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Biomedical subjects

D P Chandra

Publications and source records attributed to D P Chandra.

7 recordsLinked to original sources
PubMed1985

Determination of serum methotrexate and 7-hydroxymethotrexate concentrations. Method evaluation showing advantages of high-performance liquid chromatography.

The use of large doses of methotrexate (MTX), greater than 3 g/m2, for the treatment of some malignant disorders requires careful monitoring of serum concentrations. A simple and sensitive method for the separation of MTX and 7-hydroxymethotrexate (7-OH-MTX) by reversed-phase high-performance liquid chromatography (HPLC) is described. The method involves deproteinizing the serum sample on a Sep-Pak C18 cartridge, followed by separation on a C18 column and detection at 313 nm. The extraction efficiency of free MTX from serum is 70% and the maximum sensitivity is 2.2 X 10(-8) M. A high degree of correlation was obtained between the HPLC method of serum MTX determination and an enzyme multiplied immunoassay technique. The HPLC method separates MTX from its analogues, or drugs which may be administered concomitantly with MTX. Concentrations of MTX and 7-OH-MTX achieved over a 24-h period during high-dose therapy, (500-1000 mg/m2), and over 48 h for very-high-dose methotrexate therapy (8-12 g/m2) are described. A significant observation is the presence of 7-OH-MTX in sera of patients 6 h after commencement of infusion. This method was also utilized for monitoring cerebrospinal fluid MTX concentrations.

Chromatography, High Pressure Liquid↗
PubMed1980

Effect of hormone manipulation on oxidation, reduction and sulphurylation of dehydroepiandrosterone and oestrone in DMBA-induced rat mammary tumours.

Using the DMBA-induced mammary tumour as a model, the effect of hormone manipulation on steroid sulphurylation and on oxidative and reductive metabolism has been investigated. Oestradiol-17 beta, or oestradiol-17 beta + progesterone, administered to oophorectomized animals, had no effect on adenosine-3'-phosphate-5'-phosphosulphate formation in the tumours. Dehydroepiandrosterone sulphotransferase was also unaffected. A large increase in oestrogen sulphotransferase following administration of oestrogen + progesterone was observed in some but not all tumours, and the overall results were not statically significant. The major metabolities of dehydroepiandrosterone, by both human and carcinogen-induced rat mammary tumours in vitro, are 7-oxygenated derivatives. Oestrogen administration led to a significantly decreased production of total 7-oxygenated derivatives of dehydroepiandrosterone. Conversion to 5-androstene-3 beta, 17 beta-diol was unaffected by the hormones. The rate of formation of oestradiol-17 beta from oestrone was increased 5-fold in growing tumours from animals receiving oestrogen, or oestrogen + progesterone, compared to regressing tumours in oophorectomized control animals.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

A correlation between estrogen sulfotransferase levels and estrogen receptor status in human primary breast carcinoma.

Estrogen sulfotransferase (EC 2.8.2.4) activity and estrogen receptor levels were measured in 32 human primary breast cancer cytosol preparations. Two types of tumors were identified: type 1, in which estrogen sulfotransferase levels were low (less than 40 pmol 17 beta-estradiol 3-sulfate formed per mg protein per 2 hr) and were independent of [35S]adenosine 3'-phosphate 5'-phosphosulfate production from [35S]sulfate and adenosine triphosphate, and type 2, in which estrogen sulfotransferase levels ranged from 50 to 200 pmol 17 beta-estradiol 3-sulfate per mg protein per 2 hr and were correlated with [35S]adenosine 3'-phosphate 5'-phosphosulfate formation (r = 0.70; p less than 0.005). In type 1 tumors, 11 of 16 were estrogen receptor negative; in type 2 tumors, 2 of 16 were receptor negative. Estrogen sulfotransferase levels in receptor-negative tumors were significantly lower than the levels in receptor-positive tumors (p = 0.025).

Breast Neoplasms↗
PubMed1977

Dehydroepiandrosterone sulfotransferase as a possible shunt for the control of steroid metabolism in human mammary carcinoma.

Human primary mammary tumors were examined to determine what factors were of importance in deciding relative rates of sulfurylation of dehydroepiandrosterone and 17beta-estradiol, such rates having been shown to correlate with the patient's prognosis and response to adrenalectomy (T. L. Dao and P.R. Libby. Enzymic Synthesis of Steroid Sulfate by Mammary Cancer and Its Clinical Implications. Natl. Cancer Inst. Monographs, 34: 205-210, 1971). The sulfurylation of dehydroepiandrosterone and 17beta-estradiol was studied in 41 tumors in vitro using tumor cytosol, adenosine triphosphate, [35S]SO42-, Mg2+, and added steroid. Six tumors showed no sulfurylating ability, 9 sulfurylated dehydroepiandrosterone at a rate greater than that for 17beta-estradiol (ratio, greater than 1), and 26 sulfurylated dehydroepiandrosterone at a rate lower than that for 17beta-estradiol (ratio, less than 1). Evidence was obtained that low levels of dehydroepiandrosterone sulfotransferase were responsible for ratios of less than 1, in many instances. Adenosine 3'-phosphate 5'-phosphosulfate synthesis and steroid sulfotransferase activities were measured in 30 tumors. A significant correlation was found between synthesis of the former and levels of estrogen sulfotransferase, but this relationship did not hold for dehydroepiandrosterone sulfotransferase, again due to low levels of this enzyme in many tumors. It is suggested that dehydroepiandrosterone sulfate formation in the tumors is mainly controlled by the sulfotransferase, which acts as a shunt in regulating the level of free dehydroepiandrosterone, and related compounds, available for metabolism to steroids influencing the growth of mammary epithelial cells.

Adrenalectomy↗
PubMed1976

Steroid metabolism by human mammary carcinoma.

The ability of human mammary tumors to convert 7alpha 3H-testerone to estrogens was examined in order to determine whether this bore any relationship to estrogen receptor and steroid sulfurylation levels; such levels being indicative of hormone dependency. In 8 out of 9 tumors, formation of estradiol-17beta from testosterone was demonstrated. Those tumors showing the lowest conversion of testosterone to estradiol-17beta possessed the highest levels of dehydroepiandrosterone sulfotransferase which lends support to data implicating sulfurylation in the regulation of steroid metabolism in human tumors. All tumors activated sulfate to adenosine-3'-phospho-5'-phosphosulfate and the concentrations were significantly correlated withe the recorded levels of dehydroepiandrosterone sulfate. Estrogen receptor levels did not show any obvious relationship to the other parameters.

Breast Neoplasms↗