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I Tannock

Publications and source records attributed to I Tannock.

46 records · Page 3Linked to original sources
PubMed1982

Response of aerobic and hypoxic cells in a solid tumor to adriamycin and cyclophosphamide and interaction of the drugs with radiation.

I have assessed the relative sensitivity of aerobic and hypoxic cells to Adriamycin (ADR) and cyclophosphamide (CY) in the drug-sensitive murine 16/C tumor. The end point used was tumor response to subsequent radiation given under aerobic or acutely hypoxic conditions. Delay in tumor growth following 15 gray radiation alone to approximately 0.4 g tumors was about 3 days longer after aerobic than after hypoxic radiation. Prior treatment with CY had little effect on this difference, implying little selectivity of CY for killing aerobic or hypoxic cells, and the effects of CY and radiation were additive. Treatment with ADR abolished the difference in response to aerobic and hypoxic radiation given from 0.5 to 2 hr after the drug, suggesting that most of the cells which survived treatment with ADR were hypoxic. Difference in response to aerobic and hypoxic radiation at 6 to 24 hr after ADR was equal to or greater than that in non-drug-treated mice, implying rapid reoxygenation after ADR. Experiments on small, nonpalpable tumors with a low proportion of hypoxic cells showed that ADR was slightly more effective than against larger tumors and that some aerobic cells were spared by the drug when the hypoxic fraction was small. Misonidazole is known to be selectively toxic for hypoxic cells, and a high dose of misonidazole gave a small increase in antitumor effects of ADR without increased toxicity. My results suggest that ADR (but not CY) may spare hypoxic cells in a solid tumor and are consistent with limited diffusion of ADR from tumor blood vessels.

Aerobiosis↗
PubMed1978

Cell kinetics and chemotherapy: a critical review.

The paper reviews methods of studying cell kinetics in man, cell population kinetics of human tumors and bone marrow, drug interactions and the cell cycle, and possible applications to chemotherapy. The conclusions drawn are: (1) Cell cycle time and S-phase duration for proliferating granulocyte precursors in human bone marrow are poorly defined but are probably shorter than median values for most human tumors, including leukemia. (2) Most drugs have greater toxicity for cycling cells and some variation in toxicity at different phases of the cell cycle. There is a special need for chemotherapy directed at slowly proliferating and hypoxic tumor cells. (3) Pretreatment indices of tumor cell kinetics are of little value in choosing drugs or in predicting response. (4) Experiments in animals have demonstrated that therapeutic index may depend on schedule. Knowledge of cell kinetics in animals rarely allows prediction of the optimal schedule and is unlikely to do so in man. Optimal schedules in mice are not directly relevant to man. (5) Measurement of tumor labeling index or DNA histogram by flow microfluorimetry to detect cell synchrony is of little benefit in scheduling if concurrent changes in bone marrow are ignored; these methods are invalid at short intervals after treatment because surviving clonogenic cells are indistinguishable from a larger number of drug-damaged cells prior to their lysis. (6) The major factor determining the outcome of chemotherapy is the availability of drugs with activity for the tumor and acceptable host toxicity. Claims that complex schedules using several drugs are effective because of synchrony or kinetic differences of tumor and normal tissue are at present unsubstantiated.

Animals↗
PubMed1970

Cell proliferation in human melanoma.

The cytokinetics of subcutaneous metastases in five patients with melanoma was studied. Multiple simultaneous biopsies following pulse labeling with tritiated thymidine were performed in one patient. There was relatively uniform labeling and mitotic indices among these. Within the individual tumors, there was some variation in the labeling index with small clusters of tumor cells having significantly higher labeling indices than more sparsely infiltrating tumor cells. Repetitive biopsies following pulse labeling were performed in two patients. The per cent labeled mitosis curves were similar in the two patients. By computer analysis a median G(2) period of 5.3 hr and an S period of 21 hr were obtained. The generation time (T(e)) was highly variable with a median of 3 days. This T(e) was consistent with that calculated from grain count studies in these patients. Two patients received either intermittent or continuous tritiated thymidine over a 10-20 day period. Analysis of the labeling index curve by computer fitting indicated a growth fraction of 20-30%. The growth fraction calculated by other indirect methods was consistent with the computer analysis. The potential tumor doubling time as calculated from the T(e) and growth fraction was much shorter than the actual doubling time indicating that cell loss was approximately 70% of the rate of cell production.

Adult↗
PubMedDate not supplied

Misonidazole increases the toxicity of BCNU for hypoxic cells.

Misonidazole (MISO) increased the toxicity of BCNU for hypoxic Chinese Hamster Ovary (CHO) cells in vitro, but had no effect on aerobic toxicity of BCNU. Survival was reduced by up to 10(-3) with an exposure to MISO (ImM x 4 hr) that had no direct toxicity for hypoxic cells. Preincubation of cells with MISO under hypoxic conditions followed by exposure to BCNU in air also resulted in increased toxicity. Related effects were observed when CHO cells were exposed to serum from mice that had received BCNU alone or BCNU + MISO: hypoxic (but not aerobic) cells were more sensitive to serum from mice that had received combined treatment. Studies showed that BCNU was more toxic in serum-free medium and that MISO had little or no effect on BCNU toxicity for hypoxic cells in the absence of serum. High performance liquid chromatography (HPLC) methods showed that BCNU decays with T 1/2 = 0.5 hr in the presence of 10% fetal calf serum and T 1/2 = 1.0 hr in the absence of serum, but the decay curves were not influenced by hypoxia or by MISO. BCNU metabolism to active intermediates is known to be catabolized by albumen. The dependence of the interaction of BCNU and MISO on both serum and hypoxia is consistent with an effect of a hypoxic product of MISO metabolism to delay catabolism or excretion of protein-catalyzed active intermediates of BCNU.

Animals↗