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Clinical use of aromatase inhibitors in the treatment of advanced breast cancer.

The aim of endocrine therapy is to reduce the estrogenic stimulus for tumour growth. After failure of tamoxifen--the standard "first-line" h … h programme were to develop more potent, more selective and better tolerated AIs than our first AI, aminoglutethimide (AG). Lentaron (4-hydroxyandrostenedione, formestane), a highly selective steroidal compound was the first of the new AIs to be used in clinical trials. It is a substrate analogue, administered as an i.m. injection every 2 weeks. It is effective in …

Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia.

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consoli

Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.

BackgroundGlucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy.MethodsA systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO) and other resources were used. Data was extracted using a standar

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… There are four trials in this category: three are of tamoxifen +/- glucocorticoids and one is of aminoglutethimide +/- glucocorticoids. Results are presented in Table 4 [ 7 , 24 , 37 , 46 ]. As these trials were more similar in nature, meta-analyses of response rates and survival were undertaken. … vs hydrocortisone as second-line hormone treatment of advanced breast cancer Eur J Surg Oncol 1993 19 254 258 8314383 Wander HE Kleeberg UR Essers U Blossey HC Nagel GA Aminoglutethimide plus high-dose medroxyprogesterone acetate versus aminoglutethimide plus cortisone in therapy of metastasizing breast …

Classic and recent etiologies of Cushing's syndrome: diagnosis and therapy.

Endogenous Cushing's syndrome can result from excess adrenocorticotropic hormone (ACTH; corticotropin) production by a pituitary adenoma (Cu … erapy should be initiated. Various drugs which inhibit steroid synthesis (ketoconazole, metyrapone, aminoglutethimide, mitotane) are often effective for rapidly controlling hypercortisolism either in preparation for surgery, after unsuccessful removal of the etiologic tumor, or while awaiting the full effect of radiotherapy or more definitive therapy. Surgery is us …

Multiple mechanisms for regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5----delta 4-isomerase, 17 alpha-hydroxylase/C17-20 lyase cytochrome P450, and cholesterol side-chain cleavage cytochrome P450 messenger ribonucleic acid levels in primary cultures of mouse Leydig cells.

The regulation of mRNA levels for delta 5-3 beta-hydroxysteroid dehydrogenase/delta 5----delta 4-isomerase (3 beta HSD), 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 (P450(17 alpha] and cholesterol side-chain cleavage cytochrome P450 (P450scc) was studied in primary cultures of mouse Leydig cells. Treatment of Leydig cells with 8-bromo-cAMP (cAMP) was essential for expression of P450(17 alpha) mRNA, but not for 3 beta HSD. Treatment with cAMP caused a decrease in basal levels of 3 beta HSD mRNA. The addition of aminoglutethimide (AG), an inhibitor of cholesterol metabolism, to the cAMP-tr…

Aromatase inhibitors: past, present and future.

For the cellular physiology of sex steroid sensitive cells, the androgen/estrogen ratio may be more important than only one hormone action p … ing or deductions from in vivo observations, which led for instance to the discovery of the role of aminoglutethimide in aromatase inhibition. Subsequently, in the years 1975-1990, the molecular modeling of compounds to mimic the substrate shape of the enzyme constituted the major idea. Hundreds of chemicals were synthesized by numerous authors, ranging from the we …

An alternate pathway to androstenedione synthesis by human adrenals: evidence of a balance in 11 beta-hydroxylase and 17,20-lyase activities leading to androstenedione.

Until now, dehydroepiandrosterone and 17-hydroxyprogesterone were thought to be the main precursors for the synthesis of androstenedione by the human adrenal cortex. However, secretion of androstenedione and 11-deoxycortisol are increased when 11 beta-hydroxylase activity is impaired, e.g. by metyrapone test or by congenital adrenal hyperplasia resulting from 11 beta-hydroxylase deficiency. The present study with human adrenals shows that 11-deoxycortisol, the precursor of cortisol synthesis, is also a precursor of androstenedione in humans. Our data show that androstenedione synthesis is inve

[Acute myelomonocytic and monoblastic leukemia with polyradicular symptoms].

Meningeal leukaemia, developed in 4 female patients with M4 or M5 leukaemia during a period of haematological remission. Polyradicular symptoms and signs dominated neurologically, but 3 patients also exhibited cranial nerve palsies. The neurological findings showed no reversal following intrathecal chemotherapy with normalization of liquor cytology. Patchy demyelinization in the region of the anterior spinal roots and of the proximal segments of the affected cranial nerves were responsible for the neurological features. Peripherally located streaky demyelinization of the olfactory bulb and of

Ex vivo and in vitro testis and ovary explants: utility for identifying steroid biosynthesis inhibitors and comparison to a Tier I screening battery.

Testis and ovary explants have been proposed as in vitro screens for identifying potential inhibitors of steroid biosynthesis. The goals of … valuated using the following compounds: ketoconazole (KETO), a testosterone biosynthesis inhibitor; aminoglutethimide (AG) (only in vitro) and anastrozole (ANA), aromatase inhibitors; finasteride (FIN), a 5alpha-reductase inhibitor; 17beta-estradiol (17beta-E2), an estrogen receptor agonist; flutamide (FLUT), an androgen receptor antagonist; ICI-182,780 (ICI), an e …

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women.

BACKGROUND: Hormonal treatments for advanced or metastatic breast cancer, such as tamoxifen and the progestins megestrol acetate and medroxyprogesterone acetate, have been in use for many years. Aromatase inhibitors (AIs) are a class of compounds that systemically inhibit oestrogen synthesis in the peripheral tissues. Aminoglutethimide was the first AI in clinical use (first generation) and had a similar tumour-regressing effect to other endocrine treatments, which showed the potential of this alternative type of therapy. Other AIs have since been developed and the third generation AIs anastro…

Exploiting Literature-derived Knowledge and Semantics to Identify Potential Prostate Cancer Drugs.

In this study, we report on the performance of an automated approach to discovery of potential prostate cancer drugs from the biomedical literature. We used the semantic relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations using SemRep, to extract potential relationships using knowledge of cancer drugs pathways. Two cancer drugs pathway schemas were constructed using these relationships extracted from SemMedDB. Through both pathway schemas, we found drugs already used for prostate cancer therapy and drugs not currently listed as the prostate cancer

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… HORMONAL THERAPY | IMMUNOTHERAPEUTICS Estrogens and Progestins | Antiandrogens | Antiadrenal agents | Prednisone Diethylstilbestrol | Enzalutamide | Ketoconazole | Sipuleucel-T Chlorotrianisene | Buserelin | Aminoglutethimide | CHEMOPREVENTION Ethinyl estradiol | Flutamide | Finasteride Conjugated estrogens …

Painful boney metastases.

Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, ho

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… buserelin, goserelin, histrelin, [triptorelin-in phase II trials is a 60 month formulation triptorelin embonate that is under development]), cytochrome P450 enzyme 17A1 (CYP17A1) inhibitors [inhibition of androgen synthesis] (e.g. nonselective CYP17A1 inhibitors) ketoconazole, [aromatase inhibitors] aminoglutethimide …