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Article ; Online: Up Regulation of Ezrin and Radixin with respect to Grade of Tumors in Breast Cancer Patients

Hadiseh Mohammadpour / Reza Shirkoohi

Basic & Clinical Cancer Research, Vol 14, Iss

2023 Volume 4

Abstract: Background: Breast cancer (BC) is one of the main causes of death among women in Iran. Biomarkers involved in promotion and progression of disease is very important in management and control of BC outcomes. In this research, we aim to estimate the ... ...

Abstract	Background: Breast cancer (BC) is one of the main causes of death among women in Iran. Biomarkers involved in promotion and progression of disease is very important in management and control of BC outcomes. In this research, we aim to estimate the expression levels of Ezrin and Radixin, as two important factors in morphogenesis, endocytosis, exocytosis, adherence, and migration of cells, in BC patients and their relationship with pathological factors. Methods: One hundred and thirteen BC patients were involved in this research. Relative expression of Ezrin and Radixin genes were estimated with quantitative real-time PCR. Pathological data include the histology, tumor size, grade, lymphovascular invasion and clinical TNM (Tumor, Node, and Metastasis) staging of patients were recorded based on the pathology report and their relationship with relative expression of Ezrin and Radixin were estimated. Result: According to result Ezrin were over expressed in tumor samples in comparison to adjacent normal tissue. There is a significant relationship between over expression of Ezrin and Radixin and grade of tumor and necrosis. Also there is a direct relationship between relative expression of Ezrin and Radixin expression. Conclusions: These data support the role of Ezrin and Radixin in the biology of breast cancer and additional studies needed that determine the Ezrin and Radixin associated with phenotype and may validate them as markers of cancer progression and as a potential target for cancer therapy.
Keywords	Ezrin ; Radixin ; Breast cancer ; Grade ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular Analysis of Acquired Tamoxifen Resistance in Breast Cancer Cell Line

reza shirkoohi

Asian Pacific Journal of Cancer Biology, Vol 2, Iss

2017 Volume 2

Abstract: Tamoxifen is an FDA approved drug for the prevention and the treatment of breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Many Studies suggest that a basic biological difference exists between tumors with ... ...

Abstract	Tamoxifen is an FDA approved drug for the prevention and the treatment of breast cancer, but its therapeutic benefit is limited by the development of drug resistance. Many Studies suggest that a basic biological difference exists between tumors with acquired tamoxifen resistance and those with intrinsic resistance to the drug. However the reasons why human mammary tumors become resistant to tamoxifen therapy are mainly unknown. Changes in gene expression may occur as cells acquire resistance to tamoxifen. A better understanding of gene expression alterations associated with tamoxifen resistance will facilitate circumventing this problem. Methods: We undertook a comparative gene expression analysis of tamoxifen-sensitive (MCF7 and T47D) and acquired tamoxifen-resistant human breast cancer cell lines (T47D tamoxifen resistant) in vitro models using Real-time PCR, to analyze differential gene expression. These genes were functionally linked to 4 major groups named as ER signaling/cell cycling, EGFR signaling, cancer stem cell (CSCs) and apoptosis. Results: Our results have been widely demonstrated that the altered expression of some genes involved in apoptosis, EGFR signaling, CSCs and Cell cycle-independent expression of estrogen receptor such as ESR1, TP53, CDKN1B, Casp3, CD44, CD24, BAX, Bcl2, Her2, and PTEN in T47D tamoxifen resistant cell line can be resulted in drug resistance in long-term treatment. Conclusions: Our findings correspond with the results of many earlier studies indicated tamoxifen resistance can be a result from combination of molecular mechanisms including Her2 activation, cell cycle progression out of ESR1 control, increased ratio of CSCs and inhibition of mitochondrial apoptosis.
Keywords	Biology (General) ; QH301-705.5
Subject code	616 ; 610
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	West Asia Organization for Cancer Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A case report of the sustained and rapid response of bevacizumab in a TP53-positive breast cancer and liver metastatic patient through personalized medicine

Mohammad Reza Eskandarion / Zahra Tizmaghz / Bahram Andalib / Nasser Parsa / Seyed Amir Hossein Emami / Reza Shahsiah / Mohammad Ali Oghabian / Reza Shirkoohi

Frontiers in Oncology, Vol

2022 Volume 12

Abstract: HER2-positive metastatic breast cancer is much less frequent than other subgroups of breast cancer. Treatment options for this cancer are mostly limited to systemic chemotherapy, which leads to moderate improvements. Targeted therapy against malignant ... ...

Abstract	HER2-positive metastatic breast cancer is much less frequent than other subgroups of breast cancer. Treatment options for this cancer are mostly limited to systemic chemotherapy, which leads to moderate improvements. Targeted therapy against malignant breast cancer requires the identification of reliable biomarkers for personalized medicine to obtain the maximum benefit of this therapy. Any mutations in the TP53 signaling pathway can be considered as a significant causative factor of breast cancer, for which the identification of target genes plays an important role in selecting the appropriate treatment. The use of personalized gene expression profiling could be valuable to find the direct target of the treatment in this case. The present study assessed the genetic profile of an HER2-positive metastatic breast cancer patient (with a liver metastasis) and figured out a complete and sustained response to bevacizumab. According to the results of next-generation sequencing (NGS) analysis, the patient’s genetic profile showed an increased expression of p4EBP1 and PTEN and the activation of the mTOR signaling pathway with a mutation in the TP53 gene. Based on the common treatment of similar profiling, we administrated bevacizumab/Taxol/Gemzar chemotherapy up to six courses. Accordingly, as the response to treatment was revealed by reducing the volume of the liver metastasis from 4 to 1.4 cm, metastasectomy was performed as a complementary treatment. Hence, personalized gene expression profiling not only is useful for targeted therapy but also could be recommended to avoid prescription of non-responsive drugs.
Keywords	breast cancer ; liver metastasis ; tumor markers ; target therapy ; personalized medicine ; NGS ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	616 ; 610
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association between occludin gene expression and clinical morphological characteristics in breast cancer

Fatemeh Ganjzadeh / Reza Shirkoohi

Tehran University Medical Journal, Vol 73, Iss 1, Pp 18-

2015 Volume 23

Abstract: 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 ... ...

Abstract	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 ...
Keywords	breast neoplasms ; gene expression ; morphological and microscopic findings ; neoplasm staging ; occludin ; real-time polymerase chain reaction ; Medicine (General) ; R5-920
Subject code	616 ; 610
Language	Persian
Publishing date	2015-04-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Neoplasia from Genetic Point of View

Reza Shirkoohi / Cyrus Azimi

Acta Medica Iranica, Vol 51, Iss

2013 Volume 10

Abstract: Cancer is a genetic-epigenetic based disease which contains a complex of alterations that cause irreversible transformation of cells with a new anarchic behavior. Tumor suppressor inactivation and/or oncogene activation will lead to tumorigenesis. Based ... ...

Abstract	Cancer is a genetic-epigenetic based disease which contains a complex of alterations that cause irreversible transformation of cells with a new anarchic behavior. Tumor suppressor inactivation and/or oncogene activation will lead to tumorigenesis. Based on the genetic alteration in germ or somatic cells, the affected person will have a different fate of cancer incidence or inheritable cancer susceptibility syndrome. Knowing the mechanism of molecular and cytogenetic alterations in cancer will give an advantage in finding more practical approaches to cancer management. In this review, the cancer genetics is discussed from different aspects.
Keywords	Cancer ; Cytogenetics ; Epigenetics ; Genetics ; Oncogenes ; Tumor suppressors ; Medicine (General) ; R5-920
Language	English
Publishing date	2013-10-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gene Expression Profiling and Clinicopathological Importance of Fer1L4 and DANCR Long Non Coding RNAs in Patients with Head and Neck Squamous Cell Carcinoma

Maryam Pirhoushiaran / Sara Hesami / Naeim Ehtesham / Saman Mehrabi / Reza Shirkoohi / Nasrin Yazdani / Maryam Lotfi / Abbas Shakoori Farahani

Journal of Clinical and Diagnostic Research, Vol 15, Iss 9, Pp GC01-GC

2021 Volume 06

Abstract: Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) entails a heterogeneous group of tumours that emerge from the interaction between molecular changes and environmental factors. Dysregulated long noncoding RNAs (LncRNAs) play a major part in ... ...

Abstract	Introduction: Head and Neck Squamous Cell Carcinoma (HNSCC) entails a heterogeneous group of tumours that emerge from the interaction between molecular changes and environmental factors. Dysregulated long noncoding RNAs (LncRNAs) play a major part in tumourigenesis and could be used as cancer biomarkers and therapeutic aims. Aim: To evaluate the expression of two lncRNAs named Fer-1 Like Family Member 4 (Fer1L4) and differentiation antagonising non protein-coding RNA (DANCR) in tumoural tissue of HNSCCs patients in comparison to Adjacent Non cancerous Tissues (ANCTs) to appraise their diagnostic power and the relationship with clinicopathological parameters. Materials and Methods: The present case-control study was designed, in which fresh frozen cancerous tissues and ANCTs were taken from 50 sporadic HNSCC patients who were attended in Imam Khomeini and Amir Alam Hospitals (Tehran, Iran) from from January to December 2019. Real-time PCR was utilised for expression profiling of Fer1L4 and DANCR. By employing GraphPad Prism 8.0 GraphPad Software, Inc., San Diego, CA, the real-time quantitative PCR experiments(2-.Ct) method and the Mann-Whitney test were exerted to analyse the obtained data. The Receiver Operating Characteristic (ROC) curve analysis was employed for figuring out the discrimination potential of two selected lncRNAs between the subject tumour and ANCT. Results: The expression of Fer1L4 was significantly down-regulated in tumoural tissues by analogy to ANCTs (p-value <0.0001) and statistically significant associations were found between the stage and grade status of the tumour with the relative expression of this lncRNA (p-value=0.008 and p-value=0.002 for stage and grade, respectively). The findings in this study indicated that the expression of DANCR was not statistically significant different in different tumoural tissues compared with ANCTs (p-value=0.46). ROC curve unraveled that the Fer1L4 had good diagnostic power Area Under Curve (AUC) 0.9252; p-value <0.0001. The expression of DANCR ...
Keywords	biomarker ; differentiation antagonising non protein coding ribonucleic acid ; Medicine ; R
Subject code	616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	JCDR Research and Publications Private Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Combination of Genistein and Imatinib has an Increased Effect on Cell Proliferation Inhibition in Philadelphia Positive Leukemia Cell Lines

Ebrahim Azizi / Alireza Biglari / Ali Abolhassani / Saeid Amanpour / Samad Muhammadnejad / Mahnaz Haddadi / Mojtaba Saffari / Ali Eslamifar / Reza Shirkoohi

Basic & Clinical Cancer Research, Vol 13, Iss

2021 Volume 1

Abstract: Background: This study investigated the possible role of Genistein as a combination with Imatinib in controlling leukemia cell line proliferation. Methods: Three cell lines, K562, Kcl22, and CCRF, were cultured and analyzed for MTT, LDH, apoptosis, and ... ...

Abstract	Background: This study investigated the possible role of Genistein as a combination with Imatinib in controlling leukemia cell line proliferation. Methods: Three cell lines, K562, Kcl22, and CCRF, were cultured and analyzed for MTT, LDH, apoptosis, and cycle cell gene expression in the presence of different dosages of Imatinib and Genistein in combination or separately. Results: Data has shown a decrease in proliferation and an increase in apoptosis activity during combination treatment. LDH assay has shown no additional toxicity due to Genistein consumption in combination therapy. Analysis of the expression of responsible genes for cell cycle demonstrated both G1 (p53, p21 upregulation) and G2 (cdc25c downregulation) inhibitory effect in combination treatment. Conclusion: Altogether, this study suggests thatthe combination treatment of Imatinib and Genistein for leukemia cells resistant to Imatinib can increase treatment efficiency.
Keywords	Cell cycle ; Genistein ; Imatinib ; leukemia ; Philadelphia chromosome ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Type I EMT Inducer Eomesodermin has a Significant expression in Breast Cancer

Mina Matinzadeh / Elmira Ebrahimi / Mojtaba Saffari / Reza Shirkoohi

Basic & Clinical Cancer Research, Vol 8, Iss

2016 Volume 3

Abstract: Background: Epithelial-Mesenchymal Transition (EMT) is a fundamental stage in cancer metastasis and the presence of vascular invasion is a strong indication of the spread of the malignant tumor cells. Regulation of the EMT is a complex process in which ... ...

Abstract	Background: Epithelial-Mesenchymal Transition (EMT) is a fundamental stage in cancer metastasis and the presence of vascular invasion is a strong indication of the spread of the malignant tumor cells. Regulation of the EMT is a complex process in which several different transcription factors are involved. Eomesodermin (Eomes) as a member of the T-box gene family is an important component in the induction of germ-line layer during gastrulation. However, its role in cancer is not well understood. Thereby, in this project we aimed to assess the Eomes gene expression in tumor tissues and to find out its possible relevance with vascular invasion. Materials and Methods: Seventy one breast cancer tumors were obtained from tumor bank of Cancer Institute, Imam Khomeini Hospital. Quantitative real-time PCR (qRT-PCR) was done to evaluate Eomes gene expression at RNA level. Results: Our results have shown that Eomes has been remarkably expressed in the majority of the tumor samples. High level of expression of Eomes was concomitant with the presence of vascular invasion in 72% of samples, however no significant association was found. To the best of our knowledge this is for the first time that Eomes expression has been reported in breast cancer tumors. Conclusions: This important finding suggests that Eomes has the potential to be used as a biomarker in breast cancer.
Keywords	Breast Cancer ; Epithelial-Mesenchymal Transition ; Gene Expression ; Neoplasm Metastasis ; Transcription factors ; Medicine ; R
Subject code	616
Language	English
Publishing date	2016-11-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Synaptonemal Complex Protein 3 Transcript Analysis in Breast Cancer

Maryam Beigom MOBASHERI / Reza SHIRKOOHI / Mohammad Hossein MODARRESSI

Iranian Journal of Public Health, Vol 45, Iss 12, Pp 1618-

2016 Volume 1624

Abstract: Background: Breast cancer is the most frequent cancer in women. Cancer/Testis antigens are immunogenic proteins ectopically expressed in human neoplasms. Synaptonemal complex protein 3 (SYCP3) belongs to cancer/testis genes family involved in meiotic ... ...

Abstract	Background: Breast cancer is the most frequent cancer in women. Cancer/Testis antigens are immunogenic proteins ectopically expressed in human neoplasms. Synaptonemal complex protein 3 (SYCP3) belongs to cancer/testis genes family involved in meiotic events and spermatogenesis. The aim of this study was to express analysis of SYCP3 in breast cancer and validate it as a breast cancer biomarker. Methods: Expression of SYCP3 transcripts in 47 breast tumors, 6 breast cancer cell lines (MCF7, SKBR3, T47D, BT474, MDA-MB-231 and MDA-MB 468), 5 normal breast and 2 testis tissues was studied by Real Time RT-PCR reaction. The reference genes phosphoglucomutase 1 and hypoxanthine guanine phosphoribosyl transferase were used as reactions normalizers. The software tool REST 2009 was applied for statistical analysis of the data. The research was conducted from Apr 2014 to August 2015 in Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Results: All of the studied breast cancer cell lines showed very high levels of SYCP3 overexpression in comparison to normal breast ( P =0.001) and even to normal testis ( P =0.001), except for MCF7 cell line. Breast tumors showed moderately increasing in transcript changes in comparison to normal breast. Conclusion: SYCP3 is a known testis-specific gene, but interestingly five out of six studied breast cancer of cell lines showed higher expression levels of SYCP3 in comparison to normal testis and normal breast tissues. SYCP3 has critical role in cell division with known interaction with the tumor suppressor genes, BRCA1 and BRCA2, which are critical genes in breast cancer.
Keywords	Breast cancer biomarkers ; Targeted therapy ; Cancer/testis genes ; SYCP3 ; Breast cancer cell lines ; Public aspects of medicine ; RA1-1270
Subject code	616
Language	English
Publishing date	2016-12-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CYP17 MspA1 Gene Polymorphism and Breast Cancer Patients According to Age of Onset in Cancer Institute of Iran

Elmira EBRAHIMI / Tayebeh SABOKBAR / Sharareh ESKANDARIEH / Vahideh PEYGHAMBARI / Reza SHIRKOOHI

Iranian Journal of Public Health, Vol 46, Iss

2017 Volume 4

Abstract: Background: Exposure to endogenous hormones such as estrogen is known as a lifetime Breast Cancer (BC) risk factor. Polymorphisms in genes that are involved in the steroidogenic process, such as Cytochrome P450c17alpha (CYP17), affect individuals’ ... ...

Abstract	Background: Exposure to endogenous hormones such as estrogen is known as a lifetime Breast Cancer (BC) risk factor. Polymorphisms in genes that are involved in the steroidogenic process, such as Cytochrome P450c17alpha (CYP17), affect individuals’ susceptibility to BC. In Iran, the highest incident of BC is among young women. This study aimed to find prevalence of Single Nucleotide Polymorphisms (SNPs) in genes such as CYP17 and significant correlation with age-oriented group of breast cancer. Methods: In 2016, a case series study was conducted on a total population of 205 patients suffering from breast cancer referred to Cancer Institute, Imam Khomeini Hospital Complex, Tehran, Iran. This population consisted of 104 cases less than 40 yr old and 101 cases over 40. The genotype variants of CYP17 MspA1 were determined using PCR, followed by RFLP. The association of CYP17 MspA1 polymorphisms with the risk of BC in two different age groups was evaluated by calculating odds ratio and 95% confidence intervals using unconditional logistic regression. Results: Carriers of at least one A2 allele may have higher risk of developing breast cancer at younger age compared to patients with A1/A1 genotype (Odds Ratio: 1.99, 95% Confidence Interval: 1.11-3.57, P=0.02). Conclusion: CYP17gene polymorphisms may have influence on the early onset of breast cancer.
Keywords	Breast cancer ; CYP17 gene ; Early onset breast cancer ; Estrogen ; Late-onset breast cancer ; Public aspects of medicine ; RA1-1270
Subject code	616 ; 610
Language	English
Publishing date	2017-04-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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