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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Hepatitis C Virus,Drug resistance,Phylogenetic analysis,protease inhibitors,NS3
- چکیده:
- چکیده انگلیسی: Background: Even with the fantastic successes of direct-acting antivirals (DAA) in the treatment of Hepatitis C
Virus (HCV) infection, natural drug resistance remains a challenging obstacle for their impacts. The data regarding
protease inhibitors (PIs) resistance in Iran population are limited. The aim of this study was to investigate the variations
in NS3 protease of HCV from non-responder patients. Methods: In this cross-sectional study, 14 HCV infected patients
with genotype 1(N=5) and 3(N=9) who have not responded to Interferon-related regime were enrolled from Liver
Clinic, Shiraz. The NS3 protease region was amplified by Nested-PCR followed by product gel extraction. Besides,
some amplified protease regions were cloned into a cloning vector to improve the sensitivity of mutation detection.
Both crude and cloned sequences were then introduced into sequencing. The obtained sequences were compared with
the NS3 reference sequences and analyzed by Geno2pheno available software to find possible substitutions. In the
end, the phylogenetic tree was constructed. Results: Among variations responsible for PIs resistance, only one out of
14 (7%) sample who was infected with genotype 1a, harbored R117C+N174S double mutation, which causes reduced
susceptibility to Telaprevir. Any another resistance mutation was not found among the studied population. The most
frequent substitutions were determined as I52M(N=9), S102A(N=9), S166A(8) and V170I(8) for genotype 3a, and
F147S/A(4) for genotype 1. However, some uncharacterized substitutions on scored position, including I132L(N=1),
I170V(N=3) and N174S(N=2) were also determined among sequences. Phylogenetic analysis demonstrated that the
protease region has enough power to correctly classify enrolled samples into relevant clusters on the tree. There were 2,
3 and 9 cases of sub-genotypes 1a, 1b, and 3a, respectively. Conclusion: A low frequency of PIs resistance mutations
in our HCV infected population is a hopeful point of starting these drugs in HCV infected patients.- انتشار مقاله: 03-10-1397
- نویسندگان: Nargess Nejabat,Seyed Younes Hosseini,Jamal Sarvari,Ali Akbar Gorzin,Mohamad Reza Fattahi,Mohammad Rasoolian
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Key words: Colon cancer,PD.1,ICOS,Polymorphism
- چکیده:
- چکیده انگلیسی: Background: Positive and negative co-stimulatory molecules are important factors determining the outcome
of immune responses to the presence of tumors. Since co-stimulatory molecule expression may be affected by gene
polymorphisms, we aimed to investigate associations between variants of PD.1 and ICOS and susceptibility to colon
cancer. Material and methods: ICOS (-693A/G), ICOS (+1720C/T) and PD.1 (-538G/A) gene polymorphisms were
evaluated by the PCR-RFLP method in 76 colon cancer patients and 73 healthy controls. Results: The frequencies
of the GG genotype and the G allele at position -693 of the ICOS gene were significantly higher in the patient group
(P=0.014 and p=0.0002), while the AA genotype was significantly more common in controls (P=0.0016). At position
-538 of PD.1, GG genotype and G allele frequencies were higher in the patient group (PAA and also AG genotypes significantly predominated in controls (Pand alleles of ICOS at position +1720. Frequencies of GCG and GTG haplotypes were higher in patients compared
to those of controls (P=0.016 and P<0.0001), while, frequencies of GTA, ATA and ATG haplotypes were higher in
controls (P=0.0017, Ppatients compared to controls (P=0.0147 and P=0.0071). Conclusion: Our study clarified that PD.1 (-538G/A) and
ICOS (-693A/G) gene polymorphisms can be considered as genetic risk factors for the development of colon cancer
among Iranian patients.- انتشار مقاله: 17-03-1396
- نویسندگان: Seyedeh Azra Shamsdin,Mohammad Hossein Karimi,Seyed Vahid Hosseini,Bita Geramizadeh,Mohamad Reza Fattahi,Davood Mehrabani,Ali Moravej
- مشاهده