PURPOSE: Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue. METHODS: Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively. RESULTS: Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 microM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant. CONCLUSION: The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition may also, in addition to Delta9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.
Arachidonic Acid ; Breast ; Breast Neoplasms* ; Chromatography, Liquid ; Fatty Acid Desaturases ; Fatty Acids, Monounsaturated ; Humans ; L-Lactate Dehydrogenase ; Linoleic Acid ; Lipogenesis ; Stearoyl-CoA Desaturase* ; Tissue Culture Techniques

OBJECTIVES: The objective of this study was to evaluate the prevalence of Strongyloides stercoralis and other intestinal parasites in patients receiving immunosuppressive drugs in northern Iran and to investigate related risk factors. METHODS: This cross-sectional study was conducted among 494 patients receiving immunosuppressive drugs, including cancer patients undergoing chemotherapy (n=188) and those treated with prolonged corticosteroid administration (n=306). All fresh fecal samples were examined using the direct wet-mount, formalin ethyl acetate concentration, and agar plate culture techniques. RESULTS: In total, 16.8% of patients were positive for at least 1 intestinal parasite; the helminthic and protozoan infection rates were 5.1% and 12.3%, respectively. The infection rate was significantly higher in corticosteroid-treated individuals (19.6%) than cancer patients (12.2%) (p<0.05). The prevalence rate of S. stercoralis among patients receiving chemotherapy and those treated with corticosteroids were 4.3% and 5.2%, respectively. The prevalence rate of S. stercoralis infection was significantly higher in older patients (p<0.05). CONCLUSIONS Strongyloidiasis is one of the most common parasites among patients receiving immunosuppressive drugs in northern Iran. Early diagnosis and proper treatment of these patients are necessary to minimize the complications of severe strongyloidiasis.

OBJECTIVES: The objective of this study was to evaluate the prevalence of Strongyloides stercoralis and other intestinal parasites in patients receiving immunosuppressive drugs in northern Iran and to investigate related risk factors. METHODS: This cross-sectional study was conducted among 494 patients receiving immunosuppressive drugs, including cancer patients undergoing chemotherapy (n=188) and those treated with prolonged corticosteroid administration (n=306). All fresh fecal samples were examined using the direct wet-mount, formalin ethyl acetate concentration, and agar plate culture techniques. RESULTS: In total, 16.8% of patients were positive for at least 1 intestinal parasite; the helminthic and protozoan infection rates were 5.1% and 12.3%, respectively. The infection rate was significantly higher in corticosteroid-treated individuals (19.6%) than cancer patients (12.2%) (p<0.05). The prevalence rate of S. stercoralis among patients receiving chemotherapy and those treated with corticosteroids were 4.3% and 5.2%, respectively. The prevalence rate of S. stercoralis infection was significantly higher in older patients (p<0.05). CONCLUSIONS Strongyloidiasis is one of the most common parasites among patients receiving immunosuppressive drugs in northern Iran. Early diagnosis and proper treatment of these patients are necessary to minimize the complications of severe strongyloidiasis.