جستجوی مقالات مرتبط با کلیدواژه "colorectal cancer" در نشریات گروه "زیست شناسی"
تکرار جستجوی کلیدواژه «colorectal cancer» در نشریات گروه «علوم پایه»-
Colorectal cancer is a serious malignancy and the second leading cause of cancer-related deaths worldwide. The incidence and impact of colorectal cancer can be significantly reduced by implementing primary prevention strategies such as practicing early detection through screening. In addition to improved detection, more effective therapeutic strategies, especially those targeting novel pathways, are crucial for advancing treatment and reducing mortality from this disease. We have used bioinformatics analysis to identify potential biomarkers and therapeutic targets for colorectal cancer. Microarray data were extracted from 3 different datasets to identify differentially expressed microRNAs (DEMs), which have important roles in gene regulation and their target genes that are upregulated and downregulated according to microRNA dysregulation. Then, we used enrichment strategies to understand what pathways and gene ontologies these dysregulated genes are involved in. The protein-protein interaction network was structured, and hub genes were detected. In this study, we identified DEMs as potential biomarkers and therapeutic targets and verified their associated genes, which are considered differentially expressed genes (DEGs) in colorectal cancer. The important gene ontologies and related pathways and hub genes ofour final gene sets have also been uncovered.Keywords: Colorectal Cancer, Microrna, Microarray, Biomarker, Hub Gene
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فوزوباکتریوم نوکلئاتوم (F. nucleatum) یک باکتری بی هوازی و گرم منفی و ازنظر ریخت شناسی باسیلی کشیده با انتهای تیز است که متعلق به خانوادهBacteroidaceae است. F. nucleatum فلور طبیعی دهان است؛ اما در برخی بیماری ها در سایر اندام ها نیز وجود دارد. با توجه به نقش F. nucleatum در ایجاد و توسعه بیماری های انسانی، بررسی ویژگی ها و عملکردهای آن بسیار مهم است. برای انجام چنین مطالعاتی باید امکان جداسازی باکتری از نمونه های مختلف وجود داشته باشد؛ اما به دلیل بی هوازی اجباری بودن F. nucleatum، خالص سازی و نگهداری طولانی مدت باکتری ها با مشکلاتی مواجه است. هدف از انجام این مطالعه دستیابی به روشی بهینه به منظور خالص سازی F. nucleatum است تا بتوان زمینه مطالعه دقیق عملکردها و مکانیسم های عمل باکتری به منظور ارائه رویکردهای درمانی جدید برای کنترل یا درمان بیماری های ایجادشده توسط F. nucleatum را برای مطالعات آینده فراهم کرد. با استفاده از paper point با سایز 40 از پاکت های پریودنتال عمیق 16 بیمار با استفاده از محیط انتقالی Tryptic Soy Broth (روش اول) و محیط کشت کلمبیا آگار همراه با گاز پک نوع A و جار بی هوازی (روش دوم) نمونه گیری انجام شد. سپس نمونه ها به منظور تایید حضور F. nucleatum با مشاهدات ماکروسکوپی و میکروسکوپی، تست های بیوشیمیایی، تست PCR و توالی یابی بررسی شدند. نتایج نشان دادند محیط انتقالی Tryptic Soy Broth قادر به حفظ و زنده نگه داشتن باکتری نبوده است و F. nucleatum های خالص شده با انتقال مستقیم آنها به محیط کشت کلمبیا آگار همراه با گاز پک نوع A و جار بی هوازی جداسازی شدند. با توجه به بی هوازی اجباری بودن F. nucleatum، استفاده از محیط انتقالی به علت مواجهه بیشتر باکتری با اکسیژن هوا برای جداسازی کارآمد نیست و روش بهینه برای خالص سازی F. nucleatum دومین روش نمونه گیری است.
کلید واژگان: فوزوباکتریوم نوکلئاتوم, باکتری بی هوازی, فلور سیستم گوارش, پاکت پریودنتال, سرطان روده بزرگIntroductionFusobacterium nucleatum (F. nucleatum) is an anaerobic, gram-negative bacterium, morphologically an elongated bacillus with a sharp end belonging to the Bacteroidaceae. It is the normal flora of the mouth that is present in other organs in some diseases. Given the role of F. nucleatum in the creation and development of human diseases, it is very important to investigate its characteristics and functions. However, due to the obligate anaerobic nature of F. nucleatum, purification and long-term storage of the bacteria pose problems. The aim of this study is to find an optimal method for the purification of F. nucleatum to enable a detailed study of the functions and mechanisms of the bacteria to provide new therapeutic approaches to control or treat the diseases caused by F. nucleatum for future studies.
Materials and MethodsSamples were taken from deep periodontal pockets of 16 patients using 40 size paper points with tryptic soy broth transfer medium (first method) and Columbia agar culture medium with gas pack type A and anaerobic jar (second method). The samples were then examined for the presence of F. nucleatum by macroscopic and microscopic observations, biochemical tests, PCR and sequencing.
ResultsThe results showed that the tryptic soy broth transfer medium was not able to preserve and keep the bacteria alive, and the purified F. nucleatum was isolated by direct transfer to Columbia agar culture medium with gas pack type A and anaerobic jar.
Discussion and ConclusionDue to the obligate anaerobic nature of F. nucleatum, the use of transfer medium is not efficient for isolation due to the greater exposure of bacteria to air oxygen, and the optimal method for purification of F. nucleatum is the second sampling method.
Keywords: Fusobacterium Nucleatum, Anaerobic Bacteria, Periodontal Pocket, Gastrointestinal Flora, Colorectal Cancer -
فعالیت مسیر پیام رسانی Wnt در سرطان کولورکتال به شدت افزایش پیدا می کند. به همین دلیل، پیدا کردن تنظیم کننده های مثبت و منفی جدید برای این مسیر یک استراتژی درمانی و تشخیصی سرطان کلورکتال محسوب می شود. تجزیه و تحلیل بیوانفورماتیکی ما نشان داد که hsa-miR-424 (miR-424) می تواند بعنوان تنظیم کننده ی احتمالی مسیر پیام رسانی Wnt باشد. بر همین اساس، ابتدا سطح بیان miR-424 در بافت های سرطان کولورکتال با جفت های طبیعی مقایسه و نتایج حاصل از RT-qPCR حاکی از افزایش بیان معنی دار miR-424 (p < 0.01) بود. سپس، آنالیزهای مولکولی با تکنیک های Top/Fop Flash و RT-qPCR نشان داد که بیش بیان miR-424 منجر به افزایش فعالیت مسیر Wnt در رده سلولی SW480 می شود. علاوه بر این، از مولکول های کوچک IWP-2 و PNU-74654 برای مهار مسیر پیام رسانی Wnt استفاده و بیش بیان miR-424 حاکی از این بود که miRNA ی مذکور تاثیر خود را در سطح تخریب کمپلکس β-کاتنین اعمال می کند که بدین منظور سنجش دوگانه ی لوسیفراز miR-424 با APC انجام و برهمکنش آنها تائید شد. به طور کلی، نتایج ما miR-424 را بعنوان تنظیم کننده ی مثبت مسیر پیام رسانی Wnt معرفی کرده و miRNA ی مورد نظر می تواند یک پیش آگهی احتمالی برای سرطان کورکتال باشد.
کلید واژگان: مسیر پیام رسانی Wnt, سرطان کولورکتال, Mir-424, سنجش دوگانه ی لوسیفرازThe activity of Wnt signaling pathway is increased in colorectal cancer. For this reason, finding new positive and negative regulators for this pathway is a treatment and diagnostic strategy of colorectal cancer. Our bioinformatics analysis indicated that hsa-miR-424 (miR-424) could be a possible regulator of the Wnt signaling pathway. Accordingly, the expression level of miR-424 in colorectal cancer tissues was elevated compared with normal pairs and the results of RT-qPCR showed a significant increase in miR-424 expression (p < 0.01). Then, molecular analyzes using Top/Fop Flash and RT-qPCR techniques indicated that miR-424 overexpression leads to increased Wnt pathway activity in the SW480 cell line. In addition, the small molecules IWP-2 and PNU-74654 were used to inhibit the Wnt signaling pathway, and the miR-424 overexpression suggested that exert its effect on the level of β-catenin complex degradation. Then, dual-luciferase assay validated the interaction between miR-424 and APC. Overall, our results suggest miR-424 is a positive regulator of the Wnt signaling pathway, and it could be a possible prognosis for colorectal cancer.
Keywords: Wnt Signaling Pathway, Colorectal Cancer, Mir-424, Dual-Luciferase Assay -
To investigate the effects of thymidylate synthase (TS) 3'UTR genotype on promotor methylation of tumor-related genes in 22 patients with sporadic colorectal cancer (CRC) from southern Iran. We evaluated the correlations of TS 3'UTR genotype with promoter methylation of hTERT, hMLH1, MSH2, MMP2, CDH1, p14, p16, and p21 genes in CRC patients. The polymorphism of TS 3′UTR was evaluated through mutagenically specific PCR. The genes promoter methylation was determined using methylation-specific PCR. For 10 patients, the gene expression profile of epigenetic regulating enzymes, histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), was also examined in both tumor and normal adjacent tissues by quantitative real time PCR. There was a significant association between the hMLH1 methylation and age of patients (P= 0.039) and also between MSH2 methylation and tumor site (P= 0.036). There was insignificant association between gene-specific methylation and TS 3′UTR genotype. However, all polymorphic genotypes of TS were associated with higher methylation of hMLH1 and CDH1 and lower methylation of MSH2. The -6bp/+6bp (heterozygous mutant) and [-6bp/+6bp, +6bp/+6bp] (homozygous mutant) genotypes resulted in higher methylation of p16, and -6bp/+6bp and [-6bp/+6bp, +6bp/+6bp] genotypes were correlated with lower methylation of MMP2. The overexpression of epigenetic enzymes, HDACs and DNMTs, was also demonstrated. There was no association between DNMTs transcript levels and gene-specific hypermethylation. The polymorphic TS genotypes, especially -6bp/+6bp, could affect methylation frequencies of studied genes. Moreover, promoter methylation status was not dependent on DNMTs gene expression. Large sample size studies may contribute to validate these findings.Keywords: Thymidylate synthase, Methylation, DNA methyltransferase, Histone deacetylase, Colorectal cancer
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Colorectal cancer (CRC) is a significant public health burden, accounting for approximately 10% of all new cancer cases worldwide, making it the world’s third most deadly cancer. The causes of CRC are complex and environmental factors play a stronger role than genetic factors. The gut microbiome has been linked to several bowel cancers, such as CRC. The present study aimed to estimate differential abundance analysis of CRC versus HC groups of the colorectal microbiome. Biopsy samples were taken from the normal mucosa of 13 healthy controls (HC) and the tumor of 17 patients with CRC during colonoscopy. The microbiome of tumor tissue and normal mucosa was evaluated by 16S rRNA gene amplicon sequencing. Differential abundance analysis of CRC versus HC groups showed that Enterobacteriaceae, Bacteroides fragilis, Prevotella, Fusobacterium, Leptotrichia, Akkermansia muciniphila, Streptococcus, and Parabacteroides have drastic fold changes (P ≤ 0.05). A heat map and dendrogram of the 20 ascending operational taxonomic units (OTUs) based on the FDR (False Discovery Rate) p-value were constructed to visualize the similarity between CRC and HC samples. The significant difference in the differential abundance of bacteria taxa in CRC versus HC groups indicates that these bacteria can be important pathogens in the development and progression of CRC.
Keywords: Colorectal Cancer, Microbiome, 16S rRNA, Fusobacterium, Differential abundance analysis -
BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related mortalities across the globe. Accumulating evidence shows that individuals having sleep disorders such as insomnia are at high risk of developing CRC, yet the association of sleep disorders with CRC risk is still unclear. Here, we investigated the potential molecular connections between CRC and insomnia using integrative in silico approaches.ObjectiveThis study aims to explore the potential molecular connections between CRC and insomnia utilizing integrative in-silico methodologies.MethodsGene expression microarray datasets for CRC and insomnia samples were retrieved from the NCBI-GEO database and analyzed using R. Functional enrichment analysis of common differentially expressed genes (DEGs) was performed by the g:Profiler tool. Cytoscape software was used to construct a protein-protein interaction network and hub gene identification. Expression profiles of hub genes in TCGA datasets were also determined, and predicted miRNAs targeting hub genes were analyzed by miRNA target prediction tools.ResultsOur results revealed a total of 113 shared DEGs between CRC and insomnia datasets. Six genes (HSP8A, GAPDH, HSP90AA1, EEF1G, RPS6, and RPLP0), which were also differently expressed in TCGA datasets, were prioritized as hub genes and were found to be enriched in pathways related to protein synthesis. hsa-miR-324-3p, hsa-miR-769-3p, and hsa-miR-16-5p were identified as promising miRNA biomarkers for two diseases.ConclusionsOur in silico analysis provides promising evidence of the molecular link between CRC and insomnia and highlights multiple potential molecular biomarkers and pathways. Validation of the results by wet lab work can be utilized for novel translational and precision medicine applications to alleviate the public health burden of CRC.Keywords: Insomnia, Colorectal Cancer, In Silico Analysis, Hub Genes, Pathway Analysis
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Colorectal cancer (CRC) is one of the most dangerous cancers that occur in colon or rectum epithelial cells. Some studies disclose that CRC not only is the third most deadly cancer globally, but also, it is increasing every year. Genetic factors and environmental conditions are two main agents that participate in CRC progress. Besides, other factors, including chronic inflammation, diet, family history, and lifestyle have crucial effects on the progress of CRC. One of the most common genetic factors is microRNAs (miRNA). These molecules are a class of non-coding single-stranded RNAs with 21-23 nucleotides that play critical roles in modulating gene expression. Some studies have shown that miRNAs have contributed to the initiation and development of CRC. For example, miR-21 has played an oncogenic role in the onset of adenoma in colon tissue and miR-145 can suppress CRC by hindering cancer cell migration and invasive. However, comprehensive investigations are required to detect miRNAs in CRC for inhibition and decline of death-related CRC disease in screening programs. Moreover, the application of miRNA to target specific genes of cancer cells can help to prepare novel micro or nano formations such as micelles, carbon nanotubes, dendrimers, peptides nanocarriers, micelles, and mesoporous silica nanocarriers based on these molecules. Therefore, in this review, we have elucidated both the oncogenic and anticancer functions of important types of miRNA in CRC
Keywords: Colorectal Cancer, Genetics Factors, Adenoma, Mir-21, Mir-145, Carbon Nanotubes, Dendrimers -
The aim of this study is to evaluate the potential toxicity of acetonic and methanolic extracts derived from the Euphorbia esula L. plant on various cell lines of human colorectal cancer (HCT116 and SW480), human embryonic kidney normal cells (HEK293), Artemia salina larvae, and its bactericidal effects. The cytotoxic effect of E. esula extracts on cell lines was performed using the MTT assay. In vitro toxicity and biocompatibility of extracts were also evaluated on A. salina and red blood cells by hemolysis test, respectively. The ability of the extracts to inhibit bacterial growth was examined by using the disc diffusion method, as well as the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the microtiter broth dilution method. Results showed acetonic extract contains the highest concentration of flavonoid (16.17 µg Qu/mg) and phenol (34.84 µg GA/mg) compared to methanolic extract. The anti-proliferative effects of acetonic extract had the highest effect on HCT116 and HEK293 with IC50 of 64.80 µg/mL and 47.82 µg/mL at 72h, respectively. The hemolysis degree of the methanolic extracts was <2% at 400 μg/mL. LC50 for the acetonic and methanolic extracts exhibited moderate and low toxicities on the brine shrimp larvae, with LC50 of 381.969 µg/mL and 1905.77 µg/mL, respectively. The bactericidal effect of 50 mg/mL acetonic extracts showed a clear zone inhibitory growth on Staphylococcus aureus and Klebsiella pneumoniae with 34 mm and 35mm at the MIC and MBC values of 1000 and 2000 mg/mL, respectively. These findings could help to elucidate the anti-tumor, anti-bacterial, and toxic properties of E. esula extracts.Keywords: Antibacterial assay, Artemia salina, Brine shrimp, Colorectal cancer, Euphorbia esula, Selectivity index
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Epithelial-to-mesenchymal transition (EMT) plays a critical role in colorectal cancer (CRC) metastasis. In the present study, we evaluated the effects of annexin A5 (ANXA5) overexpression on invasiveness as well as the expression of genes involved in EMT of HCT 116 cell line. PCMV6-AC-IRES-GFP plasmid harboring ANXA5 cDNA was constructed. HCT 116 cell line was transfected with recombinant plasmids using Lipofectamine 3000. Fluorescent microscopy was used to determine the efficiency of plasmid transfection. Cell viability was determined using the MTT assay. HCT 116 cell migration was evaluated using wound healing assay and transwell migration assay. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of genes involved in EMT. The results of RT-qPCR showed overexpression of ANXA5 compared to the control group. ANXA5 overexpression had no significant effects on cell viability but significantly decreased the rate of wound closure in the wound healing assay as well as the number of migrated cells in transwell assay. Furthermore, ANXA5 overexpression decreased the expression of N-cadherin, Snail, Slug, MMP-2, and MMP-9 while the expression of E-cadherin increased following ANXA5 overexpression. However, VEGF expression did not significantly change after ANXA5 overexpression. Results of the present study suggest that ANXA5 overexpression might have inhibitory effects on the metastasis of CRC through modulating the expression of EMT- related genes.Keywords: Colorectal cancer, Epithelial to mesenchymal transition, Metastasis, ANXA5
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هدف
سرطان کولورکتال (CRC)، دومین عامل مرگ و میر در دنیا محسوب می شود و نانوذرات ترانوستیک با قابلیت درمانی و تصویربرداری به صورت همزمان به عنوان بسترهای درمانی و تشخیصی در نظر گرفته می شوند.
مواد و روشها:
در این مطالعه، نانوذرات متخلخل مغناطیسی (SPION-MSNs) با یک طراحی ویژه، به منظور عدم آزادسازی داروی شیمی درمانی 5-FU در مجاورت سلول های سالم سنتز شده و توسط کنترل گرهای دریچه ای طلا، رهایش دارو مهار شد. در گام بعد، بهکمک پلیمر دوسر عملکردی پلی اتیلن گلیکول (PEG) با هدف افزایش زیستسازگاری، سطح بیرونی نانوذرات پوشانده شده و نانوذرات غیر هدفمند سنتز شد. به علاوه، به منظور دستیابی به رویکرد درمانی فعال و تحویل انتخابی داروی 5-FU، سطح بیرونی نانوذرات مجهز به آپتامر EpCAM شد. در ادامه، خصوصیات فیزیکی و شیمیایی نانوذرات سنتز شده، ارزیابی شده و فعالیت ضدسرطانی آن ها در محیط برون تنی مورد بررسی قرار گرفت.
نتایجSPION-MSNs ساختار کروی به همراه توزیع یکنواخت را نشان دادند. داروی شیمیدرمانی 5-FU با موفقیت داخل منافذ باز نانوذرات سیلیکا بارگذاری شد و نتایج نشان داد که رهایش داروی 5-FU از نانوذره، وابسته به pH می باشد. نانوذرات هدفمند با اندازه ی حدود nm 78 و بار سطحی منفی سنتز شدند. مطالعات برون تنی سمیت معنیدار نانوذرات هدفمند را در برابر سلول های بیان کننده ی گیرنده ی EpCAM نشان داد و این سمت بر روی سلول های CHO بسیار ناچیز بود. این نتایج حاکی از کارآیی موثر اتصال آپتامر EpCAM در هدف گیری اختصاصی سلول های سرطانی می باشد.
نتیجه گیرینتایج حاصل از این مطالعه نشان داد که این نانوذرات هدفمند، می توانند به عنوان یک نانوبستر ترانوستیک امیدوارکننده جهت درمان CRC در نظر گرفته شوند.
کلید واژگان: سرطان کولورکتال, سامانه ی حمل دارو, کنترل رهایش دارو, درمان هدفمند, ترانوستیک, نانوذرات سیلیکای متخلخل مغناطیسیAimCancer is a global concern and colorectal cancer (CRC( accounts for the second most common cause of cancer related death in the world. Nanotechnology could enhance the effectiveness of chemotherapy as a common therapeutic approach through development of smart nanoparticles (NPs). In this context, theranostic nanoparticles with both imaging and therapeutic potentials are considered as promising platforms in diagnosis and treatment of advanced cancers.
Materials & MethodsHere, we designed and synthesized magnetic mesoporous silica nanoparticles (SPION-MSNs) in which release of 5-fluorouracil (5-FU) at physiological conditions was inhibited with pH-responsive gold gatekeepers. Heterofunctional polyethylene glycol (PEG) polymer was then conjugated onto the outer surface of nanoparticles and non-targeted nanoparticles were successfully synthesized. In order to achieve active and specific targeting, non-targeted nanoparticles were armed with an epithelial cell adhesion molecule (EpCAM) aptamer (Apt) for selective drug delivery of 5-FU to colorectal cancer cells. Finally, the physicochemical properties of NPs including functional groups, surface charge and their size were fully characterized with Fourier transform infrared (FTIR) spectra and dynamic light scattering (DLS) in each step. Moreover, morphology and homogeneity of SPION-MSNs were evaluated using field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HR-TEM) and atomic force microscopy (AFM). The cumulative release of 5-FU from nanoparticles was compared in buffer solutions with two different pH values (pH 7.4 and 5.4). In the final step, anti-cancer potential and cytotoxicity of free 5-FU, non-targeted, and targeted nanoparticles were assessed on human colorectal adenocarcinoma HT-29 cells and Chinese hamster ovary cells.
ResultsCore-shell NPs, SPION-MSNs, were successfully prepared and the FTIR spectra showed specific peaks at the surface of nanoparticles. Obtained results from DLS measurements showed that the synthesized formulation had negative charges with size of 20 nm. Moreover, the morphology of SPION-MSNs indicated spherical shape with uniform distribution. After introducing amine groups, the surface charge was shift to positive and the two bands at 2965 and 1,560 cm−1 in the FT-IR spectrum were appeared and assigned to CH2-CH2 and N-H groups, respectively. The results indicated, 5-FU was encapsulated in the open pores of MSNs and the encapsulation efficiency (EE%) and drug loading capacity (LC%) were about 98% and 49%, respectively. The release of 5-FU from NPs showed pH-dependent manner, with an initial rapid release (within 6 h) followed by a sustained release for 96 h at pH 5.4. interestingly, the cumulative release of 5-FU was about 3.9% in neutral medium over 96 h. the results supported the Intelligent release of cargoes from theranostic nanoparticles. At the final step, targeted nanoparticles were successfully synthesized with a final size diameter of 78 nm and negative surface charge. In vitro results demonstrated higher cytotoxicity and anti-cancer property of targeted nanoparticles against EpCAM-positive HT-29 cells as compared to the EpCAM-negative CHO cells, confirming the effectiveness of aptamer as a targeting ligand.
ConclusionThese findings suggest that application of the targeted formulation can be considered as a promising theranostic platform for EpCAM-positive CRC cells. However, further experiments are required before it can be practiced in the clinic.
Keywords: Colorectal cancer, Drug delivery system, Controlled release, Targeted therapy, theranostic, Magnetic mesoporous silica nanoparticles -
This study was designed to investigate the value of red blood cell distribution width (RDW), prealbumin (PA), platelet to lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in the diagnosis of colorectal cancer. There was 500 colorectal cancer (CRC) patients, 250 polyps of colorectal patients, and 250 healthy volunteers performed to complete blood counts with automated differential counts. The differences in RDW, PA, PLR, and CEA among the three groups were statistically significant (P<0.05). RDW, PA, PLR, CEA, and RDW+PA+PLR+CEA all had a high accuracy rate for the diagnosis of colorectal cancer. RDW, PA, PLR, CEA, and RDW+PA+PLR+CEA were divided into high-expression groups and low-expression groups according to ROC cut-off values. Age was statistically different between the high and low groups in RDW, PA, and CEA. M staging was statistically different between high and low groups in CEA, and PLR. T staging was statistically different between high and low groups in PA, CEA, PLR, and RDW+PA+CEA+ PLR. N staging and blood vessel invasion were statistically different between the high and low groups in CEA. TNM staging was statistically different between high and low groups in PA, CEA, PLR, and RDW+PA+CEA+PLR. Perineural invasion was statistically different between the high and low groups in PA and CEA. The number of lymph node metastases was significantly and positively correlated with CEA. CEA and PLR were independent risk factors for the TNM staging. And they had good diagnostic efficacy for the TNM staging of colorectal cancer.Keywords: Colorectal Cancer, Carcinoembryonic Antigen, Diagnosis, Prealbumin, Platelet To Lymphocyte Ratio, Red Blood Cell Distribution Width
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Despite various treatment options available for colorectal cancer, the survival rates for patients remain low. This study investigated the effects of hyperthermia and Ibuprofen on human colorectal adenocarcinoma cells (HT-29) viability, proliferation, and gene expression related to tumor suppression, Wnt signaling pathways, proliferation, and apoptosis The cells were exposed to hyperthermia at 42 or 43°C for 3 hours or Ibuprofen at different concentrations (700-1500 μM), and the effects were analyzed through MTT assay, trypan blue staining, and quantitative Real-time PCR. The study used quantitative Real-time PCR (qRT-PCR) to evaluate the effect of hyperthermia and Ibuprofen on the expression of various genes associated with tumor suppression, proliferation, Wnt signaling pathway, and apoptosis. The results revealed that hyperthermia caused a minor reduction in the viability and proliferation of HT-29 cells, but the decrease was not statistically significant (P<0.05). On the other hand, Ibuprofen caused a concentration-dependent decrease in the viability and proliferation of HT-29 cells. Both hyperthermia and Ibuprofen reduced the expression of WNT1, CTNNB1, BCL2, and PCNA genes, and increased the expression of KLF4, P53, and BAX genes. However, the changes in gene expression were not statistically significant in cells treated with hyperthermia. The findings suggest that Ibuprofen is more effective in reducing cancer cell proliferation by promoting apoptosis and inhibiting the Wnt signaling pathway than hyperthermia, which had some impact but was not statistically significant. The study highlights the potential of Ibuprofen as a targeted therapy for colorectal cancer.Keywords: Colorectal cancer, Hyperthermia, HT29 Cells, Ibuprofen, Wnt Signaling Pathway
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Colorectal cancer (CRC) is the third cause of cancer death globally. New evidence suggests that colorectal microbiome dysbiosis may be involved in the cause and development of CRC. This study aimed to investigate the differences in bacterial composition and diversity between CRC samples and healthy individuals (HC) based on age through high-throughput 16S rRNA sequences. Biopsy samples were obtained from 17 CRC patients and 13 healthy controls (HC). We analyzed the colon microbiome composition and diversity by alpha and beta diversity. The results showed that colon microbial diversity was significantly higher in the CRC-32-50 and CRC-50-75 groups than in the healthy controls. Still, on the other hand, the diversity of group HC-32-50 was lower than all other groups. Prevotella, Faecalibacterium, Fusobacterium, and Akkermansia were overrepresented in the CRC-32-50, while Bacteroides were in the HC-32-50 group. Our results showed that the diversity and composition of the two groups, HC-32-50 and CRC-32-50, were significantly different. These findings suggest that dysbiosis is more common in CRC patients under the age of 50 than in those over 50. Further studies on the colon microbiome are needed to determine the diversity and composition of the colon microbiome in age-related colorectal cancer to complete our understanding of the impact of the microbiome on the progression of colon cancer.
Keywords: Microbiome, Colorectal Cancer, 16S rRNA sequencing, Diversity, Dysbiosis -
هدف
هدف از این مطالعه مقایسه میزان بیان LncRNA CRNDE در نمونه های توموری و نرمال افراد مبتلا به سرطان روده بزرگ بهروش Real Time-PCR بود.
مواد و روشهاتعداد 20 نمونه از بافت توموری افراد مبتلا بهسرطان روده بزرگ و 20 نمونه بافت غیرتوموری همان افراد از بانک تومور مجتمع بیمارستانی امام خمینی دانشگاه علوم پزشکی تهران تهیه شد. پس از استخراج RNA کل از بافت های سرطانی و نرمال، DNA مکمل سنتز و با استفاده از روش Real Time-PCR سطوح بیان LncRNA CRNDE در آن ها مورد بررسی قرار گرفت. برای تجزیه و تحلیل آماری نتایج از روش ANOVA یکطرفه و تست Tukey استفاده شد.
نتایجنتایج بهدست آمده نشاندهنده افزایش دو برابری بیان LncRNA CRNDE در هر 20 نمونه سرطان روده بزرگ در مقایسه با نمونه های نرمال بود.
نتیجه گیریباتوجه بهافزایش قابل توجه بیان LncRNA CRNDE در سلول های سرطانی نسبت به سلول های نرمال، می توان از حضور این LncRNA در خون به عنوان یک نشانگر زیستی برای تشخیص زودرس و غیر تهاجمی، سرطان روده بزرگ استفاده کرد.
کلید واژگان: سرطان روده بزرگ, رونوشتهای غیر کدکننده طویل, CRNDE, نشانگر زیستیAimThis study aimed to compare the expression levels of LncRNA CRNDE in malignant colorectal tumorsand adjacent normal tissues of patients by Real Time-PCR.
Material and Methods20 pairs of colorectal tumors and adjacent normal tissue specimens were prepared from the tumor bank of Imam Khomeini Hospital in Tehran University of Medical Sciences. After total RNA extraction from cancerous and normal tissues, cDNA was synthesized, and the expression levels of LncRNA CRNDE were examined using the Real Time-PCR method. A one-way analysis of variance (ANOVA) and Tukey's HSD test used for statistical analysis of results.
ResultsThe results showed a two-fold increase in LncRNA CRNDE expression in all 20 colorectal cancer samples compared with the normal cells.
ConclusionAccording to the significant increase of the LncRNA CRNDE expression in cancer cells relative to normal cells and its presence in the bloodstream, this LncRNA maybe used as a non-invasive diagnostic biomarker for early detection of colorectal cancer.
Keywords: Long noncoding RNA, CRNDE, Colorectal cancer, Biomarker -
پیشینه مطالعه و هدف
سرطان کولورکتال یکی از شایع ترین سرطان ها است و تغییرات اپی ژنتیکی به عنوان هدف درمانی مورد توجه قرار گرفته است. سدیم بوتیرات با هایپر-استیلاسیون اجزا کروماتین قادر به تغییر در بیان ژن ها است. هدف از این مطالعه بررسی تاثیر سدیم بوتیرات بر روی بیان ژن های Bax و Bcl-2 می باشد.
روش مطالعهرده سلولی Caco-2 با غلظت های مختلف سدیم بوتیرات (25 الی 150 میلی مولار) براساس غلظت IC50 در دو بازه زمانی 24 ساعت و 48 ساعت تیمار شد. بیان ژن های Bax و Bcl-2 توسط تکنیک qReal-Time PCR به روش ΔΔCT -2 اندازه گیری و نسبت Bcl-2/Bax مورد ارزیابی قرار گرفت.
نتایجنتایج نشان داد سدیم بوتیرات باعث افزایش بیان ژن Bax و کاهش بیان ژن Bcl2 در سلول های تحت تیمار در مقایسه با گروه کنترل شد که از نظر آماری معنی دار می باشد (p <0.05). غلظت 25 میلی مولار در بازه زمانی 48 ساعت تیمار موثرترین دوز انتخاب گردید. همچنین نسبت Bcl-2/Bax در همین غلظت کاهش معنی داری را نشان داد.
نتیجه گیریسدیم بوتیرات با کاهش نسبت بیان Bcl-2/Bax باعث القا آپوپتوز در سلول های سرطانی می شود. این ماده می تواند به عنوان هدف درمانی استفاده شود ولی نیاز به بررسی بیشتر می باشد.
کلید واژگان: سرطان کولورکتال, سدیم بوتیرات, رده سلولی Caco-2, BAX, BCL-2Introduction and AimColorectal cancer is one of the most common cancers. Epigenetic change has been considered by many scientists as a therapeutic target. Hyper acetylation of chromatin components by sodium butyrate can alter gene regulation. This study aims to investigate the effects of sodium butyrate on Bax and Bcl-2 gene expression.
MethodsCaco-2 cell line was treated with different concentrations of sodium butyrate (25 mM to 150 mM) based on IC50 concentration in two time periods of 24 hours and 48 hours. Bax and Bcl-2 gene expression were measured by qReal-Time PCR technique and Bcl2/Bax ratio was evaluated.
ResultsThe results showed that sodium butyrate increased the expression of Bax gene and decreased the expression of Bcl-2 gene in treated cells compared to the control group, which was statistically significant (p < /em> <0.05), and 25 mM was selected as the most effective dose after 48 hours of treatment. Also, the Bcl-2/Bax ratio at the same concentration showed a significant decrease
ConclusionSodium butyrate induces apoptosis in cancer cells by reducing the expression ratio of Bcl-2/Bax. It can be used as a therapeutic target but needs further investigation.
Keywords: Colorectal Cancer, Sodium butyrate, Caco-2 cell line, BAX, Bcl2 -
مجله سلول و بافت، سال دهم شماره 4 (زمستان 1398)، صص 202 -213هدف
با توجه به پیشرفت و شیوع سرطان، تلاش بر این است که ترکیبهای جدید در جهت سرکوب تومور و همراه با سمیت کمتر باشند. طی دهه های گذشته به منظور توسعه سیستم انتقال دارو برای غلبه برمحدودیتهای داروهای رایج مورد استفاده در درمان بیماریها، نانو تکنولوژی بسیار مورد توجه قرار گرفته است.
مواد و روشهالذا در این مطالعه برای اولین بار نانوذرات ساماریوم با استفاده از روش شیمی سبز و به کمک عصاره زنجبیل سنتز شدند. سپس خصوصیات فیزیکوشیمیایی نانوذرات سنتزی با استفاده از تکنیک پراکنش نور دینامیکی (DLS)، طیف سنجی مادون قرمز (FT-IR) و میکروسکوپ الکترونی روبشی FE-SEM بررسی شد. در نهایت خواص ضدسرطانی و سمیت سلولی نانوذرات ساماریم در مقابل سلولهای سرطانی کولون رده سلولی HCT116 پس از 24 و 48 ساعت تیمار توسط آزمون رنگ سنجی تترازولیوم (MTT Assay) بررسی شد.
نتایجنتایج مطالعات پراکنش دینامکی نور و همچنین مطالعات مورفولوژیکی به کمک میکروسکوپ الکترونی روبشی بیانگر سنتز ناانوذرات کروی و همگن با ابعاد حدود 70 نانومتر میباشد. آزمون بقای سلولی میزان Cc50 (غلظتی از ترکیب که 50 درصد مرگ را در سلولهای سرطانی القا میکند) نانوذرات ساماریوم بر روی رده سلولی HCT116 در مدت زمان 24 و 48 ساعت بهترتیب 90 (1/23 میکروگرم بر میلیلیتر) و 81 میکرومولار (7/20 میکروگرم بر میلیلیتر) نشان داده است.
نتیجه گیریبا توجه به یافته های بهدست آمده، به نظر میرسد نانوذرات ساماریوم سنتز شده به کمک عصاره گیاه زنجبیل میتوانند به عنوان دارویی جدید در درمان سرطان کلورکتال در آیندهای نزدیک استفاده شوند.
کلید واژگان: سرطان کولورکتال, نانوذرات ساماریوم, گیاه زنجبیل, شیمی سبزAimIn the past decades, nanotechnology has received much attention in order to develop new drug delivery systems to overcome the limitations of routine drugs in the treatment of diseases. Nanotechnology offers very useful applications in the diagnosis and treatment of cancer, as nanomaterials can penetrate into body tissues at the cellular and molecular levels.
Materials and methodsIn the present study, samarium nanoparticles were synthesized by the extract of ginger using green chemistry synthesis method. The size of the synthesized nanoparticles was investigated by dynamic light scattering (DLS) technique and formation of new functional groups was investigated by FT_IR technique. The morphology of the nanoparticles was determined using FE-SEM scanning electron microscopy. Finally, the cytotoxicity and anticancer activity of samarium nanoparticles were studied against human colorectal cancer cell line of HCT116 after 24 and 48 hours incubation times using tetrazolium colorimetric assay (MTT assay).
ResultsDynamic light scattering data in agreement with Fe-SEM data revealed the formation of globular nanoparticles of 60 nm. Cell survival assay showed Ic50 values (the concentration of the compound that induces 50% death in cancer cells) of 90 (equal to 23.1 mg/ml) and 81 μM (equal to 20.7 mg/ml) of samarium nanoparticles on HCT116 cell line after 24 and 48 hours incubation times, respectively.
ConclusionIt is concluded that the newly green synthesized samarium nanoparticles with anticancer activity might be a good candidate for colon cancer therapy.
Keywords: Colorectal cancer, Samarium Nanoparticles, Ginger Plant, Green Chemistry -
سرطان روده بزرگ یا کولورکتال (CRC) یکی از شایع ترین بدخیمی های کشنده است که در اثر عوامل محیطی و ژنتیکی ایجاد می گردد. نظر به فراوانی رو به افزایش CRCدر سراسر جهان و به ویژه در ایران، اهمیت تحقیقات بر روی CRC به طور گسترده تری مشخص می گردد. مطالعه اخیر به منظور شناسایی بیومارکر جدید، بر روی مسیر های ملکولی دخیل در کارسینوژنز سرطان روده، که تشخیص و درمان سرطان را بهبود بخشد، متمرکز شده است. سرطان روده بزرگ حاصل دیسپلازی در زواید اولیه روده که به نام پولیپ شناخته می شوند، ایجاد می گردد، این زواید اولیه از لحاظ مورفولوژیکی و مکانیسم های ملکولی و توانایی ایجاد سرطان روده ناشناخته و متفاوت می باشند. هدف از این مطالعه بررسی میزان بیان ژن CUL3 در پولیپ ها و سرطان کولورکتال می باشد. در این مطالعه مقطعی، 208 نمونه بیوپسی بافتی کولورکتال از جمله 34 نمونه بافت توموری ، 60 ضایعه پیش سرطانی با بافت مجاورشان و 20 نمونه بافت نرمال جمع آوری شد. بیان ژن CUL3 با روش Real time PCR مورد بررسی قرار گرفت. اختلاف معنی داری در میزان بیان mRNA ژن CUL3 بین بافت های پولیپ و نمونه های مجاورشان مشاهده نشد (35/0 = p). نتلیج ما از نظر آماری تفاوت معنی داری در بیان ژن CUL3 بین بافت های توموری و نمونه های نرمال مجاورشان (89/0 = p) و همچنین بین گروه های توموری و پولیپی نشان نداد (48/0 = p). CUL3ممکن است از طریق تحریک تخریب پروتیوزومال سرکوبگرهای مختلف تومورها و یا انکوژن ها نقش مهمی در تنظیم سرطان و پیشرفت CRC ایفا کند. مطالعات بر روی سوبستراهای اثر پذیر توسطCUL3 در سرطان کولورکتال حایز اهمیت است.
کلید واژگان: سرطان کولورکتال, پولیپ, CUL3, کولون, رکتومThe bowel or colorectal cancer (CRC) is one of the most common fatal malignancies caused by environmental and genetic factors. The phenomenal growth in the number of people with CRC worldwide, especially in Iran highlights the importance of research on CRC.The current study focused on molecular pathways involved in the carcinogenesis of colorectal cancer to identify a new diagnostic and therapeutic biomarker for CRC.Colorectal cancer is the consequence of dysplasia in the initial intestinal appendages also known as polyps which are different and unknown in terms of morphology, molecular mechanisms, and the ability to affect intestinal carcinogenesis. In this cross-sectional study, 208 colorectal tissue biopsy specimens, including 34 tumor tissue, , 60 precancerous lesions with adjacent tissue, as well as 20 normal tissue specimens were collected. CUL3 gene expression was evaluated using real-time PCR method. No significant difference was observed in mRNA expression level of CUL3 between polyp tissues and their normal adjacent samples (p = 0.35).Our results showed a statistically significant difference in CUL3 expression neither between tumor tissues and their adjacent normal samples (p = 0.89) nor among tumor and polyp groups (p = 0.48).CUL3 could play a critical role in regulating carcinogenesis and progression of CRC through stimulating proteasomal degradation of various tumor suppressors or oncogenes. Studies on CUL3-affected substrates in colorectal cancer are of significant importance.
Keywords: Colorectal cancer, Polyp, CUL3, Colon, Rectum -
Many genetic, epigenetic, and cellular studies on cancer are underway today, and the completion of the genetic and epigenetic library of cancer could be the way to treat the disease in the future. In this study, we have investigated the parallel gene expression changes of EZH2 and miR-155. So far no study has examined the role of these two factors simultaneously and the results of this study could be useful for further studies. For this purpose, using specific shRNA, the EZH2 gene of HCT116 cells was downregulated and then the changes in expression of the miR-155 were investigated. For gene expression study, Real-time PCR as a standard quantitative method was used. The findings of this study showed that in HCT116 human colon cancer cells, downregulation of miR-155 using shRNA can reduce EZH2 expression and also can promote a significant increase in the expression of TP53INP1 gene. Based on the results, we can emphasize the interaction between these two genes. Importantly, EZH2 downregulation has been able to decrease the amount of miR-155 that has also increased expression in many types of cancers. It may be of interest in epigenetic treatments of colon cancer, because miR-155 can control a very important tumor suppressor gene, TP53INP1.
Keywords: colorectal cancer, EZH2, miR-155, epigenetic, HCT116 cell line -
Colorectal cancer (CRC) is one of the common causes of cancer death in Iranian population. Both genetic and epigenetic changes have been implicated in CRC pathogenesis. DACT2 gene as one of the WNT signaling pathway inhibitor was shown to display tumor suppressor activity in many cancers. The aim of present study was to investigate the methylation status of DACT2 gene and its association with methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in CRC patients. Fifty formalin-fixed paraffin-embedded cancerous and adjacent healthy tissues obtained from CRC patientwere investigated. Genomic DNA was isolated using a FFPE commercial DNA extraction kit. The methylation status was evaluated by methylation specific PCR. Genotyping of MTHFR C677T polymorphism was performed using PCR-RFLP technique. Statistical analysis was done by GraphPad Prism 8. Results indicated that the frequency of methylated DACT2 gene was significantly higher in cancerous tissue relative to adjacent healthy tissue (P<0.001). DACT2 gene methylation was significantly more common among carriers of MTHFR 677CC genotype (P=0.035) and significantly less common among carriers of MTHFR 677T allele (P value =0.006). In conclusion the present study identified DACT2 gene methylation as a significant risk factor for CRC development. Moreover, the low frequency of DACT2 gene methylation among carriers of MTHFR 677T allele may confer a protective role for this common polymorphism against CRC risk.Keywords: Methylation, Colorectal cancer, DACT2, Methylenetetrahydrofolate reductase
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زمینه و هدفسرطان پستان در زنان و سرطان کولورکتال در هر دو جنس جزو شایع ترین و کشنده ترین سرطان ها در سراسر جهان می باشند. با توجه به مقاوم بودن برخی از سرطان ها به درمان های رایج، در این تحقیق اثرات سمیت و القائ آپوپتوز نانوکامپوزیت گرافن اکساید کوت شده با 8-هیدروکسی کینولین بر روی سلول های رده سرطان پستان و کولون سنجیده شد.روش کاردر این مطالعه رده سلولی سرطان پستان(MCF-7)، سرطان کولون(SW-742) و رده سلول نرمال پستان(MCF-10) را با دوزهای مختلف نانوصفحات گرافن اکساید کوت شده با 8-هیدروکسی کینولین به مدت 12، 24 و 48 ساعت تیمار و سمیت این نانوکامپوزیت را با روش MTT و تاثیر ماده فوق الذکر در آپوپتوز سلولی هم از طریق بررسی بیان ژن های پیش برنده و مهار کننده آپوپتوز از جمله P53, P21, Bax و Bcl-2 نیز از طریق تست فلوسایتومتری آپوپتوز سلولی(Annexin-V/PI) صورت گرفته شد.یافته هانتایج نشان دادند که نانوکامپوزیت سبب افزایش معنادار مرگ سلولی در رده های سلولی سرطان کولون و پستان به خصوص رده MCF-7 در مقایسه با رده سلول نرمال پستان گردیده است. نتایج بیان ژن نیز حاکی از افزایش بیان ژن های پیش آپوپتوزی P53, p21 و Bax و کاهش بیان ژن ضد آپوپتوزی Bcl-2 در رده های سلول سرطانی به خصوص رده MCF-7 به نسبت رده سلول نرمال پستان است. نتایج فلوسایتومتری تست Annexin-V/PI نیز در همین راستا القائ آپوپتوز در رده های سرطانی بالاخص MCF-7 به نسبت نمونه کنترل را پس از تیمار با نانوکامپوزیت نشان داد.نتیجه گیرییکی از مکانیسم های القائ مرگ سلولی استفاده از نانوکامپوزیت با القائ آپوپتوز در آن ها می باشد.کلید واژگان: گرافن اکسید, 8-هیدروکسی کینولین, سرطان پستان, سرطان کولون, آپوپتوزInroduction &ObjectiveBreast and colorectal cancers are of the major causes of cancer-related death worldwide. The anticancer properties of 8-hydroxyquinoline (8HQ), and the increasing use of graphene oxide (GO) as a drug delivery system with anti-cancerous properties, led us to investigate toxicity and apoptosis-induction capability of 8HQ-coated GO on breast and colorectal cancer cells compared to normal breast cells.Material and MethodThe breast cancer (MCF-7), colorectal cancer (SW-742) and normal breast (MCF-10) cell lines were treated with several doses of 8-HQ-coated GO for 12, 24, and 48 hours. The toxicity of nanocomposite was measured using MTT assay and the effect of nanocomposite on cell apoptosis were determined by examining the expression of P53, P21, Bax and Bcl-2 genes, as well as Annexin-V /PI apoptosis assay.ResultsThere were significantly increased cell death in nanocomposite-treated colorectal and breast cancer cells, especially MCF-7, compared to treated normal breast cells. A significant increased expression of P53, P21 and Bax genes and reduced expression of Bcl-2 gene were found in both treated cancer cell lines compared to the normal breast cell line. Annexin-V/PI assay also illustrated a significant induction of apoptosis in the cancerous cell lines, especially MCF-7, following nanocomposite treatment.
Conclussion: Overall, 8HQ-coated GO has toxicity for breast and colorecctal cancer cell lines, and one of the mechanisms through which this nanocomposite can induce cell death is induction of apoptosis. With complementary and in vivo studies, this nanocomposite can be suggested as a nano-drug with anti-cancer properties.Keywords: Graphene Oxide, 8-Hydroxyquinoline, Breast Cancer, Colorectal Cancer, Apoptosis
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