m.a. hosseinpour feizi

This study aimed to evaluate the expression levels of TINCR in tumor and adjacent non-tumor tissues of 50 women diagnosed with invasive ductal carcinoma. The association of TINCR expression and the clinical characteristics of patients have also been studied.

Total RNA was isolated from tumor and adjacent non- tumor tissues of breast cancer patients using RNX-Plus. Then, PrimeScriptTM RT reagent was used for converting total RNA to cDNA. TINCR lncRNA levels were quantified by qRT-PCR and results was analyzed with paired sample t test. Moreover, for evaluation the TINCR biomarker potential, ROC curve analysis was used in breast cancer tumor tissues.

Reduced levels of TINCR were obtained in tumor tissues of breast cancer patients compared with adjacent non-tumor tissues (P<0.0001). TINCR expression had negative association with tumor size and lymph node metastasis in breast cancer tumor tissues.

TINCR lncRNA downregulation in tumor tissues of breast cancer patients indicates that its expression level could discriminate the tumor from non-tumor tissues in breast cancer patients. Furthermore, TINCR lncRNA have low levels in breast cancer patients with large tumor size, positive lymph node metastasis and luminal A and B subtypes.

Studies have suggested that HLA-G is involved in protecting the fetus against the motherchr('39')s immune system, and upstream polymorphisms of this gene may influence pregnancy success by effecting its expression. The aim of this study was to evaluate the association of upstream HLA-G gene polymorphism, rs1736933, with recurrent spontaneous abortion in East Azerbaijan women population.

This case-control study was performed on 80 women with at least one child and without any history of abortion, and 100 women with at least two recurrent spontaneous abortions which were diagnosed by gynecologist. 2 ml of blood was obtained from the participants and after DNA extraction, a segment of the HLA-G gene promoter was amplified by PCR and analyzed by agarose gel electrophoresis. PCR products were sequenced and genotyped. Allelic and genotypic frequencies of patient and control groups were compared.

Frequency of AA, CA, CC genotypes in the patient group were 8(8%), 37(37%), 55(55%) and in the control group were 16(20%), 33(41.25%), 31(38.75%) respectively. Comparison of genotypic frequencies between the two groups showed that CC homozygous genotype was associated with recurrent abortion (p= 0.015). Statistical analysis also showed a significant difference between the allelic frequencies of the two groups (p= 0.019).

The results of this study showed that the upstream HLA-G gene polymorphism, rs1736933, is associated with the recurrent abortion in East Azerbaijan women population.

Breast cancer is the most common cancer in women, which is associated with genetic changes such as mutations in carcinogenic genes and tumor suppressor genes. One of the most important tumor suppressor genes involved in breast cancer is the BRCA1 gene. The mutation in this gene is a common occurrence in human breast cancer. The purpose of this study is to investigate the mutations of exon 11-A of BRCA1 gene in women with breast cancer in the northwest of Iran.
In this descriptive study, blood sample were collected form 40 patients with breast cancer whose cancer was diagnosed before the age of 40 years and the exon 11-A of BRCA1 gene was examined using PCR and direct sequencing methods to detect mutations. Sequencing results were analyzed using Chromas software.
FINDING: In the present study, a nonsynonymous mutation was reported as a new mutation of BRCA1 gene for the first time: Ala584Thr mutation was also observed in two samples. The mutations of codon 694 (Ser694Ser) showed a higher incidence (52.5%). Other mutations were observed in codons 693, 356, 486, 550 and 628.
Based on the results of this study, mutations and polymorphisms of exon 11 of BRCA1 gene were observed for the first time in the northwestern population of Iran. One new case of mutation was observed in exon 11-A of BRCA1 gene.

Diagnosis of Alzheimer's disease usually occurs when serious damages have occurred in the brain and common treatments are ineffective in preventing it. One of the RNAs involved in Alzheimer's disease is a long noncoding RNA, called BDNF antisense (BDNF-AS). The aim of this study is to determine the presence and compare the BDNF-AS levels in plasma of Alzheimer's patients and healthy subjects, and to evaluate its potential as a plasma marker for Alzheimer's disease.
In this case-control study, 30 patients with late-stage Alzheimer's disease and 30 healthy subjects without neurological disease who matched the patients in terms of age were selected by a specialist according to the criteria for clinical diagnosis of Alzheimer's disease and their intravenous blood samples were collected. The plasma of the blood samples was isolated and total plasma RNA was extracted. After cDNA synthesis, the presence of BDNF-AS in plasma was examined by PCR. Finally, the relative level of BDNF-AS transcripts in plasma samples of patients with Alzheimer's disease and healthy subjects was evaluated using Real Time PCR.
FINDINGS: The results of this study showed that long noncoding RNA BDNF-AS was present in the plasma of patients and controls. Comparison of Real Time PCR data showed that BDNF-AS levels in the plasma of patients (0.107±0.021) showed significant increase compared to healthy subjects (0.039 ± 0.006).
The results of this preliminary study indicate that the levels of long noncoding RNA BDNF-AS in plasma can be used as a blood/plasma marker for the diagnosis of Alzheimer's disease.

Breast cancer is the most common cancer and the major cause of cancer death among women. The survival rate for breast cancer indicates the percentage of people that survive the disease for a specified period of time after diagnosis. The aim of this study was analyzing the survival rate of patients with breast cancer in East Azarbaijan province.
This study was a retrospective analysis. The statistical population included 79 breast cancer patients of East Azarbaijan province. Data such as age at diagnosis was obtained from the medical records and other data such as the status of survival/death was found out through telephone interview. For survival evaluation, the Kaplan-Meier method was used. The effect of covariates such as age at diagnosis on the survival duration was calculated with the Log - Rank (Mantel - Cox) method.
The 1, 3 and 5 year-survival rate were calculated to be 98%, 88% and 82%, respectively. Age at the time of diagnosis affected the survival rate of patients; patients over 40 years at the time of diagnosis had a higher survival rate than patients under 40 years (p Survival rate analysis showed the similar or higher survival rate of breast cancer patients of East Azarbaijan in comparison with other regions in Iran. The survival rate in patients older than forty years at the time of diagnosis was significantly higher than patients younger than forty. However a study on more patients is recommended to obtain more clear results.

Breast cancer is the most common invasive cancer and the second main cause of cancer death in women. Long noncoding RNAs (lncRNAs) play a critical role in different cellular and molecular activities such as carcinogenesis. Maternally Expressed Gene 3 (MEG3), is a long noncoding RNA that deregulates in various types of cancers. The aim of this study is the evaluation of MEG3 expression level and its association with clinicopathological features of breast tumor tissues.
In this case-control study, 40 fresh-frozen breast tumor specimens and their paired non-tumoral adjacent tissues were collected from breast cancer patients living in the northwestern region of Iran. All tumor samples belonged to the invasive ductal carcinoma. After RNA extraction and cDNA synthesis, the expression level of MEG3 in breast tumor tissues compared to the paired adjacent normal tissues was investigated using specific primers and quantitative real-time PCR (qRT-PCR). β2m was also used as an internal control for normalization.
Findings: MEG3 expression level in all tumor samples significantly downregulated compared to the paired adjacent nontumoral specimens, with an average fold decrease of 3.355 (p=0/042). Low level of MEG3 in tumor tissues was also related to the age of patients (p=0/007), stage Ⅲ (p=0/049) and lymph node metastasis (p=0/018).
The expression level of MEG3 significantly decreased in breast cancer and this downregulation was related to malignancy state of the tumor.

A common polymorphism 4G/5G in the promoter region of the Plasminogen activator inhibitor-1 (PAI-1) gene has been reported to influence the expression levels of PAI-1. According to the evidence, progression of breast cancer can be associated with elevated levels of PAI-1, it seems that evaluation of a possible correlation between the polymorphism and clinical status of breast cancer patients is reasonable.
This descriptive-analytical study included 160 unrelated patients from North West of Iran. According to established clinical criteria, these paitients were diagnosed with breast cancer. Based on previous study, PAI-1 4G/5G had been determined. In order to investigate the association of this polymorphism with clinicopathological features Fisher’s exact tests and SPSS software was used with a significance level of 0.05.
All declared features of breast cancer regarding PAI-1 4G/5G polymorphism were investigated. Results indicated that PAI-1 4G/5G polymorphism positive correlation with several traditional prognostic factors, including tumor size, lymph node metastases and tumor stage.
Data showed that the patients with 5G/5G genotype are more susceptible to the development of breast cancer, while the paitients with 4G/4G and 4G/5G genotypes show lower sensitivity to the breast cancer. Therefore, the 4G allele likely has a protective role against the development of breast cancer in this cohort.

Breast cancer is the most common type of malignancy in women, and TP53 tumor-suppressor gene is one of the most commonly transformed genes in human cancers. Accurate assessment of TP53 gene mutations in cancer patients can play an important role in diagnosis, prognosis, or treatment. This study aimed to identify mutations of this gene in breast cancer patients. In this descriptive study, 102 tumor samples were obtained from female breast cancer patients from Azarbaijan, Iran. All the participants were referred to hospitals of Tabriz during 2007-2009, and their DNA was extracted by Proteinase K. TP53 gene mutations in exons 7 and 8 and intron 7 were investigated using polymerase chain reaction technique and direct sequencing. Seven (6.86%) cases of mutation and 14 (13.72%) cases of polymorphisms were identified. Mutations (CGG → CAG) at codon 248 (in two cases) and (CTG → CCG) at codon 257 in exon 7 and G>T mutation in the first nucleotide of intron 7 were observed. In exon 8, GTG>ATG mutation at codon 272, CCT>TCT mutation at codon 278, and three nucleotide deletion at codon 262 were identified. The results of this study showed a different pattern of TP53 gene mutation in female breast cancer patients. Further studies could specify the role of TP53 mutations in the progression of breast cancer

Irregular sexual cycle due of improper hormone secretion is most common cause of infertility. Considering fact that women experience twice the rate of depression as men and electroconvulsive therapy (ECT) is one of used treatment methods, therefore this study was conducted to investigate the effect of electric shock on secretion of sex hormones.

In this experimental study 60 albino mice (weighting 28±1.5g and 9-12 weeks) with normal sex cycle were divided into 12 groups of 5 mice in each group after determining estrous cycle stages with vaginal smear: four control groups in our estrous cycle stages, four groups receiving one shock in each of four stages and four groups receiving two-shocks (with interval of 4 hours) in each stage of sex cycle. Shock operation was conducted with laboratory shock device and tolerable shock for mice. Blood samples were collected from mice in the same stage of receiving shock to measure sex hormones and assayed by ELISA method and compared.

Mean serum level of estrogen hormone showed significant difference only in the group receiving two shocks in metestrus stage)3.92±0.074(in comparison to control group of this stage)4.36±0.118) (p< 0.05). Only in diestrus stage, mean serum level of progesterone of one-shock group)5.264±0.243(and two shock group)5.24±0.029(showed no statistically significant difference in comparison to control group)5.466±0.102).

The result of study indicated that electroshock operation had no effect on serum level of both hormones just in diestrus stage of estrous cycle.

Krupple-like factor4 is a transcription factor which is involved in many cancers including Breast cancer. Breast cancer is the most common malignancy among women. Due to the high prevalence of these tumors، there are ongoing efforts to find molecular markers which can recognize nontumoral from tumoral tissues. Therefore، the aim of this study was to evaluate the potential usefulness of KLF4 as a potential diagnostic and therapeutic molecular marker in breast cancer. In the current study، 31 tumoral and 21 non tumoral adjacent tissues were evaluated. Transcription levels were measured by Semiquantitative Reverse Transciptase-Polymerase Chain Reaction and were normalized by the ß2m as an endogenous PCR control. Data was analyzed by spss software، one-way ANOVA and T-test. The results showed that: 1) KLF4 is over expressed in Breast tumors rather than adjacent normal tissues. 2) KLF4 is an oncogene in breast tumors (at least in IDC type). 3) The KLF4 expression levels are related significantly with nature of malignant breast tumors. Findings do not confirm KLF4 as a diagnostic marker in classification and identification of tumoral tissues from non-tumoral ones in breast، but we can use this marker to identify at least 50% of invasive Ductal Carcinoma in breast and utilize it as a potential predictive factor to demonstrate severity degree in various tumors.

Survivin gene, as an apoptosis inhibitor, plays an important role in development of breast cancer. The differential expression of survivin in cancer versus normal adult cells as well as an association between high expression of survivin and aggressive tumors has led to use of survivin as a molecular marker for diagnosis and prognosis of tumors. The underlying mechanism of survivin over expression in cancers is not recognized yet. There is a probability that some polymorphisms in this gene can result in uncontrolled manner of this gene. The C-31G, a widely studied polymorphism in the survivin promoter, could de-repress the cell cycle- dependent transcription of survivin gene, resulting in over expression of survivin. In this hospital- based, case- control study, we aimed to investigate the correlation between the genetic polymorphism of -31G/C, surviving promoter, and breast cancer (BC) in North West of Iran. In this case–control study, the -31G/C single nucleotide polymorphism (SNP) of survivin promoter in peripheral blood samples was collected from 94 breast cancer patients with pathologically confirmed BC and 82 healthy subjects. The data were analyzed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and gene sequencing. Statistical analysis showed that within breast cancer patients, genotype frequencies were 50%, 46.8% and 3.2% for -31G/G, -31G/C and -31C/C genotypes respectively, whereas they were 50%, 45.1% and 4.9 % for -31G/G, -31G/C and -31C/C genotypes in healthy individuals. Also the frequencies for -31 C allele were 26% and 27% in the cases and controls respectively. No statistically significant association was found between breast cancer and the variant genotypes (CC and CG). It seems that there was no significant association between -31G/C polymorphism, BC, and clinicopathological characteristics in the population of our study.

Survivin is a new member of the Inhibitor Apotosis Protein family (IAP) which plays an important role in the regulation of both cell cycle and apoptosis. Its distinct expression in tumor cells as compared to normal adult cells introduces Survivin as the fourth transcriptom demonstrated in tumors. Breast cancer is the most common malignancy among women and scientist`s efforts to classify it has lead to various molecular subtypes and controversial results. Because of the high prevalence of these tumors and lack of suitable molecular markers for diagnosis and prognosis, there are ongoing efforts to find molecular markers which can distinguish nontumoral from tumor tissues. In this study we evaluate the potential usefulness of Survivin and its splice variants ΔEx3, 2b and 3b as molecular markers in breast cancer. We studied 18 tumor and 17 non tumor adjacent tissues. Transcription levels were measured by Semiquantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and normalized by ß2m as an internal control. 1)Survivin and its splice variants Δex3, 2b and 3b showed differentially higher expression levels in tumors than adjacent normal tissues. 2) The expression levels of Survivin, Survivin-ΔEx3 and Survivin-3b were significantly correlated with the type of tumors. 3) Survivin-2b was expressed in a few samples. 4) Survivin-3b was detected only in tumor samples. Also, our results showed that ΔEx3 variant can be introduced as a dominant expressed variant in breast cancer. Our data indicated that the expression of Survivin, Survivin ∆Ex3 and especially, Survivin-3b were correlated with cancerous nature of tumors and Survivin-∆Ex3 was the most common expressed variant in breast carcinomas. These results besides confirming the potential usefulness of Survivin and its splice variants as molecular markers in breast cancer, demonstrated the role of the gene and its splice variants, especially 3b in these lesions that enables distinguishing normal from tumor tissues. Therefore, evaluation of the expression of Survivin and its splice variants might be used as markers to stratify breast cancer patients for more optimal treatment modalities or it could be a promising new target for therapy.

Recent molecular studies on Iranian β-thalassemia genes revealed the presence of eight common mutations associated with thalassemia. Although these mutations are frequent, there are other rare and unknown mutations that can create large problems in designing preventive programs. We detected and explained the common mutations in north-western Iran previously and detection of the rare and unknown mutations could be useful in diagnosis and design of future preventive programs.

In this study, 5ml peripheral blood from 20 Azari- β-thalassemia patients whose mutation was not revealed in the previous study was collected and DNA extraction was done by isopropanol and proteinase k method. Initially, samples were examined for the rare mutations: Codon6, Codon16, Codon41/42, Codon36/37, -88 and Codon22 by ARMS – PCR techniques and then the unknown cases were directly sequenced.

According to our results, Codon15(TGG-TGA), Codon16(-C), Codon36/37(-T), IVSII-848(C-A), IVSII-745(C-G), -28(A-C( and Codon25/26(+T) were recognized and added to the spectrom of beta globin gene mutations in Azerbaijan and Iran. Also, we detected four SNP sites: 5’UTR+20(C-T), Codon2 (CAC-CAT) , IVSII-16(C-G) and IVSII-666(T-C) in β-thalassemia genes.

Our results could be useful for developing molecular screening plans and help prenatal diagnosis of beta thalassemia in Azerbaijan , Iran and other neighboring countries.