Veronica Mariotti - Academia.edu (original) (raw)

Papers by Veronica Mariotti

doi: 10.3389/fnbeh.2010.00160 How neuroscience and behavioral genetics improve psychiatric assess... more doi: 10.3389/fnbeh.2010.00160 How neuroscience and behavioral genetics improve psychiatric assessment: report on a violent murder case

Scientific Reports, 2017

Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing soci... more Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenationlevel-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects. The world is experiencing a substantial increase in the proportion of elderly adults in the population. With an aging society comes the increase in age related frailties, which may lead to cognitive impairments and to dementia, mostly in the form of Alzheimer's Disease (AD). Age is indeed the major risk factor for dementia: the age-specific incidence rates for AD demonstrate a doubling of incidence for about every six years of added life 1. The number of people with dementia worldwide was 35.6 million in 2010 and that is estimated to increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means of reducing the incidence of this disease are introduced 2. Several epidemiological studies have demonstrated that modifiable lifestyle factors, such as practicing physical exercise, being engaged in stimulating cognitive activities, maintaining an active social life into old age, and controlling nutrition, are correlated with maintaining good brain functioning, specifically in the elderly, and with reduced risk of developing dementia 3-8. Norton et al. 9 estimated that around one third of AD cases worldwide might be attributable to potentially modifiable risk factors which include several lifestyle habits. Interventions based on cognitive training 10 , diet 11 or physical activity 7,12,13 have indeed been found to produce positive effects on cognitive status in cognitively unimpaired adult or elderly subjects. Potential mechanisms underlying the effects of cognitive and physical activity on cognition, suggested also by studies in animal models, include increased hippocampal neurogenesis, increased Cerebral Blood Flow (CBF), and enhanced brain plasticity 14,15. An important point that has recently emerged both from the human and animal research, is that enhanced physical and cognitive activities seem to have additive effects on brain plasticity and age related cognitive decline 16. In this line, a very important study is the FINGER trial 17 , in which 1260 subjects, aged 60-77 years, with cognition in the mean level for age and elevated Dementia Risk Score, were randomized to a 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring, showing that cognitive performances improved more in the intervention than in the control group.

Journal of Alzheimer's Disease, 2008

Increasing evidence suggests a role for nerve growth factor (NGFB), brain-derived neurotrophic fa... more Increasing evidence suggests a role for nerve growth factor (NGFB), brain-derived neurotrophic factor (BDNF), and their receptors, nerve growth factor receptor (NGFR), and neurotrophin tyrosine kinase receptors 1 and 2 (NTRK1 and NTRK2), in Alzheimer's disease (AD). However, genetic association between the neurotrophin system genes and AD has been poorly investigated. We genotyped 21 single nucleotide polymorphisms (SNPs) within these genes in a population of Italian AD patients and healthy controls. We found an allele-wise association of rs2072446 on NGFR with familial AD (fAD, p = 0.047), and a genotype-wise association of rs2289656 on NTRK2 with sporadic AD (sAD, p = 0.0036). rs6336 on NTRK1 resulted associated to early-onset sAD in both allele-wise (p = 0.028) and genotype-wise (p = 0.014) analysis, while rs1048218 on BDNF showed allele-wise association with late-onset sAD (p = 0.047). A trend to association with sAD and/or fAD was observed for other SNPs. Our results suggest that genetic variants of neurotrophin system genes might confer susceptibility to AD.

Frontiers in Behavioral Neuroscience, 2017

Pellegrini et al. Gene by Gender Interplay in Moral Choices than males, our results, though preli... more Pellegrini et al. Gene by Gender Interplay in Moral Choices than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process.

<b>Copyright information:</b>Taken from "TAMGeS: a Three-Array Method for Genoty... more <b>Copyright information:</b>Taken from "TAMGeS: a Three-Array Method for Genotyping of SNPs by a dual-colour approach"BMC Genomics 2007;8():10-10.Published online 9 Jan 2007PMCID:PMC1783851.s, and on the Y axis the average value of the frequency of genotyping errors. Symbols indicate the methods: squares refer to the direct Two-Array Method; diamonds refer to TAMGeS. For multiplicative variability greater than 1.8, the genotyping performance of TAMGeS results significantly better than that of direct Two-Array Method.

Behavioural Brain Research

In recent years, conflicting findings have been reported in the scientific literature about the i... more In recent years, conflicting findings have been reported in the scientific literature about the influence of dopaminergic, serotonergic and oxytocinergic gene variants on moral behavior. Here, we utilized a moral judgment paradigm to test the potential effects on moral choices of three polymorphisms of the Oxytocin receptor (OXTR): rs53576, rs2268498 and rs1042770. We analyzed the influence of each single polymorphism and of genetic profiles obtained by different combinations of their genotypes in a sample of male insurance brokers (n = 129), as compared to control males (n = 109). Insurance brokers resulted significantly more oriented to maximize outcomes than control males, thus they expressed more than controls the utilitarian attitude phenotype. When analyzed individually, none of the selected variants influenced the responses to moral dilemmas. In contrast, a composite genetic profile that potentially increases OXTR activity was associated to higher moral acceptability in brokers. We hypothesize that this genetic profile promotes outcome-maximizing behavior in brokers by focusing their attention on what represents a greater good, that is, saving the highest number of people, even though at the cost of sacrificing one individual. Our data suggest that investigations in a sample that most expresses the phenotype of interest, combined with the analysis of composite genetic profiles rather than individual variants, represent a promising strategy to find out weak genetic influences on complex phenotypes, such as moral behavior.

The human brain develops through a sophisticated process that starts a few weeks after conception... more The human brain develops through a sophisticated process that starts a few weeks after conception and reaches its completion 20–30 years later. Changes that take place over this timeframe are of primary importance, as they constitute the “hardware” of the adult brain. Both genetic and environmental factors are crucial for brain development. In particular, brain sensitivity to the environment is maximum during prenatal and early postnatal life, when brain undergoes most of its development and is extremely vulnerable to both organizing and disorganizing experiences. The quality of prenatal and early postnatal environment may then influence the trajectory of neuronal development and contribute to shape the developing brain, thus producing long-lasting effects on behavior. Epigenetic changes have been reported to represent the molecular mechanisms by which the early environment modulates the expression of genes, including NR3C1, CRH, and 11-Beta-HSD2 involved in the HPA axis activity, o...

International Journal of Psychophysiology

Neuroscience & Biobehavioral Reviews

This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt... more This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt to map anger and its components (i.e., physiological, cognitive, experiential) to the neuroscience literature (i.e., genetic markers, functional imaging of human brain networks) and to linguistic expressions used to describe anger feelings. Given the ubiquity of anger in both its normative and chronic states, specific language is used in humans to express states of anger. Following a review of the neuroscience literature, we explore the language that is used to convey angry feelings, as well as metaphors reflecting inner states of anger experience. We then discuss whether these linguistic expressions can be mapped on to the neural circuits during anger experience and to distinct components of anger. We also identify relationships between anger components, brain networks, and other affective research relevant to motivational states of dominance and basic needs for safety.

Frontiers in Behavioral Neuroscience

Experimental Biology and Medicine, 2010

Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also b... more Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also be beneficial for treatment of bipolar disorder. To examine molecular mechanisms of action of phenytoin as a potential mood stabilizer, DNA microarrays were used to study the effect of phenytoin on gene expression in the hippocampus and frontal cortex of Sprague–Dawley rats. While our particular interest is in bipolar disorder, this is the first DNA microarray study on the effect of phenytoin in brain tissue, in general. As compared with control rats, treated rats had 508 differentially expressed genes in the hippocampus and 62 in the frontal cortex. Phenytoin modulated the expression of genes which may affect neurotransmission, e.g. glutamate decarboxylase 1 ( Gad1) and γ-aminobutyric acid A receptor, alpha 5 ( Gabra5). Phenytoin also exerted an effect on neuroprotection-related genes, namely the survival-promoting and antioxidant genes v-akt murine thymoma viral oncogene homolog 1 ( Akt...

Cytotherapy, 2017

Mesenchymal stromal/stem cells (MSC) have emerged as a class of cells suitable for cellular deliv... more Mesenchymal stromal/stem cells (MSC) have emerged as a class of cells suitable for cellular delivery of nanoparticles, drugs and micro-RNA cargo for targeted treatments such as tumor and other protective mechanisms. The special properties of MSC underscore the current use for various clinical applications. Examples of applications include but are not limited to regenerative medicine, immune disorders and anti-cancer therapies. In recent years, there has been intense research in modifying MSC to achieve targeted and efficient clinical outcomes. This review discusses effects of MSC in an inflammatory microenvironment and then explains how these properties could be important to the overall application of MSC in cell therapy. The article also advises caution in the application of these cells because of their role in tumorigenesis. The review stresses the use of MSC as vehicles for drug delivery and discusses the accompanying challenges, based on the influence of the microenvironment on ...

European Journal of Cancer Supplements, 2010

Conclusions: Low retention index in LPG means radioisotope accumulation to SN is impaired. Low re... more Conclusions: Low retention index in LPG means radioisotope accumulation to SN is impaired. Low retention index in n+ suggests that metastatic tumor cells may obstruct lymphatic pathway to SN. The results suggest that retention index in preoperative LPG can be useful factor for predicting sentinel lymph node metastasis.

European Journal of Cancer Supplements, 2010

This included the reasons why IBR was not undertaken. For some patients there were multiple reaso... more This included the reasons why IBR was not undertaken. For some patients there were multiple reasons why IBR was not undertaken. In these cases, the reasons were ranked by 2 clinicians and the primary reason determined. We then examined whether patients received radiotherapy.

The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, 2010

Despite the advances in the understanding of neural and genetic foundations of violence, the inve... more Despite the advances in the understanding of neural and genetic foundations of violence, the investigation of the biological bases of a mental disorder is rarely included in psychiatric evaluation of mental insanity. Here we report on a case in which cognitive neuroscience and behavioral genetics methods were applied to a psychiatric forensic evaluation conducted on a young woman, J.F., tried for a violent and impulsive murder. The defendant had a history of multidrug and alcohol abuse and non-forensic clinical evaluation concluded for a diagnosis of borderline personality disorder. We analyzed the defendant's brain structure in order to underlie possible brain structural abnormalities associated with pathological impulsivity. Voxel-based morphometry indexed a reduced gray matter volume in the left prefrontal cortex, in a region specifically associated with response inhibition. Furthermore, J.F. 's DNA was genotyped in order to identify genetic polymorphisms associated with various forms of violence and impulsive behavior. Five polymorphisms that are known to be associated with impulsivity, violence, and other severe psychiatric illnesses were identified in J.F. 's DNA. Taken together, these data provided evidence for the biological correlates of a mental disorder characterized by high impulsivity and aggressive tendencies. Our claim is that the use of neuroscience and behavioral genetics do not change the rationale underlying the determination of criminal liability, which must be based on a causal link between the mental disorder and the crime. Rather, their use is crucial in providing objective data on the biological bases of a defendant's mental disorder.

European Journal of Cancer Supplements, 2010

Background: Hepatocellular carcinoma (HCC) is a highly aggressive and chemo resistant type of can... more Background: Hepatocellular carcinoma (HCC) is a highly aggressive and chemo resistant type of cancer. Although novel anti-HER2/neu targeted therapeutic strategies have been developed and applied in some types of malignancies, specific mechanisms of deregulation in HER2/neu (17q21) depended -signaling transduction pathway remain under investigation in HCC. Our aim was to investigate the potential role of simultaneous HER2/neu and PTEN (10q21-suppressor gene) dysregulation in HCCs. Materials and Methods: Using tissue microarray technology, fifty-two (n = 52) formalin fixed and paraffin embedded tissue samples of histologically confirmed primary HCCs were cored and re embedded in the final paraffin block (core diam 1.5 mm). Immunohistochemistry (IHC) was performed by applying anti-HER2/neu and anti-PTEN antibodies. Fluorescence in situ hybridization (FISH) analysis was also performed regarding those genes. Results: Protein over expression was observed in 12/52 (23%) cases regarding HER2/neu, whereas PTEN decreased or loss of expression in 22/52 (43%) cases. HER2/neu gene amplification was confirmed in 7/52 (13%) cases, whereas no one of the examined cases demonstrated PTEN gene numerical imbalances. Combined HER2/neu and PTEN aberrant expression was observed in 9/52 cases associated to the grade of the examined tumours (p = 0.01). Conclusions: HER2/neu up-regulation combined to PTEN down-regulation is a relatively frequent and critical genetic event in HCC correlated also with an aggressive phenotype. PTEN decreased expression maybe is a negative prognostic factor for applying anti-HER2/neu targeted monoclonal antibody therapy (high chemo-resistance levels) in patients with HCC, based on breast adenocarcinoma management experience.

Molecular and Cellular Therapies, 2014

Despite ongoing research efforts and attempts to bring new drugs into trial, the prognosis for br... more Despite ongoing research efforts and attempts to bring new drugs into trial, the prognosis for brain tumors remains poor. Patients with the most common and lethal intracranial neoplasia, glioblastoma multiforme (GBM), have an average survival of one year with combination of surgical resection, radiotherapy and temozolomide. One of the main problems in the treatment of GBM is getting drugs across the blood brain barrier (BBB) efficiently. In an attempt to solve this problem, there are ongoing experimental and clinical trials to deliver drugs within stem cells. The purpose for this method is the ease by which stem cells home to the brain. This review discusses the experimental and clinical applications of stem cells for GBM. We also discuss the different properties of stem cells. This information is important to understand why one stem cell would be advantageous over another in cell therapy. We provide an overview of the different drug delivery methods, gene-based treatments and cancer vaccines for GBM, including the stem cell subset.

doi: 10.3389/fnbeh.2010.00160 How neuroscience and behavioral genetics improve psychiatric assess... more doi: 10.3389/fnbeh.2010.00160 How neuroscience and behavioral genetics improve psychiatric assessment: report on a violent murder case

Scientific Reports, 2017

Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing soci... more Train the Brain Consortium † Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65-89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenationlevel-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects. The world is experiencing a substantial increase in the proportion of elderly adults in the population. With an aging society comes the increase in age related frailties, which may lead to cognitive impairments and to dementia, mostly in the form of Alzheimer's Disease (AD). Age is indeed the major risk factor for dementia: the age-specific incidence rates for AD demonstrate a doubling of incidence for about every six years of added life 1. The number of people with dementia worldwide was 35.6 million in 2010 and that is estimated to increase to 65.7 million by 2030 and 115.4 million by 2050 unless effective means of reducing the incidence of this disease are introduced 2. Several epidemiological studies have demonstrated that modifiable lifestyle factors, such as practicing physical exercise, being engaged in stimulating cognitive activities, maintaining an active social life into old age, and controlling nutrition, are correlated with maintaining good brain functioning, specifically in the elderly, and with reduced risk of developing dementia 3-8. Norton et al. 9 estimated that around one third of AD cases worldwide might be attributable to potentially modifiable risk factors which include several lifestyle habits. Interventions based on cognitive training 10 , diet 11 or physical activity 7,12,13 have indeed been found to produce positive effects on cognitive status in cognitively unimpaired adult or elderly subjects. Potential mechanisms underlying the effects of cognitive and physical activity on cognition, suggested also by studies in animal models, include increased hippocampal neurogenesis, increased Cerebral Blood Flow (CBF), and enhanced brain plasticity 14,15. An important point that has recently emerged both from the human and animal research, is that enhanced physical and cognitive activities seem to have additive effects on brain plasticity and age related cognitive decline 16. In this line, a very important study is the FINGER trial 17 , in which 1260 subjects, aged 60-77 years, with cognition in the mean level for age and elevated Dementia Risk Score, were randomized to a 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring, showing that cognitive performances improved more in the intervention than in the control group.

Journal of Alzheimer's Disease, 2008

Increasing evidence suggests a role for nerve growth factor (NGFB), brain-derived neurotrophic fa... more Increasing evidence suggests a role for nerve growth factor (NGFB), brain-derived neurotrophic factor (BDNF), and their receptors, nerve growth factor receptor (NGFR), and neurotrophin tyrosine kinase receptors 1 and 2 (NTRK1 and NTRK2), in Alzheimer's disease (AD). However, genetic association between the neurotrophin system genes and AD has been poorly investigated. We genotyped 21 single nucleotide polymorphisms (SNPs) within these genes in a population of Italian AD patients and healthy controls. We found an allele-wise association of rs2072446 on NGFR with familial AD (fAD, p = 0.047), and a genotype-wise association of rs2289656 on NTRK2 with sporadic AD (sAD, p = 0.0036). rs6336 on NTRK1 resulted associated to early-onset sAD in both allele-wise (p = 0.028) and genotype-wise (p = 0.014) analysis, while rs1048218 on BDNF showed allele-wise association with late-onset sAD (p = 0.047). A trend to association with sAD and/or fAD was observed for other SNPs. Our results suggest that genetic variants of neurotrophin system genes might confer susceptibility to AD.

Frontiers in Behavioral Neuroscience, 2017

Pellegrini et al. Gene by Gender Interplay in Moral Choices than males, our results, though preli... more Pellegrini et al. Gene by Gender Interplay in Moral Choices than males, our results, though preliminary and therefore in need of replication in independent samples, suggest that this increase in dopamine availability enhances the cognitive and reduces the emotional components of moral decision-making in females, thus favoring a more rationally-driven decision process.

<b>Copyright information:</b>Taken from "TAMGeS: a Three-Array Method for Genoty... more <b>Copyright information:</b>Taken from "TAMGeS: a Three-Array Method for Genotyping of SNPs by a dual-colour approach"BMC Genomics 2007;8():10-10.Published online 9 Jan 2007PMCID:PMC1783851.s, and on the Y axis the average value of the frequency of genotyping errors. Symbols indicate the methods: squares refer to the direct Two-Array Method; diamonds refer to TAMGeS. For multiplicative variability greater than 1.8, the genotyping performance of TAMGeS results significantly better than that of direct Two-Array Method.

Behavioural Brain Research

In recent years, conflicting findings have been reported in the scientific literature about the i... more In recent years, conflicting findings have been reported in the scientific literature about the influence of dopaminergic, serotonergic and oxytocinergic gene variants on moral behavior. Here, we utilized a moral judgment paradigm to test the potential effects on moral choices of three polymorphisms of the Oxytocin receptor (OXTR): rs53576, rs2268498 and rs1042770. We analyzed the influence of each single polymorphism and of genetic profiles obtained by different combinations of their genotypes in a sample of male insurance brokers (n = 129), as compared to control males (n = 109). Insurance brokers resulted significantly more oriented to maximize outcomes than control males, thus they expressed more than controls the utilitarian attitude phenotype. When analyzed individually, none of the selected variants influenced the responses to moral dilemmas. In contrast, a composite genetic profile that potentially increases OXTR activity was associated to higher moral acceptability in brokers. We hypothesize that this genetic profile promotes outcome-maximizing behavior in brokers by focusing their attention on what represents a greater good, that is, saving the highest number of people, even though at the cost of sacrificing one individual. Our data suggest that investigations in a sample that most expresses the phenotype of interest, combined with the analysis of composite genetic profiles rather than individual variants, represent a promising strategy to find out weak genetic influences on complex phenotypes, such as moral behavior.

The human brain develops through a sophisticated process that starts a few weeks after conception... more The human brain develops through a sophisticated process that starts a few weeks after conception and reaches its completion 20–30 years later. Changes that take place over this timeframe are of primary importance, as they constitute the “hardware” of the adult brain. Both genetic and environmental factors are crucial for brain development. In particular, brain sensitivity to the environment is maximum during prenatal and early postnatal life, when brain undergoes most of its development and is extremely vulnerable to both organizing and disorganizing experiences. The quality of prenatal and early postnatal environment may then influence the trajectory of neuronal development and contribute to shape the developing brain, thus producing long-lasting effects on behavior. Epigenetic changes have been reported to represent the molecular mechanisms by which the early environment modulates the expression of genes, including NR3C1, CRH, and 11-Beta-HSD2 involved in the HPA axis activity, o...

International Journal of Psychophysiology

Neuroscience & Biobehavioral Reviews

This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt... more This review of the neuroscience of anger is part of The Human Affectome Project, where we attempt to map anger and its components (i.e., physiological, cognitive, experiential) to the neuroscience literature (i.e., genetic markers, functional imaging of human brain networks) and to linguistic expressions used to describe anger feelings. Given the ubiquity of anger in both its normative and chronic states, specific language is used in humans to express states of anger. Following a review of the neuroscience literature, we explore the language that is used to convey angry feelings, as well as metaphors reflecting inner states of anger experience. We then discuss whether these linguistic expressions can be mapped on to the neural circuits during anger experience and to distinct components of anger. We also identify relationships between anger components, brain networks, and other affective research relevant to motivational states of dominance and basic needs for safety.

Frontiers in Behavioral Neuroscience

Experimental Biology and Medicine, 2010

Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also b... more Preliminary clinical trials have recently shown that phenytoin, an antiepileptic drug, may also be beneficial for treatment of bipolar disorder. To examine molecular mechanisms of action of phenytoin as a potential mood stabilizer, DNA microarrays were used to study the effect of phenytoin on gene expression in the hippocampus and frontal cortex of Sprague–Dawley rats. While our particular interest is in bipolar disorder, this is the first DNA microarray study on the effect of phenytoin in brain tissue, in general. As compared with control rats, treated rats had 508 differentially expressed genes in the hippocampus and 62 in the frontal cortex. Phenytoin modulated the expression of genes which may affect neurotransmission, e.g. glutamate decarboxylase 1 ( Gad1) and γ-aminobutyric acid A receptor, alpha 5 ( Gabra5). Phenytoin also exerted an effect on neuroprotection-related genes, namely the survival-promoting and antioxidant genes v-akt murine thymoma viral oncogene homolog 1 ( Akt...

Cytotherapy, 2017

Mesenchymal stromal/stem cells (MSC) have emerged as a class of cells suitable for cellular deliv... more Mesenchymal stromal/stem cells (MSC) have emerged as a class of cells suitable for cellular delivery of nanoparticles, drugs and micro-RNA cargo for targeted treatments such as tumor and other protective mechanisms. The special properties of MSC underscore the current use for various clinical applications. Examples of applications include but are not limited to regenerative medicine, immune disorders and anti-cancer therapies. In recent years, there has been intense research in modifying MSC to achieve targeted and efficient clinical outcomes. This review discusses effects of MSC in an inflammatory microenvironment and then explains how these properties could be important to the overall application of MSC in cell therapy. The article also advises caution in the application of these cells because of their role in tumorigenesis. The review stresses the use of MSC as vehicles for drug delivery and discusses the accompanying challenges, based on the influence of the microenvironment on ...

European Journal of Cancer Supplements, 2010

Conclusions: Low retention index in LPG means radioisotope accumulation to SN is impaired. Low re... more Conclusions: Low retention index in LPG means radioisotope accumulation to SN is impaired. Low retention index in n+ suggests that metastatic tumor cells may obstruct lymphatic pathway to SN. The results suggest that retention index in preoperative LPG can be useful factor for predicting sentinel lymph node metastasis.

European Journal of Cancer Supplements, 2010

This included the reasons why IBR was not undertaken. For some patients there were multiple reaso... more This included the reasons why IBR was not undertaken. For some patients there were multiple reasons why IBR was not undertaken. In these cases, the reasons were ranked by 2 clinicians and the primary reason determined. We then examined whether patients received radiotherapy.

The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, 2010

Despite the advances in the understanding of neural and genetic foundations of violence, the inve... more Despite the advances in the understanding of neural and genetic foundations of violence, the investigation of the biological bases of a mental disorder is rarely included in psychiatric evaluation of mental insanity. Here we report on a case in which cognitive neuroscience and behavioral genetics methods were applied to a psychiatric forensic evaluation conducted on a young woman, J.F., tried for a violent and impulsive murder. The defendant had a history of multidrug and alcohol abuse and non-forensic clinical evaluation concluded for a diagnosis of borderline personality disorder. We analyzed the defendant's brain structure in order to underlie possible brain structural abnormalities associated with pathological impulsivity. Voxel-based morphometry indexed a reduced gray matter volume in the left prefrontal cortex, in a region specifically associated with response inhibition. Furthermore, J.F. 's DNA was genotyped in order to identify genetic polymorphisms associated with various forms of violence and impulsive behavior. Five polymorphisms that are known to be associated with impulsivity, violence, and other severe psychiatric illnesses were identified in J.F. 's DNA. Taken together, these data provided evidence for the biological correlates of a mental disorder characterized by high impulsivity and aggressive tendencies. Our claim is that the use of neuroscience and behavioral genetics do not change the rationale underlying the determination of criminal liability, which must be based on a causal link between the mental disorder and the crime. Rather, their use is crucial in providing objective data on the biological bases of a defendant's mental disorder.

European Journal of Cancer Supplements, 2010

Background: Hepatocellular carcinoma (HCC) is a highly aggressive and chemo resistant type of can... more Background: Hepatocellular carcinoma (HCC) is a highly aggressive and chemo resistant type of cancer. Although novel anti-HER2/neu targeted therapeutic strategies have been developed and applied in some types of malignancies, specific mechanisms of deregulation in HER2/neu (17q21) depended -signaling transduction pathway remain under investigation in HCC. Our aim was to investigate the potential role of simultaneous HER2/neu and PTEN (10q21-suppressor gene) dysregulation in HCCs. Materials and Methods: Using tissue microarray technology, fifty-two (n = 52) formalin fixed and paraffin embedded tissue samples of histologically confirmed primary HCCs were cored and re embedded in the final paraffin block (core diam 1.5 mm). Immunohistochemistry (IHC) was performed by applying anti-HER2/neu and anti-PTEN antibodies. Fluorescence in situ hybridization (FISH) analysis was also performed regarding those genes. Results: Protein over expression was observed in 12/52 (23%) cases regarding HER2/neu, whereas PTEN decreased or loss of expression in 22/52 (43%) cases. HER2/neu gene amplification was confirmed in 7/52 (13%) cases, whereas no one of the examined cases demonstrated PTEN gene numerical imbalances. Combined HER2/neu and PTEN aberrant expression was observed in 9/52 cases associated to the grade of the examined tumours (p = 0.01). Conclusions: HER2/neu up-regulation combined to PTEN down-regulation is a relatively frequent and critical genetic event in HCC correlated also with an aggressive phenotype. PTEN decreased expression maybe is a negative prognostic factor for applying anti-HER2/neu targeted monoclonal antibody therapy (high chemo-resistance levels) in patients with HCC, based on breast adenocarcinoma management experience.

Molecular and Cellular Therapies, 2014

Despite ongoing research efforts and attempts to bring new drugs into trial, the prognosis for br... more Despite ongoing research efforts and attempts to bring new drugs into trial, the prognosis for brain tumors remains poor. Patients with the most common and lethal intracranial neoplasia, glioblastoma multiforme (GBM), have an average survival of one year with combination of surgical resection, radiotherapy and temozolomide. One of the main problems in the treatment of GBM is getting drugs across the blood brain barrier (BBB) efficiently. In an attempt to solve this problem, there are ongoing experimental and clinical trials to deliver drugs within stem cells. The purpose for this method is the ease by which stem cells home to the brain. This review discusses the experimental and clinical applications of stem cells for GBM. We also discuss the different properties of stem cells. This information is important to understand why one stem cell would be advantageous over another in cell therapy. We provide an overview of the different drug delivery methods, gene-based treatments and cancer vaccines for GBM, including the stem cell subset.