@article{ author = {Valadan, Reza and Rafiei, Alireza and Tehrani, Mohsen and Nejatollahi, Forough}, title = {Resistance to HER2-targeted therapy}, abstract ={Production and approval of trastuzumab (Herceptin®) for the treatment of metastatic breast cancer (MBC) was a millstone in antibody-based targeted therapy in the cancer treatment. However, despite the early success in the clinical trials, trastuzumab failed to appreciate the initial attraction due to development of resistance to the drug. The majority of patients who benefit from the drug acquire resistance to it and experience tumor recurrence within 1 year. Several molecular and cellular mechanisms underlying the resistance to trastuzumab have been proposed. In this review, first, we provide a brief history leading to production of trastuzumab. Also we consider the cellular and molecular antitumor effects of trastuzumab and then, we discuss the mechanisms underlying trastuzumab resistance in four levels.}, Keywords = {Trastuzumab, ErbB, Breast cancer, Mechanisms of action, Resistance}, volume = {1}, Number = {1}, pages = {1-9}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.1}, url = {http://rmm.mazums.ac.ir/article-1-35-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-35-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {Mottaghi-Dastjerdi, Negar and Soltany-Rezaee-Rad, Mohammad and Ajami, Abolghasem and Rafiei, Alireza and Abediankenari, Saeid and Gharaee, Eshrat and HashemiSooteh, Mohammad bagher and Rahbarizadeh, Fatemeh}, title = {Production of Cyclin D1 specific siRNAs by double strand processing for gene therapy of esophageal squamous cell carcinoma}, abstract ={Background: RNAi (RNA interference) is a new strategy in gene therapy and biotechnology which provides new promises in the treatment of different diseases such as cancer and viral diseases. CCND1 which is a key gene in cell cycle is amplified and over expressed in esophageal cancer. The objective of this study was production and siRNAs for CCND1, the key gene in cell cycle. Materials and Methods: We used dsRNA digestion method by using recombinant human dicer enzyme to cleave in vitro transcribed dsRNA into a pool of 22bp siRNA. Total RNA was extracted and cDNA was produced using RT-PCR. T7 promoter was added to both ends of the DNA template by PCR. RNA was produced from both strands of the DNA using T7 RNA polymerase. After annealing both strands, dsRNA was prepared. Finally siRNA pool was produced by dicer treatment. Results: RNA extraction yield from HN5 cell line was 14.69 µg/106cell. The results from beta actin control gene confirmed the cDNA integrity. After optimization, T7 promoter adding was confirmed using gel electrophoresis and DNA sequencing. After optimization dsRNA yield was improved. The best incubation condition was 18h. Each microgram of dsRNA yielded 0.5 µg siRNA. Conclusion: dsRNA digestion method includes several steps which the product of each step is used as the precursor for the next step. So optimization and increasing the specificity and product yield should be in the most important goals of the study, because the yield of each step has a direct relationship with the final product yield which is siRNA. Optimizing and increasing the yield, dsRNA digestion method could be a rapid, available and profitable method for siRNA generation, providing large amounts of siRNA.}, Keywords = {dsRNA digestion, siRNA, RNAi, dsRNA, esophageal cancer, CCND1}, volume = {1}, Number = {1}, pages = {10-15}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.10}, url = {http://rmm.mazums.ac.ir/article-1-29-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-29-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {Shahabi-Majd, Naghi and Hashemi-Sotehoh, Mohammad bagher and Habashi, Baharak and Shiran, Mohammad rez}, title = {Frequencies of two CYP2C19 defective alleles (CYP2C19*2, and *3) among Iranian population in Mazandaran Province}, abstract ={Background: Cytochrome P450 2C19 (CYP2C19) is a polymorphically expressed enzyme that shows marked interindividual and interethnic variation. CYP2C19*2 and CYP2C19*3 are the most frequently identified defective alleles in Orientals and Caucasian poor metabolizers (PM). The aim of this study was to investigate the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles and CYP2C19 genotypes in the Mazandarani ethnic group among Iranian Population.  Materials and Methods: The study was conducted in 103 unrelated healthy volunteers. DNA was extracted from leucocytes and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes (SmaI and BamH1) and then separated electrophoretically using polyacrylamide gel.. Results: Of the alleles tested, CYP2C19*1, and CYP2C19*2, but not CYP2C19*3, were detected. The frequencies for CYP2C19 alleles *1, *2, and *3 were 91%, 9.0%, and 0.0%, respectively. The frequencies of CYP2C19 genotypes *1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 were 84%, 14%, 0.0%, 2.0%, and 0.0%, respectively. Conclusion: The result of the present study showed that the two inactive alleles of CYP2C19 accounted for 9.0% of CYP2C19 alleles in our sample versus 8.8 - 40.1% reported in other populations. The frequencies of the studied alleles resulted significant differences between our sample and African and Eastern Asian populations.}, Keywords = {CYP2C19, genotype, alleles, Mazandaran, Iranian}, volume = {1}, Number = {1}, pages = {16-20}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.16}, url = {http://rmm.mazums.ac.ir/article-1-30-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-30-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {Akbari, Esmaeil and Naderi, Nima and Yaghoobi, Keyvan and Parsi, Behzad and Berijani, Sahar}, title = {Chronic intracerebroventricular administration of dimethyl sulfoxide attenuates streptozotocin-iduced memory loss in rats}, abstract ={Background: The memory impairment, obtained from intracerebroventricular (i.c.v.) infusion of streptozotocin (STZ) in rats through activation of oxidative stress, is accepted as sporadic Alzheimer’s disease (AD) model in most experimental studies. Dimethyl sulfoxide (DMSO) as a solvent is widely used in animal studies to have antioxidant effects as well. However, no report is available about DMSO effect on oxidative stress-induced cognition deficit i.e. AD. The present work was designed to assess the effect of chronic treatment of DMSO on STZ-treated rats. Materials and Methods: STZ (3 mg/ kg i.c.v. bilateral with 10 µl volume in either side days 1 and 3) using a single-day version of Morris water maze (MWM). The DMSO (2.5, 5 and 10 %v/v in saline), started from the first day, was infused for 14 days. Results: The chronic administration of DMSO 10% (but not 2.5 and 5%) improved the distance to hidden platform (P<0.01) in training sessions and time spent in the target quadrant (P<0.01) in probe tests. Neither STZ nor DMSO had any intervention on velocity and visuo-motor coordination in the visible version of MWM. Conclusion: Taken together, the results suggest that DMSO may be appropriate as adjuvant therapies for the prevention of memory impairment in the experimental models of AD. Therefore, use of DMSO as a solvent in AD animal studies should be considered having beneficial effects on cognitive function.}, Keywords = {Alzheimer’s disease , dimethyl sulfoxide, Morris water maze, streptozotocin}, volume = {1}, Number = {1}, pages = {21-28}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.21}, url = {http://rmm.mazums.ac.ir/article-1-26-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-26-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {Ajami, Abolghasem and Shadman, Mojtaba and Rafiei, Alireza and Hosseini, Vahid and TalebiBezminAbadi, Amin and Alizadeh, Ahad and Hosseini-khah, Zahr}, title = {Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with gastroduodenal disorders in northern Iran}, abstract ={Background: Cytotoxin-associated gene A (CagA)-positive strains of Helicobacter pylori are associated with gastroduodenal diseases. Evidences have suggested that the type of H pylori CagA EPIYA motifs may be associated with specific disorders (i.e., gastritis, peptic ulcer, or gastric cancer).  We investigated the prevalence of different EPIYA motifs (A, B, C, or D) in H. pylori strains isolated from patients with recurrent dyspepsia who underwent upper gastrointestinal (GI) endoscopy. Materials and Methods: H. pylori strains were isolated from biopsy specimens of 220 patients with dyspepsia symptoms. The presence of glmM gene, as a housekeeping gene CagA and pattern of cagA EPIYA motifs were genotyped using by polymerase chain reaction (PCR) method.The association between the type of motifs and disease state determined by the Chi-square test, Fisher’s exact test, and logistic regression. Results: CagA-positive H. pylori were identified in 125(57%) of patients with gastrointestinal disorders, of whom 36(28.6%) were isolated from gastritis, 31 (24.6%) from duodenal ulcer, and 58 (46.4%) from gastric cancer. The frequency of pattern of cagA EPIYA motifs were 39 (31.2%) AB motifs, 54 (43.2%) ABC motifs, and 32 (25.6%) ABCC motifs and not detected D motifs. Gastric cancer risk was estimated to be 2.57 times higher in patients infected by strains with ABCC motif when compared with gastritis and duodenal ulcer patients (P=0.03). Moreover, patients with C- containing motifs were 2.27 times more likely to be affilicted with gastric cancer than duodenal ulcer. AB motif was more associated with gastritis and duodenal ulcer than ABC and ABCC motifs. Conclusion: The results suggested that cag-EPIYA ABCC might be associated with gastric cancer, while EPIYA-AB might be is associated with duodenal ulcer.}, Keywords = {Helicobacter pylori, Cytotoxin-associated gene A, gastritis, peptic ulcer, Iran}, volume = {1}, Number = {1}, pages = {29-34}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.29}, url = {http://rmm.mazums.ac.ir/article-1-34-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-34-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {MotavalliHaghi, Seyed Mousa and Fakar, Mahdi and Sharif, Mehdi and Paghe, Abdolsatar and Sharbatkhori, Mitra and Tavakoli, Rashid and Gholami, Shirz}, title = {Molecular identification of ovine Babesia spp. in north of Iran}, abstract ={Background: Babesia is blood-tissue parasite, which are transmitted by hard ticks from Ixodidae family. The parasite is the cause of Babesiosis among ruminants. Babesia is as one of main fatal factors among livestock in endemic regions such as Iran. The aim of this study was to investigate Babesia spp infection using microscopic and molecular methods among small ruminants in Mazandaran and Golestan provinces, northern Iran, in 2011-2012. Materials and Methods: In this cross-sectional study, 22 flocks of total 220 sheep and goats were selected from different regions of these provinces. Subsequently, ten suspected animals were selected randomly and blood sample were taken from their ear. To diagnose thick and thin smears were prepared and stained with Geimsa stain and then examined under light microscope. Standard PCR and Semi nested PCR was performed to differentiate genus of Theileria and Babesia, also identify the species of Babesia.  Results: A total of 220 blood samples (160 sheep and 60 goats), 34 cases (15.4 %) had Babesia infection using microscopic. Whereas, 11 cases (5%) were found positive through Babesia spp using standard PCR and also among them, two cases were found mixed infection through Theileria spp. In addition, two microscopic negative were positive by PCR assay. Totally, using semi-nested PCR, Babesia ovis (n=10) and Babesia motasi (n=1) were detected. Conclusion: Our results showed ovine Babesiosis was common in the Iranian Northern provinces .Moreover, Babesia ovis is the main causative agent of ovine Babesiosis in this areas. The relatively high prevalence of Babesia infection in livestock indicates the epizootic stability status of babesiosis in the northern part of Iran.  }, Keywords = { Babesiosis, Small ruminant, Microscopic examination, PCR assay, Babesia ovis, Babesia motasi}, volume = {1}, Number = {1}, pages = {35-39}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.35}, url = {http://rmm.mazums.ac.ir/article-1-32-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-32-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {Hashemi, Abbas and Abediankenari, Saeid and Madani, Abdollah}, title = {Alterations in salivary IgA levels in infectious and inflammatory disorders of upper respiratory tract}, abstract ={Background: The airway surfaces are one of the most common ways of entry of infectious agents. Oral cavity associated lymphoid tissues are inductive site of humoral immune responses in inflammatory and infectious disorders of the upper respiratory tract. These lymphoid tissues play important roles in the induction of salivary IgA. The impact of upper respiratory tract diseases on salivary IgA production has not been fully understood. Therefore, in this study, we investigated the salivary IgA levels in patients suffered from upper respiratory tract diseases to indicate the effect of these diseases on salivary IgA production. Materials and Methods: In this study, salivary IgA level of 156 patients with inflammatory diseases of the upper respiratory tract including chronic rhinosinusitis, ear and pharynx diseases have been evaluated by direct immunoenzymatic determination. Results: In pharynx disorders 11.8 % of patients were IgA deficient , 76.2 % were normal and11.8 % had elevated level of IgA .In patients with chronic rhinosinusitis IgA deficiency was observed in 9.2 % , 75.9 % were normal and there was an elevation in 14.8 % of patients .In ear disorders 11.6% were IgA deficient ,76.7 % normal and 11.6 % had elevated IgA level. Conclusion: This study provided evidence for the first time that changes in salivary IgA level are almost the same in different sites of infectious and inflammatory diseases of upper respiratory tract. Our investigation revealed that local up regulation of salivary IgA is not particular interest in majority of patients with upper respiratory tract infections.}, Keywords = {Salivary IgA, Upper respiratory tract diseases, Mucosal defense.}, volume = {1}, Number = {1}, pages = {40-42}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.40}, url = {http://rmm.mazums.ac.ir/article-1-28-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-28-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} } @article{ author = {Maleki, Iradj and Zali, Mohammad Reza and Najm-Abadi, Hossei}, title = {Novel mutations in ATP7B gene of Wilson\'s disease in Iranian patients}, abstract ={Bacground: Wilson's disease is a rare autosomal recessive disorder characterized by toxic accumulation of copper in liver and brain. The disorder is caused by mutations in the ATP7B gene, encoding a copper transporting P-type ATPase. Characterization of the spectrum of mutations in this gene is important both for diagnosis and genetic counseling of the families. Materials and Methods: We enrolled 30 definitely diagnosed patients (ages ranging from 3 to 33). Genomic DNA was extracted from peripheral blood samples. All the exons of the gene were amplified by polymerase chain reaction using specified primers for each exon. The amplification products were then analyzed by direct automated sequencing. Results: 87% of our patients had liver problems while 47% of suffered from neurological problems. In this study we will report the spectrum of mutation found among Iranian families, which are mainly different from other reports. Conclusion: By performing the present study, some new mutations in ATP7B gene, Del C 3696(1232) and S1369L were identified for the first time in Wilson's disease patients.}, Keywords = {Wilson's disease, ATP7B, mutation detection, Iran}, volume = {1}, Number = {1}, pages = {43-46}, publisher = {Mazandaran University of Medical Sciences}, doi = {10.18869/acadpub.rmm.1.1.43}, url = {http://rmm.mazums.ac.ir/article-1-36-en.html}, eprint = {http://rmm.mazums.ac.ir/article-1-36-en.pdf}, journal = {Research in Molecular Medicine}, issn = {2322-1348}, eissn = {2322-133X}, year = {2013} }