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Biomedical subjects

A H Nias

Publications and source records attributed to A H Nias.

At least 19 recordsLinked to original sources
PubMed1995

Effect of azelaic acid on melanoma cells in culture.

Using a clonogenic assay in vitro, it has been shown that exposure to azelaic acid (1-100 mM) for 24 hours has a dose-dependent effect on the survival of the colony-forming ability of murine (B16) and human (HMB2, and SK23) melanoma cells as compared with a non-melanotic non-tumoral Chinese hamster cell line (CHO). Both human cell lines were more sensitive to the diacid than the murine cells, and the HMB2 cells were more sensitive than the SK23 cells. These differences may be partly correlated with differences in pigmentation and doubling times between the three melanoma cell lines. The two human lines were more pigmented than the B16, and the SK23 more than the HMB2; the human lines had a longer doubling time than the others.

Animals↗
PubMed1993

The effect of paraquat on the radiosensitivity of melanoma cells: the role of superoxide dismutase & catalase.

The activities of reactive oxygen species scavenging enzymes, superoxide dismutases (SODs) and catalase (in cells of two melanomas (mouse B16 and human SK23) and in Chinese hamster ovary (CHO) cells were examined. Melanoma cells are relatively depleted in activities of superoxide dismutases and catalase as compared to CHO cells. Short equitoxic (500 microM for CHO and B16 cells and 5 microM for SK23 cells) paraquat treatment (15 min before the X-irradiation, 45 min in postirradiation period--the total time of treatment was 1 h) caused an increase in radiation resistance, measured as colony forming ability, in two of the three lines examined. It is proposed that PQ may exert its radioprotective effect by induction of antioxidant enzymes.

Animals↗
PubMed1992

Rate of metastasis from C3H mouse mammary tumours.

Transplants from the same C3H mouse mammary tumour have been used for radiobiological experiments with curative intent for more than 8 years. During that time, the rate of metastasis to the lungs has varied between 0 and 63% and an explanation has been sought for this change. The results of immunological assays showed no obvious pattern. An inverse relationship was found between tumour latency and metastasis.

Animals↗
PubMed1992

The optimum pressure of oxygen for radiotherapy of a mouse tumour.

Our previous studies have shown that there is more regrowth delay in mammary tumours irradiated in C3H mice after 25 Gy when breathing normobaric oxygen than in those breathing air, as might be expected. However, in both cases this radiation response was reduced in anaesthetized animals in comparison with unanaesthetized control mice, when a time interval of only 10 min was allowed after anaesthesia. After 25 min, however, the response in air returned to the control level and the oxygen group now showed significantly more radiosensitization. We have now found that when tumour-bearing mice were exposed to different pressures of oxygen for that 25-min period after the induction of anaesthesia, before the tumours were treated with 25 Gy, there was even more regrowth delay with 2 atm pressure than 1, but that there was no further advantage from using 3 atm pressure of oxygen. Our data suggest that 2 atm may be the optimal pressure to use in anaesthetized mice and there is even a small benefit from using this pressure in unanaesthetized animals for a transplanted C3H mammary tumour.

Anesthesia↗
PubMed1990

Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity.

Anaemia is an important factor in the response of some human tumours to radiotherapy. The outcome is also influenced by whether the treatment is given in air or high pressure oxygen (HPO). The present study examined the relationship between anaemia and tumour response to radiation given in air or HPO in C3H mice transplanted with a mammary adenocarcinoma using a growth delay assay to assess the radiation response. Chronic anaemia was induced by the use of a low iron diet and was characterized by a significant reduction in host haematocrit and whole blood viscosity. In addition, anaemia was associated with a right shift in the oxyhaemoglobin dissociation curve and an increase in the volume doubling time of the tumour; but there was no change in the concentration of 2,3-diphosphoglycerate in the red cells. Radiation studies with these anaemic mice demonstrated that the tumour radiosensitivity was decreased when treatment was given in air. HPO was successful in overcoming the increased radioresistance associated with anaemia. This result suggested that tumours grown in anaemic mice have a higher hypoxic fraction than those grown in control mice. Changes in host physiology with chronic anaemia may contribute to the benefit seen with HPO but such alterations per se may be inadequate to maintain tumour oxygenation when treatment is given in air.

Adaptation, Physiological↗
PubMed1989

Variation of tumour radiosensitivity with time after anaesthetic.

Transplanted C3H mouse mammary tumours were given single doses of X irradiation in air or oxygen at 1 atmosphere (atm) with or without anaesthesia of the recipient mice by ketamine and diazepam. The radiation response to single doses of 25 Gy was determined in terms of the time taken to reach 3.5 times the treatment volume. Under all conditions there was more growth delay in tumours irradiated in pure oxygen than in air. In both air and oxygen, the radiation response for anaesthetized animals tended to fall below the level for non-anaesthetized ones when only 10 min had elapsed after the administration of anaesthesia. After 25 min, the response in air was back to the level for the non-anaesthetized animals but the oxygen group now showed significant sensitization compared with the oxygen without anaesthetic group. After 40 min, the air group now showed slight sensitization and the oxygen group still showed significant sensitization by the anaesthetic. These results demonstrate the importance of the time interval between anaesthesia and irradiation of mouse tumours.

Adenocarcinoma↗
PubMed1988

Modulating the oxygen tension in tumours by hypothermia and hyperbaric oxygen.

Hypothermia is associated with reduced metabolism of tissues and especially reduced oxygen consumption by tumours. If the blood supply to a hypothermic tumour can be maintained then the hypoxic fraction of cells should be reduced and the radiation response increased. This hypothesis has been tested with radiation under hyperbaric oxygen and increased tumour response has been demonstrated.

Adenocarcinoma↗
PubMed1986

Evaluation of the biochemical effects of CHIP in normal and tumour-bearing C3H mice.

The biochemical effects of CHIP have been studied in C3H mice with and without transplanted mammary tumour. The maximum tolerated dose of CHIP was first determined by lethality and intestinal crypt assays to be 40 mg kg-1 and this dose was used to assay the time course of gastric distension and the pattern of drug distribution. A high level of CHIP uptake was found in liver as well as kidney. For this reason, tests for both kidney and liver damage were undertaken up to 60 days post-treatment using a dose of 10 mg kg-1 Neoplatin for comparison. Despite the high level of platinum drug uptake in liver, there was no biochemical evidence of hepatocellular or cholestatic damage. From the renal point of view, there was the expected rise in serum urea after Neoplatin but not after CHIP and there was also a rise in urinary NAG after Neoplatin in tumour bearing mice. There was, however, evidence of suppression of protein levels including enzymes, following treatment with both drugs. Tumour-bearing mice respond differently from normal mice following treatment with platinum drugs. The study confirms that CHIP is less toxic than Neoplatin.

Acetylglucosaminidase↗
PubMed1986

Effect of hypothermia on radiosensitization.

Hypothermia reduces metabolism and oxygen utilization by tissues. If the blood supply to a solid tumour can be maintained at a sufficient level, the hypoxic fraction of tumour cells may be reduced and radiosensitivity increased. This may be achieved if hyperbaric oxygen is used in combination with the hypothermia. The blood supply and oxygen tension have been measured in C3H mouse mammary tumours under hypothermia and hyperbaric oxygen, and the enhancement of radiosensitivity by hyperbaric oxygen has been estimated in mice irradiated at different temperatures with and without anaesthesia. Measurement of xenon-133 clearance showed that the blood supply of a tumour tended to increase when anaesthetized mice became hypothermic. Oxygen cathode data showed that the oxygen tension tended to be relatively higher in tumours and lower in subcutaneous tissue when mice exposed to hyperbaric oxygen became hypothermic under anaesthesia. Hyperbaric oxygen enhanced the radiation response of the tumour in terms of an increase in regrowth delay by a factor of 1.7 when the mice had been anaesthetized, whether or not they became hypothermic. A lower factor of 1.4 was obtained without anaesthesia although induced hypothermia increased the response to a small extent. We conclude that anaesthesia and hypothermia affect oxygen metabolism in tumours by different mechanisms.

Adenocarcinoma↗
PubMed1986

Cell cycle phase sensitivity to cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum (IV) (CHIP).

Cis-dichloro-bis (isopropylamine) trans-dihydroxy platinum (IV) (CHIP) is a second generation platinum coordination complex now in Phase II clinical trials. In vitro studies with Chinese Hamster Ovary cell cultures show that CHIP is a phase-sensitive drug, being most cytotoxic to cells in early G1 phase and least toxic to late S and G2 phase cells. The dose-modifying factor between the drug sensitivity of cells treated in G1 and in late S phase is 1.6. These findings and their clinical significance are discussed with respect to the phase sensitivity of other cytotoxic agents.

Animals↗
PubMed1985

The effect of C3H mouse mammary tumour on the levels of serum and urine analytes in vivo.

A study of C3H mice implanted with mammary tumours has shown that the levels of serum total protein, alanine transaminase and alkaline phosphatase are all lower than those found in normal mice, while aspartate transaminase is higher. Serum urea values were similar to normal levels, but creatinine was lower in males and higher in females. In the male mice, urine protein and urine N-acetyl-beta-D-glucosaminidase (NAG) activity were lower than in normal mice. Comparisons were made with age and sex matched controls which was found to be important for alkaline phosphatase, as this was shown to decrease with increasing age of the mice over the period from 10-30 weeks of age. The analyte values found in this study provide useful base-line data for assessing biochemical toxicity of cancer chemotherapy agents. It has been shown that some of these values can vary with age, or can be different if tumour-bearing mice are used instead of normal mice.

Acetylglucosaminidase↗