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Biomedical subjects

N Deshpande

Publications and source records attributed to N Deshpande.

At least 37 records · Page 2Linked to original sources
PubMed1987

The effects of interferons on the activity of alpha-glycerolphosphate dehydrogenase in benign prostatic hyperplasia cells in primary culture.

Human benign prostatic hyperplasia (BPH) tissues were obtained from patients undergoing transurethral resection of the prostate and viable cells from these were successfully maintained in primary cultures grown on collagen gel. The prostatic origin of the cells was confirmed by the measurement of prostate specific acid phosphatase and by scanning and transmission electron microscopy before and after immunostaining with human prostate specific antigen-antibody. The cell cultures were treated with various interferons (IFNs), both in the presence and absence of testosterone propionate (TP), for 72 hours and the activities of seven enzymes of carbohydrate metabolism were estimated in the cytosolic fraction of the cells. Treatment with TP induced a significant decrease in the activity of alpha-glycerolphosphate dehydrogenase (alpha-GPDH). Using this enzyme activity as a marker, the effects of various types of IFNs were investigated. IFN-alpha (wellferon) increased the activity of the enzyme both in the presence of one microgram./ml. of TP and in its absence whereas IFN-gamma inhibited the activity under similar conditions. The effect of treatment with IFN-beta in the presence of TP was biphasic in that there was an increase in the activity of the enzyme at the lowest concentration while at higher concentrations an inhibition of enzymic activity was observed. In the absence of TP IFN-beta inhibited the activity. The significance of these findings in terms of the clinical usefulness of IFNs is discussed and it is postulated that IFN-alpha (wellferon) might be effective in the treatment of metastatic carcinoma of the prostate in selected patients.

Cells, Cultured↗
PubMed1986

The activity of phosphohexose isomerase in primary breast carcinomas and response to chemotherapy in patients with metastatic disease.

The activity of phosphohexose isomerase [PHI] was measured in 48 primary carcinomas from patients with breast cancer, and its usefulness as a predictor of response to cytotoxic drugs at the metastatic stage was evaluated. There was a statistically significant difference in the activity of PHI between responders and non-responders to these treatments. These preliminary findings are currently being evaluated in an extended series.

Antineoplastic Agents↗
PubMed1985

The effects of the administration of tamoxifen, ethynyloestradiol, and prednisolone on the activities of certain enzymes of carbohydrate metabolism in primary human breast carcinomas in vivo.

Postmenopausal patients with primary breast cancer were treated with tamoxifen, ethynyloestradiol or prednisolone for up to 12 days before mastectomy and the effects of pretreatments with these drugs on the activities of phosphofructokinase (PFK), 6-phosphogluconate dehydrogenase (6PGDH) and alpha-glycerolphosphate dehydrogenase (alpha-GPDH) in the carcinomas were compared with age, stage and menopausal status matched untreated controls. The administration of tamoxifen or prednisolone resulted in a significant increase in the activity of alpha-GPDH and the alpha-GPDH/6PGDH ratio, whereas ethynyl-oestradiol treatment produced a significant decrease in the activity of the enzyme and the ratio. When tamoxifen and ethynyl-oestradiol were administered together, it was found that tamoxifen failed to reverse the oestrogen-induced reduction in the activity of alpha-GPDH. Since increased activity of the enzyme or a higher alpha-GPDH/6PGDH ratio are associated with a lower risk of recurrence (Deshpande et al., 1981), it is postulated that the beneficial effects of tamoxifen or prednisolone in terms of prolongation of the relapse free interval might be mediated via alterations in the activity of alpha-GPDH in micrometastases. The activities of PFK and 6PGDH remained unaffected by these treatments.

Aged↗
PubMed1985

Deoxyribonucleic acid (DNA) content of primary carcinoma and response to endocrine or cytotoxic drug therapies in patients with advanced breast cancer.

The DNA content of primary carcinomas was estimated colorimetrically in 111 patients with carcinoma of the breast who subsequently developed metastatic disease. The data were analysed to investigate whether these measurements will assist clinicians in predicting: survival from mastectomy or recurrence, the likelihood of response to the first endocrine or the first cytotoxic drug therapy, duration of response amongst responders to these treatments, and time to treatment failure (TTTF). The DNA content of primary carcinomas failed to predict the clinical course of the disease for patients who underwent endocrine treatments. In patients who were treated by cytotoxic drug therapies, only the duration of response amongst responders to these therapies was significantly shorter in cases where the DNA content was high. The DNA content of carcinomas failed to give any useful information on other parameters. It is concluded that these measurements are unlikely to be of prognostic value in these cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Drug effects on certain enzymes of carbohydrate metabolism in MCF-7 cells in culture.

The effects of treatments with ethinyl-estradiol, tamoxifen, prednisolone, cyclophosphamide, methotrexate, 5-fluorouracil and Adriamycin on the activities of PFK, 6PGDH, alpha-GPDH and alpha-GPDH/6PGDH ratios were investigated in MCF-7 cells in monolayer cultures. The following findings are recorded. Both ethinyl-estradiol and prednisolone failed to induce alterations in the activities of these enzymes. Tamoxifen increased the activities of PFK, alpha-GPDH and alpha-GPDH/6PGDH ratios whereas ethinyl-estradiol inhibited the tamoxifen-induced rise in the activity of PFK. Treatment with cyclophosphamide alone was without any effect but in combination with either methotrexate or 5-fluorouracil induced increases in the activities of 6PGDH and alpha-GPDH. Adriamycin at a lower dose increased the activities of 6PGDH and alpha-GPDH and the alpha-GPDH/6PGDH ratio and decreased the activity of PFK. At a higher dose level it reduced the activities of all the enzymes whilst increasing the alpha-GPDH/6PGDH ratio. These data encourage us to undertake a project to test the sensitivity of individual tumours to these drugs in vitro thereby enabling the selection of appropriate drugs for adjuvant therapy.

Antineoplastic Agents↗
PubMed1983

Deoxyribonucleic acid (DNA) content of carcinomas and prognosis in human breast cancer.

DNA content was estimated in 705 breast carcinomas from patients with stage I or stage II disease undergoing mastectomy, to investigate whether it would predict the clinical course of the disease. The patients were then followed for up to 84 months during which time 166 of them developed recurrences. There were no statistically significant differences in the DNA content of carcinomas between stage I and stage II patients or between those with various numbers of involved nodes. The tumours from pre-menopausal patients as a group had significantly higher DNA content than those from post-menopausal cases. There was a gradual rise in DNA content with the malignancy grade of the carcinoma which showed significant differences between Grades I and III and between II and III. Life-table analyses showed that the measurement of DNA would not be an aid to prognosis. Furthermore, when the data were stratified according to menopausal status, stage, malignancy grade or numbers of lymph nodes involved, the results indicated that these estimation do not add significantly to the information obtained through established prognostic factors. Survival data were available on III patients with recurrent disease. There were no significant differences in tumour DNA content between short- and long-term survivors. It is concluded that these measurements seem unlikely to be a prognostic factor in human breast cancer.

Adult↗
PubMed1983

Corticotropin and morphine interaction in the regulation of phosphofructokinase activity in rat mammary gland.

The roles of corticotropin and morphine in the regulation of phosphofructokinase (PFK) activity in rat mammary glands were investigated by the administration of corticotropin, morphine and dexamethasone. Corticotropin increased the activity of PFK in the mammary glands of intact and hypophysectomised animals but was without any effect in tissues from ovariectomised and adrenalectomised animals. Morphine administration resulted in a significant decrease in the enzyme's activity in intact animals only. A combined dose of corticotropin and morphine significantly reduced the corticotropin-induced increase in the activity in both intact and hypophysectomised animals. Dexamethasone treatment resulted in a significant increase in the activity in hypophysectomised and ovariectomised plus adrenalectomised animals and morphine was able to reduce the glucocorticoid-induced rise. It is postulated that endogenous opioids might be playing a dual role in the regulation of glycolysis by inhibiting the release of corticotropin and regulating the action of glucocorticoids at the cellular level in the mammary gland.

Adrenocorticotropic Hormone↗
PubMed1983

Enzyme studies in human prostatic tissues.

The activities of six enzymes associated with carbohydrate metabolism were measured in 24 benign prostatic hyperplasias and 29 carcinomas of the prostate with the intention of investigating whether these measurements might eventually predict the clinical course of the disease. The following findings are recorded: the activities of PFK, alpha-GPDH and PHI were significantly lower in carcinomas. Comparison between well and poorly-differentiated carcinomas indicated a significantly lower activity of 6PGDH and higher alpha-GPDH/6PGDH ratios in the latter. These findings are the opposite of those observed in carcinomas of the breast.

Aged↗
PubMed1982

Effects of opiates and naloxone on certain enzymes of carbohydrate metabolism in human breast carcinomas.

The effects of administration of opiates and naloxone on the activities of PFK, 6PGDH and alpha-GPDH and alpha-GPDH/6PGDH ratios in human breast carcinomas were investigated in patients awaiting mastectomy. Injection of naloxone or fentanyl into an antecubital vein resulted in a statistically significant reduction in the activity of alpha-GPDH. Fentanyl was also effective in reducing the activity of 6PGDH. Injection of morphine into a branch of the internal mammary artery during mastectomy failed to induce changes in the activities of any of the enzymes but injection of naloxone resulted in a significant rise in the activity of 6PGDH. It is postulated that these alterations in the activities might not be associated with the binding of these drugs to opiate receptor proteins in the carcinoma. Furthermore opiate agonists or antagonists might not produce the required changes in the activities of any of the enzymes.

Breast Neoplasms↗
PubMed1981

Further observations on the hormonal regulation of alpha-glycerolphosphate dehydrogenase in rat mammary gland: a possible role for prolactin and thyrotropin.

The roles of prolactin and thyrotropin (TSH) in the regulation of alpha-glycerolphosphate dehydrogenase (alpha-GPDH) activity in rat mammary gland were investigated by the administration of thyroid releasing hormone, bromocriptine, prolactin, TSH and triiodothyronine (T3). TRH administration failed to induce alterations in the glands from intact animals but stimulated the activity in castrated and adrenalectomized animals. Bromocriptine administration was without any effect in either group of animals. Administration of ovine prolactin to hypophysectomized rats did not affect the activity, on the other hand, treatment with either TSH or T3 resulted in a highly significant increase in the activity. Combined administration of prolactin and TSH to hypophysectomized animals showed that prolactin is capable of partially inhibiting the TSH-induced increase. It is suggested that glucocorticoids exert primary control over the enzyme's activity with the pituitary hormones only playing a permissive role in its regulation.

Adrenalectomy↗
PubMed1981

Some aspects of pituitary function after neuroadenolysis in patients with metastatic cancer.

The effects of neuroadenolysis on plasma titres of beta-endorphin, beta-lipotropin, ACTH, TSH and prolactin have been investigated in five patients with metastatic cancer who responded to the treatment and have been in remission for more than four years and in five others who were undergoing the treatment for the first time for pain due to cancer metastases. beta-Endorphin, beta-lipotropin and ACTH titres were within the normal ranges of values in both categories of patients but post-neuroadenolysis titres of these peptides were higher than those before the treatment. The ability to secrete TSH and prolactin and to respond to thyroid stimulating hormone releasing hormone (TRH) remains intact following the treatment. However, whereas basal TSH titres and response to TRH was lower in the majority of patients, no such effect was observed on prolactin secretion. Plasma titres of prolactin and TSH were below the sensitivity of the method in the five patients who are in remission for more than four years. These preliminary findings suggest that neuroadenolysis probably affects some mechanism(s) associated with the control of beta-endorphin, beta-lipotropin and ACTH synthesis.

Adrenocorticotropic Hormone↗
PubMed1980

Hormone synthesis by primary breast carcinomas and prognosis in human breast cancer.

The ability of human breast carcinomas to convert pregnenolone to progesterone and dehydroepiandrosterone to delta 4-androstene-3,17-dione (delta 4) was investigated as a potential aid for prognosis, and the following observations were recorded. 1. Neither the amounts of progesterone or delta 4 synthesized nor delta 4/progesterone ratios correlated with tumour size or lymph node involvement. 2. delta 4 synthesis was lower in carcinomas from patients who had recurrences within 2 years of mastectomy than in carcinomas from those who remained free of metastases. 3. Life table analysis of the results indicated that these parameters appeared unlikely to be useful aids for prognosis.

Androgens↗
PubMed1980

Prolactin, thyrotrophin interaction in the regulation of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in rat mammary glands.

The roles of prolactin and thyrotrophin (TSH) in the regulation of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) activities in rat mammary glands were investigated by the administration of thyroid hormone-releasing hormone (TRH), bromocriptine, prolactin, TSH and triiodo-1-thyronine (T(3)). TRH failed to induce changes in the activities of these enzymes in glands from intact animals but the releasing hormone significantly increased the activities of both the enzymes in the glands of ovariectomized and adrenalectomized animals. Bromocriptine administration had no effect on the activities in both, intact and ovariectomized-adrenalectomized animals. Administration of ovine prolactin to hypophysectomized rats did not affect the activities of these enzymes. On the other hand treatment with TSH resulted in significant increases in the activities. On the other hand treatment with TSH resulted in significant increases in the activities. Similarly, administration of T(3) to these animals resulted in changes similar to those observed after TSH administration. Combined administration of prolactin and TSH showed that prolactin is capable of partially inhibiting the TSH-induced increases. It is concluded that TSH is involved in the channelling of substrates into the pathways of nucleic acid synthesis and prolactin probably plays a regulatory role in this process.

Animals↗
PubMed1980

Effects of testosterone propionate and cyproterone acetate on carbohydrate metabolism in rat mammary glands.

The effects of administration of testosterone propionate on the activities of seven of the enzymes of carbohydrate metabolism in normal rat mammary glands were investigated and the validity of the results was confirmed by simultaneous injection of the hormone and cyproterone acetate. The administration of the androgen increased the activities of phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and lactate dehydrogenase (LDH) in glands from both intact and from ovariectomized and adrenalectomized animals. Administration of cyproterone acetate alone resulted in a significant reduction in the activities of PFK and G6PDH and when given together with the androgen it inhibited increases in the activities of PFK, G6PDH, 6PGDH and LDH induced by testosterone. It was concluded that these results did not explain the known inhibitory effects of the androgen on normal mammary gland growth and function.

Adrenalectomy↗
PubMed1980

Evidence for the participation of opioids in the regulation of carbohydrate metabolism in rat mammary glands.

The possible involvement of opioids in carbohydrate metabolism in rat mammary glands was investigated by studying the effects of administration of morphine and naloxone on six enzymes. Morphine inhibited phosphofructokinase (PFK) and stimulated phosphohexose isomerase (PHI) activities. Nalozone treatment alone, to both intact and ovariectomized/adrenalectomized animals, resulted in stimulation of PFK and inhibition of PHI activities. A combined dose of morphine and naloxone to intact animals showed that the opiate antagonist was able to reverse the morphine-induced changes. Evidence is presented to show that the changes observed in PHI activity may be the result of the indirect action of opioids on luteinizing hormone releasing hormone. However, the changes observed in PFK activity might be the result of direct action of opioids. Failure to observe changes in enzyme acstivities after naloxone treatment of hypophysectomized animals suggests the opiate antagonist might be acting on the pituitary gland to block the release of endorphins.

Adrenalectomy↗