus Calmette-Guerin alone is 40 per cent, and all 7 patients whose purified protein derivative skin tests were negative continued to have negative results when percutaneous bacillus Calmette-Guerin was omitted (p equals 0.003). Among high risk patients a marked decrease in or complete prevention of recurrent tumor was observed in 82 per cent of 22 patients treated previously with chemotherapy and 11 of 14 (78 per cent) with carcinoma in situ have had a complete response.

Aged↗