Search results for: Behzad Mohammadian
3 Targeting the EphA2 Receptor Tyrosine Kinases in Melanoma Cancer, both in Humans and Dogs
Authors: Shabnam Abdi, Behzad Toosi
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Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.Keywords: ephA2, targeting, melanoma, human, canine
Procedia PDF Downloads 602 Risk of Fatal and Non-Fatal Coronary Heart Disease and Stroke Events among Adult Patients with Hypertension: Basic Markov Model Inputs for Evaluating Cost-Effectiveness of Hypertension Treatment: Systematic Review of Cohort Studies
Authors: Mende Mensa Sorato, Majid Davari, Abbas Kebriaeezadeh, Nizal Sarrafzadegan, Tamiru Shibru, Behzad Fatemi
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Markov model, like cardiovascular disease (CVD) policy model based simulation, is being used for evaluating the cost-effectiveness of hypertension treatment. Stroke, angina, myocardial infarction (MI), cardiac arrest, and all-cause mortality were included in this model. Hypertension is a risk factor for a number of vascular and cardiac complications and CVD outcomes. Objective: This systematic review was conducted to evaluate the comprehensiveness of this model across different regions globally. Methods: We searched articles written in the English language from PubMed/Medline, Ovid/Medline, Embase, Scopus, Web of Science, and Google scholar with a systematic search query. Results: Thirteen cohort studies involving a total of 2,165,770 (1,666,554 hypertensive adult population and 499,226 adults with treatment-resistant hypertension) were included in this scoping review. Hypertension is clearly associated with coronary heart disease (CHD) and stroke mortality, unstable angina, stable angina, MI, heart failure (HF), sudden cardiac death, transient ischemic attack, ischemic stroke, subarachnoid hemorrhage, intracranial hemorrhage, peripheral arterial disease (PAD), and abdominal aortic aneurism (AAA). Association between HF and hypertension is variable across regions. Treatment resistant hypertension is associated with a higher relative risk of developing major cardiovascular events and all-cause mortality when compared with non-resistant hypertension. However, it is not included in the previous CVD policy model. Conclusion: The CVD policy model used can be used in most regions for the evaluation of the cost-effectiveness of hypertension treatment. However, hypertension is highly associated with HF in Latin America, the Caribbean, Eastern Europe, and Sub-Saharan Africa. Therefore, it is important to consider HF in the CVD policy model for evaluating the cost-effectiveness of hypertension treatment in these regions. We do not suggest the inclusion of PAD and AAA in the CVD policy model for evaluating the cost-effectiveness of hypertension treatment due to a lack of sufficient evidence. Researchers should consider the effect of treatment-resistant hypertension either by including it in the basic model or during setting the model assumptions.Keywords: cardiovascular disease policy model, cost-effectiveness analysis, hypertension, systematic review, twelve major cardiovascular events
Procedia PDF Downloads 711 Improving the Biomechanical Resistance of a Treated Tooth via Composite Restorations Using Optimised Cavity Geometries
Authors: Behzad Babaei, B. Gangadhara Prusty
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The objective of this study is to assess the hypotheses that a restored tooth with a class II occlusal-distal (OD) cavity can be strengthened by designing an optimized cavity geometry, as well as selecting the composite restoration with optimized elastic moduli when there is a sharp de-bonded edge at the interface of the tooth and restoration. Methods: A scanned human maxillary molar tooth was segmented into dentine and enamel parts. The dentine and enamel profiles were extracted and imported into a finite element (FE) software. The enamel rod orientations were estimated virtually. Fifteen models for the restored tooth with different cavity occlusal depths (1.5, 2, and 2.5 mm) and internal cavity angles were generated. By using a semi-circular stone part, a 400 N load was applied to two contact points of the restored tooth model. The junctions between the enamel, dentine, and restoration were considered perfectly bonded. All parts in the model were considered homogeneous, isotropic, and elastic. The quadrilateral and triangular elements were employed in the models. A mesh convergence analysis was conducted to verify that the element numbers did not influence the simulation results. According to the criteria of a 5% error in the stress, we found that a total element number of over 14,000 elements resulted in the convergence of the stress. A Python script was employed to automatically assign 2-22 GPa moduli (with increments of 4 GPa) for the composite restorations, 18.6 GPa to the dentine, and two different elastic moduli to the enamel (72 GPa in the enamel rods’ direction and 63 GPa in perpendicular one). The linear, homogeneous, and elastic material models were considered for the dentine, enamel, and composite restorations. 108 FEA simulations were successively conducted. Results: The internal cavity angles (α) significantly altered the peak maximum principal stress at the interface of the enamel and restoration. The strongest structures against the contact loads were observed in the models with α = 100° and 105. Even when the enamel rods’ directional mechanical properties were disregarded, interestingly, the models with α = 100° and 105° exhibited the highest resistance against the mechanical loads. Regarding the effect of occlusal cavity depth, the models with 1.5 mm depth showed higher resistance to contact loads than the model with thicker cavities (2.0 and 2.5 mm). Moreover, the composite moduli in the range of 10-18 GPa alleviated the stress levels in the enamel. Significance: For the class II OD cavity models in this study, the optimal geometries, composite properties, and occlusal cavity depths were determined. Designing the cavities with α ≥100 ̊ was significantly effective in minimizing peak stress levels. The composite restoration with optimized properties reduced the stress concentrations on critical points of the models. Additionally, when more enamel was preserved, the sturdier enamel-restoration interface against the mechanical loads was observed.Keywords: dental composite restoration, cavity geometry, finite element approach, maximum principal stress
Procedia PDF Downloads 102