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Editorial 2 2 Welcome to the second issue of the AJMB. I hope you have read and enjoyed the first edition. In this issue, like the first one, there is a mix of articles covering a wide range of topics including: Promoter analysis, DNA immunization, synthesis of nanoparticles, non-coding RNAs and Intellectual property (IP) issues. I believe the article entitled "Biotechnology-Related IP Law of Iran" is the first article of its kind published in Iran in which a comprehensive review of Iranian laws pertaining to biotechnology is addressed. Therefore, I encourage those who are interested in patenting a discovery and/or product in the field of biotechnology in Iran to read this article. On different note, the sixth National Biotechnology Congress took place on 13-15 August, 2009 at the Milad Tower Convention Center in Tehran. This three day congress appeared to be one of the most successful congresses held in the field of biotechnology in Iran. It was understood that about 1000 abstracts were accepted and the majority of them were in the disciplines of agriculture, medicine and marine biology. It was interesting to learn that (according to a research carried out by the organizers of the congress) from a good number of articles published in the area of biotechnology in 2009 (and indexed by ISI), ninety nine articles belonged to the authors and research centers in Iran. As the editor, I would like to take the opportunity to invite all researchers in the field of medical biotechnology to send in their original research works, review articles, short articles, etc. for publication in the AJMB. The AJMB is now indexed in several databases worldwide and it is anticipated to be included in further lists in the near future. 54 54 Ali M. Ardekani Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Editorial 155.pdf ####

Noncoding RNAs and Cancer 2 2 The eukaryotic complexity involves the expression and regulation of genes via RNA-DNA, RNA-RNA, DNA-protein and RNA-protein interactions. Recently, the role of RNA molecules in the regulation of genes in higher organisms has become more evident, especially with the discovery that about 97% of the transcriptional output in higher organisms are represented as noncoding RNAs: rRNA, snoRNAs, tRNA, transposable elements, 5' and 3' untranslated regions, introns, intergenic regions and microRNAs. MicroRNAs function by negatively regulating gene expression via degradation or translational inhibition of their target mRNAs and thus participate in a wide variety of physiological and pathological cellular processes including: development, cell proliferation, differentiation, and apoptosis pathways. MicroRNA expression profiles in many types of cancers have been identified. Recent reports have revealed that the expression profiles of microRNAs change in various human cancers and appear to function as oncogenes or tumor suppressors. Abnormal microRNA expression has increasingly become a common feature of human cancers. In this review, we summarize the latest progress on the involvement of microRNAs in different types of cancer and their potential use as potential diagnostic and prognostic tumor biomarkers in the future. 55 70 Mozhgan Moslemi Naeini Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Ali M. Ardekani Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran BiomarkerCellular processExpressionMicro RNANoncoding RNA 9.pdf Lee RC, Feinbaum RL, Ambros V. 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DNA Immunization as an Efficient Strategy for Vaccination 2 2 The field of vaccinology provides excellent promises to control different infectious and non-infectious diseases. Genetic immunization as a new tool in this area by using naked DNA has been shown to induce humoral as well as cellular immune responses with high efficiency. This demonstrates the enormous potential of this strategy for vaccination purposes. DNA vaccines have been widely used to develop vaccines against various pathogens as well as cancer, autoimmune diseases and allergy. However, despite their successful application in many pre-clinical disease models, their potency in human clinical trials has been insufficient to provide protective immunity. Several strategies have been applied to increase the potency of DNA vaccine. Among these strategies, the linkage of antigens to Heat Shock Proteins (HSPs) and the utilization of different delivery systems have been demonstrated as efficient approaches for increasing the potency of DNA vaccines. The uptake of DNA plasmids by cells upon injection is inefficient. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target Antigen-Presenting Cells (APCs) are effective in animal models. Alternatively, different regimens called prime-boost vaccination are also effective. In this regimen, naked DNA is utilized to prime the immune system and either recombinant viral vector or purified recombinant protein with proper adjuvant is used for boosting. 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Genetically modified cellular vaccines for therapy of human papilloma virus type 16 (HPV16)-associated tumors. Curr Cancer Drug Targets 2008;8(3):180-186. ##Bhowmick S, Ali N. Recent developments in leishmaniasis vaccine delivery systems. Expert Opin Drug Deliv 2008;5(7):789-803. ##Okura Y, Matsumoto Y. DNA vaccine therapy for Alzheimer's disease: present status and future direction. Rejuvenation Res 2008;11(2):301-8. ##Reimann J, Schirmbeck R. DNA vaccines expres-sing antigens with a stress protein-capturing domain display enhanced immunogenicity. Im-munol Rev 2004;199:54-67. ##Yan Q, Cheung YK, Cheng SC, Wang XH, Shi M, Hu MH, et al. A DNA vaccine constructed with human papillomavirus type 16 (HPV16) E7 and E6 genes induced specific immune responses. Gynecol Oncol 2007;104(1):199-206. ##Kuck D, Leder C, Kern A, Müller M, Piuko K, Gissmann L, et al. Efficiency of HPV16L1/E7 DNA immunization: influence of cellular localiza-tion and capsid assembly. Vaccine 2006;24(15): 2952-2965. ##Kim TW, Hung CF, Boyd DAK, He L, Lin CT, Kaiserman D, et al. Enhancement of DNA vaccine potency by co-administration of a tumor antigen gene and DNA encoding serine protease inhibitor-6. Cancer Res 2004;64:400-405. ##Zadeh-Vakili A, Taheri T, Taslimi Y, Doustdari F, Salmanian AH, Rafati S. Immunization with the hybrid protein vaccine, consisting of Leishmania major cysteine proteinases Type I (CPB) and Type II (CPA), partially protects against leishmaniasis. Vaccine 2004;22(15-16):1930-40. ##Ahmed SB, Touihri L, Chtourou Y, Dellagi K, Bahloul C. DNA based vaccination with a cocktail of plasmids encoding immunodominant Leish-mania major antigens confers full protection in BALB/c mice.Vaccine 2009;27(1):99-106. ##Liu MA. DNA vaccines: a review. J Intern Med 2003;253(4):402-410. ##Rafati S, Zahedifard F, Nazgouee F. Prime-boost vaccination using cysteine proteinases type I and II of Leishmania infantum confers protective im-munity in murine visceral leishmaniasis. Vaccine 2006;24(12):2169-75. ##Rafati S, Salmanian AH, Taheri T, Vafa M, Fasel N. A protective cocktail vaccine against murine cutaneous leishmaniasis with DNA encoding cys-teine proteinases of Leishmania major. Vaccine 2001;19(25-26):3369-3375. ##Rafati S, Zahedifard F, Azari MK, Taslimi Y, Taheri T. Leishmania infantum: prime boost vac-cination with C-terminal extension of cysteine pro-teinase type I displays both type 1 and 2 immune signatures in BALB/c mice. Exp Parasitol 2008; 118(3):393-401. ##Rafati S, Nakhaee A, Taheri T. Protective vaccination against experimental canine visceral leishmaniasis using a combination of DNA and protein immunization with cysteine proteinases type I and II of L. infantum. Vaccine 2005;23(28): 3716-3725. ##Rafati S, Ghaemimanesh F, Zahedifard F. Comparison of potential protection induced by three vaccination strategies (DNA/DNA, Protein/ Protein and DNA/Protein) against Leishmania major infection using Signal Peptidase type I in BALB/c mice. Vaccine 2006;24(16): 3290-3297. ##Delogu G, Fadda G. The quest for a new vaccine against tuberculosis. J Infect Dev Ctries 2009;3(1): 5-15. ##Moorthy VS, Good MF, Hill AVS. Malaria vaccine developments. Lancet 2004;363(9403): 150-156. ##Sasaki S, Tsuji T, Asakura Y, Fukushima J, Okuda K. The search for a potent DNA vaccine against AIDS: the enhancement of immunogenicity by chemical and genetic adjuvants. Anticancer Res 1998;18(5D):3907-3915. ##Ulmer JB, DeWitt CM, Chastain M, Friedman A, Donnelly JJ, McClements WL, et al. Enhancement of DNA vaccine potency using conventional alu-minum adjuvants. Vaccine 1999;189(1-2):18-28. ##Weeratna R, Brazolot Millan CL, Krieg AM, Davis HL. Reduction of antigen expression from DNA vaccines by co-administered oligodeoxy-nucleotides. Antisense Nucleic Acid Drug Dev 1998;8(4):351-356. ##Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, et al. Increased DNA vac-cine delivery and immunogenicity by electropora-tion in vivo. J Immunol 2000;164(9):4635-4640. ##Kim TY, Myoung HJ, Kim JH, Moon IS, Kim TG, Ahn WS, et al. Both E7 and CpG-oligodeoxy-nucleotide are required for protective immunity against challenge with human papillomavirus 16 immortalized tumor cells: involvement of CD4+ and CD8+T cells in protection. Cancer Res 2002; 62(24):7234-7240. ##Li H, Zhou M, Han J, Zhu X, Dong T, Gao GF, et al. Generation of murine CTL by a hepatitis B virus-specific peptide and evaluation of the adju-vant effect of heat shock protein glycoprotein 96 and its terminal fragments. J Immunol 2005;174 (1):195-204. ##Peng S, Ji H, Trimble C, He L, Tsai YC, Yeatermeyer J, et al. Development of a DNA vac-cine targeting human papillomavirus type 16 onco-protein E6. J Virol 2004;78(16):8468-8476. ##Kim D, Gambhira R, Karanam B, Monie A, Hung CF, Roden R, et al. Generation and characteri-zation of a preventive and therapeutic HPV DNA vaccine. Vaccine 2008;26(3):351-360. ##Rapp UK, Kaufmann SH. DNA vaccination with gp96-peptide fusion proteins induces protection against an intracellular bacterial pathogen. Int Im-munol 2004;16(4):597-605. ##Zugel U, Sponaas AM, Neckermann J, Schoel B, Kaufmann SH. Gp96-peptide vaccination of mice against intracellular bacteria. Infect Immun 2001; 69(6):4164-4167. ##Bolhassani A, Zahedifard F, Taghikhani M, Rafati S. Enhanced immunogenicity of HPV16E7 accom-panied by Gp96 as an adjuvant in two vaccination strategies. Vaccine 2008;26(26):3362-3370. ##Hahn UK, Aichler M, Boehm R, Beyer W. Com-parison of the immunological memory after DNA vaccination and protein vaccination against an-thrax in sheep. Vaccine 2006;24(21):4595-4597. ##Martin ME, Rice KG. Peptide-guided gene deliv-ery. AAPS J 2007;9(1):E18-E29. ##Singh M, Briones M, Ott GS, O'Hagan DT. Cationic microparticles: a potent delivery system for DNA vaccines. Proc Natl Acad Sci 2000;97(2): 811-816. ##Buchan S, Gronevik E, Mathiesen I, King CA, Stevenson FK, Rice J. Electroporation as a prime/boost strategy for naked DNA vaccination against a tumor antigen. J Immunol 2005;174(10): 6292-6298. ##Ahn S, Sung Y. AIDS vaccine development: the past, the present, and the future. Immune Network 2009;9(1):1-3. ##Narayani R. Polymeric delivery systems in bio-technology: a mini review. Trends Biomater Artif Organs 2007;21(1):14-19. ##Hellgren I, Gorman J, Sylven C. Factors control-ling the efficiency of Tat-mediated plasmid DNA transfer. J Drug Target 2004;12(1):39-47. ##Bodles-Brakhop AM, Draghia-Akli R. DNA vac-cination and gene therapy: optimization and deliv-ery for cancer therapy. Expert Rev Vaccines 2008; 7(7):1085-1101. ##Lee TWR, Matthews DA, Blair GE. Novel mol-ecular approaches to cystic fibrosis gene therapy. Biochem J 2005;387(Pt-1):1-15. ##Balenga NA, Zahedifard F, Weiss R, Sarbolouki MN, Thalhamer J, Rafati S. Protective efficiency of dendrosomes as novel nano-sized adjuvants for DNA vaccination against birch pollen allergy. J Biotechnol 2006;124(3):602-614. ##Godbey WT, Wu KK, Mikos AG. Poly (ethylenimine) and its role in gene delivery. J Control Release 1999;60(2-3):149-160. ##Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc Natl Acad Sci 1995;92(16):7297-7301. ##Alexis F, Lo SL, Wang S. Covalent attachment of low molecular weight poly (ethyleneimine) im-proves Tat peptide mediated gene delivery. Ad-vanced Materials 2006;18:2174-2178. ##Jarver P, Langel U. The use of cell-penetrating peptides as a tool for gene regulation. 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Biotechnology-Related Intellectual Property Law of Iran 2 2 In this study, an attempt has been made to expound the Iranian law of intellectual property in relation to biotechnology. The most important themes studied are patents, industrial designs and trade marks. The latest relevant piece of legislation concerning the subject matters was passed in March 2008. However, the history of laws and regulations in this field goes back to early twentieth century (i.e. 1925). In this review, on the basis of the latest law passed in 2008, the topics explored are the responsible authority, patentable items and criteria, excluded items, registration procedure, rights conferred and sanctions. At the end, an attempt is made to put forward a few points as an analysis of the above Law from a critical point of view. 89 94 Mohammad Rasekh Faculty of Law, Shahid Beheshti University Bio Law and Ethics Department, Avicenna Research Institute, ACECR Faculty of Law, Shahid Beheshti University Bio Law and Ethics Department, Avicenna Research Institute, ACECR IranIran BiotechnologyIndustrial designIran IP lawPatentTrade markIP rights 11.pdf Kheirandish A, (eds). Enqelabe Bioteknology (Biotechnology Revolution). Tehran: Biotechnol-ogy Commission Publication;1382(2003),239-249. ##Gallagher W, (eds). Intellectual Property. Hampshire: Ashgate;2007,Part I. ##Chisum DS. Common Law and Civil Law Approaches to Patent Claim Interpretation: "Fence Posts" and "Sign Posts". In: Vaver D, Bently L. Intellectual Property in the New Millennium: Essays in Honour of William R. Cornish. Cambridge: CUP;2004. ##Katouzian, N. Hoquqe Madani: Amwal wa Malekiat (Civil Law: Properties and Ownership), Tehran: Dadgostar, 1380(2001),23-24; and Katouzian N. Moqadameye `Elme Hoquq (An Introduction to Law). Tehran: Sherkat Sahami Enteshar; 1386 (2007),256-271. ##Merges RP, Menell PS, Lemley MA. Intellectual property in the new technological age. 4th ed. New York: Wolters Kluwer; 2007, especially Chs. 1, 3. ##Ilardi A, Blakeney M. International encyclopaedia of intellectual property treaties. Oxford: OUP; 2004. ##Fatehnia H. Majmu`eye Qawanine Malekiate Ma` navi (Collection of Intellectual Property Laws). Tehran: Jangal;1386(2007). ##Amani T. Qawanin wa Moqarrarat Hoquq Maleki-yat Fekri (Melli wa Beynolmelali) [Law and Regulations of IP Rights (Municipal and Inter-national)]. Tehran: Behnami;1387(2008),46-48. ##See Executive By-Law of the Law of Registration of Inventions, Industrial Designs and Trade Marks (the 2009 By-Law), accessed on http://www.sabt. gov.ir/Attachment/Ghavanin2/984687500330265-1.pdf. ##Law of Registration of Inventions, Industrial Designs and Trade Marks (the 2008 Law), acces-sed on http://tarh.majlis.ir/?ShowRule&Rid=1f8b f399-3aa9-495e-b09c-382ed357c865, Sec. 53. ##Agreement on Trade-Related Aspects of Intellec-tual Property Rights (TRIPS), (1994), accessed on http://www.wto.org/english/tratop_e/trips_e/t_agm0_e.html, Part II; Convention Establishing the World Intellectual Property Organization (the WIPO Convention), 14 July 1967, accessed on http://www.wipo.int/treaties/en/convention, Article 2; Paris Convention for the Protection of Industrial Property (the Paris Convention), 20 March 1883, accessed on http://www.wipo.int/treaties/en/ip/ paris/trtdocs_wo.20.html, Article 1; and WIPO Intellectual Property Handbook: Policy, Law and Use, WIPO Publication, accessed on 2009 on http://www.Wipo.int/export/sites/www/about-ip/en/ iprm/pdf, Article 2. ##Ilardi A, Blakeney M. International Encyclopaedia of Intellectual Property Treaties. Oxford: OUP; 2004. ##Cornish WR. Intellectual Property: Patents, Copyrights, Trade Marks and Allied Rights. 4th ed. London: Sweet & Maxwell; 2001, Ch. 1. ##

Forward Modeling of the Coumarin Antifungals; SPR/SAR Based Perspective 2 2 Although, coumarins are a group of compounds which are naturally found in some plants, they can be synthetically produced as well. Because of their diverse derivatives, origin and properties most of them can be used for medicinal purposes. For example, they can be used against fungal diseases or in studying structure and biological properties of antifungal agents to discover new compounds with the similar activity. A Structure Property/Activity Relationship (SAR) can be utilized in prediction of biological activity of desired molecules. 95 103 Saeed Soltani Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran Iran Shima Dianat Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran Iran Soroush Sardari Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran Iran Antifungal activityCoumarinModelingNeural network 12.pdf Denning DW, Evans GV, Kibbler CC, Richardson MD, Roberts MM, Rogers TR, et al. Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation. Eur J Clin Microbiol Infec Dis 1997;16(6):424-436. ##Coleman DC, Rinaldi MG, Haynes KA, Rex JH, Summerbell RC, Anaissie EJ, et al. Importance of Candida species other than Candida albicans as opportunistic pathogens. Med Mycol 1998;36 (Suppl1):156-165. ##Warnock DW. Fungal infections in neutropenia: current problems and chemotherapeutic control. J Antimicro Chemother 1998;41(Suppl D):95-105. ##Pfaller MA. Epidemiology of fungal infections: the promise of molecular typing. Clin Infect Dis 1995;20:1535-1539. ##Tiew P, Ioset JR, Kokpal U, Chavasiri, W, Hostet-tmam K. Anti-fungal, anti-oxidant and larvicidal activities of compounds isolated from the heart wood of Mansonia gagei. Phytother Res 2003;17 (2):190-193. ##Zaha AA, Hazem A. Antimicrobial activity of two novel coumarin derivatives: 3-cyanonaptho [1,2-(e)] pyran-2-one and 3-cyano coumarin. New Microbiol 2002; 25(2):213-222. ##Lewis RJ, Singh OMP, Smith CV, Skarzynski T, Maxwell A, Wonacott AJ, et al. The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystal-logarphy. EMBO J 1996;15(6):1412-1420. ##Kawase M, Motohasi N, Sakagami H, Kanamato T, Nakashima H, Fereczy L, et al. Antimicrobial activity of trifluoromethyl ketones and their syner-gism with promethazine. Int J Antimicrob Agents 2001;18(2):161-165. ##Kulkarni MV, Pujar BJ, Patil VD. Studies on coumarins II. Arch Pharm 1983;316(1):15-21. ##Sardari S, Dezfulian M. Cheminformatics in anti-infective agents discovery. Mini Rev Med Chem 2007;79(2):181-189. ##Agatonovic-Kustrin S, Beresford R. Basic con-cepts of artificial neural networks (ANN) model-ling and its application in pharmaceutical research. J Pharm Biomed Anal 2000;22(5):717-727. ##Zitko V. Chemometrics in environmental analysis. Chemomet Intel Lab Sys 1998;40:119-120 ##Sun Y, Peng Y, Chen Y, Shukla AJ. Application of artificial neural networks in the design of controlled release drug delivery systems. Adv Drug Del Rev 2003;55(9):1201-1215. ##Wesolowski M, Konieczynski P. Thermo-analytical, chemical and principal component analysis of plant drugs. Int J Pharm 2003;262(1-2):29-37. ##Debeljak Z, Marohnic V, Srecnik G, Medic-Sÿaric M. Novel approach to evolutionary neural net-work based descriptor selection and QSAR model development. J Comput Aided Mol Des 2005;19 (12):835-855. ##Baumann K. Cross-validation as the objective function for variable selection techniques. Trends Analyt Chem 2003;22(6):395-406. ##Yamamura S. Clinical application of artificial neural networks (ANN) modeling to predict pharmacokinetic parameters of severely ill patients. Adv Drug Del Rev 2003;55(9):1233-1251. ##Zupan J, Novic M, Ruisanchez I. Kohonen and counterpropagation artificial neural networks in analytical chemistry. Chemomet Intellig Lab Syst 1997;38(1);1-23. ##Svetnik V, Liaw A, Tong C, Culberson JC, Sheridan RP, Feuston BP. Random Forest: A Classification and Regression Tool for Compound Classification and QSAR Modeling. J Chem Inf Comput Sci 2003;43(6):1947-1958. ##Sardari S, Mori Y, Horita K, Micetich RG, Nishibe S, Daneshtalab M. Synthesis and antifungal activity of coumarins and angular furanocoumarins. Bioorg Med Chem 1999;7(9): 1933-1940. ##Godoya MFP, Victor SR, Bellini AM, Guerreiro G, Rochab WC,Bueno OC, et al. Inhibition of the symbiotic fungus of leaf-cutting ants by coumarins. J Braz Chem Soc 2005;16(3):669-672. ##El-Seedi HR. Antimicrobial arylcoumarins from Asphodelus microcarpus. J Nat Prod 2007;70(1): 118-120. ##Daoubi M, Duran-Patron R, Hmamouchi M, Hernandez-Gala´R, Ahmed Benharref, Collado IG. Screening study for potential lead compounds for natural product-based fungicides: I. Synthesis and in vitro evaluation of coumarins against Botrytis cinerea. Pest Manag Sci 2004;60(9):927-932. ##Nath M, Jairath R, Eng G, Song X, Kumar A. Triorganotin(IV) derivatives of umbelliferone (7-hydroxycoumarin) and their adducts with 1,10-phenanthroline:synthesis, structural and biological studies. J Organomet Chem 2005; 690(1):134-144. ##Mouri T, Yano T, Kochi S, Ando T, Hori M. Synthesis and antifungal activity of new 3,4,7-Trisubstituted coumarins. 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The Anticancer Activity Compared Between Triptorelin and a New Gonadotropin Releasing Hormone Analogue 2 2 Gonadotropin releasing hormone (GnRH) plays a key role in reproduction. This decapeptide is synthesized and released by hypothalamus and induces the pituitary gonadotrop cells to release pituitary gonadotropin hormones. In some extrapituitary compartments GnRH and its receptor act as part of the autocrine regulatory system of cell proliferation. The anticancer activity of GnRH and its analogues has been observed by many researchers. In this study the anticancer activity of a new analogue of GnRH and triptorelin was investigated by cell proliferation assay. Results indicate that proliferation of human breast and ovarian cancer cell lines are dose-dependently inhibited. The inhibitory efficiency of the new analogue is proved to be higher than the original triptorelin. In addition to its antimitogenic activity, evidence was found for the involvement of the apoptotic mechanism in the action of the new analogue and triptorelin. In conclusion, the new analogue can be considered as a good pharmaceutical candidate. 105 110 Mohammad Mirzaei Saleh-Abady Department of Biophysics, School of Basic Science, Tarbiat Modares University Department of Biophysics, School of Basic Science, Tarbiat Modares University Iran Abdolali Alizadeh Department of Organic Chemistry, School of Basic Science, Tarbiat Modares University Department of Organic Chemistry, School of Basic Science, Tarbiat Modares University Iran Fereshteh Shamsipour Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Hossein Naderi-Manesh Department of Biophysics, School of Basic Science, Tarbiat Modares University Department of Biophysics, School of Basic Science, Tarbiat Modares University Iran Anticancer activityBreast cancerLHRH analogueOvarian cancerPeptidomimeticsTriptorelin 13.pdf Maudsley S, Davidson L, Pawson AJ, Chan R, Lopez de Maturana R, Millar RP. Gonadotropin-Releasing Hormone (GnRH) antagonists promote proapoptotic signaling in peripheral reproductive tumor cells by activating a Gai-coupling state of the type I GnRH receptor. Cancer Res 2004;64 (20):7533-7544. ##Schally AV. Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. Peptides 1999;20(10):1247-1262. ##Seeburg PH, Adelman P. Characterization of cDNA for precursor of human luteinizing hormone releasing hormone. Nature 1984;311(5987):666-668. ##Oikawa M, Dargan C, Ny T, Hsueh AJ. Expres-sion of gonadotropin-releasing hormone and pro-thymosin-alpha messenger ribonucleic acid in the ovary. Endocrinology 1990;127(5):2350-2356. ##Palmon A, Aroya NB, Tel-Or S, Burstein Y, Fridkin M, Koch Y. The gene for the neuropeptide gonadotropin releasing hormone is expressed in the mammary gland of lactating rats. Proc Natl Acad Sci USA 1994;91(11):4994-4996. ##Azad N, Emanuele NV, Halloran MM, Tentler J, Kelley MR. Presence of luteinizing hormone-releasing hormone (LHRH) mRNA in rat spleen lymphocytes. Endocrinology 1991;128(3):1679-1681. ##Emons G, Schröder B, Ortmann O, Westphalen S, Schulz K, Schally AV. High Affinity Binding and Direct Antiproliferative Effects of Luteinizing hormone-releasing hormone analogs in human endometrial cancer Cell Lines. J Clin Endocrinol Metab1993;77(6):1458-1464. ##Gründker C, Günthert AR, Westphalen S, Emons G. Biology of the gonadotropin-releasing hormone system in gynecological cancers. Eur J Endocrinol 2002;146(1):1-14. ##Völker P, Gründker C, Schmidt O, Schulz KD, Emons G. Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: frequency, autoregulation and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues. Am J Obstet Gynecol 2002;186(2):171-179. ##Emons G, Grundker C, Gunthert AR, Westphalen S, Kavanagh J, Verschraegen C. GnRH antagon-ists in the treatment of gynecological and breast cancers. Endocr Relat Cancer 2003;10(2):291-299. ##Kovacs M, Vincze B, Horvath JE, Seprodi J. Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin- releasing hormone (GnRH)-III analogs. Peptides 2007;28(4):821-829. ##Freidinger RM. Nonpeptidic ligand for peptide and protein receptors. Curr Opin Chem Biol 1999;3 (4):395-406. ##Goodman M. Synthesis of peptide and peptidomi-metics. E22C. 1st ed. Stuttgart: Thieme; 2004. ##Sealfon SC, Weinstein H, Millar RP. Molecular mechanisms of ligand interaction with the gonado-tropin-releasing hormone receptor. Endocr Rev 1997;18(2):180-205. ##Arabanian A, Mohammadnejad M, Balalaie S, Gross JH. Synthesis of novel Gn-RH analogues using Ugi-4MCR. Bioorg Med Chem Lett 2009;19 (3):887-890. ##Engeland M, Ramaekers FCS, Schutte B, Reutelingsperger CPM. A novel assay to measure loss of plasma membrane asymmetry during apop-tosis of adherent cells in culture. Cytometry 1996; 24(2):131-139. ##Cascioal-Rosen L, Rosen A, Petri M, Schlissel M. Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: Implications for coagulation events and antigenic spread in system-ic lupus erythematosus. Proc Natl Acad Sci USA 1996;93(4):1624-1629. ##Söderhäll JA, Polymeropoulos EE, Paulini K, Günther E, Kühne R. Antagonist and agonist binding models of the human gonadotropin-re-leasing hormone receptor. Biochem Biophys Res Commun 2005;333(2):568-582. ##Palyi I, Vincze B, Lovas S, Mezo I, Pato J, Kalnay A, et al. Gonadotropin-releasing hormone ana-logue conjugates with strong selective antitumor activity. Proc Natl Acad Sci USA 1999;96(5): 2361-2366. ##Fister S, Günthert AR, Emons G, Gründker C. 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Green Synthesis of Small Silver Nanoparticles Using Geraniol and Its Cytotoxicity against Fibrosarcoma-Wehi 164 2 2 Many reports have been published about the biogenesis of silver nanoparticles using several plant extracts such as Pelargonium graveolens (P.graveolens- geranium) and Azadirachta indica (neem) but the capacity of their natural reducing constituents to form silver nanoparticles has not yet been studied. In this research the synthesis of silver nanoparticles using geraniol has been investigated. We successfully synthesized uniformly dispersed silver nanoparticles with a uniform size and shape in the range of 1 to 10 nm with an average size of 6 nm. Also the cytotoxicity of the prepared silver nanoparticles was investigated using a cancer cell line (Fibrosarcoma-Wehi 164). The cytotoxicity analysis of the sample shows a direct dose-response relationship; cytotoxicity increased at higher concentrations. At concentration of 1 µg/ml, silver nanoparticles was able to inhibit the cell line’s growth by less than 30%. Conversly, the presence of 5 µg/ml of silver nanoparticlse significantly inhibited the cell line’s growth (> 60%). The concentration necessary to produce 50% cell death was 2.6 µg/ml for this silver nanoparticles preapared with geraniol. 111 115 Mona Safaepour Department of Pharmaceutical Biotechnology and Biotechnology Research center, Faculty of Pharmacy, Tehran University of Medical Sciences Department of Pharmaceutical Biotechnology and Biotechnology Research center, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Ahmad Reza Shahverdi Department of Pharmaceutical Biotechnology and Biotechnology Research center, Faculty of Pharmacy, Tehran University of Medical Sciences Department of Pharmaceutical Biotechnology and Biotechnology Research center, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Hamid Reza Shahverdi Department of Material Science, Faculty of Engineering, Tarbiat Modares University Department of Material Science, Faculty of Engineering, Tarbiat Modares University Iran Mohammad Reza Khorramizadeh Department of Pathobiology, Faculty of Public Health, Tehran University of Medical Sciences Department of Pathobiology, Faculty of Public Health, Tehran University of Medical Sciences Iran Ahmad Reza Gohari Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences Iran Fibrosarcoma-Wehi 164GeraniolGreen synthesisSilver nanoparticle 14.pdf Raveendran P, Fu J, Wallen SL. A simple and ‘‘green’’ method for the synthesis of Au, Ag, and Au-Ag alloy nanoparticles. Green Chem 2006;8: 34-38. ##Armendariz V, Gardea-Torresdey JL, Jose Ya-caman M, Gonzalez J, Herrera I, Parsons JG. Gold nanoparticle formation by oat and wheat biomasses. Proceedings of Conference on Applica-tion of Waste Remediation Technologies to Agricultural Contamination of Water Resources; 2002 Jul 30- Aug 1; Kansas City, Mo, USA. ##Magudapathy P, Gangopadhyay P, Panigrahi B K, Nair KGM, Dhara, S. Electrical transport studies of Ag nanoclusters embedded in glass matrix. Physica B 2001;299(1-2):142-146. ##Joerger R, Klaus T, Granqvist CG. Biologically produced silver-carbon composite materials for optically functional thin-film coatings. Adv Mater 2000;12(6):407-409. ##Kohler JM, Csaki A, Reichert J, Moller R, Straube W, Fritzsche W. Selective labeling of oligonucleo-tide monolayers by metallic nanobeads for fast optical readout of DNA Chips. Sens Actuators B Chem 2001;76(1-3):166-172. ##Panacek A, Kvitek L, Prucek R, Kolar M, Vecerova R, Pizurova N, et al. Silver colloid nano-particles: Synthesis, characterization, and their antibacterial activity. J Phys Chem B 2006;110 (33):16248-16253. ##Shankar SS, Rai A, Ahmad A, Sastry M. Rapid synthesis of Au, Ag and bimetallic Au core-Ag shell nanoparticles using Neem (Azadirachta indica) leaf broth. J Colloid Interface Sci 2004; 275(2):496-502. ##Shankar SS, Ahmad A, Sastry M. Geranium leaf assisted biosynthesis of silver nanoparticles. Bio-technol Prog 2003;19(6):1627-1631. ##Saadat F, Zomorodian K, Pezeshki M, Khorramizadeh MR. The potential role of non-steroidal anti-inflammatory drugs (NSAIDS) in chemoprevention of cancer. Pak J Med Sci 2003 (3);19:13-17. ##Ahmad A, Mukherjee P, Senapati S, Mandal D, Islam Khan M, Kumar R, et al. Extracellular biosynthesis of silver nanoparticles using the fungus Fusarium oxysporum. Colloid Surf B Bio-interfaces 2003;28(4):313-318. ##Henglein A. Physicochemical properties of small metal particles in solution: “microelectrode” reac-tions, chemisorption, composite metal particles, and the atom-to-metal transition. J Phys Chem 1993;97(21):5457-5471. ##Sastry M, Mayya KS, Bandyopadhyay K. pH Dependent changes in the optical properties of carboxylic acid derivatized silver colloidal par-ticles. Colloids Surf A Physicochem Eng Asp 1997;127(1-3):221-28. ##

New Variations in the Promoter Regions of Human DOCK4 and RAP1A Genes, and Coding Regions of RAP1A in Sporadic Breast Tumors 2 2 Breast cancer is the most common cancer among women in developed countries. The prevalence of the disease is increasing in the world. Its annual incidence among Iranian women is about 7000 cases. RAP1A, a tumor suppressor gene, is located at 1p13.3 and plays an important role in the cellular adhesion pathway and is involved in the pathogenesis of breast cancer. The DOCK4 gene, which is located at 7q31.1, specifically activates RAP1A gene. In the present study, DNA samples from 64 cases of sporadic breast tumors (referred to Mehrad Hospital in Tehran) were screened using PCR-SSCP method and the number of observed variations compared with the control group (100 normal women). Mutation detection for coding exons of RAP1A gene and the 500 bp upstream of transcription initiation site as promoters of both DOCK4 and RAP1A were carried out and compared with the control group. The promoter region of DOCK4 showed a heterozygous mutation with G>A transition at nucleotide -303 in a fibroadenoma case. With regard to RAP1A we found a heterozygous mutation, G>A transition in an adenoid cystic carcinoma case, and another heterozygous mutation, G>T transversion in an intraductal papilloma case both at nucleotide +45. A homozygous variation, T>A transversion was also found at nucleotide +29 of a fibroadenoma case. The differences in the frequency of variations mentioned above were not statistically significant. However Fisher’s exact showed significant difference for T>A transversion. Although, the higher frequency of these mutations and variations may be related to the disease, a larger sample size is needed for the confirmation of our findings. 117 123 Akram Jalali Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Iran Hassan Ebrahimi Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Iran Mina Ohadi Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Iran Masood Karimloo Epidemiology and Biostatistics Department, University of Social Welfare and Rehabilitation Sciences Epidemiology and Biostatistics Department, University of Social Welfare and Rehabilitation Sciences Iran Atena Irani Shemirani Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR Iran Behrokh Mohajer Maghari Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR Iran Hamid Reza Khorram Khorshid Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences Reproductive Biotechnology Research Centre, Avicenna Research Institute, ACECR IranIran DOCK4Loss of heterozygosity (LOH)PCR-SSCPRAP1ASporadic breast tumor 15.pdf Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA Cancer J Clin 2005;55 (2):74-108. ##Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, et al. Breast cancer in Iran: an epidemiological review. Breast J 2007;13(4):383-391. ##Hedau S, Jain N, Husain SA, Mandal AK, Ray G, Shahid M, et al. Novel germ line mutations in breast cancer susceptibility genes BRCA1, BRCA2 and p53 gene in breast cancer patients from India. Breast Cancer Res Treat 2004;88(2): 177-186. ##Osborne C, Wilson P, Tripathy D. Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. Oncologist 2004;9(4):361-377. ##Mitchell EL, Santibanez-Koref MF. 1p13 is the most frequently involved band in structural chromosomal rearrangements in human breast cancer. Genes Chromosomes Cancer 1990;2(4): 278-289. ##Price LS, Hajdo-Milasinovic A, Zhao J, Zwart-kruis FJ, Collard JG, Bos JL. RAP1 regulates E-cadherin-mediated cell-cell adhesion. J Biol Chem 2004;279(34):35127-35132. ##Bieche I, Champeme MH, Matifas F, Cropp C, Callahan R, Lidereau R. Demonstration of two regions involved in chromosome 1p deletion in breast tumors. Bull Cancer 1994;81(2):108-113. ##Bieche I, Khodja A, Lidereau R. Deletion mapping of chromosomal region 1p32-pter in primary breast cancer. Genes Chromosomes Cancer 1999; 24(3):255-263. ##Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, Wahrer DC, et al. DOCK4, a GTPase activator, disrupted during tumorogenesis. Cell 2003;112(5):673-684. ##Reif K, Cyster J. The CDM protein DOCK2 in lymphocyte migration. Trends Cell Biol 2002;12 (8):368-373. ##Nolan KM, Barrett K, Lu Y, Hu KQ, Vincent S, Settleman J. Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes. Genes Dev 1998;12(21): 3337-3342. ##Schmutzler RK, Homann A, Bierhoff E, Wiestler OD, Von Daimling A, Krebs D. Detection of gen-etic alterations in sporadic breast tumors. Gynakol Geburtshilfliche Rundsch 1995;35(Suppl 1):63-67. ##Sztan M, Besznyak , Kovacs T, Toth J, Szemel , Olah E. Lack of correlation between survival and allele loss on chromosome 7q31-32 in primary breast cancer. Pathol Oncol Res 1996;2(1-2):48-51. ##Balkhi SS. Semiquantitative analysis of RAP1A gene expression in sporadic breast cancer. Disser-tation submitted for MSc in Human Genetics, 2006, Genetic Research Centre, Social welfare and Rehabilitation Sciences University. ##National Center for Biotechnology Information, U.S. National Library of Medicine [Internet], Bethesda (MD) [updated 2009 February 4; cited 2009 April 18]. Available from: http://www.ncbi. nlm.nih.gov/. ##Genome browse ENSEMBL [internet] Cambridge [updated 2009 March 3; cited 2009 April 18]. 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Ectopic Expression of Sortilin 1 (NTR-3) in Patients with Ovarian Carcinoma 2 2 Gene expression profiling of ovarian carcinoma tissues has shown an increase of four-fold expression of SORT1 gene. Sortilin 1 (NTR-3) is a 95-100 kDa protein normally expressed in heart, brain, placenta, skeletal muscle, spinal cord, thyroid, and testis. However, its expression has never been reported in normal ovary. Here, we report expression of sortilin 1 in ovarian carcinoma tissues both at gene and protein levels. Sortilin 1 was expressed in all ovarian carcinoma patients (n=15) as well as ovarian carcinoma cell lines (n=5) regardless of their phenotypic characteristics. Non-malignant ovaries (n=6) did not express sortilin 1. The molecular basis for this ectopic expression is not yet clear. Our results showed a major cell surface expression of sortilin 1 rather than ER-Golgi compartment where it is mainly expressed. This finding may introduce sortilin 1 as a novel tumor marker for diagnosis of ovarian carcinoma and may signify its therapeutic value in targeted therapy. 125 131 Shayda Hemmati Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Department of Cell and Molecular Biology, Khatam University Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Department of Cell and Molecular Biology, Khatam University IranIran Amir-Hassan Zarnani Nanobiotechnology Research Center, Avicenna Research Institute Immunology Research Center, Faculty of Medicine, Iran University of Medical Sciences Nanobiotechnology Research Center, Avicenna Research Institute Immunology Research Center, Faculty of Medicine, Iran University of Medical Sciences IranIran Ahmad Reza Mahmoudi Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Iran Mohammad Reza Sadeghi Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Haleh Soltanghoraee Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Mohammad Mehdi Akhondi Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Majid Tarahomi Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR Iran Mahmood Jeddi-Tehrani Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Immune and Gene Therapy Lab, CCK, Department of Oncology-Pathology, Karolinska University Hospital Solna, Karolinska Institutet Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Immune and Gene Therapy Lab, CCK, Department of Oncology-Pathology, Karolinska University Hospital Solna, Karolinska Institutet IranSweden Hodjattallah Rabbani Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Immune and Gene Therapy Lab, CCK, Department of Oncology-Pathology, Karolinska University Hospital Solna, Karolinska Institutet Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR Immune and Gene Therapy Lab, CCK, Department of Oncology-Pathology, Karolinska University Hospital Solna, Karolinska Institutet IranSweden EctopicExpressionNTROvarian carcinomaSortilin 16.pdf Donninger H, Bonome T, Radonovich M., Pise-Masison CA, Brady J, Shih J, et al. Whole genome expression profiling of advance stage papillary se-rous ovarian cancer reveals activated pathways. Oncogene 2004;23(49):8065-77. ##Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, et al. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem 1997;272(6):3599-3605. ##Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM. Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J Biol Chem 1999;274(13):8832-8836. ##Botta R, Lisi S, Pinchera A, Giorgi F, Marcocci C, Taddei AR, et al. Sortilin is a putative post-endocytic receptor of thyroglobulin. Endocrin-ology 2009;150(1):509-518. ##Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, et al. Sortilin is essential for proNGF-induced neuronal cell death. Nature 2004;427 (6977):843-848. ##Elek J, Pinzon W, Park KH, Narayanan R. Rele-vant genomics of neurotensin receptor in cancer. Anticancer Res 2000;20(1A):53-58. ##Arnett MG, Ryals JM, Wright DE. Pro-NGF, sortilin, and p75NTR: potential mediators of injury-induced apoptosis in the mouse dorsal root ganglion. Brain Res 2007;1183:32-42. ##Dal Farra C, Sarret P, Navarro V, Botto JM, Mazella J, Vincent JP. Involvement of the neurotensin receptor subtype NTR3 in the growth effect of neurotensin on cancer cell lines. Int J Cancer 2001;92(4):503-509. ##Morris NJ, Ross SA, Lane WS, Moestrup SK, Petersen CM, Keller SR, et al. Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipo-cytes. J Biol Chem1998;273(6):3582-3587. ##Rohe M, Carlo AS, Breyhan H, Sporbert A, Militz D, Schmidt V, et al. Sortilin-related receptor with A-type repeats (SORLA) affects the amyloid pre-cursor protein-dependent stimulation of ERK signaling and adult neurogenesis. J Biol Chem 2008;283(21):14826-14834. ##Reed E, Zerbe CS, Brawley OW, Bicher A, Stein-berg SM. Analysis of autopsy evaluations of ovari-an cancer patients treated at the National Cancer Institute, 1972-1988. Am J Clin Oncol 2000;23(2): 107-116. ##Pectasides D, Pectasides M, Economopoulos T. Brain metastases from epithelial ovarian cancer: a review of the literature. Oncologist 2006;11(3): 252-260. ##