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Biomedical subjects

S Bruno

Publications and source records attributed to S Bruno.

At least 145 records · Page 8Linked to original sources
PubMed1983

Enhancement of T lymphocyte proliferative response to mitogens by indomethacin in breast and colorectal cancer patients.

The present study confirms previous observations that in vitro T lymphocyte proliferative response to mitogens is depressed in only some untreated patients with advanced or metastatic breast and colorectal cancer. Indomethacin, a prostaglandin synthetase inhibitor, at 1.0 microgram or 0.1 microgram/ml concentration significantly enhances the PHA, Con A or PWM response in these patients with breast and colorectal cancer (P less than 0.05 - P less than 0.01). Indomethacin has no mitogenic activity. Ethyl alcohol (0.01%), in which indomethacin is dissolved, also has no mitogenic or cytotoxic activity. Although the in vitro effect of indomethacin has been well-demonstrated, the in vivo effect of this agent on cell-mediated immunity in man has not yet been thoroughly investigated and thus, further studies of the effect of indomethacin administration on in vivo and in vitro cellular immunity seem warranted.

Adult↗
PubMed1982

Current status of clinical trials of m-AMSA, dihydroxyanthracenedione, and deoxycoformycin.

The current status of three drugs of clinical interest to the National Cancer Institute is reviewed. m-AMSA, a drug with a wide spectrum of activity in murine tumors, is now in phase II trial and has shown itself to have a high order of activity in acute nonlymphocytic leukemia. Dihydroxyanthracenedione, a compound with some of the characteristics of anthracyclines but with no cardiac toxicity in animal toxicology studies, is in phase I evaluation. Deoxycoformycin, an adenosine analog which is a potent inhibitor of adenosine deaminase, has shown moderate activity in acute leukemia patients in phase I trials, and has the potential to produce synergistic antitumor toxicity when used with arabinofuranosyladenine.

Adenosine Deaminase Inhibitors↗
PubMed1982

Phase I study of high-dose methotrexate with thymidine and low-dose leucovorin.

A total of 15 patients with advanced neoplastic disease, 13 with different solid tumors, one with lymphoma, and one with acute lymphocytic leukemia, underwent treatment consisting of continuous infusion of methotrexate (2 g/sq m/day) with concomitant thymidine (8 g/sq m/day) and leucovorin (1 mg/sq m/day). The dose of methotrexate was increased progressively by lengthening the methotrexate infusion from 2 to 7 days. After cessation of methotrexate infusion, thymidine and leucovorin were continued until the plasma level of methotrexate decreased to 2 X 10(-8) M. Toxicity was mucositis (23 of 27 evaluable courses), leukopenia (15 of 26 evaluable courses), thrombocytopenia (10 of 26 evaluable courses), renal and hepatic toxicity and diarrhea. Plateau levels of plasma methotrexate or methotrexate plasma half-life did not correlate with toxicity.

Adult↗
PubMed1982

Phase I trial and pharmacokinetics of a daily x 5 schedule of 3-deazauridine.

The uridine analog 3-deazauridine has been given to 19 patients in a phase I and pharmacokinetic study. Only mild toxicity was seen at doses less than 1200 mg/m2/day for 5 days. At a dose of 1200 mg/m2/day x 5, leukopenia (mean wbc count nadir of 2650/mm3) was seen in nine of 12 patients and thrombocytopenia (mean platelet count nadir of 47,000/mm3) in five of 12 patients. Nausea and vomiting and oral toxicity were each seen in two patients, and diarrhea and skin toxicity occurred in one patient each. Pharmacokinetic studies indicate a biphasic plasma decay with a beta-half-life of 6.9 hours and urinary excretion, mostly of unchanged drug, as the most important route for drug elimination. A dose of 1200 mg/m2/day x 5 is recommended for phase II studies and great caution is advised in administering the drug in the presence of renal impairment.

3-Deazauridine↗
PubMed1982

Current status of chemotherapy, hormonal therapy, and immunotherapy in the treatment of renal cell carcinoma.

Renal cell carcinoma is an uncommon but lethal disease. Since many patients initially present with metastatic disease and/or fail primary local therapy, therapeutic alternatives are needed. In our review of single agents none emerge as uniformly effective, although a number of chemotherapeutic agents are somewhat active, as is the hormonal agent, medroxyprogesterone. Combination chemotherapy, with and without hormonal agents and immunotherapeutics, appears to be somewhat more active, with several reports of CRs. Immunotherapeutic agents alone show promise in the limited studies reported to date. Several studies are now in progress, attempting to study new agents and combinations in this disease. Physicians are urged to participate in these studies.

Adenocarcinoma↗
PubMed1982

Phase II study of 3-deazauridine in advanced colorectal adenocarcinoma.

A phase II study of 3-deazauridine (DAUR) showed poor activity in previously treated patients with advanced colorectal adenocarcinoma. There were no responses among 15 patients treated on a dose schedule of 1200 mg/m2/day for 5 days repeated at 3-week intervals. Toxicity included mild nausea and vomiting, occasional mucositis, diarrhea, and dizziness. A minimal degree of myelosuppression was observed.

3-Deazauridine↗
PubMed1982

PCNU: a new nitrosourea in clinical oncology.

PCNU is a new nitrosourea compound which has recently entered clinical trials. Preclinically it has been found to be effective against a variety of tumor models. Biochemically, PCNU was found to have optimal lipophilic, alkylating, and carbamoylating properties as compared to other nitrosourea agents. PCNU is able to diffuse into the CSF as demonstrated by pharmacokinetic studies. Clinical phase I studies indicate that the main toxicity is myelosuppression; nausea and vomiting were less frequently observed with PCNU than with other nitrosourea compounds. Human antitumor activity has been reported in a number of tumors, but most consistently in brain tumors. Phase II studies are now underway to confirm the antitumor activity of PCNU.

Animals↗
PubMed1981

Hypersensitivity reactions to cancer chemotherapeutic agents.

Hypersensitivity reactions from cytotoxic agents have not been accorded much attention. Certain drugs (L-asparaginase, cisplatin, intravenous melphalan, topical mechlorethamine, zinostatin, and teniposide) produce reactions often enough to be a clinical problem. Others (cyclophosphamide, doxorubicin, daunorubicin, methotrexate, and procarbazine) do so only occasionally. Bleomycin uniquely produces an occasional hyperpyrexic reaction with clinical findings similar to anaphylaxis. Some cytotoxic agents have never been known to produce hypersensitivity reactions. This paper reviews the frequency and clinical information about such reactions, factors augmenting or decreasing the frequency, and, where possible, the etiologic mechanisms.

Alkylating Agents↗
PubMed1981

Indications for cholecystectomy in ligation of the hepatic artery.

Ligation of the hepatic artery has been successfully used in the management of massive bleeding, secondary to hepatic trauma, and in the treatment of metastatic neoplastic disease. The indications for a concomitant cholecystectomy are less well defined. It is generally accepted that cholecystectomy should be performed when ligation is used to control bleeding. In our study, ligation of the hepatic artery was performed, leaving the gallbladder in situ. At autopsy, no pathologic process could be detected in the gallbladder. Microscopic analysis showed fibrosis in the mucosal surface, mild chronic inflammation and nonspecific mononuclear infiltration. We conclude that the changes are insufficient to warrant the removal of a normal gallbladder when ligation of the hepatic artery is performed as treatment for neoplastic disease.

Adult↗
PubMed1981

ICRF-187 in clinical oncology.

Although the mechanism of action of ICRF-159 and 187 has not been clearly defined, it is evident from both preclinical and early clinical studies that these compounds are of interest. There are three distinct characteristics of these ICRF compounds that deserve careful clinical evaluation. First, these drugs are apparently alkylating agents with modest, predictable and noncumulative bone marrow toxicity that makes them good potential candidates for combination chemotherapy regimens. The second characteristic that should be investigated is the suggestion that combination of ICRF-187 with an anthracycline may ameliorate the cardiac toxicity of the latter. The third factor in the preclinical evaluation of the bis-diketopiperazines that may have clinical application is the evidence that suggests that these drugs have an antimetastatic effect.

Animals↗
PubMed1981

2'-deoxycoformycin. A new anticancer agent.

2'-deoxycoformycin (2'-dCF) is a powerful inhibitor of adenosine deaminase (ADA), an enzyme found in high concentrations in lymphoid tissue. Although inactive in preclinical tumor models, 2'-dCF has shown clinical antitumor activity as a single agent in lymphoid malignancies. This drug has the added potential of being useful as a potentiator of other antitumor agents which are deactivated by ADA. It is also possible that the drug has potential as an immunosuppressive agent. Phase I studies are ongoing and phase II trials are planned to define the antitumor spectrum of this agent.

Animals↗
PubMed1981

Current status of chemotherapy in the treatment of advanced carcinoma of the thyroid gland.

An extensive review of the literature was undertaken to identify single agents and chemotherapeutic combinations active against advanced thyroid carcinoma. The two most intensively studied agents were Adriamycin and bleomycin, both of which appear to have definite activity against advanced disease. Studies of 25 other single agents and 17 drug combinations were also reviewed but most of the studies suffered from extremely poor patient accrual, thus precluding statistical analysis. Two cooperative group protocols are in progress which will hopefully accrue enough patients for meaningful interpretation. Physicians treating advanced thyroid carcinoma patients are urged to participate in these studies.

Drug Therapy, Combination↗
PubMed1981

Acivicin. An antitumor antibiotic.

Acivicin [(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid; AT-125; NSC-163501] is a fermentation product of Streptomyces sviceus which is active in a variety of mouse tumor models including the L1210 and P388 leukemias, the M5076 ovarian carcinoma, and the MX-1 human breast tumor xenograft. Antitumor activity is probably mediated through the inhibition of enzymes catalyzing amido transfer from L-glutamine, especially CTP synthetase and XMP aminase. In mice, acivicin is absorbed systemically via the p.o., I.P., and S.C. routes and is predominantly excreted in the urine in unchanged form. Although a wide variety of toxicities, including myelosuppression, were noted in dogs and monkeys, vomiting, diarrhea, and pathologic lesions of the GI tract predominated in both species. A marked cumulative toxicity was noted in dogs with 16 mg/m2/day being the lethal dose on the daily x 5 schedule compared to 1000 mg/m2 on the single-dose schedule. An interesting phenomenon was noted in mice wherein older male mice were more resistant to the toxic effects of the drug than female or younger male mice. This sex and age difference in susceptibility to acivicin toxicity was shown to be correlated with differences in pharmacokinetics; older male mice cleared acivicin at approximately twice the rate of females or younger males. No sex differences in toxicity were noted in dogs or monkeys. Because of its activity in mouse tumor systems and acceptable preclinical toxicology patterns, the drug is being introduced into clinical phase I studies under the sponsorship of the National Cancer Institute.

Animals↗