Publications by authors named "Reihaneh Alsadat Mahmoudian"

15 Publications

  • Page 1 of 1

Genetically engineered mouse models of esophageal cancer.

Exp Cell Res 2021 09 28;406(2):112757. Epub 2021 Jul 28.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Esophageal cancer is the most common cause of cancer-related death worldwide with a diverse geographical distribution, poor prognosis, and diagnosis in advanced stages of the disease. Identification of the mechanisms involved in esophageal cancer development is evaluative to improve outcomes for patients. Genetically engineered mouse models (GEMMs) of cancer provide the physiologic, molecular, and histologic features of the human tumors to determine the pathogenesis and treatments for cancer, hence exhibiting a source of tremendous potential for oncology research. The advancement of cancer modeling in mice has improved to the extent that researchers can observe and manipulate the disease process in a specific manner. Despite the significant differences between mice and humans, mice can be great models for human oncology researches due to similarities between them at the molecular and physiological levels. Due to most of the existing esophageal cancer GEMMs do not propose an ideal system for pathogenesis of the disease, genetic risks, and microenvironment exposure, so identification of challenges in GEM modeling and well-developed technologies are required to obtain the most value for patients. In this review, we describe the biology of human and mouse, followed by the exciting esophageal cancer mouse models with a discussion of applicability and challenges of these models for generating new GEMMs in future studies.
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http://dx.doi.org/10.1016/j.yexcr.2021.112757DOI Listing
September 2021

Correlation between the immune checkpoints and EMT genes proposes potential prognostic and therapeutic targets in ESCC.

J Mol Histol 2021 Jun 21;52(3):597-609. Epub 2021 Apr 21.

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3, crucial immune checkpoint molecules in the tumor microenvironment, identify as key targets for cancer immunotherapy. There is a correlation between immune cells and epithelial-mesenchymal transition (EMT)-related genes expression in varies human cancers. In this study, we aimed to investigate the probable association between expression of immune checkpoints and EMT in esophageal squamous cell carcinoma (ESCC) with clinical treats for providing the new therapeutic targets and prognostic value for the disease. Quantitative real-time PCR was used to investigate the gene expression profile of immune checkpoints (PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3) and EMT (TWIST1 and MMP-13) genes based on the mRNA expression levels in 51 ESCC tissues. The upregulation of CTLA-4, PD-1, PD-L1, TIM-3, LAG-3, MMP-13, and TWIST1 were observed in 31.37%, 29.41%, 21.56%, 39.21%, 25.49%, 60.78%, and 56.86% of ESCC cases at the mRNA level, respectively. Dysregulation of immune checkpoints was related to lymph node involvement, stage of tumor progression, and depth of tumor invasion (P < 0.05). While overexpression of MMP-13 and TWIST1 was associated with lymph node involvement, stage of tumor progression, and grade of tumor differentiation (P < 0.05). The mRNA expression of immune checkpoint genes was significantly correlated to each other's (P = 0.000). Of importance, the data explored the significant association between the concomitant expression of immune checkpoints and EMT-related genes with each other in a variety of clinicopathological traits (P < 0.05). Consequently, immune checkpoints were positively correlated with EMT status in ESCC. The correlation between tumor immune microenvironment with the elevation of multiple immune checkpoints and EMT status may help to identify potential biomarkers for the simultaneous clinical use of multiple immune checkpoints blockade and other immunotherapies approaches for advanced ESCC patients.
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http://dx.doi.org/10.1007/s10735-021-09971-3DOI Listing
June 2021

Interaction between LINC-ROR and Stemness State in Gastric Cancer Cells with Helicobacter pylori Infection.

Iran Biomed J 2021 Mar 1;25(3):157-68. Epub 2021 Mar 1.

Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Large intergenic non-coding RNA regulator of reprogramming (LINC-ROR), as a cancer-related Long non-coding RNA, has vital roles in stem cell survival, pluripotency, differentiation, and self-renewal in human embryonic stem cell. However, cancer-related molecular mech¬anisms, its functional roles, and clinical value of LINC-ROR in gastric cancer (GC) remain unclear. In this study, we aimed to investigate probable interplay between LINC-ROR with SALL4 stemness regulator and their role with the development of the disease.

Methods: The mRNA expression profile of LINC-ROR and SALL4 was assessed in tumoral and adjacent non-cancerous tissues of GC patients, using quantitative real-time PCR.

Results: Significant LINC-ROR underexpression and SALL4 overexpression were observed in 55.81% and 75.58% (p < 0.0001) of samples, respectively. The expression of LINC-ROR and SALL4 were significantly correlated with each other (p = 0.044). There was an association between the underexpression of LINC-ROR and sex, stage of tumor progression, tumor type, and location of tumor (p < 0.05), and Helicobacter pylori infection with SALL4 expression (p = 0.036). There were also significant correlations between concomitant mRNA expression of SALL4 and LINC-ROR in tumors located at distal noncardiac, positive for H. pylori infection, tumors with invasion into the muscle layer of the stomach, and grade II tumor (p < 0.05).

Conclusion: The clinical results of the SALL4-LINC-ROR association propose a probable functional interaction between these markers in tumor maintenance and aggressiveness. Our study can help to understand one of the mechanisms involved in the progression of gastric cancer through the function of these regulators.
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http://dx.doi.org/10.29252/ibj.25.3.157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183384PMC
March 2021

Crosstalk between MMP-13, CD44, and TWIST1 and its role in regulation of EMT in patients with esophageal squamous cell carcinoma.

Mol Cell Biochem 2021 Jun 19;476(6):2465-2478. Epub 2021 Feb 19.

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Matrix metalloproteinases (MMPs) play key roles in epithelial-mesenchymal transition (EMT) for the development of cancer cell invasion and metastasis. MMP-13 is an extracellular matrix (ECM)-degrading enzyme that plays crucial roles in angiogenesis, cell cycle regulation, niche maintenance, and transforming squamous epithelial cells in various tissues. CD44, a transmembrane glycoprotein expressed on esophageal tumor cells, is required for EMT induction and invasion in esophageal squamous cell carcinoma (ESCC). The transcription factor TWIST1, as EMT and stemness marker, regulates MMPs expression and is identified as the downstream target of CD44. In this study, we aimed to investigate the probable interplay between the expression of key genes contributing to ESCC development, including MMP-13, TWIST1, and CD44 with clinical features for introducing novel diagnostic and therapeutic targets in the disease. The gene expression profiling of MMP-13, TWIST1, and CD44 was performed using quantitative real-time PCR in tumor tissues from 50 ESCC patients compared to corresponding margin non-tumoral tissues. Significant overexpression of MMP-13, CD44S, CD44V3, CD44V6, and TWIST1 were observed in 74%, 36%, 44%, 44%, and 52% of ESCC tumor samples, respectively. Overexpression of MMP-13 was associated with stage of tumor progression, metastasis, and tumor location (P < 0.05). There was a significant correlation between TWIST1 overexpression and grade (P < 0.05). Furthermore, overexpression of CD44 variants was associated with stage of tumor progression, grade, tumor invasion, and location (P < 0.05). The results indicated the significant correlation between concomitant expression of MMP-13/TWIST1, TWIST1/CD44, and CD44/MMP-13 with each other in a variety of clinicopathological traits, including depth of tumor invasion, tumor location, stage of tumor, and lymph node involvement in ESCC tissue samples (P < 0.05). Collectively, our results indicate that the TWIST1-CD44-MMP-13 axis is involved in tumor aggressiveness, proposing these genes as regulators of EMT, diagnostic markers, and therapeutic targets in ESCC.
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http://dx.doi.org/10.1007/s11010-021-04089-2DOI Listing
June 2021

Crosstalk between MEIS1 and markers of different cell signaling pathways in esophageal squamous cell carcinoma.

Mol Biol Rep 2020 May 5;47(5):3439-3448. Epub 2020 May 5.

Department of Biology, Damghan branch, Islamic Azad University, Cheshmeh-Ali boulevard, Sa'dei square, Damghan, Islamic Republic of Iran.

The homeobox transcription factor MEIS1 is involved in cell fate decision, stem cells properties, gastrointestinal (GI) tract development, and progression of several malignancies such as esophageal squamous cell carcinoma (ESCC). Increasing evidences suggest the crosstalk between MEIS1 and cell signaling pathways. Therefore, our aim in present study was to investigate the probable linkage of MEIS1 expression with key genes of different cell signaling pathways in ESCC tumorigenesis, and their correlation with clinicopathological feature of the patients. The gene expression profiling of MEIS1 and different cell signaling genes including SALL4, SIZN1, and HEY1 (stemness state, BMP, and NOTCH signaling pathways, respectively) was performed using quantitative real-time reverse transcription polymerase chain reaction (PCR) in fresh tumoral compared to margin normal tissues of 50 treatment-naive ESCC samples. The mRNA expression of MEIS1/SIZN1, SIZN1/HEY1, and SIZN1/SALL4 were significantly associated to each other (P < 0.05). There were remarkable correlations between concomitant mRNA expression of MEIS1 and SIZN1 in tumors with invasion to adventitia, early stages of tumor progression and poorly differentiated tumors. Moreover, expression of MEIS1 and HEY1 was correlated to each other in primary stages of tumor progression and non-invaded tumors. Expression of MEIS1 was significantly associated with SALL4 in poorly differentiated tumors. Our results indicated that correlation between different cell signaling pathway-related genes may lead to esophageal tumorigenesis. It is illustrated that MEIS1 as a HOX gene has a significant correlation with stemness state, BMP, and NOTCH signaling pathways via the SIZN1.
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http://dx.doi.org/10.1007/s11033-020-05423-5DOI Listing
May 2020

The Role of Interleukin-4 and 13 Gene Polymorphisms in Allergic Rhinitis: A Case Control Study.

Rep Biochem Mol Biol 2019 Jul;8(2):111-118

Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Allergic Rhinitis (AR) is an IgE-mediated inflammatory disorder with high morbidity rates. The eitiology of this disease is understood to occur from a complex interaction between genetic and environmental factors. T helper type 2 cells have been shown to have a crucial role in atopic disease due to their production of the cytokines, intelukin and , involved in inflammation. Research has shown single nucleotide polymorphisms (SNP) of the and genes to be associated increased levels of IgE and with allergic diseases such as, allergic rhinitis, asthma, and atopic dermatitis. Specifically, the rs2243250 SNP of IL-4 and the rs20541 SNP of have been shown to be associated with AR.

Methods: A case-control study was designed to investigate the relationship between the two SNPs rs2243250 and rs20541 with the incidence of AR. The SNPs were examined in patients with AR and healthy controls (86 patients and 86 controls). Blood samples were collected and DNA was extracted to evaluate the SNPs by RFLP-PCR.

Results: Recessive analysis model of the gene (GG vs. AA+AG) revealed that the GG genotype was more common in AR patients (P=0.36) )OR=0.8 [81% CI 0.38-1.6]). For the gene (TC vs. TT+CC), the TC genotype was more common in AR patients (P = 0.0022)) OR=0.71 [60% CI 1.41-5.02]). Furthermore, in the IL-4 gene, the 590 T>C polymorphism had a significant association with AR. However, no association was found between AR and the rs20541 polymorphism.

Conclusion: Our findings suggest that the polymorphism (rs20541, Exo 4, G>A, Arg130Gln) and IL-4 polymorphism (rs2243250= C-590T, promoter, T>C) are co-associated with AR and sensitivity to aeroallergens. However, this study used a cohort of AR patients and healthy controls from the northeast of Iran. Given the influence of ethnicity and environment on genetics, further investigation is needed to elucidate the role of SNPs in and in AR among different populations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844616PMC
July 2019

MEIS1 knockdown may promote differentiation of esophageal squamous carcinoma cell line KYSE-30.

Mol Genet Genomic Med 2019 07 14;7(7):e00746. Epub 2019 May 14.

Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

Background: MEIS1 (Myeloid ecotropic viral integration site 1), as a homeobox (HOX) transcription factor, has a dual function in different types of cancer. Although numerous roles are proposed for MEIS1 in differentiation, stem cell function, gastrointestinal development and tumorigenesis, the involved molecular mechanisms are poor understood. Our aim in this study was to elucidate the functional correlation between MEIS1, as regulator of differentiation process, and the involved genes in cell differentiation in human esophageal squamous carcinoma (ESC) cell line KYSE-30.

Methods: The KYSE-30 cells were transduced using recombinant retroviral particles containing specific shRNA sequence against MEIS1 to knockdown MEIS1 gene expression. Following RNA extraction and cDNA synthesis, mRNA expression of MEIS1 and the selected genes including TWIST1, EGF, CDX2, and KRT4 was examined using relative comparative real-time PCR.

Results: Retroviral transduction caused a significant underexpression of MEIS1 in GFP-hMEIS1 compared to control GFP cells approximately 5.5-fold. While knockdown of MEIS1 expression caused a significant decrease in EGF and TWIST1 mRNA expression, nearly -8- and -12-fold respectively, it caused a significant increase in mRNA expression of differentiation markers including KRT4 and CDX2, approximately 34- and 1.14-fold, correspondingly.

Conclusion: MEIS1 gene silencing in KYSE-30 cells increased expression of epithelial markers and decreased expression of epithelial-mesenchymal transition (EMT) marker TWIST1. It may highlight the role of MEIS1 in differentiation process of KYSE-30 cells. These results may confirm that MEIS1 silencing promotes differentiation and decreases EMT capability of ESC cell line KYSE-30.
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http://dx.doi.org/10.1002/mgg3.746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625128PMC
July 2019

Whole Exome Sequencing Reveals a Novel Damaging Mutation in Human Fibroblast Activation Protein in a Family with Esophageal Squamous Cell Carcinoma.

J Gastrointest Cancer 2020 Mar;51(1):179-188

Immunology research center, Mashhad university of Medical Sciences, Mashhad, Iran.

Purpose: Esophageal squamous cancer cell (ESCC), with late diagnosis and poor rate of survival, is a significant cause of mortality in the developing countries. The hypothesis of rare high penetrance with mutations in new genes may explain the underlying predisposition in some of these familial cases.

Methods: Exome sequencing was performed in the patients with ESCC with strong disease aggregation, two sisters with ESCC cancer, and one with breast cancer. Data analysis selected only very rare variants (0-0.1%) located in genes with a role compatible with cancer. In addition, the homology modeling of the novel mutation (A459D) discovered in FAP gene was performed by using the online Swiss-Prot server for automated modeling and the resulted structure has been modified and analyzed by using bioinformatics software to thoroughly study the structural deficiencies caused by the novel mutation.

Results: Ten final candidate variants were selected and six genes validated by Sanger sequencing. Correct family segregation and somatic studies were used to categorize the most interesting variants in FAP, BOD1L, RAD51, Gasdermin D, LGR5, and CERS4. A novel, human mutation C1367A encoding Ala459 Asp (accession number: KT988039), occurring in the blade of the β propeller domain, was identified in two sisters with ESCC.

Conclusions: We identified novel mutations in three drug delivery genes, a tumor suppressor and also a stem cell marker of esophageal that may have a role in cancer treatment and are involved in cellular pathways, which supports their putative involvement in germ-line predisposition to this neoplasm.
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http://dx.doi.org/10.1007/s12029-019-00224-xDOI Listing
March 2020

Induction of T cell-mediated immune response by dendritic cells pulsed with mRNA of sphere-forming cells isolated from patients with gastric cancer.

Life Sci 2019 Feb 12;219:136-143. Epub 2019 Jan 12.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Gastric cancer (GC) as the third most common cause of cancer-associated mortality worldwide is one of the cancers with very high heterogeneity. Cancer stem cells (CSCs) as a small subset of cancer cells in solid tumors with the self-renewal, differentiation and tumorigenic ability are responsible for tumor initiation, progression, recurrence, metastasis, and resistance to current treatments. Therefore, eradication of CSCs is very vital to cure cancer. Here, we first isolated and identified sphere-forming cells in tumor tissue from four GC patients and then analyzed T cell responses induced by monocyte-derived dendritic cells (DCs) loaded with total mRNA of sphere-forming cells in terms of interferon-gamma (IFN-γ) gene expression and specific cytotoxicity. Spheroid colonies were formed in serum-free media. Sphere-forming cells dissociated from tumorspheres heterogeneously expressed CD44, CD54, and epithelial cell adhesion molecule (EpCAM) markers and generated one tumor in nude mice. These results demonstrated that gastric CSCs were enriched in tumorspheres. Cytokine-matured DCs loaded with mRNA of sphere-forming cells were able to induce IFN-γ gene expression in T-lymphocytes after a 12-day co-culture. mRNA level of IFN-γ gene in these lymphocytes was more highly expressed compared to stimulated T-lymphocytes by DCs transfected with normal tissue (6.4-9.39 folds). Cytotoxic activity of primed T-lymphocytes with antigens of sphere-forming cells was significantly higher than normal tissue antigens and mock DCs (P ≤ 0.0001). Taken together, DCs loaded with mRNA of sphere-forming cells that elicit effectively specific T cell-mediated immune responses in vitro, may be considered as a promising therapeutic vaccination in GC patients in future.
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http://dx.doi.org/10.1016/j.lfs.2019.01.016DOI Listing
February 2019

Association of Two CD44 Polymorphisms with Clinical Outcomes of Gastric Cancer Patients

Asian Pac J Cancer Prev 2018 May 26;19(5):1313-1318. Epub 2018 May 26.

Department of Cellular and Molecular Biology, University of Science and Culture, Tehran, Iran.

Objective: CD44 is an important cell adhesion molecule that plays a key role in growth, invasion, proliferation and metastasis of cancer cells. CD44 protein over-expression is associated with a poor prognosis of gastric cancer (GC) and previous studies have shown that CD44 gene polymorphisms could affect survival and recurrence. In this study, we tested the hypothesis that polymorphisms impacting on the CD44 signaling pathway may predict clinical outcomes in patients with GC. Materials and Methods: DNA was extracted from blood of 150 healthy individuals and formalin-fixed paraffin-embedded (FFPE) tumor tissue of 150 patients. The two polymorphisms rs187116 and rs7116432 were studied by RFLP-PCR and sequencing techniques. Results: There was a strong significant correlation between single nucleotide polymorphisms (SNPs) in the CD44 gene, tumor recurrence, and overall survival (p <0.0001). The existence of a significant relationship between tumor recurrence and overall survival was proved in this study, with at least one allele G for the polymorphism rs187116 and at least one allele A for polymorphism rs7116432. Conclusion: These results provide evidence of a relationship between CD44 gene polymorphisms and clinical outcomes in our GC patients. This result could help identify individuals with GC who have a high risk of tumor recurrence.
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http://dx.doi.org/10.22034/APJCP.2018.19.5.1313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031830PMC
May 2018

Biological and Clinicopathological Significance of Cripto-1 Expression in the Progression of Human ESCC.

Rep Biochem Mol Biol 2017 Apr;5(2):83-90

Immunology Research Center, BuAli Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Human Cripto-1, a member of the EGF-CFC family, is involved in embryonic development, embryonic stem cell maintenance, and tumor progression. It also participates in multiple cell signaling pathways including Wnt, Notch, and TGF-β. Remarkably, it is expressed in cancer stem cell (CSC) compartments, boosting tumor cell migration, invasion, and angiogenesis. Although Cripto-1 is overexpressed in a variety of human malignant tumors, its expression in esophageal squamous cell carcinoma (ESCC) remains unclear. Our aim in this study was to evaluate the possible oncogenic role of Cripto-1 in ESCC progression and elucidate its association with clinicopathological parameters in patients.

Methods: In this study, Cripto-1 expression in 50 ESCC tissue samples was analyzed and compared to corresponding margin-normal esophageal tissues using quantitative real-time PCR.

Results: Cripto-1 was overexpressed in nearly 40% of ESCC samples compared with normal tissue samples. Significant correlations were observed between Cripto-1 expression and tumor differentiation grade, progression stage, and location (p < 0.05).

Conclusions: Our results indicate that overexpression of Cripto-1 is involved in the development of ESCC. Further assessment will be necessary to determine the role of Cripto-1 cross talk in ESCC tumorigenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346274PMC
April 2017

Expression analysis of matrix metalloproteinase-13 in human gastric cancer in the presence of Helicobacter Pylori infection.

Cancer Biomark 2017 ;18(4):349-356

Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Matrix metalloproteinases (MMPs) can degrade essentially the extracellular matrix (ECM) components. MMPs are important regulators of tumor growth; hence the enzymes are considered as important targets for cancer therapy. MMP-13 is specially activated in gastric cancer and promotes the invasiveness of the primary tumors. Helicobacter Pylori (H.pylori) interacts with gastric epithelial cells and stimulates it to produce MMP-13in vitro.

Objective: The relation between MMP-13 gene expression and clinicopathological characteristics of gastric cancer in the presence of H.pylori infection was investigated in fifty patients.

Methods: The level of MMP-13 gene expression was measured by quantitative Real-time PCR method and was evaluated between two groups of normal and carcinomatous tissues.

Results: The results showed 30% elevation of MMP-13 expression in tumor tissues. H.pylori infection did not have a significant effect on the expression of MMP-13. There was a correlation between gene expression and tumor type (P value = 0.032). In addition, there was a significant correlation between MMP-13 gene expression and tumor stage in intestinal group (P value = 0.023).

Conclusions: Based on the results, it might be concluded that in intestinal group, immune system plays an important role in reducing gene expression. Results also showed over expression (60%) in diffuse group. These findings suggest that using MMP-13 inhibitors in diffuse group might contribute to the control of tumor growth.
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http://dx.doi.org/10.3233/CBM-160127DOI Listing
March 2018

Applying Subtractive Hybridization Technique to Enrich and Amplify Tumor-Specific Transcripts of Esophageal Squamous Cell Carcinoma.

Pathol Oncol Res 2017 Apr 15;23(2):271-279. Epub 2016 Jul 15.

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Bu-Ali Sq, Khorasan Razavi, Mashhad, 9196773117, Iran.

Subtractive hybridization (SH) as an efficient and powerful approach can be applied to isolate differentially expressed transcripts as well as detect of involved mRNAs in various cellular processes, particularly diseases and malignancies. This procedure leads to the enrichment of specific low copy transcripts of tumor cells. Having developed a new approach for SH to isolate tumor specific transcripts, we facilitated discovery of uniquely expressed genes in esophageal squamous cell carcinoma (ESCC). Total RNA was extracted from the fresh tumoral and their adjacent normal tissues, and purified using the Switch Mechanism At the 5' end of Reverse Transcript (SMART) method. Following cDNA synthesis of normal mRNAs using magnetic beads, it was hybridized with tumor mRNAs. To enhance efficiency of subtraction, hybridization was repeated three rounds. Finally, amplification of subtracted tumor-specific transcripts was carried out using in vitro transcription. The subtracted tumoral mRNAs was analyzed quantitatively using real-time PCR for both tumor-specific and housekeeping genes. The subtracted mRNA was confirmed as tumor-specific mRNA pool using RT-PCR and quantitative real-time PCR assessment. The elevated level of tumor-specific transcripts such as MAGE-A4 and CD44 as well as declined copy number of housekeeping genes such as GAPDH, β actin and β2-microglobulin, were confirmed in subtracted tumoral mRNA. The presence of tumor genes was confirmed after the SH procedure. The designed SH method in combination with SMART technique can isolate and amplify high quality tumor-specific transcripts even from small amount of tumor tissues. Removal of common transcripts from the extracted tumoral mRNAs using SH, leads to the enrichment of tumor-specific transcripts. The isolated transcripts are of interest because of their probable roles in ESCC progression and development. In addition, these tumor-specific mRNAs can be applied for future vaccine cancer studies.
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http://dx.doi.org/10.1007/s12253-016-0090-5DOI Listing
April 2017

Evaluation of thymic stromal lymphopoietin (TSLP) and its correlation with lymphatic metastasis in human gastric cancer.

Med Oncol 2015 Aug 15;32(8):217. Epub 2015 Jul 15.

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Bu-Ali square, 9196773117, Mashhad, Iran.

Thymic stromal lymphopoietin (TSLP) is an IL-7-like type 1 inflammatory cytokine that is mainly produced by epithelial cells in the skin, lungs, thymus, and gastrointestinal tract. This cytokine is a master regulator involved in T helper 2 cell-type inflammation immune responses. Various cell types, including T, B, mast, dendritic, and cancer or cancer-associated cells, are activated via TSLP. TSLP expression is also associated with various human cancers and produced by Helicobacter pylori-infected human gastric epithelial cells. TSLP is a multi-functional protein that can act as both an oncogene and a tumor suppressor. The aim of this study was to examine the role of TSLP in the progression of gastric cancer (GC) and its correlation with clinicopathological features in GC patients. Because of the relationship between H. p ylori infection and GC, we also examined gastric tissue specimens for H. p ylori DNA. In this study, fresh tumoral tissues and distant tumor-free samples from 50 GC patients were assessed for TSLP mRNA expression by quantitative real-time PCR. The GC samples were also assessed for H. p ylori DNA using primers specific for H. p ylori 16S rRNA and the UreC genes by PCR. TSLP mRNA was overexpressed in 20 of the 50 (40%) GC samples relative to their corresponding normal tissues. TSLP overexpression was significantly correlated with tumor cell metastasis to lymph nodes. Of the 20 patients with TSLP overexpression, 17 (85.0%) had metastasis to lymph nodes (p = 0.023). In addition, the presence of H. p ylori was confirmed by PCR in 22 of the 50 (44%) cases and 10 (50%) of the 20 TSLP overexpressors. We show that human GC cells produce TSLP and a significant correlation was seen between TSLP overexpression and GC metastasis to lymph nodes. This is the first report to indicate that TSLP may play a role in lymph node involvement in GC patients.
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http://dx.doi.org/10.1007/s12032-015-0653-4DOI Listing
August 2015

Expression analysis of CD44 isoforms S and V3, in patients with esophageal squamous cell carcinoma.

Iran J Basic Med Sci 2015 Apr;18(4):380-4

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: CD44 is a member of the cell adhesion molecules family. Naturally, CD44S, along with CD44V3 influence the cell motility, migration, and adhesion, while in tumor cells they lead to tumor invasion, progression, and metastasis. The purpose of this research is to evaluate the CD44S and CD44V3 expression in Esophageal Squamous Cell Carcinoma (ESCC) and to reveal their correlations with clinicopathological features of patients.

Materials And Methods: Fresh tumoral and distant tumor-free esophageal tissues were obtained from 50 patients with ESCC. Using quantitative real-time PCR, the expression levels of CD44S and CD44V3 were quantified and compared in both groups of cells. The patients had not received any therapeutic interference, such as chemotherapy or radiation, prior to sampling.

Results: Significant overexpression of CD44S and CD44V3 mRNA was observed in 13 (26.0%, P=0.03) and 11 (22.0%, P=0.007) tumor specimens, respectively. The expression of the genes were significantly correlated not only with each other (P=0.0001), but also with differentiation grade of tumor (P=0.033), stage of tumor progression (P=0.003), and depth of tumor invasion (P=0.00). In addition, low level of CD44V3 mRNA expression was attended to be associated with tumor invasion.

Conclusion: There is no correlation between CD44S expression with clinicopathological features of patients; however, simultaneous expression of these genes has an important effect on tumorigenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439453PMC
April 2015
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