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Chromogenic In Situ Hybridisation Test for Breast Cancer Patients with Equivocal IHC Results - a Study from Iran

  • Mehrazma, Mitra;Kalantari, Elham;Rezvani, Hamid;Bahar, Babak;Basi, Ali;Razavi, Seyed Mohsen;Rakhshani, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7695-7700
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    • 2015
  • Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3%) and 246 were CISH negative (73.7%). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9% concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90% and 53.8%, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing.

Leukemia in Iran: Epidemiology and Morphology Trends

  • Koohi, Fatemeh;salehiniya, Hamid;Shamlou, Reza;Eslami, Soheyla;Ghojogh, Ziyaeddin Mahery;Kor, Yones;Rafiemanesh, Hosein
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7759-7763
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    • 2015
  • Background: Leukemia accounts for 8% of total cancer cases and involves all age groups with different prevalence and incidence rates in Iran and the entire world and causes a significant death toll and heavy expenses for diagnosis and treatment processes. This study was done to evaluate epidemiology and morphology of blood cancer during 2003-2008. Materials and Methods: This cross-sectional study was carried out based on re-analysis of the Cancer Registry Center report of the Health Deputy in Iran during a 6-year period (2003 - 2008). Statistical analysis for incidence time trends and morphology change percentage was performed with joinpoint regression analysis using the software Joinpoint Regression Program. Results: During the studied years a total of 18,353 hematopoietic and reticuloendothelial system cancers were recorded. Chi square test showed significant difference between sex and morphological types of blood cancer (P-value<0.001). Joinpoint analysis showed a significant increasing trend for the adjusted standard incidence rate (ASIR) for both sexes (P-value<0.05). Annual percent changes (APC) for women and men were 18.7 and 19.9, respectively. The most common morphological blood cancers were ALL, ALM, MM and CLL which accounted for 60% of total hematopoietic system cancers. Joinpoint analyze showed a significant decreasing trend for ALM in both sexes (P-value<0.05). Conclusions: Hematopoietic system cancers in Iran demonstrate an increasing trend for incidence rate and decreasing trend for ALL, ALM and CLL morphology.

Relationship of Amplification and Expression of the C-MYC Gene with Survival among Gastric Cancer Patients

  • Khaleghian, Malihea;Shakoori, Abbas;Razavi, Amirnader Emami;Azimi, Cyrus
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7061-7069
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    • 2015
  • Background: During the past decades, the incidence and mortality rate of stomach cancer has demonstrated a great decrease in the world, but it is still one of the most common and fatal cancers especially among men worldwide, including Iran. The MYC proto-oncogene, which is located at 8q24.1, regulates 15% of genes and is activated in 20% of all human tumors. MYC amplification and overexpression of its protein product has been reported in 15-30% of gastric neoplasias. The aim of this investigation was to find the relative efficacy of CISH (chromogenic in situ hybridization) or IHC (immunohistochemistry) in diagnosis and prognosis of gastric cancer, as well as the relationship of amplification and expression of C-MYC gene with patient survival. Materials and Methods: In this cross-sectional study, 102 samples of gastric cancer were collected from patients who had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences, from July 2009 to March 2014. All samples were randomly selected from those who were diagnosed with gastric adenocarcinomas. CISH and IHC methods were performed on all of them. Results: Patients were classified into two groups. The first consisted of stage I and II cases, and the second of stage III and IV. Survival tests for both groups was carried out with referrnce to CISH test reults. Group II (stage III & IV) with CISH+ featured lower survival than those with CISH- (p=0.233), but group I (stage I & II) patients demonstrated no significant variation with CISH+ or CISH- (p=0.630). Kaplan-Meier for both groups was carried out with IHC test findings and showed similar results. This data revealed that both diffuse and intestinal types of gastric cancer occurred significantly more in men than women. Our data also showed that CISH+ patients (43%) were more frequent in comparison with IHC+ patients (14.7%). Conclusions: For planning treatment of gastric cancer patients, by focusing on expanding tumors, which is the greatest concern of the surgeons and patients, CISH is a better and more feasible test than IHC, in regard to sensitivity and specificity. Therefore, CISH can be used as a feasible test for tumor growth and prognosis in stage III and IV lesions. This study also indicated that C-MYC amplification in gastric cancer is correlated with survival in advanced stages.

Comparison of Chemical Composition and Radical Scavenging Activity of Pomegranate Extracts from Different Growing Areas

  • Lee, Hyun-Jung;Cho, Hye-Jin;Lee, Hyun-Sun;Kwon, Ki-Han;Hong, Yang-Hee;Kim, Seon-Hee;Suh, Hyung-Joo
    • Preventive Nutrition and Food Science
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    • v.14 no.3
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    • pp.214-219
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    • 2009
  • The pomegranate (Punica granatum L.) is a promising source of functional food, which contains several phytochemicals that perform important roles in reducing the risk of pathological diseases. Chemical compositions, such as the total sugar, uronic acid, polyphenols, and anthocyanin contents, and radical scavenging activity were determined and compared among PEs from six different cultivation areas. Total anthocyanin contents (TAC) and total polyphenol contents (TPC) from various growing areas were detected in the following order, respectively: Spain (19.08 ${\mu}g$/mL)> Turkey (12.91 ${\mu}g$/mL)> Iran-A (6.67 ${\mu}g$/mL)> Taiwan (4.77 ${\mu}g$/mL)> Uzbekistan (1.88 ${\mu}g$/mL)> Iran-B (0.76 ${\mu}g$/mL) and Turkey (639.52 ${\mu}g$/mL)> Uzbekistan (502.19 ${\mu}g$/mL)> Spain (306.40 ${\mu}g$/mL)> Iran-B (249.20 ${\mu}g$/mL)> Taiwan (162.78 ${\mu}g$/mL)> Iran-A (143.93 ${\mu}g$/mL). PEs from six different cultivation areas were determined to vary in ellagic acid content from 8.90 ${\mu}g$/mL to 332.52 ${\mu}g$/mL. The amounts of total sugars in PE from Iran-A evidenced relatively high total sugar contents, but low uronic acid levels (11.92 mg/mL). DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activities were as follows: Turkey> Uzbekistan $\gg$ Spain> Iran-B> Iran-A> Taiwan. ABTS [2,20-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activities were detected in the following order: Turkey$\geq$ Uzbekistan$\gg$ Spain> Iran-B> Iran-A> Taiwan. These results indicate that the PEs from Turkey with higher levels of TPC, TAC, ellagic acid, and higher radical scavenging activity may constitute a promising functional source for the prevention of several degenerative diseases.

Sensitive High-Resolution Melting Analysis for Screening of KRAS and BRAF Mutations in Iranian Human Metastatic Colorectal Cancers

  • Niya, Mohammad Hadi Karbalaie;Basi, Ali;Koochak, Aghigh;Tameshkel, Fahimeh Safarnezhad;Rakhshani, Nasser;Zamani, Farhad;Imanzade, Farid;Rezvani, Hamid;Adib sereshki, Mohammad Mahdi;Sohrabi, Masoud Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5147-5152
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    • 2016
  • Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes.

Prevalence and Type Distribution of Human Papillomavirus Infection Using the INNo-Lipa Assay, Kerman, Southeast Iran

  • Afshar, Reza Malekpour;Mollaie, Hamid Reza;Fazlalipour, Mehdi;Arabzadeh, Seyad Alimohammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5287-5291
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    • 2013
  • The human papilloma virus (HPV) causes skin and mucous membrane infections. It crosses from one person to another by skin-to-skin contact, such as sexual contact. There are more than 100 types of HPV that can influence different parts of the body. Some types of HPV can cause cancer (such as cervical or anal cancer) and others can cause warts (such as genital or plantar warts). HPV infection is one of the most common sexually transmitted infections (STIs) in Iran and around the world. Considerable molecular evidence suggests a role for human papilloma virus (HPV) in the pathogenesis of carcinoma. Epidemiological studies on human papilloma viruses (HPVs) infections in general population are critical for the performing of health policy guidelines for developing the strategies to hinder the primary and secondary different cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study was therefore to report the prevalence ratse of HPV types among Iranian patients. To study the risk of human papilloma virus (HPV) infection, we managed a retrospective study in Kerman province, southeast of Iran. For this purpose, 410 patients tested for the presence of HPV DNA using PCR and INNo-Lipa assays. HPV DNA was detected in 108 out of 410 patients (26.34%), while it was not detected in any of the control group samples. Patients included 23 (21.1%) males and 86 (78.8%) females. HPV type 6 was the most common (49%) followed by HPV type 16 (10.1%), and also HPV type11 (9.2%). The prevalence of HPV in Iran is comparable to those reported in other regions of the world. In a similar manner, it seems that HPV types 6, 16 and11 are the most common types in Kerman. Additional studies on larger group of patients, particularly in those with pre-invasive forms of disease, are needed to explain the roles of different HPV types in this location of Iran.

An Analysis of Iran's Maritime Strategy from a Structural Perspective on Middle East International Relations: Focusing on Defensive Realism (중동 국제관계에 대한 구조적 관점에서의 이란 해양전략에 대한 분석: 방어적 현실주의 관점을 중심으로)

  • Oh, Dongkeon
    • Maritime Security
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    • v.1 no.1
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    • pp.93-117
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    • 2020
  • Four cargo ships were ambushed by bombs in 2019 while navigating in the Strait of Hormuz. It was not clear who attacked those ships, however, many nations including the United States argued that it was Iran due to several reasons. The United States established the maritime collective defense system named International Maritime Security Construct (IMSC) in order to protect the maritime security in the Strait of Hormuz, without disclosure against whom it is aimed. Persian, who uses the Persian language unlike other countries in the Middle East, is the major ethnic group in Iran, and most of them believe Shi'ah Islam while most of the Arabs in the Gulf countries adhere to Sunni Islam. It seems that historic and religious motives caused the bipolar system in the Middle East, however, it is plausible to analyze the system of international affairs in the Middle East via defensive or structural realism. Iran has attempted to maintain its hegemony in the region by supporting Shi'ah muslims in the neighboring countries as well as in the world by using military and economic means. In this context, Iran's maritime strategy is to maintain its maritime hegemony on the Persian Gulf via countering threats and cooperating with friendly navies by using the Islamic Republic of Iran Navy(IRIN) and the Islamic Revolutionary Guard Corps Navy(IRGCN). IRIN acts like other navies in the world: protecting national interest at sea, expending its operational areas to the outer seas, and enhancing cooperation with other navies. Meanwhile, IRGCN plays a role as an asymmetric force at sea. It is composed of small and fast asymmetric assets, which can ambush ships fast and furious. Considering the poor study for Iran's maritime strategy in Korea, analyzing the strategy is meaningful for the Republic of Korea Navy, which has operated the Cheonghae Unit for more than ten years since it has extended its operational area over the Strait of Hormuz. In order not to be drawn into the conflict in the Strait, research on the maritime strategy of Iran and other countries in the Middle East should be started.

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Genetic diversity in merozoite surface protein(MSP)-1 and MSP-2 genes of Plasmodium falciparum in a major endemic region of Iran

  • Heidari Aliehsan;Keshavarz Hossein;Rokni Mohammad B.;Jelinek Tomas
    • Parasites, Hosts and Diseases
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    • v.45 no.1 s.141
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    • pp.59-63
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    • 2007
  • Merozoite surface protein-1(MSP-1) and merozoite surface protein-2(MSP-2) were used to develop vaccines and to investigate the genetic diversity in Plasmodium falciparum malaria in Iran. Nested polymerase chain reaction amplification was used to determine polymorph isms of block 2 of the MSP-1 and the central domain of MSP-2 genes. A total of 67 microscopically positive P. falciparum infected individuals from a major endemic region, southeast Iran, were included in this trial. Nine alleles of MSP-1 and 11 alleles of MSP-2 were identified. The results showed that amplified product from these surface antigen genes varied in size and there was specific pattern for each isolate. Besides, regarding this pattern, 23 multiple infections with at least 2 alleles were observed. While the endemic regions of malaria in Iran is classified in low to moderate group, but extensive polymorphism was observed for each marker and the MSP-2 central repeat was the most diverse that could be considered in designing malaria vaccine.

Combined TGE-SGE Expression of Novel PAI-1-Resistant t-PA in CHO DG44 Cells Using Orbitally Shaking Disposable Bioreactors

  • Davami, Fatemeh;Barkhordari, Farzaneh;Alebouyeh, Mahmoud;Adeli, Ahmad;Mahboudi, Fereidoun
    • Journal of Microbiology and Biotechnology
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    • v.21 no.12
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    • pp.1299-1305
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    • 2011
  • An important modification of thrombolytic agents is resistance to plasminogen activator inhibitor-1 (PAI-1). In previous studies, a new truncated PAI-1-resistant variant was developed based on deletion of the first three domains in t-PA and the substitution of KHRR 128-131 amino acids with AAAA in the truncated t-PA. The novel variant expressed in a static culture system of Chinese Hamster Ovary (CHO) DG44 cells exhibited a higher resistance to PAI-1 when compared with the full-length commercial drug; Actylase. In the present study, the truncated-mutant protein was expressed in CHO DG44 cells in 50 ml orbital shaking bioreactors. The final yield of the truncated-mutant in the culture was 752 IU/ml, representing a 63% increase compared with the static culture system. Therefore, these results suggest that using the combined features of a transient and stable expression system is feasible for the production of novel recombinant proteins in the quantities needed for preclinical studies.