این نتایج نشان می دهد پپتید های طراحی شده در این مطالعه اثر بالقوه بر علیه رسپتور TRK B و در نتیجه سلو لهای سرطانی مورد مطالعه دارد.
Conclusion
رسپتور Trk B به عنوان یک عامل انکوژن می باشد و نتایج بدست آمده نشان داد که روش های بیوانفورماتیکی یک روش مناسبی برای طراحی آپتامر های پپتیدی می باشد و مهار رسپتور Trk B توسط پپتید های طراحی شده باعث مهار رشد در سلولهای سرطانی و مهار مسیر سیگنالینگ سلولی در جهت آنژیوژنسیس می شود و با توجه به نتایج بدست آمده در MTT assay ، فلوسایتومتری و western blotting پپتید های طراحی شده در غلظت ۳۵۰ نانو مولار اثر سیتو توکسیسیتی بهتری نسبت به سیکلوتراکسین دارد.
پیشنهادات
۱٫ مطالعه تاثیر پپتید های طراحی شده درin vivo.
۲٫ سیکلیک کرن پپتید های طراحی شده و بررسی اثر آنها درin vitro و in vivo .
۳٫ تعیین میزان تمایل پپتید های طراحی شده به رسپتور با بهره گرفتن از روش های labeling.
۴٫ استفاده کردن از الکتروفورز ۲ بعدی برای تشخیص تاثیر پپتید ها در مسیرهای سیگنالینگ مختلف سلولی.

برای دانلود متن کامل پایان نامه به سایت fotka.ir مراجعه نمایید.

منابع

۱٫ Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011. CA: A Cancer Journal for Clinicians. 2011;61(4):212-36.
۲٫ Rodu B, Cole P. The fifty-year decline of cancer in America. Journal of clinical oncology. 2001;19(1):239-41.
۳٫ McPhee SJ, Papadakis MA, Rabow MW. Current medical diagnosis & treatment 2010: McGraw-Hill Medical; 2010.
۴٫ Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. International Journal of Cancer. 1975;15(4):617-31.
۵٫ Ames BN. Identifying environmental chemicals causing mutations and cancer. Jurimetrics J. 1979;20:326.
۶٫ Hill M, Hawksworth G, Tattersall G. Bacteria, nitrosamines and cancer of the stomach. British journal of cancer. 1973;28(6):562.
۷٫ Issenberg P, editor. Nitrite, nitrosamines, and cancer. Federation proceedings; 1976.
۸٫ Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. New England Journal of Medicine. 1997;336(20):1401-8.
۹٫ Ford D, Easton D, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. American journal of human genetics. 1998;62(3):676.
۱۰٫ Levine AJ. The tumor suppressor genes. Annual review of biochemistry. 1993;62(1):623-51.
۱۱٫ Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994;73(8):2013-26.
۱۲٫ Osborne C, Wilson P, Tripathy D. Oncogenes and Tumor Suppressor Genes in Breast Cancer: Potential Diagnostic and Therapeutic Applications. The Oncologist. 2004;9(4):361.
۱۳٫ Latif F, Tory K, Gnarra J, Yao M, Duh F-M, Orcutt ML, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science (New York, NY). 1993;260(5112):1317.
۱۴٫ Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin H, Liebermann DA, et al. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994;9(6):1799.
۱۵٫ Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994;78(5):773.
۱۶٫ Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, et al. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science (New York, NY). 1995;269(5224):682.
۱۷٫ Ehrlich M. Cancer-linked DNA hypomethylation and its relationship to hypermethylation. DNA Methylation: Development, Genetic Disease and Cancer. 2006:251-74.
۱۸٫ Choi SH, Worswick S, Byun HM, Shear T, Soussa JC, Wolff EM, et al. Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer. International Journal of Cancer. 2009;125(3):723-9.
۱۹٫ Shao C, Lacey M, Dubeau L, Ehrlich M. Hemimethylation footprints of DNA demethylation in cancer. Epigenetics. 2009;4(3):165-75.
۲۰٫ BOZKURT C, BOZKURT S, ARDA N, ERTEM AU, ŞAHİN G, YÜKSEK N, et al. P16 and p27 tumor suppressor gene methylation status in childhood Wilms tumor cases. TurkJMedSci. 2011;41(4):633-8.
۲۱٫ Suzuki Y, Tamura G, Satodate R, Fujioka T. Infrequent Mutation of p53 Gene in Human Renal Cell Carcinoma Detected by Polymerase Chain Reaction Single‐strand Conformation Polymorphism Analysis. Cancer science. 1992;83(3):233-5.
۲۲٫ Lim D-S, Hasty P. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Molecular and cellular biology. 1996;16(12):7133-43.
۲۳٫ Wittekind C, Compton CC, Greene FL, Sobin LH. TNM residual tumor classification revisited. Cancer. 2002;94(9):2511-6.
۲۴٫ Varricchio CG. A cancer source book for nurses: Jones & Bartlett Learning; 2004.
۲۵٫ Miller A, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47(1):207-14.
۲۶٫ Strong LC. Genetic etiology of cancer. Cancer. 2006;40(S1):438-44.
۲۷٫ Lingeman C. Etiology of cancer of the human ovary: a review. Journal of the National Cancer Institute. 1974;53(6):1603.
۲۸٫ Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS, Holland JF, et al. Holland-Frei cancer medicine. 2003.
۲۹٫ Alfreda L, Claudiab S, Svend G, Norbertd G, Peterb K. Complementary and alternative treatment methods in children with cancer: A population-based retrospective survey on the prevalence of use in Germany. Eur J Cancer. 2008;44:2233-40.
۳۰٫ Aina OH, Sroka TC, Chen ML, Lam KS. Therapeutic cancer targeting peptides. Peptide Science. 2002;66(3):184-99.
۳۱٫ Lien S, Lowman HB. Therapeutic peptides. Trends in biotechnology. 2003;21(12):556-62.
۳۲٫ Shadidi M, Sioud M. Selective targeting of cancer cells using synthetic peptides. Drug resistance updates. 2003;6(6):363-71.
۳۳٫ Zhang B, Zhang Y, Wang J, Zhang Y, Chen J, Pan Y, et al. Screening and identification of a targeting peptide to hepatocarcinoma from a phage display peptide library. Molecular Medicine. 2007;13(5-6):246.
۳۴٫ Press OW, Eary JF, Appelbaum FR, Martin PJ, Badger CC, Nelp WB, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. New England Journal of Medicine. 1993;329(17):1219-24.
۳۵٫ Shu Y-Z. Recent natural products based drug development: a pharmaceutical industry perspective. Journal of natural products. 1998;61(8):1053-71.
۳۶٫ Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M. Synthetic therapeutic peptides: science and market. Drug discovery today. 2010;15(1):40-56.
۳۷٫ Gordon EM, Kerwin JF. Combinatorial chemistry and molecular diversity in drug discovery: Wiley-Liss New York; 1998.
۳۸٫ Crawford M, Woodman R, Ferrigno PK. Peptide aptamers: tools for biology and drug discovery. Briefings in Functional Genomics & Proteomics. 2003;2(1):72-9.
۳۹٫ Saxena SK, Saxena S, Saxena R, Arvinda M, Swamy AG, Nair MP. Emerging Trends, Challenges and Prospects in Antiviral Therapeutics and Drug Development for Infectious Diseases. Electronic Journal of Biology. 2010;6(2):26-31.
۴۰٫ Hicke BJ, Stephens AW, Gould T, Chang Y-F, Lynott CK, Heil J, et al. Tumor targeting by an aptamer. Journal of Nuclear Medicine. 2006;47(4):668-78.
۴۱٫ Nagant C, Tré-Hardy M, El-Ouaaliti M, Savage P, Devleeschouwer M, Dehaye J-P. Interaction between tobramycin and CSA-13 on clinical isolates of Pseudomonas aeruginosa in a model of young and mature biofilms. Applied microbiology and biotechnology. 2010;88(1):251-63.
۴۲٫ Vincenti MP,
Clark IM, Brinckerhoff CE. Using inhibitors of metalloproteinases to treat arthritis. Easier said than done? Arthritis & Rheumatism. 1994;37(8):1115-26.
۴۳٫ Leszczyńska K, Namiot A, Cruz K, Byfield F, Won E, Mendez G, et al. Potential of ceragenin CSA‐۱۳ and its mixture with pluronic F‐۱۲۷ as treatment of topical bacterial infections. Journal of applied microbiology. 2011;110(1):229-38.
۴۴٫ Flowers LO, Subramaniam PS, Johnson HM. A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells. Oncogene. 2005;24(12):2114-20.
۴۵٫ Bairoch A, Apweiler R, Wu CH, Barker WC, Boeckmann B, Ferro S, et al. The universal protein resource (UniProt). Nucleic Acids Research. 2005;33(suppl 1):D154-D9.
۴۶٫ Klein R, Nanduri V, Jing S, Lamballe F, Tapley P, Bryant S, et al. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991;66(2):395.
۴۷٫ Klein R, Lamballe F, Bryant S, Barbacid M. The< i> trk</i> B tyrosine protein kinase is a receptor for neurotrophin-4. Neuron. 1992;8(5):947-56.
۴۸٫ Barbacid M. Neurotrophic factors and their receptors. Current opinion in cell biology. 1995;7(2):148-55.
۴۹٫ Zirrgiebel U, Ohga Y, Carter B, Berninger B, Inagaki N, Thoenen H, et al. Characterization of TrkB Receptor‐Mediated Signaling Pathways in Rat Cerebellar Granule Neurons: Involvement of Protein Kinase C in Neuronal Survival. Journal of neurochemistry. 1995;65(5):2241-50.
۵۰٫ Islam O, Loo TX, Heese K. Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling pathways. Current Neurovascular Research. 2009;6(1):42-53.
۵۱٫ Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, et al. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell stem cell. 2011;8(1):59-71.
۵۲٫ Encinas M, Iglesias M, Llecha N, Comella J. Extracellular‐Regulated Kinases and Phosphatidylinositol 3‐Kinase Are Involved in Brain‐Derived Neurotrophic Factor‐Mediated Survival and neuritogenesis of the Neuroblastoma Cell Line SH‐SY5Y. Journal of neurochemistry. 2002;73(4):1409-21.
۵۳٫ Gaiddon C, Loeffler J, Larmet Y. Brain‐Derived Neurotrophic Factor Stimulates AP‐۱ and Cyclic AMP‐Responsive Element Dependent Transcriptional Activity in Central Nervous System Neurons. Journal of neurochemistry. 1996;66(6):2279-86.
۵۴٫ Ito Y, Yamamoto M, Li M, Mitsuma N, Tanaka F, Doyu M, et al. Temporal expression of mRNAs for neuropoietic cytokines, interleukin-11 (IL-11), oncostatin M (OSM), cardiotrophin-1 (CT-1) and their receptors (IL-11Rα and OSMRβ) in peripheral nerve injury. Neurochemical research. 2000;25(8):1113-8.
۵۵٫ Labouyrie E, Dubus P, Groppi A, Mahon FX, Ferrer J, Parrens M, et al. Expression of neurotrophins and their receptors in human bone marrow. The American journal of pathology. 1999;154(2):405-15.
۵۶٫ Pearse RN, Swendeman SL, Li Y, Rafii D, Hempstead BL. A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival. Blood. 2005;105(11):4429-36.
۵۷٫ Desmet C, Peeper D. The neurotrophic receptor TrkB: a drug target in anti-cancer therapy? Cellular and molecular life sciences. 2006;63(7):755-9.
۵۸٫ Marchetti A, Felicioni L, Pelosi G, Del Grammastro M, Fumagalli C, Sciarrotta M, et al. Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung. Human mutation. 2008;29(5):609-16.
۵۹٫ Zhang Z, Han L, Liu Y, Liang X, Sun W. Up-regulation of Tropomyosin related kinase B contributes to resistance to detachment-induced apoptosis in hepatoma multicellular aggregations. Molecular biology reports. 2009;36(5):1211-6.
۶۰٫ Huang EJ, Wilkinson GA, Fariñas I, Backus C, Zang K, Wong SL, et al. Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC. Development. 1999;126(10):2191-203.
۶۱٫ Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annual review of neuroscience. 2001;24:677.