Tehran University Medical Journal

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Teratomas are emberyonal neoplasms derived from totipotential cells that contain tissue from at least two and more often three germ layers (ectoderm, enoderm and mesoderm) in the midline or paraxial location from brain to sacrococcygeal region. The primary objective of this study is to determine this rather common newborn and children teratomas in different areas of the body. The secondary objective is studying the incidence and its pathology and comparison of the data with literatures. In this research, 91 involved children in two hospital of the Tehran university of medical sciences from 1982 to 1999 has been studied. From 91 children 60 cases were sacrococcygeal teratoma, 14 cases were sacrococcygeal and pelvic (tot...74), 9 cases in ovaries, 3 cases in the retroperitoneum 2 cases oropharyngeal, 2 cases in testis and one case in neck area. From these cases, 71 were neonate, the rest were infant or were more than 2 years old. From the cases 88 underwent surgical treatment, 3 cases died because of surgical complications and 3 cases died before operation. In this study, 84 percent of teratomas were benign and 16 percent were malignant. The comparison of these findings with literature showed little differences.

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Background: Transrectal ultrasonography guided needle biopsy of prostate frequently used for early detection of cancer has faced the pathologists with a major diagnostic challenge. In recent years P504S has been used as a tumor cell marker for definitive diagnosis of prostatic cancer in small biopsy specimens.

Methods: 70 prostate needle biopsies and 6 transurethral resections (TURP) containing atypical foci as well as 40 morphologically unequivocal prostate cancer biopsies, including 8 with foamy features, were stained with P504S.

Results: 36 specimen out of 40 biopsies with unequivocal cancer, showed variable P504S staining (sensitivity, 90%) 2 minute cancer and 2 foamy cancer lacked P504S staining. of 76 cases with atypical foci (70 biopsies, 6 TURP), 18 were diagnosed as high-grade prostatic intraepithelial neoplasia (HGPIN) - 16 of them showing diffuse moderate P504S staining - and 58 had foci of atypical small acinar proliferation. 14 of the latter cases were highly suggestive of cancer, 4 of which lacked P504S staining. In 44 cases with benign atypical foci, 2 out of 14 cases with atypical adenomatous hyperplasia (AAH) and 1 of 2 post-radiation atypias showed focal weak P504S staining with remaining 28 cases being negative.

Conclusions: P504S has slightly lower sensitivity for detection of prostate cancer than that found previously. Heterogeneous expression patterns may explain negativity in some biopsy specimens with minute cancer. In atypical small acinar proliferations, diffuse positive P504S staining in atypical glands strongly supports cancer diagnosis, but negative staining does not exclude it. P504S seems to have low sensitivity for detecting minute and foamy prostate cancers. Most HGPINs show diffuse moderate P504S staining. AAH and benign glands may show focal P504S staining. We recommend using P504S along with morphologic examination and conventional basal cell markers.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Routine oophorectomy in women with colorectal cancer is under debate, the aim of this study is to determine incidence, clinicopathologic features and prognostic factors of ovarian involvement in primary colorectal cancer (CRC) and to clear the role of prophylactic oophorectomy.
Methods: Data from primary CRC women treated between years 1990 and 2004 were retrieved and clinical and pathologic features of those who had undergone oophorectomy during CRC surgery were reviewed.
Results: One hundred eighty cases (mean age 47.5 years) were included. In 120(66.6%), ovaries were preserved and 60(33.3%) cases underwent bilateral oophorectomy in addition to primary CRC resection. Reasons for oophorectomy were prophylactic in 22(36.6%), abnormal morphology in 35(58.3%), and undetermined in 3(5%) cases. There were five metastatic carcinomas, eight primary ovarian tumors and 47 normal ovaries in pathologic evaluation. No complication directly related to oophorectomy was noted. Patients with ovarian metastases had higher stages of tumor. Ovarian metastases were not related to menstrual status, CRC location, size, differentiation, and mucin production, as well as abnormal morphology of ovary. The global prevalence of ovarian metastasis in CRC was 2.7%, and isolated ovarian metastases occurred in less than half of them. Of 120 women that underwent colectomy alone, eight (6.6%) developed ovarian metastasis during two years of follow-up. Only three cased had isolated ovarian metastases. No patient with synchronous or metachronous ovarian metastases from CRC survived five years.
Conclusion: Isolated ovarian metastases from primary CRC occur with a low frequency and this may partially explain the debate regarding prophylactic oophorectomy at the time of curative resection for primary CRC.

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Background: McGill pain questionnaire is the most useful standard tools for assessing pain. McGill pain questionnaire contains 78-word descriptive of the 20 subclasses form-ing in three main sensory, affective and evaluative domains. Due to cultural differences, the questionnaire has been translated into several languages. This study aimed to transl-ate MPQ into Persian language and assess its reliability, validity and acceptability in patients with cancer.
Methods: The study performed in Medical Oncology Department of Cancer Institute in Imam Khomeini Hospital in the Spring 2012. After translation of MPQ by two experts fluent in English, Persian version was returned to English. Then that backward transla-tion was compared with the original questionnaire and words that did not match were reviewed.  Patients with different types of cancer who suffering from chronic pain were admitted in our study. They did not receive any kind of pain killer drugs during the pre-vious 24 hours. There was no restriction of age, sex, education, type of cancer or treat-ment modality. The reliability and validity of Persian-McGill pain questionnaire after interviewing patients was assessed by test–retest reliability and internal consistency (Cronbach’s alpha).
Results: In total, 84 patients were interviewed and 30 patients who were available after 24 hour with the same condition recomplete the questionnaire. Cronbach’alpha of each domain was in 0.622-0.743 and total Crobach’s alpha (n=84) was 0.85. Evaluative aspect has only one subgroup and because of this, it is not have Crobach’s alpha. The stability coefficient (n=30) in all areas (sensory, emotional, and other domains) were 0.812-0.964. Stability coefficient among the 20 Persian McGill Pain Questionnaire (PMPQ) subclasses showed significant and reliable relationships over time for all groups.
Conclusion: This study is the first study that assessed psychometric properties and use-fulness of the MPQ in Iranian patients with cancer, showed that it is a potentially useful measure with a high validity and reliability standards.

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Background: Patients with hematologic malignancies are at risk of advanced tuberculosis. The prevalence of tuberculosis between these patients is 2.1- 2.6 percent. The cellular immune deficiency caused by hematologic malignancies and or its treatment increases the risk of tuberculosis in these patients. Multiple Myeloma is malignant proliferations of plasma cells that involves different classes of immune system. Cellular and humeral immune deficiency due to the Multiple Myeloma and drugs for its treatment results in susceptibility to unusual infections. Infections are of the important factors of morbidity and mortality in patients suffering from multiple myeloma ,but coincidence of Multiple Myeloma and tuberculosis  is rare and very little has been reported
Case presentation: In this paper a 60-year-old woman from Kermanshah, Iran who is suffering from back pain, weight loss, weakness and sweating will be introduced. Spondylitis was seen in her lumbar imaging. Her husband suffered from pulmonary tuberculosis. In diagnostic studies tuberculose spondylitis and multiple myeloma were diagnosed simultaneously.
Conclusion: Although the accompanying of Multiple Myeloma and tuberculosis is not common, but immunodeficiency caused by a hematologic malignancy as well as a history of close contact with a patient with tuberculosis resulted in tuberculosis of spine in this patient. Clinical features of abovementioned diseases are very similar. But in endemic area for tuberculosis, this disease should be considered because delay in diagnosis leads to increment in mortality and morbidities. Diagnosis of tuberculos spondylitis is based on radiologic and histologic features of the disease and on the response to treatment because the sensitivity of definitive diagnostic tests such as culture and PCR is low in extra pulmonary tuberculosis. 

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Background: Recently the use of “two tier" grading system in which ovarian serous carcinoma was classified as low-grade or high-grade in comparing to preceding system has improved authority in prognosis and survival. This approach is simplistic, reproducible, and based on biologic evidence. In this study, we reclassified ovarian serous carcinoma by a new two-tier system for grading and then evaluation of P53 expression in these tumors by immunohistochemistry method. Methods: We retrospectively reviewed 32 cases of ovarian serous carcinoma with previous diagnosis of well differentiated (eight cases) and moderate to poorly differentiated serous carcinoma (24 cases) and according "two tier" grading system in low-grade vs. high-grade serous carcinoma reclassified. Subsequntly all cases immunostained by P53 marker. Also clinical data related to survival of patients (with or without recurrence of tumor and death) and paraclinical findings such as presurgical blood serum level of CA125 are gathered. Results: Out of total eight patients with previously diagnosis well diferentiated serous carcinoma and of 24 patients with moderate to poorly differentiated serous carcinoma reclassified as low-grade and high-grade ovarian serous carcinoma respectively and a statistically significant difference was found between two groups. (P<0.005) Also of total 24 cases with high grade serous carcinoma, in 12 cases (54%) P53 immunostaining was detected but in non of all low grade serous carcinoma was seen. All 8 low grade serous carcinoma were alive without recurrence of tumor. In 10 and 12 out of 24 cases with high grade serous carcinoma recurrence of tumor and death were seen respectively. Conclusion: Since the presence of P53 negative expression in all of low-grade serous carcinoma by immunostaining and low-grade serous carcinoma accounts for small pupulation of all ovarian serous carcinoma and also few cases in our study, we did not find significant differences between P53 expression and survival in two low-grade vs high-grade serous carcinoma groups.

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Background: Colorectal carcinoma is considering as a curable disease. Treatment of recurrent cases is hard and sometimes impossible. Evaluation of the rate and affecting factors of recurrence in each hospital would help to decreasing recurrent cases. The aim of this study is evaluation of the rate, clinical and pathologic features, and outcome of recurrent colorectal carcinoma in a referral teaching hospital in Tehran. Methods: Clinical data of 166 curative resections of colorectal carcinoma who were operated between Mehr 1384 and Mehr 1388 (between 23 September 2005 and 23 September 2009) in Imam Khomeini Hospital and were accessible for follow up was collected. Follow up data was collected prospectively up to Farvardin 1391 (19 April 2012). Forty nine recurrences were happened in this period. We compared recurrent and non-recurrent cases for different variables Results: Average age of the patients was 53.5 years, and 47% of them were female. The median time to the diagnosis of recurrent disease was 12 months (range 1 months to 54 months). There were no significant differences between recurrent and non-recurrent patients about age, sex, sub-site of the tumor and sub-type of primary operation. Rate of overall recurrence, local recurrence and distant metastasis were 29.5%, 15.7% and 12.1% respectively. Local recurrence rate was higher in colon cancer (16.44% vs. 15.05%) but distant metastasis rate was higher in rectal cancer (12.9% vs. 10/96%). Rate of curative re-resection was about 25%. Overall survival of the recurrent patients who underwent surgery was better than who underwent chemo or radiotherapy (66.7% vs. 56.8%). Median survival time of recurrent patients after primary surgery was 28 months, and after diagnosis was 12 months (9.28- 14.72,95% CI). Conclusion: In this study the rate of overall recurrence was 29.5%. Local recurrence rate was higher in colon cancer (16.44% vs. 15.05%) but distant metastasis rate was higher in rectal cancer (12.9% vs. 10/96%).

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Background: Apoptin is a protein from chicken anemia virus that could induce apoptosis specifically in the cancer cells but it has not any effect in the normal cells. Phage therapy is a novel field of cancer therapy and phage nanobioparticles (NBPs) such as λ phage could be modified to deliver and express genetic cassettes into eukaryotic cells safely in contrast with animal viruses. The bacteriophages like Lambda could be manipulated to deliver genetic cassettes into eukaryotic cells and express the gene safely. We developed the safe way for the expression of Apoptin gene via Lambda bacteriophage in the human tumors. Methods: At first the Apoptin clone was produced and then transferred into ZAP-CMV plasmid through BamH-I and HinD-III restriction sites. Then this construct inserted into the Lambda phage in the Escherichia coli host cell. The expression of Apoptin in the recombinant construct was evaluated via RT-PCR and Western Blot analysis. The anti tumor function of expressed protein was measured in the BT-474 cells that was hosted by nude mice. Results: Transfection of breast carcinoma cells by Lambda bacteriophage containing λZAP-Apoptin-CMV was inhibited the tumor growth significantly but did not any effect on normal cells. The expression of this protein was very high in tumor cells and prevented the death of tumor bearing nude mice. The penetration and spreading of Apoptin construct by bacteriophage Lambda was significantly high but the Apoptin plasmid had very little expression in BT-474 cell, directly. Transfection with NBPs carrying λZAP-CMV-Apoptin significantly inhibited growth of all the breast carcinoma cell lines in vitro, but had no effect on normal cells. Conclusion: Utilization of recombinant Lambda bacteriophage as a safe expression vector has been confirmed. Apoptin was induced apoptosis specifically in the tumors in vivo. Use of such construct is a very safe way to treat cancer in human. The results presented here reveal important features of λ nanobioparticles to serve as safe delivery and expression platform for human cancer therapy.

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Background: Primary cardiac tumors are rare tumors which should be operated urgently. In this study, cardiac myxoma have been evaluated from diagnosis until dis-charge in a 10 years period and then results including presenting symptoms, approach to the patients were compared with similar study in this center a decade ago. Methods: Patients who underwent operation for myxoma from year 2003 until 2013 in the Shahid Modarres Hospital were included in this study. Results: Eighteen patients included in the study, 11 female and seven male. Patients’ ages were in the range of 13 to 76 years (mean 53 years). Mean time from diagnosis to operation was 5.8 days and mean time from surgery to discharge was 8.6±6.1 days. Most common presenting symptoms were first clinical presentation in four patients. In all patents echocardiography was the main diagnostic modality. In addition to trans thoracic echocardiography (TTE), in five patients TEE was used and in 13 patients coronary angiography was used to rule out concomitant coronary artery disease. 94.4% of all tumors (17 cases) were primary cardiac tumors and only one tumor (5.6%) was recurrent. In 16 patients (88.9%) tumor were found in the Left Atrium (L.A) and in one case, tumor was found in both atria and in another case, tumor was in the ventricle. After tumor excision, atrial septum was repaired primarily in seven cases (38.9%) and with pericardial patch in 9 cases. One patient underwent concomitant coronary artery bypass graft (CABG) and another patient underwent concomitant pulmonary valve repair. 14 patients (77.8%) discharged from hospital without any post operative complication. Heart block occurred in one patient and cerebral emboli with secondary cerebrovascular accident (CVA) developed in two patients. One patient died (5.6%). Conclusion: Comparing results from two similar studies in two consecutive decades revealed that mean time from diagnosis to operation obviously was reduced but ad-vances in diagnostic modalities were unable to change clinical presentation or reduce age of tumor diagnosis or complications or size.

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Background: Radiotherapy has been used to treat many types of cancers over the past years. Radiotherapy generates side effects on normal tissues. Radiosensitizer products provide decrease in tumor proliferation and reduce radiation dose in radiotherapy. Docosahexaenoic Acid (DHA) as an omega-3 polyunsaturated fatty acid has anti-proliferative effects on malignant cells. In this study, the effects of DHA accompanied by ionizing radiation on growth rate and survival fraction of HT29 colorectal cancer cells were evaluated. Methods: The present study was performed at the Institute of Biotechnology, affiliated to Urmia University, Urmia, Iran in the year 2013. In this laboratory experiment, ma-lignant cells were cultured in RPMI-1640 supplemented with 10% fetal bovine serum. HT-29 cells were cultured at 5105 cells/well into 6-well culture plates for overnight. Thereafter, the cells were pretreated with either 50 or 100 µM DHA for 4 hours and malignant cells were irradiated with either dose of 2 or 10 Gy. Cell viability was evalu-ated by trypan blue staining after 48 hours. Moreover, malignant cells were pretreated with either 50 or 100 µM DHA for 48 hours and irradiated with dose of 2 to 10 Gy. Thereafter, survival rate was evaluated by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay after 6 days. Results: Cell viabilities were found to be 59.8% and 17.5% for 50 µM DHA in combi-nation with doses of 2 and 10 Gy respectively. Using 100 µM DHA diminished cell vi-ability up to 47% and 13.9% following doses of 2 and 10 Gy respectively. Treatment of cells with DHA accompanied by increasing doses of γ-rays significantly diminished survival rate. In treated cells with 50 and 100 µM DHA, survival rate were measured to be 79.1%, 57.6%, 42.8%, 40.5%, 34% and 55.8%, 43.7%, 33.6%, 27.9%, 23.5% for doses of 2, 4, 6, 8 and 10 Gy respectively. Conclusion: Our study indicates that DHA decreases colorectal cancer cells prolifera-tion and could provide a new radiosensitizer drug to enhance the efficacy of colorectal cancer radiotherapy.

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Background: Colorectal cancer is the third most common cancer in the world. Non-coding RNA especially miRNAs have important regulatory roles in cancer. miRNAs are small non coding RNA 21-23 nucleotides long which have different levels of expression between tumors and normal tissues. This study was designed to compare expression level of miRNA-21 between Iranian population colorectal cancer tissues and normal tissue. Methods: This case-control study has performed in medical genetics department of Tehran University of Medical Sciences from January to November 2013. We used 35 samples. The samples were isolated from tumor and adjacent normal tissues of colon. Thirty-five samples were divided into different groups according to cliniopathologic features including tumor size (>4 and <4 cm), metastasis (+ and -) and stage. After small RNA extraction from tissues by small RNA purification kit the quality and quan-tity of extracted RNA was determined using spectrophotometry. cDNAs were synthe-sized and real-time polymerase chain reaction carried out. Finally expression levels were statistically analyzed by LinRegPCR and REST software. Results: miRNA-21 expression ratio in stages I, II and III were 1/804 and 4/574, re-spectively, the increase from stage III was statistically significant (P= 0.037). The ex-pression were also studied according to different clinicopathologic status of colon can-cer, tumor size (>4 and <4 cm) and metastatic (+ and -), miRNA-21 over expressed in both groups, however the increase was not statistically significant. Conclusion: In this study, we found miR-21 over-expression in advanced stage in tu-moral tissue comparing with normal adjacent tissue. This means perhaps in the future it would be possible to use miRNA-21 as an informative prognostic biomarker to guide for better treatment strategies for colorectal cancer patients. Our findings also indicate that miRNA-21 is a promising new molecular target for designing novel therapeutic strategies to control colorectal cancer.

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Background: Leptin is an adipokine made by fat cells and plays a key role in proliferation, cell survival, migration and immune response. Several studies have suggested that individuals with high serum leptin concentrations would increase the risk of breast cancer. G -2548A polymorphism in the leptin gene is located in the promoter region and is associated with the change of leptin serum level. In this study, the association between G -2548A polymorphism in leptin gene and breast cancer susceptibility was investigated. Methods: This case-control study was done on 374 Iranian women. This study was performed from March 2013 to February 2013. Blood samples from 203 women with breast cancer and 171 age (±5)- matched healthy women were collected. Breast cancer patients were selected from Namazi Hospital in Shiraz city. Genomic DNA was extracted from blood samples. The G -2548A polymorphism of leptin gene was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was performed by SPSS version 18. Logistic regression analysis was used for association of breast cancer susceptibility and G -2548A polymorphism of leptin gene. Results: The A allele frequency was 60% in control group and 72% in breast cancer patients. There was a significant association between A allele in -2548 position of leptin gene and breast cancer susceptibility (OR: 1.8, 95% CI: 1.3-2.4, P<0.001). In the reces-sive effect of the A allele (comparison between AA vs. AG+GG), AA genotype in -2548 region of leptin promoter sequence was significantly increased the risk of breast cancer (OR=2.2, 95% CI: 1.5-3.4, P<0.001). Conclusion: It is concluded that A allele in the -2548 promoter region of leptin gene may act as a recessive allele and increase the breast cancer risk.

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Background: Colorectal cancer is a major cause of morbidity and mortality throughout the world, and its treatments include surgery, chemo-radiotherapy. Despite improvements in clinical outcomes of patients with this tumor over the past decades, prognosis remains poor with a 5-year survival rate of <10%. Angiogenesis inhibitor agents have been recently added to the treatment regimen of this disease. In the past two decades, it has been recognized that selective inhibitors of the cyclooxygenase -2 (Cox-2) enzyme result in the regression in the size of colorectal tumor, and one of its reasons is attributed to angiogenesis inhibition. The present study aimed at identifying the molecular pathways of angiogenesis inhibition by celecoxib. Methods: HCT-116, which is one of the cell lines of Colorectal cancer (separated from human colorectal adenocarcinoma) was provided by the National Cell bank of Iran (NCBI) affiliated to Pasteur Institute. It was then cultured in DMEM (high glucose) culture medium containing 10% FBS, and then treated in the active substance of celecoxib at pharmacological concentrations of 50 mM (C50) and 100 mM (C100). Afterwards, RNA was extracted and cDNA was prepared. The oligonucleotide of HIF-1 Alpha gene (angiogenesis initiator) was prepared and the level of HIF-1 alpha gene expression was assessed with a real-time PCR device in three control, C50 and C100 groups. Results: HIF-1 alpha gene expression significantly decreased in the celecoxib treatment group (compared with control group) with the concentration of C100 (P< 0.001), but no change was observed in the concentration of C50. Conclusion: Angiogenesis is a key factor in the carcinogenesis process and FDA today approved bevacizumab as a first-line treatment for patients with metastatic colorectal cancer. The results of this study showed one of the causes of angiogenesis reduction in celecoxib-treated colorectal cancer. According to clinical findings and basic studies, celecoxib will be hopefully used as a first-line therapy along with chemotherapy in the near future in colorectal cancer. The advantages of this treatment method include its low cost and low side effects.

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Background: Radiotherapy can cause DNA damage in normal cells, misrepaired or unrepaired double strand breaks in DNA lead to chromosomal breaks. As a result patient experience early and late effects in normal tissue during and after radiotherapy. Cytogenetic techniques can be used as a cancer predictive assay because there is an association between chromosome abnormalities and the risk of developing cancer. Also it can assess patient's complications during the therapy. The aim of the present study was evaluation of the cytogenetic alteration in peripheral blood lymphocytes of esophageal cancer patients treated with radiotherapy. Methods: The present study is an experimental and prospective research. It was done at radiotherapy department at Omid Center in Urmia from January to December 2012. Blood samples were obtained from 15 esophageal cancer patients, before (0 Gy), during (21.6 Gy), and after radiotherapy treatment (43.2 Gy). Blood samples were cultured in RPMI-1640 complete medium containing 1% phytohaemagglutinin and incubated in a CO2 incubator. Cytochalasin-B was added to the cultures at a final concentration of 5 µg/ml. Finally, harvesting, slide making, and analysis were performed according to standard procedures. Results: This study consisted of 15 patients, including 7 men and 8 women from 55 to 84 years old (70.07±11.548). Results indicate that, in the middle of treatment the average frequency of micronuclei increased significantly compared with their concurrent pre-treatment samples (greater than four-fold). Also, an increase in chromosome damage (MN frequency) proportional increasing radiation doses at the end of treatment was observed (P=0.001). Conclusion: Increasing in the MN frequency in the second and third stages is due to radiation effects. Thus, the use of the MN technique for assessing of the side effects in patients during the therapy is very helpful. Moreover, MN assay can be used as a predictive assay for detecting individuals (patient or healthy) with intrinsic radiosensitivity.

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Helicobacter pylori (H. pylori) is the causative agent in development of gastroduode-nal diseases, such as chronic atrophic gastritis, peptic ulcers, mucosa associated lym-phoid tissue (MALT) lymphoma, and gastric cancer. H. pylori has been associated with inflammation in cardia, showing the fact that infection with this bacterium could also be a risk factor for gastric cardia cancer. Gastric cancer is the fourth most common cancer worldwide. This is the second leading cause of cancer-related deaths, and ap-proximately 700,000 people succumb each year to gastric adenocarcinoma. It has been estimated that 69% of the Iranian population currently harbor H. pylori infection. The prevalence of duodenal ulcer and gastric cancer is high in Iranian populations. However, this has been largely influenced by geographic and/or ethnic origin. Epidemi-ology studies have shown that host, environmental, and bacterial factors determine the outcome of H. pylori infection. The bacterium contains allelic diversity and high genet-ic variability into core- and virulence-genes and that this diversity is geographically and ethnically structured. The genetic diversity within H. pylori is greater than within most other bacteria, and its diversity is more than 50-fold higher than that of human DNA. The maintenance of high diversification makes this bacterium to cope with particular challenges in individual hosts. It has been reported that the recombination contributed to the creation of new genes and gene family. Furthermore, the microevolution in cagA and vacA genes is a common event, leading to a change in the virulence phenotype. These factors contribute to the bacterial survival in acidic conditions in stomach and protect it from host immune system, causing tissue damage and clinical disease. In this review article, we discussed the correlation between H. pylori virulence factors and clin-ical outcomes, microevolution of H. pylori virulence genes in a single host, microevolu-tion of H. pylori during primary infection and progression of atrophic gastritis to ade-nocarcinoma, and H. pylori infection status in Iran. Finally, we put forward the hy-pothesis that if the pattern of nucleotide sequence evolution shifts from recombination (r) to mutation (m) and the r/m ratio is reduced, bacterial pathogenicity may be re-duced while maintaining the bacterial life. However, this hypothesis should be further studied with future experiments.

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Background: Endometrial carcinoma is considered the most common gynecological cancer in the world. Pelvic and para-aortic lymphadenectomy is widely advised based on FIGO staging system. Intra-operative frozen sections analysis is used to identify pa-tients at high risk for pelvic and para-aortic nodal metastasis evading lymphadenec-tomy in low-risk patients. However there is still some controversy concerning the effi-ciency of IFS. The aim of this study was to determine the validity and precision of fro-zen section diagnosis and gross examination of uterine specimen compared to the final histological results in patients with endometrial cancer. Methods: Patients diagnosed as endometrial cancer based on office biopsy using a Pipelle or D&C who underwent surgical staging were compared for frozen section anal-ysis and permanent diagnosis. Patients with the history of radiotherapy or other types of cancer or co existence malignancies were excluded. Results: There was no relation between the tumor size and lymph node involvement and the results were not significant (P= 0.1). Frozen section analysis was significantly accurate and correct in predicting final histopathological results (P< 0.0001). It has been shown that in more than 90% of patients the diagnosis made by frozen section analysis was in accordance with final pathology with considerable sensitivity and spec-ificity. Gross examination was also precise in determining myometrial microscopic in-vasions (P< 0.0001). Conclusion: Although the sample size of the studied population was small but our study results support the previous data and suggest that in early stages and low grade tumors, gross examination and frozen section diagnosis are conveniently predictive of lymph node metastasis. These data might be useful for prediction of tumor invasion using frozen section and gross examination in low grade tumors and early stages and for doing complete surgical staging and lymph node sampling. However the im-portance of surgical staging always must be considered in patients who need systemat-ic lymphadenectomy. In overall these data might help to come up with new guidelines for surgical risk assessment in endometrial cancer.

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Background: Helicobacter pylori vacA (vacuolating toxin A) gene is comprised of mid- (m), intermediate- (i) and signal-regions. Recently, the vacA-i region genotype has been suggested to be a better predictor of disease severity than either the s- or m-region. The main aim of the present study was to determine the associations of i region poly-morphisms of vacA gene with gastric cancer (GC) and peptic ulcer disease (PUD) in Azerbaijan Province patients. Methods: A number of 89 patients were enrolled. The biopsy samples were taken from patients referring to the endoscopy units of Imam Reza and Shahid Madani Hospitals, Tabriz, Iran from August 2012 to May 2013. The genotype frequencies of vacA-i1 and i2 in were studied using polymerase chain reaction (PCR). Results: The frequency of vacA-i1 and i2 was 51.68% and 48.31%, respectively. The genotypic frequency of vacA-i1 in patients with GC (21/24, 87.5%) was significantly higher than in those with non-atrophic gastritis, NAG (19/48, 39.58%). In contrast, the genotypic frequency of vacA-i2 in patients with NAG, PUD, and GC was 60.42%, 64.70%, and 14.28%, respectively. The results of multiple linear and logistic regression analyses confirmed the intensity of correlation of vacA-i1 allele with GC compared with control group (NAG). No significant correlation was found between the vacA-i-region alleles and PUD risk. Conclusion: We have proposed that the H. pylori vacA-i1 genotype could be an im-portant biomarker for predicting the gastric cancer risk in Azerbaijan Province in Iran. However, due to the difference in the allelic frequency of this gene in H. pylori strains from different parts of the world, the vacA-i1 genotype usefulness in predicting the gas-trointestinal diseases is dependent to the geographic origin of the strains.

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Background: Metastasis associated miRNA (metastamiR) opened a new field of anti-metastatic therapy which have a great potential of treatment for the most lethal aspect of cancer, metastasis. The pleiotropic nature of gene regulation exhibited by certain miRNAs that showed that miRNAs might be endowed with a capacity to function as crucial modulators of tumor metastasis. MiR-31 is a pleiotropic anti-metastatic miRNA whose expression decreased significantly in metastatic breast cancer cells. MiR-31 has multiple roles in metastasis cascade. Therefore, using the miR-31-restoration based therapy could be an efficient anti-metastatic strategy for cancer therapy. Methods: This research was performed from May 2014 to October 2015 in Tarbiat Modares University in Tehran, Iran. The double-strand oligo of mature miR-31 was cloned into pcDNA 6.2gw/EmGFP according to the manufacturer instruction. The MDA-MB231, MCF-7 breast cancer cell lines were cultured and their miRNAs have been extracted. The expression of miR-31 has been quantified by Real time-PCR be-fore transfection of construct contained miR-31 into two cell lines and in normal breast cells. Then the constructs contain miR-31 have been transfected in to two cell lines. The expression of miR-31 has been quantified after 48 hours. Scratch and invasion as-say have been carried out for assessing the level of migration and invasion. Results: The result of Real time-PCR before transfection of constructs contained miR-31 have been shown 4 fold and more than 100 fold reduction in expression of miR-31 in MCF-7 and MDA-MB231 respectively in comparison to miR-31 expression in nor-mal breast cells, but after transfection of miR-31 construct to MDA-MB231 the quan-tification of expression showed the significant increase in mir-31 expression and 20 fold reduction in invasive and 10 fold reduction in migratory characteristics of MDA-MB231 in comparison to MCF-7. Conclusion: Metastasis associated miRNA have been represented a promising candi-dates in the field of anti-metastatic therapy and miR-31 as a powerful member of this family can function very effectively in order to inhibit the metastasis and introduce the new possibility of metastasis inhibition.

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Background: The molecular studies indicate some of the genes in the promoter region itself, will undergo methylation. Methylation of CpG islands in the promoter region of that cause silence or reduced expression of genes involved in cell growth pathways, which are colorectal cancer causing agents. Detection of methylation status can be used as a marker for cancer diagnosis and prediction of disease. CDKN2A tumor suppressor gene encodes a protein, which inhibit CDK 4/6 and loss of retinoblastoma protein phosphorylation (pRb) is involved. The purpose of this study was to investigate the molecular hypermethylation in exon 1 of CDKN2A gene in patients with colorectal cancer and normal subjects. Methods: In this case-control study, the study population consisted of 20 patients with colorectal cancer and 10 healthy persons. Samples in paraffin blocks were prepared in pathology department of Mehr Hospital, Tehran, Iran, from December 2010 to June 2012. Then, specific primers were designed for the methylation and Non-methylation of CDKN2A gene. To determine the level of exon 1 methylation of CDKN2A gene, methylation-specific polymerase chain reaction (MSP) method was performed. Results: In this study, hypermethylation in exon 1 of CDKN2A gene were observed in 80% of tumor tissues (16 cases) and 20% of normal tissues (2 cases). The patients aged older than 50 years, had a higher CDKN2A gene methylation and frequency than patients younger than 50 years old (66% vs 34%) (P<0/001). Conclusion: The result of this study has been confirmed the role of CDKN2A gene promoter methylation of CpG sites of colorectal cancer as the leading cause of colorectal cancer. These data suggest that epigenetic silencing via aberrant methylation of the CDKN2A promoter plays a critical role in the inactivation of this tumor suppressor gene in colorectal cancer and can be used as a marker for early detection and identification of potential applications.

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Background: Breast cancer is the second most common cancer in the world after lung cancer also is the fifth cause of cancer mortality. About 90 percent of cancer mortality is because of metastasis and devastating between cell attachments, especially tight cell junctions. Epithelial mesenchymal transition is a phenomena involved in metastasis and starts with cell detachment. Occludin is the integral membrane protein which is located in tight junctions. Obviously distressing tight junction, which facilitates the stages of metastasis in cancer cells are very critical step. The aim of this study was to demonstrate the importance of occludin expression and its relationship with invasiveness in human breast cancer. Methods: In a cross sectional study we evaluated 30 patients who were referred to Caner Institute of Imam Khomeini Hospital Complex, Tehran, Iran, from March 2013 to April 2013. Samples were derived from fresh frozen tumor of patients suffering from breast cancer after inform consent assignment in the Tumor Bank of Iran (TBI). RNA was extracted from tumor tissue followed by reverse transcription, polymerase chain reaction (PCR), conventional Real-time PCR and data analysis for the occludin gene expression. Data were analyzed based on clinical staging of breast cancer patients which were cited in data bank of TBI. Results: Results of this study have demonstrated that the occludin gene expression was increased with the advanced stage. In 22 of patients the expression of gene was elevated compared with normal samples. On the other hand, the expression was significantly increased in stage II in comparison with stage I. Conclusion: The expression of occludin has increased by elevation of stage compared with normal tissue. It is suggested that alteration in the expression of this gene might be a possible factor which could affect on patient’s prognosis the same as other factors which are belonging to the same family. Increasing in expression of this gene might be considered as one of the possible markers which predict the possibility of invasion and metastasis.