A simple technique for maintaining low oxygen concentrations (0.1-20%) is described. These conditions were then used to study the effect of oxygen on colony growth of neoplastic cells in soft-agar. Physiologically low oxygen concentrations (0.1-10%) compared to 20% O2 were found to enhance plating efficiency and colony size of tumour cells. The optimal oxygen concentration for plating efficiency varied with tumour studied and may be as low as 0.1%. Having established that tumour cell colonies will grow better at 0.1-10% O2 compared to 20% O2, the mechanism by which this enhancement occurs was investigated. Observations on the effect of free radical scavengers and superoxide dismutase on plating efficiency of Ehrlich's ascites tumour cells suggests that this phenomenon occurs through oxygen toxicity mediated by superoxide anion.

Agar↗

PubMed1984

Eradication of cultured human melanoma cells by immune interferon and leukocytes.

For the determination of the conditions for the most effective cytolysis of human melanoma cells, leukocyte interferon (IFN-alpha), fibroblast interferon (IFN-beta), and immune interferon (IFN-gamma) were compared for their abilities to kill cultured human melanoma cells in the presence and absence of peripheral blood mononuclear leukocytes (PBL). A microassay was employed in which the viability of melanoma target cells was determined after various times of incubation with interferons alone or with PBL. On 7 human melanoma cell lines (from 6 different patients), IFN-gamma had significantly greater direct anticellular effect than IFN-alpha or IFN-beta. When PBL were added, all target cells were killed after 48 hours with IFN-gamma, but they were not killed with IFN-alpha or IFN-beta. When IFN-gamma was added to either IFN-alpha or IFN-beta, a potentiation of the anticellular effect was observed both with and without PBL. The actions of this "natural" IFN-gamma could be reproduced with recombinant IFN-gamma and could be neutralized by an antibody to a synthetic peptide encoded by the 5'-end of IFN-gamma complementary DNA. It was concluded that IFN-gamma is significantly more active against these human melanoma cell lines than either IFN-alpha or IFN-beta and, most significantly, that eradication can occur in the presence of IFN-gamma and PBL. Furthermore, synergistic anticellular action can be observed when IFN-gamma is added to IFN-alpha or IFN-beta. These findings point to the need for preclinical trials to evaluate eradication in vivo.

Cell Line↗

PubMed1984

Marked cytolysis of human tumor cells by interferon gamma and leukocytes.

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Animals↗

PubMed1984

Amelia with exomphalos major.

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Arm↗

PubMed1984

Learning as a function of haptic discriminability among items.

In Experiment 1, braille symbols for the letters A-J were found to be more haptically discriminable from one another than braille symbols for the letters K-T. In Experiment 2, subjects learned the names for the A-J symbols faster than for the K-T symbols. Experiment 3 demonstrated that faster learning of the names for the A-J than for the K-T symbols is attributable to characteristics of the symbol sets themselves (probably to the discriminability of the items from one another) and not to what they are called. The effects of discriminability on learning in these experiments are similar to those from experiments in which other modalities have been used.

Blindness↗

PubMed1983

Serum gamma glutamyl transferase in Indian childhood cirrhosis.

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Adult↗

PubMed1983

Correlation of in vitro clonogenic assay data with in vivo growth delays and cell cycle changes of a human melanoma xenograft.

We have reported previously that, in a human melanoma xenograft line, plating efficiency and drug sensitivity in vitro were enhanced under hypoxic conditions. In the present study, we show that the in vitro chemosensitivity data using clonogenic assays at 5% oxygen also correlate better with the drug-induced in vivo growth delay. Tumors implanted in bilaterally symmetrical locations grew at different rates, and response to chemotherapy was also variable. Cell cycle changes in the xenograft, as monitored by flow cytometry, suggest that major changes in cell cycle traverse occur when a drug is active in vitro and also causes in vivo growth delay. These studies indicate the usefulness of the nude mouse human xenografts to study correlations between soft agar clonogenic assays, in vivo growth delay, and cell cycle traverse in response to chemotherapeutic manipulation.

Animals↗

PubMed1982

Effect of oxygen concentration on the growth and drug sensitivity of human melanoma cells in soft-agar clonogenic assay.

Tumor cells from a human melanoma xenograft show better colony growth and plating efficiency in soft agar when incubated in a 5% O2 atmosphere that at a higher concentration of 20% O2. Exposure to low drug concentrations under a 20% (but not 5%) O2 atmosphere stimulated plating efficiency. Enhanced sensitivity (4- to 20-fold) to a variety of chemotherapeutic agents was seen in cells incubated under low but not the higher O2 concentration. These studies suggest the important role of O2 concentration in tumor colony growth, plating efficiency, and drug cytotoxicity for human solid tumors in vitro.

Agar↗

PubMed1981