ارزیابی اثرات برخی پپتید های اتصال یابنده به رسپتور Trk Bبر روی رده های سلولی Sk-ov-3 و Ov-car-3
توضیحات تکمیلی
ارزیابی اثرات برخی پپتید های اتصال یابنده به رسپتور Trk Bبر روی رده های سلولی Sk-ov-3 و Ov-car-3این پایان نامه در قالب فرمت word قابل ویرایش ، آماده پرینت و ارائه به عنوان پروژه پایانی میباشد.سرطان به عنوان دومین عامل مرگ ومیر بعد از بیماریهای قلبی ساخته شده است،یکی از مهمترین پروتئینهای انکوژن TREKB می باشد که لیگاند اختصاصی آن BDNF(Brain derived neutrophic factor) می باشد وبیان بیش از حد این گیرنده در سرطانهای پروستات و مولتیپل مایلوما و تخمدان و تیروئید مشاهده شده است. BDNF با اتصال خود به گیرنده TRK B باعث دایمراسیون در این گیرنده و ایجاد سیگنالهایی در مسیرآنژیوژنسیس و افزایش میزان تعداد سلولها می شود ،هدف این مطالعه طراحی پپتیدهایی بر علیه گیرنده TRK B (Tropomyosin Receptor B Kinase) به عنوان مهار کننده می باشد،در این مطالعه ابتدا در قسمت Insilico کتابخانه پپتیدی با روش sequence tolerance و backrub ساخته شد و بهینه سازی انرژی پپتید با با استفاده از روش مونتو کارلوانجام شد و پپتیدهایی با حداکثر پایداری بر اساس انرژی توسط نرم افزارRانتخاب شدند و سپس ساختار سه بعدی پپتیدها با استفاده از روش دینامیک مولکولی با استفاده از نرم افزار7 Hyperchem تعیین گردیدو Docking این پپتید ها توسط نرم افزار HADDOCK تکمیل گردید،نحوه اتصال آنها توسط نرم افزار Lighplot انالیز شد و ساختار سه بعدی این پپتید ها با گیرنده توسط نرم افزار PYMOL نمایش داده شد و در نهایت توالی 2 عدد از بهترین پپتیدها با کمترین انرژی توسط شرکت Tag copeghene دانمارک سنتز شدند . در قسمت آزمایشگاهی، ابتدا با انجام تست MTT اثر توکسیک پپتید یک و دو در غلظتهای 50 ،200 ،350، 500 نانو مولار و سیکلو تراکسین در غلظت 200 نانو مولار به عنوان کنترل مثبت بر روی رده سلولی ,RPMI822, Sk-ov-3,Ov-car-3U266 مطالعه شد و سپس فلوسایتومتری برای سلولها با کیت ّّّFITC-Annexin V در غلظتهای 450 و 350 نانو مولار برای پپتید یک و دو و در غلظت 200 نانو مولار برای سیکلو تراکسین انجام گردید، سپس پروتینها بعد از تیمار با استفاده از لیز بافر ، لیز شده و پروتئین های آنها استخراج گردید و غلظت پروتئین توسط دستگاه اسپکترومتری برادفورد مشخص شد و سپس Western blotting برای بررسی میزان بیان پروتئینها بعداز تیمار انجام شد. یافته هانشان داد که پپتیدهای طراحی شده دارای تمایل اتصال بالایی به رسپتور TrkBمی باشند و باعث مهار رشد سلولی در رده سلولی مذکور شده اند و نتایج این مطالعه نشان داد که مهار رسپتور Trk B می تواند به توقف رشد سلول سرطانی منجر شود. سرطان سلولها به طور غیر عادی تقسیم و تکثیر شده و بافتهای سالم را از بین برده می شود. سلولهای سرطانی از حالت عادی تقسیم و رشد سلولها جدا می شود. سرطان به عنوان دومین عامل مرگ ومیر در جهان بعد ازسکته قلبی شناخته شده است و در واقع سرطان به علت مرگ بالای آن به عنوان یک عامل کشنده محسوب می شود و طبق آمار جهانی در سال 2011 در حدود 1596670 نفر مبتلا و در حدود 571950 نفر در اثر این بیماری جان خود را از دست داده اند<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Siegel20114767(1)4767<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4767<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>ref-type name="Journal Article">17Siegel, RebeccaWard, ElizabethBrawley, OtisJemal, AhmedinCancer statistics, 2<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>011<span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>title>CA: A Cancer Journal for CliniciansCA: A Cancer Journal for Clinicians212-23661420110007923510.3322/caac.20121<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(1)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'>. آمار نشان داده است مرگ در اثر سر طان 1 نفر از هر 4 آمریکایی می باشد و در ایران سر طان به عنوان سومین عامل مرگ ومیر می باشد<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Rodu20014857(2)4857<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4857<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>ref-type name="Journal Article">17Rodu, BradCole, PhilipThe fifty-year decline of cancer in AmericaJournal of clinical oncologyJournal of clinical oncology239-24119120010732-183X<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(2)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'>. بیشترین سرطانهای شایع شامل سرطان های ریه، معده ، کولورکتال، کبد و سرطان پستان می باشد<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE McPhee20104858(3, 4)4858<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4858<ref-type name="Book">6McPhee, Stephen JPapadakis, Maxine ARabow, Michael WCurrent medical diagnosis & treatment 20102010McGraw-Hill Medical0071624449Armstrong197548594859<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4859<ref-type name="Journal Article">17Armstrong, BruceDoll, RichardEnvironmental factors and cancer incidence and mortality in different countries, with special reference to dietary practicesInternational Journal of CancerInternational Journal of Cancer617-63115419751097-0215<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(3, 4)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>. سرطان دارای دو جنبه محیطی( در حدود 90% ) و ژنتیکی ( در حدود 10%) می باشد که از علتهای محیطی می توان به سیگار، رژیم های غذایی و چاقی، پرتوافکنی، عفونت، استرس، فقدان فعالیت فیزیکی وآلودگی محیطی اشاره نمود<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Ames19794860(5)4860<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4860<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>ref-type name="Journal Article">17Ames, Bruce NIdentifying environmental chemicals causing mutations and cancerJurimetrics J.Jurimetrics J.326201979<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(5)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'>. تنباکو دارای چندین عامل کارسینوژن شامل نیتروزامین و هیدروکربن های آروماتیک است که ارتباط مستقیم با سرطان ریه و حنجره دارند و رژیم غذایی و کمبود فعالیت فیزیکی علت 30% از سرطان ها می باشد<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Hill19734861(6, 7)4861<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4861<ref-type name="Journal Article">17Hill, MJHawksworth, GTattersall, GBacteria, nitrosamines and cancer of the stomachBritish journal of cancerBritish journal of cancer5622861973Issenberg197648624862<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4862<ref-type name="Conference Proceedings">10<span dir=RTL><span lang=FA style='font-size:14.0pt;line-height:150%; font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>type>Issenberg, PNitrite, nitrosamines, and cancerFederation proceedings132235<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>1976<span dir=LTR style='font-size:14.0pt; line-height:150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>year>0014-9446<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(6, 7)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>. پرتوافکنی یونیزه و غیر یونیزه با سرطان در ارتباط می باشند. شکست DNA بوسیله پرتو افکنی منجر به فعالیت ژنی، خاموش شدن و حذف شدگی در کروموزوم می شود. وراثت در بسیاری از سرطانها نقش مهمی ندارد ولی بعضی از جهش ها در ژن BRCA1 منجر به سرطان پستان و تخمدان می شود که به عدم تعادل تولید سلولها و مرگ سلولی منجر می شود که دو جنبه مهم در چرخه سلولی می باشند<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE<span lang=FA dir=LTR style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE.DATA<span lang=FA style='font-size: 14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'> 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<span style='mso-element:field-separator'>(8, 9) 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<span lang=FA style='font-size: 14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span style='mso-element:field-end'>. عوامل ژنتیکی به 2 گروه طبقه بندی می شوند، انکوژن ها که منجر به رشد سلولی می شود و گروه دیگر که نقش مهمی در مهار رشد و تقسیم سلولی دارند به نام تومور ساپرسور هاشناخته شده اند<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Levine19934865(10, 11)4865<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4865<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>keys><ref-type name="Journal Article">17Levine, Arnold JThe tumor suppressor genesAnnual review of biochemistry<span dir=RTL><span lang=FA style='font-size:14.0pt;line-height:150%; font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>periodical>Annual review of biochemistry623-65162119930066-4154Kerr1<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>994<span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>Year>48664866<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4866<ref-type name="Journal Article">17Kerr, John FRWinterford, Clay MHarmon, Brian VApoptosis. Its significance in cancer and cancer therapyCancer<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>Cancer2013-202673819941097-0142<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(10, 11)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>. از مهمترین انکوژن ها می توان RAS ,WNT ,MYC ,ERK و TRK را نام برد<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Osborne20044867(12)4867<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4867<ref-type name="Journal Article">17Osborne, CynthiaWilson, PaschalTripathy, DebuOncogenes and Tumor Suppressor Genes in BreastCancer: Potential Diagnostic and Therapeutic ApplicationsThe OncologistThe Oncologist361942<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>004<span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>year><span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(12)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'> و از تومور ساپرسورها می توان به p21, p27 p53, p16, p15, p19 وp18 که در سرطانهای مختلف یافت شده اند اشاره کرد<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Latif19934869(13, 14)4869<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4869<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>keys><ref-type name="Journal Article">17Latif, FaridaTory, KalmanGnarra, JamesYao, MasahiroDuh, Fuh-MeiOrcutt, Mary Lou<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'>><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>author>Stackhouse, ThomasKuzmin, IgorModi, WilliamGeil, LauraIdentification of the von Hippel-Lindau disease tumor suppressor gene<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>Science (New York, NY)Science (New York, NY)1317260511219930036-8075Miyashita199448704870<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4870<ref-type name="Journal Article">17<span dir=RTL><span lang=FA style='font-size:14.0pt;line-height:150%; font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>type>Miyashita, ToshiyukiKrajewski, StanislawKrajewska, MWang, Hong GangLin, HKLiebermann, Dan AHoffman, Barbara<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'>><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>author>Reed, John CTumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivoOncogeneOncogene17999619940950-9232<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(13, 14)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>. البته لازم به ذکر است که تغییرات ژنتیکی برای ایجاد بعضی از سرطان ها لازم می باشد که این جهش ها به میزان متفاوتی در سرطان های مختلف رخ می دهند. اخیرا نشان داده شده است که تعدادی از پروتو انکوژن ها و تومور ساپرسور ها در سلول به وسیله سیستم تخریبی ubiquitin-proteasome کنترل می شوند<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Palombella19944871(15, 16)4871<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4871<ref-type name="Journal Article">17Palombella, Vito JRando, Oliver JGoldberg, Alfred LManiatis, TomTheubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa BCellCell77378519940092-8674Pagano199548724872<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4872<ref-type name="Journal Article">17Pagano, MicheleTam, Sun WTheodoras, Anne MBeer-Romero, PeggyDel Sal, GianninoChau, VincentYew, P RenéeDraetta, Giulio FRolfe, MarkRole of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27Science (New York, NY)Science (New York, NY)682269522419950036-8075<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(15, 16)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>، از عوامل دیگری که درایجاد سرطان نقش دارند می توان به تغییرات اپی ژنتیک شامل هایپومتیلاسیون و هایپرمتیلاسیون در سطح DNA اشاره کرد<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Ehrlich20064873(17, 18)4873<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4873<ref-type name="Journal Article">17Ehrlich, MCancer-linked DNA hypomethylation and its relationship to hypermethylationDNA Methylation: Development, Genetic Disease and CancerDNA Methylation: Development, Genetic Disease and Cancer251-2742006Choi200948744874<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4874<ref-type name="Journal Article">17Choi, Si HoWorswick, ScottByun, Hyang<span dir=LTR style='font-size:14.0pt;line-height:150%;font-family: 'Cambria Math','serif';mso-bidi-font-family:'Cambria Math';mso-bidi-language: FA'>‐<span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family: 'B Nazanin';mso-bidi-language:FA'>MinShear, TaliaSoussa, John CWolff, Erika MDouer, DanGarcia<span dir=LTR style='font-size: 14.0pt;line-height:150%;font-family:'Cambria Math','serif';mso-bidi-font-family: 'Cambria Math';mso-bidi-language:FA'>‐<span dir=LTR style='font-size: 14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language: FA'>Manero, GuillermoLiang, GangningYang, Allen SChanges in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancerInternational Journal of CancerInternational Journal of Cancer723-729125320091097-0215<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(17, 18)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>، هایپر متیلاسیون منطقه پروموتور ژن های ساپرسور منجر به کاهش ترجمه این ژنها می شود که به سلول اجازه می دهد بصورت افسار گریخته رشد کند. ژن های جهش یافته در رشد و مرگ سلولی، اندرکنش های سلول –سلول و مسیر های سیگنالینگ سلولی نقش دارند، بی نظمی در چرخه سلولی به عنوان یک عامل خیلی مهم در پاتولوژی سرطان مطرح می باشد<span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span style='mso-element:field-begin'><span dir=LTR style='font-size: 14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language: FA'>ADDIN EN.CITE Shao20094875(19, 20)4875<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4875<ref-type name="Journal Article">17Shao, ChunboLacey, MichelleDubeau, LouisEhrlich, MelanieHemimethylation footprints of DNA demethylation in cancerEpigeneticsEpigenetics165-1754320091559-2294BOZKURT201148764876<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4876<ref-type name="Journal Article">17BOZKURT, CeyhunBOZKURT, SüreyyaARDA, NilüferERTEM, Ayşe UlyaŞAHİN, GürsesYÜKSEK, Nazmiye<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>author>GÜÇ, DicleKANSU, EminP16 and p27 tumor suppressor gene methylation status in childhood Wilms tumor casesTurkJMedSci<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>full-title>TurkJMedSci633-6384142011<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(19, 20)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>، بطوری که جهش درژن هایی از قبیل p53 در 50% از موارد سرطانها دیده شده است<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Suzuki19924877(21, 22)4877<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4877<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>keys><ref-type name="Journal Article">17Suzuki, YasushiTamura, GenSatodate, RyoichiFujioka, TomoakiInfrequent Mutation of p53 Gene in Human Renal Cell Carcinoma Detected by Polymerase Chain Reaction Single<span dir=LTR style='font-size:14.0pt;line-height:150%; font-family:'Cambria Math','serif';mso-bidi-font-family:'Cambria Math'; mso-bidi-language:FA'>‐<span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>strand Conformation Polymorphism AnalysisCancer scienceCancer science233-23583319921349-7006Lim199648784878<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4878<ref-type name="Journal Article">17Lim, Dae-SikHasty, Paul<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>title>A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53Molecular and cellular biologyMolecular and cellular biology7133-7143161219960270-7306<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(21, 22)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'> در سرطان تغییرات ژنومی، باعث ایجاد موتاسیون هایی می شود که در نهایت منجر به تولید ژن های انکوژن با عملکرد غالب واز دست رفتن عملکرد ژن های ساپرس کننده تومور می شود، که باعث رشد سلولی بیش از حد و غیر نرمال می شود. تومورها به دو گروه طبقه بندی می شوند که شامل تومورهای خوش خیم و بدخیم می باشند<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE Wittekind20024879(23)4879<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4879<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>keys><ref-type name="Journal Article">17Wittekind, ChristianCompton, Carolyn CGreene, Frederick LSobin, Leslie HTNM residual tumor classification revisitedCancerCancer2511-25169492002<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>1097-0142<span dir=LTR style='font-size:14.0pt; line-height:150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>isbn><span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(23)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'> سرطان دارای انواع مختلفی می باشد: کارسینوما که از سلو لهای اپی تلیال منشا می گیرند که بیشترین موارد سرطان را شامل می شوند<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin'; mso-bidi-language:FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE<span lang=FA dir=LTR style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'><span dir=LTR style='font-size:14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin'; mso-bidi-language:FA'>ADDIN EN.CITE.DATA<span lang=FA style='font-size: 14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'> 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<span style='mso-element:field-separator'>(24, 25) 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<span lang=FA style='font-size: 14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span style='mso-element:field-end'>، سارکوما که از بافت های پیوندی مانند استخوان و غضروف و غیره منشاء می گیرند که در حقیقت از سلو لهای مزانشیمی منشا گرفته اندو لوکمیا که از دو نوع از سلولهای هماتوپوئتیک و سلو لهای لنفوما منشا می گیرد و در کودکان حدود 30 % از تومور ها را شامل می شوند، تو مور های سلول زایا در سلو لهای بیضه ، تخمدان و بلاستوما (که از سلو لهای جفتی منشا می گیرد) دیده می شوند<span lang=FA style='font-size: 14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span style='mso-element:field-begin'><span dir=LTR style='font-size: 14.0pt;line-height:150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language: FA'>ADDIN EN.CITE Strong20064882(26, 27)4882<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4882<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>-<span dir=LTR style='font-size:14.0pt;line-height:150%; mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>keys><ref-type name="Journal Article">17Strong, Louise CGenetic etiology of cancerCancer<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>Cancer438-44440S120061097-0142Lingeman197448834883<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4883<ref-type name="Journal Article">17Lingeman, CH<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>title>Etiology of cancer of the human ovary: a reviewJournal of the National Cancer InstituteJournal of the National Cancer Institute1603<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>><span dir=LTR style='font-size:14.0pt;line-height: 150%;mso-bidi-font-family:'B Nazanin';mso-bidi-language:FA'>volume>53619740027-8874<span dir=RTL><span lang=FA style='font-size:14.0pt; line-height:150%;font-family:'B Nazanin';mso-bidi-language:FA'><span dir=RTL>>(26, 27)<span lang=FA style='font-size:14.0pt;line-height:150%;font-family:'B Nazanin';mso-bidi-language: FA'>. درمان سرطان امروزه روشهای مختلفی برای درمان سرطان وجود دارد که شامل جراحی، شیمی درمانی، رادیو تراپی، هورمون درمانی و ژن درمانی و اخیرا از داروهای بیولوژیکی مانند مونوکلونال آنتی ابادی، میکرو RNA، نوکلئوتید اسیدها و پپتید تراپی برای درمان سرطان استفاده می شود<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family: 'Times New Roman';mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span style='mso-element:field-begin'><span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Kufe20034811(28, 29)4811<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4811<ref-type name="Journal Article">17Kufe, Donald WPollock, Raphael EWeichselbaum, Ralph RBast, Robert CGansler, Ted SHolland<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>, <span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>James FFrei, EmilHolland-Frei cancer medicine2003Alfreda200848844884<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4884<ref-type name="Journal Article">17Alfreda, LaenglerClaudiab, SpixSvend, GottschlingNorbertd, GrafPeterb, KaatschComplementary and alternative treatment methods in children with cancer: A population-based retrospective survey on the prevalence of use in GermanyEur J CancerEur J Cancer2233-2240442008<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>><span style='font-size: 14.0pt;line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>urls><span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(28, 29)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>، که با توجه به پیشرفتی های اخیر در علم پوتئومیکس، امروزه پپتید درمانی به عنوان یک روش درمانی توجه بسیاری از محققین را به خود جلب کرده است<span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; 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<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family: 'Times New Roman';mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span style='mso-element:field-end'>، با ظهور کتابخانه پپتیدی، پپتید درمانی یک نقش مهم را در درمان بیماریهای مختلف از آلزایمر تا سرطان را ایفا می کنند<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Zhang20074888(33, 34)4888<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4888<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>-<span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>keys>17Zhang, BinghuaZhang, YanqiongWang, JiweiZhang, YangdeChen, JijiPan, YifengRen, LifengHu, ZhiyuanZhao, JingfengLiao, MingmeiScreening and identification of a targeting peptide to hepatocarcinoma from a phage display peptide libraryMolecular MedicineMolecular Medicine246135-62007<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>><span style='font-size: 14.0pt;line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>Cite>Press199348894889<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4889<ref-type name="Journal Article">17Press, Oliver WEary, Janet FAppelbaum, Frederick RMartin, Paul JBadger, Christopher CNelp, Wil BGlenn, StephanButchko, GregFisher, DarrellPorter, BruceRadiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow supportNew England Journalof MedicineNew England Journal of Medicine1219-12243291719930028-4793<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(33, 34)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>، در حال حاضر پپتید ها با سایزها ی مختلف به عنوان دارو در بازار موجود می باشند (جدول شماره1)، پپتید ها با دو روش بیوسنتتزی (از طریق قطعات میکروبیال نوترکیب یا طبیعی ) یا شیمیایی (از طریق کونژوکه شدن با مولکولهای کوچک یا الحاق با آمینو اسید های غیر طبیعی با طراحی های مختلف ) سنتز شوند<span lang=FA dir=RTL style='font-size:14.0pt; line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span style='mso-element:field-begin'><span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Shu19984890(35, 36)4890<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4890<ref-type name="Journal Article">17Shu, Yue-ZhongRecent natural products based drug development: a pharmaceutical industry perspectiveJournal of natural productsJournal of natural products1053-107161819980163-3864Vlieghe201047904790<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4790<ref-type name="Journal Article">1<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>7<span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ref-type>Vlieghe, PatrickLisowski, VincentMartinez, JeanKhrestchatisky, MichelSynthetic therapeutic peptides: science andmarketDrug discovery todayDrug discovery today40-5615120101359-6446<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL><span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>isbn><span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(35, 36)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>در درمان سرطان سایز کوچک پپتیدها به عنوان یکی از مزایای آنها در درمان مطرح می باشد چون می تواند به راحتی وارد سلول شود و همچنین تحقیقاتی در مورد کاربرد پپتید ها در واکسیناسیون و هدف درمانی دارو (Drug targeting) در سرطان مطرح شده است<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Gordon19984891(3, 37)4891<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4891<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>-<span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>keys><ref-type name="Book">6Gordon, Eric MKerwin, James FCombinatorial chemistry and molecular diversity in drug discovery<span dir=RTL><span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%; font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman';mso-fareast-font-family: Calibri;mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US; mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>><span style='font-size:14.0pt;line-height:115%; font-family:'Times New Roman','serif';mso-fareast-font-family:Calibri; mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>year>1998Wiley-Liss New York0471155187McPhee201048584858<key app="EN" db-id<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>="<span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4858<ref-type name="Book">6McPhee, Stephen JPapadakis, Maxine ARabow, Michael WCurrent medical diagnosis & treatment 20102010McGraw-Hill Medical0071624449<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(3, 37)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>. بیشتر درمانها که اخیرا برای درمان سرطان استفاده می شود دارای اختصاصیت پایین و همچنین دارای عوارض جانبی زیادی می باشند ولی پپتید ها به عنوان دارو دارای مزایایی از قبیل اختصاصیت بالا و عوارض جانبی کمتر می باشند<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE<span lang=FA style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE.DATA<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'> 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<span style='mso-element:field-separator'>(3, 38, 39) 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<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family: 'Times New Roman';mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span style='mso-element:field-end'> بنابراین به علت افزایش جذب سلولی و مزایای دیگر آن که اشاره خواهد شد در درمان و حتی در واکسیناسیون درمانی هم استفاده می شوند<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Hicke20064894(40)4894<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4894<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>><span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>ref-type name="Journal Article">17Hicke, Brian JStephens, Andrew WGould, TyChang, Ying-FonLynott, Cynthia KHeil, James<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>author>Borkowski, SandraHilger, Christoph-StephanCook, GaryWarren, StephenTumor targeting by an aptamerJournal of Nuclear MedicineJournal of Nuclear Medicine668-67847420060161-5505<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(40)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>، در مطالعات انجام شده بر روی سرطان، پپتید ها در مواردی به عنوان مهار کننده آنژیوژنسیس استفاده شده اند که باعث مهار اتصال آلفا 5 انتگرین به لیگاندهایش می شود که خود منجر به توقف رشد سلولهای سرطانی می گردد<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Nagant20104895(41)4895<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4895<ref-type name="Journal Article">17Nagant, CaroleTré-Hardy, MarieEl-Ouaaliti, MalikaSavage, PaulDevleeschouwer, MichelDehaye<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>, <span style='font-size:14.0pt; line-height:115%;font-family:'Times New Roman','serif';mso-fareast-font-family: Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>Jean-PaulInteraction between tobramycin and CSA-13 on clinical isolates of Pseudomonas aeruginosa in a model of young and mature biofilmsApplied microbiology and biotechnologyApplied microbiology and biotechnology251-26388120100175-7598<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(41)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>، در مواردی پپتیدها به عوامل سایتو توکسیک مانند دکسوروبیسین متصل و اثر درمانی می گذارد، که در یک مطالعه پپتید ها به منظور افزایش اثر دارو و کاهش سمیت سلولی بکار گرفته شده اند<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Vincenti19944896(42)4896<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4896<ref-type name="Journal Article">17Vincenti, Matthew PClark, Ian MBrinckerhoff, Constance EUsing inhibitors of metalloproteinases to treat arthritis. Easier said than done?Arthritis & RheumatismArthritis & Rheumatism1115-112637819941529-0131<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(42)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>، پپتید های با خاصیت آنتی میکروبیال می توانند به عنوان القاءکننده آپوپتوزیس مورد استفاده قرار گیرند<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'><span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>ADDIN EN.CITE Crawford20034897(38, 43)4897<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4897<ref-type name="Journal Article">17Crawford, MargaretWoodman, RobFerrigno, Paul KoPeptide aptamers: tools for biology anddrug discoveryBriefings in Functional Genomics & ProteomicsBriefings in Functional Genomics & Proteomics72-792120032041-2649Leszczyńska201148984898<key app="EN" db-id="fvvzfsfrlw5zvretfz05a9pm9tvzxasr0x5t">4898<ref-type name="Journal Article">17Leszczyńska, KNamiot, ACruz, KByfield, FJWon, EMendez, GSokołowski, WSavage, PBBucki, RJanmey, PAPotential of ceragenin CSA<span style='font-size:14.0pt;line-height:115%; font-family:'Cambria Math','serif';mso-fareast-font-family:Calibri;mso-bidi-font-family: 'Cambria Math';mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: FA'>‐<span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>13 and its mixture with pluronic F<span style='font-size:14.0pt;line-height:115%;font-family: 'Cambria Math','serif';mso-fareast-font-family:Calibri;mso-bidi-font-family: 'Cambria Math';mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: FA'>‐<span style='font-size:14.0pt;line-height:115%;font-family:'Times New Roman','serif'; mso-fareast-font-family:Calibri;mso-bidi-font-family:'B Nazanin';mso-ansi-language: EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'>127 as treatment of topical bacterial infectionsJournal of applied microbiologyJournal of applied microbiology229-238110120111365-2672<span dir=RTL><span lang=FA dir=RTL style='font-size: 14.0pt;line-height:115%;font-family:'B Nazanin';mso-ascii-font-family:'Times New Roman'; mso-fareast-font-family:Calibri;mso-hansi-font-family:'Times New Roman'; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:FA'><span dir=RTL>>(38, 43)<span lang=FA dir=RTL style='font-size:14.0pt;line-height:115%;font-family:'B Nazanin'; mso-ascii-font-family:'Times New Roman';mso-fareast-font-family:Calibri; mso-hansi-font-family:'Times New Roman';mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:FA'>