Side Effects of Anticancer Drugs used in Chemotherapy

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Breast cancer is the most common type of cancer in women and is a leading cause of cancer related deaths worldwide. Adjuvant chemotherapy is standard systemic treatment for breast cancer patients after surgical removal of tumor [1]. The anticancer drugs used in chemotherapy for tumors, kill cancer cells predominantly by triggering apoptosis in them [2]. Susceptibility of cancer cells to apoptosis depends on their capabilities to express the components of apoptosis pathway and to activate them in response to extrinsic or intrinsic death signals [3]. The extrinsic pathways are mediated by the death receptor- and the cytotoxic granule-mediated pathways. On the other hand, the intrinsic death mechanisms are mediated by the mitochondrial pathway [3,4]. FasR/FasL system, cytotoxic granule mediated pathway and mitochondrial pathway are major regulators of apoptosis involved in cancer cell death induced by immune system and chemotherapeutic agents [4]. The FasR/FasL system is a key signal pathway involved in regulation of apoptosis in several different cell types [2, 5]. Fas (CD 95), a 48 kDa type I transmembrane receptor, is expressed in activated lymphocytes, in variety of tissues of lymphoid or non-lymphoid origin as well as tumor cells [2,6]. Fas ligand (CD 95L), a 40 kDa type II transmembrane molecule occurs in membrane bound and soluble form, generated through cleavage by metalloproteinase. FasL is produced by activated T cells and plays a crucial role in the regulation of immune system by triggering autocrine suicide or paracrine death in neighboring lymphocytes or other target cells including tumors [2]. It has been shown that FasL expression is induced following chemotherapy [7]. Granzyme B is a serine protease found in the cy... ... middle of paper ... ...J, Radaszkiewicz T, Meijer CJ. Granzyme B expressing peripheral T-cell lymphomas: Neoplastic equivalents of activated cytotoxic T cells with preference for mucosa-associated lymphoid tissue localization. Blood, 1994; 84(11): 3785-91. 23. Spaeny-Dekking EHA, Hanna WL, Wolbink AM, Wever PC, Kummer JA, Swaak AJ, Middeldorp JM, Huisman HG, Froelich CJ, Hack CE. Extracellular granzymes A and B in humans: Detection of native species during CTL responses in vitro and in vivo. J Immunol, 1998; 160: 3610-6. 24. Boivin WA, Cooper DM, Hiebert PR, Granville DJ. Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma. Lab Invest, 2009; 89: 1195-1220. 25. Tsavaris N, Kosmas C, Vadiaka M, Kanelopoulos P, Boulamatsis D. Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes. Br J Cancer, 2002;87: 21-7.

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