Mohamad Reza Eskandari
15.64· M.D, Psychiatrist, Smart Neuropsychology Systems, Toronto, ON
Skills and Expertise
Research Items (16)
In this paper, mathematical models have been evaluated using differential equations in order to evaluate the tumor behavior and the main components of the immune system on deal with each other. One of main purposes of mathematical modeling of cancer, which has been discussed here, is finding quality and structure of growth of cancer cells and determining a control pattern suitable for drug injection to patients. In this paper we have evaluated some of recent developments in mathematical modeling of glioma that has been started with a model of untreated glioma and results have been evaluated with glioma chemotherapy and surgery models.
Childhood autism is a severe form of complex genetically heterogeneous and behaviorally defined set of neurodevelopmental diseases, collectively termed as autism spectrum disorders (ASD). Reverse transcriptase quantitative real-time PCR (RT-qPCR) is a highly sensitive technique for transcriptome analysis, and it has been frequently used in ASD gene expression studies. However, normalization to stably expressed reference gene(s) is necessary to validate any alteration reported at the mRNA level for target genes. The main goal of the present study was to find the most stable reference genes in the salivary transcriptome for RT-qPCR analysis in non-syndromic male childhood autism. Saliva samples were obtained from nine drug naïve non-syndromic male children with autism and also sex-, age-, and location-matched healthy controls using the RNA-stabilizer kit from DNA Genotek. A systematic two-phased measurement of whole saliva mRNA levels for eight common housekeeping genes (HKGs) was carried out by RT-qPCR, and the stability of expression for each candidate gene was analyzed using two specialized algorithms, geNorm and NormFinder, in parallel. Our analysis shows that while the frequently used HKG ACTB is not a suitable reference gene, the combination of GAPDH and YWHAZ could be recommended for normalization of RT-qPCR analysis of salivary transcriptome in non-syndromic autistic male children.
Conclusion: Our findings from the analysis of telomere length in saliva samples taken form drug-naïve patients with non-syndromic childhood autism among the Iranian population are in line with the earlier report by from the Chinese population. Considering significant differences between the two studied populations, the similar findings regarding telomere lengths suggests that telomere biology may be one of the main factors involved in the etiology of childhood autism.
- Apr 2015
- Systems Biology of Cancer
Although genetic and epigenetic codes instruct cellular regeneration that is required to maintain structural integrity and to secure normal functionality of living organisms, food is the main source of materials to construct the building units and the whole structure of an organism. Naturally, any shortage or surplus of these materials may lead to structural and/or functional defects and disease phenotype. While DNA synthesis is dependent on the nutritional state, metabolism of nutrients as well as contaminants and toxins present in food or generated during metabolism of nutritional elements/components (e.g. reactive oxygen species) are reliant on the genetic landscape. Nutritional imbalance can also result in epigenetic aberrations leading to development and/or progression of cancer and other complex diseases. In fact, carcinogenesis is characterized by the distribution of different factors including the inheritance of mutated genes, and the exposure to endogenous and/or exogenous agents during the life. In this chapter we discuss the potential impacts of dietary and nutritional components on genetic and epigenetic codes involved in cancer development and highlight the importance of bioactive dietary and nutritional components in cancer prevention and therapy. Considering the current status of human knowledge of the nutritional science and advanced techniques for the detection of genetic and epigenetic vulnerabilities and aberrations, it is time to promote efforts to identify new bioactive dietary and nutritional components to prevent or treat cancer and other complex diseases.
- Mar 2015
- Epigenetics Territory and Cancer
Schizophrenia (SCZ), a major mental disease, is associated with reduced risk for different types of cancers, with the exception of breast, endometrial and pancreatic cancers. The lower risk of cancer in first-degree relatives of SCZ patients rules out the drug effects as the cause of reduced cancer risk in SCZ. While genetic polymorphisms were attributed to the reduced cancer risk in SCZ, since hundreds of genes have been linked to SCZ and the effect size of each gene is small (< 1 %), the reduced cancer risk cannot be due to specific genetic polymorphisms. The same is true in cancer, as specific genetic changes are correlated to only 5–10 % of all cancers. In post-mortem brain studies we found abnormal DNA methylation of the regulatory regions of several genes such as RELN, MB-COMT, MAOA, 5-HTT and HTR2A associated with corresponding altered expression in SCZ patients. As a subset of these epigenetic alterations (e.g. MB-COMT, HTR2A, and 5-HTT) are retained in DNA derived from the saliva of drug naïve SCZ patients, these alterations are not limited to brain and are independent of drug use. In addition to RELN, MB-COMT and MAOA, dysfunctionality of TGFβ, immune system, VGEF, FOXO and specific miRNAs are linked to both SCZ and cancer. Interestingly, the changes in SCZ are often opposite in nature to those observed in cancer suggesting that they may predispose to SCZ, but reduce cancer risk. Therefore, knowledge from one disease may help to understand the molecular basis of the other disease and assist the implementation of therapeutic strategies.
- Jan 2015
Although genetic and epigenetic codes instruct cellular regeneration that is required to maintain structural integrity and to secure normal functionality of living organisms, food is the main source of materials to construct the building units and the whole structure of an organism. Naturally, any shortage or surplus of these materials may lead to structural and/or functional defects and disease phenotype. While DNA synthesis is dependent on the nutritional state, metabolism of nutrients as well as contaminants and toxins present in food or generated during metabolism of nutritional elements/components (e.g., reactive oxygen species) are reliant on the genetic landscape. Nutritional imbalance can also result in epigenetic aberrations leading to development and/or progression of cancer and other complex diseases. In fact, carcinogenesis is characterized by the contribution of different factors including the inheritance of mutated genes, and the exposure to endogenous and/or exogenous agents during the life span. It is now well documented that gene–environment interactions are among the most important functions implemented by living organisms to fine tune gene expression levels to adapt with the changing environment. Nutritional elements and components are among immediate environmental factors that modulate gene expression levels on a daily basis and many developmental diseases originate from nutritional imbalance. The half life of most human cells is so short that we require successive and continuous regeneration to maintain the structural and functional integrity of the organism. For instance in adults, the half life of epithelial cells of the elementary tract, the skin, and blood cells are only a few days, weeks, and months, respectively. Although a limited number of human cells such as neurons are not extensively regenerated, overall we lose and regenerate the equivalent of our total body weight during a year as the result of a balanced apoptosis and reproduction (Davies and Morris, 1997). While genetic codes instruct this cellular regeneration from differentiated and undifferentiated stem cells to make 100 trillion human cells (Trosko, 2003), a vast majority of required materials are provided by food containing amino acids and other essential elements such as vitamins, minerals, and other nutrients in a range of concentrations extended from deficient to toxic levels.
- Dec 2011
- 22nd Anual meeting and symposium of American Academy of Addiction Psychiatry
Background: Alcohol abuse is the 3rd preventable leading cause of death in the US. In (2001-2002), only 10% of the 18 million Americans with alcohol problem sought treatment and less than 5% received Pharmacotherapy. NIAAA strongly recommends adjunctive pharmacotherapy to the conventional treatment methods and calls for new medication to improve the high relapse rate. Based on the dopamine (DA) theory of addiction, we considered utilizing inhibition of COMT enzyme, (the predominant DA-degrading factor), as a new method to combat alcohol craving. Methods: Entacapone a COMT-Inhibitor was tried, (open label, intent to treat), in 25 volunteered psychiatric out-patient population with alcohol dependence, who had exhausted standard available pharmacologic treatments. Subjects were studied for a period of 12 weeks. Relapse was detected by patient’s interview and serial alcohol Ethyl-Glucoronide (EtG) urine test. CGI improvement was defined based on abstinent for at least four weeks or on significant decrease in craving of alcohol in the first four weeks of taking medicine. All subjects were rated by a non-treating psychiatrist. Results: Entacaopne showed robust anti-craving effect in 88% of study subjects. The average dose of treatment was 1600 mg/day. Entacapone which had been given in addition to their routine psychiatric medication didn’t cause any worsening of side-effects and was also remained beneficial for maintenance of abstinence in those who chose to stay on it for an extra 6 months. Conclusions: For decades a need has been recognized for a tolerable, non-habit forming compound to balance out the hypodopaminergic state of drug craving. In our study population, Entacapone was effective to counteract both forms of cravings (cue craving as well as ordinary mental craving which is usually a product of nostalgia from getting high on drugs or feelings of boredom). Entacapone showed also to be effective in alleviating alcoholic post-withdrawal dysphoria. This is the first study of its kind demonstrating the use of COMT-Inhibition as a potential novel beneficial pharmacological method to combat alcohol craving. Placebo controlled double blind studies to re-examine this concept are warranted.
- Aug 2011
The failure in the discovery of etiology of psychiatric diseases, despite extensive genetic studies, has directed the attention of neuroscientists to the contribution of epigenetic modulations, which play important roles in fine-tuning of gene expression in response to environmental factors. Previously, we analyzed 115 human post-mortem brain samples from the frontal lobe and reported DNA hypo methylation of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene promoter, associated with an increased gene expression, as a risk factor for schizophrenia (SCZ) and bipolar disorder (BD). Since most epigenetic modifications are tissue specific and the availability of brain tissue to identify epigenetic aberrations in living subjects is limited, detection of epigenetic abnormalities in other tissues that represent the brain epigenetic marks is one of the critical steps to develop diagnostic and therapeutic biomarkers for mental diseases. Here, hypothesizing that; those factors that lead to the brain MB-COMT promoter DNA hypo-methylation may also cause concurrent epigenetic aberrations in peripheral tissues, we analyzed MB-COMT promoter methylation in DNA derived from the saliva in SCZ, BD and their first-degree relatives (20 cases each) as well as 25 control subjects. Using bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP), we found that similar to the brain, MB-COMT promoter was hypo-methylated (∼50%) in DNA derived from the saliva in SCZ and BD compared to the control subjects (p = 0.02 and 0.037, respectively). These studies suggest that DNA methylation analysis of MB-COMT promoter in saliva can potentially be used as an available epigenetic biomarker for disease state in SCZ and BD.
- Jul 2011
Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the -1438A/G polymorphism site, -1420 and -1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were ∼70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypo-methylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications.
- Jan 2010
Huntingtin protein (Htt) interplays with a large numbers of proteins and participates in diverse cellular pathways. Wide variety of Htt binding partners have been identified, including the Htt‐Interacting protein‐1 (HIP1) and Htt‐associated protein‐1 (HAP1). Htt has been shown pro‐apoptotic activity, and malfunctioning of Htt may result in cell outgrowth. HIP1 is involved in endocytosis and receptor trafficking and introduced as an oncoprotein. An altered expression of HIP1 has been reported in various cancers including breast cancer. HAP1 maintains the normal level of membrane TrkA by preventing the degradation of internalized TrkA. Recent evidence supports a role of HAP1 in micro‐tubule‐dependent organells transport, but its role in cancer development and progression has not been studied. We propose that the HAP1 and HIP1 may serve as a pair of “Ying‐Yang” modulators on the Htt functions and that the Htt‐HAP1‐HIP1 pathway may play an important role in the development and progression of breast cancer. We further propose that dietary/nutritional components that target this pathway may have chemopreventive effects on breast cancer. The objective of this study was to evaluate the differential expression and epigenetic modification patterns of Htt pathway related genes in normal and cancerous breast cells treated by dietary active components. Human breast cancer cells were treated with dietary components known to prevent cancer cell growth and the effects of these components on HAP1, HIP1 and HTT expressions and promoter DNA methylations were investigated by using real‐time PCR, Methylation Specific PCR (MSP) and bisulfite sequencing. HAP1 gene was silenced in several breast cancer cell lines including MCF7, MDA‐MB231, MB453, SKBR3 and in much lower extent in immortalized MCF10A cells, but not in normal human mammary epithelial cell line (HMEC). Epigenetic analysis for Htt, HIP1 and HAP1 showed severe HAP1 promoter DNA hypermethylation in breast cancer cell lines, but not in HMEC. When the cells were treated with 5‐AZaC (a DNA demethylating agent) and butyrate (a HDAC inhibitor), we found that 5‐AZaC treatment significantly increased HAP1 expression by over 100 times, but butyrate had little effects. Treatment of the cells with dietary active compounds, sulfuraphane, EGCG, oridonin, tanshinone 2A and cryptotanshinone increased expression of HAP1 and HTT genes and decreased expression of HIP1 gene in HMEC, more significantly in cancer cell lines MCF7 and MB453. Preliminary studies indicate that these dietary components acted through modulation of HAP1 promoter methylation and further experiments are taking place to construct HTT and HAP‐1 expressing plasmids for further in vitro and in vivo gene function studies. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A60.
- Mar 2007
- 15th Association of European Psychiatrists
Introduction: Run away Behavior in young girls is a complex social problem in Iranian adolescents. Psychiatric disorders may play an important role in run away behavior in young girls. Method: Homeless young girls between the ages of 12 and 18 years (n = 100) referred to Zanjan Welfare Organization conducted structured clinical interview for DSM and personality questionnaire (MMPI-2) to assess the Axis I and II disorders. Results: Most common Psychiatric Disorders were mood disorders (89%), Adjustment disorders (56%), Conduct disorder (36%), substance related disorders (12%), schizophrenia and other psychotic disorders (6%), in Axis I and, Cluster B Personality Disorders (53%) and mental retardation (6%) in Axis II. Conclusion: Prevalence of mental disorders is high among young homeless girls that runaway from home and service providers should consider this important issue. A focus on familial problems may lead to other important reasons being overlooked. Services and supports need to take into account whether young girls leave home because of family problem or because they suffer mental disorders.
Background Stubbornness, disobedience and, talking back to parents may cause parents to be anxious and defiant about their children. Researches suggest that proper parenting has an important role to play in helping children to become adjusted, and that the first few months and years of a child's life are especially important in establishing patterns of emotional, cognitive, and social functioning which will in turn influence the child's future development and in particular, their mental health. Stubbornness will appear if this point is not materialized, and this research is in line with this idea. Method and material 24 children aged less than 5 (13 girls and 11 boys) with stubbornness were assessed with Child Behavior Check List and clinical interview during 20 months.31 parents were also evaluated with General Health Questionnaire, Husband Satisfaction Scale and Structured Clinical Interview. Parents with psychiatric disorders and impaired household interpersonal relationship were counseled and trained in 3 individual skills sessions, and in some cases they received drugs. Results Stubbornness, talking back to parents, and disobedience were most frequent symptoms reported by parents. At least one of the parents in %87.1 (N=27) of cases had psychiatric problem or marriage dissatisfaction. Depressive symptoms and complaining about non-participation of another parent in the child nurturing were most frequent. In three month survey %77.8 of children (6 boys and 8 girls) had no symptom. ANOVA showed no sex effect on treatment results (P > 0.05). Conclusion This study supports the use of Parent-oriented treatment for children with stubbornness aged less than 5. Psychiatric disorders were reported high in these children’s parents.
- May 2005
- American Psychiatric Association
Introduction: Addicts have two kinds of control factors: external locus of control and internal locus of control. Internal control factors depend on one's personality and causes internal control on addiction. By the external locus of controls patient believe in chance and luck. Patients with internal locus of control try more than other group to treat there addiction. Method: This study was carried out on 62 addict (57 male and 5 female) admitted to hospital during one year and assessed by two questionnaires including demographic information and second one was Rutter test. Results: Mean age of smoking beginning was 18 .3 and 24 .7yr were mean age of onset of addiction. Loci of control in 41.96% of cases were internal and in 58.06% were external. In 62.9% of cases that friends reported as main cause of addiction, 60% had external locus of control these cases had less efforts to over come psychological problem. Conclusion: According to this study most of addicts have external locus of control such as their friends and treatment seeking is low in this patients. Administration of instructive method for increasing internal controls can be improving treatment outcome in opioids addicts.