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1.
Mol Med Rep ; 14(6): 4942-4946, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27748930

ABSTRACT

Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate. Recent evidence has indicated that microRNAs (miRNAs or miRs), a large group of small non­coding oligonoucleotides, may play a significant role in the development of Ca and major psychiatric disorders, such as SZ, bipolar disorder, autism spectrum disorders, suicidality and depression, through their interference with the expression of multiple genes. For instance, the possible role of let­7, miR­98 and miR­183 as biomarkers for Ca and SZ was investigated in our previous research studies. Therefore, further investigations on the expression profiles of these regulatory, small RNA molecules and the molecular pathways through which they exert their control may provide a plausible explanation as to whether there is a correlation between psychiatric disorders and low risk of developing Ca.


Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , MicroRNAs/genetics , Neoplasms/genetics , Schizophrenia/genetics , Animals , Gene Expression Regulation , Humans
2.
Oncol Rep ; 28(6): 2200-4, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23007659

ABSTRACT

Previous studies have suggested that schizophrenia is associ-ated with a reduced risk of cancer. Genes that are involved in cell cycle regulation seem to have additional functions in post-mitotic neurons involved in neuronal migration and synaptic plasticity. MicroRNAs (miRNAs) play a dominant role in the regulation of gene expression in the central nervous system (CNS). Due to their involvement in a large number of CNS pathways, miRNAs pose as appealing molecules for further investigation, with potential diagnostic, prognostic and therapeutic value. In the present study, we investigated the potential association between cancer and schizophrenia in 2 patient sample groups. We analyzed a large number of miRNAs in a control group of 6 schizophrenic patients and a study group of 8 schizophrenic patients with a solid tumor. A comparison between the control and study groups showed that only miR-183 was differentially expressed. Specifically, a significant downregulation of miR-183 in the samples of the study group was observed. Although a larger sample size is required to validate this result for the general patient population, our findings provide a first indication that miR-183 may play a role in regulating the expression of other genes with onco-suppressor activity. Our results are in agreement with the theory that patients with schizophrenia may have a tumor suppressor gene or enhanced neuronal apoptotic activities. Further studies are required in order to shed light on the role of miRNAs and particularly, on the suppressive role of miR-183 in the neurobiological pathways involved in schizophrenia.


Subject(s)
MicroRNAs/genetics , Neoplasms/genetics , Schizophrenia/genetics , Adult , Aged , Apoptosis/genetics , Biomarkers, Tumor/genetics , Down-Regulation , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Humans , Male , Middle Aged , Neoplasms/complications , Schizophrenia/complications
4.
Eur Neuropsychopharmacol ; 20(2): 132-6, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19740630

ABSTRACT

The imaging of the dopamine transporter could demonstrate the implication of dopaminergic pathway in the appearance of tardive dyskinesia. We report a case with psychotic and tardive dyskinesia symptoms. A DAT scan showed decreased dopamine transporter uptake in the area of brain's basal gaglia. A trial with quetiapine improved both psychotic and TD symptoms while a second DAT scan showed improvement status. We conclude that increased dopamine transporter uptake seemed to associate with the improvement of TD.


Subject(s)
Corpus Striatum/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Dyskinesia, Drug-Induced/metabolism , Schizophrenia/metabolism , Tomography, Emission-Computed, Single-Photon , Aged , Antipsychotic Agents/therapeutic use , Corpus Striatum/diagnostic imaging , Corpus Striatum/drug effects , Dibenzothiazepines/therapeutic use , Dyskinesia, Drug-Induced/diagnostic imaging , Dyskinesia, Drug-Induced/drug therapy , Female , Humans , Quetiapine Fumarate , Schizophrenia/complications , Schizophrenia/diagnostic imaging , Schizophrenia/drug therapy
5.
Nucleic Acids Res ; 28(12): E65, 2000 Jun 15.
Article in English | MEDLINE | ID: mdl-10871388

ABSTRACT

We report here modifications of human beta-globin PAC clones by homologous recombination in Escherichia coli DH10B, utilising a plasmid temperature sensitive for replication, the recA gene and a wild-type copy of the rpsL gene which allows for an efficient selection for plasmid loss in this host. High frequencies of recombination are observed even with very small lengths of homology and the method has general utility for introducing insertions, deletions and point mutations. No rearrangements were detected with the exception of one highly repetitive genomic sequence when either the E.COLI: RecA- or the lambdoid phage encoded RecT and RecE-dependent recombination systems were used.


Subject(s)
Cloning, Molecular/methods , Globins/genetics , Bacteriophage P1/genetics , Escherichia coli , Escherichia coli Proteins , Genes, Bacterial , Genetic Markers , Genetic Vectors , Globins/metabolism , Humans , Plasmids , Rec A Recombinases/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Recombination, Genetic , Ribosomal Protein S9
6.
Am J Hum Genet ; 62(4): 890-903, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9529352

ABSTRACT

Darier disease (DD) (MIM 124200) is an autosomal dominant skin disorder characterized by loss of adhesion between epidermal cells and by abnormal keratinization. We present linkage analysis showing, in four families, key recombination events that refine the location of the DD locus on chromosome 12q23-24.1 to a region of <1 cM. We have constructed a YAC/P1 artificial chromosome (PAC)/bacterial artificial chromosome (BAC)-based physical map that encompasses this refined DD region. The map consists of 35 YAC, 69 PAC, 16 BAC, and 2 cosmid clones that were ordered by mapping 54 anonymous sequence-tagged sites. The critical region is estimated to be 2.4 Mb in size, with an average marker resolution of 37.5 kb. The refinement of the critical interval excludes the ALDH2, RPL6, PTPN11, and OAS genes, as well as seven expressed sequence tags (ESTs) previously mapped in the DD region. The three known genes (ATP2A2, PPP1CC, and SCA2) and the 10 ESTs mapped within the critical region are not obvious candidates for the DD gene. Therefore, this detailed integrated physical, genetic, and partial transcript map provides an important resource for the isolation of the DD gene and, possibly, other disease genes.


Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 12 , Darier Disease/genetics , Chromosomes, Artificial, Yeast , Chromosomes, Bacterial , DNA, Recombinant , Female , Haplotypes , Humans , Male , Pedigree
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