Publications by authors named "Fahimeh Fattahi"

11 Publications

  • Page 1 of 1

Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis.

Diagn Pathol 2021 Mar 22;16(1):26. Epub 2021 Mar 22.

Oncopathology Research Center, Iran University of Medical Sciences , Postal Code: 14496-14530, Hemmat Street (Highway), Next to Milad Tower, Tehran, Iran.

Background: TWIST1 and CD105, which contribute to tumor malignancy, are overexpressed in cancers. Accordingly, TWIST1 enhances epithelial-to-mesenchymal transition (EMT) and promotes the formation of cancer stem cells (CSCs). Also, CD105 is a neoangiogenesis marker in endothelial cells, which is introduced as a CSC marker in tumoral epithelial cells in several types of cancers. The present study was aimed to investigate expressions of TWIST1 and CD105 in colorectal cancer (CRC) patients.

Methods: Expressions of TWIST1 and CD105 in 250 CRC tissue samples were evaluated using immunohistochemistry on tissue microarrays (TMAs). In this regard, TWIST1 expression was investigated in the subcellular locations (cytoplasm and nucleus), while CD105 was mapped in endothelial cells and cytoplasmic tumor cells of CRC tissues. The association between the expression of these markers and clinicopathological parameters, as well as survival outcomes were analyzed.

Results: Results indicate a statistically significant association between higher nuclear expression levels of TWIST1 and distant metastases in CRC (P = 0.040) patients. In addition, it was shown that the increased nuclear expression of TWIST1 had a poor prognostic value for disease-specific survival (DSS) and progression-free survival (PFS) (P = 0.042, P = 0.043, respectively) in patients with CRC. Moreover, analysis of CD105 expression level has revealed that there is a statistically significant association between the increased expression of CD105 in tumoral epithelial cells and more advanced TNM stage (P = 0.050).

Conclusions: Our results demonstrate that nuclear TWIST1 and cytoplasmic CD105 expressions in tumor cells had associations with more aggressive tumor behavior and more advanced diseases in CRC cases.
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http://dx.doi.org/10.1186/s13000-021-01088-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983220PMC
March 2021

High expression of tumor susceptibility gene 101 (TSG101) is associated with more aggressive behavior in colorectal carcinoma.

J Cancer Res Clin Oncol 2021 Feb 22. Epub 2021 Feb 22.

Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Tehran, 14496-14530, Iran.

Introduction: Identification of genetic determinants such as exosomal content that drives progression and metastasis of colorectal cancer (CRC) has received considerable attention. The present study aims to identify a suitable biomarker in CRC tissues and exosomes based on bioinformatics data to evaluate its expression patterns in CRC tissues as well as its clinicopathological significance.

Materials And Methods: Protein-protein interaction (PPI) network and enrichment analysis were applied to identify up-regulated genes that contributed in CRC exosomes to select the marker. The expression patterns and clinical significance of selected exosomal marker were evaluated in tissue microarrays (TMAs) of 445 CRC tumors and 39 adjacent normal tissues using immunohistochemistry method.

Results: Based on bioinformatics data, TSG101 gene was prominent amongst the tumor tissues and exosomes. Expression of TSG101 was significantly up-regulated in tumor cells compared to adjacent normal tissues (p-value = 0.04). Moreover, higher expressions of TSG101 (cytoplasmic and nuclear) were significantly associated with tumor differentiation (p-value = 0.042) and distant metastasis (p-value = 0.027). A significant association was found in the cytoplasmic expression of TSG101 between well and moderate tumor differentiation (p-value = 0.005) as well as moderate and poor differentiation (p-value = 0.050).

Conclusion: These findings indicate that the exploration of crosstalk between exosome content and CRC may be valuable for the development of novel exosomal biomarkers. Increased expression of TSG101, as a promising exosome marker, is more associated with more aggressive tumor behaviors, metastasis, and progression of CRC, which paves the way for therapeutic strategies and CRC management. However, further investigations are warranted to clarify the molecular mechanisms of TSG101 in CRC.
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http://dx.doi.org/10.1007/s00432-021-03561-2DOI Listing
February 2021

Dynamic Signature of tRNA-Derived Small RNAs in Cancer Pathogenesis as a Promising Valuable Approach.

Crit Rev Eukaryot Gene Expr 2020 ;30(5):391-410

Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Aim: Noncoding RNAs are a cluster of RNAs that do not encode functional proteins. Instead, they are incorporated into DNA structure and regulate gene expression. Of these two classes, transfer RNAs (tRNAs) belong to the former, and small RNAs (sRNAs) belong to the latter. Recently, tRNA-derived small RNAs (tsRNAs/tDRs) were discovered among small noncoding RNAs, as the newly discovered regulatory small RNA. They play a role in pathological and physiological processes, in which gene expression is frequently dysregulated. TsRNAs can be bound to Argonaute proteins and Piwi proteins, such as miRNAs and piRNAs sequentially.

Methods: In initial searches, 2,744 articles were identified with the following literature databases, up to February 25, 2020: PubMed, Embase, Web of Science, Scopus, and Google Scholar. Finally, after full-text assessment, 48 articles were identified that are related to gene expression profiling of tsRNA in cancer.

Results: The development of cancer biomarkers based on noncoding RNAs is a thriving area of biomedical research that has expanded significantly. Currently, several groups of tsRNA/tDR biomarkers should be considered in updating the latest findings.

Conclusion: In this systematic review, we summarized the most recent findings related to the expression of tsRNAs in 17 cancer types. We suggested that use of tsRNAs in the cancer field attracted researcher focus and facilitated diagnostic and therapeutic approaches.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2020035372DOI Listing
January 2020

The epigenetic alterations of human sperm cells caused by heroin use disorder.

Andrologia 2021 Feb 25;53(1):e13799. Epub 2020 Oct 25.

Cellular and Molecular Research Center & Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran.

The molecular mechanisms of drug use on sexual health are largely unknown. We investigated, the relationship between heroin use disorder and epigenetic factors influencing histone acetylation in sperm cells. The volunteers included twenty-four 20- to 50-year-old men with a normal spermogram who did not consume any drugs and twenty-four age- to BMI-matched men who consume only the drug heroin for more than last four months. HDAC1 and HDAC11 mRNA expression levels in spermatozoa and miR-34c-5p and miR-125b-5p expression levels in seminal plasma were measured. The heroin-user group showed significantly increased white blood cell counts and decreased sperm motility and survival rates (8.61 ± 1.73, 21.50 ± 3.11, 69.90 ± 4.69 respectively) as compared to the control group (1.49 ± 0.32, 38.82 ± 3.05, 87.50 ± 0.99 respectively) (p ≤ .001). An increase in DNA fragmentation index (DFI) (heroin-user group: 41.93 ± 6.59% and control group: 10.14 ± 1.43%, p = .003), a change in frequency of HDAC1 (heroin-user group: 1.69 ± 0.55 and control group: 0.45 ± 0.14, p = .045) and HDAC11 (heroin-user group: 0.29 ± 0.13 and control group: 2.36 ± 0.76, p = .019) in spermatozoa and a significant decrease in seminal miR-125b-5p abundance (heroin-user group: 0.37 ± 0.11 and control group: 1.59 ± 0.47, p = .028) were reported in heroin consumers. Heroin use can lead to male infertility by causing leukocytospermia, asthenozoospermia, DFI elevation in sperm cells and alterations in seminal RNA profile.
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http://dx.doi.org/10.1111/and.13799DOI Listing
February 2021

Low expression of Talin1 is associated with advanced pathological features in colorectal cancer patients.

Sci Rep 2020 10 20;10(1):17786. Epub 2020 Oct 20.

Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next To Milad Tower, Tehran, Iran.

To explore the proper prognostic markers for the likelihood of metastasis in CRC patients. Seventy-seven fresh CRC samples were collected to evaluate the mRNA level of the selected marker using Real-time PCR. Moreover, 648 formalin-fixed paraffin-embedded CRC tissues were gathered to evaluate protein expression by immunohistochemistry (IHC) on tissue microarrays. The results of Real-Time PCR showed that low expression of Talin1 was significantly associated with advanced TNM stage (p = 0.034) as well as gender (p = 0.029) in mRNA levels. Similarly, IHC results indicated that a low level of cytoplasmic expression of Talin1 was significantly associated with advanced TNM stage (p = 0.028) as well as gender (p = 0.009) in CRC patients. Moreover, decreased expression of cytoplasmic Talin1 protein was found to be a significant predictor of worse disease-specific survival (DSS) (p = 0.011) in the univariate analysis. In addition, a significant difference was achieved (p = 0.039) in 5-year survival rates of DSS: 65% for low, 72% for moderate, and 88% for high Talin1 protein expression. Observations showed that lower expression of Talin1 at both the gene and protein level may drive the disparity of CRC patients' outcomes via worse DSS and provide new insights into the development of progression indicators because of its correlation with increased tumor aggressiveness.
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http://dx.doi.org/10.1038/s41598-020-74810-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576823PMC
October 2020

Effect of a Peptide Construct on Differentiated Macrophage MMP-2 and MMP-9 Levels of Varicose Patients.

Curr Pharm Des 2019 ;25(40):4303-4309

Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.

Background: The Matrix Metalloproteinase (MMPs) secreted from macrophages can affect the extracellular matrix remodeling process and improve varicose veins.

Aim: The aim of this study was to investigate the MMP-2 and MMP-9 gene expression and activity levels in the differentiated macrophages M2 of subjects with varicose veins, and to evaluate a peptide construct on their catalytic functions.

Methods: The macrophages were differentiated from the monocytes using M-CSF. The MMP-2 and MMP-9 gene expression and activity levels were measured by RT-qPCR and Zymography techniques, respectively. A peptide construct (ESLCG) was predicted with bioinformatics tools, and was prepared for the study of enzyme functions as compared to Batimastat. Furthermore, the docking studies were obtained for the evaluation of interactions between peptide construct, Batimastat and enzyme 3D structures.

Results: The results showed significant increases in MMP2 and MMP9 gene expression levels (P<0.001 and P<0.004, respectively) and gelatinolytic activities (P<0.001 and P<0.0001, respectively) in the macrophages. In agreement with the inhibitory effects of Batimastat, the peptide construct inhibited the MMP-2 and MMP-9 gelatinolytic activities up to 6.8 and 6.5 folds in the concentration of 150 µM. The docking analyses showed that the Lys187, Arg98, Leu49, Gly189, Leu190, Met97, Tyr53 and Phe57 residues of MMP-2 and the Leu187, His190, Glu402, His401, His405 and His411 residues of MMP-9 are interacted with the atoms of Batimastat and ESLCG peptide.

Conclusion: The ESLCG peptide may be applied as an inhibitor of MMP-2 and MMP-9 enzymes in the subjects with varicose veins.
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http://dx.doi.org/10.2174/1381612825666191029105203DOI Listing
June 2020

Enrichment of Up-regulated and Down-regulated Gene Clusters Using Gene Ontology, miRNAs and lncRNAs in Colorectal Cancer.

Comb Chem High Throughput Screen 2019 ;22(8):534-545

Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.

Aim And Objective: It is interesting to find the gene signatures of cancer stages based on the omics data. The aim of study was to evaluate and to enrich the array data using gene ontology and ncRNA databases in colorectal cancer.

Methods: The human colorectal cancer data were obtained from the GEO databank. The downregulated and up-regulated genes were identified after scoring, weighing and merging of the gene data. The clusters with high-score edges were determined from gene networks. The miRNAs related to the gene clusters were identified and enriched. Furthermore, the long non-coding RNA (lncRNA) networks were predicted with a central core for miRNAs.

Results: Based on cluster enrichment, genes related to peptide receptor activity (1.26E-08), LBD domain binding (3.71E-07), rRNA processing (2.61E-34), chemokine (4.58E-19), peptide receptor (1.16E-19) and ECM organization (3.82E-16) were found. Furthermore, the clusters related to the non-coding RNAs, including hsa-miR-27b-5p, hsa-miR-155-5p, hsa-miR-125b-5p, hsa-miR-21-5p, hsa-miR-30e-5p, hsa-miR-588, hsa-miR-29-3p, LINC01234, LINC01029, LINC00917, LINC00668 and CASC11 were found.

Conclusion: The comprehensive bioinformatics analyses provided the gene networks related to some non-coding RNAs that might help in understanding the molecular mechanisms in CRC.
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http://dx.doi.org/10.2174/1386207321666191010114149DOI Listing
September 2020

Common molecular markers between circulating tumor cells and blood exosomes in colorectal cancer: a systematic and analytical review.

Cancer Manag Res 2019 25;11:8669-8698. Epub 2019 Sep 25.

Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Nearly half of patients with colorectal cancer (CRC), the third leading cause of cancer deaths worldwide, are diagnosed in the late stages of the disease. Appropriate treatment is not applied in a timely manner and nearly 90% of the patients who experience metastasis ultimately die. Timely detection of CRC can increase the five-year survival rate of patients. Existing histopathological and molecular classifications are insufficient for prediction of metastasis, which limits approaches to treatment. Detection of reliable cancer-related biomarkers can improve early diagnosis, prognosis, and treatment response prediction and recurrence risk. Circulating tumor cells (CTCs) and exosomes in peripheral blood can be used in a liquid biopsy to assess the status of a tumor. Exosomes are abundant and available in all fluids of the body, have a high half-life and are released by most cells. Tumor-derived exosomes are released from primary tumors or CTCs with selective cargo that represents the overall tumor. The current systematic review highlights new trends and approaches in the detection of CRC biomarkers to determine tumor signatures using CTC and exosomes. When these are combined, they could be used to guide molecular pathology and can revolutionize detection tools. Relevant observational studies published until July 24, 2019 which evaluated the expression of tumor markers in CTCs and exosomes were searched in PubMed, Scopus, Embase, and ISI Web of Science databases. The extracted biomarkers were analyzed using String and EnrichR tools.
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http://dx.doi.org/10.2147/CMAR.S219699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768129PMC
September 2019

The Increase of pFAK and THBS1 Protein and Gene Expression Levels in Vascular Smooth Muscle Cells by Histamine-treated M1 Macrophages.

Iran J Allergy Asthma Immunol 2019 Feb;18(1):72-79

Department of Biochemistry, Iran University of Medical Sciences, Tehran, Iran.

Atherosclerosis is developed due to the formation of atheroma plaques in the coronary arteries. In this process, M1 macrophages and vascular smooth muscle cells (VSMCs) are the main functional cells. Inflammatory mediators such as histamine may inflame M1 macrophages. The aim of this study was to determine the effect of M1 macrophage secretion contents on the gene and protein expression levels of focal adhesion kinase (FAK), vasodilator-stimulated phosphoprotein (VASP), and thrombospondin1 (THBS1). Whole blood samples from the six healthy subjects (stenosis<5%), and six patients (stenosis>70%) were prepared and peripheral blood mononuclear cells (PBMCs) were isolated. Then monocytes were differentiated into M1 macrophages using 100 ng/mL granulocyte-macrophage colony stimulating factor (GM-CSF). The differentiated M1 macrophages were treated with histamine (10-6 M), and their secretion contents were harvested and added to the culture medium of VSMCs. The FAK, VASP, and THBS1 gene expression and protein levels were measured using RT-qPCR and western blot techniques in VSMCs, respectively. The FAK and THBS1 gene expression levels significantly increased in VSMCs after adding secretion contents obtained from histamine-treated M1 macrophages (p=0.023 and 0.05, respectively), while significant results were not observed for VASP gene (p=0.45). In converse with the phosphorylated VASP (pVASP) (p<0.34), the phosphorylated FAK (pFAK) and THBS1 protein levels increased in VSMCs (p<0.001). We concluded that in inflammatory conditions, the immune events could affect the macrophages by histamine. The activated macrophages could locally activate signaling pathways via FAK and THBS1 genes that are effective in the proliferation and migration of VSMCs.
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February 2019

Altered pattern of Naïve and memory B cells and B1 cells in patients with chronic granulomatous disease.

Iran J Allergy Asthma Immunol 2014 Jun;13(3):157-65

Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran and Department of Immunology and Allergy, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naïve and memory B cells and B1a cells in peripheral whole blood from Iranian patients with CGD. Flow cytometric analysis was performed on peripheral blood samples from 31 CGD patients and 23 healthy controls (HC) to study naïve (IgD+/CD27-), memory (CD27+) B and B1a (CD5+) cells. Soluble CD27 (sCD27) and immunoglobulins were also measured by ELISA and the nephelometric method, respectively. We found significantly higher levels of naïve B cells and B1a cells but lower levels of memory B cells in CGD patients compared to HC.. There was no significant difference in soluble CD27 (sCD27) alteration between CGD patients and HC. Our findings suggested a role for NADPH oxidase in process of B cell differentiation and impairing conversion of naïve B cells to memory B cells and altered B1a cells in CGD patients. Increased susceptibility of CGD patients to opportunistic infections and autoimmune disorders could be partly explained by the altered phenotype of B lymphocytes in these patients.
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June 2014

FNA diagnostic value in patients with neck masses in two teaching hospitals in Iran.

Acta Med Iran 2011 ;49(2):85-8

Department of Pathology, Bu-Ali Hospital, School of Medicine, Azad University of Tehran, Iran.

The FNA (fine needle aspiration) procedure is simple, inexpensive, available and a safe method for the diagnosis of a neck mass. FNA has numerous advantages over open surgical biopsies as an initial diagnostic tool; therefore we decided to compare the accuracy of this method with open biopsy. This retrospective as well as descriptive study comparing preoperative FNA results with existing data in the Pathology Department in Bu-Ali and Amir Alam Hospitals. Our study included 100 patients with neck masses of which 22 were thyroid masses, 31 were salivary gland masses, and 47 were other masses. Age ranged from 3 years to 80 years with the mean age of 42.6 years. There were 59 men and 41 women. The Sensitivity was 72%, Specificity 87%, PPV 85%, NPV 75% and diagnostic Accuracy 79%. In this study we had also 26% false negative and 15% false positive. FNA is a valuable diagnostic tool in the management of neck masses; also it has been used for staging and planning of treatment for the wide and metastatic malignancy. This technique reduces the need for more invasive and costly procedures. According to the high sensitivity and high accuracy in this study, FNA can be used as the first step of diagnoses test in neck masses.
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September 2011