• 생물정신의학
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• 제17권2호
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• pp.65-69
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• 2010

Gene-environment interactions are important in pathogenesis of suicide or suicidal behavior. Twin and adoption studies and family studies show that genetic factors play a critical role in suicide or suicidal behavior. Given the strong association between serotonergic neurotransmission and suicide, recent molecular genetic studies have focused on polymorphisms of serotonin genes, especially on serotonin transporter and tryptophan hydroxylase genes. Some studies have revealed a significant interaction between s allele of the serotonin transporter gene and the risk of suicide attempt associated with childhood trauma. In addition, the polymorphism of brain-derived neurotrophic factor gene also may influence the effect of childhood trauma in relation to the risk of attempting suicide. Future studies should explore genetic and environmental factors in suicide or suicidal behavior and examine for gene and environment interaction.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.781-784
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• 2012

The aim of this study was to evaluate the effect of the adenovirus-mediated double suicide gene (CD/TK) for selective killing of gastric cancer cells. Gastric cancer cells SCG7901 and normal gastric epithelial cell lines were infected by adenoviruses Ad-survivin/GFP and Ad-survivin/CD/TK. GFP expression and CD-TK were detected by fluorescence microscopy and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. After treatment of the infected cells with the pro-drugs ganciclovir (GCV) and/or 5-FC, the cell growth status was evaluated by methyl thiazolyl tetrazolium assay. Cell cycle changes were detected using flow cytometry. In nude mice bearing human gastric cancer, the recombinant adenovirus vector was injected directly into the tumor followed by an intraperitoneal injection of GCV and/or 5-FC. The subsequent tumor growth was then observed. The GFP gene driven by survivin could be expressed within the gastric cancer line SCG7901, but not in normal gastric epithelial cells. RT-PCR demonstrated the presence of the CD/TK gene product in the infected SCG7901 cells, but not in the infected normal gastric epithelial cells. The infected gastric cancer SCG7901, but not the gastric cells, was highly sensitive to the pro-drugs. The CD/TK fusion gene system showed significantly greater efficiency than either of the single suicide genes in killing the target cells (P<0.01). Treatment of the infected cells with the pro-drugs resulted in increased cell percentage in G0-Gl phase and decreased percentage in S phase. In nude mice bearing SCG7901 cells, treatment with the double suicide gene system significantly inhibited tumor growth, showing much stronger effects than either of the single suicide genes (P<0.01). The adenovirus-mediated CD/TK double suicide gene driven by survivin promoter combined with GCV an 5-FC treatment could be an effective therapy against experimental gastric cancer with much greater efficacy than the single suicide gene CD/TK combined with GCV or 5-FC.

• 한국발생생물학회지:발생과생식
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• 제16권3호
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• pp.155-168
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• 2012

Therapeutic cancer is a long lasting and turbulent history accompany with the milestones in surgical intervention, chemotherapy and radiotherapy. In the past decade, however, metastatic cancer still obstinately exists challenging the professional scientist. Beside the major forms of cancer treatment, Diphtheria toxin (DT) which is produced by a pathogenic strain of bacterium Corynebacterium diphtheria to shield themselves against the other dangerous organism, have been researched as a potential candidate to overcome the drawback such as non-specific, non-effect to drug resistant cancer cell and side effects when using chemotherapy and radiotherapy. In the context of suicide gene therapy, the DT expression under controlling of tissue-specific promoter will be targeted in cancer cell but defect in normal cell. The molecular mechanism, characteristic of DT-bases therapy and prominent achievements of preclinical and clinical studies for the past decade are summarized and discussed in this review.

• 생물정신의학
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• 제11권2호
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• pp.110-116
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• 2004

Objectives:Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. Methods:The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan$^{(R)}$ assay using primers based on previous studies. Results:The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). Conclusion:These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1997년도 한국생물과학협회 학술발표대회
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• pp.85-85
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• 1997

No Abstract, See Full Text

• Journal of Korean Neurosurgical Society
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• 제30권sup1호
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• pp.13-19
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• 2001

Objective : We investigated the feasibility of a double suicide gene/prodrug therapy, involving direct introduction of the herpes simplex virus Type 1 thymidine kinase(TK) gene and the Escherichia coli cytosine deaminase(CD) gene, via a recombinant adenoviral vector and ganciclovir(GCV) and/or 5-fluorocytosine(5-FC) treatment, in C6 glioma cells. Methods : Efficient gene transfer and transduction of C6 glioma cells via a recombinant adenovirus were evaluated by infecting cells with adenovirus bearing the ${\beta}$-galactosidase gene and then staining cells with 5-bromo-4-chloro-3-indolyl-13-D-galactoside. CD/TK expression in cells infected with adenovirus bearing the CD/TK gene(ad-CD/TK) was examined by immunoblotting analysis. For in vitro cytotoxicity experiments, the cells were infected with ad-CD/TK or ad-${\Delta}E1$(as a control). After addition of a variety of concentrations of GCV and 5-FU, either separately or in combination, cell viability was determined by staining the cells with crystal violet solution 6 days after infection. Result : C6 glioma cells were efficiently transduced with recombinant adenoviral vector at multiplicities of infection of 200 or more. In vitro cytotoxicity of GCV and/or 5-FC, either alone or in combination, was exclusively observed in the cells transduced with ad-CD/TK. Obvious cytotoxicity(>50% inhibition) was observed in the presence of 5-FC at concentrations greater than 30ug/ml or GCV at concentrations greater than 0.3ug/ml at a multiplicity of infection of 100. Additionally, cytotoxicity in the presence of both GCV and 5-FC was greater than that after sinlge-prodrug treatments, indicating additive effects of the prodrug treatments. Conclusion : The administration of a double-suicide gene/prodrug therapy might have great potential in the treatment of brain tumors.

• 생물치료정신의학
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• 제24권3호
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• pp.129-141
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• 2018

Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall into sorrow and suffering therefore this suicide is a huge loss to family and society. There have been attempts to reduce and prevent suicide by understanding the mechanism of suicide. The mechanism of suicide can be thought of as psychological mechanism and biological mechanism. In the past, if we considered the psychological and biological mechanisms separately, the development of neuroscience now connects and integrates these two. Psychological factors affect biological factors and biological temperaments also affect perception or thinking about the situation and increase psychological vulnerability. Distant factors in suicidal behavior-such as childhood adversity and family and genetic predisposition-increase the lifetime risk of suicide. They alter the response to stress and other processes through changes in gene expression and regulation of emotional and behavioral characteristics. Distant factors affect the biological system and consequently changes in these systems can increase the risk of suicide. In other words, the distal factor does not directly induce suicidal behavior but rather acts indirectly through developmental or mediating factors. These mediating factors are impulsive aggressive and anxious trait, and chronic use of substances. The mechanism of this disorder is the abnormality of the serotonin system and the abnormality of the lipid level. Proximal factors are associated with the onset of suicide events and include changes in the major neurotransmitter systems, inflammatory changes, and dysfunction of glial cells in the brain. A series of studies, including a variety of research methods and postmortem and in-vivo imaging studies, show the impairment of the serotonergic neurotransmitter system and hypothalamic-pituitary-adrenal axis stress response system for suicidal behavior. These disorders lead to suicidal behavior due to difficulty in cognitive control of mood, pessimism, reactive aggression, abnormality in problem solving abilities, excessive response to negative social signals, severe emotional distress, and cognitive dysregulation of suicidal ideation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2121-2127
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• 2012

Objective: Deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) mutants have been reported to exert suicide gene effects in combined gene/chemotherapy of cancer. Here, we aimed to further evaluate the capacity of the mutanted enzyme and its potential for inhibiting cancer cell growth. Methods: We altered the sequence of the last 10 amino acids of Dm-dNK to perform site-directed mutagenesis and constructed active site mutanted Dm-dNK (Dm-dNKmut), RT-PCR and western bloting studies were used to reveal the expression of lentivirus mediated Dm-dNKmut in a breast cancer cell line (Bcap37), a gastric cancer cell line (SGC7901) and a colorectal cancer cell line (CCL187). [3H]-labeled substrates were used for enzyme activity assays, cell cytotoxicity was assessed by MTT assays, cell proliferation using a hemocytometer and apoptosis induction by thenannexin-V-FITC labeled FACS method. In vivo, an animal study was set out in which BALB/C nude mice bearing tumors were treated with lentivirus mediated expression of Dm-dNKmut with the pyrimidine nucleoside analog brivudine (BVDU, (E)-5-(2-bromovinyl)-(2-deoxyuridine). Results: The Dm-dNKmut could be stably expressed in the cancer cell lines and retained its enzymatic activity. Moreover, the cells expressing Dm-dNKmut exhibited increased sensitivity in combination with BVDU, with induction of apoptosis in vitro and in vivo. Conclusion: These findings underlined the importance of BVDU phosphorylated by Dm-dNKmut in transduced cancer cells and the potential role of Dm-dNKmut as a suicide gene, thus providing the basis for future intensive research for cancer therapy.

• IMMUNE NETWORK
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• 제1권1호
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• pp.45-52
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• 2001

Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.

• 대한수의학회지
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• 제39권2호
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• pp.327-337
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• 1999

The transposon TnphoA was used to generate avirulent mutants from a type A Pasteurella multocida. A suicide vector plasmid pRT733 carrying TnphoA, having the kanamycin resistant gene and harbored in Escherichia coli K-12 strain SM10(${\lambda}pir$), was mated with streptomycin resistant P. multocida P-1059 strain as recipient. This resulted in the generation of two TnphoA insertion mutants (transconjugants, tc95-a and tc95-b) which were resistant both to kanamycin ($Km^{R}$) and streptomycin ($Sm^{R}$), secreted alkaline phosphatase, and were avirulent to turkeys. Southern blot hybridization using two probes derived from internal fragments of TnphoA, confirmed the insertion of TnphoA into 12.9kb or 13.7kb DNA fragment from the EcoRV digested genomic fragments of transconjugants. The two transconjugants, tc95-a and tc95-b, were distinguishable from their parent strains by differences in ribotypes, and outer membrane protein profiles. TnphoA insertion in both transconjugants also resulted in constitutive expression of a 33Kd iron regulated outer membrane protein (IROMP). The gene encoding $Sm^{R}$ was also located within the same 12.9kb EcoRV genomic fragment from both transconjugants. Furthermore, our finding that the recipient P. multocida P-1059 $Sm^{R}$ strain and both transconjugants were avirulent to turkeys suggest that the either 12.9kb or 13.7kb genomic DNA contains the virulence gene and speculate that the presence of $Sm^{R}$ gene or TnphoA insertion may be responsible for regulating and inactivating the gene(s) encoding virulence in P. multocida.