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Biomedical subjects

T S Herman

Publications and source records attributed to T S Herman.

At least 127 records · Page 7Linked to original sources
PubMed1981

Reversal of resistance to methotrexate by hyperthermia in Chinese hamster ovary cells.

Our Chinese hamster ovary cells are extremely resistant to methotrexate (MTX) (100% survival after 500 microgram/ml for 13 hr). However, exposure to 43 degrees (but not 41 degrees or 42 degrees) for 1 hr sensitizes the cells to MTX so that a 50% cell kill in excess of that due to hyperthermia occurs. Treatment of cells at 43 degrees increases net MTX uptake by about 30% at 30 min but causes a substantial reduction after 1 hr. This negative effect is greater in cells continually heated at 43 degrees than in those exposed for only 1 hr. Treatment at 43 degrees for 1 hr also markedly increases efflux of MTX out of cells over the that 2 hr. Dihydrofolate reductase activity was found to decrease to about 50% of control values by 4 to 5 hr after exposure to 43 degrees. The biological half-life of dihydrofolate reductase in Chinese hamster ovary cells was determined to be about 4.5 hr, indicating that hyperthermia-induced cessation of protein synthesis may explain both the decrease in dihydrofolate reductase activity and the sensitization to MTX observed with heat exposure. In scheduling experiments, lethality due to exposure to 43 degrees for 1 hr in conjunction with MTX was maximum when 1-hr drug exposure began just at the end of heat treatment.

Animals↗
PubMed1980

Phase I clinical trial f mitoxantrone: a new anthracenedione anticancer drug.

Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia (but not neutropenia or thrombocytopenia) occurred in four of six patients given 4 mg/m2/week after a mean of 2.75 doses (range, 2-4 doses) and in all three patients given 5 mg/m2/week after three doses. Only one patient had mild nausea and vomiting. No patient experienced alopecia or mucositis, and none showed evidence of any cardiac, renal, hepatic, or pulmonary abnormality. Mitoxantrone treatment induced two partial remissions (patients with metastatic squamous cell carcinomas of the hypopharynx and rectum) and one mixed response (patient with gastric carcinoma). For phase II studies the starting dose, when used on a weekly schedule, should be 5 mg/m2 in patients who are known to have adequate bone marrow reserve.

Aged↗
PubMed1979

Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy.

Two double-blind, crossover trials comparing the antiemetic effectiveness of nabilone, a new synthetic cannabinoid, with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy. Of 113 patients evaluated, 90 (80 per cent) responded to nabilone therapy, whereas only 36 (32 per cent) responded to prochlorperazine (P less than 0.001). Complete relief of symptoms was infrequent, occurring only in nine patients (8 per cent) given nabilone. When both drugs were compared, both nausea (P less than 0.01) and vomiting episodes (P less than 0.001) were significantly lower in patients given nabilone. Moreover, patients clearly favored nabilone for continued use (P less than 0.001). Predominant side effects noted by patients were similar for both agents and included somnolence, dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone. In addition, four patients (3 per cent) taking nabilone had side effects (hallucinations in three, hypotension in one) that required medical attention. Euphoria associated with nabilone was infrequent (16 per cent) and mild.

Adolescent↗
PubMed1979

Patterns of relapse in patients with small cell carcinoma of the lung treated with adriamycin-cyclophosphamide chemotherapy and radiation therapy.

Twenty-seven patients with small cell carcinoma of the lung were treated sequentially with induction chemotherapy (adriamycin and cyclophosphamide), radiation therapy (chest and whole-brain), and then maintenance chemotherapy for 2 years. Twenty responding patients were followed to relapse and patterns of recurrence were observed. This combined treatment resulted in a complete remission rate of 80% and a median survival of 565 days in limited-disease patients. Relapse overwhelmingly occurred in the chest, but patients receiving higher-dose radiation (4000-4500 rads in split-course) had a significant prolongation of time to recurrence compared to patients receiving 3000 rads in a single course of radiation (540 versus 270 days). Despite a long mean survival, only one limited-disease patient relapsed outside of the brain or chest, suggesting that chemotherapy had a good protective effect against micrometastatic disease. Three patients relapsed in the brain at 330, 450, and 520 days, suggesting that in future studies the prophylactic whole-brain radiation (3000 rads) should be intensified.

Carcinoma, Small Cell↗
PubMed1978

Systematic restaging in patients with Hodgkin's disease: a Southwest Oncology Group Study.

Eighty-two patients with advanced Hodgkin's disease who were in apparent complete remission (CR) after receiving 10 courses of combination chemotherapy were systematically reevaluated for persisting disease. Occult Hodgkin's disease was found in 10 (12%) of these patients and was predominantly present in nodal sites (91%) which were known to have been involved at initial staging (100%). Repeat chest radiography, Gallium-67 tumor scanning and lymphography were the most helpful procedures for detecting residual disease. Nine of the 72 (13%) patients felt to be free of disease after negative restaging subsequently relapsed within 8 months. Sites of early relapse, like the sites of disease found at restaging, occurred almost always in previously involved nodal areas. We conclude that systematic restaging should be incorporated into subsequent lymphoma trials in order to define more clearly complete remission and that every patient treated for lymphoma should undergo a careful restaging evaluation before therapy is discontinued.

Adult↗
PubMed1977

Nabilone: a potent antiemetic cannabinol with minimal euphoria.

Nabilone is a cannabinol derivative which has potent central antiemetic effects in animals. We observed that the drug significantly reduced the nausea and vomiting induced by cancer chemotherapy in 10 of 13 patients who were refractory to conventional antiemetics. A dose-response effect was apparent. The drug was generally well-tolerated, although it also had sedative effects. Additionally, dizziness, decreased coordination and postural hypotension were observed in some patients. Euphoric effects of the agent were minimal at antiemetic dosage levels.

Adolescent↗
PubMedDate not supplied

Selective cytotoxicity of 3-amino-L-tyrosine correlates with peroxidase activity.

In the presence of 3-amino-L-tyrosine (3-AT), abundant brown pigment forms in human HL-60 cells, but not in a variety of other cell lines, which are reported to be lower in mean myeloperoxidase (MPO) content than HL-60. Cells were assessed for peroxidase activity with an ABTS-based colorimetric assay and compared to values obtained with known amounts of human myeloperoxidase. HL-60 cells were estimated to contain the equivalent of 37.1 ng myeloperoxidase/10(6) cells versus 26.1 and 5.0 ng/10(6) cells for human K562 and murine RAW 264.7 cell lines, respectively. HL-60 cells exhibited a nearly 60% inhibition of proliferation and > 70% reduction in cell viability after 4 d of culture in the presence of 100 microg 3-AT per ml. Higher concentrations of 3-AT (up to 400 microg/ml) for 4 d reduced HL-60 proliferation by 80% and decreased viability to 1-3%. Comparable levels of cytotoxicity were achieved in KG-1 cells after 7 d with 200 or 400 microg 3-AT per ml. K562 cells exhibited a 40% reduction in cell number after 7 d with 400 microg 3-AT per ml, but concentrations less than 400 microg/ml did not significantly affect K562 proliferation. K562 viability remained unchanged with doses of 3-AT up to 400 microg/ml. RAW 264.7 cells exhibited unchanged viability and proliferation in the presence of 3-AT at concentrations up to 400 microg 3-AT per ml. K562, KG-1, and RAW 264.7 cells exhibited no evidence of brown pigment formation in the presence of 3-AT and medium containing 10% fetal bovine serum. However, RAW 264.7 cells that were converted to protein-free medium and exposed to 3-AT exhibited intense brown pigment in some cell nuclei. A high percentage of HL-60 cells treated with 3-AT exhibited membrane blebbing, pyknosis, and nuclear fragmentation, which was not observed among other 3-AT-treated cell lines. A mechanism involving toxic intermediates of peroxidase-mediated "aminomelanin" formation is hypothesized.

Animals↗
PubMedDate not supplied

Interaction of hyperthermia with Taxol in human MCF-7 breast adenocarcinoma cells.

Hyperthermia treatments (43 degrees C, 1 h) were performed on exponentially growing MCF-7 breast adenocarcinoma cells at the beginning, middle, or end of 24 h incubations of the cells in vitro with Taxol (paclitaxel). When the cells were heated at the beginning or middle of the Taxol incubation, the hyperthermia treatment protected against the toxic effect of each of the Taxol concentrations examined (5, 10 and 100 nM). Consistent with earlier studies, Taxol treatment at 37 degrees C resulted in an accumulation of greater than 94% of the cells in G2/M at 24 h. Heating the cells at the middle or end of the Taxol treatment resulted in a similar accumulation. However, heat treatment during the first hour of Taxol exposure resulted in a significantly smaller percentage of cells (approximately 50%) in G2/M. HPLC analysis showed that at 37 degrees C, Taxol uptake into MCF-7 cells approached maximum within 0.25 h and increased only slightly more over the next 11.75 h. The parental Taxol level was markedly lower by 24 h. In contrast, 1 h hyperthermia treatments at the beginning or middle of the Taxol incubation resulted in higher Taxol concentrations at 12 and 24h, and higher intracellular concentrations overall than at 37 degrees C. These results indicate that hyperthermia inhibits Taxol related cell cycle effects and cytotoxicity, in spite of causing higher concentrations of Taxol to be present in heated cells.

Adenocarcinoma↗