Major adverse effects include myelosuppression (mainly affecting white cells and platelets), bladder toxicity in the form of hemorrhagic cystitis, dysuria, and increased urinary frequency. It is used widely in the treatment of breast cancer, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, ovarian cancer, bone and soft-tissue sarcoma, rhabdomyosarcoma, and neuroblastoma. Cyclophosphamide is a cell cycle-nonspecific agent that is active in all phases of the cell cycle. Both metabolites can cause DNA cross-links, resulting in an inhibition of DNA synthesis. Upon activation by the cytochrome P450 microsomal system, the cytotoxic metabolites phosphoramide mustard and acrolein are formed. Gilman, in Cancer Immunotherapy, 2007 8 Cyclophosphamide (Cytoxan®)Ĭyclophosphamide (N,N-bis(2-chloroethyl)-2-oxo-1-oxa-3-aza-2u-phosphacyclohexan-2-amine) is a mustard compound that is activated in the liver. In addition, through interference with gene expression, changes in the level of cellular proteins, numerous injury mechanisms, and compromising the immune system, sulfur mustard causes long-term injuries to the lungs, skin, and eyes. Moreover, mustard has cholinergic effects and stimulates muscarinic and nicotinic receptors. Since the first effects of mustard gas start with alkylation of DNA and changes in other macromolecules, these changes end in disorders in the dermoepidermal junction and complete blisters are formed following active inflammatory responses in the affected tissue. It has been shown that sulfur mustard causes overactivation of serine and matrix metalloproteinase. In addition, through releasing inflammatory mediators and cytokines, sulfur mustard results in the release of prostaglandins and activation of NF-kB. Moreover, sulfur mustard induces apoptosis through intrinsic and extrinsic pathways. Sulfur mustard can damage the DNA molecule directly and indirectly and activates poly(adenosine diphosphate-ribose) polymerase and decreases nicotine adenine dinucleotide, eventually resulting in apoptosis. An example of the theories of the mechanisms of mustard gas injury and the related pathways.
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