Hormonal Methotrexate

MRP1 (ABCC1) Glucuronides and sulfate conjugates of steroid hormones and bile salts, colchicine, doxorubicin, daunorubicin, epirubicin, folate, irinotecan, methotrexate, pacitaxel, vinblastine, vincristine, and others... 

Examples discussed in this book include digitalis glycosides, which act by inhibiting Na+,K+ ATPase in cell membranes methotrexate, which inhibits the enzyme dihydrofolate reductase and glucocorticoid hormones. 

Antagonists of folic acid include aminoplerin (4-aniino-ptcroylglulamic acidj. methotrexate tamethopterin), pyrimethamine, and 4-ammo-picroylas-partic acid. Synergists include biotin, pantothenic acid, niacin, vitamins B. Bo Bf, B 2. C, and E. somatotrophin (growth hormone), and testosterone. 

The management of cancer includes treatment with alkylating agents (nitrogen mustards and alkyl sulfonates), antimetabolites (methotrexate and purine analogs), natural products (vinca alkaloids and antibiotics), miscellaneous compounds (hydroxyurea, procarbazine, and cis-platinum), hormones (estrogens and corticosteroids), and radioactive isotopes (see Chapter 62). 

The OATP-C, also referred to as liver specific transporter 1 (LST-1) or OATP2, was cloned by number of groups (8,24,25) and was shown to be exclusively expressed in the basolateral membrane of the liver (25). As with OATP-A, OATP-C has broad substrate specificity and transports bile acids (13), sulfate and glucuronide conjugates (25), thyroid hormones (13), and peptides (16), and drugs such as pravastatin (24), methotrexate (26), and rifampin (27). Given its liver-specific expression and broad substrate... 

Drugs used in cancer chemotherapy are cytotoxic drugs, hormones, plant derivatives, radioactive isotopes, and miscellaneous agents (e.g., procarbazine, hydroxyurea, mitotane). The plant-based drugs vincristine, vinblastine, vinorel-bine, etoposide, and campothecins. Radioactive isotopes, such as 131 iodine (131 I), are used in the treatment of thyroid tumors. Cytotoxic drugs (e.g., cis-platin, cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, and methotrexate are used for the treatment of cancer. 

O ATP4G1 is the first member of OATP family predominantly expressed in the kidney and consists of 724 amino adds. It transports cardiac glycosides (digoxin and ouabain), thyroid hormones (T3 and T4), cAMP, and methotrexate. It might be a first step in the transport pathway of digoxin and various compounds into urine in the kidney (Table 3.2) [4]. 

Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative cohtis and Crohn s disease, given parenterally, orally, or rectally. Corticosteroids are believed to modulate the immune system and inhibit production of cytokines and mediators. It is not clear whether the most important steroid effects are systemic or local (mucosal). Budesonide is a corticosteroid that is administered orally in a controlled-release formulation. The drug undergoes extensive first-pass metabolism, so systemic exposure is thought to be minimized. Immunosuppressive agents such as azathioprine, mercaptopurine (a metabolite of azathioprine), methotrexate, or cyclosporine are sometimes used for the treatment of IBD. ... 

Docetaxel and prednisone have recently been shown to improve survival in hormone-refractory metastatic prostate cancer and should be considered standard therapy. Single agents with modest activity in prostate cancer include cyclophosphamide, estramustine, 5-fluorouracil, methotrexate, dacarbazine, mitoxantrone, doxorubicin, pachtaxel, gemcitabine, vinorelbine, and cisplatin. If disease stabilization is included as a favorable response, response rates np to 46% have been reported. Several trials have evalnated the varions combination regimens containing the most active single agents. ... 

Hormonal therapy and chemotherapy versus chemotherapy alone as adjuvant treatment in breast cancer was studied in 236 patients (H8). All presented axillary node involvement and had ERP levels greater than or equal to 10 fmol/mg protein and/or PRP levels greater than or equal to 15 ftnol/mg protein. They were randomized to receive either chemotherapy alone, with 9 courses of cyclophosphamide, methotrexate, and 5-fluorouracil over 6 months, or chemotherapy plus hormonal therapy, with tamoxifen for 2 years. The two groups of patients were comparable except for the mean number of axillary nodes involved (3.4 for the chemotherapy... 

Breast carcinoma (stages 1 and II) CMP regimen Cyclophosphamide plus methotrexate and fluorouracil, or doxorubicin for methotrexate (CAP regimen) tamoxifen if hormone receptor-positive... 

---