Tehran University Medical Journal

Cancer/testis antigens (CTAs) are a kind of antigens that their expression mostly is restricted in testis and female’s genital organs. Tumor cells often express antigens whose expression is normally limited to germ cells. CTAs are composed of a vast gene family of closely related members and are commonly classified into two groups: the CT-X antigens that are encoded by the X chromosome and the non-X CTAs that are encoded by the autosomes. CTA are extensively and variably dispersed between tumors of diverse histotypes. CTA are broadly expressed in tumors, but not in normal tissue except for testis that is not available to the immune system, actually, the blood-testis barrier and the lack of HLA class I expression on the surface of germ cells avoid the immune system from the interaction with CTA proteins to be identified as non-self-structures. Consequently, CTA can be regarded as fundamentally tumor-specific targets. With extensive investigations on the function of this important biological molecules, their functions are somewhat revealed. Because of their high immunogenicity, tumor-limited, and biased expression, detection of these molecules provides unprecedented chances for further research and clinical development in the field of immunotherapy and cancer diagnosis. Also, growing evidence discloses that a number of CTAs stimulate epithelial mesenchymal transition (EMT) and generation of cancer stem-like cells, increasing metastasis, invasion and tumorigenesis. According to recent clinical attention, more features of CTA regulation are explored. CTA expression has been confirmed in a variety of human cancer tissues and some of them have been discovered to cause humoral and/or cellular immune responses in cancer patients, likewise, they displayed intertumor and intratumor heterogeneity in expression levels. CTAs are excellent targets for targeted tumor therapy, anticancer drug discovery, and diagnostic biomarkers, similarly, appreciated genes in the study of promoting tumorigenesis, immunotherapy, and malignant progression. This review summaries and classifies our current understanding of the complex and biased process of CTAs mRNA and protein expression in cancer, and provide the most current information on their function and regulation.
 

Immunotoxins such as pseudomonas exotoxin are Molecules with a unique structure like toxin-antibody part. These immunotoxins are two functional which crossing the cell membrane and enters the target cell and destroy the cell. Toxin-based treatments are a widespread research field and can have broad applications in the biology and public health. Immunotoxins act selectively against cancer cells and have a good potential for detecting and targeting cancer cells. Specific immunotoxins to target immune cells due to the selection type antibody and antibodies are responsible for the identification of the target cells. Cancer is becoming a major cause of death in most developed countries. In order to have a strong factor in cancer repression, that agent must target the cancer cells directly and specifically. Often, but not always, immunotoxins are produced for disabling and killing cancer cells, that this issue is one of new therapeutic approaches in recently. Clinical aims to designing and create new cancer therapies focused with this approach, a lot of information about the toxin and intracellular pathways have been obtained. So, toxins in medicine are useful for the treatment of human disease and study of professional cellular functions. So, immunotoxins have a high potential for cancer treatment. Other applications of immunotoxins, including immune system regulation and treatment of viral diseases and parasites diseases. More research is needed to improve the immunotoxin effects and to reduce their side effects. On the whole, with design creative, clever and experienced programs, many human diseases, particularly cancers can be in a short period of time and faster than other methods of treatment that the treatment of long, to be treated. Following the design and implementation of clinical trials, the effects of immunotoxins on animal tumorigenic models were performed. In fact, in this study, we focus on the use of protein-bound toxins with bacterial and herbal sources and more specifically Pseudomonas immunotoxins which attached to antibodies to target cancer cells.

Background: Ovarian cancer is a leading metastatic disease. The epithelial ovarian cancer is one of the most common malignant cancers that usually remains asymptomatic up to metastasis stages, and most patient when diagnosed are in the advanced stage of the disease. Studies have shown that in the majority of epithelial cancers mesenchymal factor expression such as Vimentin increases, and the epithelial factor expression such as E-cadherin decreases, as a result, it causes an epithelial-mesenchymal transition (EMT). The aim of this study was to determine the expression level of these genes and association between EMT phenomenon and development of ovarian cancer based on clinical and morphological findings.
Methods: In the present case series study, 70 samples were chosen from the tumor Bank of Cancer Institute taken from patients at Imam Khomeini Hospital, Tehran, Iran. The amount of expression of two genes, E-cadherin and vimentin, was investigated by real-time PCR method from February 2016 to September 2017. The RNA extraction was done manually, and then cDNA synthesis was performed; In each sample the expression level of vimentin and E-cadherin was measured with real-time PCR method. The patient’s clinical information with other data were analyzed with nonparametric statistical methods in SPSS software, version 19 (SPSS Inc., Chicago, IL, USA).
Results: There was a significant relationship between expression of vimentin gene and the stage (P=0.026) of the disease and metastasis (P=0.009), There was no significant relationship between vimentin gene expression and tumor grade (P=0.207), age (P=0.11), tumor size (P=0.71) and family history (P=0.6). There was a significant correlation between E-cadherin gene expression and metastasis (P=0.027), no significant correlation was found between E-cadherin gene expression with tumor grade (P=0.690), stage (P=0.753), age (P=0.09), tumor size (P=0.537) and family history (P=0.56).
Conclusion: According to the changes in expression of vimentin and E-cadherin genes in ovarian tumor cells, and association between these two genes with clinical and morphological findings and the role of these genes in the migration and invasion, we can use the both genes, vimentin and E-cadherin, as genes involved in the EMT process to assess disease progression and incidence of cell invasion in ovarian cancer.

Background: Most of colorectal cancers arise 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. Failure of apoptosis is one of the causes of cancers. One of the key molecules in this pathway is Bid gene which connects the extrinsic to the intrinsic apoptosis pathways. The aim of this study was to investigate the quantitative expression of Bid gene in colorectal adenomatous polyps compared to control group.
Methods: The investigated population was chosen from the cases with colonic polyps that referred to the Taleghani Hospital, Tehran, Iran, from April 2014 to May 2016. 22 biopsy samples from patients with adenomatous polyps and 10 samples from healthy individuals as control group were selected. Demographic and clinical properties were collected from patients' files. The Bid gene expression was evaluated using Real-time PCR by ABI 7500 (Applied Biosystems Inc., Foster City, CA, USA). Results were analyzed by the ABI 7500 system SDS version 2.3 and GraphPad Prism, version 5 (GraphPad Software Inc., La Jolla, CA, USA). the expression changes of the intended gene in target groups were compared with the normal tissues using the 2-∆∆CT equation.
Results: Based on the quantitative real-time PCR, the gene expression of Bid gene significantly increased in adenomatous polyps in comparison with the control group (healthy individuals) (RQ>2). Also, polyps were seen in ascending colon, transverse colon, descending colon and rectum showed increased expression compared to control group, but in the sigmoid section of the intestine, there was no change in expression of Bid gene compared to control group.
Conclusion: According to the present study, the expression of Bid gene increased in adenomatous polyps, compared with the normal tissue (healthy group). It suggests that Bid gene by increasing the expression in response to the onset of dysplasia and disruption of the apoptotic cycle, it tries to compensate for the apoptosis.

Background: Breast cancer is a malignant proliferation of epithelial cells that lining the ducts or lobules of the breast. Breast cancer is the second common cancer (after lung cancer) in women. Gallic acid, being a polyphenols, has been reported for its antiproliferative activity against many cancer cell lines. Objective of the present study is effect of gallic acid on proliferation and apoptosis of the human breast adenocarcinoma cell lines SKBR3 and normal fibroblasts cells.
Methods: This experimental study was performed in cellular and developmental biology of Shahrekord Islamic Azad University, Iran from April to August 2015. For anti-cancer activity, in this study SKBR3 cells and normal fibroblast cells (HU-02) were cultured in Dulbecco's modified eagle's medium, DMEM (Gibco, Life Technologies, Inc., New York, USA) medium with 10% fetal bovine serum, FBS (Gibco, Life Technologies, Inc., New York, USA). The SKBR3 and normal fibroblast cells were treated in the medium of DMEM medium and gallic acid (20, 40, 80, 100 and 200 µg/ml) for 24, 48 and 72 hours. Cells viability was assessed by MTS (Methyl- Thiazol-) assay. Cells were seeded at 5×103 cells/ml in 96 well plates and incubated for 24 hours. Then metabolites of bacteria were added, after indicated times MTS (20µl) was added and the absorbance was measured at 492 nm using ELISA plate reader. The percentage of apoptosis induction was determined by flow cytometry analysis using Annexin-V fluorescein isothiocyanate (FITC) kit (BioVision Products, CA, USA) in 20, 40, 80, 100 and 200 µg/ml concentration of gallic acid at 48 hours incubation.
Results: Gallic acid decreases significantly the viability of SKBR3 cell line in a time and dose dependent manner. So that the most effective concentration of this substance was 200 µg/ml and 72 hours after treatment (P< 0.05). According to the data of Annexin-PI, the highest apoptosis induction rate was seen in 200 µg/ml (P< 0.05). While gallic acid in various concentrations had no significant effect on normal fibroblast cells.
Conclusion: Objective of the present study is effect of gallic acid on proliferation and apoptosis of the human breast adenocarcinoma cell lines SKBR3 and normal fibroblasts cells.

Cancer is one of the most dangerous health problems of today modern societies which has an increasing rate especially in developing countries. There are many diverse ongoing treatment attempts trying to defeat cancer. Despite that, scientists have been unable to find a permanent cure for this disease. In many cases although there is a successful first response in patients, cancer cells are finally able to withstand therapeutic procedures and even use chemo-resistance to take advantage of treatments to facilitate tumor growth, resulting in cancer remission. Therefore, and mostly in recent two decades, scientists have been trying to choose their treatments just as smart to be able to conquer cancer. One of the best methods of this smart defense is to target weak points of neoplastic cells and use them for designing drugs. In this case it would be most probable for cancer cells not to have a chance to confront and cause chemo-resistance. Total endeavors to fulfill this goal are named “targeted cancer therapy”. This therapeutic approach is mostly consisted of two different procedures: 1- designing and using specific drugs to target cancer cells’ mutated genes; which will be defined by checking the genetic background of tumor cells for each specific cancer type. EGFR, RAS, VEGF and HIF-1α are among the pathways that have already been used as targets. 2- The other procedure could be methods that would carry drugs directly to unhealthy cells to prevent further side effects for normal cells of patients. It would be possible by designing specific antibodies to target antigens of neoplastic cells. Ribonucleic sequences (miRNAs and siRNAs) are also very promising as new drugs and nanoparticles have enabled us to increase drug concentration in tumors. The ultimate goal of these new experiments is to suggest specific drugs for each patient based on the nature of one's disease and genetic background, which will bring about "personalized medicine" era. Using valid new references, this review article first presents targets that are currently being used for this targeted therapy, their logic of choice and the drugs that have already been produced for clinical trials. Smart methods of drug delivery are also presented and discussed afterwards.

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. It has been proposed that the specific genotypes of Helicobacter pylori (H. pylori) are the causative agents in the development of gastroduodenal diseases, such as chronic atrophic gastritis, peptic ulcerations, and GC. However, disease progression to GC occurs in only a small proportion of infected patients. Recently, we identified a novel polymorphic site in the 3ʹ-end region of H. pylori vacA gene. The vacA c1 genotype increased the risk of GC. This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. Therefore, treatment of H. pylori infection may be an effective way to prevent GC. Expression of cytokines and their associations with inflammatory responses has been shown. Several cytokine polymorphisms, such as IL-1B, IL-8, IL-10, and TNF-α have been considered as risk factors for GC. It has been shown that the interaction of bacterial genotypes and host factors plays an essential role in developing GC. Several altered molecular pathways are involved in the pathogenesis of GC. Micro-RNAs are small, non-coding RNAs of 18-25 nucleotides in length that regulate the expression of target mRNAs. Expression pattern of cancer cells is different compared with the normal cells. Micro-RNAs plays a critical role in apoptosis and classified in two groups: pro- and anti-apoptotic agents. Recent studies have confirmed the oncogenic or tumor suppression role of micro-RNAs in cancer cells. They play a significant role in the GC cell physiology and tumor progression, by translational suppression of target genes. These small RNAs have therefore emerged as a new type of GC biomarker with immeasurable clinical potential. Generally, a variety of micro-RNAs involved in different stages of cancer, including tumorigenesis, angiogenesis, and metastasis. Considering to this issue more than 50% of cancers can be cured, if they were diagnosed in the early stages. Hence, identifying the biomarkers of GC could play an important role in prevention, early diagnosis and rapid treatment of patients. In this review article, we have reviewed the latest findings about bacterial and tissue biomarkers of GC

Background: Using natural compounds with low toxicity on normal cells and high efficacy on malignant cells is highly appreciated for treatment of colorectal cancer (CRC). In the present study, the effect of fish-oil derived eicosapentaenoic acid (EPA) on the cell number, cell proliferation rate and caspase-3 enzyme activity in LS174T human colorectal cancer cell line was investigated.
Methods: This experimental study was performed in cell culture lab, Institute of Biotechnology, affiliated to the Urmia University, Urmia, Iran from April to September 2017. LS174T colorectal cancer cells at a density of 5×105 cells per well were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and kept at 37 °C in a humidified incubator with 5% CO2 for 24 hours. Thereafter, the cells were treated with 50, 100, 150 and 200 μmol EPA for 48 hours and cell numbers were counted using neobauer chamber and caspase-3 activities were measured by performing the caspase-3 colorimetric assay (Abcam, Cambridge, MA, USA). Furthermore, 5×103 LS174T colorectal cancer cells were cultured and treated with the above-mentioned EPA concentrations for 24, 48 and 72 hours, after which cell proliferation rate was evaluated by WST-1 proliferation assay (Roche Diagnostics, Mannheim, Germany).
Results: Treatment of LS174T colorectal cancer cells with 50, 100, 150 and 200 μmol EPA decreased the number of cells in a dose-dependent manner. We also found that treatment of malignant cells with increasing EPA concentrations (50 to 200 μmol) significantly decreased cell proliferation in a dose and time dependent manner. After a 72 hours treatment of LS174T cells with 200 μmol EPA, cell proliferation was calculated to be 30.3% compared to untreated control cells. Following 48 hours treatment, caspase-3 activity increased with increasing EPA concentrations in which at 200 μmol EPA, caspase-3 activity increased by 3.4 fold compared to untreated control cells.
Conclusion: Fish-oil derived eicosapentaenoic acid as a safe compound decreases the number of colorectal cancer cells and their proliferation rate and activates caspase-3 enzyme, as an executor protein in apoptosis.

Background: Breast cancer is a common malignancy in which early breast cancer detection by the help of imaging can improve the treatment outcome. Thermography utilizes infrared beams which are fast, non-invasive, and non-contact and the output created images by this technique are flexible and useful to monitor the temperature of the human body.
Case presentation: Our patient is a 25-year-old woman who was referred to Tehran's Imam Khomeini Hospital, Tehran University of Medical Sciences, in October 2014 and June 2017 to perform clinical examinations of breast cancer at the Invasive and New Radiology Research Center of Tehran. The results of the sonography for the left breast and bilateral axillary regions and sonography guided biopsy from the left axillary region indicated that:  it was consistent with the tangential prominence at 11-12 O’ clock in the left breast tissue and echo gene was found without any suspected findings. Then, using the non-contact infrared imaging camera VisIR 640 (Thermoteknix Systems Ltd, Cambridge, UK), the feasibility of thermography method in the patient's follow-up was investigated.
Conclusion: Thermography can be used to detect abnormal areas in the breast tissue that may have cystic origin. The results indicated that the accuracy of the identification and matching of patient cysts in mammography and ultrasonography with the results of thermography in both periods of October 2014 and June 2017. Considering the results, it is noteworthy that the diagnostic clock of the breast cysts in the patient is consistent with the results of the clinical trials with the thermography. Moreover, in a 2 years intervals, the status of thermal morphology status of the cystic region did not considerably change which showed a relatively stable status.

Cancer immunotherapy refers to any intervention that leverages the immune system to eliminate a malignancy. Successful cancer immunotherapies generate an anti-cancer response that is systemic, specific, and durable and overcome to the primary limitations of traditional cancer treatment modalities. In this review paper, the effective methods in immune system to treat cancer, such as immunosuppression in tumor microenvironment (TME), cancer vaccines and T cell adaptive therapy are mentioned. Engineered T cells can use for destruction of the different cancer tissues to diagnose tumor surface antigens. Promotion in culture of T cell methods and their engineering with retroviral vectors that carry T cell receptors or chimeric antigen receptors (CAR) by co-stimulator domains, provide opportunity to treat tumor by T cells. The tumors with high genome mutation, such as lung and melanoma, have severe environmental mutagenesis that is induced by ultra violet light in melanoma and Tobacco in lung cancers. Expression of tumor specific receptors is increased by engineered T cells. The neo-antigens conduct the intensity of intra tumor T cell response. The present of CD8+ in tumor site with more mutation is higher and the mutation load is showed strong relation with the clinical response. In addition to the successful approaches to cancer immunotherapy, the other combination and molecular therapies by nanomaterials are listed. Nanomaterials as efficient modulators and diverse vaccine have been developed in the treatment of cancer. In recent cancer vaccine development has been on subunit vaccines that contain purified tumor antigens or antigenic epitopes as an antigen source. However, soluble bolus-based subunit vaccines typically induce weak cytotoxic T lymphocyte responses which limit their utility for cancer. To overcome this, nanoscale colloids can be used to promote more efficient antigen presentation by acting as phagocytic substrates. Nanomaterials are showed co-suppression and immunization in tumor microenvironment by multiple additive functions in preclinical models. In this manner, they exhibited good prospects because of the good results in overcoming the limitations of current therapies. In this review paper is tried to provide new prospect for therapies and hope it creates highest efficacy and lowest side effects for the treatment of patients in the near future.

Background: Estrogen-negative breast cancers have different clinical course, prognostic features and treatment response in comparison to estrogen receptor-positive (ER-positive) breast cancers. Human epidermal growth factor receptor 2 (HER2) oncoprotein has found to have a pivotal role in natural cell growth and cell division and is suggested to be directly related to tumor invasiveness in breast cancer patients. The purpose of this study was to retrospectively assess the mammography, ultrasound, and magnetic resonance imaging (MRI) features of estrogen negative breast cancers with and without overexpression of HER2/neu receptor.
Methods: In this cross-sectional retrospective study, mammographic, ultrasound and MRI features as well as HER2 status were assessed in patients with ER-negative breast cancer that were referred to Cancer Institute of Imam Khomeini Hospital Complex in Tehran from October 2015 to October 2017. Clinicopathologic data and mammography, ultrasound, and MRI features were reviewed and were correlated with HER2 status of estrogen-negative tumors.
Results: Of the 172 patients with ER-negative breast cancer, 101 patients were positive for HER2/neu receptor (58.8%). There was a significant correlation between HER2-positivity and tumor type (P=0.004). Among estrogen negative breast cancers, significant association were found between HER2 and tumor histologic grade (P=0.024) and TNM stage (P=0.021). HER2-positive tumors were more likely to present with microcalcification (P=0.007) and have irregular shapes (P=0.034) in mammography than HER2-negative tumors. No association was found between HER-2 status and tumor size, shape, margin, posterior feature, halo or orientation of the tumor in ultrasound. We also found no correlation between HER2 status and MRI features including mass shape or margin, internal enhancement pattern or curve type among estrogen-negative breast cancers.
Conclusion: Findings of this study showed that among estrogen-negative breast cancers, HER2/neu positive tumors are more likely to be diagnosed at higher stage and have higher histologic grade at the time of diagnosis. Tumor mass shape and microcalcification in mammography are found to be associated with HER2 status among patients with estrogen-negative breast cancer. 

Background: The average age of women with breast cancer in Iran is at least 10 years lower in comparison to developed countries and the incidence of the disease in Iranian women is on a rise. According to studies, diets that are diverse in food groups can play a role in protecting against chronic diseases including cardiovascular diseases and cancer. Diet diversity score is an indicator used to measure diversity between and within food groups. This study aimed to assess the relationship between diet diversity score and breast cancer risk.
Methods: This case-control study was carried out from April 2014 to February 2015 at Shohada Hospital in Tajrish, Tehran. Demographic and anthropometric data of 298 participants including 149 breast cancer cases and 149 apparently healthy women were collected. A valid food frequency questionnaire containing 168 food items was completed to assess usual dietary intake through face to face interviews. Energy was calculated using Nutritionist 4 software (First Databank Inc., Hearst Corp., San Bruno, CA, USA) and diet diversity score was calculated using five food group scoring. Odds ratios with 95% confidence intervals were obtained using logistic regression test to evaluate the association between breast cancer risk and diet diversity score tertiles.
Results: There was no significant difference in weight, height, body mass index between the two groups, but physical activity level and daily energy intake showed a significant difference (P<0.001). After adjusting for the effect of confounding variables including energy, body mass index, physical activity, menopause status, family history of breast cancer, contraceptive use, number of pregnancy, age of menarche and smoking, the risk for developing breast cancer was 86% lower in those in the highest tertile of diet diversity score compared to those in the first tertile (OR=0.14, 95% CI=0.06-0.31). An inverse and significant association was found between breast cancer risk and diversity scores of fruits and milk groups (P<0.001).
Conclusion: Higher diet diversity score is associated with reduced risk of breast cancer.

Background: Gastric cancer is among the most common malignancies in certain parts of the world, such as northwest Iran. miRNAs are small and single-stranded noncoding RNAs with about 19-23 nucleotides. Several studies have shown that miRNAs play important roles in gastric tumorigenesis. The aim of this study was to determine the effect of miRNA-1266-5p repression on the cell survival and alterations of the cell cycle in gastric cancer cell line of AGS (NCBI Code: C131, Gastric epithelial cell line).
Methods: This experimental study was performed from April to December 2017 in Cellular-Molecular Research Center of Ardabil University of Medical Sciences, Iran. In this study, AGS cells were cultured in RPMI-1640 medium containing 10% serum and 1% antibiotic. The cells were transfected with miR-1266-5p mimic, miR-1266-5p inhibitor and HiPerFect reagent alone as negative control. The miR-1266-5p expression and transfection efficiency were analyzed by Stem-loop TaqMan qRT-PCR. The cell proliferation and cell cycle alterations were determined using MTT calorimetric assay and flow cytometry, respectively. The results were analyzed using SPSS 19.0 statistics software (SPSS Inc., Chicago, IL, USA) and presented as the means±standard deviation (SD).
Results: miR-1266-5p expression was increased in AGS cells transfected with miR-1266-5p mimic compared to control cells (P=0), while miR-1266-5p expression was decreased in transfected cells with the inhibitor compared to controls (P=0). Among different time points, the most effects of miR-1266-5p mimic and inhibitor were noticed after 48 hours of transfection. The upregulated miR-1266-5p significantly decreased cell growth, in contrast, inhibitor promoted cell proliferation (P=0). In addition, miR-1266-5p upregulation induced cell cycle arrest at the transition of G1 to S phase and led to G0/G1 entry (P=0), while of miR-1266-5p led to G2/M entry (P=0.001).
Conclusion: According to the results obtained from this study, miR-1266-5p can reduce cell survival and induce cell cycle arrest and act as a tumor suppressor in AGS cells. While its inhibition can increase cell survival and reduce apoptosis.

Background: Hookah smoking has been growing among people because consumers believe that smoking in the form of hookahs has lesser health effects than cigarettes. However, recent reports showed that water pipe smoking (WSP) increased heart rate, blood pressure, impaired pulmonary function and carbon monoxide intoxication. Chronic bronchitis, emphysema and coronary artery disease are serious problems of long-term use of this kind of smoking. Lung, gastric and esophageal cancers are associated with WPS, as well as periodontal disease, and obstetrical complications. Hence purpose of this study was to survey the relationship between lung cancer and tobacco consumption in the form of hookah through meta-analysis.
Methods: In this meta-analysis study we conducted an electronically search in databases PubMed, MEDLINE and EMBASE to find relevant articles regarding the adverse effects of hookah smoking, using the terms ‘water pipe’ and its synonyms (hookah, shisha, goza, narghileh, arghileh and hubble-bubble) in various spellings in Iran University of Medical Sciences (IUMS), Tehran, Iran from January to May 2017. All articles including Cohort and case-control studies published between 1980 and 2017 and conducted in the world were included without restriction regarding publication language. The cross-sectional studies, case reports, conference abstracts, reviews and studies not conducted on humans were excluded. The article selection process and data extraction were performed by two independent investigators. The articles were evaluated using odds ratios, heterogeneity and distribution models.
Results: In this study, 120 articles related to the effect of hookah smoke on health were found. Of these articles, there were 9 articles related to the effect of hookah smoke on lung cancer. The results showed that hookah smoking could increases the risk of lung cancer with a chance ratio of 3.72 and a confidence interval of 4.85-2.60. Heterogeneity and distribution were not observed among selected articles.
Conclusion: There is accumulating evidence about the association of water pipe tobacco smoking with of lung cancer, which increases the risk of lung cancer due to water pipe tobacco smoking consumption.

Background: Diffusion-weighted imaging (DWI) is one of methods in evaluation of breast lesions. We aimed to investigate the apparent diffusion coefficient (ADC) values in breast tumors and their accuracy in differentiating benign versus malignant lesions.
Methods: In this cross-sectional study, 72 patients with 88 breast lesions were investigated by 1.5-T breast MRI from 2015 to 2017 in Athari Imaging Center in Tehran, Iran. Nearly all patients has undergone histopathology evaluation. One small region of interest (ROI) were placed on the most restricted region inside the solid part on the ADC map. Care was taken to avoid cystic or necrotic, fatty regions and hematoma inside the mass. A large round ROIs were placed in healthy fibroglandular tissue of contralateral breast ADC values were measured and compared in normal breast tissue and in most restricted parts of breast lesions (mass and non-mass). After determining cut-off for differentiation of benign and malignant lesions, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.
Results: Mean age of patients was 43.3 years. The average tumor size of benign and malignant lesions were calculated 26.0 mm, 35.3 mm respectively and 23 mm and 46 mm in mass and non-mass respectively. Invasive ductal carcinoma include the majority of pathology result (in 37.5% of the patients). Our results revealed that the measured ADC values in normal breast tissue were higher than breast lesions (P≤0.01). Mean ADC value in benign lesions was 1.40×10-3 mm²/s and for malignant lesion was 1.08×10-3 mm²/s. ADC value in the normal breast tissue was 1.79×10-3 mm2/s and was significantly higher than ADC value of breast lesions (benign and malignant). Cut-off value in non-mass was not valid, but in mass was 1.19×10-3 mm²/s with sensitivity, specificity, positive predictive value, negative predictive and accuracy of 89.7%, 83.8%, 87.5%, 86.6%, and 87.1% respectively.
Conclusion: In DWI imaging, ADC value can differentiate benign and malignant masses with high sensitivity and specificity but not helpful in non-mass lesions.

Background: Prostate cancer is currently the third malignant disease in Iran and fifth common cancer worldwide. The aim of this study was to determine the expression of GPRC6A, E.cadherin, and ZEB1 genes in prostate cancer in comparison with benign tumor. Since early detection of cancer plays an important role in treatment, this study aims to identify the role of GPRC6A, E.cadherin and ZEB1 genes in screening of prostate cancer.
Methods: In this case-control study, 30 samples including 15 samples of malignant prostate cancer and 15 samples of benign tumor were collected from the patients. RNA was extracted from the tissues, followed by cDNA preparation. In the last step, expression of GPRC6A, E.cadherin and ZEB1 genes was measured using the Real-time polymerase chain reaction (PCR) technique and the Relative expression software tool (REST), Version 2009 (http://rest.gene-quantification.info/).
Results: In this study, the expression of GPRC6A genes compared to its benign tumor increased 3-fold, ZEB1 expression in prostate cancer, compared to its benign tumor, increased 2-fold, and expression of E.cadherin gene in cancerous samples compared to benign tumor declines 10 was equal. In this study, there was no significant relationship between the expression of genes in benign and malignant samples with common diagnostic factors in this type of disease such as age, Prostate-specific antigen (PSA), pathologic stage and Gleason score.
Conclusion: According to this study and similar studies, increased expression of GPRC6A in prostate cancer cells can stimulate the progression of cancer cells by regulating cell proliferation and invasive response to various ligands. Increasing the expression of ZEB1 and decreasing the expression of E.cadherin is also due to the lack of binding of cells and spread of metastasis. As a result, tumors express ZEB1 with absence of E.cadherin is associated with advanced disease or metastases, which indicates that ZEB1 induces EMT and tumor progression in clinical cancers. Therefore examined genes have potential for screening prostate cancer and they can be used as a diagnostic marker for prostate cancer with further investigation.

Background: Intensity-modulated radiotherapy (IMRT) is one of the most usable methods in prostate radiotherapy that is used with different techniques. The aim of this study was to evaluate and compare the dosimetric and radiobiological effects of prostate IMRT techniques regarding to joint volume between the target tissue and organs at risk as a patients anatomical parameter.
Methods: This research was a cross-sectional, analytical, and quantitative study that was carried out from April 2016 to June 2018 at the radiotherapy and oncology center of Shoheday-e-Tajrish Hospital and Medical Physics Department of Tarbiat Modarres University Tehran, Iran. Four various prostate IMRT techniques (9, 7 and 5 fields and automatic) were planned on 63 prostate cancer patients CT scans. Radiobiological effects were calculated using Relative Seriality model for the organs at risk (bladder and rectum) and target tissue. Results of mentioned prostate IMRT techniques were compared based on the patient’s anatomical parameter. 
Results: For the patients with joint volumes ranged from 0 to 15%, statistical differences were not observed among various IMRT techniques. The tumor control probability and complication free tumor control probability values decreased as a function of joint volume. The normal tissue complication probability value increased as a function of joint volume. The 9 and 7 fields IMRT techniques had not any significant differences (P=0.06) in all of the joint volume ranges. In patients with the joint volumes higher than 30%, the 9 and 7 fields techniques showed significantly better radiobiological values in comparison with 5 fields and automatic techniques (P=0.009).
Conclusion: In the patients with lower percentage of joint volume, all the mentioned prostate IMRT techniques showed same radiobiological effects; however, in the patients with higher joint volume percentages (> 30%), the 9 and 7 fields techniques have better results. It is proposed to use the 7 fields technique instead of the 9 fields technique, especially in prostate cancer cases with high uncertainty in patients’ setup.

Background: Breast cancer is one of the most common diseases in women and causes more deaths rather than other cancers. The increasing trend of breast cancer in Iran makes clear the need of extensive breast cancer research in this area. Some studies showed that in the variety countries and even in the different areas in one country has different risk of breast cancer incidence and this is a reason that there is a correlation between region of life and risk of breast cancer. The purpose of this study was to determine the spatial structure associated with the incidence of breast cancer based on statistical models and identification of areas with high incidence of breast cancer in Iran.
Methods: This ecological study was conducted in Kermanshah University of Medical Sciences, Iran, from February to July 2018. Data on breast cancer patients in all provinces of Iran (30 provinces) were investigated since 2004 to 2009. Risk factors in this study included fruit and vegetable consumption, physical activity, overweight or obesity, and human development index. In this study, we have used routine and spatial Poisson's generalized linear mixed models for data analysis.
Results: In both routine and spatial models, direct and significant correlation was found between the incidence of breast cancer and the human development index (P<0.05). In addition to human development index, overweight or obesity factors were also had direct and significant relationship to the incidence of breast cancer in the spatial Poisson's generalized linear mixed model (P<0.05). In the spatial Poisson's generalized linear mixed model with correlation structure of Besag Yorg Molie (BYM), two provinces of Gilan and East Azerbaijan had the highest risk of breast cancer incidence and province of Kohgiluyeh and Boyer Ahmad had the lowest risk of breast cancer incidence.
Conclusion: The results showed that the distribution of breast cancer incidence in Iran has a spatial structure. That is, the adjacent provinces have similar incidences of this disease.

Background: Due to the incidence and recurrence of bladder cancer (BC), it could be categorized as a clinical and social problem that often occurs at an advanced age. This study was designed to determine the incidence of BC in Isfahan, Iran.
Methods: A retrospective descriptive survey of information based on bladder cancer (ICD-O, third edition; C67) was obtained from the Isfahan Deputy of Health. The study was in conducted to the department of Urology and Kidney Transplantation Research Center and approved by the University Ethics Committee. The Isfahan Cancer Program is intended to record all cancer cases in the Isfahan. From 20 March 2016 to 19 March 2017, records with linkage to using of pathology, demographic and clinical information were recorded in Microsoft Excel 2013 (Microsoft Corp., Redmond, WA, USA) and analyzed by SPSS statistical software, version 22 (IBM, Armonk, NY, USA). The incidence rates (Irs) were calculated by dividing new cases of BC during the year of study to the population at risk during the same time period×100000.
Results: A total of 417 patients that corresponded to Irs of 8 per 100000 persons were studied. The overall recorded number was comprised of 361 males (IRs of 13.9 per 100000) and 56 females (Irs of 2.2 per 100000). The mean±SD age of patients was 64.7±13 years. The minimum age in males versus females was 12 versus 25 years old respectively. Age in the most patients (80% of cases) was more than 50 years old. The invasion of the muscle was recorded in 44% of cases. Geographical distribution in 65% of cases was related to Isfahan City as a place of birth-residence and in the next categories were Khomeinishahr (7.6%), Najafabad (6.8%), Lenjan (4.5%), Mobarekeh (3.7%) and Felavarjan (2.8%) respectively.
Conclusion: Comparison of BC incidence rate between the year 2014 and 2016 showed that incidence rates decreased by 18.2%. In the 44%, invasive neoplasm of BC was recorded for the population studied. The highest frequency of BC was associated with Isfahan City and then Khomeinshahr, Najaf abad, Lenjan, Mobarakeh and Falavarjan.

Background: Metalloproteinase enzymes can lead to the digestion of the extracellular matrix and its compounds and ultimately facilitate the metastasis of cancer cells to other tissues. This study aimed to evaluate the activity of matrix metalloproteinases (MMPs) 1 and 13 in the tissue and plasma samples of the patients with breast cancer and their relationship with clinical features of the disease.
Methods: In this experimental study, twenty-five patients with the diagnosis of non-metastatic luminal A breast cancer in the stage 2 or 3 from the patients referred to the Cancer Institute of Iran, as well as eight healthy subjects which was performed in the Cancer Research Center of Tehran University of Medical Sciences from March 2017 to September 2017, were entered into the study. After obtaining written consent, a few biopsies of breast tumor tissues and 10 cc of the whole blood were collected from all the subjects. Then, the collagen zymography assay was used to evaluate the activity of MMPs 1 and 13.
Results: The results of the present study showed that the activity of MMPs 1 and 13 in the plasma samples was significantly increased in comparison with the healthy group (respectively P=0.0055 and P=0.0263). Unlike the MMP-13, the activity level of the MMP-1 in the tumor and plasma samples was significantly different (P=0.0227). Plasma activity levels of MMP-1 (P=0.0037) and MMP-13 (P=0.0311) were also significantly different in stages 2 and 3 of the disease. Unlike the MMP-13, the activity level of MMP-1 was significantly different in lymph nodes between the tissue and plasma samples (respectively P=0.03 and P=0.015). Moreover, there was no significant difference in the activity level of MMPs 1 and 13 with menopausal and non-menopausal status between the tissue and plasma samples.
Conclusion: The results of the present study showed that plasma concentrations of the MMPs 1 and 13 in comparison with their tissue concentrations could be an appropriate diagnostic tool for breast cancer patients.