Another possibility can be explained by the fact that Hsp27 might not be a direct tumor antigen but involved only in antigens presentation to the surface of tumor cells. to several types of injury, heat shock, oxidative stress and other unfavorable conditions in order to offset the deleterious effects of cellular stresses (Ciocca et al., 1993; Ferns et al., 2006; Mehlen et al., 1995). Besides its chaperone function, Hsp27 has also been shown to have an anti-apoptotic role by inhibition of caspase-dependent apoptosis, preventing a wide variety of apoptotic brokers from causing cell death (Calderwood et al., 2006; Mehlen et al., 1996; Vidyasagar et al., 2012). This may confers a survival advantage to cells and may contribute to the reduction in apoptosis TCS 401 free base (Batchelder et al., 2009). With respect to the anti-apoptotic role, Hsp27 is overexpressed in various cancers and display a relationship with patients survival or response to therapy in specific cancer types and may serve as a biomarker of disease and novel therapeutic target. Several studies have shown an association between Hsp27 with many types of cancer including gastric, liver, and prostate TCS 401 free base carcinoma, osteosarcoma, rectal, lung, and breast cancer especially in terms of prognosis and treatment (Ciocca and Calderwood, 2005; Kang et al., 2008; Tweedle et al., 2010; Vidyasagar et al., 2012). It has been reported that the up-regulation of anti-apoptotic pathways induced by Hsp27 enhanced the resistance of cancer cells to apoptosis and may also be implicated in resistance to chemotherapy in breast cancer and is associated with drug-resistant phenotypes (Calderwood et al., 2006). Therefore, it seems to be the most important to control Hsp27 in cancer cells to conquer the cancers. However, Hsps can also become targets for cancer therapy drugs, as well as targets for the immune system. In vitro studies have shown that Hsps are released from cells exposed to stress, and increased serum concentrations have been implicated in the immune response against HSPs (Burut TCS 401 free base et al., 2010; Child et al., 1995; Liao et al., 2000). In turn, TCS 401 free base the immune response against Hsps has been implicated in the pathogenesis of some diseases including atherosclerosis, cardiovascular disease and cancer in the general population (Burt et al., 2009; Mandal et al., 2004; Trieb et al., 2000). After being released into the systemic circulation, Hsp27 can induce an autoimmune response with the production of anti- Hsp27 antibodies (Conroy et al., 1998). The development of breast cancer is a complex molecular process that arise from terminal ductal lobular units (Batchelder et al., 2009). Several lines of evidence exist to indicate that expression of Hsp27 may be of some prognostic value in breast carcinomas (Love and King, 1994; Thor et al., 1991). It is also reported that increased expression of Hsp27 in cancer cells causes the development of chemotherapeutic drug resistance and conversely, down-regulation of Hsp27 in breast cancer cell line MCF-7/MG with antisense- Hsp27 enhanced the sensitivity of the cells to doxorubicin (Oesterreich et al., 1993). Because overexpression of Hsp27 correlates with poor survival in breast cancer patients, investigating whether patients with breast cancer have circulating antibodies to Hsp27, may also be of importance. Conroy et al. have previously reported that high plasma antibody titres against Hsp27 are associated with improved survival in patients with breast cancer (Conroy et al., 1998), but further studies in other groups TCS 401 free base of subjects may be helpful to investigate a more subtle effect of this Hsp27 and anti- Hsp27 antibody in development of this serious cancer phenotype. The present study was aimed to investigate changes in serum HSP antigen and anti- Hsp27 antibody concentrations associated with GLB1 breast cancer complications and 2-year disease-free survival and also to correlate them with clinical features and prognosis of the disease. Materials and Methods Subjects Sera from 97 patients with breast cancer (mean age: 47.2 years, range 27.0C74.0) diagnosed at Omid and Ghaem hospitals (Mashhad, Iran) between 2009 and 2011 along with sera from 65 genetically.
