Publications by authors named "Amir Avan"

315 Publications

The Potential Therapeutic Value of Renin-Angiotensin System Inhibitors in the Treatment of Colorectal Cancer.

Curr Pharm Des 2021 Oct 11. Epub 2021 Oct 11.

Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad. Iran.

Colorectal cancer is the third most common cancer globally. Despite extensive preclinical and clinical studies, it is still among the leading causes of cancer-related death, and a need for new therapeutic options is required. The renin-angiotensin system plays an important role in regulating blood pressure and cell growth. In addition to their hemodynamic effects, some of the renin-angiotensin system components, such as angiotensin, are also growth factors that promote cell proliferation and angiogenesis, and its dysregulation is reported to be associated with poor prognosis in colorectal cancer. Here we describe the critical role of the renin-angiotensin system pathway in colorectal cancer as well as the preclinical and clinical investigations renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as a potential therapeutic target in the treatment of colorectal cancer. Several studies have been shown that the inhibition of these pathways can reduce tumor growth and metastasis; however, some of the data remain inconsistent. There is accumulating evidence of the therapeutic potential of some inhibitors, such as Losartan which are now in clinical phases in the treatment of several malignancies using Nivolumab in combination with FOLFIRINOX in pancreatic cancer. Further investigations are warranted to improve the efficacy and selectivity of current and future anticancer strategies targeting renin-angiotensin systems.
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http://dx.doi.org/10.2174/1381612827666211011113308DOI Listing
October 2021

Cyclin Dependent Kinase-1 (CDK-1) Inhibition as a Novel Therapeutic Strategy against Pancreatic Ductal Adenocarcinoma (PDAC).

Cancers (Basel) 2021 Aug 30;13(17). Epub 2021 Aug 30.

Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90123 Palermo, Italy.

The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce stem cell properties, which can contribute to the development of cancer stem cells (CSCs). CSCs promote tumor-initiation and metastasis and play a crucial role in the development of PDAC. Targeting CDK1 showed promising results for PDAC treatment in different preclinical models, where CDK1 inhibition induced cell cycle arrest in the G2/M phase and led to induction of apoptosis. Next to this, PDAC CSCs are uniquely sensitive to CDK1 inhibition. In addition, targeting of CDK1 has shown potential for combination therapy with both ionizing radiation treatment and conventional chemotherapy, through sensitizing tumor cells and reducing resistance to these treatments. To conclude, CDK1 inhibition induces G2/M cell cycle arrest, stimulates apoptosis, and specifically targets CSCs, which makes it a promising treatment for PDAC. Screening of patients for CDK1 overexpression and further research into combination treatments is essential for optimizing this novel targeted therapy.
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http://dx.doi.org/10.3390/cancers13174389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430873PMC
August 2021

Association of a genetic variant in Interleukin-10 gene with increased risk and inflammation associated with cervical cancer.

Gene 2022 Jan 28;807:145933. Epub 2021 Aug 28.

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

Background: Cervical-cancer is among the most commonly diagnosed cancers in women, and infection with human papillomavirus (HPV) is associated with an increased risk of cervical cancer and altered serum concentrations of inflammatory cytokines. We have explored the association between a genetic variation in the Interleukin-10 (IL-10) gene (rs1800896) and cervical cancer risk and its relationship with tissue Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-β), Tumor necrosis factor alpha (TNF-α) concentrations in women with cervical cancer.

Methods: A total of 315 women with, or without cervical cancer, were recruited into the study. DNA was extracted from cervical cells, and genotyping was undertaken using Taq-man real-time PCR. The genotype frequency and allele distribution were analyzed together with their association with pathological data. The association of the rs1800896 gene variation with tissue levels of the inflammatory cytokines was also investigated.

Results: Our data showed a significant association between the A allele of the rs1800896 gene variant and the presence of cervical cancer. In particular, patients with AG/AA genotypes had an increased risk of cervical cancer with an odds ratio of 1.929 (95% confidence interval [CI]: 0.879-4.23, P < 0.001) in a recessive model, compared with the GG genotype. Also, the tissue concentrations of IFN-γ, TGF-β, and TNF-α in cervical tissues were significantly higher in women with cervical cancer (P < 0.001) and were associated with the AA genotype.

Conclusion: We have found an association between the polymorphism rs1800896 in the IL-10 gene and an increased risk of cervical cancer as well as a higher level of tissue inflammatory cytokines. Further investigations are necessary on the value of emerging biomarkers for the risk stratification for the management of cervical cancer patients.
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http://dx.doi.org/10.1016/j.gene.2021.145933DOI Listing
January 2022

Interaction between the genetic variant of rs696217-ghrelin and food intake and obesity and dyslipidemia.

Ann Hum Genet 2021 Aug 26. Epub 2021 Aug 26.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

In this study, we aimed to investigate the relationship between the genetic variant of rs696217-ghrelin and fasted lipid profile, indices of obesity, and environmental parameters. Amplification refractory mutation system-polymerase chain reaction (ARMs-PCR) was used for genotyping 1118 individuals recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) cohort study. The interaction between the presence of the genetic variant of rs696217-ghrelin and nutritional intake and other major determinants of obesity and lipid profile was examined in the MASHAD study population. Individuals with the TT genotype at the locus had the lowest prevalence of obesity compared to other genotypes among the individuals. No significant relationship was found between the two groups regarding the lipid profile and TT genotype. Furthermore, no significant association was found between dietary intake and the genetic variant of rs696217-ghrelin in the population under study. Individuals with a TT or GT genotype appear to be at a higher risk of obesity, compared to those with a GG genotype. The results of the current study revealed a significant association between the genetic variant of rs696217-ghrelin and obesity; however, this gene did not correlate with the risk factors of cardiovascular diseases and dyslipidemia in the Iranian population.
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http://dx.doi.org/10.1111/ahg.12443DOI Listing
August 2021

The Association Between rs1748195 and rs11207997 Variants of the ANGPTL3 Gene and Susceptibility to Cardiovascular Disease in the MASHAD Cohort Study.

Biochem Genet 2021 Aug 21. Epub 2021 Aug 21.

Biochemistry of Nutrition Research Center, School of Medicine, Iranian UNESCO Center of Excellence for Human Nutrition, Mashhad University of Medical Sciences, 99199-91766, Mashhad, Iran.

There is a strong genetic predisposition to cardiovascular disease (CVD). Loss-of-function variants of the angiopoietin-like 3 (ANGPTL3) gene have been reported to be associated with several lipid-related CVD risk factors that include serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) level, and total cholesterol (TC). We aimed to determine the association of two genetic variants, rs1748195 and rs11207997, of the ANGPTL3 locus and CVD risk in the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. The participants were 1002 individuals in the MASHAD cohort, with or without CVD, during the 6 years of follow-up. The subjects were categorized into two groups according to serum HDL concentration. DNA was extracted by the routine salting-out method, and genotyping of rs1748195 and rs11207997 variants of the ANGPTL3 gene was performed using the ARMS PCR method. Univariate and multivariate statistical analysis was used to assess the two gene variants' association with incident CVD and baseline lipid profile. There was a significant relationship between rs1748195 GG genotype and CVD risk in the individuals with a normal serum HDL-C. There was a significant association between the CT genotype of the rs11207997 polymorphism and CVD risk in individuals with a low serum HDL-C. Furthermore, carriers of the GG genotype of the rs1748195 and CT genotype of rs11207997 variant of ANGPTL3 had a higher risk of developing CVD disease. We have shown that the 1748195(GG) and 11207997(CT) gene variants of the ANGPTL3 locus are associated with an increased risk of CVD in an Iranian population sample.
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http://dx.doi.org/10.1007/s10528-021-10122-2DOI Listing
August 2021

Metformin inhibits polyphosphate-induced hyper-permeability and inflammation.

Int Immunopharmacol 2021 Oct 13;99:107937. Epub 2021 Jul 13.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Circulating inflammatory factor inorganic polyphosphate (polyP) released from activated platelets could enhance factor XII and bradykinin resulted in increased capillary leakage and vascular permeability. PolyP induce inflammatory responses through mTOR pathway in endothelial cells, which is being reported in several diseases including atherosclerosis, thrombosis, sepsis, and cancer. Systems and molecular biology approaches were used to explore the regulatory role of the AMPK activator, metformin, on polyP-induced hyper-permeability in different organs in three different models of polyP-induced hyper-permeability including local, systemic short- and systemic long-term approaches in murine models. Our results showed that polyP disrupts endothelial barrier integrity in skin, liver, kidney, brain, heart, and lung in all three study models and metformin abrogates the disruptive effect of polyP. We also showed that activation of AMPK signaling pathway, regulation of oxidant/anti-oxidant balance, as well as decrease in inflammatory cell infiltration constitute a set of molecular mechanisms through which metformin elicits it's protective responses against polyP-induced hyper-permeability. These results support the clinical values of AMPK activators including the FDA-approved metformin in attenuating vascular damage in polyP-associated inflammatory diseases.
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http://dx.doi.org/10.1016/j.intimp.2021.107937DOI Listing
October 2021

Rigosertib elicits potent anti-tumor responses in colorectal cancer by inhibiting Ras signaling pathway.

Cell Signal 2021 Sep 29;85:110069. Epub 2021 Jun 29.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Science, Mashhad, Iran. Electronic address:

Background: The therapeutic potency of Rigosertib (RGS) in the treatment of the myelodysplastic syndrome has been investigated previously, but little is known about its mechanisms of action.

Methods: The present study integrates systems and molecular biology approaches to investigate the mechanisms of the anti-tumor effects of RGS, either alone or in combination with 5-FU in cellular and animal models of colorectal cancer (CRC).

Results: The effects of RGS were more pronounced in dedifferentiated CRC cell types, compared to cell types that were epithelial-like. RGS inhibited cell proliferation and cell cycle progression in a cell-type specific manner, and that was dependent on the presence of mutations in KRAS, or its down-stream effectors. RGS increased both early and late apoptosis, by regulating the expression of p53, BAX and MDM2 in tumor model. We also found that RGS induced cell senescence in tumor tissues by increasing ROS generation, and impairing oxidant/anti-oxidant balance. RGS also inhibited angiogenesis and metastatic behavior of CRC cells, by regulating the expression of CD31, E-cadherin, and matrix metalloproteinases-2 and 9.

Conclusion: Our findings support the therapeutic potential of this potent RAS signaling inhibitor either alone or in combination with standard regimens for the management of patients with CRC.
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http://dx.doi.org/10.1016/j.cellsig.2021.110069DOI Listing
September 2021

Dynamic Evaluation of Circulating miRNA Profile in -Mutated NSCLC Patients Treated with EGFR-TKIs.

Cells 2021 06 16;10(6). Epub 2021 Jun 16.

Department of Medical Oncology, Amsterdam UMC, VU University, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.

Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of -mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a surrogate for predicting EGFR-TKI performance in -mutated NSCLC patients.

Methods: Plasma samples of 39 advanced -mutated NSCLC patients treated with EGFR-TKIs were collected at different points in time and miRNA levels were assessed by RT-PCR.

Results: Higher basal values of miR-21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) ( = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR-21 ( = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR-TKI treatment showed that patients who experienced SD had an increase in miR-21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR ( = 0.029). The same tendency was observed for miR-27a (FC = 3.1) and miR-181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR-21 levels in NSCLC cells that became resistant after exposure to EGFR-TKIs.

Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR-21, and their dynamic change over time in predicting EGFR-TKI response in -mutated NSCLC.
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http://dx.doi.org/10.3390/cells10061520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235748PMC
June 2021

Therapeutic potential of active components of saffron in post-surgical adhesion band formation.

J Tradit Complement Med 2021 Jul 20;11(4):328-335. Epub 2021 Jan 20.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Abdominal adhesions are common and often develop after abdominal surgery. There are currently no useful targeted pharmacotherapies for adhesive disease. Saffron and its active constituents, Crocin and Crocetin, are wildly used in traditional medicine for alleviating the severity of inflammatory or malignant disease.

Purpose: The aim of this study was to investigate the therapeutic potential of the pharmacological active component of saffron in attenuating the formation of post-operative adhesion bands using different administration methods in a murine model.

Material Method: saffron extract (100 mg/kg), Crocin (100 mg/kg), and Crocetin (100 mg/kg) were administered intraperitoneally and by gavage in various groups of male Wistar rat post-surgery. Also three groups were first treated intra-peritoneally by saffron extract, Crocin, and Crocetin (100 mg/kg) for 10 days and then had surgery. At the end of the experiments, animals sacrificed for biological assessment.

Result: A hydro-alcoholic extract of saffron and crocin but not crocetin potently reduced the adhesion band frequency in treatment and pre-treatment groups in the mice given intra-peritoneal (i.p) injections. Following the saffron or crocin administration, histological evaluation and quantitative analysis represented less inflammatory cell infiltration and less collagen composition, compared to control group. Moreover, the oxidative stress was significantly reduced in treatment groups.

Conclusion: These findings suggest that a hydro-alcoholic extract of saffron or its active compound, crocin, is a potentially novel therapeutic strategy for the prevention of adhesions formation and might be used as beneficial anti-inflammatory or anti-fibrosis agents in clinical trials.

Taxonomy: Abdominal surgeries/post-surgical adhesions.
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http://dx.doi.org/10.1016/j.jtcme.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240116PMC
July 2021

The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-Surgical Adhesions.

Curr Pharm Des 2021 Jun 25. Epub 2021 Jun 25.

Metabolic Syndrome Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, little improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered as a blood pressure regulator. However, recent studies also indicate that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and the wound healing process. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion.

Methods: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion.

Results: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are being used for targeting the RAS system. Some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including Telmisartan, valsartan, and enalapril.

Conclusion: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting Renin-Angiotensin System may help prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered as a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation.
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http://dx.doi.org/10.2174/1381612827666210625153011DOI Listing
June 2021

Inhibition of angiotensin II type 1 receptor by candesartan reduces tumor growth and ameliorates fibrosis in colorectal cancer.

EXCLI J 2021 7;20:863-878. Epub 2021 May 7.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Colorectal cancer (CRC) is an important cause of cancer-related mortality. Aberrant activation of the renin-angiotensin system (RAS) is reported to be associated with poor clinical outcomes in patients with CRC. This study was designed to explore the anti-tumor effects of the angiotensin receptor blocker Candesartan either alone or in combination with 5-FU in and models of CRC. The cytotoxic effects of Candesartan were assessed using the MTT assay in two colorectal cancer cell lines (CT-26 and SW-480). To investigate the potential regulatory role of Candesartan on tumor growth, apoptosis, and migration, the expression levels of Cyclin D1, Survivin, MMP3, MMP9, and E-cadherin mRNAs were evaluated. The oxidant/antioxidant balance was also examined by determining the levels of MDA, thiols, SOD, and CAT. We used a xenograft model of colon cancer to investigate the effects of Candesartan alone, or in combination with 5-FU, on tumor growth following histological staining (Hematoxylin & Eosin and Masson trichrome staining) and biochemical studies as well as gene expression analyses by RT-PCR and western blotting. Candesartan suppressed tumor cell proliferation and migration by modulating Cyclin D1, MMP3/9, and E-cadherin. Treatment with Candesartan either alone, or in combination with 5-FU decreased tumor size in the mouse model, and also increased the level of oxidative markers MDA and reduced CAT, SOD, and thiols. Histological evaluation showed that Candesartan increased tumor necrosis, reduced tumor density and attenuated collagen deposition reducing tumor fibrosis in tumor xenograft. Candesartan, an inhibitor of the RAS, when used in combination with 5-FU reduced tumor growth by inhibiting fibrosis and inducing ROS production, supporting further clinical studies on this therapeutic approach for treatment of CRC.
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http://dx.doi.org/10.17179/excli2021-3421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192880PMC
May 2021

Anticancer activity of Helicobacter pylori ribosomal protein (HPRP) with iRGD in treatment of colon cancer.

J Cancer Res Clin Oncol 2021 Oct 12;147(10):2851-2865. Epub 2021 Jun 12.

Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Purpose: As the conventional therapeutic approaches were not completely successful in the treatment of colon cancer, there is still a need for finding the most efficient therapeutic agents. Here we investigated the anticancer activity of HPRP-A1 that was derived from the N-terminal region of Helicobacter pylori ribosomal protein L1 (RpL1) alone or in combination with tumor-homing peptide iRGD and 5-Fluorouracil (5FU) on colon cancer cell lines (CT26 and HT29) and isograft models of colon cancer.

Method: We assessed the tumor growth inhibitory activity of HPRP-A1 with or without iRGD and 5FU on colon cancer in vitro and in vivo. In the in vitro part, we investigate the effect of HPRP-A1 alone and in combination with iRGD/5FU.

Results: Our results demonstrated that co-administration of HPRP-A1 with iRGD increased the apoptosis, while these two peptides in combination with 5FU increased the intracellular level of p53 that upregulate the pro-apoptotic gene BAX and downregulate the anti-apoptotic gene BCL2. HPRP-A1 blocks the cell cycle progression in G0/G1. Co-administration of two peptides significantly reduced the size and weight of the tumors, while the group that received 5FU in combination with the peptides increased the necrotic and decrease the fibrotic area significantly in the tumor tissues, which also disrupt the oxidant/antioxidant balance.

Conclusions: Our results indicated that HPRP-A1 could be considered an effective agent toward colon cancer in vitro and in vivo with the ability to enhance the effects of conventional chemotherapy agent 5FU.
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http://dx.doi.org/10.1007/s00432-021-03683-7DOI Listing
October 2021

Association between a genetic variant in scavenger receptor class B type 1 and its role on codon usage bias with increased risk of developing coronary artery disease.

Clin Biochem 2021 Sep 5;95:60-65. Epub 2021 Jun 5.

Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address:

Objective: Coronary artery disease (CAD) as an important cause of morbidity and mortality globally. The scavenger receptor class B type 1 (SCARB1) plays an essential role in the reverse cholesterol transport. We have explored the association between a genetic variant, rs5888, in the SCARB1 gene with CAD and serum HDL-C levels.

Methods: Patients were categorized into two groups' angiogram positive (>50% coronary stenosis) and angiogram negative (<50% coronary stenosis). Genotyping was carried out using polymerase chain reaction-amplification refractory mutation system. The association between the SNP rs5888 and serum HDL-C was analyzed using a logistic regression model.

Results: The results showed that the subjects carrying a T allele was associated with a decreased serum HDL-C levels compared to the C allele in total population (p < 0.001). The risk of angiogram positivity in subjects carrying a T allele was 3.1-fold higher than for the control group (p < 0.001).

Conclusion: CVD patients carrying the T allele of rs5888 variant in the SCARB1 gene was associated with decreased serum level of HDL.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.06.001DOI Listing
September 2021

The Therapeutic Potential of Targeting Autophagy in The Treatment of Cancer.

Curr Cancer Drug Targets 2021 Jun 1. Epub 2021 Jun 1.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Autophagy is a mechanism by which unwanted cellular components are degraded through a pathway that involves the lysosomes and contributes to several pathological conditions such as cancer. Gastrointestinal cancers affect the digestive organs from the esophagus to the anus and are among the most commonly diagnosed cancers globally. The modulation of autophagy using pharmacologic agents potentially offers a great potential for cancer therapy. In this review, some commonly used compounds, together with their molecular target and the mechanism through which they stimulate or block the autophagy pathway as well as their therapeutic benefit in treating patients with gastrointestinal cancers, are summarized.
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http://dx.doi.org/10.2174/1568009621666210601113144DOI Listing
June 2021

Serum HDL cholesterol uptake capacity in subjects from the MASHAD cohort study: Its value in determining the risk of cardiovascular endpoints.

J Clin Lab Anal 2021 Jun 24;35(6):e23770. Epub 2021 May 24.

Iranian UNESCO Center of excellence for human nutrition, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The efficiency of high-density lipoprotein (HDL) to efflux cholesterol contributes to the reverse cholesterol transport (RCT) pathway as one of HDL's proposed functions and depends on the ability of HDL to uptake cholesterol. We aimed to investigate cholesterol uptake capacity (CUC) by a newly developed assay in samples from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorders) cohort study.

Method: The study population comprised 153 individuals developed CVD diagnosed by a specialist cardiologist, over 6 years of follow-up, and 350 subjects without CVD. We used a modified CUC method to evaluate the functionality of HDL in serum samples.

Result: The CUC assay was highly reproducible with values for inter- and intra-assay variation of 13.07 and 6.65, respectively. The mean serum CUC was significantly lower in the CVD group compared to control (p = 0.01). Although, there were no significant differences in serum HDL-C between the groups and there was no significantly association with risk of progressive CVD. Multivariate logistic regression analysis showed that there was a significantly negative association between CUC and risk of CVD after adjustment for confounding parameters (OR = 0.57, 95% CI = 0.38-0.87, p = 0.009). The CUC was also inversely and independently associated with the risk of CVD event using Cox proportional hazards models analysis (HR = 0.62; 95% CI = 0.41-0.94, p = 0.02). We determined the optimum cutoff value of 1.7 a.u for CUC in the population. Furthermore, the CUC value was important in determining the CVD risk stratification derived from data mining analysis.

Conclusions: Reduced HDL functionality, as measured by CUC, appears to predict CVD in population sample from north-eastern Iran.
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http://dx.doi.org/10.1002/jcla.23770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183926PMC
June 2021

Delivery of oxaliplatin to colorectal cancer cells by folate-targeted UiO-66-NH.

Toxicol Appl Pharmacol 2021 07 13;423:115573. Epub 2021 May 13.

Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Oxaliplatin is being used in different malignancies and several side effects are reported for patients taking Oxaliplatin, including peripheral neuropathy, nausea and vomiting, diarrhea, mouth sores, low blood counts, fatigue, loss of appetite, etc. Here we have developed a targeted anticancer drug delivery system based on folate-conjugated amine-functionalized UiO-66 for the delivery of oxaliplatin (OX). UiO-66-NH (U) and UiO-66-NH-FA(FU) were pre-functionalized by the incorporation of folic acid (FA) into the structure via coordination of the carboxylate group of FA. The FTIR spectra of drug-loaded U and FU showed the presence of new carboxylic and aliphatic groups of OX and FA. Powder X-ray diffraction (PXRD) patterns were matched accordingly with the reference pattern and FESEM results showed semi-spherical particles (115-128 nm). The evaluated amounts of OX in U and FU were calculated 304.5 and 293 mg/g respectively. The initial burst release of OX was 15.7% per hour for U(OX) and 10.8% per hour for FU(OX). The final release plateau gives 62.9% and 52.3% for U(OX) and FU(OX). To evaluate the application of the prepared delivery platform, they were tested on colorectal cancer cells (CT-26) via MTT assay, cell migration assay, and spheroid model. IC values obtained from MTT assay were 21.38, 95.50, and 18.20 μg/mL for OX, U(OX), and FU(OX), respectively. After three days of treatment, the CT26 spheroids at two doses of 500 and 50 μg/mL of U(OX) and FU(OX) showed volume reduction. Moreover, the oxidative behavior of the prepared systems within the cell was assessed by total thiol, malondialdehyde, and superoxide dismutase activity. The results showed that FU(OX) had higher efficacy in preventing the growth of CT-26 spheroid, and was more effective than oxaliplation in cell migration inhibition, and induced higher oxidative stress and apoptosis.
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http://dx.doi.org/10.1016/j.taap.2021.115573DOI Listing
July 2021

When metal-organic framework mediated smart drug delivery meets gastrointestinal cancers.

J Mater Chem B 2021 05;9(19):3967-3982

Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran.

Cancers of the gastrointestinal tract constitute one of the most common cancer types worldwide and a ∼58% increase in the global number of cases has been estimated by IARC for the next twenty years. Recent advances in drug delivery technologies have attracted scientific interest for developing and utilizing efficient therapeutic systems. The present review focuses on the use of nanoscale MOFs (Nano-MOFs) as carriers for drug delivery and imaging purposes. In pursuit of significant improvements to current gastrointestinal cancer chemotherapy regimens, systems that allow multiple concomitant therapeutic options (polytherapy) and controlled release are highly desirable. In this sense, MOF-based nanotherapeutics represent a significant step towards achieving this goal. Here, the current state-of-the-art of interdisciplinary research and novel developments into MOF-based gastrointestinal cancer therapy are highlighted and reviewed.
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http://dx.doi.org/10.1039/d1tb00155hDOI Listing
May 2021

Inhibition of transforming growth factor-beta by Tranilast reduces tumor growth and ameliorates fibrosis in colorectal cancer.

EXCLI J 2021 9;20:601-613. Epub 2021 Mar 9.

Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Transforming Growth Factor-beta (TGF-β) is dysregulated in colorectal cancer and there is growing evidence that it is associated with a poor prognosis and chemo-resistance in several malignances, including CRC. In this study we have explored the therapeutic potential of targeting TGF-β using Tranilast in colon cancer. The anti-proliferative activity of Tranilast was evaluated in 2- and 3-dimensional cells. We used a xenograft model of colon cancer to investigate the activity of Tranilast alone or in combination with 5-FU on tumor growth using histological staining and biochemical studies, as well as gene expression analyses using RT-PCR and Western blotting. Tranilast alone or in combination with 5-FU inhibited tumor growth and was associated with a reduction of TGF-β expression and CD31 positive endothelial cells. Histological evaluation showed that Tranilast increased tumor necrosis and reduced tumor density and angiogenesis. Tranilast increased MDA and ROS production. It was also found that Tranilast reduced total thiol concentration and reduced SOD and catalase activity. Tranilast plus 5-FU was also found to attenuate collagen deposition, reducing tumor fibrosis in tumor xenografts. Our results show that Tranilast, a TGF inhibitor, in combination with 5-FU reduces tumor growth by inhibiting fibrosis and inducting ROS, thus supporting this therapeutic approach in CRC treatment.
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http://dx.doi.org/10.17179/excli2020-2932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056055PMC
March 2021

Angiotensin receptor blocker Losartan inhibits tumor growth of colorectal cancer.

EXCLI J 2021 1;20:506-521. Epub 2021 Mar 1.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

The renin-angiotensin system (RAS) is up-regulated in patients with colorectal cancer (CRC) and is reported to be associated with poor prognosis and chemo-resistance. Here we explored the therapeutic potential of targeting RAS in CRC using Losartan, an angiotensin receptor blocker. An integrative-systems biology approach was used to explore a proteome-level dataset of a gene signature that is modulated by Losartan. The anti-proliferative activity of Losartan was evaluated using 2- and 3-dimensional cell culture models. A xenograft model of colon cancer was used to investigate tumor growth with Losartan alone and in combination with 5-FU followed by histological staining (Hematoxylin & Eosin and Masson trichrome staining), biochemical analyses, gene expression analyses by RT-PCR, western blot/IHC, or MMP Gelatin Zymography studies. Effects on cell cycle and cell death were assessed by flow cytometry. Losartan inhibited cell growth and suppressed cell cycle progression, causing an increase in CRC cells in the G1 phase. Losartan significantly reduced tumor growth and enhanced tumor cell necrosis. An impact on the inflammatory response, including up-regulation of pro-inflammatory cytokines and chemokines in CRC cells are potential mechanisms that could partially explain Losartan's anti-proliferative effects. Moreover, metastasis and angiogenesis were reduced in Losartan-treated mice as observed by inhibited matrix metalloproteinase-2 and -9 activities and decreased tumor vasculature. These data demonstrate the therapeutic potential of combining chemotherapeutic regimens with Losartan to synergistically enhance its activity and target the renin-angiotensin system as a new approach in colorectal cancer treatment.
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http://dx.doi.org/10.17179/excli2020-3083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056058PMC
March 2021

Cerium oxide nanoparticles acts as a novel therapeutic agent for ulcerative colitis through anti-oxidative mechanism.

Life Sci 2021 Aug 20;278:119500. Epub 2021 Apr 20.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Cerium (IV) oxide (CeO) exhibit anti-inflammatory activity via scavenge free radicals and decreasing the oxygen species (ROS) production. Here we aimed to exhibit the therapeutic effect of this nanoparticle in experimental colitis models.

Methods: Cerium oxide nanoparticles (CeONPs) were synthesized via using UiO-66 as a precursor. We used dextran sodium sulfate (DSS) to induce colitis in experimental models to investigate the anti-inflammatory effect of CeONPs. Colitis models are divided into four groups to receive the treatment, including control, colitis, cerium oxide, and sulfasalazine. We evaluated the therapeutic effects of CeONPs for the increased colitis clinical symptoms and attenuated the histological damage to colon tissue in colitis.

Result: This nanoparticle was significantly able to reduce the clinical symptoms of colitis. Moreover, CeONPs can enhance the disease activity index such as body lose weight, diarrhea, rectal bleeding, colon length, and spleen weight. Moreover, CeONPs showed a significant reduction in the histological characteristics of the colitis models.

Conclusion: These results suggest that CeONPs can be considered as promising therapeutic agents in treating the ulcerative colitis.
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http://dx.doi.org/10.1016/j.lfs.2021.119500DOI Listing
August 2021

The Clinical Application of Circulating Tumor Cells and DNAs as Prognostic and Predictive Biomarkers in Gastrointestinal Cancer.

Curr Cancer Drug Targets 2021 Mar 10. Epub 2021 Mar 10.

Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad. Iran.

Gastrointestinal (GI) cancer is one of the most common cancers globally. Genetic and epigenetic mechanisms are involved in its pathogenesis. The conventional methods for diagnosis and screening for GI cancers are often invasive and have other limitations. In the era of personalized medicine, a novel non-invasive approach called liquid biopsy has been introduced for the detection and management of GI cancers, which focuses on the analysis of circulating tumor cells (CTCs) and circulating cell-free tumor DNA (ctDNA). Several studies have shown that this new approach allows for an improved understanding of GI tumor biology and will lead to an improvement in clinical management. The aim of the current review is to explore the clinical applications of CTCs and ctDNA in patients with GI cancer.
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http://dx.doi.org/10.2174/1568009621666210311090531DOI Listing
March 2021

Cytokines and the immune response in obesity-related disorders.

Adv Clin Chem 2021 24;101:135-168. Epub 2020 Sep 24.

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

The increasing prevalence of obesity and the associated morbidity and mortality are important public health problems globally. There is an important relationship between an unhealthy lifestyle and increased serum inflammatory cytokines. Adipocytes secrete several pro-inflammatory cytokines involved in the recruitment and activation of macrophages resulting in chronic low-grade inflammation. Increased cytokines in obese individual are related to the progression of several disorders including cardiovascular disease, hypertension, and insulin resistance. In present review we have summarized the crucial roles of cytokines and their inflammatory functions in obesity-related immune disorders.
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http://dx.doi.org/10.1016/bs.acc.2020.06.004DOI Listing
July 2021

A mini review on the pathogenesis, diagnosis and treatment options for COVID-19.

Infect Disord Drug Targets 2021 Mar 1. Epub 2021 Mar 1.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad. Iran.

Coronavirus disease 2019 (COVID-19) is a serious viral disease caused by SARS-CoV-2, associated with a high morbidity and mortality, and represents the greatest public health crisis worldwide. Despite recent efforts for developing novel antiviral agents, no specific drugs are approved for management and treatment of COVID-19. The immune responses to viral infection followed by cytokine storm and acute respiratory distress syndrome are serious issues that may cause death in patients with severe COVID-19. Therefore, developing a novel therapeutic strategy for management of COVID-19 is urgently needed to control the virus spread and improving patient survival rate and clinical outcomes. In this mini review, we summarize the symptoms, pathogenesis and therapeutic approaches that are currently being used to managing the spread of SARS-CoV-2.
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http://dx.doi.org/10.2174/1871526521666210301142223DOI Listing
March 2021

Programmed cell death 1 as prognostic marker and therapeutic target in upper gastrointestinal cancers.

Pathol Res Pract 2021 Apr 18;220:153390. Epub 2021 Feb 18.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Gastrointestinal (GIs) cancers are among the most common causes of cancer related death, and hence the importance for the identification of novel prognostic/predictive biomarkers for detection of patients at an early stage, and for using these to identify novel targeted therapies to improve the efficacy of existing chemotherapeutic regimens. Programmed cell death 1 has been reported as a potential target in several malignancies, and targeting agents are being developed, some already approved by FDA, such as: pembrolizumab, Atezolizumab, Nivolumab. Pembrolizumab that have been approved for the treatment of metastatic non-small cell lung cancer. Here we provide an overview of the mechanism of action PD-1/PD-L1, prognostic value and current progress in clinical trials using PD-1/PD-L1 inhibitors, and the resistant mechanisms at underlie the inhibitory effect of these agents in the treatment of gastrointestinal cancers.
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http://dx.doi.org/10.1016/j.prp.2021.153390DOI Listing
April 2021

A haplotype of the ANGPTL3 gene is associated with CVD risk, diabetes mellitus, hypertension, obesity, metabolic syndrome, and dyslipidemia.

Gene 2021 May 23;782:145525. Epub 2021 Feb 23.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Iranian UNESCO Center of Excellence for Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Subject: There have been a few studies on the association between the angiopoietin-like 3 (ANGPTL3) single nucleotide polymorphisms (SNPs) and the risk of cardiovascular disease (CVD). But there is no consensus about the association of ANGPTL3 haplotypes and cardiometabolic disorders. We aimed to determine the association of three variants of the ANGPTL3 gene and CVD risk factors, which included: diabetes mellitus, hypertension, obesity, metabolic syndrome, and dyslipidaemia in the MASHAD population cohort.

Method: DNA extraction and genotyping were undertaken in1002 individuals who were recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort. The association between the rs1748195, rs11207997, and rs10789117 variants with CVD event following 6 years follow-up and individual CVD risk factors were assessed using multivariate analysis.

Result: Individuals with a GTC haplotype had a reduced risk of CVD, dyslipidaemia, obesity, and DM. Moreover, we found that of all 8 haplotypes, the CTC was associated with a 1.5-fold higher risk of HTN. Carriers of an uncommon allele of the ANGPTL3 gene had a lower risk of obesity, HTN, MetS and DM (rs10789117), and in those with the rs1748195 variant there was a lower risk of obesity compared to the wild-type genotype.

Conclusion: We found that the GTC and CTC haplotypes of the ANGPTL3 gene may help identify individuals with a genetic susceptibility to cardiometabolic disorders.
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http://dx.doi.org/10.1016/j.gene.2021.145525DOI Listing
May 2021

The beneficial effect of combination therapy with sulfasalazine and valsartan in the treatment of ulcerative colitis.

EXCLI J 2021 5;20:236-247. Epub 2021 Feb 5.

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Inflammatory bowel disease (IBD) is defined by the chronic inflammation of the digestive tract. Ulcerative colitis is one of the most prevalent chronic IBDs. The increase in the mucosal expression of angiotensin II (AT-II) in colitis suggests a possible role of AT-II in colitis-associated inflammation. Here, we examined the potential therapeutic effects of combination therapy regarding valsartan (Val), as an AT-II receptor blocker, with sulfasalazine (SSZ) in a murine colitis model. DSS induced colitis was initiated by the administration of dextran sodium sulfate (DSS) in male C57BL/6 mice for 1 week. Val (160 mg/kg/day, gavage) was given on the third day and continued for seven days. SSZ (100 mg/kg/day) was used as reference drug and also used in combination in one group (Val; 160 mg/kg/day and/or SSZ; 100 mg/kg/day). Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. The disease activity index in DSS-treated mice, including weight loss, stool consistency, and rectal bleeding, were significantly lower in the group of mice receiving the combination of valsartan and sulfasalazine compared to the DSS-treated group. Valsartan and sulfasalazine treatment was associated with a lower reduction in colon length, diminished colon weight, and high sensitivity C-reactive protein level in mice with DSS-induced colitis. Valsartan and sulfasalazine also reduced markers of oxidative stress after DSS administration. Our findings demonstrate the anti-inflammatory and anti-fibrotic activities of a combination therapy with sulfasalazine and valsartan in experimentally induced colitis, indicating its value as a potential therapeutic option for the treatment of colitis.
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http://dx.doi.org/10.17179/excli2021-3370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898046PMC
February 2021

Association of a variant in the tumor necrosis factor alpha gene with risk of cervical cancer.

Mol Biol Rep 2021 Feb 8;48(2):1433-1437. Epub 2021 Feb 8.

Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the regulation of the immune system and potentially the progression of cervical neoplastic lesions. In this study, we aimed to explore the possible relationship between polymorphisms of the TNF-α gene and susceptibility to cervical cancer. The relationship between a single nucleotide polymorphism (SNP) in the TNF-α gene (rs1800629) and the risk of cervical cancer was evaluated in a total of 445 subjects with (n = 153), or without (n = 292) cancer. Genotyping was performed using a Taq-Man based real time PCR method. Logistic regression analysis showed that individuals with AG/AA genotypes had an increased risk of cervical cancer compared to those with a GG genotype (OR 3.79, 95% CI 2.4-5.7, < 0.001). Our findings demonstrated that a genetic variant in the TNF-α gene (rs1800629) was associated with increased level and risk of developing cervical cancer, suggesting its potential use as a genetic risk factor for cervical neoplasia.
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http://dx.doi.org/10.1007/s11033-021-06185-4DOI Listing
February 2021

The therapeutic potential of renin-angiotensin system inhibitors in the treatment of pancreatic cancer.

Life Sci 2021 Apr 3;270:119118. Epub 2021 Feb 3.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Pancreatic cancer is among the most lethal malignancies with poor prognosis and patients become chemoresistant to current therapies, supporting further investigations to identify new therapeutic regimens in the treatment of this condition. Preclinical and clinical studies now appear to support the role of the renin-angiotensin system (RAS) in the regulation of tumor growth, angiogenesis, and metastasis in different malignancies including pancreatic cancer. These studies suggest that RAS blockers; Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs); could have anti-carcinogenic effects and improve clinical outcomes in the management of pancreatic cancer. Here we provided an overview of ACE inhibitors and ARBs as a potential therapeutic option in the treatment of pancreatic cancer.
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http://dx.doi.org/10.1016/j.lfs.2021.119118DOI Listing
April 2021

Association of Interleukin-10 -592 C > A gene polymorphism with coronary artery disease: A case-control study and meta-analysis.

Cytokine 2021 03 17;139:155403. Epub 2021 Jan 17.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Coronary-artery-disease (CAD) is the leading cause of death worldwide, and hence there is a need to identify reliable markers for identifying individuals at high risk of developing CAD. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is associated with an increased risk of developing both atherosclerosis and acute coronary events. The study aimed to explore the association of a genetic variant in IL-10 with the risk of developing CAD and the severity of the disease. To further explore, a systematic review and meta-analysis was performed. The cumulative results of the relationship between IL and 10 -592 C > A polymorphism and CAD in Iranian population have also been presented.

Methods: In this cross sectional study, a total of 948 individuals including 307 healthy controls and 641 patients that among cases, four hundred and fifty-five of the patients had > 50% stenosis (angiogram positive group) and 186 patients had < 50% stenosis (angiogram negative group) were recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders cohort. Genotyping for the IL-10 -592 C > A polymorphism was performed using a PCR-RFLP technique, and statistical analysis undertaken by univariate and multivariate analyses. PubMed, Google Scholar and Scopus were searched for papers related to this polymorphism up to October 2019. The Meta-analysiswas done based on the random effect model using a Meta-analysis.

Results: In our study, the frequency of the variant A allele of the IL-10 -592 C > A was significantly higher in CAD patients than the control group (P value = 0.043). Moreover, subjects carrying AA genotype had a significantly higher risk of CAD (OR: 1.8, 95%CI: 1.04-3.16), p = 0.03), compared to those with the wild type genotype. The results of meta-analysis of 9336 cases and 8461 controls did not also show any significant association between IL and 10 -592 C > A and CAD in dominant and recessive genetic models but only in co-dominant model when fix effect was applied.

Conclusion: Although our research findings support a significant association of genetic polymorphism in the IL10 gene with cardiovascular diseases, this finding cannot be confirmed in meta-analysis. Further functional analysis and evaluation of this marker in a multicenter setting are needed to establish its value as a risk stratification marker.
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http://dx.doi.org/10.1016/j.cyto.2020.155403DOI Listing
March 2021

The association of a genetic variant in CDKN2A/B gene and the risk of colorectal cancer.

EXCLI J 2020 14;19:1316-1321. Epub 2020 Sep 14.

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

Colorectal cancer is among the most aggressive tumors, and its development involves an interplay between various genetic and environmental familial risk factors. Several genetic polymorphisms have been reported to be associated with colorectal cancer in recent studies. In this current study, we aimed to evaluate the possible relationship between a CDKN2A/B, single nucleotide polymorphisms (SNP) (rs10811661), with the risk of colorectal cancer. A total of 541 individuals with, or without cancer were recruited. DNA was extracted, and genotyped using a Taq-Man based real-time PCR method. The rs10811661 SNP was associated with an increased risk of colorectal cancer (additive model: OR=3.46, CI= 1.79-6.69, p<0.0001 and recessive model: 5.72, CI= 3.12-10.49, p<0.0001). The distribution of minor alleles in the total population for homozygote allele was 9.2 %, while this was 20.1 % for heterozygotes. In summary, our findings indicate that the rs10811661 polymorphism of the CDKN2A/B gene was strongly related to the occurrence of colorectal cancer suggesting its potential role as a prognostic biomarker for the management of colorectal cancer.
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http://dx.doi.org/10.17179/excli2020-2051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588726PMC
September 2020
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