Cancer dactinomycin

Wolff J A, Newton WA Jr, KrivitW, etal. Single versus multiple dose dactinomycin therapy of Wilms s tumor. A controlled co-operative study conducted by the Children s Cancer Study Group A (formerly Acute Leukemia Co-operative Chemotherapy Group A). N Engl J Med 1968 279(6) 290-294. 

Cytotoxic agents which are used both for the treatment of cancer as for their immunosuppressive activity include cyclophosphamide, methotrexate, chlorambucil, vincristine, vinblastine and dactinomycin. 

Unfortunately, many human cancers have a large proportion of cells in the resting phase, and these cells are also resistant to the class 3 agents, which include cyclophosphamide, dactinomycin, and fluorouracil. 

See Chapter 40 in Lippincott s Illustrated Reviews Pharmacology (3rd Ed.) and Chapter 38 (2nd Ed.) for a discussion of dactinomycin in treating cancer. 

The mechanism of action of mithramycin (Mithracin) is similar to that of dactinomycin. It is used in patients with advanced disseminated tumors of the testis and for the treatment of hypercalcemia associated with cancer. Mithramycin may cause gastrointestinal injury, bone marrow depression, hepatic and renal damage, and hemorrhagic tendency (see Chapter 62). 

Screening of microbial products has led to the discovery of a number of growth inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, dactinomycin, bleomycin, and mitomycin. 

Microbial sources have been a very rich source for cancer chemotherapeutic agents. Of particular note is the Strep-tomyces spp., which has been responsible for the production of many approved anticancer agents that are in clinical practice. These agents are represented by highly diverse structural classes exemplified by the anthracycline family (e.g., doxom-bicin, 73) (72-74), actinomycin family (e.g., dactinomycin, 74), glycopeptides family (e.g., bleomycins A2 and B2, 75 and 76) (75), and mitomycin family (e.g., mitomycin C, 77) (72, 76). All these compounds specifically interact with DNA for then-mode of action. 

Dactinomycin is nsed to treat cancers in children, in par-ticnlar Wilms tnmor. It has similar adverse effects to doxombicin. 

Green DM, Finklestein JZ, Norkool P, D Angio GJ. Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine. A report of the National Wilms Tumor Study. Cancer 1988 62(2) 270-3. 

Dactinomycin is mainly used to treat cancers in children. 

Crisantaspase - chemotherapy of cancers Cyclophosphamide - alkylating agent, cancer chemotherapy Cytarabine - chemotherapy of leukaemia Dactinomycin - chemotherapy of cancers Dantrolene - skeletal muscle relaxant spasticity Desflurane - general anaesthetic... 

Among all ABC transporters, P-gp, also known as MDRl protein, ABCBl or CD243, is probably the most studied and characterized member. It was first found as a 170-kDa ATP-dependent membrane glycoprotein that acts as a drug efflux pump [15], P-gp is a broad-spectrum transporter, capable of transporting several structurally and functionally unrelated substrate molecules. Its substrates are typically hydrophobic, amphipathic products, including many chemotherapeutic compounds used for cancer treatment, e.g., vinca alkaloids (vincristine, vinblastine), taxanes (paclitaxel, docetaxel), epipodophyllotoxins (etoposide, teniposide), anthracyclines (doxorubicin, daunorubicin, epirubicin), topotecan, dactinomycin, and mitomycin-C [37]. 

Dactinomycin, or actinomycin D as it was called when first introduced, has shown striking curative properties in Wilms s tumour of the kidney which forms a high proportion of all malignant tumours in children. Under its influence, even pulmonary metastases caused by this tumour regress (Farber and Mitus, 1968). Forms of cancer requiring longer treatment are not suitable for this drug, which has only moderate selectivity. 

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