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Results for “MEDROXYPROGESTERONE”

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At least 1,405 records · Page 78Linked to original sources
PubMed2000

Biphasic effect of medroxyprogesterone-acetate (MPA) treatment on proliferation and cyclin D1 gene transcription in T47D breast cancer cells.

While progesterone is a known differentiation-inducing factor in the human endometrium, for the breast epithelium both proliferation-inducing and -inhibiting effects have been described. Cyclin D1, which is required for cell cycle progression in G1 and has been shown to play an important role in the pathogenesis of breast cancer has been implicated as a possible mediator of such effects. In the present study we thus investigated the effects of the progestin agonist MPA (medroxy-progesterone acetate) on proliferation of T47D breast cancer cells. In parallel experiments, the regulation of the human cyclin D1 promoter as well as cyclin D1 protein levels under the influence of MPA were studied. Our results show an increase of proliferative activity in T47D cells after 24 and 48 h of MPA treatment followed by inhibition of proliferation after 72 h. In Western blot analysis an increased expression level of cyclin D1 protein can be observed after 24h of MPA stimulation, while at 72h the protein levels are barely detectable. Transient transfection experiments with a luciferase reporter plasmid containing the human cyclin D1 promoter showed an induction of the promoter after 24 and 36h of MPA treatment followed by a reduction in promoter activity. In conclusion, our results confirm the existence of a biphasic response of T47D cell proliferation in response to MPA treatment, consisting of stimulation of proliferation followed by inhibition, and further implicate cyclin D1 as a mediator of these effects, since the cyclin D1 promoter shows a similar biphasic response in this context.

Antineoplastic Agents, Hormonal↗
PubMed1993

A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia.

Patients with breast cancer treated with MPA often report an improvement in appetite. Similar appetite stimulation is seen in patients treated with some corticosteroids, but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect. MPA (100 mg tds orally) has therefore been compared with placebo in 60 patients with advanced malignant disease. Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy. Patients were treated for 6 weeks and were assessed at weeks 0, 3 and 6 for appetite, energy, mood and pain using visual analogue scales. Nutritional status was assessed by the measurement of serum proteins and anthropometrics. Karnofsky score was recorded as a measure of performance status. There was a significant improvement in appetite in the MPA group between weeks 0 (pre-study) and 3 (P = 0.0002) and 0 and 6 (P = 0.015). There was no significant improvement in appetite in the placebo group. Supporting this finding was the significant increase in serum thyroid binding pre-albumin and retinol binding protein in the MPA group between weeks 0 and 3 and 0 and 6 (P = 0.023 and P = 0.039 respectively). These two parameters showed no significant change in the placebo group. There was no change in anthropometric measurements, weight, performance status, energy, mood or pain in either group. These data indicate that there was a significant increase in appetite in anorexic patients with advanced cancer treated with MPA which was reflected in increases in rapid turnover proteins reported to reflect nutritional status. However, this apparent increase in appetite did not result in improved weight, performance status, energy levels, mood or relief of pain. Further studies to investigate the effect of higher doses of MPA are indicated.

Appetite↗
PubMed2003

Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease.

Current therapies for Burkitt's lymphoma (BL) utilise combined cytotoxic chemotherapy, but these treatments are not always available in areas where the disease is endemic and are also markedly less successful in AIDS-related BL. Therefore, additional therapies are urgently required. We demonstrate here that combined fibrates and MPA exert powerful, antiproliferative actions against well-characterised Daudi, Raji and L3055 BL cell lines and primary BL cells. Detailed studies in L3055 demonstrated that this activity was mediated by induced apoptosis and confirmed by observations that overexpression of the antiapoptotic genes bcl-2 or bcl-x(L) conferred significant protection against the drugs. Importantly, since fibrates and MPA are inexpensive and stable with minimal-associated toxicities, we suggest that these drugs should be considered as adjuncts to currently available treatments for BL in endemic and AIDS-related disease.

Antineoplastic Agents, Hormonal↗
PubMed1982

Influence of esterified estrogens and medroxyprogesterone on lipid metabolism and sex steroids. A study in oophorectomized women.

Eight oophorectomized women were given 1.25 mg esterified estrogens (EE) daily for 21 days and 5 mg medroxyprogesteroneacetate (MPA) daily for 5 days in a sequence combination. The effects on sex steroids, gonadotrophins, lipids and lipoproteins as well as the relative fatty acid composition of lecithin and cholesterol ester induced by treatment were studied. Esterified estrogens were readily absorbed with estrogen levels corresponding to those of a normal luteal phase. A favourable estrone/estradiol ratio was found during treatment. After two days without EE no estrogens could be detected. Androstenedione was significantly depressed after the MPA period, otherwise it remained unchanged. Minor changes were induced in serum lipids and lipoproteins. A decrease in cholesterol ester of 12 and 23 per cent was found for palmitic and stearic acid concomitant with an increase of arachidonic acid of about 20 per cent after three weeks of estrogen treatment. After the MPA period increases in free cholesterol, total cholesterol and phospholipids in HDL were assessed. It was concluded that MPA in this experiment from a lipid metabolic point of view seemed to be a favourable progestogen complement.

Adult↗
PubMed2004

Painless Depo-medroxyprogesterone acetate (DMPA) injections using the 'pinch technique'.

This study was done to see if pinching the skin, prior to injection of DMPA, would reduce the pain of the injection, as suggested by the gate theory. Seventy-eight patients scheduled to receive DMPA for contraception were enrolled into a randomised controlled trial. The injections were given in the gluteal region, with 39 receiving a pinch before and during the injection, while 39 others received the injection only. They were all asked if the pain was severe. Six of 39 patients in the pinch group were positive for severe pain while 15 of 39 in the injection only group were positive (P = 0.02). This simple technique appears to be useful to ensure compliance for the DMPA injection.

Contraceptive Agents, Female↗
PubMed2006

Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin.

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.

Adenocarcinoma↗