Steroids tumors

A., Renauld, J. A. (1965). The isolation and structural elucidation of a novel steroidal tumor inhibitor from Acnistus arborescens. J. Am. Chem. Soc., 87, 5805-5806. 

Busam KJ, Iversen K, Coplan KA, et al. Immunoreactivity for A103, an antibody to melan-A (MART-1) in adrenocortical and other steroid tumors. Am J Surg Pathol. 1998 22 57-63. 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Soto AM, Soimenschein C. 1985. The role of estrogens on the prohferation of human breast tumor cells (MCE-7). J Steroid Biochem 23 87-94. 

Braughler, J.M., Chase, R.L., NefF, G.L., Yonkers, P.A., Day, J.S., HaU, E.D., Sethy, V.H. and Lahti, R.A. (1988). A new 21-amino steroid antioxidant lacking glucocorticoid activity stimulates ACTH secretion and blocks arachidonic acid release from mouse pituitary tumor (ArT-20) cells. J. Pharmacol. Exp. Ther, 244, 423-427. 

Evaluate patient comorbidities and medications to determine if additional work-up is necessary prior to tumor debulking surgery. Do any medications need to be stopped or changed prior to surgery (e.g., aspirin, warfarin, or non-steroidal anti-inflammatory agents) ... 

The answer is a. (Hardman, p 1302.) Cyclophosphamide, an alkylating agent, reacts with purine and pyrimidine bases of DNA to form bridges and dimers. These products interfere with DNA replication. 5-FU, methotrexate, and 6-thioguanine are anti metabolites, and the steroid prednisone has some tumor-suppressive effects. 

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Progestins, steroid compounds similar to progesterone, such as hydroxyprogesterone caproate (28.3.6), medroxyprogesterone acetate (28.3.7), and megestrol acetate (28.3.7), are used for palliative treatment of breast carcinomas and renal tumors. Progestins can have a direct local effect on cells, and can simultaneously lower the quantity of leutenizing hormone. 

The steroid Ci7(20)lyase is an enzyme that is involved in the biosynthesis of andro-stenedione and of dehydroepiandrosterone from progesterone and pregnenolone, respectively. As androgen and estrogen hormones are necessary for the growth of tumors, this enzyme is a potential therapeutic target for the treatment of prostate cancer and in hormone-dependent breast cancers. 

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