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The role of para aortic lymphadenectomy in early stage of ovarian cancer
Zohreh Yousefi , Sima Kadkhodayan , Maliheh Hasanzadeh Mofrad , Behroz Davachi , Mansoureh Mottaghi , Elham Hoseini , Monavar Afzalaghaee , Asieh Maleki ,
Volume 74, Issue 9 (12-2016)
Abstract

Background: Surgical staging is the standard treatment of ovarian cancer. Pelvic and para-aortic lymphadenectomy is the important part of the surgery. The aim of this study was to evaluate the effect of para aortic lymph node dissection in early stage of patients with ovarian cancer.

Methods: This descriptive cross-sectional cohort study was performed on all stage I of ovarian cancer patients admitted in department of gynecology oncology of Ghaem Hospital, Mashhad University of Medical Sciences in November 2012 to March 2014. Every patient with clinical early stage of ovarian cancer candidate to surgical treatment selected. All cases underwent surgical staging surgery with concurrent systematic pelvic and para-aortic lymphadenectomy. In laparotomy after identification of left and right iliac artery, all lymph nodes have been properly exposed and dissected as a part of a staging laparotomy. The dissection was continued up to the nodal tissues surrounding the aorta, and inferior vena cava, until inferior mesenteric artery lymphadenectomy level. The procedure performed only by gynecologist oncologist. In addition, we assessed other parameters such as operation time, estimated blood loss, associated mortality and morbidity and vascular injuries. Finally, the effect of para aortic lymph node dissection in early stage of ovarian cancer evaluated.

Results: Among a total of 57 ovarian cancer patients, 27 of them apparent stage I disease cases were selected. Surgical staging surgery with concurrent systematic pelvic and para-aortic lymphadenectomy was carried for all of them. Positive para-aortic lymph node was found only in one case. The average number removed para-aortic lymph nodes in the pelvis was 9 and in para aortic was 7, respectively. In addition, 20 minutes increase in total length of operation time was observed duo to para-aortic lymphadenectomy. Also the rate increase in intra-abdominal hemorrhage rate was estimated 60 ml.

Conclusion: Lymph node dissection will produce a significant benefit in accurate and complete surgical staging. Staging surgery in addition to systematic pelvic and para aortic lymph adenoctomy in early stage ovarian cancer is preferred in gynecologic oncology centers.

BCG: the only available vaccine against tuberculosis: review article
Roghayeh Teimourpour , Zahra Meshkat , Mohsen Arzanlou , Hadi Peeridogaheh , Aida Gholoobi ,
Volume 74, Issue 10 (1-2017)
Abstract

Background: Despite advances in the vaccinology and chemotherapy in the past century, tuberculosis is still responsible for two million deaths every year. Emergence of multi-drug resistant strain and coinfection of TB-HIV make it a serious concern. Treatment and control of tuberculosis is a great health burden in every community. Active tuberculosis in children has very severe consequences especially those who are under 5-years-old, therefore vaccine indication should be taken. Bacille Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used for providing immunity or protection against tuberculosis (TB). In addition, BCG provides relative protection against leprosy and Buruli ulcer, it also can be used for treatment of bladder cancer. BCG is the most widely administered vaccine around the world. It has been given to over three billion individuals over the past decades. At first it was developed in 1908 at the Pasteur Institute in Lille by Albert Calmette and Camille Guérin. In fact BCG is a strain of Mycobacterium bovis that bear deletion in its genome following too long subculture in special media. Deletion in region of deletion 1 (RD1), a specific region of Mycobacterium bovis genome, has decreased pathogenicity of BCG strain. Following culture of BCG on different media since 1921 make genetic variation in the BCG strains that have specific characteristics. BCG should begin given to only immune-competent individuals and should not be administered to immunocompromised people. This vaccine is not effective in people formerly infected or sensitized with environmental mycobacteria. Previous meta-analysis studies indicate that BCG has variable range of protection from 0 to 80 percent against pulmonary TB, but is very effective against severe disseminated forms such as meningitis and miliary form of TB. Despite many research and develop new generation vaccine against TB, BCG vaccine still remains as the only effective vaccine because many efforts to replace it with better ones were unsuccessful.


The A-kinase anchoring proteins correlation with disease free survival in breast cancer
Rezvan Esmaeili , Tannaz Samadi , Nasrin Abdoli , Keivan Majidzadeh-Ardebili , Leila Farahmand , Malihe Salehi ,
Volume 74, Issue 10 (1-2017)
Abstract

Background: Researchers are always trying to find specific markers which express specifically in cancer. These specific markers help to diagnose and treat cancer without affecting normal tissues. Cancer-testis antigens are among the new promising biomarkers, especially for targeted therapy. These markers are specially expressed in testis. Various studies have been reported individual expression of these proteins in some tumor tissues. Since testis is an immune privilege organ, abnormal expression of the above mentioned genes raises immune response and the serum antibody against them (CT antigene) can be detected as a marker of cancer. However, understanding their differential role in normal and cancer tissues may introduce them as new candidates of cancer biomarkers. The aim of this study was to evaluate AKAP3 gene expression in breast cancer and its correlation with clinicopathologic features of the disease.

Methods: This study is a case-control study conducted at the Brest Cancer Research Center (BCRC)- Iran, between October 2014 to May 2016. AKAP3 gene expression was investigated with real-time PCR in breast samples including: 74 tumors, 73 normal adjacents and 15 normal tissues. On the other hand the correlation between gene expression, clinicopathologic features of the tumors and treatment regimen were evaluated.

Results: Statistical analysis showed a significant correlation between lack of AKAP3 expression, tumor size (P=0.01) and stage (P=0.04). The association between poor prognosis and the absence of AKAP3 expression in normal adjacent tissues were observed. Kaplan Meier plot showed a significant better disease free survival in the normal adjacent patients group that are expressed AKAP3.

Conclusion: It was observed that the better free survival in the normal adjacent group is because of the different AKAP3 expression, not treatment variations between two patient groups. As a result, AKAP3 can be a suitable candidate biomarker for breast cancer patients. Also, the study of gene expression in normal tissue of patients may be used to predict response to therapy.

Designing the colorectal cancer core dataset in Iran
Sara Dorri , Alireza Atashi , Safoura Dorri , Ebrahim Abbasi , Mohsen Alijani-Zamani , Najme Nazeri ,
Volume 74, Issue 10 (1-2017)
Abstract

Background: There is no need to explain the importance of collection, recording and analyzing the information of disease in any health organization. In this regard, systematic design of standard data sets can be helpful to record uniform and consistent information. It can create interoperability between health care systems. The main purpose of this study was design the core dataset to record colorectal cancer information in Iran.

Methods: For the design of the colorectal cancer core data set, a combination of literature review and expert consensus were used. In the first phase, the draft of the data set was designed based on colorectal cancer literature review and comparative studies. Then, in the second phase, this data set was evaluated by experts from different discipline such as medical informatics, oncology and surgery. Their comments and opinion were taken. In the third phase refined data set, was evaluated again by experts and eventually data set was proposed.

Results: In first phase, based on the literature review, a draft set of 85 data elements was designed. In the second phase this data set was evaluated by experts and supplementary information was offered by professionals in subgroups especially in treatment part. In this phase the number of elements totally were arrived to 93 numbers. In the third phase, evaluation was conducted by experts and finally this dataset was designed in five main parts including: demographic information, diagnostic information, treatment information, clinical status assessment information, and clinical trial information.

Conclusion: In this study the comprehensive core data set of colorectal cancer was designed. This dataset in the field of collecting colorectal cancer information can be useful through facilitating exchange of health information. Designing such data set for similar disease can help providers to collect standard data from patients and can accelerate retrieval from storage systems.

Effects of cyclophosphamide on proliferation and viability of malignant HN5 cell line and comparing with embryonic fibroblast cells
Elham Hoveizi , Tayebeh Mohammadi ,
Volume 74, Issue 11 (2-2017)
Abstract

Background: One of the major causes of death in the world is cancer and therefore any study in the field of cancer biology is of great importance. Head and neck cancers represent approximately 2-5% of neoplasms which is higher in some countries. The most appropriate therapy for various cancers is identifying effective and efficient ways that contribute to initiation of apoptosis. Cyclophosphamide is an alkylating agent that stops the replication of DNA and then, it stops the cell proliferation and viability. Therefore, cyclophosphamide is used to treat various types of cancer. In this study we evaluate the cytotoxic effects of cyclophosphamide on viability of (head and neck cancer cells) HN5 cell line and compare it with fibroblast cells as noncancerous cells.

Methods: This experimental study was done in cell and developmental laboratory in faculty of science, Shahid Chamran University of Ahvaz in Spring of 2016. HN5 cell line and embryonic fibroblast cells were grown in DMEM supplemented with 10% fetal bovine serum (FBS), penicillin/streptomycin (100 U/ml, 100 µg/ml) at 37 °C, then the effects of different concentrations of cyclophosphamide on cell viability was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. 4',6-diamidino-2-phenylindole (DAPI) staining was performed to determine the proportion of apoptotic cells by manually counting pyknotic nuclei. According to standard procedures from day 13 embryos of outbred strains naval medical research institute (NMRI), fibroblast cells were isolated. In this study HN5 cell line and fibroblasts were exposed to cytostatics for 72 hours.

Results: Various concentrations of cyclophosphamide were effective in cytotoxicity of HN5 cancer and fibroblast cells. A significant cytotoxicity was observed with the examined concentration of 1 µg/ml of cyclophosphamide with 50% in 3th day and P< 0.001. Interestingly, at low concentrations, cyclophosphamide was more toxic than at higher concentrations.

Conclusion: Totally cyclophosphamide had low toxicity effects on both of the cell lines but the toxicity effects of cyclophosphamide on HN5 were significantly greater than fibroblast cells. These results indicate that cyclophosphamide can be a potential anticancer agent.

Germline mutation of RET proto-oncogene’s exons 17 and 18 in Iranian medullary thyroid carcinoma patients
Marjan Zarif Yeganeh , Samira Kabiri , Sara Sheikholeslami , Hosna Hesanmanesh , Mehdi Hedayati ,
Volume 74, Issue 12 (3-2017)
Abstract

Background: Thyroid carcinoma is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) approximately accounts for 5-10% of all thyroid carcinoma. Nowadays, it is obviously, the mutations in REarranged during transfection (RET) proto-oncogene, especially, mutations in exons 10, 11 and 16 are associated with MTC pathogenesis and occurrence. Thus, early diagnosis of MTC by mutation detection in RET proto-oncogene allows to identify patients who do not have any developed symptoms. The aim of this study was to screening of germline mutations in RET proto-oncogene exons 17 and 18 in MTC patients and their first degree relatives in Iranian population.

Methods: In this cross-sectional study, three hundred eleven participates (190 patients, 121 their relatives) were referred to endocrine research center, Shahid Beheshti University of Medical Science during September 2013 until September 2015. The inclusion criteria were pathological and clinical diagnosis. After whole blood sampling, genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection in exons 17 and 18 was performed using PCR and direct DNA sequencing methods.

Results: In this study, twenty missense mutations [CGC>TGC, c.2944C>T, p.Arg982Cys (rs17158558)] which included 16 heterozygote and 4 homozygote mutations were found in codon 982 (exon 18). In the present study, 154 G>A (rs2742236) and 4 C>T (rs370072408) nucleotide changes were detected in exons 18 and intron 17 respectively. There was no mutation in exon 17.

Conclusion: It seems that because of arginine to cysteine substitutions in RET tyrosine kinase protein structure and its polyphen score (0.955) and SIFT score (0.01) the mutation in codon 982 (exon 18) could be have pathogenic effects. On the other hands, the mentioned mutation frequency was 6.4% among MTC patients, so this mutation of exon 18 could be checked in genetic screening tests of RET proto-oncogene. Although this needs more study.

Oxidative stress: development and progression of breast cancer:review article
Arash Salmaninejad , Parisa Kangari , Abbas Shakoori ,
Volume 75, Issue 1 (4-2017)
Abstract

Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS) that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause free radicals which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances known as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated by hope that better exploration of the factors involved in the occurrence and spread of cancer will improve the identification of treatment aims.


The relationship between intake of macronutrients and vitamins involved in one carbon metabolism with breast cancer risk
Mahshid Hatami , Mohammad Esmaeil Akbari , Morteza Abdollahi , Marjan Ajami , Yasaman Jamshidinaeini , Sayed Hossein Davoodi ,
Volume 75, Issue 1 (4-2017)
Abstract

Background: Breast cancer is the most common cancer among females in the world. Identifying the nutrients that modify the risk of the disease is one of the key strategies for improving the quality of life and reducing treatment costs. Epidemiological studies support the role of macronutrients and vitamins involved in one carbon metabolism in the etiology of the disease. This study aimed in investigation of the relationship between the intake of macronutrients and vitamins involved in one carbon metabolism with breast cancer risk.

Methods: This case-control hospital base study was conducted at Shohada Hospital, Tehran from April to February 2015. Demographic data, physical activity level and nutrients’ intake from diet and supplements were collected through interview from 151 cases and 154 controls. Dietary intake was assessed by a valid and reliable 168-item semi-quantitative food frequency questionnaire. Then intake of macronutrients and B vitamins was assessed by Nutritionist 4 software (First Databank Inc., CA, USA). Comparing categorical variables between the two groups was done by Chi-squared test and the relationship between intake of studied nutrients and risk of breast cancer was determined using logistic regression test.

Results: There were no difference in age, menarche age, menopause age, body mass index (BMI), number of live births between two groups. But the difference in physical activity, energy intake, marital status, educational level, occupation, oral contraceptives use was significant (P< 0.001). After modifying the effects of confounding variables, the risk of breast cancer was significantly lower in the highest intake quartile category relative to the lowest quartile category for total protein, total fiber, intake of vitamins B2, B6, B12 and folate (Ptrend< 0.001). Before modifying the effects of confounding variables, the risk of breast cancer was significantly higher in the highest intake quartile category relative to the lowest quartile category for carbohydrate and fat; but after modifying the effects of confounding variables, results were not significant.

Conclusion: The results showed that high intake of protein, fiber, vitamins B2, B6, B12 and folate are associated with lower risk of breast cancer.


The anti-cancer effect of octagon and spherical silver nanoparticles on MCF-7 breast cancer cell line
Mehrdad Khatami, Sam Kharazi , Zeinab Kishani Farahani , Hakim Azizi , Marcos Augusto Lima Nobre,
Volume 75, Issue 1 (4-2017)
Abstract

Background: The modern science of nanotechnology is an interdisciplinary science that has contributed to advances in cancer treatment. This study was performed to evaluate the therapeutic effects of biosynthesized silver nanoparticles on breast cancer cell of line MCF-7 in vitro.

Methods: This analytical study was performed in Kerman and Bam University of Medical Sciences, Bam City, Kerman Province, Iran from March 2015 to March 2016. Silver nanoparticles suspension was synthesized using palm kernel extract. The resulting silver nanoparticles were studied and characterized. The ultraviolet-visible spectroscopy and transmission electron microscopy used for screening of physicochemical properties. The average particle size of the biosynthesized silver nanoparticles was determined by transmission electron microscopy. The properties of different concentrations of synthesized silver nanoparticles (1 to 3 μg/ml) and palm kernel extract (containing the same concentration of the extract was used for the synthesis of silver nanoparticles) against MCF-7 human breast cancer cells were determined by MTT assay. MTT is used to assess cell viability as a function of redox potential. Actively respiring cells convert the water-soluble MTT to an insoluble purple formazan.

Results: The ultraviolet-visible spectroscopy showed strong absorption peak at 429 nm. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) images revealed the formation of silver nanoparticles with spherical and octagon shape and sizes in the range between 1-40 nm, with an average size approximately 17 nm. The anti-cancer effect of silver nanoparticles on cell viability was strongly depends on the concentration of silver nanoparticles and greatly decrease with increasing the concentration of silver nanoparticles. The IC50 amount of silver nanoparticle was 2 μg/ml.

Conclusion: The biosynthesized silver nanoparticles showed a dose-dependent toxicity against MCF-7 human breast cancer cells.

Micronuclei in peripheral blood lymphocytes of patients with of the gastrointestinal cancer
Bahareh Abbasi , Nafiseh Ansarinejad , Farshid Fardad , Tayeb Ramim ,
Volume 75, Issue 2 (5-2017)
Abstract

Background: The Micronuclei has been discussed as an indicator of chromosomal damage in radiotherapy. This study aimed to investigate the changes of micronuclei in peripheral blood lymphocytes of patients with of the gastrointestinal cancers pre- and post-chemo-radiation.

Methods: This cross-sectional study was conducted in patients with gastrointestinal cancers who referred to oncology ward of Rasool Akram Hospital in Tehran from January to March, 2016. After obtaining informed consent from all patients, 3 cc of peripheral blood samples was obtained for cytogenetic assessment in two stages, before treatment and 4 weeks after treatment. The frequency of micronuclei was examined per 1,000 lymphocytes with two nuclei.

Results: Sixty-one patients were evaluated and 11 patients were excluded at the end of study. Fifty patients (34 males, 16 females) with a 59.74±13.34 years old were evaluated. 24 (48%) and 26 patients (52%) were in the less than 60 years’ age group and more than one, respectively. 37 cases (74%) with gastric cancer and 13 cases (26%) with esophageal cancer enrolled in the study. The significant differences were meaningful pre- and post-treatment (44.88 vs. 364.4 /1000 cells) (P=0.005). Also, there were no significant differences of the mean number of micronuclei between pre- and post-treatment according the type of cancer, sex and age groups. Further analysis according by age, sex and cancer of the esophagus or stomach showed no statistically significant differences between the groups in micronuclei number. In other words, chemotherapy and radiation in patients, regardless of age, sex and type of gastrointestinal cancer is very significant impact on the micronuclei production in peripheral blood of patients.

Conclusion: The number of micronuclei in peripheral blood increased significantly in patients with gastrointestinal tract cancer (esophagus and stomach) under the chemo-radiation therapy. It seems that this increase was not correlated with age, sex and type of cancer (stomach or esophagus).


TOX3 Gene polymorphisms and breast cancer; effects and implications of the variations: review article
Amir Tajbakhsh, Fahimeh Afzal Javan , Mostafa Fazeli, Mahdi Rivandi, Mohammad Mahdi Kushyar, Mohammadreza Nassiri, Alireza Pasdar,
Volume 75, Issue 5 (8-2017)
Abstract
Breast carcinoma is the most common cause of cancer mortality among women globally. Primary and secondary prevention through avoiding known risk factors, screening for early detection of tumors with different methods as well as timely treatment, can be effective in reduction of the burden of this devastating disease. This can in turn prevent death and also increase survival in patients with breast cancer. Both environmental and genetic factors are involved in the pathogenesis of breast cancer. Multiple genetic factors can influence the risk and development of breast cancer. Identification of genetic variants including single nucleotide polymorphisms (SNPs), which are associated with the risk of breast cancer development, are mostly done through genetic association studies. It is demonstrated that SNP allele frequencies vary amongst different populations. It has been shown that genetic risk factors like variations in TOX high mobility group box family member 3 (TOX3), which affect the liability for neoplasm, play an important role in the development of breast cancer. Although TOX3 is expressed mainly in the brain, its expression in other tissues especially breast has also been reported. TOX3 maps to chromosome 16q12 and encodes the nuclear high-mobility group (HMG)-box. It has calcium (Ca2+)-dependent transcriptional activities and is a co-factor of cAMP response element (CRE)-binding protein (CREB) and CREB-binding protein (CBP). TOX3, activated with Ca2+, is related with activation of the promoter of some other genes including BCL2 and C3 complement and also CITED1 gene expression. It also induces activation of the c-fos promoter and therefore its expression. Genome-wide association studies (GWAS) in different populations including European, Asian and African-American have demonstrated that a SNP near its 5ʹ end and the promoter of TOX3 gene appears to be significantly associated with breast cancer susceptibility. Furthermore, breast cancer–associated SNPs lead to enhanced FOXA1 bindings and in turn, a reduction in TOX3 gene expression. This review has highlighted the importance of TOX3 function, SNPs and its association with breast cancer risk and also its potential effects on breast cancer treatment; TOX3 plays dual and somehow conflicting roles in cancer initiation and progression which remains to be further investigated.

Comparison of sexual dysfunction in women with breast cancer: case control study
Soudabeh Shahid Sales , Malihe Hasanzadeh , Seyyedeh Sania Saggade , Seyed Amir Al Davoud ,
Volume 75, Issue 5 (8-2017)
Abstract
Background: Breast cancer is the most common cancer in women and can have several profound effects on women’s life. Estrogen and androgens reduction cause sexual problems. Reduction of hormones produce problems such as vaginal dryness, vaginal and vulvar tissue thinning, loss of elasticity of the vagina, hot flashes and other problems. Depression in these patients is also a factor in reducing sexuality. Disruption at any sexual stage can cause sexual problems. In this article; we compare sexual dysfunction in patients with breast cancer and healthy people.
Methods: According to the women’s case-control study with simple un-randomized sampling method a total of 245 patients with breast cancer in Ghaem and Emam Reza and Omid hospital from july 2011 to july 2013 entered the study. All patients were on follow-up after therapy, and had a therapy portfolio. In order to achieve better results, questionnaires were distributed among 126 healthy subjects that matched our patient group in terms of age and other factors and were used as the control group. Female sexual function index (FSFI) questionnaire was filled out by an independent interviewer and all medical, personal and social ethics were applied. The data was then gathered and the score were analyzed with statistical tests.
Results: The study was performed on patients 20 to 50 years, mainly in patients aged 35 to 45 years (51.8%). The average age was 41.44±5.87 years. In our study, the most dysfunction was in sexual desire (57.6%), vaginal moisture (53.1%), sexual excitement (48.2%), orgasm (44.1%), and dyspareunia (52.2%) in breast cancer patients. There was significant difference between two group (P<0.001).There is no difference about sexual satisfaction between two groups (P=0.262).
Conclusion: Sexual dysfunction is common in breast cancer patients compared to healthy women. Dysfunction in orgasm, dyspareunia, reducing vaginal moisture and sexual desire were common in the breast cancer patient. The results of this study should be used to inform patients and physician about sexual problems.

Relative quantification of AXIN2 mRNA expression in different pathological types of colorectal polyps
Mina Golmohammadi , Hamid Asadzadeh Aghdaei , Hossein Maghsoudi , Ehsan Nazemalhosseini Mojarad,
Volume 75, Issue 5 (8-2017)
Abstract
Background: Most of colorectal cancers (CRC) have originated from intestinal polyps. Evaluating of the expression level of genes that are involved in tumors growth and development, may consider as diagnostic factor of malignancy in the polyps. AXIN2 regulates the level of nuclear β-catenin in a negative-feedback loop there by being a negative regulator and target gene at the same time. The aims of current study were to examine the expression level of the AXIN2 in the colonic polyps and its linkage with the pathological features of the polyps.
Methods: In the present analytical-descriptive study, the investigated population was chosen from the cases with colonic polyps that referred to the Gastroenterology and Liver Diseases Research Center, Taleghani Hospital, Tehran, Iran, from October 2014 to April 2015. Forty four biopsy polyp samples and 10 normal tissue samples were collected, as well as the demographic and clinical properties of the patients and the expression level of AXIN2 gene was quantified by Real-time PCR. The outcomes were analyzed by the ABI Prism 7500 Sequence Detection System (SDS) software, version 2.1.0 (Applied Biosystems Inc., Foster City, CA, USA) and GraphPad Prism, version 3 (GraphPad Software Inc., La Jolla, CA, USA) Also, the expression changes of the intended gene in target groups were compared with the normal tissues using the 2-ΔΔCt equation.
Results: The data showed enhanced level of the expression of AXIN2 gene in the colonic polyps in comparison to the normal tissues (RQ>2), which was significantly upper in adenoma polyps compared to the hyperplastic group (P=0.015). Also, unlike the rectum, the AXIN2 gene activity in colon area was higher than normal tissue.
Conclusion: The results of the current study show that the expression pattern of AXIN2 gene, was markedly changed during the transformation of the normal tissue to polyp. The increased expression level of this gene could be applied as a diagnostic marker in dissociation of the adenoma polyps from hyperplastic ones. On the other hand, the location of the polyps modulates the AXIN2 gene function. Taking together, evaluating the changes of AXIN2, has a precise diagnostic value in the CRC related studies.

Plasma levels of calcitonin in medullary thyroid carcinoma patients with and without the RET proto-oncogene mutations in exons 10 and 11
Samira Ehyayi , Mehdi Hedayati , Marjan Zarif Yeganeh , Sara Sheikholeslami , Sayed Asadollah Amini,
Volume 75, Issue 6 (9-2017)
Abstract
Background: Thyroid carcinoma is the most common endocrine malignancy and approximately accounts 2% of all cancer cases. Medullary thyroid cancer (MTC) is an endocrine tumor with differentiation of Parafollicular or C-cells and is categorized into hereditary or sporadic types. Medullary thyroid carcinoma approximately accounts for 5-10% of all thyroid carcinoma. Germ-line and somatic mutations in exons 10 and 11 RET (Rearranged during Transfection) proto-oncogene are responsible for the occurrence of the familial and sporadic types, respectively. Calcitonin is a key marker in MTC diagnose and has been demonstrated to be highly sensitive for differential diagnosis prognostic assessment, follow-up and evaluation of MTC treatment. The aim of this study was to investigate the relationship between plasma levels of calcitonin in MTC patients with or without RET mutation.
Methods: In this cross-sectional study, the population consist of MTC patients who have referred to the endocrine and metabolism research center of Shahid Beheshti University of medical sciences since October 2013 till October 2016. Genomic DNA was extracted from peripheral blood leucocytes using the standard salting out/proteinase K method. Nucleotide change detection in exons 10 and 11 was performed using polymerase chain reaction (PCR) and direct DNA sequencing methods. Participants were then divided into two groups with or without mutation (43 individuals in each group). Plasma calcitonin levels were determined by enzyme-linked immunosorbent assay (ELISA) method in both groups.
Results: Evaluation of the level of plasma calcitonin in 43 patients with a molecular mutation in RET proto-oncogene (mean age 31 years) and 43 patients without molecular mutations in RET proto-oncogene (mean age 43 years) were 7.6 pmol/mL and 3.07 pmol/mL respectively. This difference is statistically significant (P=0.0014).
Conclusion: Routine measurement of calcitonin has been investigated as a screening method for the diagnosis of medullary thyroid carcinoma patients. Nevertheless, additional data are required to definitely support routine measurement of calcitonin due to the role of RET proto-oncogene.

Common mutations assay of KRAS and BRAF genes in patients affected with Head and neck squamous cell carcinoma (HNSCC)
Razieh Zarifian Yeganeh , Abbas Shakoori Garakani , Saman Mehrabi , Nader Ebadi, Maziar Motiee Langroudi , Mohammad Reza Noori Daloii,
Volume 75, Issue 7 (10-2017)
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is the malignancy of squamous cells (the epidermal layer of skin) in cavities in head and neck includes: larynx, pharynx, paranasal sinuses and oral cavity. The main goal of this research was to understand the effect of mutations in two important genes (KRAS and BRAF) in RAS/MAP kinase (EGFR) signaling pathway in tumor cells with head and neck squamous cell carcinoma in Iran.
Methods: The present cross-sectional study performed from October 2015 to September 2016 on 40 patients suffering from head and neck squamous cell carcinoma, all confirmed by pathology department of Imam Khomeini hospital. Tumor samples were achieved from the surgical cancer department of Imam Khomeini hospital and stored in liquid nitrogen until starting tests. The tests done in genetic laboratory of Tehran University of Medical Sciences. Techniques we used in this research, were DNA extraction based on phenol-chloroform approach, Multiplex PCR (M-PCR) to amplify mentioned exons and KRAS/BRAF strip assays to detect mutations in mutated hotspots in exon 2 of KRAS and codon V600E in BRAF gene.
Results: In this study, we observed 7 mutations in codons 12 and 13 exon 2 in KRAS gene (about 17.5%) and 4 mutations in codon V600E in BRAF gene (about 10%) of obtained tumor samples. The hotspot mutation in codon 12 were Asp (10%) and Ser (5%) respectively. In BRAF, the most common mutation, as we expected according to other researches, was observed in codon V600E. We also observed that 29 people of these patients were male (about 72.5%) and 11 patients were female (about 27.5%). Moreover, 28 patients were over 50 years, while 7 patients were below the age of 50.
Conclusion: The results of this study showed that mutations in genes KRAS and BRAF especially in studied hotspots, and the effects on their molecules in EGFR signaling pathway are important in involving head and neck squamous cell carcinoma, as other cancers. These findings may be considered in choosing drugs for targeted chemotherapy.

Sentinel lymph node mapping using methylene blue and Technetium-99 in early endometrial cancer
Fariba Behnamfar , Matina Jafari , Masoud Moslehi ,
Volume 75, Issue 8 (11-2017)
Abstract
Background: Endometrial cancer (EC) is the most prevalent genital related cancer of females. One of the controversial points about endometrial cancer surgery is preserving or dissection of sentinel lymph nodes (SLNs). Lymphatic mapping and sentinel nodes sample has been used widely for diverse solid tumors in order of finding metastasis in lymph nodes. The aim of current study was to evaluate diagnostic value of technetium-99 and methylene blue in diagnosis of sentinel lymph node involvement in low-risk endometrial cancer.
Methods: This cross-sectional study was conducted through 2016 on 14 patients with low-grade endometrial cancer referred to Al-Zahra and Shahid Beheshti Hospitals (affiliated to Isfahan University of Medical Sciences), Iran, in 2016-17. Eighteen and twenty-four hours before operation, patients underwent technetium-99 (Tc-99) injection to uterine cervix. Twenty-four hours prior to surgery, patients were referred to resident of gynecology and filled demographic checklist. In next day during operation, Tc-99 was detected by gamma probe. Methylene blue was injected in operation room and blue nodes were detected by naked eye. All patients underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Dissected lymph nodes were sent for frozen section and assessment of positive/negative metastasis. Then data were analyzed with SPSS software, version 20 (SPSS Inc., Chicago, IL, USA).
Results: Mean age of our patients was 60.64±9.18 years. Total number of 80 SLNs was dissected. 18.8% of nodes were detected using methylene blue, 12.5% using tecnethium-99 and 6.3% were in common with both methods. Number of two nodes was metastatic and was detected by blue dye and Tc-99. Sensitivity, negative predictive value and detection rate of Tc-99 alone, methylene blue alone and their combination was 100% and false negativity of all above was 100%.
Conclusion: Due to findings of our study, as sensitivity, detection rate, negative predictive value and false negativity of methods lonely and in combination were similar thus based on higher probability of blue dye adverse effects, use of Tc-99 lonely may be adequate.
 

Expression of KLK2 gene in prostate cancer
Sajad Shafai , Elham Moslemi , Mehdi Mohammadi , Kasra Esfahani , Amir Izadi ,
Volume 75, Issue 10 (1-2018)
Abstract
Background: Prostate cancer is one of the most common diseases that affect men. Although prostate cancer is not the fatal flaw in most cases, detection of effective factors for early diagnosis and treatment is essential. Research results have shown that the use of KLK2 plus PSA can be a good biomarker for diagnosing prostate cancer. During prostate cancer, expression of KLK2 gene increases which can be used as a prostate cancer biomarker. The aim of this study is an assessment of KLK2 gene expression as a potential factor in the prostate cancer diagnosis.
Methods: In this case study, 50 prostate cancer urine samples from patients and 50 urine samples from normal individuals who were referred to Mehr Hospital of Tehran (from December 2014 to February 2016) were obtained and stored in the central research laboratory of Shahid Beheshti University of Medical Sciences, Tehran, till tests were being done. The age of collected samples between the 46 up to 71 years. RNA of samples were extracted, and then cDNA was synthesized by using M-MuLV enzyme, Oligo dt, and Random hexamer primers. KLK2 specific primers designed by Primer Express software, version 3.0 (Applied Biosystems, Foster City, CA, USA), and KLK2 gene expression evaluated by using ∆∆ct methods.
Results: In comparison with patients and normal sample`s gene expression, the mean increase expression of KLK2 gene in patients less than 50 years was 2.32 and in patients more than 50 years, it was 5.79, P<0.0001. In addition, gene expression results with respect to GS (Gleason grading system) classification shown that patients with GS6 had the lowest gene expression (3.40) and in the patients with GS8, had the highest gene expression (10.74) in comparison with normal group (P<0.0001).
Conclusion: The expression of KLK2 gene in people with prostate cancer is the higher than the healthy person; finally, according to the results, it could be mentioned that the KLK2 gene considered as a useful factor in prostate cancer, whose expression is associated with progression and development of the prostate cancer.

A review of the etiology and biomarkers of pancreatic cancer, with emphasis on the role of diabetes: review article
Akram Pourshams, Bahram Kazemi , Sima Kalantari ,
Volume 75, Issue 11 (2-2018)
Abstract
Cancer is the major cause of death in the world and the rate of mortality is higher in developed countries. Therefore, lifestyle could be effective in promoting the cancer. The pancreatic tumors, are 8th cause of mortality due to cancer, which have several types, among them ductal adenocarcinoma is the most common and includes 85% of cases. Since, it is almost impossible to diagnosis the tumor in early stages of the disease, it contributes to high rates of mortality, although if it diagnosis in early stage and the surgery performed for them only 10-20% of patients will be survived. Metastasis occurs when the tumor is smaller than 2 cm in size and because the pancreas is located in the depth of abdomen, typically, it happens after tumor is spread to other organs. A combination of medical imaging, blood tests, and examination of tissue samples are usually made for diagnosis and based on the cancer stage, surgery, radiotherapy and chemotherapy are chosen as treatment options. Some rare genetic variations can cause pancreatic cancer and about 5-10% of cases are linked to inherited genes. However, major risk factors are including age, obesity, tobacco smoking and diabetes. Smoking counts for about 25% of cases, and the diabetes is the main symptoms of pancreatic cancer, which observed in about 80% of cases. But, it is still unclear whether diabetes is a predisposing factor in pancreatic cancer, or the outcome of tumor progression. Recent studies have shown that, diabetes is unique in pancreatic cancer which is not related to common types. Currently, CA 19-9 is the only reliable tumor marker for pancreatic cancer that its frequency also increases in non-bad conditions, such as pancreatitis and obstructive jaundice, so is not sensitive and specific enough for diagnosis of this cancer. Due to researches continue to find more specific markers. In this review the etiology of pancreatic cancer, diabetes associated with this type of cancer and significant biomarkers for diagnosis will be considered.

Genetic and epigenetic alteration in thyroid cancer: review article
Elham Shakiba , Monireh Movahedi , Ahmad Majd , Mehdi Hedayati ,
Volume 75, Issue 12 (3-2018)
Abstract
Thyroid cancer is one of the most common endocrine malignancies and in the last two decades the number of involved people in the world has been increased. Thyroid cancer in Iran is the seventh most common cancer in women and 14th in men. In recent years many achievements regarding to molecular pathogenic factors such as the substantial role of signaling pathways and molecular abnormalities have been made. Nowadays there is no efficient treatment for progressed thyroid cancer that does not respond to radioiodine therapy which are included poorly differentiated, anaplastic and metastatic or recurrent differentiated thyroid cancer. Although the results of some clinical trials in phase II for treatment of progressed thyroid cancer are rewarding but none of the treated patients responded to treatment and only a few of them responded partially to the treatment which indicates that the treatment can only control the condition of patients with advanced disease, therefore it is needed to consider other alternative solutions which would be helpful in controlling the disease. Epigenetic is referred to study of heritable changes in gene expression without changes in primary DNA sequence. The main mechanisms of genetic and epigenetic alterations are including mutations, increasing the gene copy number and aberrant gene methylation. Epigenetic defects are prevalent in different types of cancers. Aberrant methylation of genes that control cell proliferation and invasion (p16INK4A, RASSF1A, PTEN, Rap1GAP, TIMP3, DAPK, RARβ2, E-cadherin, and CITED1), as well as specific genes involved in differentiation of thyroid cancer (Na+/I- symport, TSH receptor, pendrin, SL5A8, and TTF-1) in association with genetic alterations, leads to tumor progression. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression or function. Many of these molecular changes can be used as molecular markers for prognosis, diagnosis and new therapeutic targets for thyroid cancer. This article is about the most common genetic and epigenetic alterations in thyroid cancer which can be complementary together in recognition of new treatments for the disease.

Evaluation of the DAPK gene expression level in peripheral blood lymphocytes of patients with breast cancer
Sirous Naeimi,
Volume 75, Issue 12 (3-2018)
Abstract
Background: The main causes and difficulties of cancer are the imbalance between cell growth and cell death. This event is the results of changes in the expression level of genes related to these mechanisms. Among genes including in this case, death-associated protein kinase (DAPK) can be mentioned. Studies have shown that the expression of genes is influenced by the methylation of promoter regions. The purpose of this research was to evaluate the expression of the mentioned gene and the effect of methylation on the expression of this gene and its relationship with developing breast cancer in women.
Methods: Eighty patients with breast cancer and 80 healthy individuals participated in this case-control study which has been referred to Shahid Faghihi and Namazi hospitals, Shiraz city, from August 2014 to March 2017. This study was carried out at the Genetic Research Center of Islamic Azad University, Kazerun Branch, Iran. Peripheral blood lymphocytes were lysed and the mRNAs were extracted using the InViSorb™ RNA preparation kit II (Cat#1062100300, Invitek GmbH, Berlin, Germany) and cleaned up with Qiagen RNeasy spin columns. The first-strand cDNA was synthesized affording to the high capacity cDNA reverse transcription kit procedure. For DAPK gene expression, (Thermo Fisher Scientific, Waltham, MA, USA) PCR technique combines the quantitative performance of SYBR® Green-based real-time PCR, used. This technique is gainful, easy-to-use, and emphases only on the genes that you want. We designated 18S-rRNA gene, as our house-keeping gene. For determine of methylation, methylation-specific polymerase chain reaction (MS-PCR) method was used. 
Results: The achieved results from this research show that the levels of DAPK gene expression have a significant difference. The rate of expression in patients was significantly reduced compared with the control group (P=0.0156). Also, the relationship between expression of DAPK factor and lymph node involvement was investigated. The results show the relationship between the factors studied. On the other hand, there was no significant relationship between the expression level of this gene and its promoter methylation (P=0.13).
Conclusion: This research shows that reduction in the rate of DAPK gene expression plays an effective role in the patients with breast cancer.

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