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1.
Adv Biomed Res ; 12: 241, 2023.
Article in English | MEDLINE | ID: mdl-38073736

ABSTRACT

Background: Colorectal cancer (CRC) has been often the main reason for dying worldwide. Many factors are implicated in the progress of colorectal carcinoma, one of the chiefs of which is DNA methylation. Insulin-like growth factor-binding protein 3 (IGFBP3) and twist homolog 1 (TWIST1) genes have already been studied and are potential biomarkers for early colorectal diagnosis. Therefore, we designed this research to assess the levels of methylation of these genes in stool specimens of patients with CRC. Materials and Methods: A whole of 80 specimens containing 40 stool specimens from CRC patients and 40 specimens from healthy individuals as a control group was investigated. DNA was extracted using the bisulfate method and methylation of the candidate genes was assessed using methylation-sensitive high-resolution melting method. Differences in the methylation levels between CRC patients and controls were assessed by statistical analysis. Results: Our study showed significant hypomethylation in both IGFBP3 and TWIST1 promoters in patients' samples compared with normal individuals and notably the promoter hypomethylation found in these genes appeared to occur simultaneously (P < 0.0001 and P < 0.0025, respectively). Meantime, hypomethylation of these genes had not any significant connection with medical results. Conclusion: Our results propose that the IGFBP3 and TWIST1 genes' methylation status can serve as potential biomarkers for early CRC diagnosis. However, more studies are still necessary to better appreciate the methylation pattern of these two genes in CRC and to prove their effects on protein levels.

2.
Adv Biomed Res ; 12: 184, 2023.
Article in English | MEDLINE | ID: mdl-37694246

ABSTRACT

Background: There is an emergency need in discovering an efficient profile of molecular biomarkers for early diagnosis of Non-small cell lung cancer (NSCLC). Transcription factors as important groups of regulators that are able to adjust the cell cycles have attracted the attention of most researchers recently. NFATc2 and PPARG are two important factors that have been selected for this project to assess their potential for being a biomarker for NSCLC. Materials and Methods: Here in this study, 50 NSCLC patients were included. During bronchoscopy, which was their routine diagnostic approach, we collected tumoral and marginal normal tissues. After the extraction of the total RNA from the tissues, cDNA was synthesized, and the transcriptional level of NFATc2 and PPARG was examined by quantitative real-time PCR. Subsequently, the data were analyzed by proper statistical analyses. Results: The mRNA expression of NFATc2 and PPARG were down-regulated in biopsy tissues of NSCLC patients compared with their pair marginal tissues (Pvalues were 0.0011 and <0.0001 respectively). Moreover, both of them had significant AUC (area under the curve) in the ROC curve analysis (0.65 for NFATc2 and 0.81 for PPARG, Pvalue <0.05). Conclusion: It appears that mRNA expression of NFATc2 and PPARG possesses the potential to be regarded as a diagnostic or prognostic biomarker for NSCLC.

3.
Bioimpacts ; 12(2): 127-138, 2022.
Article in English | MEDLINE | ID: mdl-35411299

ABSTRACT

Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential. Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals. Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient's exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome. Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.

4.
Cancers (Basel) ; 13(10)2021 May 17.
Article in English | MEDLINE | ID: mdl-34067631

ABSTRACT

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.

5.
Hum Immunol ; 82(9): 668-678, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34020831

ABSTRACT

Inflammation promotes cancer development. To a large extent, this can be attributed to the recruitment of myeloid-derived suppressor cells (MDSCs) to tumors. These cells are known for establishing an immunosuppressive tumor microenvironment by suppressing T cell activities. However, MDSCs also promote metastasis and angiogenesis. Critically, as small non-coding RNAs that regulate gene expression, microRNAs (miRNAs) control MDSC activities. In this review, we discuss how miRNA networks regulate key MDSC signaling pathways, how they shape MDSC development, differentiation and activation, and how this impacts tumor development. By targeting the expression of miRNAs in MDSCs, we can alter their main signaling pathways. In turn, this can compromise their ability to promote multiple hallmarks of cancer. Therefore, this may represent a new powerful strategy for cancer immunotherapy.


Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Neoplasms/etiology , Neoplasms/metabolism , Animals , Biomarkers , Cell Communication , Disease Management , Disease Susceptibility , Humans , Molecular Targeted Therapy , Neoplasms/pathology , Signal Transduction , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
6.
J Gastrointest Cancer ; 52(2): 600-605, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32529394

ABSTRACT

PURPOSE: The role of Lnc_OC1 in gastric cancer (GC) has not been well documented. The very purpose of the present study was to determine not only the expression of Lnc_OC1 in gastric tissues but also its role in the formation of GC. Furthermore, the expression levels of Lnc-OC1 were examined in H. pylori-positive versus H. pylori-negative GC tissues. METHODS: Tumor and adjacent normal tissues were collected from 43 patients with GC. RNA extraction and cDNA synthesis were performed. Then, qRT-PCR was carried out. Finally, an independent sample t test was run to examine the expression level of Lnc_OC1 in a GC and normal tissues using SPSS program. RESULTS: The results revealed a significantly higher expression level of Lnc_OC1 in the GC tissues as compared with the normal tissues (p = 0.0037). The correlations between the expression level of Lnc_OC1 and the clinical features of patients were not statistically significant (p > 0.05). Moreover, the expression of Lnc-OC1 was significantly higher in H. pylori-positive patients as compared with H. pylori-negative patients (p = 0.01). CONCLUSION: The findings of the present study revealed that deregulation of Lnc_OC1 may have a role in the H. pylori-associated pathogenesis of GC. Moreover, a direct association can be speculated between GC formation and Lnc_OC1 expression. The mentioned findings highlight the potential role of Lnc_OC1 as a prognostic biomarker of GC. Hence, further evaluations are required in this respect.


Subject(s)
Biomarkers, Tumor/metabolism , Gastric Mucosa/pathology , Helicobacter Infections/genetics , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Adult , Aged , Biomarkers, Tumor/analysis , Biopsy , Female , Gastric Mucosa/diagnostic imaging , Gastric Mucosa/microbiology , Gastroscopy , Gene Expression Regulation, Neoplastic , Helicobacter Infections/diagnosis , Helicobacter Infections/microbiology , Helicobacter Infections/pathology , Helicobacter pylori/isolation & purification , Humans , Iran , Male , Middle Aged , RNA, Long Noncoding/analysis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/microbiology , Stomach Neoplasms/pathology
7.
Front Immunol ; 11: 613215, 2020.
Article in English | MEDLINE | ID: mdl-33679700

ABSTRACT

Cancer cells escape immune destruction. From this perspective, myeloid-derived suppressor cells (MDSCs), which are immunosuppressive in various cancers including breast cancer (BC), are significant. However, the precise mechanisms are unknown. We isolated HLA-DR-CD33+ MDSCs and CD3+ T cells from BC patients' peripheral blood and healthy donors through MACS and immunophenotyped by flow cytometry. Transfection of short-interfering RNAs and treatment with a TLR7/8 agonist altered pathway activities in vitro. Gene expression was analyzed using qRT-PCR, western blotting, and immunohistochemistry. Our findings showed an association between the progression of BC and increased levels of circulating HLA-DR-CD33+ MDSCs. These cells strongly suppress both autologous and analogous CD3+ T cell proliferation and enter the tumor microenvironment. We also identified increased STAT3 signaling and increased IDO and IL-10 expression in BC-derived MDSCs as immunosuppression mechanisms. Further, STAT3 inhibition and TLR7/8 pathway stimulation reduce the immunosuppressive activity of patient-derived MDSCs on T cells by inducing MDSC repolarization and differentiation into mature myeloid cells. This also alters the expression of critical cytokines and transcription factors in CD3+ T cells and, importantly, reduces breast cancer cells' proliferation. Finally, while chemotherapy is able to significantly reduce circulating MDSCs' level in patients with breast cancer, these MDSCs remained highly T cell-suppressive. We identified a novel molecular mechanism of MDSC-mediated immunosuppression. STAT3 inhibition and TLR7/8 pathway stimulation in MDSCs repolarize and suppress MDSCs from breast cancer patients. This offers new opportunities for BC immunotherapy.


Subject(s)
Breast Neoplasms/immunology , Myeloid-Derived Suppressor Cells/immunology , STAT3 Transcription Factor/immunology , Signal Transduction/immunology , Toll-Like Receptor 7/immunology , Toll-Like Receptor 8/immunology , CD3 Complex/immunology , Cell Differentiation/immunology , Cell Proliferation/physiology , Cytokines/immunology , Female , HLA-DR Antigens/immunology , Humans , Immune Tolerance/immunology , Immunophenotyping/methods , Middle Aged , Myeloid Cells/immunology , T-Lymphocytes/immunology , Tumor Microenvironment/immunology
8.
J Chin Med Assoc ; 82(3): 215-220, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30913118

ABSTRACT

BACKGROUND: Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound vesicles with complex cargoes including proteins, lipids, and nucleic acids. EVs have received significant attention due to their specific features including stability under harsh conditions and involvement in cell-to-cell communication. Circulating EVs and the molecules associated with them are important in the diagnosis and prognosis of cancers. MicroRNAs (miRNAs) are a group of small noncoding RNAs that have a role in regulating gene expression. Current literature shows that circulating miRNAs can be used as noninvasive biomarkers for early detection of cancers. The present study was set to investigate the potential role of serum exosomal miRNA expression levels in colorectal cancer (CRC) patients and evaluate their correlation with clinicopathologic features. METHODS: Exosome-enriched fractions were isolated from the serum of 25 CRC patients and 13 age- and sex-matched healthy controls using a polymer-based precipitation method. During the pilot phase, real-time polymerase chain reaction (RT-PCR) was carried out on 12 CRC patients and eight healthy participants to evaluate the expression difference of 11 candidate miRNAs between CRC patients and tumor free subjects. Finally, the results were validated in a separate group, which was similar in size to the pilot group. The clinicopathologic data were also collected and the relationship between aberrant miRNA expression and clinicopathological parameters were investigated. RESULTS: There were high expressions of exosomal miR-23a and miR-301a in serum samples of CRC patients compared to normal controls in training and validation phases; these differences were not significantly correlated with clinicopathologic features. Receiver operating characteristic curve analysis showed that miR-301a and miR-23a were able to discriminate CRC patients from normal subjects. CONCLUSION: The findings provide evidence on the roles of miR-301a and miR-23a in CRC development and their potential roles as noninvasive biomarkers for early detection of CRC.


Subject(s)
Colorectal Neoplasms/genetics , MicroRNAs/physiology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Exosomes , Female , Humans , Male , MicroRNAs/blood , Middle Aged
9.
Rep Biochem Mol Biol ; 8(3): 244-252, 2019 Oct.
Article in English | MEDLINE | ID: mdl-32274396

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most commonly-diagnosed malignancies throughout the world and the fourth-leading cause of cancer deaths globally. Angiogenesis and the resultant tumor neovascularization is a well-known cancer hallmark. Here we investigated the expression of FLT1 and KDR, the influential genes in angiogenesis regulation, in CRC patients. METHODS: We assessed FLT1 and KDR mRNA expression in 47 CRC samples and matched adjacent noncancerous tissues (ANCT) by quantitative real-time PCR. The Spearmen correlation coefficient and receiver operating characteristic (ROC) curves were also examined. RESULTS: Both genes were expressed at significantly greater levels in CRC tissues than in ANCT (p < 0.05). A significant association was found between KDR expression and disease stage and lymph status in CRC patients. Furthermore, the Spearman correlation demonstrated a moderate correlation between FLT1 and KDR expression in CRC samples. Finally, ROC curve analysis demonstrated that FLT1 had the greatest sensitivity (85.1%), while the greatest specificity was achieved by a combination of the two genes. CONCLUSION: The dysregulated FLT1 and KDR expression, in addition to the observed correlation and ROC curve results, indicate the critical importance of angiogenesis among the cancer pathways in CRC. These data can broaden our current knowledge of angiogenesis in CRC to improve disease diagnosis and patient treatment.

10.
J Cell Physiol ; 234(4): 3515-3525, 2019 04.
Article in English | MEDLINE | ID: mdl-30362521

ABSTRACT

Evading immune destruction is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3+ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA-DR - CD33 + MDSCs in peripheral blood is about 10-fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA-DR - CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient-derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient-derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC.


Subject(s)
Breast Neoplasms/pathology , Myeloid-Derived Suppressor Cells/pathology , Tumor Escape , Tumor Microenvironment , Adult , Aged , Breast Neoplasms/blood , Breast Neoplasms/immunology , Case-Control Studies , Cell Proliferation , Cells, Cultured , Coculture Techniques , Female , HLA-DR Antigens/blood , Humans , Lymphatic Metastasis , Lymphocyte Activation , Middle Aged , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Neoplasm Staging , Phenotype , Sialic Acid Binding Ig-like Lectin 3/blood , T-Lymphocytes/immunology
11.
J Gastrointest Oncol ; 9(5): 791-796, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30505577

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Cofilin is a key regulatory protein in the dynamics of actin filaments. Previous studies have shown cofilin 1's major role in cell migration process and its role in tumor cell migration and invasion. Therefore, cofilin 1 may have the potential as a novel diagnostic tumor marker in various cancers. In this study, differential expression of CFL1 in CRC tissues in comparison with adjacent non-tumor tissues was investigated and the diagnostic value of this protein in CRC was evaluated. METHODS: Synthesized cDNA from extracted RNAs of 30 patients were subjected to qRT-PCR to quantify relative expression of cofilin 1. The relationship between cofilin 1 expression and clinicopathological features of patients were studied too. RESULTS: The study showed significant upregulation of cofilin 1 in CRC tissue samples compared to adjacent non-tumor tissue samples (P<0.05). The receiver operating characteristic curve analysis showed higher area under the curve (0.85). There was no significant correlation between cofilin 1 expression levels and clinicopathological features of patients. CONCLUSIONS: According to the obtained results, cofilin 1 can serve as a candidate for clinically useful diagnostic biomarker or therapeutic target for CRC.

12.
Clin Lab ; 64(5): 871-876, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29739049

ABSTRACT

BACKGROUND: Stromal cell-derived factor-1 (also called CXCL12) and its receptor, CXCR4, have a key role in the pathogenesis and tumorigenesis of various cancers. The aims of the current study were to quantitatively examine the expression of CXCR4 and CXCL12 genes in colorectal cancer and to correlate their expression degree with clinicopathological features. METHODS: Tumor tissue samples were collected from 47 patients with CRC. Total RNA was isolated from resection tissues and real-time PCR analysis was performed to examine mRNA levels of CXCL12 and CXCR4 genes. RESULTS: No significant differences were observed for both CXCL12 and CXCR4 between tumor tissues and the adjacent non-affected tissues, although a borderline significant correlation (p = 0.052) were detected between gene expression of CXCL12 and CXCR4 in tumor tissues. Our results also indicated that there was no significant correlation between expression pattern of CXCL12/CXCR4 and clinicopathological variables. CONCLUSIONS: Our data showed that CXCL12 and CXCR4 are expressed simultaneously in colorectal carcinoma tissues, suggesting that expression of these chemokines and corresponding receptors may play a pivotal role in colorectal tumorigenesis, although it cannot be as a predictive factor for disease progression.


Subject(s)
Biomarkers, Tumor/genetics , Chemokine CXCL12/genetics , Colorectal Neoplasms/genetics , Gene Expression Profiling/methods , Receptors, CXCR4/genetics , Adult , Aged , Carcinogenesis/genetics , Colorectal Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Young Adult
13.
J Clin Med ; 7(5)2018 Apr 27.
Article in English | MEDLINE | ID: mdl-29702569

ABSTRACT

Periampullary tumors are highly malignant masses with poor prognosis. Surgical resection is the only treatment for patients with this disease. The preoperative evaluation of masses is essential to determine the tumor resectability and vascular invasion. The aim of this study was to determine the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) in detecting the resectability of periampullary masses. A cross-sectional study was conducted on patients with a definite diagnosis of periampullary cancer. All the participants underwent an MDCT scan before the surgical pancreaticoduodenectomy. The preoperative results were compared to the intraoperative findings and the diagnostic accuracy was determined based on the sensitivity and specificity of the MDCT. From June 2015 until June 2016, 32 patients with periampullary carcinoma were enrolled in the study. Of 32 masses, one of them considered nonresectable because of the gross vascular invasion in th CT images. After the operation, the overall resectability rate was 81.3%. The sensitivity and specificity of MDCT for tumor resectability was 100% and 16.7%, respectively, with an overall accuracy of 84.4%. To sum up, MDCT had high sensitivity but low specificity in the preoperative evaluation of preampullary carcinomas. The low specificity resulted from the low accuracy of the CT scan in detecting vascular involvement.

14.
Adv Clin Exp Med ; 27(3): 305-311, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29558042

ABSTRACT

BACKGROUND: To date, 4 classes of histone deacetylases (HDACs) have been identified in humans. Class I HDACs are zinc-dependent and NAD+-independent enzymes, and include 4 isoforms closely related to yeast RPD3: HDAC1, 2, 3, and 8. OBJECTIVES: The aims of the study were to quantitatively evaluate the expression of HDAC3 in colorectal cancer (CRC) and to correlate its expression levels with clinicopathological parameters. MATERIAL AND METHODS: We characterized expression patterns of HDAC3 as class I HDAC isoforms in a cohort of 48 CRC patients by quantitative (real-time) reverse transcription polymerase chain reaction (RT-PCR). In addition, the potential relationship between HDAC3 expression levels and clinicopathological parameters in patients suffering from CRC was explored. RESULTS: We found that HDAC3 was highly expressed in colorectal tumors compared to normal colorectal tissues (p < 0.05). Furthermore, we found significant correlations between HDAC3 expression levels and tumor differentiation grades (p < 0.05). CONCLUSIONS: In this prospective study we identified a pronounced HDAC3 expression pattern in CRC. Our findings support an important role of HDAC3 as a complementary molecular marker for existing histopathological diagnostic elements; it might also have applications in prognostic and targeted therapy. Furthermore, HDAC3 can be used as a biomarker to differentiate between tumor borders and margins, and it may also be useful for characterizing field cancerization in CRC.


Subject(s)
Colonic Neoplasms/enzymology , Colorectal Neoplasms/enzymology , Histone Deacetylases/metabolism , Cell Proliferation , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Disease Progression , Down-Regulation , Histone Deacetylases/genetics , Humans , Prognosis , Prospective Studies , Reverse Transcriptase Polymerase Chain Reaction
15.
Drug Res (Stuttg) ; 68(8): 450-456, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29482257

ABSTRACT

BACK GROUND: Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. METHODS: First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. RESULTS: The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. CONCLUSION: The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.


Subject(s)
Adipose Tissue/drug effects , Histone Deacetylase Inhibitors/therapeutic use , Mesenchymal Stem Cells/drug effects , Peptides/therapeutic use , Adipose Tissue/metabolism , Adult , Biomarkers/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , RNA, Messenger/metabolism , S Phase/drug effects , Signal Transduction/drug effects , Up-Regulation/drug effects , Young Adult
16.
Bosn J Basic Med Sci ; 17(3): 255-261, 2017 Aug 20.
Article in English | MEDLINE | ID: mdl-28504924

ABSTRACT

Transcription factors are involved in cell cycle and apoptosis regulation and thus have a key role in the carcinogenesis of different tumors. Nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors are important in the carcinogenesis of colorectal cancer (CRC). In this study, we examined whether the expression of NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC. A total of 47 tumor samples and matched normal tissue margins were collected during surgery from patients with CRC. In addition, three CRC cell lines (HCT119, SW480, and HT29) and healthy cell line were used. After total RNA extraction and cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real-time polymerase chain reaction. The results showed that NFATc2 is overexpressed in the tumor tissues compared with normal tissue margins (p ≤ 0.05). However, the mRNA expression levels of PPARG were not significantly different between the tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as an early diagnostic or predictive biomarker for CRC as well as a therapeutic target, providing that upcoming studies confirm these results.


Subject(s)
Adenocarcinoma/genetics , Colorectal Neoplasms/genetics , NFATC Transcription Factors/biosynthesis , PPAR gamma/biosynthesis , RNA, Messenger/biosynthesis , Adenocarcinoma/pathology , Biomarkers, Tumor/analysis , Carcinogenesis , Cell Line, Tumor , Colorectal Neoplasms/pathology , DNA, Complementary/biosynthesis , DNA, Complementary/genetics , DNA, Neoplasm/biosynthesis , DNA, Neoplasm/genetics , Humans , NFATC Transcription Factors/genetics , PPAR gamma/genetics , RNA, Messenger/genetics
17.
Clin Lab ; 62(3): 463-9, 2016.
Article in English | MEDLINE | ID: mdl-27156337

ABSTRACT

BACKGROUND: Stanniocalcin-1 (STC1) and nuclear factor (NF)-κB subunit p65 transcription factor are involved in various types of human malignancies. The roles of STC1 and NFκB-p65 in colorectal cancer (CRC) are still not fully understood. We investigated expression levels of NF-κB p65 and STC1 and also correlations between STC1 and NF-κB p65 expression and clinicopathological features in CRC. METHODS: Tumor tissue samples were collected from 48 patients with CRC. RT-PCR and Real-time PCR analysis was performed to examine mRNA levels of STC1 and NF-κB p65. RESULTS: The relative mRNA levels of STC1 and NF-κB p65 were significantly higher in tumor tissues than in adjacent mucosa (p = 0.025 and p = 0.044, respectively). The data also showed that STC1 and NF-κB p65 mRNA levels were not significantly associated with clinicopathological characteristics. In addition, there was no association between expression levels of STC1 and NF-κB p65 in tumor samples. CONCLUSIONS: Our data indicate that STC1 and NF-κBp65 is activated constitutively in colorectal carcinoma tissues, suggesting that activation of these factors might play an important role in colorectal tumorigenesis. Future studies should examine STC1 and NF-κBp65 as a molecular target for the treatment of CRC.


Subject(s)
Colorectal Neoplasms/metabolism , Glycoproteins/genetics , Transcription Factor RelA/genetics , Adult , Aged , Colorectal Neoplasms/etiology , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , RNA, Messenger/analysis
18.
Cancer Biomark ; 16(3): 499-505, 2016.
Article in English | MEDLINE | ID: mdl-27062707

ABSTRACT

Colorectal cancer (CRC) is one of the most common cancers in the world; therefore, extensive research is needed to find new molecular therapeutic targets and biomarkers. LncRNA (long non-coding RNA), a new class of non-coding RNAs, has a crucial role in the onset and progression of various cancers including colorectal cancer. Research on lncRNA is still at initial stages and underlying molecular mechanisms of the vast majority of lncRNA have remained unclear. LOC100287225 is one of these novel lncRNAs (long intergenic non-coding RNA) located in the long arm of the chromosome 18. The purpose of this study was to determine the expression of LOC100287225 in colorectal tissue, and its misregulation in CRC patients. Quantitative real-time-PCR (qRT-PCR) was used to investigate the LOC100287225 expression in pairs of tumorous and adjacent tumor-free tissues of 39 colorectal cancer patients. Also, the relationship between the clinicopathology and expression of LOC100287225 was determined. QRT-PCR results revealed that not only is LOC100287225 expressed in the intestinal tissue, but has also been misregulated during tumorigenesis. Moreover, LOC100287225 RNA relative expression levels were significantly lower in tumor tissues compared with adjacent tumor-free tissues (P< 0.001). RNA expression level of LOC100287225 did not show significant correlation with clinical characteristics. In conclusion, our study demonstrated that LOC100287225 misregulation could be a potential target for gene therapy in colorectal cancer.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , RNA, Long Noncoding/biosynthesis , RNA, Long Noncoding/genetics , Biomarkers, Tumor/biosynthesis , Colorectal Neoplasms/pathology , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Prognosis , Real-Time Polymerase Chain Reaction
19.
Clin Lab ; 61(5-6): 475-80, 2015.
Article in English | MEDLINE | ID: mdl-26118178

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. The high frequency of positive families shows the importance of public awareness and screening strategies in those families. Cancer/testis (CT) antigens such as Aurora-C and Survivin are a group of antigens expressed in various tumor types of human cancers. Therefore, the aim of this study was to investigate the expression of Aurora-C and Survivin genes in malignant and normal tissues and their correlation to clinicopathological characteristics. METHODS: Tumor samples were obtained from 33 patients and adjacent non-tumorous tissues from 7 patients were also used as control. Patients were diagnosed with various stages of colorectal cancer. The level of Aurora-C and Survivin genes were evaluated by using real-time quantitative Polymerase Chain Reaction. RESULTS: The expression pattern of Survivin and Aurora-C revealed significant changes in tumor tissues when compared with normal tissues (p < 0.05). Also, these expressions were associated with the grade of disease and tumor size. There was no significant relationship between the expression of Survivin and Aurora-C genes (p > 0.05). CONCLUSIONS: In conclusion, the overexpression of Aurora-C and Survivin genes may play an important role in the development of colorectal cancer and may play a potential role in cancer therapy.


Subject(s)
Aurora Kinase C/metabolism , Carcinoma/metabolism , Colorectal Neoplasms/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Intestinal Mucosa/metabolism , Adult , Aged , Biomarkers/metabolism , Carcinoma/pathology , Case-Control Studies , Colorectal Neoplasms/pathology , Female , Humans , Intestinal Mucosa/pathology , Male , Middle Aged , Survivin , Young Adult
20.
Chem Biol Drug Des ; 85(3): 268-79, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25059576

ABSTRACT

MicroRNAs are small non-coding RNAs that regulate key processes of the stem cells. Although, microRNAs have emerged as powerful regulators of differentiation, few studies have been focused on the post-transcriptional regulation of hepatic differentiation in mesenchymal stem cells (MSCs) by microRNAs. The aim of this study was to evaluate the specific effect of let-7 microRNAs in particular let-7b in hepatic commitment of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The dynamic expression profile of let-7a, b, c microRNAs and two liver-enriched transcription factors (LETFs) HNF4a and HNF6 was studied during in vitro hepatic differentiation of hAT-MSCs. Let-7b was used for transient overexpression and knockdown investigations. It was shown that the expression of LETFs is inversely correlated with those of let-7 miRNAs during differentiation progress (p < 0.05). Inhibition of let-7b caused upregulation of LETFs, an increase in the expression of miR-122 (p < 0.01) emulating the features of functional hepatocytes, and accumulation of hAT-MSCs in the G0 /G1 phase of cell cycle, triggering initiation of hepatic commitment. In conclusion, transient inhibition of let-7b activates hepatic differentiation of hAT-MSCs. The findings of this work might help optimization of in vitro hepatogenic differentiation utilizing microRNAs and hAT-MSCs that could be used for therapeutic purposes.


Subject(s)
Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 6/genetics , Liver/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Up-Regulation , Adipose Tissue/cytology , Adult , Cell Differentiation , Cell Survival , Cells, Cultured , Female , G1 Phase Cell Cycle Checkpoints , Hep G2 Cells , Hepatocyte Nuclear Factor 4/metabolism , Hepatocyte Nuclear Factor 6/metabolism , Hepatocytes/cytology , Hepatocytes/metabolism , Humans , Male , Mesenchymal Stem Cells/cytology , Middle Aged , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/metabolism
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