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Cell Journal، جلد ۱۳، شماره Supplement، صفحات ۰-۰
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عنوان انگلیسی I-11: Copro-Antiapoptotic Protein Survivin and Lactoferrin Biomarkers for Improved Detection and Nanodelivery to Colon Cancer
چکیده انگلیسی مقاله We and others have found that survivin, a member of the family of inhibitor of apoptosis proteins that is overexpressed in several human tumours. Lactoferrin is also known to express in inflammatory diseases such as inflammatory bowel disease and Crohn's disease. We assessed the differential expression of survivin, other apoptotic biomarkers and lactoferrin in stool and serum samples of colorectal cancer (CRC) patients. We compared serum and stool samples from CRC patients and samples from healthy volunteers using an in vitro enzyme-linked immunosorbent assay to evaluate the survivin and lactoferrin response in patients. The sensitivity of the anti-survivin and lactoferrin response from patients with CRC was 65% and 70%, the specificity was 62% and 75% respectively with good predictive positivity and predictive negativity. Combined detection using survivin and lactoferrin produced better sensitivity (65%) and specificity (90%), respectively. In conclusion a positive association between survivin and lactoferrin concentrations in sera and stool samples of patients with CRCs was established. Our results suggest that analysis of both parameters would assist in screening patients with CRC. Our findings also suggest that the reduction in the serum survivin and copro-lactoferrin levels of advanced CRC patients after chemotherapy can be used as a predictor of response to the chemotherapy but not that of survival. In addition, we developed dominant negative mutant of survivin (SurR9-C84A) and loaded into Alginate enclosed chitosan- calcium phosphate nano carriers (ACSC-NCs), in order to improve the oral bioavailability and to protect the peptide from the locale of gastro intestinal tract. These CSC-NCs loaded with SurR9-C84A were tested in a xenograft mice model of colon cancer. We found all tumor bearing mice regressed tumors significantly. Antitumor activity was mediated by inducing apoptosis and necrosis in tumours. There was significant decrease in angiogenesis and vasculature in the CSC NCs-SurR9- C84A as compared to empty CSC-NCs ingested control tumor mice. In the present study we developed a safe, nontoxic, mucoadhesive, completely biodegradable, compatible and sustain released CSC-NCs as a proof of concept in colon cancer which can be used for other cancer types. Thus, these CSC-NCs can be exploited for oral administration to protect from variable pH in intestinal track and resistance to gastric enzymes which otherwise digest proteins in gastrointestinal tract.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/1494
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