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Sample records for tumor-specific suicide gene

  1. Tumor-specific expression of shVEGF and suicide gene as a novel strategy for esophageal cancer therapy.

    Science.gov (United States)

    Liu, Ting; Wu, Hai-Jun; Liang, Yu; Liang, Xu-Jun; Huang, Hui-Chao; Zhao, Yan-Zhong; Liao, Qing-Chuan; Chen, Ya-Qi; Leng, Ai-Min; Yuan, Wei-Jian; Zhang, Gui-Ying; Peng, Jie; Chen, Yong-Heng

    2016-06-21

    To develop a potent and safe gene therapy for esophageal cancer. An expression vector carrying fusion suicide gene (yCDglyTK) and shRNA against vascular endothelial growth factor (VEGF) was constructed and delivered into EC9706 esophageal cancer cells by calcium phosphate nanoparticles (CPNP). To achieve tumor selectivity, expression of the fusion suicide gene was driven by a tumor-specific human telomerase reverse transcriptase (hTERT) promoter. The biologic properties and therapeutic efficiency of the vector, in the presence of prodrug 5-fluorocytosine (5-FC), were evaluated in vitro and in vivo. Both in vitro and in vivo testing showed that the expression vector was efficiently introduced by CPNP into tumor cells, leading to cellular expression of yCDglyTK and decreased VEGF level. With exposure to 5-FC, it exhibited strong anti-tumor effects against esophageal cancer. Combination of VEGF shRNA with the fusion suicide gene demonstrated strong anti-tumor activity. The shVEGF-hTERT-yCDglyTK/5-FC system provided a novel approach for esophageal cancer-targeted gene therapy.

  2. Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter.

    Science.gov (United States)

    Ahn, M; Lee, S-J; Li, X; Jiménez, J A; Zhang, Y-P; Bae, K-H; Mohammadi, Y; Kao, C; Gardner, T A

    2009-01-01

    Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 microg ml(-1)), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy.

  3. Anti-tumor effect of adenovirus-mediated suicide gene therapy under control of tumor-specific and radio-inducible chimeric promoter in combination with γ-ray irradiation in vivo

    International Nuclear Information System (INIS)

    Sun Wenjie; Yu Haijun; Xiongjie; Xu Yu; Liao Zhengkai; Zhou Fuxiang; Xie Conghua; Zhou Yunfeng

    2011-01-01

    Objective: To detect the selective inhibitory effects of irradiation plus adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) suicide gene system using tumor-specific and radio-inducible chimeric promoter on human hepatocellular carcinoma subcutaneously xenografted in nude mouse. Methods: Recombinant replicated-deficient adenovirus vector containing HRP gene and chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 radio-inducible CArG elements was constructed. A human subcutaneous transplanting hepatocellular carcinoma (MHCC97 cell line) model was treated with γ-ray irradiation plus intra-tumor injections of adenoviral vector and intra-peritoneal injections of prodrug IAA. The change of tumor volume and tumor growth inhibiting rate, the survival time of nude mice, as well as histopathology of xenograft tumor and normal tissues were evaluated. Results: Thirty one days after the treatment, the relative tumor volumes in the negative, adenovirus therapy, irradiation, and combination groups were 49.23±4.55, 27.71±7.74, 28.53±10.48 and 11.58±3.23, respectively.There was a significantly statistical difference among them (F=16.288, P<0.01).The inhibition effect in the combination group was strongest as compared with that in other groups, and its inhibition ratio was 76.5%. The survival period extended to 43 d in the combination group, which showed a significantly difference with that in the control group (χ 2 =18.307, P<0.01). The area of tumors necrosis in the combination group was larger than that in the other groups, and the normal tissues showed no treatment-related toxic effect in all groups. However, multiple hepatocellular carcinoma metastases were observed in the liver in the control group, there were a few metastases in the monotherapy groups and no metastasis in the combination group. Conclusions: Adenovirus-mediated suicide gene therapy plus radiotherapy dramatically could inhibit tumor growth and prolong

  4. Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

    International Nuclear Information System (INIS)

    Chang, Joe Y.; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

    2006-01-01

    Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival

  5. TUMOR-SPECIFIC EXPRESSION AND ALTERNATIVE SPLICING OF THE COL6A3 GENE IN PANCREATIC CANCER

    Science.gov (United States)

    Arafat, Hwyda; Lazar, Melissa; Salem, Khalifa; Chipitsyna, Galina; Gong, Qiaoke; Pan, Te-Cheng; Zhang, Rui-Zhu; Yeo, Charles J.; Chu, Mon-Li

    2011-01-01

    Introduction Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease in which a prominent desmoplastic reaction is a defining characteristic. Fibrillar collagens, such as collagen I and to a lesser extent, collagen III and V comprise the majority of this stromal fibrosis. Type VI collagen (COL6) forms a microfibrillar network associated with type I collagen fibrils. The expression of COL6 has been linked to inflammation and survival. Importantly, tumor-specific alternative splicing in COL6A3 has been identified in several cancers by genome exon arrays. We evaluated the expression and localization of COL6A3 in PDA and premalignant lesions and explored the presence of alternative splicing events. Methods We analyzed paired PDA-normal (n=18), IPMN (n=5), pancreatic cystadenoma (n=5), and eight PDA cell lines with RT-PCR, using unique primers that identify total COL6A3 gene and alternative splicing sites in several of its exons. Western blot analysis and immunohistochemistry were used to analyze the expression levels and localization of COL6A3 protein in the different lesions, and in two animal models of PDA. Results COL6A3 protein levels were significantly upregulated in 77% of the paired PDA-adjacent tissue examined. COL6A3 was mainly present in the desmoplastic stroma of PDA, with high deposition around the malignant ducts and in between the sites of stromal fatty infiltration. Analysis of the COL6A3 splice variants showed tumor-specific consistent inclusion of exons 3 and 6 in 17 of the 18 (94%) paired PDA-adjacent tissues. Inclusion of exon 4 was exclusively tumor-specific, with barely detectable expression in the adjacent tissues. IPMN and pancreatic cystadenomas showed no expression of any of the examined exons. Total COL6A3 mRNA and exon 6 were identified in six PDA cell lines, but only two cell lines (MIA PACA-2 and ASPC-1) expressed exons 3 and 4. In both the xenograft and transgenic models of PDA, COL6A3 immunoreactivity was present in the stroma

  6. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Hop Paul Brousse, INSERM, Hepatobiliary Ctr, U785, F-94800 Villejuif (France); Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Univ Paris Sud, Fac Med, F-94800 Villejuif (France); Boisgard, R.; Tavitian, B. [INSERM, U803, F-91400 Orsay (France); Boisgard, R.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Lab Imagerie Mol Expt, F-91400 Orsay (France); Roux, J.; Cales, P. [Univ Angers, UPRES EA 3859, Lab Hemodynam Interact Fibrose et Invas Tumorale H, Angers (France); Clerc, J. [Hop Cochin, AP HP, Dept Nucl Med, F-75014 Paris (France)

    2008-07-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III {alpha}, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of {sup 131}I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. {sup 131}I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  7. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    International Nuclear Information System (INIS)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Boisgard, R.; Tavitian, B.; Boisgard, R.; Tavitian, B.; Roux, J.; Cales, P.; Clerc, J.

    2008-01-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III α, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of 131 I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. 131 I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  8. Tumor-specific mutations in low-frequency genes affect their functional properties

    NARCIS (Netherlands)

    L. Erdem-Eraslan (Lale); D. Heijsman (Daphne); M. De Wit (Maurice); A.E. Kremer (Andreas); A. Sacchetti (Andrea); P.J. van der Spek (Peter); P.A.E. Sillevis Smitt (Peter); P.J. French (Pim)

    2015-01-01

    textabstractCausal genetic changes in oligodendrogliomas (OD) with 1p/19q co-deletion include mutations in IDH1, IDH2, CIC, FUBP1, TERT promoter and NOTCH1. However, it is generally assumed that more somatic mutations are required for tumorigenesis. This study aimed to establish whether genes

  9. Hypoxia-Inducible Regulation of a Prodrug-Activating Enzyme for Tumor-Specific Gene Therapy

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    Toru Shibata

    2002-01-01

    Full Text Available Previous studies have suggested that tumor hypoxia could be exploited for cancer gene therapy. Using hypoxia-responsive elements derived from the human vascular endothelial growth factor gene, we have generated vectors expressing a bacterial nitroreductase. (20NTR gene that can activate the anticancer prodrug CB1954. Stable transfectants of human HT1080 tumor cells with hypoxia-inducible vectors were established with G418 selection. Hypoxic induction of NTR protein correlated with increased sensitivity to in vitro exposure of HT 1080 cells to the prodrug. Growth delay assays were performed with established tumor xenografts derived from the same cells to detect the in vivo efficacy of CB1954 conversion to its cytotoxic form. Significant antitumor effects were achieved with intraperitoneal injections of CB1954 both in tumors that express NTR constitutively or with a hypoxia-inducible promoter. In addition, respiration of 10% O2 increased tumor hypoxia in vivo and enhanced the antitumor effects. Taken together, these results demonstrate that hypoxia-inducible vectors may be useful for tumor-selective gene therapy, although the problem of delivery of the vector to the tumors, particularly to the hypoxic cells in the tumors, is not addressed by these studies.

  10. BJ-TSA-9, a novel human tumor-specific gene, has potential as a biomarker of lung cancer.

    Science.gov (United States)

    Li, Yunyan; Dong, Xueyuan; Yin, Yanhui; Su, Yanrong; Xu, Qingwen; Zhang, Yuxia; Pang, Xuewen; Zhang, Yu; Chen, Weifeng

    2005-12-01

    Using bioinformatics, we have identified a novel tumor-specific gene BJ-TSA-9, which has been validated by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). BJ-TSA-9 mRNA was expressed in 52.5% (21 of 40) of human lung cancer tissues and was especially higher in lung adenocarcinoma (68.8%). To explore the potential application of BJ-TSA-9 for the detection of circulating cancer cells in lung cancer patients, nested RT-PCR was performed. The overall positive detection rate was 34.3% (24 of 70) in peripheral blood mononuclear cells (PBMCs) of patients with various types of lung cancers and was 53.6% (15 of 28) in PBMCs of lung adenocarcinoma patients. In combination with the detection of two known marker genes SCC and LUNX, the detection rate was increased to 81.4%. A follow-up study was performed in 37 patients after surgical removal of tumor mass. Among nine patients with persistent detection of two to three tumor marker transcripts in PBMCs, six patients had recurrence/metastasis. In contrast, 28 patients with transient detection of one tumor marker or without detection of any tumor marker were all in remission. Thus, BJ-TSA-9 may serve as a marker for lung cancer diagnosis and as a marker, in combination with two other tumor markers, for the prediction of the recurrence and prognosis of lung cancer patients.

  11. Suicide and the selfish gene.

    Science.gov (United States)

    Satora, Leszek

    2005-01-01

    The application of an evolutionary perspective to human behaviour generates philosophical, political and scientific controversy. Modern human symbolic consciousness is not the cumulation of the long trend that natural selection would predict. The new archaeological data suggested the anatomical and behavioural innovation has been episodic and rare separated by long periods of stagnate. New behavioural mode and the new skeletal structure of modem human arose as an incidental exaptation. Additionally the genetic basis dysfunction connected with suicide behaviour and growing statistic suicide among teenager is contradictory to the theory that our behaviour are programmed in any detail by selfish genes. In this cases genetically determined suicidal behaviour should be rapidly eliminated by natural selection.

  12. Cancer suicide gene therapy: a patent review.

    Science.gov (United States)

    Navarro, Saúl Abenhamar; Carrillo, Esmeralda; Griñán-Lisón, Carmen; Martín, Ana; Perán, Macarena; Marchal, Juan Antonio; Boulaiz, Houria

    2016-09-01

    Cancer is considered the second leading cause of death worldwide despite the progress made in early detection and advances in classical therapies. Advancing in the fight against cancer requires the development of novel strategies, and the suicide gene transfer to tumor cells is providing new possibilities for cancer therapy. In this manuscript, authors present an overview of suicide gene systems and the latest innovations done to enhance cancer suicide gene therapy strategies by i) improving vectors for targeted gene delivery using tissue specific promoter and receptors; ii) modification of the tropism; and iii) combining suicide genes and/or classical therapies for cancer. Finally, the authors highlight the main challenges to be addressed in the future. Even if many efforts are needed for suicide gene therapy to be a real alternative for cancer treatment, we believe that the significant progress made in the knowledge of cancer biology and characterization of cancer stem cells accompanied by the development of novel targeted vectors will enhance the effectiveness of this type of therapeutic strategy. Moreover, combined with current treatments, suicide gene therapy will improve the clinical outcome of patients with cancer in the future.

  13. A small interfering RNA screen of genes involved in DNA repair identifies tumor-specific radiosensitization by POLQ knockdown

    DEFF Research Database (Denmark)

    Higgins, Geoff S; Prevo, Remko; Lee, Yin-Fai

    2010-01-01

    The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor...... radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B......) and irradiated normal tissue cells (MRC5). Using gammaH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA...

  14. Promoter Hypermethylation of the Eyes Absent 4 Gene is a Tumor-Specific Epigenetic Biomarker in Iranian Colorectal Cancer Patients

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    Matineh Barati Bagerabad

    2018-02-01

    Full Text Available The aim of this study was to investigate whether hypermethylation of Eyes Absent 4 (EYA4 is also implicated in Iranian Colorectal Cancer (CRC patients or not. From fresh frozen tissues, samples from 38 paired (cancer and normal CRC tissue specimens were used in this study, the DNA was isolated, sodium bisulfite treated and analyzed by methylation-specific polymerase (MSP chain reaction using primers specific for unmethylated or methylated promoter sequences of the EYA4 gene. We also analyzed EYA4 mRNA expression using real time RT-PCR. Demographic characteristics of these patients including age, sex, tumor grade, location, stage, and TNM classification were evaluated and the relationship between methylation status of the gene and clinicopathological features was analyzed. Current study indicated that EYA4 promoter hypermethylation has a sensitivity of 81.57% and specificity of 78.94%. Findings showed lower expression of EYA-4 in methylated samples in comparison with its normal adjacent tissue, although it was not significant (P>0.05. No significant associations were observed between EYA4 hypermethylation and the clinicopathological characteristics. Although the clinical patient outcome of our 38 CRC patients was not associated with EYA4 promoter hypermethylation, the high frequency of this methylation and its high sensitivity and specificity to neoplastic cells may qualify EYA4 promoter methylation as a potential candidate screening marker in Iranian population and may help to improve early detection of CRC.

  15. Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

    Directory of Open Access Journals (Sweden)

    Jianqing Pan

    Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

  16. Bacterial Toxins for Oncoleaking Suicidal Cancer Gene Therapy.

    Science.gov (United States)

    Pahle, Jessica; Walther, Wolfgang

    For suicide gene therapy, initially prodrug-converting enzymes (gene-directed enzyme-producing therapy, GDEPT) were employed to intracellularly metabolize non-toxic prodrugs into toxic compounds, leading to the effective suicidal killing of the transfected tumor cells. In this regard, the suicide gene therapy has demonstrated its potential for efficient tumor eradication. Numerous suicide genes of viral or bacterial origin were isolated, characterized, and extensively tested in vitro and in vivo, demonstrating their therapeutic potential even in clinical trials to treat cancers of different entities. Apart from this, growing efforts are made to generate more targeted and more effective suicide gene systems for cancer gene therapy. In this regard, bacterial toxins are an alternative to the classical GDEPT strategy, which add to the broad spectrum of different suicide approaches. In this context, lytic bacterial toxins, such as streptolysin O (SLO) or the claudin-targeted Clostridium perfringens enterotoxin (CPE) represent attractive new types of suicide oncoleaking genes. They permit as pore-forming proteins rapid and also selective toxicity toward a broad range of cancers. In this chapter, we describe the generation and use of SLO as well as of CPE-based gene therapies for the effective tumor cell eradication as promising, novel suicide gene approach particularly for treatment of therapy refractory tumors.

  17. Assisted suicide of a selfish gene.

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    Thomson, M S; Beeman, R W

    1999-01-01

    Medea (M) factors and the hybrid incompatibility factor (H) are involved in two incompatibility systems in flour beetles that were previously thought to be independent. M factors are a novel class of selfish genes that act by maternal lethality to nonself. The H factor causes the death of hybrids with a paternally derived H gene and previously uncharacterized maternal cofactors. We now find that M factors exhibit their selfish behavior only in the absence of the H factor. Furthermore, we show that the previously uncharacterized maternal cofactors required for H-associated hybrid inviability are identical to M factors. We propose that incompatibility between H strains and M strains is due to suppression by the H factor of the self-rescuing activity of the lethal M genes. This interaction has the effect of converting M elements from selfish into self-destructive or "suicidal" genes. M factors are globally widespread, but are conspicuously absent from India, the only country where the H factor is known to occur. Such a mechanism could prevent the spread of selfish M elements by establishing an absolute barrier to hybridization in the boundary between M and non-M zones.

  18. Different stress-related gene expression in depression and suicide

    NARCIS (Netherlands)

    Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

    OBJECTIVE: Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an

  19. Different stress-related gene expression in depression and suicide.

    Science.gov (United States)

    Zhao, J; Qi, X-R; Gao, S-F; Lu, J; van Wamelen, D J; Kamphuis, W; Bao, A-M; Swaab, D F

    2015-09-01

    Suicide occurs in some, but not all depressed patients. So far, it remains unknown whether the studied stress-related candidate genes change in depression, suicide or both. The prefrontal cortex (PFC) is involved in, among other things, impulse control and inhibitory behavior and plays an important role in both suicide and depression. We have employed qPCR to study 124 anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC) brain samples, obtained from two brain banks, from: i) young depressed patients (average age 43 years) who committed suicide (MDD-S) and depressed patients who died from causes other than suicide (MDD-NS) and from ii) elderly depressed patients (average age 75 years) who did not commit suicide (DEP). Both cohorts were individually matched with non-psychiatric non-suicide control subjects. We determined the transcript levels of hypothalamic-pituitary-adrenal axis-regulating molecules (corticotropin-releasing hormone (CRH), CRH receptors, CRH binding protein, mineralocorticoid receptor/glucocorticoid receptor), transcription factors that regulate CRH expression, CRH-stimulating cytokines, chaperone proteins, retinoid signaling, brain-derived neurotrophic factor and tropomyosin-related kinase B, cytochrome proteins, nitric oxide synthase (NOS) and monoamines. In the MDD-S group, expression levels of CRH and neuronal NOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) were increased. Other changes were only present in the DEP group, i.e. decreased NIDD, and increased and 5-hydroxytryptamine receptor 1A (5-HT1A) expression levels. Changes were found to be more pronounced in the anterior cingulate cortex than in the dorsolateral PFC. Depressed patients who committed suicide have different gene expression patterns than depressed patients who died of causes other than suicide. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Glucocorticoid Receptor Related Genes: Genotype And Brain Gene Expression Relationships To Suicide And Major Depressive Disorder

    Science.gov (United States)

    Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A.; Mann, J. John

    2016-01-01

    Introduction We tested the relationship between genotype, gene expression and suicidal behavior and MDD in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior and major depressive disorder (MDD); FK506 binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2) and Glucocorticoid Receptor (NR3C1). Materials and Methods Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N=277) and a postmortem sample (N=209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9) (N=59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, that was associated with increased risk of suicide attempt (OR=1.58, t=6.03, p=0.014). Six SNPs on this gene, three SNPs on SKA2 and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex. One NR3C1 transcript had lower expression in suicide relative to non-suicide sudden death cases (b=-0.48, SE=0.12, t=-4.02, adjusted p=0.004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the prefrontal cortex. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. PMID:27030168

  1. Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric promoter-mediated suicide gene therapy in an immunocompetent mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yu, E-mail: xuyu1001@gmail.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Liu, Zhengchun, E-mail: l135027@126.com [Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Kong, Haiyan, E-mail: suppleant@163.com [Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Sun, Wenjie, E-mail: wendy11240325@163.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Liao, Zhengkai, E-mail: fastbeta@gmail.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Zhou, Fuxiang, E-mail: happyzhoufx@sina.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); Xie, Conghua, E-mail: chxie_65@hotmail.com [Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071 (China); Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, 169 Donghu Road, Wuhan 430071 (China); and others

    2011-09-09

    Highlights: {yields} A novel chimeric promoter consisting of CArG element and hTERT promoter was developed. {yields} The promoter was characterized with radiation-inducibility and tumor-specificity. {yields} Suicide gene system driven by the promoter showed remarkable cytotoxicity in vitro. {yields} Co-expression of IL12 enhanced the promoter mediated suicide gene therapy in vivo. -- Abstract: The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expression of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.

  2. Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric promoter-mediated suicide gene therapy in an immunocompetent mouse model

    International Nuclear Information System (INIS)

    Xu, Yu; Liu, Zhengchun; Kong, Haiyan; Sun, Wenjie; Liao, Zhengkai; Zhou, Fuxiang; Xie, Conghua

    2011-01-01

    Highlights: → A novel chimeric promoter consisting of CArG element and hTERT promoter was developed. → The promoter was characterized with radiation-inducibility and tumor-specificity. → Suicide gene system driven by the promoter showed remarkable cytotoxicity in vitro. → Co-expression of IL12 enhanced the promoter mediated suicide gene therapy in vivo. -- Abstract: The human telomerase reverse transcriptase (hTERT) promoter has been widely used in target gene therapy of cancer. However, low transcriptional activity limited its clinical application. Here, we designed a novel dual radiation-inducible and tumor-specific promoter system consisting of CArG elements and the hTERT promoter, resulting in increased expression of reporter genes after gamma-irradiation. Therapeutic and side effects of adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter were evaluated in mice bearing Lewis lung carcinoma, combining with or without adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus promoter. The combination treatment showed more effective suppression of tumor growth than those with single agent alone, being associated with pronounced intratumoral T-lymphocyte infiltration and minor side effects. Our results suggest that the combination treatment with HRP/IAA system driven by the novel chimeric promoter and the co-expression of IL12 might be an effective and safe target gene therapy strategy of cancer.

  3. Nanoparticle-mediated delivery of suicide genes in cancer therapy.

    Science.gov (United States)

    Vago, Riccardo; Collico, Veronica; Zuppone, Stefania; Prosperi, Davide; Colombo, Miriam

    2016-09-01

    Conventional chemotherapeutics have been employed in cancer treatment for decades due to their efficacy in killing the malignant cells, but the other side of the coin showed off-target effects, onset of drug resistance and recurrences. To overcome these limitations, different approaches have been investigated and suicide gene therapy has emerged as a promising alternative. This approach consists in the introduction of genetic materials into cancerous cells or the surrounding tissue to cause cell death or retard the growth of the tumor mass. Despite promising results obtained both in vitro and in vivo, this innovative approach has been limited, for long time, to the treatment of localized tumors, due to the suboptimal efficiency in introducing suicide genes into cancer cells. Nanoparticles represent a valuable non-viral delivery system to protect drugs in the bloodstream, to improve biodistribution, and to limit side effects by achieving target selectivity through surface ligands. In this scenario, the real potential of suicide genes can be translated into clinically viable treatments for patients. In the present review, we summarize the recent advances of inorganic nanoparticles as non-viral vectors in terms of therapeutic efficacy, targeting capacity and safety issues. We describe the main suicide genes currently used in therapy, with particular emphasis on toxin-encoding genes of bacterial and plant origin. In addition, we discuss the relevance of molecular targeting and tumor-restricted expression to improve treatment specificity to cancer tissue. Finally, we analyze the main clinical applications, limitations and future perspectives of suicide gene therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong

    2005-01-01

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  5. The development of herpes simplex virus thymidine kinase suicide gene imaging

    International Nuclear Information System (INIS)

    Xing Yan; Zhao Jinhua

    2006-01-01

    Suicide gene treatment of tumor catches more and more attention in recent years. Cells transferred with suicide gene from virus or bacteria will express specific enzymes and transform innocuous prodrugs into highly toxic chemotherapeutic drugs. As a result, the cells will be killed. Radionuclide labeled probe can display the biologic characteristics of suicide gene in vivo. This article reviews the development of HSV-tk gene imaging. (authors)

  6. Prefrontal alterations in GABAergic and glutamatergic gene expression in relation to depression and suicide.

    NARCIS (Netherlands)

    Zhao, Juan; Verwer, R.W.H.; Gao, S.; Qi, Xin-Rui; Lucassen, P.J.; Kessels, H.W.; Swaab, D.F.

    2018-01-01

    People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to

  7. Prefrontal alterations in GABAergic and glutamatergic gene expression in relation to depression and suicide

    NARCIS (Netherlands)

    Zhao, J.; Verwer, R.W.H.; Gao, S.-F.; Qi, X.-R.; Lucassen, P.J.; Kessels, H.W.; Swaab, D.F.

    People that committed suicide were reported to have enhanced levels of gene transcripts for synaptic proteins in their prefrontal cortex (PFC). Given the close association of suicide with major depressive disorder (MDD), we here assessed whether these changes are related to suicide or rather to

  8. Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy

    DEFF Research Database (Denmark)

    Khan, Z.; Knecht, Wolfgang; Willer, Mette

    2010-01-01

    The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen...... suicide gene therapy system in combination with stem cell mediated gene delivery promises new treatment of malignant gliomas....

  9. An association study of suicide and candidate genes in the serotonergic system

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette N; Flint, Tracey J; Foldager, Leslie

    2013-01-01

    Introduction: Strong evidence demonstrates a genetic susceptibility to suicidal behaviour and a relationship between suicide and mental disorders. The aim of this study was to test for association between suicide and five selected genetic variants, which had shown association with suicide in other...... populations. Method: We performed a nationwide case-control study on all suicide cases sent for autopsy in Denmark between the years 2000 and 2007. The study comprised 572 cases and 1049 controls and is one of the largest genetic studies in completed suicide to date. The analysed markers were located within...... the Serotonin Transporter (SLC6A4), Monoamine Oxidase-A (MAOA) and the Ttyptophan Hydroxylase I and II (TPH1 and TPH2) genes. Results: None of the genetic markers within SLC6A4, MAOA, TPH1 and TPH2 were significantly associated with completed suicide or suicide method in the basic association tests. Exploratory...

  10. Gene expression associated with suicide attempts in US veterans (Open Access)

    Science.gov (United States)

    2017-09-05

    depression , bipolar disorder, alcohol use disorder9 and intermittent explosive disorder.8 However, because suicide attempts occur in the context of many... suicidal ideation in a genome wide associa- tion study of depressed inpatients.25 These results provide partial replication of gene expression...OPEN ORIGINAL ARTICLE Gene expression associated with suicide attempts in US veterans JD Flory1,2,7, D Donohue3,7, S Muhie3, R Yang4, SA Miller3, R

  11. Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.

    Science.gov (United States)

    van Duijn, Erik; Vrijmoeth, Eslie M; Giltay, Erik J; Bernhard Landwehrmeyer, G

    2018-03-01

    Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior. We included 1451 HD gene expansion carriers (age 48.4 years (SD 14.0), 54.8% female) of the REGISTRY study of the European Huntington's Disease Network. Lifetime suicidal ideation and suicidal behavior were assessed with the Columbia-Suicidal Severity Rating Scale. Motor symptoms and disease stage were assessed using subscales of the Unified Huntington's Disease Rating Scale, and depressed mood and irritability were assessed by the Problem Behaviors Assessment. Lifetime passive suicidal ideation was reported by 21.2%. Participants in stage II showed the highest prevalence rate of suicidal ideation, while participants in stage IV/V showed the highest prevalence of suicidal behavior. A lifetime suicide attempt was reported by 6.5% of the HD gene expansion carriers. In multivariate regression analyses, both suicidal ideation and suicidal behavior were associated with a depressed mood, and to a lesser extend to irritability. Results may have been affected by denial or recall bias and no conclusions can be made about the temporal and causal relationships with depressed mood and irritability because of the cross-sectional analyses. Given the high prevalence of suicidal ideation and suicidal behavior in all stages of HD, it is important to screen HD gene expansion carriers for suicidal ideation and suicidal behavior on a regular basis in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Suicide

    Science.gov (United States)

    Suicide is the tenth most common cause of death in the United States. People may consider suicide when they are hopeless and can't see ... event. People who have the highest risk of suicide are white men. But women and teens report ...

  13. Naturally occurring, tumor-specific, therapeutic proteins.

    Science.gov (United States)

    Argiris, Konstantinos; Panethymitaki, Chrysoula; Tavassoli, Mahvash

    2011-05-01

    The emerging approach to cancer treatment known as targeted therapies offers hope in improving the treatment of therapy-resistant cancers. Recent understanding of the molecular pathogenesis of cancer has led to the development of targeted novel drugs such as monoclonal antibodies, small molecule inhibitors, mimetics, antisense and small interference RNA-based strategies, among others. These compounds act on specific targets that are believed to contribute to the development and progression of cancers and resistance of tumors to conventional therapies. Delivered individually or combined with chemo- and/or radiotherapy, such novel drugs have produced significant responses in certain types of cancer. Among the most successful novel compounds are those which target tyrosine kinases (imatinib, trastuzumab, sinutinib, cetuximab). However, these compounds can cause severe side-effects as they inhibit pathways such as epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor, which are also important for normal functions in non-transformed cells. Recently, a number of proteins have been identified which show a remarkable tumor-specific cytotoxic activity. This toxicity is independent of tumor type or specific genetic changes such as p53, pRB or EGFR aberrations. These tumor-specific killer proteins are either derived from common human and animal viruses such as E1A, E4ORF4 and VP3 (apoptin) or of cellular origin, such as TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and MDA-7 (melanoma differentiation associated-7). This review aims to present a current overview of a selection of these proteins with preferential toxicity among cancer cells and will provide an insight into the possible mechanism of action, tumor specificity and their potential as novel tumor-specific cancer therapeutics.

  14. GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.

    Science.gov (United States)

    Yin, Honglei; Galfalvy, Hanga; Pantazatos, Spiro P; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, J John

    2016-06-01

    We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = -0.48, SE = 0.12, t = -4.02, adjusted P = .004). We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. © 2016 Wiley Periodicals, Inc.

  15. Suicide

    Science.gov (United States)

    ... Mind Sexual Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & ... Do Teens Try to Kill Themselves? Depression Substance Abuse Suicide Is Not Always Planned Warning Signs What ...

  16. Double suicide genes selectively kill human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Liu Lunxu

    2011-02-01

    Full Text Available Abstract Background To construct a recombinant adenovirus containing CDglyTK double suicide genes and evaluate the killing effect of the double suicide genes driven by kinase domain insert containing receptor (KDR promoter on human umbilical vein endothelial cells. Methods Human KDR promoter, Escherichia coli (E. coli cytosine deaminase (CD gene and the herpes simplex virus-thymidine kinase (TK gene were cloned using polymerase chain reaction (PCR. Plasmid pKDR-CDglyTK was constructed with the KDR promoter and CDglyTK genes. A recombinant adenoviral plasmid AdKDR-CDglyTK was then constructed and transfected into 293 packaging cells to grow and harvest adenoviruses. KDR-expressing human umbilical vein endothelial cells (ECV304 and KDR-negative liver cancer cell line (HepG2 were infected with the recombinant adenoviruses at different multiplicity of infection (MOI. The infection rate was measured by green fluorescent protein (GFP expression. The infected cells were cultured in culture media containing different concentrations of prodrugs ganciclovir (GCV and/or 5-fluorocytosine (5-FC. The killing effects were measured using two different methods, i.e. annexin V-FITC staining and terminal transferase-mediated dUTP nick end-labeling (TUNEL staining. Results Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed and they infected ECV304 and HepG2 cells efficiently. The infection rate was dependent on MOI of recombinant adenoviruses. ECV304 cells infected with AdKDR-CDglyTK were highly sensitive to GCV and 5-FC. The cell survival rate was dependent on both the concentration of the prodrugs and the MOI of recombinant adenoviruses. In contrast, there were no killing effects in the HepG2 cells. The combination of two prodrugs was much more effective in killing ECV304 cells than GCV or 5-FC alone. The growth of transgenic ECV304 cells was suppressed in the presence of prodrugs. Conclusion AdKDR-CDglyTK/double prodrog system may be a useful

  17. Suicidal gene therapy with rabbit cytochrome P450 4B1/4-ipomeanol, 2-aminoanthracene system in glioma cell

    International Nuclear Information System (INIS)

    Jang, Su Jin; Kang, Joo Hyun; Kim, Kwang Il; Lee, Tae Sup; Lee, Yong Jin; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

    2010-01-01

    Suicidal gene therapy is based on the transduction of tumor cells with 'suicide' genes encoding for prodrugactivating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4- ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/4-ipo or CYP4B1/2-AA system

  18. Suicidal gene therapy with rabbit cytochrome P450 4B1/4-ipomeanol, 2-aminoanthracene system in glioma cell

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Su Jin; Kang, Joo Hyun; Kim, Kwang Il; Lee, Tae Sup; Lee, Yong Jin; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2010-10-15

    Suicidal gene therapy is based on the transduction of tumor cells with 'suicide' genes encoding for prodrugactivating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4- ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/4-ipo or CYP4B1/2-AA system

  19. Suicide

    Science.gov (United States)

    ... leading cause of death in the United States, accounting for more than 1% of all deaths; Suicide ... of weakness or will somehow interfere with their career. It‘s important to remember that actual weakness poses ...

  20. Suicide

    DEFF Research Database (Denmark)

    Bjerregaard, Peter; Lynge, Inge

    2006-01-01

    The incidence of youth suicides has increased dramatically among the Inuit in Greenland since the modernization started in the 1950s. Suicides currently peak at age 15-24 Men: 400-500, Women: 100-150 per 100,000 person-years. The methods are drastic: shooting or hanging. An early peak was seen...... in the capital, a later peak in the rest of West Greenland, and high and increasing rates in remote East Greenland. Suicidal thoughts occur more often in young people who grew up in homes with a poor emotional environment, alcohol problems and violence. There is a definite correlation with several aspects...... of the modernization process but it is hard to pinpoint causal relationships. It is rather the "modernization package" that should be regarded as risk factors for suicides....

  1. Suicide attempts in children and adolescents: The place of clock genes and early rhythm dysfunction.

    Science.gov (United States)

    Olliac, Bertrand; Ouss, Lisa; Charrier, Annaëlle

    2016-11-01

    Suicide remains one of the leading causes of death among young people, and suicidal ideation and behavior are relatively common in healthy and clinical populations. Suicide risk in childhood and adolescence is often approached from the perspective of nosographic categories to which predictive variables for suicidal acts are often linked. The cascading effects resulting from altered clock genes in a pediatric population could participate in biological rhythm abnormalities and the emergence of suicide attempts through impaired regulation of circadian rhythms and emotional states with neurodevelopmental effects. Also, early trauma and stressful life events can alter the expression of clock genes and contribute to the emergence of suicide attempts. Alteration of clock genes might lead to desynchronized and abnormal circadian rhythms impairing in turn the synchronization between external and internal rhythms and therefore the adaptation of the individual to his/her internal and external environment with the development of psychiatric disorders associated with increased risk for suicide attempts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Improving the Safety of Cell Therapy Products by Suicide Gene Transfer

    Directory of Open Access Journals (Sweden)

    Antonio eDi Stasi

    2014-11-01

    Full Text Available Adoptive T-cell therapy can involve donor lymphocyte infusion (DLI after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte (TILs expanded ex-vivo, or more recently the use of T cell receptor (TCR or chimeric antigen receptor (CAR redirected T cells. However cellular therapies can pose significant risks, including graft-versus-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The ‘ideal’ suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of ‘all’ and ‘only’ the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase (HSV-TK and inducible-caspase-9 (iCasp9.

  3. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.

    Directory of Open Access Journals (Sweden)

    Patrick O McGowan

    Full Text Available BACKGROUND: Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription. METHODOLOGY/PRINCIPAL FINDINGS: We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor. CONCLUSIONS/SIGNIFICANCE: This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.

  4. Composing a Tumor Specific Bacterial Promoter.

    Directory of Open Access Journals (Sweden)

    Igor V Deyneko

    Full Text Available Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.

  5. The combination of suicide gene therapy and radiation enhances the killing of nasopharyngeal carcinoma xenographs

    International Nuclear Information System (INIS)

    Xia Jiahui; Xia Kun; Feng Yong

    2004-01-01

    Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast cytosine deaminase (CD), yeast CD/uracil phosphoribosyl-transferase (UPRT), and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-fluorocytosine (5-FC) and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p<0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies. (author)

  6. Tumor-Specific Immunotherapy of Mammary Cancer

    National Research Council Canada - National Science Library

    Ostrand-Rosenberg, Suzanne

    1998-01-01

    .... To enhance the activation of CD4(+) T helper cells, autologous mouse mammary tumor cells have been transfected with syngeneic MHC class II genes plus costimulatory and antigen presentation accessory molecules, including B7-1, B7-2...

  7. Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.

    Directory of Open Access Journals (Sweden)

    Adolfo Sequeira

    Full Text Available Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0 in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides, the anterior cingulate cortex (ACC: 6NS, 9S and the nucleus accumbens (NAcc: 8NS, 13S. ANCOVA was used to control for age, gender, pH and RNA degradation, with P ≤ 0.01 and fold change ± 1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A and three were down-regulated in the NAcc (MT1F, MT1G, MT1H. Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

  8. Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.

    Science.gov (United States)

    Sequeira, Adolfo; Morgan, Ling; Walsh, David M; Cartagena, Preston M; Choudary, Prabhakara; Li, Jun; Schatzberg, Alan F; Watson, Stanley J; Akil, Huda; Myers, Richard M; Jones, Edward G; Bunney, William E; Vawter, Marquis P

    2012-01-01

    Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P ≤ 0.01 and fold change ± 1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain.

  9. Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Monica Casucci, Attilio Bondanza

    2011-01-01

    Full Text Available Chimeric antigen receptors (CARs are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb with the signal transduction machinery of the T-cell receptor (TCR. The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT, wherein allorecognition causes both the graft-versus-leukemia (GVL effect and graft-versus-host disease (GVHD. Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.

  10. Monitoring HSVtk suicide gene therapy : the role of [F-18]FHPG membrane transport

    NARCIS (Netherlands)

    Buursma, AR; van Dillen, IJ; van Waarde, A; Vaalburg, W; Hospers, GAP; Mulder, NH; de Vries, EFJ

    2004-01-01

    Favourable pharmacokinetics of the prodrug are essential for successful HSVtk/ganciclovir (GCV) suicide gene therapy. [F-18] FHPG PET might be a suitable technique to assess the pharmacokinetics of the prodrug GCV noninvasively, provided that [F-18] FHPG mimics the behaviour of GCV. Since membrane

  11. A novel double-enhanced suicide gene therapy in a colon cancer cell line mediated by gef and apoptin.

    Science.gov (United States)

    Boulaiz, Houria; Aránega, Antonia; Cáceres, Blanca; Blanca, Cáceres; Alvarez, Pablo; Pablo, Alvarez; Serrano-Rodríguez, Fernando; Fernando, Rodríguez-Serrano; Carrillo, Esmeralda; Esmeralda, Carrillo; Melguizo, Consolación; Consolación, Melguizo; Prados, Jose; Jose, Prados

    2014-02-01

    Double-suicide gene therapy is a promising strategy for the treatment of advanced cancer. It has become an important research line in the development of gene therapy to overcome the drawbacks of single-gene therapy. The aim of this study was to investigate the usefulness of double-suicide gene therapy with the two suicide genes, gef and apoptin, in colon carcinoma. gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system. Expression of both genes in the DLD-1 cell line was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Cell viability was determined with the sulforhodamine B colorimetric assay, and the cell cycle was studied by propidium iodide (PI) staining. Annexin V-FITC and PI assays were used to evaluate apoptosis, and the results were confirmed by electron microscopy. The mitochondrial membrane potential was measured by JC-1 assay. Our results showed that the combined expression of gef and apoptin genes was strikingly more effective than the expression of either gene alone. Co-expression of gef and apoptin synergistically enhanced the decrease in cell viability, increasing necrosis and inducing apoptosis in colon cancer cells via the mitochondrial pathway, which can be deficient in advanced or metastatic colon cancer. Double-suicide gene therapy based on gef and apoptin genes may be a candidate for the development of new colon cancer strategies, and further studies are warranted to establish the usefulness of double-suicide gene therapy in vivo.

  12. Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress

    Directory of Open Access Journals (Sweden)

    Kwang eChoi

    2011-07-01

    Full Text Available Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database (www.stanleygenomics.org and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK, the cyclin-dependent kinase (CDK, the mitogen-activated protein kinase (MAPK, and the protein kinase C (PKC in the prefrontal cortex (PFC of mood disorder patients died with suicide (n=45 and without suicide (N=38. We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (n=46. The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (FDR-adjusted p < 0.05, fold change > 1.1. Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05. These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress-associated neural plasticity and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.

  13. Navigating cancer network attractors for tumor-specific therapy

    DEFF Research Database (Denmark)

    Creixell, Pau; Schoof, Erwin; Erler, Janine Terra

    2012-01-01

    understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies....

  14. Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

    Directory of Open Access Journals (Sweden)

    Robyn Jane McQuaid

    2016-07-01

    Full Text Available Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243, conducted among White university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP within the oxytocin receptor gene (OXTR, rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the ‘protective allele’ was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation.

  15. Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Ko, Young-Hoon; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

    2014-04-01

    Although several studies have investigated possible associations between norepinephrine neurotransmitter transporter gene (SLC6A2) polymorphisms and depression, few studies have examined associations between SLC6A2 polymorphisms and suicide. Three single-nucleotide polymorphisms (rs2242446, rs28386840, and rs5569) were measured in 550 patients: 201 with major depressive disorder (MDD) and suicide attempt/s, 160 with MDD without suicide attempts, and 189 healthy controls. Analysis of single-nucleotide polymorphisms (SNPs) and haplotype was conducted for the three groups. Subsequently, multivariate logistic regression analysis adjusting for age and gender was conducted to identify independent influences of each SNP. A possible association between suicide lethality and SLC6A2 polymorphisms was also investigated. In the genotype and allele frequency analysis, there were significant differences in rs28386840 between suicidal MDD patients and healthy controls. In the haplotype analysis, TAA (rs2242446-rs28386840-rs5569, from left to right) was associated with suicide attempts in MDD, although the significance (p=0.043) disappeared after Bonferroni correction. There were no relationships between lethality scores and SLC6A2 polymorphisms in suicidal MDD. Modest sample size and a single type of neurotransmitter analyzed (norepinephrine) are the primary limitations. Our results suggest that SLC6A2 polymorphisms were associated with suicide risk in patients with MDD. Future studies are warranted to elucidate possible mechanisms by which SLC6A2 polymorphisms influence suicide risk. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Effect of suicidal gene combined with irradiation on esophageal carcinoma cell line

    International Nuclear Information System (INIS)

    Pan Jianji; Wang Jiezhong; Zheng Tianrong; Zheng Qiuhong

    2005-01-01

    Objective: As generally known that non-cytotoxic pro-drag can be transformed into cytotoxic drug by suicide gene, this work is to investigate the effect of Coli cytosine deaminase/5-fluorocytosine suicide gene (CD/5-FC) used alone or combined with irradiation in esophageal carcinoma cell line(EC). Methods: CD gene was amplified from Coli DNA genome library with PCR technique, with the eukaryotic vector pcDNA3.1-CD then constructed. ECl09 cells were transfected with pcDNA3.1-CD by liposome method. The cytotoxic effect, bystander effect and radiosensitization effect of CD/5-FC in ECl09 was analyzed. Results: The transfection of CD gene into ECl09 and its transcription was confirmed by RT-PCR method. In vitro, 5-FC showed significantly cytotoxic effect on the EPC cell transfected with CD gene. After adding 5-FC , the survival rate of cultured cell containing 5 % transfect CD gene cell was 41.8 % ± 14.2% while that in the control group was 94.6 ± 4.3 %, (t=3.14, P < 0.05). The survival rate of cultured cell containing 10% transfected CD gene cell was 37.8 ± 4.4% compared to 95.6% ± 5.4% in the control group, (t=9.75, P<0.01). CD/5-FC showed significant radiosen-sitization effect, the survival fraction of CD transfected cell was much lower in 5-FC combined with irradiation, when compared with 5-FC alone and radiotherapy alone group together, (F=11.50, P < 0.01 ). When it was compared with 5-FC alone group and irradiation alone group separately, the difference was also significant( F=4.11, P < 0.05 and F10.53, P < 0.01, respectively). Conclusions: Suicide gene CD/5-FC shows conspicuous by-stander effect and radiosensitization effect. (authors)

  17. MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ronald, J A; Katzenberg, R; Nielsen, Carsten Haagen

    2013-01-01

    In hepatocellular carcinoma (HCC), tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs (miRNAs) are powerful negative regulators of gene expression and many are downregulated in human HCC. We identified seven miRNAs that are also downregulated in tumors...

  18. Radiation effects on tumor-specific DTH response, 2

    International Nuclear Information System (INIS)

    Nobusawa, Hiroshi; Hachisu, Reiko.

    1991-01-01

    Tumor-specific immunity was induced in C3H mice by immunizing with syngeneic MH134 hepatoma cells. Radiation sensitivity of anti-tumor activity of immunized spleen cells were examined and compared with the radiation sensitivity of the delayed-type hypersensitivity (DTH)-response. The spleen cells were irradiated in vitro, then mixed with the tumor cells. DTH-response intensity was determined from the footpad increment twenty-four hours after inoculation of tumor cells with immunized spleen cells. Anti-tumor activity of the spleen cells, based on growth inhibition of tumor cells, was measured by a cytostatic test in vivo with diffusion chambers. Tumor-specific DTH response was suppressed dose-dependently in the range of 12-24 Gy irradiation. No suppression was observed below 12 Gy. Without irradiation, growth of tumor cells was inhibited by immunized spleen cells more effectively than by normal spleen cells. Anti-tumor activity of immunized and normal spleen cells was diminished by irradiation doses of 20 Gy and 10 Gy, respectively. Comparing our report with others that analyzed the type of anti-tumor effector cells induced in this experimental system, we concluded that tumor-specific anti-tumor activity (tumor growth inhibition in vivo) that was radiosensitive at 10-20 Gy depended on a DTH-response. (author)

  19. The effect of genetic variation of the serotonin 1B receptor gene on impulsive aggressive behavior and suicide.

    Science.gov (United States)

    Zouk, Hana; McGirr, Alexander; Lebel, Véronique; Benkelfat, Chawky; Rouleau, Guy; Turecki, Gustavo

    2007-12-05

    Impulsive-aggressive behaviors (IABs) are regarded as possible suicide intermediate phenotypes, mediating the relationship between genes and suicide outcome. In this study, we aimed to investigate the putative relationship between genetic variation at the 5-HT1B receptor gene, which in animal models is involved in impulse-aggression control, IABs, and suicide risk. We investigated the relationship of variation at five 5-HT1B loci and IAB measures in a sample of 696 subjects, including 338 individuals who died by suicide and 358 normal epidemiological controls. We found that variation at the 5-HT1B promoter A-161T locus had a significant effect on levels of IABs, as measured by the Buss-Durkee Hostility Inventory (BDHI). Suicides also differed from controls in distribution of variants at this locus. The A-161T locus, which seems to impact 5-HT1B transcription, could play a role in suicide predisposition by means of mediating impulsive-aggressive behaviors. 2007 Wiley-Liss, Inc.

  20. Dual monitoring using 124I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

    International Nuclear Information System (INIS)

    Lee, T. S.; Kim, J. H.; Kwon, H. C.

    2007-01-01

    Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[ 124 I] iodouracil ( 124 I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ( 124 I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, 124 I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, 124 I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by 124 I-FIAU PET imaging. 124 I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. 124 I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials

  1. DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid biosynthesis associated with depression and suicide risk.

    Science.gov (United States)

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-Yu; Cooper, Thomas B; Burke, Ainsley K; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

  2. DNA methylation perturbations in genes involved in polyunsaturated fatty acid biosynthesis associated with depression and suicide risk

    Directory of Open Access Journals (Sweden)

    Fatemeh eHaghighi

    2015-04-01

    Full Text Available Polyunsaturated fatty acid (PUFA status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6 and α-linolenic acid (ALA, 18:3n-3. We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD with (n=22 and without (n=39 history of suicide attempt, and age- and sex-matched healthy volunteers (n=59. Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1 and 2 (Fads2, and elongation of very long chain fatty acids protein 5 (Elovl5, were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator (LASSO logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

  3. Hypoxia-targeted suicidal gene therapy system enhances antitumor effects of radiotherapy

    International Nuclear Information System (INIS)

    Liu Junye; Guo Yao; Guo Guozhen

    2006-01-01

    Objective: To explore the effects of hypoxia-targeted suicidal gene therapy system combined with radiotherapy on pancreatic cancer. Methods: The recombinant adenovirus Ad-5HRE/hCMVmp-BCD was constructed by DNA recombinant technique. Western blot was used to detect hypoxia-induced expression of bacterial cytosine deaminase (BCD). Cell growth inhibition assay was used to determine the sensitivity of human pancreatic cancer cells MIA-PACA2 to 5-fluorocytosine (5-FC). Tumor xenograft growth delay assays was used to evaluate the effects of Ad-5HRE/hCMVmp-BCD/5-FC combined with radiotherapy on pancreatic cancer. Results: Western blot analysis demonstrated that hypoxia-induced BCD protein expression was achieved in MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD. With hypoxia treatment, the sensitivity of MIA-PACA2 cells infected with Ad-5HRE/hCMVmp-BCD to 5-FC significantly increased. Administration of either Ad-5HRE/hCMVmp-BCD/5-FC or radiotherapy could inhibit the growth of MIA-PACA2 xenografts in nude mice. Moreover, combination of Ad-5HRE/hCMVmp-BCD/5-FC could significantly enhance suppressing effects of radiotherapy on MIA-PACA2 xenografts. Conclusion: Hypoxia-targeted suicidal gene therapy system Ad-5HRE/hCMVmp-BCD/5-FC could enhance antitumor effects of radiotherapy on pancreatic cancer and can be used as a powerful adjunct to conventional radiotherapy. (authors)

  4. A suicide gene therapy approach to treat epidermolysis bullosa-associated skin cancer

    International Nuclear Information System (INIS)

    Gruber, C.

    2009-01-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disease causing extensive blister formation within the basal membrane zone (BMZ) of the skin and mucous membranes. It is caused by premature STOP mutations in the COL7A1 gene, which is indispensable for proper skin assembling. RDEB is associated with the development of a highly malignant skin cancer (squamous cell carcinoma, SCC) in early adulthood that displays a life threatening complication within this patient group. To date, neither chemo- nor radiotherapies showed successful results and due to the high metastatic potential of RDEB SCC wide surgical excision is still favoured. In this study we could reveal a new promising cancer treatment using spliceosome mediated RNA trans-splicing (SMaRT) using a suicide gene therapy approach. First we identified the tumour marker gene MMP-9 expressed by RDEB SCC cells in cell culture which was used to generate various pre-mRNA trans-splicing molecules (PTM). PTMs are able to facilitate trans-splicing between a tumour target gene and a cell death inducing peptide/toxin, encoded by the PTM. As a consequence the toxin is expressed in cancer cells leading to the induction of cell death. This technique offers high specificity in cancer cell targeting compared to other conventional cDNA expression studies. Various trans-splicing molecules were pre-evaluated in a fluorescence screening model for their best trans-splicing efficiency with the target molecule. Herein we identified two potent PTMs (PTM BD0 and PTM BD6), that were further adapted for endogenous suicide studies by inserting the toxin streptolysin O. In two independent in vitro cell culture assays we were able to confirm that the trans-splicing molecules are able to induce expression of the toxin resulting in cell membrane permeabilization and increased cell death induction. The results indicate that SMaRT technology offers a new platform for a suicide gene therapy approach to treat malignant squamous cell

  5. Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

    International Nuclear Information System (INIS)

    Tirkey, Bulbul; Bhushan, Bharat; Uday Kumar, S.; Gopinath, P.

    2017-01-01

    Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

  6. Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tirkey, Bulbul [Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Bhushan, Bharat; Uday Kumar, S. [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Gopinath, P., E-mail: pgopifnt@iitr.ernet.in [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India)

    2017-04-01

    Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

  7. Suicide and suicidal behavior

    Science.gov (United States)

    ... than prescribed medicines) can reduce the risk of suicide. In homes with children or teenagers: Keep all prescription medicines high up ... or attempted suicide. Alternative Names Depression - suicide; Bipolar - suicide ... in children Depression among the elderly References American Psychiatric Association. ...

  8. Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis

    Science.gov (United States)

    Shen, Keyue; Luk, Samantha; Elman, Jessica; Murray, Ryan; Mukundan, Shilpaa; Parekkadan, Biju

    2016-02-01

    Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor-associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy.

  9. Application of HSVtk suicide gene to X-SCID gene therapy: Ganciclovir treatment offsets gene corrected X-SCID B cells

    International Nuclear Information System (INIS)

    Uchiyama, Toru; Kumaki, Satoru; Ishikawa, Yoshinori; Onodera, Masafumi; Sato, Miki; Du, Wei; Sasahara, Yoji; Tanaka, Nobuyuki; Sugamura, Kazuo; Tsuchiya, Shigeru

    2006-01-01

    Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human γc chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the γc chain, the cells were treated with ganciclovir (GCV). The γc chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the γc chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial

  10. Suicidal behavior and haplotypes of the dopamine receptor gene (DRD2 and ANKK1 gene polymorphisms in patients with alcohol dependence--preliminary report.

    Directory of Open Access Journals (Sweden)

    Andrzej Jasiewicz

    Full Text Available Suicide is a significant public health issue and a major cause of death throughout the world. According to WHO it accounts for almost 2% of deaths worldwide. The etiology of suicidal behavior is complex but the results of many studies suggest that genetic determinants are of significant importance. In our study,--we have analyzed selected SNPs polymorphisms in the DRD2 and ANKK1 genes in patients with alcohol dependence syndrome (169 Caucasian subjects including a subgroup of individuals (n = 61 who have experienced at least one suicide attempt. The aim of the study was to verify if various haplotypes of selected genes, comprising Taq1A, Taq1B, and Taq1D single nucleotide polymorphisms (SNP, play any role in the development of alcohol dependence and suicidal behavior. The control group comprised 157 unrelated individuals matched for ethnicity, gender,- and age and included no individuals with mental disorders. All subjects were recruited in the North West region of Poland. The study showed that alcohol dependent subjects with a history of at least one suicidal attempt were characterized by a significantly higher frequency of the T-G-A2 haplotype when compared to individuals in whom alcohol dependence was not associated with suicidal behavior (p = 0.006. It appears that studies based on identifying correlation between SNPs is the future for research on genetic risk factors that contribute to the development of alcohol addiction and other associated disorders. To sum up, there is a necessity to perform further research to explain dependencies between the dopaminergic system, alcohol use disorders and suicidal behavior.

  11. Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

    DEFF Research Database (Denmark)

    Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

    2012-01-01

    Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

  12. Hypoxia targeted bifunctional suicide gene expression enhances radiotherapy in vitro and in vivo

    International Nuclear Information System (INIS)

    Sun, Xiaorong; Xing, Ligang; Deng, Xuelong; Hsiao, Hung Tsung; Manami, Akiko; Koutcher, Jason A.; Clifton Ling, C.; Li, Gloria C.

    2012-01-01

    Purpose: To investigate whether hypoxia targeted bifunctional suicide gene expression-cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) with 5-FC treatments can enhance radiotherapy. Materials and methods: Stable transfectants of R3327-AT cells were established which express a triple-fusion-gene: CD, UPRT and monomoric DsRed (mDsRed) controlled by a hypoxia inducible promoter. Hypoxia-induced expression/function of CDUPRTmDsRed was verified by western blot, flow cytometry, fluorescent microscopy, and cytotoxicity assay of 5-FU and 5-FC. Tumor-bearing mice were treated with 5-FC and local radiation. Tumor volume was monitored and compared with those treated with 5-FC or radiation alone. In addition, the CDUPRTmDsRed distribution in hypoxic regions of tumor sections was visualized with fluorescent microscopy. Results: Hypoxic induction of CDUPRTmDsRed protein correlated with increased sensitivity to 5-FC and 5-FU. Significant radiosensitization effects were detected after 5-FC treatments under hypoxic conditions. In the tumor xenografts, the distribution of CDUPRTmDsRed expression visualized with fluorescence microscopy was co-localized with the hypoxia marker pimonidazole positive staining cells. Furthermore, administration of 5-FC to mice in combination with local irradiation resulted in significant tumor regression, as in comparison with 5-FC or radiation treatments alone. Conclusions: Our data suggest that the hypoxia-inducible CDUPRT/5-FC gene therapy strategy has the ability to specifically target hypoxic cancer cells and significantly improve the tumor control in combination with radiotherapy.

  13. Gene environment interaction studies in depression and suicidal behavior: An update.

    Science.gov (United States)

    Mandelli, Laura; Serretti, Alessandro

    2013-12-01

    Increasing evidence supports the involvement of both heritable and environmental risk factors in major depression (MD) and suicidal behavior (SB). Studies investigating gene-environment interaction (G × E) may be useful for elucidating the role of biological mechanisms in the risk for mental disorders. In the present paper, we review the literature regarding the interaction between genes modulating brain functions and stressful life events in the etiology of MD and SB and discuss their potential added benefit compared to genetic studies only. Within the context of G × E investigation, thus far, only a few reliable results have been obtained, although some genes have consistently shown interactive effects with environmental risk in MD and, to a lesser extent, in SB. Further investigation is required to disentangle the direct and mediated effects that are common or specific to MD and SB. Since traditional G × E studies overall suffer from important methodological limitations, further effort is required to develop novel methodological strategies with an interdisciplinary approach. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Suicide and Suicidal Thoughts

    Science.gov (United States)

    ... the best way to identify risk. Murder and suicide In rare cases, people who are suicidal are ... access to a firearm Starting antidepressants and increased suicide risk Most antidepressants are generally safe, but the ...

  15. Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: a 22-year longitudinal gene-environment study.

    Science.gov (United States)

    Brezo, J; Bureau, A; Mérette, C; Jomphe, V; Barker, E D; Vitaro, F; Hébert, M; Carbonneau, R; Tremblay, R E; Turecki, G

    2010-08-01

    To investigate similarities and differences in the serotonergic diathesis for mood disorders and suicide attempts, we conducted a study in a cohort followed longitudinally for 22 years. A total of 1255 members of this cohort, which is representative of the French-speaking population of Quebec, were investigated. Main outcome measures included (1) mood disorders (bipolar disorder and major depression) and suicide attempts by early adulthood; (2) odds ratios and probabilities associated with 143 single nucleotide polymorphisms in 11 serotonergic genes, acting directly or as moderators in gene-environment interactions with childhood sexual or childhood physical abuse (CPA), and in gene-gene interactions; (3) regression coefficients for putative endophenotypes for mood disorders (childhood anxiousness) and suicide attempts (childhood disruptiveness). Five genes showed significant adjusted effects (HTR2A, TPH1, HTR5A, SLC6A4 and HTR1A). Of these, HTR2A variation influenced both suicide attempts and mood disorders, although through different mechanisms. In suicide attempts, HTR2A variants (rs6561333, rs7997012 and rs1885884) were involved through interactions with histories of sexual and physical abuse whereas in mood disorders through one main effect (rs9316235). In terms of phenotype-specific contributions, TPH1 variation (rs10488683) was relevant only in the diathesis for suicide attempts. Three genes contributed exclusively to mood disorders, one through a main effect (HTR5A (rs1657268)) and two through gene-environment interactions with CPA (HTR1A (rs878567) and SLC6A4 (rs3794808)). Childhood anxiousness did not mediate the effects of HTR2A and HTR5A on mood disorders, nor did childhood disruptiveness mediate the effects of TPH1 on suicide attempts. Of the serotonergic genes implicated in mood disorders and suicidal behaviors, four exhibited phenotype-specific effects, suggesting that despite their high concordance and common genetic determinants, suicide attempts

  16. Suicide gene reveals the myocardial neovascularization role of mesenchymal stem cells overexpressing CXCR4 (MSC(CXCR4.

    Directory of Open Access Journals (Sweden)

    Jialiang Liang

    Full Text Available BACKGROUND: Our previous studies indicated that MSC(CXCR4 improved cardiac function after myocardial infarction (MI. This study was aimed to investigate the specific role of MSC(CXCR4 in neovascularization of infarcted myocardium using a suicide gene approach. METHODS: MSCs were transduced with either lentivirus-null vector/GFP (MSC(Null as control or vector encoding for overexpressing CXCR4/GFP. The MSC derived-endothelial cell (EC differentiation was assessed by a tube formation assay, Dil-ac-LDL uptake, EC marker expression, and VE-cadherin promoter activity assay. Gene expression was analyzed by quantitative RT-PCR or Western blot. The suicide gene approach was under the control of VE-cadherin promoter. In vivo studies: Cell patches containing MSC(Null or MSC(CXCR4 were transduced with suicide gene and implanted into the myocardium of MI rat. Rats received either ganciclovir (GCV or vehicle after cell implantation. After one month, the cardiac functional changes and neovascularization were assessed by echocardiography, histological analysis, and micro-CT imaging. RESULTS: The expression of VEGF-A and HIF-1α was significantly higher in MSC(CXCR4 as compared to MSC(Null under hypoxia. Additionally, MSC(CXCR4 enhanced new vessel formation and EC differentiation, as well as STAT3 phosphorylation under hypoxia. STAT3 participated in the transcription of VE-cadherin in MSC(CXCR4 under hypoxia, which was inhibited by WP1066 (a STAT3 inhibitor. In addition, GCV specifically induced death of ECs with suicide gene activation. In vivo studies: MSC(CXCR4 implantation promoted cardiac functional restoration, reduced infarct size, improved cardiac remodeling, and enhanced neovascularization in ischemic heart tissue. New vessels derived from MSC(CXCR4 were observed at the injured heart margins and communicated with native coronary arteries. However, the derived vessel networks were reduced by GCV, reversing improvement of cardiac function. CONCLUSION: The

  17. The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

    DEFF Research Database (Denmark)

    Saetre, Peter; Lundmark, Per; Wang, August

    2010-01-01

    Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been...... affected individuals having attempted suicide at least once and patients with no history of suicide attempts (P = 0.84). A systematic literature review and meta-analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.......07-1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I(2) = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80-1.16]). We conclude that the TPH1 A218...

  18. Dual monitoring using {sup 124}I-FIAU and bioluminescence for HSV1-tk suicide gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T. S.; Kim, J. H.; Kwon, H. C. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2007-07-01

    Herpes simplex virus type I thymidine kinase (HSV-tk) is the most common reporter gene and is used in cancer gene therapy with a prodrug nucleoside analog, ganciclovir (GCV). The aim of this study is to evaluate therapeutic efficacy of suicide gene therapy with 2'-fluoro-2'-deoxy-1-D-arabinofuranosyl-5-[{sup 124}I] iodouracil ({sup 124}I - FIAU) and bioluminescence in retrovirally HSV -tk and firefly luciferase transduced hepatoma model. The HSV -tk and firefly luciferase (Luc) was retrovirally transduced and expressed in MCA rat Morris hepatoma cells. Nude mice with subcutaneous tumors, MCA and MCA-TK-Luc, were subjected to GCV treatment (50mg/Kg/d intraperitoneally) for 5 day. PET imaging and biodistribution with ({sup 124}I-FIAU) were performed at before and after initiation of therapy with GCV. Bioluminescent signal was also measured during GCV treatment. Before GCV treatment, no significant difference in tumor volume was found in tumors between MCA and MCA-TK-Luc. After GCV treatment, tumor volume of MCA-TK-Luc markedly reduced compared to that of MCA. In biodistribution study, {sup 124}I-FIAU uptake after GCV therapy significantly decreased compared with pretreatment levels (34.8 13.67 %ID/g vs 7.6 2.59 %ID/g) and bioluminescent signal was also significantly decreased compared with pretreatment levels. In small animal PET imaging, {sup 124}I-FIAU selectively localized in HSV -tk expressing tumor and the therapeutic efficacy of GCV treatment was evaluated by {sup 124}I-FIAU PET imaging. {sup 124}I-FIAU PET and bioluminescence imaging in HSV-tk suicide gene therapy were effective to evaluate the therapeutic response. {sup 124}I-FIAU may serve as an efficient and selective agent for monitoring of transduced HSV1-tk gene expression in vivo in clinical trials.

  19. The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.

    Science.gov (United States)

    Höfer, Peter; Schosser, Alexandra; Calati, Raffaella; Serretti, Alessandro; Massat, Isabelle; Kocabas, Neslihan Aygun; Konstantinidis, Anastasios; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Juven-Wetzler, Alzbeta; Montgomery, Stuart; Kasper, Siegfried

    2013-08-01

    Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.

  20. The study of irradiation combined with targeted suicide gene therapy for prostate cancer xenografts

    International Nuclear Information System (INIS)

    Lu Xueguan; Milas, L.

    2007-01-01

    Objective: To study whether RGD-4C AAVP HSV-TK/GCV, one of suicide gene therapy targeting to Integrin αv, can enhance radiotherapeutic effect for DU145 prostate cancer xenografts or not. Methods: When the diameter of tumor in 48 nude mice bearing DU145 prostate cancer in the right leg attained 6.0 mm (5.8-6.3 mm), the mice were entered into the experiment. There were 6 experimental groups (8 mice per group), including the control, radiotherapy only (RT), RGD-4C AAVP HSV-TK/GCV only (Targeted, RGD-4C), AAVP HSV-TK/GCV (Non-targeted, non RGD-4C ), radiotherapy plus RGD- 4C AAVP HSV-TK/GCV(XRT + RGD-4C) and radiotherapy plus AAVP HSV-TK/GCV group (XRT + Non RGD-4C). The effect of treatment was assessed by tumor growth delay ( the time required when tumor grew from 6.0 mm to 12.0 mm) and tumor cure. Results: Five mice died during the treatment course. There were 6 mice without tumor after treatment, including 1 in RT group, 1 in RGD-4C group, 1 in non RGD-4C group and 3 in XRT + RGD-4C group, respectively. For tumor growth delay analysis in 37 mice, the absolute growth delay (AGD) for RGD-4C, non RGD-4C and RT group was 24.4 ± 9.0, 22.6±11.3 and 28.3 ±5.5 days, respectively. When RGD-4C AAVP HSV-TK/GCV or AAVP HSV-TK/GCV combined with radiotherapy, their AGD was 64.7±23.8 and 35.4±9.6 days, and nominal growth delay (NGD) was 40.3 ± 23.8 and 12.8 ± 9.6 days, respectively. The enhancement factor of RGD-4C AAVP HSV-TK/GCV and AAVP HSV-TK/GCV for radiotherapy were 1.42 and 0.45. Conclusion: RGD-4C AAVP HSV-TK/GCV can enhance radiotherapeutic effect for DU145 prostate cancer xenografts. Further study is needed. (authors)

  1. X chromosome and suicide.

    Science.gov (United States)

    Fiori, L M; Zouk, H; Himmelman, C; Turecki, G

    2011-02-01

    Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90  kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.

  2. In vivo cation exchange in quantum dots for tumor-specific imaging.

    Science.gov (United States)

    Liu, Xiangyou; Braun, Gary B; Qin, Mingde; Ruoslahti, Erkki; Sugahara, Kazuki N

    2017-08-24

    In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide. Subsequent etching quenches excess quantum dots, leaving a highly tumor-specific signal provided by the intact quantum dots remaining in the extravascular tumor cells and fibroblasts. No toxicity is noted. The system also facilitates the detection of peritoneal tumors with high specificity upon intraperitoneal tumor targeting and selective etching of excess untargeted quantum dots. In vivo cation exchange may be a promising strategy to enhance specificity of tumor imaging.The imaging of tumors in vivo using nanoprobes has been challenging due to the lack of sufficient tumor specificity. Here, the authors develop a tumor-specific quantum dot system that permits in vivo cation exchange to achieve selective background quenching and high tumor-specific imaging.

  3. The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal behavior: systematic review and meta-analysis.

    Science.gov (United States)

    González-Castro, Thelma B; Hernandez-Diaz, Yazmín; Juárez-Rojop, Isela E; López-Narváez, Lilia; Tovilla-Zárate, Carlos A; Rodriguez-Perez, José M; Sánchez-de la Cruz, Juan P

    2017-12-01

    The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.

  4. Resequencing three candidate genes discovers seven potentially deleterious variants susceptibility to major depressive disorder and suicide attempts in Chinese.

    Science.gov (United States)

    Rao, Shitao; Leung, Cherry She Ting; Lam, Macro Hb; Wing, Yun Kwok; Waye, Mary Miu Yee; Tsui, Stephen Kwok Wing

    2017-03-01

    To date almost 200 genes were found to be associated with major depressive disorder (MDD) or suicide attempts (SA), but very few genes were reported for their molecular mechanisms. This study aimed to find out whether there were common or rare variants in three candidate genes altering the risk for MDD and SA in Chinese. Three candidate genes (HOMER1, SLC6A4 and TEF) were chosen for resequencing analysis and association studies as they were reported to be involved in the etiology of MDD and SA. Following that, bioinformatics analyses were applied on those variants of interest. After resequencing analysis and alignment for the amplicons, a total of 34 common or rare variants were found in the randomly selected 36 Hong Kong Chinese patients with both MDD and SA. Among those, seven variants show potentially deleterious features. Rs60029191 and a rare variant located in regulatory region of the HOMER1 gene may affect the promoter activities through interacting with predicted transcription factors. Two missense mutations existed in the SLC6A4 coding regions were firstly reported in Hong Kong Chinese MDD and SA patients, and both of them could affect the transport efficiency of SLC6A4 to serotonin. Moreover, a common variant rs6354 located in the untranslated region of this gene may affect the expression level or exonic splicing of serotonin transporter. In addition, both of a most studied polymorphism rs738499 and a low-frequency variant in the promoter region of the TEF gene were found to be located in potential transcription factor binding sites, which may let the two variants be able to influence the promoter activities of the gene. This study elucidated the potentially molecular mechanisms of the three candidate genes altering the risk for MDD and SA. These findings implied that not only common variants but rare variants could make contributions to the genetic susceptibility to MDD and SA in Chinese. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Association between a genetic variant in the serotonin transporter gene (SLC6A4 and suicidal behavior in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Lindholm Carlström Eva

    2012-05-01

    Full Text Available Abstract Background The serotonin (5-hydroxytryptamin; 5-HT system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT is associated with schizophrenia and suicidal behavior. In this study, we wanted to elucidate whether SLC6A4 variations is involved in attempted suicide among patients with schizophrenia in a Scandinavian case–control sample. Methods Patients diagnosed with schizophrenia from three Scandinavian samples were assessed for presence or absence of suicide attempts, based on record reviews and interview data. Seven SLC6A4 single nucleotide polymorphisms (SNPs were genotyped in 837 schizophrenia patients and 1,473 control individuals. Association analyses and statistical evaluations were performed with the program UNPHASED (version 3.0.9. Results We observed an allele association between the SNP rs16965628, located in intron one of SLC6A4, and attempted suicide (adjusted p-value 0.01, among patients with schizophrenia. No association was found to a diagnosis of schizophrenia, when patients were compared to healthy control individuals. Conclusion The gene SLC6A4 appears to be involved in suicidal ideation among patients with schizophrenia. Independent replication is needed before more firm conclusions can be drawn.

  6. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  7. Association between a genetic variant in the serotonin transporter gene (SLC6A4) and suicidal behavior in patients with schizophrenia

    DEFF Research Database (Denmark)

    Lindholm Carlstrom, Eva; Saetre, Peter; Rosengren, Anders

    2012-01-01

    ABSTRACT: BACKGROUND: The serotonin (5-hydroxytryptamin; 5-HT) system has a central role in the circuitry of cognition and emotions. Multiple lines of evidence suggest that genetic variation in the serotonin transporter gene (SLC6A4; 5-HTT) is associated with schizophrenia and suicidal behavior. ...

  8. Noninvasive theranostic imaging of HSV-TK/GCV suicide gene therapy in liver cancer by folate-targeted quantum dot-based liposomes

    NARCIS (Netherlands)

    Shao, D.; Li, J.; Pan, Y.; Zhang, X.; Zheng, X.; Wang, Z.; Zhang, M.; Zhang, H.; Chen, L.

    2015-01-01

    Theranostics is emerging as a popular strategy for cancer therapy; thanks to the development of nano-technology. In this work, we have combined an HSV-TK/GCV suicide gene system and near-infrared quantum dots, as the former is quite effective in liver cancer treatment and the latter facilitates

  9. Therapeutic potential of bleomycin plus suicide or interferon-β gene transfer combination for spontaneous feline and canine melanoma

    Science.gov (United States)

    Agnetti, Lucrecia; Fondello, Chiara; Villaverde, Marcela S.; Glikin, Gerardo C.; Finocchiaro, Liliana M. E.

    2017-01-01

    We originated and characterized melanoma cell lines derived from tumors of two feline and two canine veterinary patients. These lines reestablished the morphology, physiology and cell heterogeneity of their respective parental tumors. We evaluated the cytotoxicity of bleomycin (BLM) alone, or combined with interferon-β (IFN-β) or HSVtk/GCV suicide gene (SG) lipofection on these cells. Although the four animals presented stage III disease (WHO system), SG treated feline tumors displayed stable disease in vivo, while the canine ones exhibited partial response. Their derived cell lines reflected this behavior. Feline were significantly more sensitive than canine cells to IFN-β gene transfer. BLM improved the antitumor effects of both genes. The higher levels of reactive oxygen species (ROS) significantly correlated with membrane and DNA damages, emphasizing ROS intervention in apoptotic and necrotic cell death. After 3 days of BLM alone or combined with gene treatments, the colony forming capacity of two canine and one feline treatments survivor cells almost disappeared. Taken together, these results suggest that the treatments eradicated tumor initiating cells and support the clinical potential of the tested combinations. PMID:29344558

  10. Differential gene expression for suicide-substrate serine proteinase inhibitors (serpins) in vegetative and grain tissues of barley

    DEFF Research Database (Denmark)

    Roberts, T.H.; Marttila, S.; Rasmussen, S.K.

    2003-01-01

    centres in vitro, were ubiquitous at low levels, but the protein could not be detected. EST analysis showed that expression of genes for serpins with BSZx-type reactive centres in vegetative tissues is widespread in the plant kingdom, suggesting a common regulatory function. For BSZ4 and BSZ7, expression...... their irreversible inhibitory mechanism in the inhibition of exogenous proteinases capable of breaking down seed storage proteins, and in the defence of specific cell types in vegetative tissues.......Proteins of the serpin superfamily (similar to43 kDa) from mature cereal grains are in vitro suicide-substrate inhibitors of specific mammalian serine proteinases of the chymotrypsin family. However, unlike the 'standard-mechanism' serine proteinase inhibitors (

  11. In vivo and in vitro experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy

    International Nuclear Information System (INIS)

    Chen Daozhen; Xue Wenqun; Zhan Huiying; Zhu Yunxia; Yang Youyi; Liu Lu; Tang Qiusha

    2006-01-01

    Objective: To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60 Co radiotherapy on human cervical cancer HeLa cell line in vivo and in vitro, and to explore radiosensitization by the HSV-TK/GCV system. Methods: The HSV-TK/GCV suicide gene therapy system and 60 Co radiotherapy were used separately or in combination for human cervical cancer HeLa cell line in vivo and in vitro to compare their effects. Colony formation test and the rate of radiosensitization effect(E/O) were employed to observed the radiosensitization by the HSV-TK/GCV system. Results: The HSV-TK/GCV suicide gene therapy system showed strong therapeutic effects on HeLa cells both in vitro and in vivo (the inhibition rates were 45.8% and 39.5%, respectively). Moreover, the combined application of gene therapy and radiotherapy exhibited stronger therapeutic effects in vitro and in vivo (the inhibition rate was 87.5% in vitro, and was 87.9% in vivo) (P 1.4), indicating the HSV-TK/GCV system could exert a sensitizing effect on 60 Co radiotherapy of the transplanted human cervical cancer cells in nude mice. Conclusion: The HSV-TK/GCV system has radiosensitizationaction. Gene therapy combined with radiotherapy may be a good supplementary method for synthetic treatment of cervical cancer. (authors)

  12. Suicide Awareness

    Science.gov (United States)

    ... View Cart | ({{Header.numItems}} Item s ) Home Health & Wellness Mental Health Suicide March 15, 2018 @ 9:56 AM | 3 Min Read | 10105 Views Suicide Awareness Suicide is a serious concern in military communities; ...

  13. Elderly Suicide

    Science.gov (United States)

    Elderly Suicide Fact Sheet Based on 2012 Data (2014) Overview • The elderly (ages 65 and older) made up 13. ... population; they accounted for 16.37% of all suicides in the US. • The rate of suicides for ...

  14. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

    Science.gov (United States)

    Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

    2016-01-01

    Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

  15. Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

    Science.gov (United States)

    Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

    2016-12-01

    Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

  16. Radiobiology effects of radiation-induced horseradish peroxidase/indole-3-acetic suicide gene expression in lung cancer cells

    International Nuclear Information System (INIS)

    Xiong Jie; Zhou Yunfeng; Wang Weifeng; Sun Wenjie; Liao Zhengkai; Zhou Fuxiang; Xie Conghua

    2010-01-01

    Objective: To detect specific cell killing effect of radiation combined with horseradish peroxidase (HRP)/indole-3-acetic (IAA) suicide gene therapy controlled by a novel radio-inducible and cancer-specific chimeric gene promoter in lung cancer. Methods: We constructed a plasmid expressing HRP enzyme under the control of chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 CArG elements, a plasmid expressing HRP enzyme under the control of hTERT promoter carrying single CArG element, and two control plasmids, which named pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc, respectively. After radiation, the proliferation inhibition and apoptosis induction effect of each type of plasmid in lung cancer cells (A549, SPC-A1) and normal lung cells (hEL) was detected by cell counting and Annexin V-FITC staining. The change of radiosensitivity of lung cancer cells with plasmid system was also detected by clonogenic assays. Results: After a single dose radiation of 6 Gy,the average proliferation inhibition rates of pE6-hTERT-HRP, phTERT-HRP, pControl-HRP, and pControlluc systems were 72.92% ,40.60% , 51.00% and 25.19% (F= 67.31, P< 0.01) in A549 cells, 64.63%, 30.02%, 48.23% and 23.16% (F=64.94, P< 0.01) in SPC-A1 cells, and 20.81%, 18.05%, 44.20% and 18.32% (F=52.19, P<0.01) in normal hEL cells, respectively. The average early apoptosis rates of these four plasmid systems were 36.63%, 22.30%, 24.33% and 12.53% (F =50.99, P <0.01) in A549 cells, 33.73%, 17.37%, 22.43% and 11.20% (F = 20. 76, P < 0.01) in SPC-A1 cells, and 13.53 %, 12.5%, 21.93% and 12.16% (F = 15.08, P < 0.01) in normal hEL cells,respectively. The sensitizing enhancement ratios of the four plasmid systems were 3.45, 2.29, 3.05 and 1.21 in A549 cells, while 2.68, 2.15, 3.05 and 1.21 in SPC-A1 cells, respectively. Conclusions: The new suicide gene system controlled by chimeric promoter may provide a novel therapeutic modality for lung cancer. (authors)

  17. Image-aided Suicide Gene Therapy Utilizing Multifunctional hTERT-targeting Adenovirus for Clinical Translation in Hepatocellular Carcinoma.

    Science.gov (United States)

    Kim, Yun-Hee; Kim, Kyung Tae; Lee, Sang-Jin; Hong, Seung-Hee; Moon, Ju Young; Yoon, Eun Kyung; Kim, Sukyoung; Kim, Eun Ok; Kang, Se Hun; Kim, Seok Ki; Choi, Sun Il; Goh, Sung Ho; Kim, Daehong; Lee, Seong-Wook; Ju, Mi Ha; Jeong, Jin Sook; Kim, In-Hoo

    2016-01-01

    Trans-splicing ribozyme enables to sense and reprogram target RNA into therapeutic transgene and thereby becomes a good sensing device for detection of cancer cells, judging from transgene expression. Previously we proposed PEPCK-Rz-HSVtk (PRT), hTERT targeting trans-splicing ribozyme (Rz) driven by liver-specific promoter phosphoenolpyruvate carboxykinase (PEPCK) with downstream suicide gene, herpes simplex virus thymidine kinase (HSVtk) for hepatocellular carcinoma (HCC) gene therapy. Here, we describe success of a re-engineered adenoviral vector harboring PRT in obtaining greater antitumor activity with less off-target effect for clinical application as a theranostics. We introduced liver-selective apolipoprotein E (ApoE) enhancer to the distal region of PRT unit to augment activity and liver selectivity of PEPCK promoter, and achieved better transduction into liver cancer cells by replacement of serotype 35 fiber knob on additional E4orf1-4 deletion of E1&E3-deleted serotype 5 back bone. We demonstrated that our refined adenovirus harboring PEPCK/ApoE-Rz-HSVtk (Ad-PRT-E) achieved great anti-tumor efficacy and improved ability to specifically target HCC without damaging normal hepatocytes. We also showed noninvasive imaging modalities were successfully employed to monitor both how well a therapeutic gene (HSVtk) was expressed inside tumor and how effectively a gene therapy took an action in terms of tumor growth. Collectively, this study suggests that the advanced therapeutic adenoviruses Ad-PRT-E and its image-aided evaluation system may lead to the powerful strategy for successful clinical translation and the development of clinical protocols for HCC therapy.

  18. Adolescent Suicide and Suicidal Behavior

    Science.gov (United States)

    Bridge, Jeffrey A.; Goldstein, Tina R.; Brent, David A.

    2006-01-01

    This review examines the descriptive epidemiology, and risk and protective factors for youth suicide and suicidal behavior. A model of youth suicidal behavior is articulated, whereby suicidal behavior ensues as a result of an interaction of socio-cultural, developmental, psychiatric, psychological, and family-environmental factors. On the basis of…

  19. Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells.

    Science.gov (United States)

    Haabeth, Ole Audun Werner; Lorvik, Kristina Berg; Yagita, Hideo; Bogen, Bjarne; Corthay, Alexandre

    The role of inflammation in cancer is controversial as both tumor-promoting and tumor-suppressive aspects of inflammation have been reported. In particular, it has been shown that pro-inflammatory cytokines, like interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor α (TNFα), may either promote or suppress cancer. However, the cellular and molecular basis underlying these opposing outcomes remains enigmatic. Using mouse models for myeloma and lymphoma, we have recently reported that inflammation driven by tumor-specific T helper 1 (Th1) cells conferred protection against B-cell cancer and that interferon-γ (IFN-γ) was essential for this process. Here, we have investigated the contribution of several inflammatory mediators. Myeloma eradication by Th1 cells was not affected by inhibition of TNF-α, TNF-related weak inducer of apoptosis (TWEAK), or TNF-related apoptosis-inducing ligand (TRAIL). In contrast, cancer elimination by tumor-specific Th1 cells was severely impaired by the in vivo neutralization of both IL-1α and IL-1β (collectively named IL-1) with IL-1 receptor antagonist (IL-1Ra). The antitumor functions of tumor-specific Th1 cells and tumor-infiltrating macrophages were both affected by IL-1 neutralization. Secretion of the Th1-derived cytokines IL-2 and IFN-γ at the incipient tumor site was severely reduced by IL-1 blockade. Moreover, IL-1 was shown to synergize with IFN-γ for induction of tumoricidal activity in tumor-infiltrating macrophages. This synergy between IL-1 and IFN-γ may explain how inflammation, when driven by tumor-specific Th1 cells, represses rather than promotes cancer. Collectively, the data reveal a central role of inflammation, and more specifically of the canonical pro-inflammatory cytokine IL-1, in enhancing Th1-mediated immunity against cancer.

  20. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

    Science.gov (United States)

    Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

    2016-01-01

    Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  1. Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

    Directory of Open Access Journals (Sweden)

    Chun-Nun Chao

    Full Text Available Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV infection. Therefore, we designed that the JCPyV virus-like particle (VLP packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp or thymidine kinase gene (pSPB-tk under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549 and large cell carcinoma (H460 cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV, a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

  2. An experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy

    International Nuclear Information System (INIS)

    Chen, Daozhen; Tang, Qiusha

    2010-01-01

    To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with 60 Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system. HSV-TK/GCV suicide gene therapy system and 60 Co radiotherapy were used separately or in combination on human cervical cancer Hela cell line in vitro and in vivo to compare their effects. Colony formation test and the rate of radiosensitization effect (E/O) were employed to observed the radiosensitization by HSV-TK/GCV system. HSV-TK/GCV suicide gene therapy system had strong therapeutic effects on Hela cells in vitro and in vivo (the inhibition rates were 45.8% and 39.5%, respectively), moreover, the combined administration of gene therapy and radiotherapy had stronger therapeutic effects in vitro and in vivo (the inhibition rate was 87.5% in vitro, and the inhibition rate was 87.9% in vivo) (P < 0.01). The inhibition rate by radiotherapy alone was 42.4% in vitro and 35.8% in vivo. The sensitivity of combined therapy to radiotherapy increased more than that of therapy alone, the ability of colony formation decreased (P < 0.01). The rate of radiosensitivity effect (E/O) was 3.17(> 1.4), indicating HSV-TK/GCV system could exert a sensitizing effect on 60 Co radiotherapy of the transplanted human cervical cancer cell in nude mice. HSV-TK/GCV system had radiosensitization. Gene therapy combined with radiotherapy may be a good supplementary method for cervix cancer synthetic treatment

  3. The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis

    DEFF Research Database (Denmark)

    Saetre, Peter; Lundmark, Per; Wang, August

    2010-01-01

    Serotonin (5-hydroxytryptamin; 5-HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5-monooxygenase; TPH) is the rate-limiting enzyme in the biosynthesis of 5-HT, and sequence variation in intron 6 of the TPH1 gene has been...... associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs......) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility (P = 0.019). However there were no differences in allele frequencies of these loci between...

  4. Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex virus thymidine kinase suicide gene

    International Nuclear Information System (INIS)

    Hlavaty, J.; Hlubinova, K.; Altanerova, V.; Liska, J.; Altaner, C.

    1997-01-01

    The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase (HSVtk) gene was constructed. The vector was transfected into the packaging cell line PG13. It was shown that individual transfected cells differ in the production of recombinant retrovirus and in their susceptibility to be killed by ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduced the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to influence subcutaneous and intracerebral tumors developed after injection of C 6 rat glioma cells with subsequent injection of HSVtk retrovirus producing cells. (author)

  5. Elimination of the truncated message from the herpes simplex virus thymidine kinase suicide gene

    NARCIS (Netherlands)

    Chalmers, D; Ferrand, C; Apperley, JF; Melo, JV; Ebeling, S; Newton, [No Value; Duperrier, A; Hagenbeek, A; Garrett, E; Tiberghien, P; Garin, M

    Introduction of the Herpes simplex virus thymidine kinase (HSV-tk) gene into target cells renders them susceptible to killing by ganciclovir (GCV). We are studying the use of HSV-tk-transduced T lymphocytes in the context of hematopoietic stem cell transplantation. We have previously shown, in vitro

  6. Hispanic Suicide

    Science.gov (United States)

    ... 1 The following hypotheses have been presented regarding suicidal behavior among Hispanics: • Family needs are placed above individual ... the parents and elders is of major importance • Suicidal behavior among Hispanic femails may be related to the ...

  7. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    International Nuclear Information System (INIS)

    Nanda, Dharmin; Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter; Vogels, Ronald; Havenga, Menzo; Driesse, Maarten; Avezaat, Cees; Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard; Smitt, Peter Sillevis

    2002-01-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-β-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of 123 I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with 123 I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). 123 I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-β-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with 123 I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after 123 I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with the transgene in the former E1

  8. Imaging expression of adenoviral HSV1-tk suicide gene transfer using the nucleoside analogue FIRU

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Dharmin [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands); Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Jong, Marion de; Bakker, Willem; Bijster, Magda; Cox, Peter [Department of Nuclear Medicine, University Hospital Rotterdam (Netherlands); Vogels, Ronald; Havenga, Menzo [Crucell Holland BV, Leiden (Netherlands); Driesse, Maarten; Avezaat, Cees [Department of Neurosurgery, University Hospital Rotterdam (Netherlands); Morin, Kevin; Naimi, Ebrahim; Knaus, Edward; Wiebe, Leonard [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Smitt, Peter Sillevis [Department of Neurology, Daniel den Hoed Cancer Centre, University Hospital Rotterdam (Netherlands)

    2002-07-01

    Substrates for monitoring HSV1-tk gene expression include uracil and acycloguanosine derivatives.The most commonly used uracil derivative to monitor HSV1-tk gene transfer is 1-(2-fluoro-2-deoxy-{beta}-D-arabinofuranosyl)-5-[*I]iodouracil (fialuridine; I*-FIAU), where the asterisk denotes any of the radioactive iodine isotopes that can be used. We have previously studied other nucleosides with imaging properties as good as or better than FIAU, including 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-[*I]iodouracil (FIRU). The first aim of this study was to extend the biodistribution data of {sup 123}I-labelled FIRU. Secondly, we assessed the feasibility of detecting differences in HSV1-tk gene expression levels following adenoviral gene transfer in vivo with {sup 123}I-FIRU. 9L rat gliosarcoma cells were stably transfected with the HSV1-tk gene (9L-tk+). {sup 123}I-FIRU was prepared by radioiodination of 1-(2-fluoro-2-deoxy-{beta}-D-ribofuranosyl)-5-tributylstannyl uracil (FTMRSU; precursor compound) and purified using an activated Sep-Pak column. Incubation of 9L-tk+ cells and the parental 9L cells with {sup 123}I-FIRU resulted in a 100-fold higher accumulation of radioactivity in the 9L-tk+ cells after an optimum incubation time of 4 h. NIH-bg-nu-xid mice were then inoculated subcutaneously with HSV1-tk (-) 9L cells or HSV1-tk (+) 9L-tk+ cells into both flanks. Biodistribution studies and gamma camera imaging were performed at 15 min and 1, 2, 4 and 24 h p.i. At 15 min, the tumour/muscle, tumour/blood and tumour/brain ratios were 5.2, 1.0 and 30.3 respectively. Rapid renal clearance of the tracer from the body resulted in increasing tumour/muscle, tumour/blood and tumour/brain ratios, reaching values of 32.2, 12.5 and 171.6 at 4 h p.i. A maximum specific activity of 22%ID/g tissue was reached in the 9L-tk+ tumours 4 h after {sup 123}I-FIRU injection. Two Ad5-based adenoviral vectors containing the HSV1-tk gene were constructed: a replication-incompetent vector with

  9. From the Cover: A polymer library approach to suicide gene therapy for cancer

    Science.gov (United States)

    Anderson, Daniel G.; Peng, Weidan; Akinc, Akin; Hossain, Naushad; Kohn, Anat; Padera, Robert; Langer, Robert; Sawicki, Janet A.

    2004-11-01

    Optimal gene therapy for cancer must (i) deliver DNA to tumor cells with high efficiency, (ii) induce minimal toxicity, and (iii) avoid gene expression in healthy tissues. To this end, we generated a library of >500 degradable, poly(-amino esters) for potential use as nonviral DNA vectors. Using high-throughput methods, we screened this library in vitro for transfection efficiency and cytotoxicity. We tested the best performing polymer, C32, in mice for toxicity and DNA delivery after intratumor and i.m. injection. C32 delivered DNA intratumorally 4-fold better than one of the best commercially available reagents, jetPEI (polyethyleneimine), and 26-fold better than naked DNA. Conversely, the highest transfection levels after i.m. administration were achieved with naked DNA, followed by polyethyleneimine; transfection was rarely observed with C32. Additionally, polyethyleneimine induced significant local toxicity after i.m. injection, whereas C32 demonstrated no toxicity. Finally, we used C32 to deliver a DNA construct encoding the A chain of diphtheria toxin (DT-A) to xenografts derived from LNCaP human prostate cancer cells. This construct regulates toxin expression both at the transcriptional level by the use of a chimeric-modified enhancer/promoter sequence of the human prostate-specific antigen gene and by DNA recombination mediated by Flp recombinase. C32 delivery of the A chain of diphtheria toxin DNA to LNCaP xenografts suppressed tumor growth and even caused 40% of tumors to regress in size. Because C32 transfects tumors locally at high levels, transfects healthy muscle poorly, and displays no toxicity, it may provide a vehicle for the local treatment of cancer. prostate | cationic polymers

  10. Teen Suicide

    Science.gov (United States)

    ... episodes, or a mix of both types. Some teens will try to hide depression or thoughts of suicide. They might withdraw, or act out. This can ... teen depression? What should I do if my teen is depressed? Did I do ... antidepressants cause suicide? Once my teenager is treated for suicide or ...

  11. Suicidal behaviour

    NARCIS (Netherlands)

    Neeleman, J

    2001-01-01

    -Prevention of suicidal behaviour remains difficult, despite increasing knowledge of its determinants. Health service efforts hardly affect suicide rates. -Recent shifts in the epidemiology of suicidal behaviour are rising rates among the young and increasing use of violent methods. these can be

  12. Suicidal communication signifies suicidal intent in Chinese completed suicides.

    Science.gov (United States)

    Zhou, Xue Mei; Jia, Shu Hua

    2012-11-01

    Recognizing suicidal communication from the distressful catharsis in a high-risk group with suicidal tendencies is essential for suicide prevention. This study analyzes whether suicidal communication can indicate the severity of suicidal intent. Various types of suicidal communication are defined, and their clinical significance is further explored. A comprehensive analysis of the psychological autopsy data of 200 victims of completed suicide, including their general socio-demographic status, suicidal communication methods, previous suicide attempts, mental disorders, and psychosocial situation. Our results showed that 39.5% of all the subjects were suicidal communicators, 23.0% had previously attempted suicide, and 14.0% left suicide notes; 32.4% of 142 subjects free of physical disease suffered from mental disorders. Suicidal communication included verbal communication, behavioral communication, and suicidal notes. Younger people with a higher level of education were more inclined to communicate their suicidal intent by leaving a suicide note. Suicide notes, but not previous suicide attempts or psychosocial situation, were significantly correlated with suicidal intent. Suicidal communicators showed higher depression scores than non-communicators. Those who suffered from mood disorders with higher levels of both depression and suicidal intent were more likely to expose their intent through behavioral communication. The present study provides strong evidence that suicidal communication can indicate the severity of suicidal intent. Current findings help interpret high-risk, self-destructive behavior and consequently provide the theoretical basis for a feasible suicide prevention program.

  13. An HTS-compatible 3D colony formation assay to identify tumor-specific chemotherapeutics.

    Science.gov (United States)

    Horman, Shane R; To, Jeremy; Orth, Anthony P

    2013-12-01

    There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laser-scanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.

  14. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

    Directory of Open Access Journals (Sweden)

    Li-Xin Wang

    Full Text Available Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC, a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS, acute myeloid leukemia (AML and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+, but not CD4(+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

  15. Low Dose Decitabine Treatment Induces CD80 Expression in Cancer Cells and Stimulates Tumor Specific Cytotoxic T Lymphocyte Responses

    Science.gov (United States)

    Zhou, Ji-Hao; Yao, Yu-Shi; Li, Yong-Hui; Xu, Yi-Han; Li, Jing-Xin; Gao, Xiao-Ning; Zhou, Min-Hang; Jiang, Meng-Meng; Gao, Li; Ding, Yi; Lu, Xue-Chun; Shi, Jin-Long; Luo, Xu-Feng; Wang, Jia; Wang, Li-Li; Qu, Chunfeng; Bai, Xue-Feng; Yu, Li

    2013-01-01

    Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8+, but not CD4+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy. PMID:23671644

  16. Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

    Science.gov (United States)

    Wang, Li-Xin; Mei, Zhen-Yang; Zhou, Ji-Hao; Yao, Yu-Shi; Li, Yong-Hui; Xu, Yi-Han; Li, Jing-Xin; Gao, Xiao-Ning; Zhou, Min-Hang; Jiang, Meng-Meng; Gao, Li; Ding, Yi; Lu, Xue-Chun; Shi, Jin-Long; Luo, Xu-Feng; Wang, Jia; Wang, Li-Li; Qu, Chunfeng; Bai, Xue-Feng; Yu, Li

    2013-01-01

    Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

  17. Mechanism study of tumor-specific immune responses induced by laser immunotherapy

    Science.gov (United States)

    Li, Xiaosong; Zhou, Feifan; Le, Henry; Wolf, Roman F.; Howard, Eric; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2011-03-01

    Laser immunotherapy (LIT) has shown its efficacy against late-stage, metastatic cancers, both in pre-clinical studies and clinical pilot trials. However, the possible mechanism of LIT is still not fully understood. In our previous studies, we have shown that LIT induces tumor-specific antibodies that strongly bind to the target tumors. Tumor resistance in cured animals demonstrated long-term immunological effect of LIT. Successful transfer of adoptive immunity using spleen cells from LIT-cured animals indicated a long-term immunological memory of the host system. In clinical trials for the treatment of late-stage melanoma patients and breast cancer patients, the similar long-term, systemic effects have also been observed. To further study the immunological mechanism of LIT, immuno-histochemical analysis of patient tumor samples has performed before and after LIT treatment. Our results showed strong evidence that LIT significantly increases the infiltration of immune cells in the target tumors. Specifically, LIT appeared to drive the infiltrating immune cell populations in the direction of CD4, CD8 and CD68 T-cells. It is possible that activation and enhancement of both humeral and cellular arms of the host immune system are achievable by the treatment of LIT. These special features of LIT have contributed to the success of patient treatment. The underlying mechanism of LIT appears to be an in-situ autologous whole-cell cancer vaccination, using all components of tumors as sources of tumor antigens. Our preliminary mechanistic studies and future in-depth studies will contribute to the understanding and development of LIT as an effective modality for the treatment of late stage cancer patients who are facing severely limited options.

  18. Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene.

    Science.gov (United States)

    Casucci, Monica; Falcone, Laura; Camisa, Barbara; Norelli, Margherita; Porcellini, Simona; Stornaiuolo, Anna; Ciceri, Fabio; Traversari, Catia; Bordignon, Claudio; Bonini, Chiara; Bondanza, Attilio

    2018-01-01

    Chimeric antigen receptor (CAR)-T cell immunotherapy is at the forefront of innovative cancer therapeutics. However, lack of standardization of cellular products within the same clinical trial and lack of harmonization between different trials have hindered the clear identification of efficacy and safety determinants that should be unveiled in order to advance the field. With the aim of facilitating the isolation and in vivo tracking of CAR-T cells, we here propose the inclusion within the CAR molecule of a novel extracellular spacer based on the low-affinity nerve-growth-factor receptor (NGFR). We screened four different spacer designs using as target antigen the CD44 isoform variant 6 (CD44v6). We successfully generated NGFR-spaced CD44v6 CAR-T cells that could be efficiently enriched with clinical-grade immuno-magnetic beads without negative consequences on subsequent expansion, immuno-phenotype, in vitro antitumor reactivity, and conditional ablation when co-expressing a suicide gene. Most importantly, these cells could be tracked with anti-NGFR monoclonal antibodies in NSG mice, where they expanded, persisted, and exerted potent antitumor effects against both high leukemia and myeloma burdens. Similar results were obtained with NGFR-enriched CAR-T cells specific for CD19 or CEA, suggesting the universality of this strategy. In conclusion, we have demonstrated that the incorporation of the NGFR marker gene within the CAR sequence allows for a single molecule to simultaneously work as a therapeutic and selection/tracking gene. Looking ahead, NGFR spacer enrichment might allow good manufacturing procedures-manufacturing of standardized CAR-T cell products with high therapeutic potential, which could be harmonized in different clinical trials and used in combination with a suicide gene for future application in the allogeneic setting.

  19. Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene

    Directory of Open Access Journals (Sweden)

    Monica Casucci

    2018-03-01

    Full Text Available Chimeric antigen receptor (CAR-T cell immunotherapy is at the forefront of innovative cancer therapeutics. However, lack of standardization of cellular products within the same clinical trial and lack of harmonization between different trials have hindered the clear identification of efficacy and safety determinants that should be unveiled in order to advance the field. With the aim of facilitating the isolation and in vivo tracking of CAR-T cells, we here propose the inclusion within the CAR molecule of a novel extracellular spacer based on the low-affinity nerve-growth-factor receptor (NGFR. We screened four different spacer designs using as target antigen the CD44 isoform variant 6 (CD44v6. We successfully generated NGFR-spaced CD44v6 CAR-T cells that could be efficiently enriched with clinical-grade immuno-magnetic beads without negative consequences on subsequent expansion, immuno-phenotype, in vitro antitumor reactivity, and conditional ablation when co-expressing a suicide gene. Most importantly, these cells could be tracked with anti-NGFR monoclonal antibodies in NSG mice, where they expanded, persisted, and exerted potent antitumor effects against both high leukemia and myeloma burdens. Similar results were obtained with NGFR-enriched CAR-T cells specific for CD19 or CEA, suggesting the universality of this strategy. In conclusion, we have demonstrated that the incorporation of the NGFR marker gene within the CAR sequence allows for a single molecule to simultaneously work as a therapeutic and selection/tracking gene. Looking ahead, NGFR spacer enrichment might allow good manufacturing procedures-manufacturing of standardized CAR-T cell products with high therapeutic potential, which could be harmonized in different clinical trials and used in combination with a suicide gene for future application in the allogeneic setting.

  20. Extracellular NGFR Spacers Allow Efficient Tracking and Enrichment of Fully Functional CAR-T Cells Co-Expressing a Suicide Gene

    Science.gov (United States)

    Casucci, Monica; Falcone, Laura; Camisa, Barbara; Norelli, Margherita; Porcellini, Simona; Stornaiuolo, Anna; Ciceri, Fabio; Traversari, Catia; Bordignon, Claudio; Bonini, Chiara; Bondanza, Attilio

    2018-01-01

    Chimeric antigen receptor (CAR)-T cell immunotherapy is at the forefront of innovative cancer therapeutics. However, lack of standardization of cellular products within the same clinical trial and lack of harmonization between different trials have hindered the clear identification of efficacy and safety determinants that should be unveiled in order to advance the field. With the aim of facilitating the isolation and in vivo tracking of CAR-T cells, we here propose the inclusion within the CAR molecule of a novel extracellular spacer based on the low-affinity nerve-growth-factor receptor (NGFR). We screened four different spacer designs using as target antigen the CD44 isoform variant 6 (CD44v6). We successfully generated NGFR-spaced CD44v6 CAR-T cells that could be efficiently enriched with clinical-grade immuno-magnetic beads without negative consequences on subsequent expansion, immuno-phenotype, in vitro antitumor reactivity, and conditional ablation when co-expressing a suicide gene. Most importantly, these cells could be tracked with anti-NGFR monoclonal antibodies in NSG mice, where they expanded, persisted, and exerted potent antitumor effects against both high leukemia and myeloma burdens. Similar results were obtained with NGFR-enriched CAR-T cells specific for CD19 or CEA, suggesting the universality of this strategy. In conclusion, we have demonstrated that the incorporation of the NGFR marker gene within the CAR sequence allows for a single molecule to simultaneously work as a therapeutic and selection/tracking gene. Looking ahead, NGFR spacer enrichment might allow good manufacturing procedures-manufacturing of standardized CAR-T cell products with high therapeutic potential, which could be harmonized in different clinical trials and used in combination with a suicide gene for future application in the allogeneic setting. PMID:29619024

  1. In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma

    International Nuclear Information System (INIS)

    Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph.; Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R.

    2010-01-01

    Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

  2. Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

    International Nuclear Information System (INIS)

    Bathe, Oliver F; Dalyot-Herman, Nava; Malek, Thomas R

    2003-01-01

    Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several

  3. Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

    International Nuclear Information System (INIS)

    Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

    2016-01-01

    Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

  4. Tumor specific cytotoxicity of arctigenin isolated from herbal plant Arctium lappa L.

    Science.gov (United States)

    Susanti, Siti; Iwasaki, Hironori; Itokazu, Yukiyoshi; Nago, Mariko; Taira, Naoyuki; Saitoh, Seikoh; Oku, Hirosuke

    2012-10-01

    The effectiveness of cancer chemotherapy is often limited by the toxicity to other tissues in the body. Therefore, the identification of non-toxic chemotherapeutics from herbal medicines remains to be an attractive goal to advance cancer treatments. This study evaluated the cytotoxicity profiles of 364 herbal plant extracts, using various cancer and normal cell lines. The screening found occurrence of A549 (human lung adenocarcinoma) specific cytotoxicity in nine species of herbal plants, especially in the extract of Arctium lappa L. Moreover, purification of the selective cytotoxicity in the extract of Arctium lappa L. resulted in the identification of arctigenin as tumor specific agent that showed cytotoxicity to lung cancer (A549), liver cancer (HepG2) and stomach cancer (KATO III) cells, while no cytotoxicity to several normal cell lines. Arctigenin specifically inhibited the proliferation of cancer cells, which might consequently lead to the induction of apoptosis. In conclusion, this study found that arctigenin was one of cancer specific phytochemicals, and in part responsible for the tumor selective cytotoxicity of the herbal medicine.

  5. His-tag ELISA for the detection of humoral tumor-specific immunity

    Directory of Open Access Journals (Sweden)

    Disis Mary L

    2008-05-01

    Full Text Available Abstract Background The application of high throughput molecular techniques such as SEREX are resulting in the identification of a multitude of tumor associated antigens. As newly identified antigens are incorporated into a variety of clinical trials, standardization of immunologic monitoring methods becomes increasingly important. We questioned whether mammalian cell expression of a histadine-linked human protein could be used to produce antigen suitable for detecting tumor-specific humoral immunity and whether such an assay could be amenable to standardization for clinical use. Methods We designed a his-tagged capture ELISA based on lysate from genetically engineered CHO cells for detection of antibodies to insulin-like growth factor binding protein 2, a novel tumor antigen. We performed technical and preliminary clinical validation studies, including comparison to a standard indirect ELISA based on commercially prepared recombinant antigen. Results The his-tagged capture ELISA could be standardized. Precision experiments resulted in CVs 2 values of 0.99. In comparison to Western blot analysis, his-tag and indirect ELISA accurately identified 88% and 93% of samples, respectively. Sample concordance between capture and indirect assays was highly significant (p = 0.003. Furthermore, significantly greater levels of IGFBP-2 antibody immunity were found in cancer patients compared to normal controls (p = 0.008. Conclusion A genetically engineered cell lysate based ELISA can be amenable to standardization and can detect increased levels of antibody immunity to tumor-associated antigen in cancer patients compared to non tumor-bearing healthy controls.

  6. Development of a magnetic beam guiding system for tumor-specific radiotherapy using heavy, charged particles

    International Nuclear Information System (INIS)

    Haberer, T.

    1994-06-01

    An active, magnetic beam guiding system was developed and tested for the purpose of enhanced and tumor-specific irradiation of irregularly shaped target volumina. Combining intensity-controlled wobbling in rapidly changing magnetic fields with the heavy-ion synchrotron's capacity of fast energy variation achieved a new technique allowing good range modulation. This technique allows the calculated dose distribution to be exactly matched to target contours, and at the same time guarantees best possible quality of the radiation beam, since there is no need for use of mechanical beam shaping members. The components of the scanning system and a specifically designed instrumentation and control concept for this configuration were integrated into the synchrotron's control system, so that there is now a system available offering free selection of beam characteristics combined with energy variation along with the pulsed operation of the accelerator. The system was tested at the biophysical measuring unit of the GSI implementing an elaborated irradiation method at this unit equipped with tools for physico-technical irradiation planning and performance. Methods were designed and tested for optimizing the beam path within a given contour, the optimization taking into account the effects of transmission functions of the scanner components on the results of radiation treatments. (orig.) [de

  7. USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination

    Directory of Open Access Journals (Sweden)

    Laura Novellasdemunt

    2017-10-01

    Full Text Available The tumor suppressor gene adenomatous polyposis coli (APC is mutated in most colorectal cancers (CRCs, resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of the APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation, and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumor-specific therapeutic target for most CRCs.

  8. USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by Mediating β-Catenin Deubiquitination.

    Science.gov (United States)

    Novellasdemunt, Laura; Foglizzo, Valentina; Cuadrado, Laura; Antas, Pedro; Kucharska, Anna; Encheva, Vesela; Snijders, Ambrosius P; Li, Vivian S W

    2017-10-17

    The tumor suppressor gene adenomatous polyposis coli (APC) is mutated in most colorectal cancers (CRCs), resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of the APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID) in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation, and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumor-specific therapeutic target for most CRCs. Copyright © 2017 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

  9. Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope

    International Nuclear Information System (INIS)

    Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.

    1999-01-01

    Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

  10. Effect of chemotherapy and immunotherapy on tumor-specific immunity in melanoma.

    Science.gov (United States)

    Mitchell, M S; Mokyr, M B; Davis, J M

    1977-01-01

    The effects of chemotherapy, with nitrosoureas or dimethyl-triazeno-imidazole-carboxamide (DTIC), or immunotherapy with Bacillus Calmette-Guérin (BCG), on cell-mediated immunity (CMI), and serum blocking factor (BF) to melanoma cells were studied in 23 patients. Studies were performed with autologous or allogenic melanoma target cells obtained from recent biopsy, in 16 mm diameter plastic wells. Assays for lymphocyte-mediated cytotoxicity and BF were performed at weekly intervals over the course of 3-4 mo, with some studies extending beyond 3 yr. The specificity of cytotoxicity was good with these methods. Nine patients given nitrosoureas, predominantly methyl-chloroethyl-cyclohexyl-nitrosourea, showed a transient decline in CMI from 42.2 to 14% 3 wk after administration of a single dose of the agent, with a rapid recovery within 1 week. 10 patients given 5-day courses of DTIC at 3-wk intervals showed no decline in CMI after two courses, and 7 of the 10 had no decline even after three courses. Three of the four patients who achieved a remission lost BF previously present: BF reappeared in both patients studied during a subsequent relapse. BCG intradermally or intralesionally elevated CMI within 2 mo after initiation of therapy, but despite continuation of the injections CMI returned to base line in all but two of the nine patients studied. These results indicate that chemotherapy for melanoma with nitrosoureas or DTIC at these schedules is not profoundly immunosuppressive towards tumor-specific immunity, as measured by our procedures. Putative immunotherapy with BCG at these schedules was likewise only transiently stimulatory. PMID:863999

  11. Physician suicide.

    Science.gov (United States)

    Preven, D W

    1981-01-01

    The topic of physician suicide has been viewed from several perspectives. The recent studies which suggest that the problem may be less dramatic statistically, do not lessen the emotional trauma that all experience when their lives are touched by the grim event. Keeping in mind that much remains to be learned about suicides in general, and physician suicide specifically, a few suggestions have been offered. As one approach to primary prevention, medical school curriculum should include programs that promote more self-awareness in doctors of their emotional needs. If the physician cannot heal himself, perhaps he can learn to recognize the need for assistance. Intervention (secondary prevention) requires that doctors have the capacity to believe that anyone, regardless of status, can be suicidal. Professional roles should not prevent colleague and friend from identifying prodromal clues. Finally, "postvention" (tertiary prevention) offers the survivors, be they family, colleagues or patients, the opportunity to deal with the searing loss in a therapeutic way.

  12. In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Kentaro Minagawa

    Full Text Available Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia.We developed an immunotherapeutic strategy targeting the CD33 myeloid antigen, expressed in ~ 85-90% of patients with acute myeloid leukemia, using chimeric antigen receptor redirected T-cells. Considering that administration of CAR T-cells has been associated with cytokine release syndrome and other potential off-tumor effects in patients, safety measures were here investigated and reported. We genetically modified human activated T-cells from healthy donors or patients with acute myeloid leukemia with retroviral supernatant encoding the inducible Caspase9 suicide gene, a ΔCD19 selectable marker, and a humanized third generation chimeric antigen receptor recognizing human CD33. ΔCD19 selected inducible Caspase9-CAR.CD33 T-cells had a 75±3.8% (average ± standard error of the mean chimeric antigen receptor expression, were able to specifically lyse CD33+ targets in vitro, including freshly isolated leukemic blasts from patients, produce significant amount of tumor-necrosis-factor-alpha and interferon-gamma, express the CD107a degranulation marker, and proliferate upon antigen specific stimulation. Challenging ΔCD19 selected inducible Caspase9-CAR.CD33 T-cells with programmed-death-ligand-1 enriched leukemia blasts resulted in significant killing like observed for the programmed-death-ligand-1 negative leukemic blasts fraction. Since the administration of 10 nanomolar of a non

  13. The newsworthiness of suicide.

    Science.gov (United States)

    Pirkis, Jane; Burgess, Philip; Blood, R Warwick; Francis, Catherine

    2007-06-01

    There is a paucity of studies examining which suicides are considered news-worthy. By combining data on media reports of individuals' suicides with routinely collected suicide data, it was found that 1% of Australian suicides were reported over a 1-year period. There was evidence of over-reporting of suicides by older people and females, and those involving dramatic methods. Reported suicides fell into three groups: suicides reported in a broader context; suicides by celebrities; and suicides involving unusual circumstances/methods. The data suggest a need for media professionals and suicide experts to work together to balance newsworthiness against the risk of copycat behavior.

  14. TU-F-CAMPUS-T-03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods

    International Nuclear Information System (INIS)

    Diagaradjane, P; Deorukhkar, A; Sankaranarayanapillai, M; Singh, P; Manohar, N; Tailor, R; Cho, S; Goodrich, G; Krishnan, S

    2015-01-01

    Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x

  15. TU-F-CAMPUS-T-03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Diagaradjane, P [M.D. Anderson Cancer Center, Houston, TX (United States); Deorukhkar, A; Sankaranarayanapillai, M; Singh, P [The UT MD Anderson Cancer Center, Houston, TX (United States); Manohar, N; Tailor, R; Cho, S [UT MD Anderson Cancer Center, Houston, TX (United States); Goodrich, G [Nanospectra Biosciences Inc, Houston, TX (United States); Krishnan, S [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over-expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116-colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250-kVp x-rays and clinically relevant 6-MV radiation beams. Results: cGNRs displayed excellent cell-surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250-kVp and 6-MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000-fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250-kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x

  16. Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model

    International Nuclear Information System (INIS)

    Freytag, Svend O.; Paielli, Dell; Wing, Mark; Rogulski, Ken; Brown, Steve; Kolozsvary, Andy; Seely, John; Barton, Ken; Dragovic, Alek; Kim, Jae Ho

    2002-01-01

    Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic injection (10 10 vp) of the replication-competent Ad5-CD/TKrep adenovirus. Two days later, mice were administered 4 weeks of 5-fluorocytosine + GCV prodrug therapy and 56 Gy EBRT to the pelvic region. The toxicity of trimodal therapy was assessed by histopathologic analysis of major organs and clinical chemistries. Results: In both the i.m. DU145 and intraprostatic LNCaP C4-2 tumor models, trimodal therapy significantly improved primary tumor control beyond that of EBRT alone. In the DU145 model, trimodal therapy resulted in a tumor growth delay (70 days) that was more than twice that (32 days) of EBRT alone. Whereas EBRT failed to eradicate DU145 tumors, trimodal therapy resulted in 25% tumor cure. In the LNCaP C4-2 tumor model, EBRT slowed the growth of intraprostatic tumors, but resulted in no tumor cures, and 57% of the mice developed retroperitoneal lymph node metastases at 3 months. By contrast, trimodal therapy resulted in 44% tumor cure and reduced significantly the percentage (13%) of lymph node metastases relative to EBRT alone. Overall

  17. Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study.

    Directory of Open Access Journals (Sweden)

    Marcus Sokolowski

    Full Text Available Suicidal behavior (SB has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs, as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA in offspring as main outcome (n = 660 trios. We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (100 kb CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having

  18. In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma;Controle par IRM bas champ in vivo de l'efficacite d'une therapie genique par gene suicide dans un modele murin de glioblastome orthotopique

    Energy Technology Data Exchange (ETDEWEB)

    Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph. [Service de biophysique et medecine nucleaire, hopital de Hautepierre, CHRU de Strasbourg, 67 - Strasbourg (France); Institut de mecanique des fluides et des solides, CNRS, universite de Strasbourg, 67 - Strasbourg (France); Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R. [Transgene SA, parc d' innovation, 67 - Illkirch Graffenstaden (France)

    2010-03-15

    Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

  19. Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.

    Science.gov (United States)

    He, Wei; Kularatne, Sumith A; Kalli, Kimberly R; Prendergast, Franklyn G; Amato, Robert J; Klee, George G; Hartmann, Lynn C; Low, Philip S

    2008-10-15

    Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ml; p < 0.001, chi(2)). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, chi(2)). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.

  20. A new mutation in WFS1 gene (C.1522-1523delTA, Y508fsX421) may be responsible for early appearance of clinical features of Wolfram syndrome and suicidal behaviour.

    Science.gov (United States)

    Aluclu, Mehmet Ufuk; Bahceci, Mithat; Tuzcu, Alpaslan; Arikan, Senay; Gokalp, Deniz

    2006-12-01

    Wolfram syndrome (WS) is an autosomal recessive disorder characterized by the association of juvenile-onset diabetes mellitus and optic atrophy. It is also known by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We diagnosed Wolfram syndrome in 2 male siblings and determined a new mutation (c. 1522-1523delTA, Y508fsX421). Both affected siblings were homozygous, other family members were heterozygous. Dilated renal outflow tracts in the third decade, and neuropsychiatric disorders including bipolar disorder and neurosensorial deafness appear in the fourth decade in ordinary WS, whereas these features appeared in second decade in our patients. This mutation may be responsible for early appearance of dilated renal outflow tracts and multiple neurological abnormalities. Psychiatric disturbances such as suicide were reported at increased frequency in Wolfram patients and in heterozygous carriers. Suicidal behaviour occurred in our patients when they were yet 11 and 13 years old. Therefore, our findings may indicate that there may be a relationship between this WFS1 mutation and mood disorder such as suicidal behaviour. We determined a new mutation (c. 1522-1523delTA, Y508fsX421) in WS1 gene in 2 siblings with Wolfram syndrome. This mutation may be responsible for early appearance of clinical features of Wolfram syndrome, and there may be a relationship between this mutation and suicidal behaviour.

  1. Cell suicide

    International Nuclear Information System (INIS)

    May, E.; Coffigny, H.

    2000-01-01

    In the fight of the cell against the damages caused to its DNA by genotoxic agents and specially by ionizing radiations, the p53 protein plays a central part. It intervenes in the proliferation control and the differentiation but also in the keeping of genome integrity. It can direct the damages cells toward suicide, or apoptosis, to avoid the risk of tumor appearance that would be fatal to the whole organism. That is by the disordered state of cells suicide programs that the tumor cells are going to develop. The knowledge of apoptosis mechanisms, to eventually start them on demand, rises up broad hopes in the cancer therapy. (N.C.)

  2. SpxB is a suicide gene of Streptococcus pneumoniae and confers a selective advantage in an in vivo competitive colonization model.

    Science.gov (United States)

    Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M; Lipsitch, Marc; Malley, Richard

    2007-09-01

    The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H(2)O(2)), not LytA, and that the gene responsible for H(2)O(2) production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H(2)O(2) in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing DeltaspxB mutants that do not produce H(2)O(2). Likewise, addition of H(2)O(2) to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While DeltalytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H(2)O(2) has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the DeltaspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization.

  3. Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer.

    Science.gov (United States)

    Li, Yining; Xu, Shuxiong; Wang, Xiangwei; Shi, Hua; Sun, Zhaolin; Yang, Zhao

    2013-02-01

    To explore the exact mechanism of Pokemon in prostate cancer. Pokemon is a member of the POK family of transcriptional repressors. Its main function is suppression of the p14ARF (alternate reading frame) tumor suppressor gene. Although Pokemon expression has been found to be increased in various types of lymphoma, the exact mechanism of the gene in prostate cancer is not clear. In the present study, prostate cancer cells were transfected with the specific short hairpin ribonucleic acid (RNA) expression vector targeting Pokemon. The expression of Pokemon messenger RNA and its protein was detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The cell growth and cell apoptosis were also examined using the methyl thiazolyl tetrazolium assay and flow cytometry. The results demonstrated that specific RNA interference (RNAi) could decrease the expression levels of Pokemon gene messenger RNA and protein in prostate cancer cells. In addition, that specific RNAi significantly inhibited the cell proliferation and increased the apoptotic rate. In vivo experiments showed that specific RNAi inhibited the tumorigenicity of prostate cancer cells and significantly suppressed tumor growth. Therefore, an RNAi-targeted Pokemon gene strategy could be a potential approach to prostate cancer therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Suicide Prevention

    Science.gov (United States)

    ... or mania, decrease the effectiveness of medication, enhance impulsive behavior, and severely cloud judgment. Beginning to feel better It might sound strange, but someone dealing with depression may be most likely to attempt suicide just when he or she seems to have ...

  5. Suicide Prevention

    Science.gov (United States)

    ... corresponding to World Suicide Prevention Day, to celebrate life, hope, and reasons to live. SAMHSA is committed to ... members, and helping people navigate the struggles of life to find a sustainable sense of hope, meaning, and purpose. For information about how you ...

  6. Introduction of Exogenous HSV-TK Suicide Gene Increases Safety of Keratinocyte-Derived Induced Pluripotent Stem Cells by Providing Genetic “Emergency Exit” Switch

    Directory of Open Access Journals (Sweden)

    Maciej Sułkowski

    2018-01-01

    Full Text Available Since their invention in 2006, induced Pluripotent Stem (iPS cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors. This remains their main disadvantage and hazard which, until resolved, prevents utilization of iPS cells in clinic. Here, we present an approach for increasing iPS cells safety by introducing genetic modification—exogenous suicide gene Herpes Simplex Virus Thymidine Kinase (HSV-TK. Its expression results in specific vulnerability of genetically modified cells to prodrug—ganciclovir (GCV. We show that HSV-TK expressing cells can be eradicated both in vitro and in vivo with high specificity and efficiency with low doses of GCV. Described strategy increases iPS cells safety for future clinical applications by generating “emergency exit” switch allowing eradication of transplanted cells in case of their malfunction.

  7. Introduction of Exogenous HSV-TK Suicide Gene Increases Safety of Keratinocyte-Derived Induced Pluripotent Stem Cells by Providing Genetic "Emergency Exit" Switch.

    Science.gov (United States)

    Sułkowski, Maciej; Konieczny, Paweł; Chlebanowska, Paula; Majka, Marcin

    2018-01-09

    Since their invention in 2006, induced Pluripotent Stem (iPS) cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES) cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors. This remains their main disadvantage and hazard which, until resolved, prevents utilization of iPS cells in clinic. Here, we present an approach for increasing iPS cells safety by introducing genetic modification-exogenous suicide gene Herpes Simplex Virus Thymidine Kinase ( HSV-TK ). Its expression results in specific vulnerability of genetically modified cells to prodrug-ganciclovir (GCV). We show that HSV-TK expressing cells can be eradicated both in vitro and in vivo with high specificity and efficiency with low doses of GCV. Described strategy increases iPS cells safety for future clinical applications by generating "emergency exit" switch allowing eradication of transplanted cells in case of their malfunction.

  8. National Suicide Prevention Lifeline

    Science.gov (United States)

    ... Initiatives Best Practices Our Network Media Resources National Suicide Prevention Lifeline We can all help prevent suicide. The ... Call The Lifeline Everyone Plays A Role In Suicide Prevention Here are some helpful links: GET HELP NOW ...

  9. Determination of Patients’ Breast Tumor-Specific Immunity and Its Enhancement with In Vitro Stimulation and Gene Therapy

    Science.gov (United States)

    1998-03-01

    cancer therapy. Am. J. Clin. Oncol., 22:368-380. Overgaard, J., Gonzalez Gonzalez, D., Hulshof , M.C.C.M., Arcangeli, G., Dahl, O., Mella, O., and... Hulshof , M.C.C.M., Arcangeli, G., Dahl, O., Mella, O., and Bentzen, S.M. (1996) Hyperthermia as an adjuvant to radiation therapy of recurrent or

  10. Tumor specific HMG-CoA reductase expression in primary pre-menopausal breast cancer predicts response to tamoxifen

    LENUS (Irish Health Repository)

    Brennan, Donal J

    2011-01-31

    Abstract Introduction We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. Methods HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. Results HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive\\/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as

  11. Suicide and Murder-Suicide Involving Aircraft.

    Science.gov (United States)

    Kenedi, Christopher; Friedman, Susan Hatters; Watson, Dougal; Preitner, Claude

    2016-04-01

    This is a systematic review of suicide and homicide-suicide events involving aircraft. In aeromedical literature and in the media, these very different events are both described as pilot suicide, but in psychiatry they are considered separate events with distinct risk factors. Medical databases, internet search engines, and aviation safety databases were searched in a systematic way to obtain relevant cases. Relevant articles were searched for additional references. There were 65 cases of pilot suicide and 6 cases of passengers who jumped from aircraft found. There were also 18 cases of homicide-suicide found involving 732 deaths. Pilots perpetrated 13 homicide-suicide events. Compared to non-aviation samples, a large percentage of pilot suicides in this study were homicide-suicides (17%). Homicide-suicide events occur extremely rarely. However, their impact in terms of the proportion of deaths is significant when compared to deaths from accidents. There is evidence of clustering where pilot suicides occur after by media reports of suicide or homicide-suicide. Five of six homicide-suicide events by pilots of commercial airliners occurred after they were left alone in the cockpit. This, along with a sixth incident in which active intervention by a Japan Air crew saved 147 lives, suggests that having two flight members in the cockpit is potentially protective. No single factor was associated with the risk for suicide or homicide-suicide. Factors associated with both events included legal and financial crises, occupational conflict, mental illness, and relationship stressors. Drugs and/or alcohol played a role in almost half of suicides, but not in homicide-suicides.

  12. Suicidal behavior and assisted suicide in dementia.

    Science.gov (United States)

    Draper, Brian M

    2015-10-01

    Concerns about suicide risk in people with dementia have been increasing in recent years along with a discourse about rational suicide and assisted suicide. A systematic narrative literature review of suicidal behavior and assisted suicide in persons with dementia. Most studies that have examined the spectrum of suicidal ideation, attempted suicide and suicide in dementia have methodological limitations but the overall suicide risk does not appear to be increased. When suicidal behavior does occur, common themes include the presence of psychiatric comorbidity, mainly depression; occurrence early in the dementia course with preserved insight and capacity; and an increased risk in younger people. The emerging discourse on rational and assisted suicide has been spurred by early and pre-symptomatic diagnosis and poses a number of ethical challenges for clinicians including the role of proxy decision-makers. Although dementia might not confer a significant overall risk for suicidal behavior, clinicians still need to consider the potential for suicide in vulnerable individuals particularly early in the dementia course.

  13. Biological basis of suicide and suicidal behavior

    Science.gov (United States)

    Pandey, Ghanshyam N

    2013-01-01

    Objective Suicide is a major public health concern as each year 30,000 people die by suicide in the US alone. In the teenage population, it is the second leading cause of death. There have been extensive studies of psychosocial factors associated with suicide and suicidal behavior. However, very little is known about the neurobiology of suicide. Recent research has provided some understanding of the neurobiology of suicide, which is the topic of this review. Methods Neurobiology of suicide has been studied using peripheral tissues, such as platelets, lymphocytes, and cerebral spinal fluid obtained from suicidal patients or from the postmortem brains of suicide victims. Results These studies have provided encouraging information with regard to the neurobiology of suicide. They show an abnormality of serotonergic mechanism, such as increased serotonin receptor subtypes and decreased serotonin metabolites, such as 5-hydroxyindoleacetic acid. These studies also suggest abnormalities of receptor-linked signaling mechanisms, such as phosphoinositide and adenylyl cyclase signaling mechanisms. Other biological systems that appear to be dysregulated in suicide are the hypothalamic-pituitary-adrenal (HPA) axis, and abnormalities of neurotrophins and neurotrophin receptors. More recently, several studies also indicate abnormalities of neuroimmune functions in suicide. Conclusions These studies have been discussed in detail in the following review. Some encouraging information has emerged, primarily related to some of these neurobiological mechanisms. It is hoped that neurobiological studies may eventually result in identifying appropriate biomarkers for suicidal behavior as well as appropriate therapeutic targets for its treatment. PMID:23773657

  14. Development of one control and one tumor-specific induced pluripotent stem cell line from laryngeal carcinoma patient

    Directory of Open Access Journals (Sweden)

    Yamin Zhang

    2017-12-01

    Full Text Available Skin fibroblasts and tumor fibroblasts were extracted from a 64-year old male patient clinically diagnosed with laryngeal carcinoma. Control and tumor specific induced pluripotent stem cells were reprogrammed with 5 reprogramming factors, Klf-4, c-Myc, Oct-4, Sox-2, and Lin-28, using the messenger RNA reprogramming system. The transgene-free iPSC lines showed pluripotency, confirmed by immunofluorescence staining. The iPSC lines also showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This in vitro cellular model can be used to study the oncogenesis and pathogenesis of laryngeal carcinoma.

  15. Statewide Suicide Prevention Council

    Science.gov (United States)

    State Employees Statewide Suicide Prevention Council DHSS State of Alaska Home Divisions and Agencies National Suicide Prevention Lifeline Alaska Community Mental Health Centers National Survivors of Suicide Meetings Presentations 2010 Alaska Statewide Suicide Prevention Summit: Mending the Net Connect with us on

  16. Rethinking Impulsivity in Suicide

    Science.gov (United States)

    Klonsky, E. David; May, Alexis

    2010-01-01

    Elevated impulsivity is thought to facilitate the transition from suicidal thoughts to suicidal behavior. Therefore, impulsivity should distinguish those who have attempted suicide (attempters) from those who have only considered suicide (ideators-only). This hypothesis was examined in three large nonclinical samples: (1) 2,011 military recruits,…

  17. Alcoholism and Suicide.

    Science.gov (United States)

    Roy, Alec; Linnoila, Markku

    1986-01-01

    Reviews knowledge about suicide in alcoholism: how commonly suicide among alcoholics occurs; which alcoholics commit suicide and why; suicide among alcoholic women and alcoholic physicians; possible predisposing biological factors; possible linkages with depression, adverse life events, and personality disorder; and future research and directions.…

  18. Memes and suicide.

    Science.gov (United States)

    Lester, David

    2009-08-01

    The concept of memes is analyzed, and its applicability to suicidology explored. Proposals are made for possible memes implicated in suicidal behavior. A classification of suicidal memes is proposed and the relationship between memes and archetypes of suicide is discussed. It is suggested that the terminology of meme theory can sharpen research into imitation effects in suicide.

  19. A ternary-complex of a suicide gene, a RAGE-binding peptide, and polyethylenimine as a gene delivery system with anti-tumor and anti-angiogenic dual effects in glioblastoma.

    Science.gov (United States)

    Choi, Eunji; Oh, Jungju; Lee, Dahee; Lee, Jaewon; Tan, Xiaonan; Kim, Minkyung; Kim, Gyeungyun; Piao, Chunxian; Lee, Minhyung

    2018-04-13

    The receptor for advanced glycation end-products (RAGE) is involved in tumor angiogenesis. Inhibition of RAGE might be an effective anti-angiogenic therapy for cancer. In this study, a cationic RAGE-binding peptide (RBP) was produced as an antagonist of RAGE, and a ternary-complex consisting of RBP, polyethylenimine (2 kDa, PEI2k), and a suicide gene (pHSVtk) was developed as a gene delivery system with dual functions: the anti-tumor effect of pHSVtk and anti-angiogenic effect of RBP. As an antagonist of RAGE, RBP decreased the secretion of vascular-endothelial growth factor (VEGF) in activated macrophages and reduced the tube-formation of endothelial cells in vitro. In in vitro transfection assays, the RBP/PEI2k/plasmid DNA (pDNA) ternary-complex had higher transfection efficiency than the PEI2k/pDNA binary-complex. In an intracranial glioblastoma animal model, the RBP/PEI2k/pHSVtk ternary-complex reduced α-smooth muscle actin expression, suggesting that the complex has an anti-angiogenic effect. In addition, the ternary-complex had higher pHSVtk delivery efficiency than the PEI2k/pHSVtk and PEI25k/pHSVtk binary-complexes in an animal model. As a result, the ternary-complex induced apoptosis and reduced tumor volume more effectively than the PEI2k/pHSVtk and PEI25k/pHSVtk binary-complexes. In conclusion, due to its dual anti-tumor and anti-angiogenesis effects, the RBP/PEI2k/pHSVtk ternary-complex might be an efficient gene delivery system for the treatment of glioblastoma. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Suicidality and interrogative suggestibility.

    Science.gov (United States)

    Pritchard-Boone, Lea; Range, Lillian M

    2005-01-01

    All people are subject to memory suggestibility, but suicidal individuals may be especially so. The link between suicidality and suggestibility is unclear given mixed findings and methodological weaknesses of past research. To test the link between suicidality and interrogative suggestibility, 149 undergraduates answered questions about suicidal thoughts and reasons for living, and participated in a direct suggestibility procedure. As expected, suggestibility correlated with suicidality but accounted for little overall variance (4%). Mental health professionals might be able to take advantage of client suggestibility by directly telling suicidal persons to refrain from suicidal thoughts or actions.

  1. The gene suicide system NTR/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis

    Directory of Open Access Journals (Sweden)

    RICARDO N FELMER

    2004-01-01

    Full Text Available The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1 transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss

  2. Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zwicker, F.; Roeder, F.; Debus, J.; Huber, P.E. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology; Kirsner, A.; Weber, K.J. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Peschke, P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology

    2013-08-15

    Background: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. Materials and methods: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. Results: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. Conclusion: DCA induced tumor-specific radiosensitization in vitro but not in vivo

  3. Suicide note themes and suicide prevention.

    Science.gov (United States)

    Foster, Tom

    2003-01-01

    The aim was to determine if suicide note themes might inform suicide prevention strategies. The themes of 42 suicide notes from the Northern Ireland Suicide Study (major psychological autopsy study) were examined. The commonest themes were "apology/shame" (74%), "love for those left behind" (60%), "life too much to bear" (48%), "instructions regarding practical affairs post-mortem" (36%), "hopelessness/nothing to live for" (21%) and "advice for those left behind" (21%). Notes of suicides with major unipolar depression were more likely than notes of suicides without major unipolar depression to contain the themes "instructions regarding practical affairs post-mortem" (67% versus 19%, p = 0.005) and "hopelessness/nothing to live for" (40% versus 11%, p = 0.049). Notes of suicides with a previous history of deliberate self-harm were less likely than notes of suicides without a history of deliberate self-harm to contain the theme "apology/shame" (58% versus 87%, p = 0.04). Notes of elderly suicides were more likely than non-elderly notes to contain the theme "burden to others" (40% versus 3%, p = 0.03). The fact that three quarters of suicide notes contained the theme "apology/shame" suggests that the deceased may have welcomed alternative solutions for their predicaments. Scrutiny of suicide note themes in the light of previous research findings suggests that cognitive therapy techniques, especially problem solving, may have an important role to play in suicide prevention and that potential major unipolar depressive (possibly less impulsive) suicides, in particular, may provide fertile ground for therapeutic intervention (physical and psychological). Ideally all primary care doctors and mental health professionals working with (potentially) suicidal people should be familiar with basic cognitive therapy techniques, especially problem solving skills training.

  4. Suicide Neurosis--A Study of Sixty Young Suicide Attempters.

    Science.gov (United States)

    Chinnian, R. Rawlin; Johnson, Shelonitda

    Suicide and deviance are related because loss in social interaction is a consequence of deviance and an antecedent to suicide. This study examined the cognitive and affective experiences of suicidal individuals for evidence of neurosis. Sixty young attempted suicides with a history of a serious suicidal attempts attending the suicide prevention…

  5. A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species

    Directory of Open Access Journals (Sweden)

    Hongliang Zong

    2015-12-01

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous and fatal disease with an urgent need for improved therapeutic regimens given that most patients die from relapsed disease. Irrespective of mutation status, the development of aggressive leukemias is enabled by increasing dependence on signaling networks. We demonstrate that a hyperactive signalosome drives addiction of AML cells to a tumor-specific Hsp90 species (teHsp90. Through genetic, environmental, and pharmacologic perturbations, we demonstrate a direct and quantitative link between hyperactivated signaling pathways and apoptotic sensitivity of AML to teHsp90 inhibition. Specifically, we find that hyperactive JAK-STAT and PI3K-AKT signaling networks are maintained by teHsp90 and, in fact, gradual activation of these networks drives tumors increasingly dependent on teHsp90. Thus, although clinically aggressive AML survives via signalosome activation, this addiction creates a vulnerability that can be exploited with Hsp90-directed therapy.

  6. Inhibitory effects of various oxygenated sterols on the differentiation and function of tumor-specific cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Spangrude, G.J.; Sherris, D.; Daynes, R.A.

    1982-01-01

    Irradiation of skin with ultraviolet light (UVL) is capable of causing many biological and biochemical changes in this complex organ. One early consequence is the oxidation of epidermal plasma membrane cholesterol, causing the induction of a wide variety of photoproducts. It is well recognized that some oxygenated sterols possess potent biological activity on mammalian cells by their ability to inhibit endogeneous mevalonate and cholesterol biosynthesis. In the few immunological systems that have been studied, there is general agreement that lymphocyte function is lacking, as both afferent and efferent blockades have been suggested. These studies were undertaken to determine the effect of various oxygenated sterols (representing a number of known cholesterol-derived photoproducts) on the generation (afferent) and function (efferent) of cytotoxic T lymphocytes (CTLs). Cell-mediated immune responses which result in the generation of both alloantigen-specific and syngeneic tumor-specific CTLs were evaluated

  7. Surviving relatives after suicide

    DEFF Research Database (Denmark)

    Nørrelykke, Helle; Cohrt, Pernille

    and that suicide has become a subject of research, prevention and treatment. Auxiliary Strategies In the 1990s there have been established the Centre for Suicide Research and the Centre for Prevention of Suicide in Denmark and there has been drafted a national policy document which focuses on the need......We would like to focus on the surviving relatives after suicides, because it is generally accepted that it is especially difficult to recover after the loss from suicide and because we know as a fact that one suicide affects five persons on average. Every year approximately 700 people commit...... suicide in Denmark. This means that at least 400 people undergo the trauma it is when one of their near relatives commits suicide. We also know that the loss from suicide involves a lot of conflicting feelings - like anger, shame, guilt and loss and that the lack of therapy/treatment of these difficult...

  8. Suicide announcement on Facebook.

    Science.gov (United States)

    Ruder, Thomas D; Hatch, Gary M; Ampanozi, Garyfalia; Thali, Michael J; Fischer, Nadja

    2011-01-01

    The media and the Internet may be having an influence on suicidal behavior. Online social networks such as Facebook represent a new facet of global information transfer. The impact of these online social networks on suicidal behavior has not yet been evaluated. To discuss potential effects of suicide notes on Facebook on suicide prevention and copycat suicides, and to create awareness among health care professionals. We present a case involving a suicide note on Facebook and discuss potential consequences of this phenomenon based on literature found searching PubMed and Google. There are numerous reports of suicide notes on Facebook in the popular press, but none in the professional literature. Online social network users attempted to prevent planned suicides in several reported cases. To date there is no documented evidence of a copycat suicide, directly emulating a suicide announced on Facebook. Suicide notes on online social networks may allow for suicide prevention via the immediate intervention of other network users. But it is not yet clear to what extent suicide notes on online social networks actually induce copycat suicides. These effects deserve future evaluation and research.

  9. Suicide in the Middle Years

    Science.gov (United States)

    Coombs, David W.; Hodges, Debra K.; Kohler, Connie

    2012-01-01

    This article presents an overview of adult suicide in the United States and Alabama. This includes the latest available information on the prevalence of suicide in the US and Alabama, demographic characteristics of suicide victims, trends in suicide, and known reasons behind adult suicide. With respect to adult suicide in Alabama, it focuses on…

  10. Examining suicide: imaging's contributions.

    Science.gov (United States)

    Church, Elizabeth J

    2015-01-01

    For many people, the death of hope leads inexorably to the conclusion that the only viable solution, the only way to put an end to unendurable pain, is suicide. What leads a person to commit this final, desperate act, and how might we predict, intervene, and prevent suicide? Health care workers, including radiologic technologists, can play an important role in detecting warning signs in patients and in better understanding what factors may lead to suicide. Although certain forms of suicide such as suicide bombings and assisted suicide are beyond its scope, this article explores medical imaging's contributions to the study of this phenomenon.

  11. Personal suicidality in reception and identification with suicidal film characters.

    Science.gov (United States)

    Till, Benedikt; Vitouch, Peter; Herberth, Arno; Sonneck, Gernot; Niederkrotenthaler, Thomas

    2013-04-01

    The authors investigated the impact of suicidality on identity work during film exposure. Adults with low suicidality (n = 150) watched either It's My Party or The Fire Within, censored versions of these films not depicting the suicide, or the control film that concluded with a non-suicidal death. Baseline suicidality was measured with questionnaires before the movie. Identity work and identification with the protagonist were measured after the movie. Suicidality was directly associated with identity work during film dramas depicting suicide methods. The reception of suicide-related media content seems to partially depend on personal suicidality. Potential implications for suicide prevention are discussed.

  12. Suicide: current trends.

    Science.gov (United States)

    Bailey, Rahn K; Patel, Tejas C; Avenido, Jaymie; Patel, Milapkumar; Jaleel, Mohammad; Barker, Narviar C; Khan, Jahanzeb Ali; Ali, Shahid; Jabeen, Shagufta

    2011-07-01

    Suicide is the act of a human being intentionally causing his or her own death. More than 1 million people commit suicide every year. It is the 13th leading cause of death worldwide, with China, India, and Japan accounting for almost half of all suicides. In less than 50 years, the rate of suicide among Sri Lankans has risen from a modest level to one of the highest in the world (118 per 100,000). Suicide is a major preventable cause of premature death. It is influenced by psychosocial, cultural, and environmental risk factors. The impact of suicide can be devastating for all concerned. It is common in people who are living with chronic mental illness. Individuals with severe clinical depression and alcohol use disorders are at highest risk if untreated. On an interpersonal level, friends and families of suicide victims require social support. On a national level, governments need to recognize the causes of suicide and protect those most vulnerable. If governments commit to defining national responses to prevent suicide, significant progress can be made. On a global scale, research and health organizations can identify global trends and encourage the sharing of information in effective prevention activities. In September 2010, World Suicide Prevention Day, with a theme of "Many faces, many places: suicide prevention across the world," encouraged public awareness worldwide to unite in commitment and action to promote understanding about suicide and removal of stigmatization'. There is compelling evidence that adequate prevention and awareness can reduce suicide rates.

  13. Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response.

    Science.gov (United States)

    Zhang, Xuanwei; Niedermann, Gabriele

    2018-05-01

    Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment. In mice bearing 2 B16-CD133 melanoma tumors, the primary tumor was irradiated with 3 × 9.18 Gy in 3 or 5 days or with 5 × 6.43 Gy in 10 days; an anti-PD1 antibody was given weekly. The mice were monitored for tumor growth and survival. T-cell responses were determined on days 8 and 15 of treatment. The role of regional lymph nodes was studied by administering FTY720, which blocks lymph node egress of activated T cells. Tumor growth measurements after combination treatment using short or extended hRT and control treatment were also performed in the wild-type B16 melanoma and 4T1 breast carcinoma models. In the B16-CD133 model, growth inhibition of irradiated primary and nonirradiated secondary tumors and overall survival were similar with all 3 hRT/anti-PD1 combinations, superior to hRT and anti-PD1 monotherapy, and was strongly dependent on CD8 + T cells. TIL infiltration and local and systemic tumor-specific CD8 + T-cell responses were also similar, regardless of whether short or extended hRT was used. Administration of FTY720 accelerated growth of both primary and secondary tumors, strongly reduced their TIL infiltration, and increased tumor-specific CD8 + T cells in the lymph nodes draining the irradiated tumor. In the 4T1 model, local and abscopal tumor control was also similar, regardless of whether short or extended hRT was used, although the synergy between hRT and anti-PD1 was weaker. No

  14. Terrorists and Suicide Attacks

    National Research Council Canada - National Science Library

    Cronin, Audrey K

    2003-01-01

    Suicide attacks by terrorist organizations have become more prevalent globally, and assessing the threat of suicide attacks against the United States and its interests at home and abroad has therefore...

  15. Secondary combined suicide pact.

    Science.gov (United States)

    Jayanth, S H; Girish Chandra, Y P; Hugar, Basappa S; Kainoor, Sunilkumar

    2014-03-01

    This article reports a combined suicide pact, where in a young couple; a 26 year old male and a 20 year old female committed suicide by using two methods. The couple had resorted to hanging and self-immolation to prevent failure of single method alone. In secondary combined suicides, several other methods of suicide are tried after the first method chosen has failed. It is primary combined suicide only when two or more methods are used simultaneously. Both types of combined suicide by one individual is well reported in the literature whereas the same by two persons together is rare. In this report, the deceased were disappointed lovers, poor and the family members were against their marriage. The investigation of scene, methods employed to commit suicide, autopsy findings and the interview with their relatives altogether suggested that it was a secondary combined suicide pact. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  16. Schizophrenia and Suicide

    Directory of Open Access Journals (Sweden)

    Ozlem Cetin

    2011-12-01

    Full Text Available Suicide is one of the major causes of premature death among patients with schizophrenia. Follow-up studies have estimated that 4-5% of these patients die by suicide. Reducing the high rates of suicide in schizophrenia is possible with understanding of predictive risk factors. Various studies have identified risk factors for suicide in schizophrenia patients. Clinical risk factors include previous suicide attempts, comorbid depression, feelings of hopelessness, concept of insight and substance abuse. Biopsychosocial factors, such as a high intelligence quotient and high level of premorbid functioning, have also been associated with an increased risk of suicide in patients with schizophrenia. The risk of suicide is considered to be highest in the early course of illness. Antipsychotic drugs, in particular clozapine and antidepressants may be helpful in reducing the risk of suicide in schizophrenia.

  17. Depression and Suicide Risk

    Science.gov (United States)

    ... due to another medical disorder Relationship Between Depression & Suicide: 1. Depression is the psychiatric diagnosis most commonly associated with ... of patients with treated depression eventually die by suicide. xiv 4. Depression is present in at least 50 percent of ...

  18. Teen Suicide and Guns

    Science.gov (United States)

    ... Issues Listen Text Size Email Print Share Teen Suicide and Guns Page Content Article Body Protect Your ... of a passing problem, not the outcome! Teen Suicide—A Big Problem Suicide is one of the ...

  19. Editorial: Reducing adolescent suicide.

    Science.gov (United States)

    Bloch, Michael H

    2016-07-01

    Suicide is currently the second leading cause of death in young people ages 10-19 (CDC, 2015). Current statistics suggest that in the US one in every seven youths has seriously considered or made a plan to commit suicide and one in every 13 youths has attempted suicide in the previous year (CDC, 2015). Suicide represents a - if not the - major public health problem in adolescents. © 2016 Association for Child and Adolescent Mental Health.

  20. Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide.

    Science.gov (United States)

    Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J

    2017-01-03

    Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.

  1. Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide

    Science.gov (United States)

    Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, J

    2017-01-01

    Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. Suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers. PMID:28045465

  2. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  3. Suicide. Useful Information on...

    Science.gov (United States)

    Moore, Pamela S.; Lewis, Dorothy B., Ed.

    This booklet was written to provide information on suicide. It begins with a brief explanation of the role of suicide in history. A section describing those who commit suicide looks at various populations: elderly persons, children, adolescents and young adults, males, females, blacks, and persons of different marital status. The next section…

  4. [Improving suicide prevention].

    Science.gov (United States)

    Debout, Michel

    2017-04-01

    Suicidal thoughts precede a suicide attempt. Knowing the people who are exposed to such thoughts enables prevention to be improved. The results of a study of the general population show that one in five French people claim to have already seriously considered committing suicide. This represents a particularly concerning public health issue. Copyright © 2017. Published by Elsevier Masson SAS.

  5. Youth Suicide Prevention.

    Science.gov (United States)

    Gould, Madelyn S.; Kramer, Rachel A.

    2001-01-01

    Reviews research literature on youth suicide that has emerged during the past two decades and examines the possibility of linking this research to the practice of suicide prevention. Such research could be used to develop and evaluate appropriate crisis centers and hotlines as well as school-based suicide awareness curriculum programs. Table…

  6. Youth Suicide: A Review

    Science.gov (United States)

    Gould, Madelyn S.; Greenberg, Ted; Velting, Drew M.; Shaffer, David

    2006-01-01

    Following a comprehensive review of the research literature on youth suicide, the authors discuss the rates and patterns of completed suicides and suicide attempts. The state of research on potential risk and protective factors is also reviewed, covering personal characteristics, family characteristics, adverse life circumstances, and…

  7. College Student Suicide

    Science.gov (United States)

    Taub, Deborah J.; Thompson, Jalonda

    2013-01-01

    Suicide is the second-leading cause of death among college students, and it is estimated that 1,088 college students die by suicide each year (National Mental Health Association and the Jed Foundation, 2002). This chapter presents the context of college student mental health within which the problem of college student suicide is situated. Because…

  8. African American Suicide

    Science.gov (United States)

    African American Suicide Fact Sheet Based on 2012 Data (2014) Overview • In 2012, 2,357 African Americans completed suicide in the U.S. Of these, 1,908 (80. ... rate of 9.23 per 100,000). The suicide rate for females was 1.99 per 100, ...

  9. Military Suicide Research Consortium

    Science.gov (United States)

    2014-10-01

    Box. American Association of Suicidology, Suicide Prevention Social Media - Weekly Twitter Chats with Expert Guests. September 21, 2014. Gutierrez...T. E. Jr. (2012). Sleep problems outperform depression and hopelessness as cross-sectional and longitudinal predictors of suicidal ideation and...associated with suicidal ideation , even after accounting for symptoms of depression , hopelessness, PTSD diagnosis, anxiety symptoms and drug and alcohol

  10. Suicide and Personality

    Directory of Open Access Journals (Sweden)

    K. Nahit Ozmenler

    2009-07-01

    Full Text Available Many factors may play role in the emergence of suicidal behavior. Familial tendency including some features of personality structure, hopelessness, affective disorder, and suicide behavior have attracted close attention recently. Personality disorders seem to be prevalent in individuals who attempt suicide. Beside it has been reported that personality disorders and other psychiatric disorder comorbidity increase the risk of suicide. To present the relationship between suicide and personality is quite important for developing strategies in order to prevent suicide attempt. In this field, the data show variability based on scales used for the evaluation of personality, its definition and classification in the research. For example, while some authors used DSM criteria or ICD criteria, others preferred to focus on the temperament and character dimensions of personality. In studies based on diagnostic criteria; B group personality disorders, such as antisocial and borderline personality disorders were found to be most common comorbid personality disorder diagnosis. In studies aiming to investigate the relationship among suicide attempt, temperament and character features, the suicide attempters were found to have lower levels of self directedness, cooperativeness, and higher scores for self transcendence. Suicidal patients were inclined to have higher scores in several temperament groups like harm avoidance, novelty seeking, and reward dependence. Tendency to impulsive behavior is reported as a common denominator for suicidal patients. Individuals, who have familial or acquired tendency of impulsivity, could react more dramatically and present with depressive and pessimistic mood when they have difficulties and encounter stress factors in their daily routine and could easily develop depressive disorders. These factors as a whole could lead to self destructive actions like suicide. Individual or familial history of suicide attempts or completed

  11. Suicide and Suicidal Behavior among Transgender Persons.

    Science.gov (United States)

    Virupaksha, H G; Muralidhar, Daliboyina; Ramakrishna, Jayashree

    2016-01-01

    Suicide rate and suicidal tendencies among transgender persons are considerably high compared to general population. Hence, this review is an attempt to understand the issues around the suicide and suicidal behavior among transgender persons. The literature search conducted using three sources, i.e., electronic databases (PubMed, ProQuest, Google Scholar, PsycInfo), manual search (library catalog), and gray literature (consultation with experts). The suicide attempt rate among transgender persons ranges from 32% to 50% across the countries. Gender-based victimization, discrimination, bullying, violence, being rejected by the family, friends, and community; harassment by intimate partner, family members, police and public; discrimination and ill treatment at health-care system are the major risk factors that influence the suicidal behavior among transgender persons. In spite of facing a number of hardships in their day-to-day life, the transgender community holds a number of resiliency factors. Further, this community needs to be supported to strengthen their resiliency factors and draw culturally sensitive and transgender-inclusive suicide prevention strategies and increase protective factors to tackle this high rate of suicidality.

  12. A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder.

    Science.gov (United States)

    Yin, Honglei; Pantazatos, Spiro P; Galfalvy, Hanga; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, John J

    2016-04-01

    Gamma-amino butyric acid (GABA) and glutamate are the major inhibitory and excitatory neurotransmitters in the mammalian central nervous system, respectively, and have been associated with suicidal behavior and major depressive disorder (MDD). We examined the relationship between genotype, brain transcriptome, and MDD/suicide for 24 genes involved in GABAergic and glutamatergic signaling. In part 1 of the study, 119 candidate SNPs in 24 genes (4 transporters, 4 enzymes, and 16 receptors) were tested for associations with MDD and suicidal behavior in 276 live participants (86 nonfatal suicide attempters with MDD and 190 non-attempters of whom 70% had MDD) and 209 postmortem cases (121 suicide deaths of whom 62% had MDD and 88 sudden death from other causes of whom 11% had MDD) using logistic regression adjusting for sex and age. In part 2, RNA-seq was used to assay isoform-level expression in dorsolateral prefrontal cortex of 59 postmortem samples (21 with MDD and suicide, 9 MDD without suicide, and 29 sudden death non-suicides and no psychiatric illness) using robust regression adjusting for sex, age, and RIN score. In part 3, SNPs with subthreshold (uncorrected) significance levels below 0.05 for an association with suicidal behavior and/or MDD in part 1 were tested for eQTL effects in prefrontal cortex using the Brain eQTL Almanac (www.braineac.org). No SNPs or transcripts were significant after adjustment for multiple comparisons. However, a protein coding transcript (ENST00000414552) of the GABA A receptor, gamma 2 (GABRG2) had lower brain expression postmortem in suicide (P = 0.01) and evidence for association with suicide death (P = 0.03) in a SNP that may be an eQTL in prefrontal cortex (rs424740, P = 0.02). These preliminary results implicate GABRG2 in suicide and warrant further investigation and replication in larger samples. © 2016 Wiley Periodicals, Inc.

  13. Seasonality of Suicidal Behavior

    Science.gov (United States)

    Woo, Jong-Min; Okusaga, Olaoluwa; Postolache, Teodor T.

    2012-01-01

    A seasonal suicide peak in spring is highly replicated, but its specific cause is unknown. We reviewed the literature on suicide risk factors which can be associated with seasonal variation of suicide rates, assessing published articles from 1979 to 2011. Such risk factors include environmental determinants, including physical, chemical, and biological factors. We also summarized the influence of potential demographic and clinical characteristics such as age, gender, month of birth, socioeconomic status, methods of prior suicide attempt, and comorbid psychiatric and medical diseases. Comprehensive evaluation of risk factors which could be linked to the seasonal variation in suicide is important, not only to identify the major driving force for the seasonality of suicide, but also could lead to better suicide prevention in general. PMID:22470308

  14. Multifactorial Causes of Suicide

    Directory of Open Access Journals (Sweden)

    Antemir Cristina-Laura

    2017-12-01

    Full Text Available The science of psychology is well placed to the advantage of understanding why some people are trying to take their lives, and others do not. Understanding the psychological processes underlying the idea of suicide and the decision to act on suicidal thoughts is particularly important. Especially since interventions should be targeted at the suicidal ideation when it first appears before it becomes an attempt of suicide. Factors associated with suicidal risk can be classified into four groups: personality and individual differences, cognitive factors, social factors and life-threatening factors. Each of these factors can contribute to the emergence of suicide risk independently or together with other factors. Some of them are associated with the emergence of suicidal ideation, while others increase the likelihood that these thoughts will come to life.

  15. Prevention of suicide

    Directory of Open Access Journals (Sweden)

    Rajiv Gupta

    2017-01-01

    Full Text Available Suicide is a major public health problem in India, probably even bigger than in the West. Suicidal behavior is the best conceptualized as a multifaceted complex problem involving social factors and mental illnesses. Broadly, there are two approaches to suicide prevention; population preventive strategies and high-risk preventive strategies. Population preventive strategies include reducing availability of means for suicide, education of primary care physicians, influencing media portrayal of suicidal behavior, education of the public, telephone helplines, and addressing economic issues associated with suicidal behavior. High-risk preventive strategy includes identifying individuals with high risk of committing suicide, intensively treating mental illness if present, and providing psychosocial support. Thus, prevention requires a multipronged effort with collaboration from various sectors including mental health professionals, social justice department, and macroeconomic policy makers.

  16. Multiple sclerosis and suicide.

    Science.gov (United States)

    Feinstein, Anthony; Pavisian, Bennis

    2017-06-01

    Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.

  17. Generation of autologous tumor-specific T cells for adoptive transfer based on vaccination, in vitro restimulation and CD3/CD28 dynabead-induced T cell expansion

    DEFF Research Database (Denmark)

    Brimnes, Marie Klinge; Gang, Anne Ortved; Donia, Marco

    2012-01-01

    Adoptive cell transfer (ACT) of in vitro expanded autologous tumor-infiltrating lymphocytes (TIL) has been shown to exert therapeutic efficacy in melanoma patients. We aimed to develop an ACT protocol based on tumor-specific T cells isolated from peripheral blood and in vitro expanded by Dynabeads...

  18. Suicide Mortality, Suicidal Ideation and Psychological Problems in Dutch Anaesthesiologists

    NARCIS (Netherlands)

    Liem, M.C.A.; Liem, A.L.; Dongen, van E.P.A.; Carels, I.C.; Egmond, van M.; Kerkhof, A.J.F.M.

    2015-01-01

    Previous studies reveal an elevated suicide rate for anaesthesiologists. We sought to examine anaesthesiologist suicide mortality and its underlying explanatory factors. Two studies were conducted in order to establish the suicide mortality figures among Dutch anaesthesiologists and to investigate

  19. Wolfram syndrome and suicide: Evidence for a role of WFS1 in suicidal and impulsive behavior.

    Science.gov (United States)

    Sequeira, Adolfo; Kim, Caroline; Seguin, Monique; Lesage, Alain; Chawky, Nadia; Desautels, Alex; Tousignant, Michel; Vanier, Claude; Lipp, Olivier; Benkelfat, Chawki; Rouleau, Guy; Turecki, Gustavo

    2003-05-15

    There is evidence suggesting that subjects affected with the Wolfram syndrome (WFS) and normal carriers present an increased risk of psychiatric disorders, particularly depression and suicidal behavior. We investigated a possible role of the gene involved in WFS (WFS1) in the neurobiology of suicide and the potential modulatory effect on traits associated to suicidal behavior. Genetic variation at WFS1 (H611R, R456H, and I333V) was investigated in 111 suicide victims and 129 normal controls. Possible effects on psychopathology and behavioral traits were investigated in a subsample of suicide cases (N = 31) for whom phenotyping was carried out by means of structured psychiatric interviews and questionnaires adapted for psychological autopsies. We found a significantly higher frequency of the 611R/611R genotype in suicide completers as compared to controls (chi(2) = 19.21, df=2, P = 0.001). Suicide completers with this genotype had higher scores on measures of impulsivity (t = -3.15, df = 15.3, P = 0.006); novelty seeking (NS) (t = -3.35, df = 13.8, P = 0.005); and conversely, lower scores of persistence (t = 2.4, df = 16.6, P = 0.028). Scores of impulsivity and NS remained higher in subjects with the associated genotype after adjusting for age, gender, and psychopathology. These results suggest a role for WFS1 in the pathophysiology of impulsive suicide, and are consistent with previous clinical reports suggesting an increased risk of suicidal behavior in WFS homozygotes and heterozygotes. However, these findings are preliminary and should be confirmed in independent samples. Copyright 2003 Wiley-Liss, Inc.

  20. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  1. Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

    Science.gov (United States)

    Fritsch, Michael K; Bridge, Julia A; Schuster, Amy E; Perlman, Elizabeth J; Argani, Pedram

    2003-01-01

    Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we

  2. WE-AB-202-10: Modelling Individual Tumor-Specific Control Probability for Hypoxia in Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, S; Warren, DR; Wilson, JM; Muirhead, R; Hawkins, MA; Maughan, T; Partridge, M [University of Oxford, Oxford, Oxfordshire (United Kingdom)

    2016-06-15

    Purpose: To investigate hypoxia-guided dose-boosting for increased tumour control and improved normal tissue sparing using FMISO-PET images Methods: Individual tumor-specific control probability (iTSCP) was calculated using a modified linear-quadratic model with rectal-specific radiosensitivity parameters for three limiting-case assumptions of the hypoxia / FMISO uptake relationship. {sup 18}FMISO-PET images from 2 patients (T3N0M0) from the RHYTHM trial (Investigating Hypoxia in Rectal Tumours NCT02157246) were chosen to delineate a hypoxic region (GTV-MISO defined as tumor-to-muscle ratio > 1.3) within the anatomical GTV. Three VMAT treatment plans were created in Eclipse (Varian): STANDARD (45Gy / 25 fractions to PTV4500); BOOST-GTV (simultaneous integrated boost of 60Gy / 25fr to GTV +0.5cm) and BOOST-MISO (60Gy / 25fr to GTV-MISO+0.5cm). GTV mean dose (in EQD2), iTSCP and normal tissue dose-volume metrics (small bowel, bladder, anus, and femoral heads) were recorded. Results: Patient A showed small hypoxic volume (15.8% of GTV) and Patient B moderate hypoxic volume (40.2% of GTV). Dose escalation to 60Gy was achievable, and doses to femoral heads and small bowel in BOOST plans were comparable to STANDARD plans. For patient A, a reduced maximum bladder dose was observed in BOOST-MISO compared to BOOST-GTV (D0.1cc 49.2Gy vs 54.0Gy). For patient B, a smaller high dose volume was observed for the anus region in BOOST-MISO compared to BOOST-GTV (V55Gy 19.9% vs 100%), which could potentially reduce symptoms of fecal incontinence. For BOOST-MISO, the largest iTSCPs (A: 95.5% / B: 90.0%) assumed local correlation between FMISO uptake and hypoxia, and approached iTSCP values seen for BOOST-GTV (A: 96.1% / B: 90.5%). Conclusion: Hypoxia-guided dose-boosting is predicted to improve local control in rectal tumors when FMISO is spatially correlated to hypoxia, and to reduce dose to organs-at-risk compared to boosting the whole GTV. This could lead to organ

  3. Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy

    Directory of Open Access Journals (Sweden)

    Wu B

    2017-06-01

    Full Text Available Bo Wu,1,* Bing Wan,2,* Shu-Ting Lu,1 Kai Deng,3 Xiao-Qi Li,1 Bao-Lin Wu,1 Yu-Shuang Li,1 Ru-Fang Liao,1 Shi-Wen Huang,3 Hai-Bo Xu1,2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Department of Radiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 3Department of Chemistry, Key Laboratory of Biomedical Polymers, Ministry of Education, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: The major challenge in current clinic contrast agents (CAs and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed “bomb-like” light-triggered CAs (LTCAs for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quenching. Then, the release of CAs was triggered by near-infrared (NIR light laser irradiation, which will lead to fluorescence and MRI activation and enable imaging of inflammation. In vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a promising platform for NIR-activated multimodal imaging and photothermal therapy. Keywords: light triggered, near-infrared light, tumor-specific, multimodal imaging, photothermal therapy, contrast agents

  4. Suicide Lethality: A Concept Analysis.

    Science.gov (United States)

    DeBastiani, Summer; De Santis, Joseph P

    2018-02-01

    Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

  5. Hotel room suicide.

    Science.gov (United States)

    Zarkowski, Paul; Avery, David

    2006-10-01

    The objective of our research was to quantify the increased risk of suicide associated with registering in local hotels/motels. Medical examiner case files of suicide in King County, Washington, were reviewed for years 2002-2004. The incidence of suicide in local residents registering in local hotels/motels was 223/100,000 which is significantly greater than the incidence of suicide in the general population of King County (11.7/100,000 p Hotel/motel guests from outside Washington had a significantly reduced incidence of suicide (3.9/100,000 p = 0.002). The study results suggest that there is an increased risk of suicide in local residents who register in local hotel rooms.

  6. [Suicide, a social fact].

    Science.gov (United States)

    Baudelot, Christian

    2017-04-01

    Treating suicide as a social fact means disregarding its individual and dramatic dimensions. Sociologists do not reason on the basis of specific cases but by studying the variations, in space and time, of suicide rates. Their contribution relates essentially to a renewed perspective on society: suicide is in fact a very accurate indicator of the intensity and quality of the bonds which unite or isolate individuals in a society. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Suicidal ideation and behaviour

    OpenAIRE

    Korczak, Daphne J

    2015-01-01

    Suicide is a leading cause of death among Canadian adolescents. The present practice point provides paediatricians and child health professionals with a framework for assessing the adolescent with suicidal thoughts and/or behaviours. The epidemiological context, general considerations and practical suggestions for how to approach the suicidal adolescent are reviewed. Paediatricians can and should screen youth for mental illness and significant psychosocial stressors. Early identification and ...

  8. Suicide with cesium 137

    International Nuclear Information System (INIS)

    Krushkov, I.; Vassileva, B.

    1978-01-01

    Report on first case of suicide with radioactive substance in Bulgaria is given. A defectoscopist with cyclothymic structure of character and psychotraumatic family environment made a second and successful attempt at suicide, this time by means of external irradiation with 137 Cs with an activity of 5.3 C in the course of two hours. He irradiated his heart region and the first three fingers of his right hand. A grave picture of acute, local irradiation injury lasting four months with lethal outcome. The authors treat the psychological motives in the behaviour of these suicides and the reasons which determine the small number of suicide carried out with radioactive substance. (author)

  9. Psychological models of suicide.

    Science.gov (United States)

    Barzilay, Shira; Apter, Alan

    2014-01-01

    Suicidal behavior is highly complex and multifaceted. Consequent to the pioneering work of Durkheim and Freud, theoreticians have attempted to explain the biological, social, and psychological nature of suicide. The present work presents an overview and critical discussion of the most influential theoretical models of the psychological mechanisms underlying the development of suicidal behavior. All have been tested to varying degrees and have important implications for the development of therapeutic and preventive interventions. Broader and more in-depth approaches are still needed to further our understanding of suicidal phenomena.

  10. Suicidality in Body Dysmorphic Disorder

    Science.gov (United States)

    Phillips, Katharine A.

    2008-01-01

    Suicidal ideation, suicide attempts, and completed suicide appear common in individuals with body dysmorphic disorder (BDD). Available evidence indicates that approximately 80% of individuals with BDD experience lifetime suicidal ideation and 24% to 28% have attempted suicide. Although data on completed suicide are limited and preliminary, the suicide rate appears markedly high. These findings underscore the importance of recognizing and effectively treating BDD. However, BDD is underrecognized in clinical settings even though it is relatively common and often presents to psychiatrists and other mental health practitioners, dermatologists, surgeons, and other physicians. This article reviews available evidence on suicidality in BDD and discusses how to recognize and diagnose this often secret disorder. Efficacious treatments for BDD, ie, serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy, are also discussed. Although data are limited, it appears that SRIs often diminish suicidality in these patients. Additional research is greatly needed on suicidality rates, characteristics, correlates, risk factors, treatment, and prevention of suicidality in BDD. PMID:18449358

  11. Emile Durkheim and altruistic suicide.

    Science.gov (United States)

    Stack, Steven

    2004-01-01

    Altruistic suicides are marked by cultural approval and benefit the social order. They occur in social groups where there is a low value placed on the individual. The principle loci of altruistic suicide are primitive societies and the modern military. Subtypes of altruistic suicide (obligatory, optional, acute) are delineated and evaluated. Military suicide rates are seen as being inversely related to civilian suicide rates. Key limitations of Durkheim's model are discussed including his exaggerating the prevalence of obligatory suicide. Suggested points of departure for future research on altruistic suicide include comparative analyses of suicide in the modern military, and application of the concept of optional altruistic suicide to the impact of suicide acceptability on national suicide rates.

  12. Some Syndromes Among Suicidal People: The Problem of Suicide Potentiality.

    Science.gov (United States)

    Wold, Carl I.

    An on-going research project at the Los Angeles Suicide Prevention Center is attempting to describe the potential suicide. Comparisons on a rating scale were made among patients who commit suicide and a random sample of case histories from the coroner's office. Approximately 10 syndromes or subgroupings of people who commit suicide have been…

  13. Personal Suicidality in Reception and Identification with Suicidal Film Characters

    Science.gov (United States)

    Till, Benedikt; Vitouch, Peter; Herberth, Arno; Sonneck, Gernot; Niederkrotenthaler, Thomas

    2013-01-01

    The authors investigated the impact of suicidality on identity work during film exposure. Adults with low suicidality ("n" = 150) watched either "It's My Party" or "The Fire Within," censored versions of these films not depicting the suicide, or the control film that concluded with a non-suicidal death. Baseline…

  14. Assessing the Effects of Peer Suicide on Youth Suicide

    Science.gov (United States)

    Feigelman, William; Gorman, Bernard S.

    2008-01-01

    Using data from all waves of the National Longitudinal Survey of Adolescent Health, we investigated the short-term and long-term impact of an adolescent friend's suicide on an adolescent's depression and suicidality. Results suggest that a friend's suicide is associated with heightened suicide thoughts and attempts and greater depression during…

  15. Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

    Science.gov (United States)

    Heimberger, Amy B; Archer, Gary E; Crotty, Laura E; McLendon, Roger E; Friedman, Allan H; Friedman, Henry S; Bigner, Darell D; Sampson, John H

    2002-01-01

    Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious. C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII. Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced. In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.

  16. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

    Science.gov (United States)

    Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

    2013-02-01

    The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

  17. Suicide and religion.

    Science.gov (United States)

    Cook, Christopher C H

    2014-01-01

    Much of the evidence that religion provides a protective factor against completed suicide comes from cross-sectional studies. This issue of the Journal includes a report of a new prospective study. An understanding of the relationship between spirituality, religion and suicide is important in assessing and caring for those at risk.

  18. Surviving After Suicide

    Science.gov (United States)

    ... fewer tools for communicating their feelings. Surviving After Suicide Fact Sheet 3 Children are especially vulnerable to feelings of guilt and ... to take care of them. Secrecy about the suicide in the hopes of protecting children may cause further complications. Explain the situation and ...

  19. Suicide in the Ukraine.

    Science.gov (United States)

    Kondrichin, Sergei V; Lester, David

    2002-01-01

    The suicide rates of the 24 provinces (oblasts) of the Ukraine were found to be strongly associated with indices of social disintegration (such as divorce and illegitimacy rates), with the Western provinces incorporated in the USSR later than other Ukrainian territories having lower suicide rates and lower levels of social disintegration.

  20. Youth Suicidal Behavior

    Science.gov (United States)

    ... self-injury x Exposure to friends’/family members’ suicide xii Low self-esteem xiii Protective Factors Family and school connectedness iii ... Reduced access to firearms vii Academic achievement ix Self-esteem xi Talking to teens about suicide does not make them want to kill themselves. ...

  1. Endocrinology and Suicide.

    Science.gov (United States)

    Rich, Charles L

    1986-01-01

    Concludes that thyroid and adrenal gland disease unquestionably can produce severe mental disturbances. Most of these are "organic" in nature, but depressive symptoms are common as well. Cautions that a connection between these diseases and suicide has not been established. Advises treating all depressed, suicidal persons with the same…

  2. Suicide and Ethics.

    Science.gov (United States)

    Battin, Margaret P., Ed.; Maris, Ronald W., Ed.

    1983-01-01

    Presents five articles by philosophers and a psychiatrist on the ethics of suicide, as well as comments and a literature review. Discusses the rationality and morality of suicide from several philosophical viewpoints including self-ownership, Kant's theories, and a libertarian perspective. (JAC)

  3. Register for Suicide Attempts

    DEFF Research Database (Denmark)

    Christiansen, Erik; Jensen, Børge Frank

    2004-01-01

    The Register for Suicide Attempts (RSA) is a product of the WHO research project "WHO/Euro Multicentre Study on Parasuicide", which, among other things, had the purpose of collecting data on suicide attempts from 13 European countries. Data is collected in order to calculate trends and identify...

  4. Suicide and Western culture.

    Science.gov (United States)

    Pridmore, Saxby; McArthur, Milford

    2009-02-01

    The aim of this paper is to examine the cultural roots and transmission of Western suicide and suicidal behaviour. We explored a period of antiquity (mythical Greece-61 CE) and selected accounts of 10 prominent suicides. The precipitating circumstances were tabulated and an assessment made of the most likely attendant emotions. The same process was followed for a recent period (1994-2008), from which 10 suicides were identified. The precipitating circumstances and the attendant emotions were compared. These circumstances and emotions were then compared to statements commonly encountered in clinical practice from people demonstrating suicidal behaviour. Finally, we looked for evidence that these stories (and the response models) had entered Western culture. Precipitating circumstances, loss of a loved one, actual or imminent execution or imprisonment, other losses and public disgrace, and the negative emotions of shame, guilt, fear, anger, grief and sorrow were common to both historical periods. These circumstances and emotions are similar to those commonly expressed by people who have demonstrated suicidal behaviour. There was a clear record (literature, visual arts) of these stories forming part of our cultural heritage. Models of maladaptive responses to certain adverse circumstances are part of Western culture. Suicide as a response to certain circumstances and negative emotions can be traced back more than 2000 years. Cultural change will be necessary to minimize suicide.

  5. Suicide in Batman, Southeastern Turkey

    Science.gov (United States)

    Altindag, Abdurrahman; Ozkan, Mustafa; Oto, Remzi

    2005-01-01

    The southeastern part of Turkey has comparatively high female suicide rates. We aimed to research social, economic, cultural, and psychiatric reasons of suicides in Batman in a case-controlled psychological autopsy study comparing suicides with matched community controls. The female suicide rate was 9.3 per 100.000 and the female/male ratio was…

  6. The suicidal desire of Tolstoy.

    Science.gov (United States)

    Pridmore, Saxby; Pridmore, William

    2011-06-01

    To explore whether a healthy, successful individual may experience suicidal desires. Examination of "A Confession" by Leo Tolstoy. Confirmation that a physically and mentally healthy, well resourced individual may experience suicidal desires. To reduce suicide rates, a broader understanding of the factors which contribute to suicidal desires is required.

  7. Characteristics of Suicidality among Adolescents.

    Science.gov (United States)

    Wetzler, Scott; And Others

    1996-01-01

    Examines the characteristics of suicidality and psychopathology (including depression, aggression, impulsivity, and stressful life events) among four groups of depressed adolescent outpatients. The nonsuicidal group was differentiated from the three suicidal groups on the basis of suicidality and psychopathology. The three suicidal groups were…

  8. Mental Disorders and Suicidal Intention.

    Science.gov (United States)

    Litman, Robert E.

    1987-01-01

    Explores use of psychological autopsies to clarify intention in suicide. Compares clinical experience with courtroom experience. Discusses the "decriminalization" of suicide and insurance concerns, mental disorders, and intention to commit suicide. Notes that capacity to have the intent to commit suicide is lost due to mental disorders only under…

  9. NIMH Answers Questions about Suicide

    Science.gov (United States)

    ... else? Q: What if someone seems suicidal on social media? Q: What if I want to write a story about suicide? Q: Where can I go for more information on suicide prevention? Reprints Menu Q: How common is suicide in children and teens? Q: What are some of the ...

  10. The inducible caspase-9 suicide gene system as a ‘safety switch’ to limit on-target, off-tumor toxicities of chimeric antigen receptor T-cells.

    Directory of Open Access Journals (Sweden)

    Tessa eGargett

    2014-10-01

    Full Text Available Immune modulation has become a central element in many cancer treatments, and T cells genetically engineered to express chimeric antigen receptors (CAR may provide a new approach to cancer immunotherapy. Autologous CAR T cells that have been re-directed towards tumor-associated antigens (TAA have shown promising results in phase 1 clinical trials, with some patients undergoing complete tumor regression. However this T-cell therapy must carefully balance effective T-cell activation, to ensure antitumor activity, with the potential for uncontrolled activation that may produce immunopathology. An inducible Caspase 9 (iCasp9 ‘safety switch’ offers a solution that allows for the removal of inappropriately activated CAR T cells. The induction of iCasp9 depends on the administration of the small molecule dimerizer drug AP1903 and dimerization results in rapid induction of apoptosis in transduced cells, preferentially killing activated cells expressing high levels of transgene. The iCasp9 gene has been incorporated into vectors for use in preclinical studies and demonstrates effective and reliable suicide gene activity in phase 1 clinical trials. A third-generation CAR incorporating iCasp9 re-directs T cells towards the GD2 TAA. GD2 is over-expressed in melanoma and other malignancies of neural crest origin and the safety and activity of these GD2-iCAR T cells will be investigated in CARPETS and other actively recruiting phase 1 trials.

  11. Suicide and multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E N; Stenager, Egon; Koch-Henriksen, N

    1992-01-01

    In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR...... with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age......, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males...

  12. Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior.

    Science.gov (United States)

    Pulay, Attila J; Réthelyi, János M

    2016-09-01

    Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n = 999, suicidal n = 358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n = 1,753, suicidal n = 245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n = 35), gene expression data of microRNA genes, (Geneset2, n = 68) and their target genes (Geneset3, n = 11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt  suicide and the cross-disorder association of DICER1. Polygenic risk prediction of the selected miRNA genes indicates that the miRNA system may play a mediating role, but with considerable pleiotropy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Suicide in New Zealand

    Directory of Open Access Journals (Sweden)

    Said Shahtahmasebi

    2005-01-01

    Full Text Available This paper explores and questions some of the notions associated with suicide including mental illness. On average, about two-thirds of suicide cases do not come into contact with mental health services, therefore, we have no objective assessment of their mental status or their life events. One method of improving our objective understanding of suicide would be to use data mining techniques in order to build life event histories on all deaths due to suicide. Although such an exercise would require major funding, partial case histories became publicly available from a coroner's inquest on cases of suicide during a period of three months in Christchurch, New Zealand. The case histories were accompanied by a newspaper article reporting comments from some of the families involved. A straightforward contextual analysis of this information suggests that (i only five cases had contact with mental health services, in two of the cases this was due to a previous suicide attempt and in the other three it was due to drug and alcohol dependency; (ii mental illness as the cause of suicide is fixed in the public mindset, (iii this in turn makes psychological autopsy type studies that seek information from families and friends questionable; (iv proportionally more females attempt, but more men tend to complete suicide; and (v not only is the mental health-suicide relationship tenuous, but suicide also appears to be a process outcome. It is hoped that this will stimulate debate and the collaboration of international experts regardless of their school of thought.

  14. Emotional Impact of a Video-Based Suicide Prevention Program on Suicidal Viewers and Suicide Survivors

    Science.gov (United States)

    Bryan, Craig J.; Dhillon-Davis, Luther E.; Dhillon-Davis, Kieran K.

    2009-01-01

    In light of continuing concerns about iatrogenic effects associated with suicide prevention efforts utilizing video-based media, the impact of emotionally-charged videos on two vulnerable subgroups--suicidal viewers and suicide survivors--was explored. Following participation in routine suicide education as a part of the U.S. Air Force Suicide…

  15. BDNF, impulsiveness and avoidant focused coping in suicide attempters

    OpenAIRE

    AMBRUS, LIVIA

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is an important protein for neuroplasticity and neurogenesis. In this thesis the role of BDNF, in suicidal behaviour was investigated with focus on possible risk factors for suicidal behaviour such as avoidant focused coping, dysfuntional personality traits like impulsiveness and hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis.Paper I: The association between avoidant focused coping and the BDNF Val66Met gene polymorphism in two differen...

  16. A Content Analysis of Online Suicide Notes: Attempted Suicide Versus Attempt Resulting in Suicide.

    Science.gov (United States)

    Synnott, John; Ioannou, Maria; Coyne, Angela; Hemingway, Siobhan

    2017-09-28

    Fifty suicide notes of those who died by suicide and 50 suicide notes of those who survived their suicide attempt were analyzed using Smallest Space Analysis. The core of all suicide notes was discovered to be constructed with the use of four variables: saying goodbye to their audience, feelings of loneliness, method used to attempt suicide, and negative self-image. Furthermore, three different suicide note themes of those who died and three suicide note themes from those who survived were also identified. The analysis revealed that suicide note writers who died by their attempt were more likely to combine a dislike of themselves and a concern for loved ones. The implications of the work in terms of suicide prevention are discussed. © 2017 The American Association of Suicidology.

  17. Association of Hormonal Contraception With Suicide Attempts and Suicides

    DEFF Research Database (Denmark)

    Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel

    2017-01-01

    OBJECTIVE: The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception. METHOD: The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women...... in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt......, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal...

  18. Suicides and suicide ideation in the Bible: an empirical survey.

    Science.gov (United States)

    Koch, H J

    2005-09-01

    The aim of this review is to summarize all data on suicidal behaviour reported in the Bible and to discuss basic implications for medical ethical positions. All books of the Jerusalem Bible, including the apocrypha accepted in the Catholic canon, were searched for all cases of suicide, attempted suicide and suicidal ideation clearly identifiable as such. The Bible including the apocrypha reports about 10 completed suicides and 11 cases of suicide attempt or ideation. The Bible considers human life as a divine gift but suicide per se is neither condemned nor approved. Those suffering from suicidal thoughts are treated with respect and support is offered. Theological teaching on suicide was influenced for centuries by the biased negative opinion of the early fathers of the church and scholastic savants, but these opinions are not substantiated by a thorough reading of the Bible. Copyright (c) 2005 Blackwell Munksgaard

  19. Prioritizing research to reduce youth suicide and suicidal behavior.

    Science.gov (United States)

    Bridge, Jeffrey A; Horowitz, Lisa M; Fontanella, Cynthia A; Grupp-Phelan, Jackie; Campo, John V

    2014-09-01

    The goal of the National Action Alliance for Suicide Prevention is to reduce suicide and suicide attempts in the U.S. by 40% in the next decade. In this paper, a public health approach is applied to suicide prevention to illustrate how reductions in youth suicide and suicidal behavior might be achieved by prioritizing research in two areas: (1) increasing access to primary care-based behavioral health interventions for depressed youth and (2) improving continuity of care for youth who present to emergency departments after a suicide attempt. Finally, some scientific, clinical, and methodologic breakthroughs needed to achieve rapid, substantial, and sustained reductions in youth suicide and suicidal behavior are discussed. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Surviving a Suicide Attempt

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Harrasi

    2016-09-01

    Full Text Available Suicide is a global phenomenon in all regions of the world affecting people of all age groups. It has detrimental consequences on patients, their families, and the community as a whole. There have been numerous risk factors described for suicide including mental illness, stressful life situations, loss of social support, and general despair. The association of suicide with Islam has not been extensively studied. The common impression from clinical practice is that being a practicing Muslim reduces the risk of suicide. Another factor associated with suicide is starting a patient on antidepressants. However, this has been questioned recently. This report describes a middle-aged man with depression and multiple social stressors who survived a serious suicide attempt. The discussion will focus on the factors that lead him to want to end his life and the impact of the assumed protective factors such as religious belief and family support on this act of self-harm. Such patients can be on the edge when there is an imbalance between risk factors (such as depression, insomnia, and psychosocial stressors and protective factors (like religious affiliation and family support. All physicians are advised to assess the suicide risk thoroughly in patients with depression regardless of any presumed protective factor.

  1. Suicide as social logic.

    Science.gov (United States)

    Kral, M J

    1994-01-01

    Although suicide is not viewed as a mental disorder per se, it is viewed by many if not most clinicians, researchers, and lay people as a real or natural symptom of depression. It is at least most typically seen as the unfortunate, severe, yet logical end result of a chain of negative self-appraisals, negative events, and hopelessness. Extending an approach articulated by the early French sociologist Gabriel Tarde, in this paper I argue that suicide is merely an idea, albeit a very bad one, having more in common with societal beliefs and norms regarding such things as divorce, abortion, sex, politics, consumer behavior, and fashion. I make a sharp contrast between perturbation and lethality, concepts central to Edwin S. Shneidman's theory of suicide. Evidence supportive of suicide as an idea is discussed based on what we are learning from the study of history and culture, and about contagion/cluster phenomena, media/communication, and choice of method. It is suggested that certain individuals are more vulnerable to incorporate the idea and act of suicide into their concepts of self, based on the same principles by which ideas are spread throughout society. Just as suicide impacts on society, so does society impact on suicide.

  2. [Suicide in adolescence].

    Science.gov (United States)

    Bouvard, M P; Doyen, C

    1996-12-01

    With 1500 death each year, suicide does represent the second cause of death in young people (between 15 and 25 years). There is a clear increase of suicide rate during adolescence, with an higher rate of suicide attempts in females, but an higher mortality in boys. Suicidal behaviors in adolescents are clinically characterized by impulsivity, rhythmicity (during schooling) and seasonality. Risks factors are numerous. However, psychiatric disorders represent the main one, especially depressive states, conduct disorders and their association. In adolescents familial and environment events may have an important role in suicidal behaviors, especially the role of imitation behavior. These different factors interact and constitute dynamic models. The role of each factor can be involved differently considering the sex. Dangerosity of suicide in adolescents should not be under-estimated, as it has been the case in the past. It is particularly true if we consider the high rate of recidive (approximatively 50%) in this population. These data emphasized the importance of a careful evaluation of all suicidal adolescents more precisely of depressive symptoms and aggressive and/or delinquent behavior and of prevention.

  3. Suicide among War Veterans

    Directory of Open Access Journals (Sweden)

    Vsevolod Rozanov

    2012-07-01

    Full Text Available Studies aiming to identify if war veterans are at higher risk of suicide have often produced inconsistent results; this could be due to the complexity of comparisons and different methodological approaches. It should be noted that this contingent has many risk factors, such as stressful exposures, wounds, brain trauma and pain syndrome. Most recent observations confirm that veterans are really more likely to die of suicide as compared to the general population; they are also more likely to experience suicidal ideation and suffer from mental health problems. Suicides are more frequent in those who develop PTSD, depression and comorbid states due to war exposure. Combat stress and its’ frequency may be an important factor leading to suicide within the frame of the stress-vulnerability model. According to this model, the effects of stress may interact with social factors, interpersonal relations and psychological variables producing suicidal tendencies. Modern understanding of stress-vulnerability mechanisms based on genetic predispositions, early life development, level of exposure to stress and stress-reactivity together with interpersonal aspects may help to build more effective suicide prevention programs based on universal/selective/indicated prevention principles.

  4. Suicide among war veterans.

    Science.gov (United States)

    Rozanov, Vsevolod; Carli, Vladimir

    2012-07-01

    Studies aiming to identify if war veterans are at higher risk of suicide have often produced inconsistent results; this could be due to the complexity of comparisons and different methodological approaches. It should be noted that this contingent has many risk factors, such as stressful exposures, wounds, brain trauma and pain syndrome. Most recent observations confirm that veterans are really more likely to die of suicide as compared to the general population; they are also more likely to experience suicidal ideation and suffer from mental health problems. Suicides are more frequent in those who develop PTSD, depression and comorbid states due to war exposure. Combat stress and its' frequency may be an important factor leading to suicide within the frame of the stress-vulnerability model. According to this model, the effects of stress may interact with social factors, interpersonal relations and psychological variables producing suicidal tendencies. Modern understanding of stress-vulnerability mechanisms based on genetic predispositions, early life development, level of exposure to stress and stress-reactivity together with interpersonal aspects may help to build more effective suicide prevention programs based on universal/selective/indicated prevention principles.

  5. Suicide research before Durkheim.

    Science.gov (United States)

    Goldney, Robert D; Schioldann, Johan A; Dunn, Kirsten I

    2008-01-01

    The casual reader could be forgiven for assuming that there had been little systematic research on suicide before the work of the French sociologist, Emile Durkheim, published in 1897. This historical review demonstrates that there had been extensive studies in the preceding centuries, addressing not only the importance of social factors, but also those factors which are now subsumed in the medical model. In fact, some earlier reviews can now be seen as more balanced and comprehensive than that of Durkheim. In the twentieth century. the predominant focus of suicide research was on the importance of psychosocial factors, a focus which was undoubtedly a legacy of the influential work of Durkheim. Indeed, in 1971 Alvin Alvarez stated that the study of suicide had become the subject of intensive scientific research. The change began in 1897 with the publication of Emile Durkheim's classic Suicide: A Study in Sociology, and more recently Alexander Murray noted that, if the study of suicide had its own era it would divide into two ages, before and after that book ... Le Suicide ... which, more than any other, established its subject as a specialization. Therefore it is not unexpected that many believe that there had not been any substantial suicide research before Durkheim, let alone any which had addressed illness and biological factors and their inter-relationship with society.

  6. A Tumor-specific MicroRNA Recognition System Facilitates the Accurate Targeting to Tumor Cells by Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Yingting Yu

    2016-01-01

    Full Text Available Targeted therapy for cancer is a research area of great interest, and magnetic nanoparticles (MNPs show great potential as targeted carriers for therapeutics. One important class of cancer biomarkers is microRNAs (miRNAs, which play a significant role in tumor initiation and progression. In this study, a cascade recognition system containing multiple plasmids, including a Tet activator, a lacI repressor gene driven by the TetOn promoter, and a reporter gene repressed by the lacI repressor and influenced by multiple endogenous miRNAs, was used to recognize cells that display miRNA signals that are characteristic of cancer. For this purpose, three types of signal miRNAs with high proliferation and metastasis abilities were chosen (miR-21, miR-145, and miR-9. The response of this system to the human breast cancer MCF-7 cell line was 3.2-fold higher than that to the human breast epithelial HBL100 cell line and almost 7.5-fold higher than that to human embryonic kidney HEK293T cells. In combination with polyethyleneimine-modified MNPs, this recognition system targeted the tumor location in situ in an animal model, and an ≃42% repression of tumor growth was achieved. Our study provides a new combination of magnetic nanocarrier and gene therapy based on miRNAs that are active in vivo, which has potential for use in future cancer therapies.

  7. Cultural Aspects of Suicide

    Directory of Open Access Journals (Sweden)

    Hari D. Maharajh

    2005-01-01

    Full Text Available Undefined cultural factors cannot be dismissed and significantly contribute to the worldwide incidence of death by suicide. Culture is an all embracing term and defines the relationship of an individual to his environment. This study seeks to investigate the effect of culture on suicide both regionally and internationally. Culture-bound syndrome with suicidal behaviours specific to a particular culture or geographical region are discussed. Opinions are divided as to the status of religious martyrs. The law itself is silent on many aspects of suicidal behaviour and despite decriminalization of suicide as self-murder, the latter remains on the statutes of many developing countries. The Caribbean region is of concern due to its steady rise in mean suicide rate, especially in Trinidad and Tobago where socio-cultural factors are instrumental in influencing suicidal behaviour. These include transgenerational cultural conflicts, psycho-social problems, media exposure, unemployment, social distress, religion and family structure. The methods used are attributed to accessibility and lethality. Ingestion of poisonous substances is most popular followed by hanging. The gender differences seen with regard to suicidality can also be attributed to gender related psychopathology and psychosocial differences in help-seeking behaviour. These are influenced by the cultural environment to which the individual is exposed. Culture provides coping strategies to individuals; as civilization advances many of these coping mechanisms are lost unclothing the genetic predisposition of vulnerable groups. In the management of suicidal behaviour, a system of therapeutic re-culturation is needed with an emphasis on relevant culture- based therapies.

  8. Suicide Methods in Asia: Implications in Suicide Prevention

    Directory of Open Access Journals (Sweden)

    Paul S. F. Yip

    2012-03-01

    Full Text Available As the largest continent in the World, Asia accounts for about 60% of World suicides. Preventing suicide by restricting access to suicide methods is one of the few evidence-based suicide prevention strategies. However, there has been a lack of systematic exploration of suicide methods in Asian countries. To amend this shortage, the current review examines the leading suicide methods in different Asian countries, their trend, their age- and sex- specific characteristics, and their implications for suicide prevention. In total, 42 articles with leading suicide methods data in 17 Asian countries/regions were retrieved. The epidemiologic characteristics and recent trends of common suicide methods reflect specific socio-cultural, economic, and religious situations in the region. Common suicide methods shift with the introduction of technologies and constructions, and have specific age- or sex-characteristics that may render the restriction of suicide methods not equally effective for all sex and age sub-groups. Charcoal burning, pesticide poisoning, native plant poisoning, self-immolation, and jumping are all prominent examples. In the information society, suicide prevention that focuses on suicide methods must monitor and control the innovation and spread of knowledge and practices of suicide “technologies”. It may be more cost-effective to design safety into technologies as a way of suicide prevention while there is no rash of suicides yet by the new technologies. Further research on suicide methods is important for public health approaches to suicide prevention with sensitivity to socio-cultural, economic, and religious factors in different countries.

  9. Suicide Methods in Asia: Implications in Suicide Prevention

    Science.gov (United States)

    Wu, Kevin Chien-Chang; Chen, Ying-Yeh; Yip, Paul S. F.

    2012-01-01

    As the largest continent in the World, Asia accounts for about 60% of World suicides. Preventing suicide by restricting access to suicide methods is one of the few evidence-based suicide prevention strategies. However, there has been a lack of systematic exploration of suicide methods in Asian countries. To amend this shortage, the current review examines the leading suicide methods in different Asian countries, their trend, their age- and sex- specific characteristics, and their implications for suicide prevention. In total, 42 articles with leading suicide methods data in 17 Asian countries/regions were retrieved. The epidemiologic characteristics and recent trends of common suicide methods reflect specific socio-cultural, economic, and religious situations in the region. Common suicide methods shift with the introduction of technologies and constructions, and have specific age- or sex-characteristics that may render the restriction of suicide methods not equally effective for all sex and age sub-groups. Charcoal burning, pesticide poisoning, native plant poisoning, self-immolation, and jumping are all prominent examples. In the information society, suicide prevention that focuses on suicide methods must monitor and control the innovation and spread of knowledge and practices of suicide “technologies”. It may be more cost-effective to design safety into technologies as a way of suicide prevention while there is no rash of suicides yet by the new technologies. Further research on suicide methods is important for public health approaches to suicide prevention with sensitivity to socio-cultural, economic, and religious factors in different countries. PMID:22690187

  10. Suicide on Death Row.

    Science.gov (United States)

    Tartaro, Christine; Lester, David

    2016-11-01

    Despite the level of supervision of inmates on death row, their suicide rate is higher than both the male prison population in the United States and the population of males over the age of 14 in free society. This study presents suicide data for death row inmates from 1978 through 2010. For the years 1978 through 2010, suicide rates on death row were higher than that for the general population of males over the age of 15 and for state prisons for all but 2 years. © 2016 American Academy of Forensic Sciences.

  11. [Suicide attempts among Chilean adolescents].

    Science.gov (United States)

    Valdivia, Mario; Silva, Daniel; Sanhueza, Félix; Cova, Félix; Melipillán, Roberto

    2015-03-01

    Suicide mortality rates are increasing among teenagers. To study the prevalence and predictive factors of suicide attempts among Chilean adolescents. A random sample of 195 teenagers aged 16 ± 1 years (53% males) answered an anonymous survey about their demographic features, substance abuse, the Osaka suicidal ideation questionnaire, Smilksten familial Apgar. Beck hopelessness scale, Beck depression scale and Coppersmith self-esteem inventory. Twenty five percent of respondents had attempted suicide at least in one occasion during their lives. These attempts were significantly associated with female gender, absent parents, family dysfunction, drug abuse, smoking, low self-esteem, hopelessness, depression and recent suicidal ideation. A logistic regression analysis accepted female gender, smoking and recent suicidal ideation as significant independent predictors of suicide attempt. Suicide attempted is common among teenagers and its predictors are female sex, smoking and previous suicidal ideation.

  12. Factors predicting recovery from suicide in attempted suicide patients.

    Science.gov (United States)

    Sun, Fan-Ko; Lu, Chu-Yun; Tseng, Yun Shan; Chiang, Chun-Ying

    2017-12-01

    The aim of this study was to explore the factors predicting suicide recovery and to provide guidance for healthcare professionals when caring for individuals who have attempted suicide. The high rate of suicide is a global health problem. Suicide prevention has become an important issue in contemporary mental health. Most suicide research has focused on suicidal prevention and care. There is a lack of research on the factors predicting suicidal recovery. A cross-sectional design was adopted. A correlational study with a purposive sample of 160 individuals from a suicide prevention centre in southern Taiwan was conducted. The questionnaires included the Brief Symptom Rating Scale-5, Suicidal Recovery Assessment Scale and Beck Hopelessness Scale. Descriptive statistics and linear regressions were used for the analysis. The mean age of the participants was 40.2 years. Many participants were striving to make changes to create a more stable and fulfilling life, had an improved recovery from suicide and had a good ability to adapt or solve problems. The linear regression showed that the Beck Hopelessness Scale scores (ß = -.551, p suicidal behaviour (ß = -.145, p = .008) were significant predictors of individuals' recovery from suicide. They accounted for 57.1% of the variance. Suicidal individuals who have a lower level of hopelessness, a better ability to cope with their mental condition and fewer past suicidal behaviours may better recover from suicide attempts. The nurses could use the results of this study to predict recovery from suicide in patients with attempted suicide. © 2017 John Wiley & Sons Ltd.

  13. Managing suicidal adolescents

    African Journals Online (AJOL)

    2008-05-09

    May 9, 2008 ... Adolescents with suicidal tendencies have a rather distinct set of problems compared with ... Disorders (4th edition, text revision) (DSM IV)1 represent a fairly standardised approach. ... Depressed mood. Reduced interest in ...

  14. Youth Suicide Prevention Programs

    Science.gov (United States)

    Kalafat, John

    2006-01-01

    Youth suicide prevention programs are described that promote the identification and referral of at-risk youth, address risk factors, and promote protective factors. Emphasis is on programs that are both effective and sustainable in applied settings.

  15. Settings for Suicide Prevention

    Science.gov (United States)

    ... Suicide Populations Racial/Ethnic Groups Older Adults Adolescents LGBT Military/Veterans Men Effective Prevention Comprehensive Approach Identify ... Based Prevention Settings American Indian/Alaska Native Settings Schools Colleges and Universities Primary Care Emergency Departments Behavioral ...

  16. HOMICIDE FOLLOWED BY SUICIDE

    OpenAIRE

    SAMANTHA DUBUGRAS; BLANCA SUSANA GUEVARA WERLANG

    2007-01-01

    Homicide followed by suicide (H/S) is a complex and poorly studied phenomenon. This research aims at identifyingH/S cases occurred in Porto Alegre from 1996 throughout 2004. Information on H/S was extracted from newspapers,police reports and interviews with the informants. From the 14 identified cases, men were the killers/suicides andwomen and children their victims. The most frequently used weapons were firearms. In general, the aggressor was animpulsive, aggressive individual showing probl...

  17. Military Suicide Research Consortium

    Science.gov (United States)

    2016-10-01

    effectiveness NIMH PhenX Suicide-specific Toolkit Dr. Gutierrez served on the PhenX workgroup to develop the toolkit , which is available to NIMH...Fernquist, R. Career development strategies in suicide research #1: Working with a mentor. Panel presented at the American Association of...Suicidology conference, Miami, FL, April 15, 2004. Conwell, Y., Silverman, M., Gutierrez, P. M., Konick, L. C., & Muehlenkamp, J. J. Career development

  18. Suicide and crisis management

    Directory of Open Access Journals (Sweden)

    B S Chavan

    2015-01-01

    Full Text Available Suicide among the general population is a major public health problem and thus is a cause of concern for India. Since suicide is the outcome of multiple factors including socioeconomic, cultural, religious, and political; intervention and prevention strategies will vary from region to region. The legal framework and guidelines in a country can influence the suicide rate by eliminating barriers to mental health services, by adopting and strictly implementing policies on access to firearms for persons with risk of suicide, providing services for treatment of substance abuse patients, and by training of school personnel so that they can identify and assist vulnerable youth in accessing help. Mental Healthcare Bill (MHCB, 2013, will soon become the guiding law for the treatment and rehabilitation of persons suffering from mental health issues. Although MHCB has been criticized on many fronts, it still has laudable provisions that attempt to address reducing treatment gap through the proposal of availability of minimum mental health facilities at primary health center, proposing comprehensive treatment facilities including rehabilitation and the proposal to remove attempted suicide from Section 309 of IPS, etc., which might contribute in suicide prevention and other mental health crisis situations.

  19. Modeling suicide in bipolar disorders.

    Science.gov (United States)

    Malhi, Gin S; Outhred, Tim; Das, Pritha; Morris, Grace; Hamilton, Amber; Mannie, Zola

    2018-02-19

    Suicide is a multicausal human behavior, with devastating and immensely distressing consequences. Its prevalence is estimated to be 20-30 times greater in patients with bipolar disorders than in the general population. The burden of suicide and its high prevalence in bipolar disorders make it imperative that our current understanding be improved to facilitate prediction of suicide and its prevention. In this review, we provide a new perspective on the process of suicide in bipolar disorder, in the form of a novel integrated model that is derived from extant knowledge and recent evidence. A literature search of articles on suicide in bipolar disorder was conducted in recognized databases such as Scopus, PubMed, and PsycINFO using the keywords "suicide", "suicide in bipolar disorders", "suicide process", "suicide risk", "neurobiology of suicide" and "suicide models". Bibliographies of identified articles were further scrutinized for papers and book chapters of relevance. Risk factors for suicide in bipolar disorders are well described, and provide a basis for a framework of epigenetic mechanisms, moderated by neurobiological substrates, neurocognitive functioning, and social inferences within the environment. Relevant models and theories include the diathesis-stress model, the bipolar model of suicide and the ideation-to-action models, the interpersonal theory of suicide, the integrated motivational-volitional model, and the three-step theory. Together, these models provide a basis for the generation of an integrated model that illuminates the suicidal process, from ideation to action. Suicide is complex, and it is evident that a multidimensional and integrated approach is required to reduce its prevalence. The proposed model exposes and provides access to components of the suicide process that are potentially measurable and may serve as novel and specific therapeutic targets for interventions in the context of bipolar disorder. Thus, this model is useful not only

  20. [Clinical psychiatry and suicide prevention].

    Science.gov (United States)

    Cho, Yoshinori

    2012-01-01

    People do not commit suicide all of a sudden. There is a suicidal process where negative life events are there in the beginning, and social support and help-seeking behavior play an important role in impeding the progress of the process. Mental disturbance would be deeply associated with the suicidal process around the final stage, thinking of the fact that approximately 90% of the suicides suffered from mental disorders at the time of suicide. In considering the strategies for suicide prevention, there are two perspectives: a community model and a medical model. A community model is thought to be related mainly to the first half of the suicidal process and a medical model to the latter half. It is an ideal that both community and medical approaches are put into practice simultaneously. However, if resources available for suicide prevention are limited, a medical-model approach would be more efficient and should be given priority. Starting from a medical model and considering treatment and social resources necessary for suicidal people, the range of suicide prevention activities would be expand more efficiently than starting from a community-model approach. Clinical psychiatry plays a greatly important role in preventing suicide. It is found that approximately 20% of seriously injured suicide attempters were diagnosed as adjustment disorder in Japan, which means that even the mildly depressed can commit suicide. Therefore, no one can take a hands-off approach to suicidality as long as he/she works in the field of clinical psychiatry. It is earnestly desired to detect and treat properly the suicidal patients, but there is no perfect method. It would be helpful to pay attention to patients' personality development, stress-coping style and present suicidal ideation. Besides, as suicide prevention is not completed only in a consulting room, it is important for psychiatrists to look for teamwork.

  1. CONTEMPORARY PRINCIPLES OF SUICIDE PREVENTION.

    Science.gov (United States)

    Ljusic, Dragana; Ravanic, Dragan; Filipovic Danic, Snezana; Soldatovic, Ivan; Cvetkovic, Jovana; Stojanovic Tasic, Mirjana

    2016-11-01

    Suicide remains a significant public health problem worldwide. This study is aimed at analyzing and presenting contemporary methods in suicide prevention in the world as well as at identifying specific risk groups and risk factors in order to explain their importance. in suicide prevention. The literature search covered electronic databases PubMed, Web of Science and Scopus. In order to select the relevant articles, the authors searched for the combination of key-words which included the following medical subject heading terms (suicide or suicide ideation or attempted) and (prevention or risk factors) and (man or elders or mental disorders). Data analysis covered meta-analyses, systematic reviews and original scientific papers with different characteristics of suicide preventions, risk factors and risk groups. Worldwide evidence-based interventions for suicide prevention are divided in universal, selective and indicated interventions. Restricted approach to various methods of committing suicide as well as pharmacotherapy contributes to a lower suicide rate. Suicide risk factors can be categorized as proximal and distal. The following groups are at highest risk of committing suicide: males. older persons and persons with registered psychiatric disorders. There is a lot of evidence that suicide is preventable. It is known that only 28 coun tries in the world have national suicide prevention strategies and Serbia is not one of them.

  2. Suicide in ancient Greece.

    Science.gov (United States)

    Laios, K; Tsoukalas, G; Kontaxaki, M-I; Karamanou, M; Androutsos, G

    2014-01-01

    The theme of suicide appears several times in ancient Greek literature. However, each such reference acquires special significance depending on the field from which it originates. Most of the information found in mythology, but the suicide in a mythological tale, although in terms of motivation and mental situation of heroes may be in imitation of similar incidents of real life, in fact is linked with the principles of the ancient Greek religion. In ancient drama and mainly in tragedies suicide conduces to the tragic hypostasis of the heroes and to the evolution of the plot and also is a tool in order to be presented the ideas of poets for the relations of the gods, the relation among gods and men and the relation among the men. In ancient Greek philosophy there were the deniers of suicide, who were more concerned about the impact of suicide on society and also these who accepted it, recognizing the right of the individual to put an end to his life, in order to avoid personal misfortunes. Real suicides will be found mostly from historical sources, but most of them concern leading figures of the ancient world. Closer to the problem of suicide in the everyday life of antiquity are ancient Greek medicines, who studied the phenomenon more general without references to specific incidents. Doctors did not approve in principal the suicide and dealt with it as insane behavior in the development of the mental diseases, of melancholia and mania. They considered that the discrepancy of humors in the organ of logic in the human body will cause malfunction, which will lead to the absurdity and consequently to suicide, either due to excessive concentration of black bile in melancholia or due to yellow bile in mania. They believed that greater risk to commit suicide had women, young people and the elderly. As therapy they used the drugs of their time with the intention to induce calm and repression in the ill person, therefore they mainly used mandragora. In general, we would say

  3. Googling suicide: surfing for suicide information on the Internet.

    Science.gov (United States)

    Recupero, Patricia R; Harms, Samara E; Noble, Jeffrey M

    2008-06-01

    This study examined the types of resources a suicidal person might find through search engines on the Internet. We were especially interested in determining the accessibility of potentially harmful resources, such as prosuicide forums, as such resources have been implicated in completed suicides and are known to exist on the Web. Using 5 popular search engines (Google, Yahoo!, Ask.com, Lycos, and Dogpile) and 4 suicide-related search terms (suicide, how to commit suicide, suicide methods, and how to kill yourself), we collected quantitative and qualitative data about the search results. The searches were conducted in August and September 2006. Several coraters assigned codes and characterizations to the first 30 Web sites per search term combination (and "sponsored links" on those pages), which were then confirmed by consensus ratings. Search results were classified as being prosuicide, antisuicide, suicide-neutral, not a suicide site, or error (i.e., page would not load). Additional information was collected to further characterize the nature of the information on these Web sites. Suicide-neutral and anti-suicide pages occurred most frequently (of 373 unique Web pages, 115 were coded as suicide-neutral, and 109 were anti-suicide). While pro-suicide resources were less frequent (41 Web pages), they were nonetheless easily accessible. Detailed how-to instructions for unusual and lethal suicide methods were likewise easily located through the searches. Mental health professionals should ask patients about their Internet use. Depressed, suicidal, or potentially suicidal patients who use the Internet may be especially at risk. Clinicians may wish to assist patients in locating helpful, supportive resources online so that patients' Internet use may be more therapeutic than harmful.

  4. Homicide Followed by Suicide: A Comparison with Homicide and Suicide

    Science.gov (United States)

    Liem, Marieke; Nieuwbeerta, Paul

    2010-01-01

    Homicide-suicides are a rare yet very serious form of lethal violence which mainly occurs in partnerships and families. The extent to which homicide-suicide can be understood as being primarily a homicide or a suicide event, or rather a category of its own is examined. In total, 103 homicide-suicides were compared to 3,203 homicides and 17,751…

  5. Suicide and suicide risk factors: A literature review | Masango ...

    African Journals Online (AJOL)

    Suicide can be defined as intentional self-inflicted death. 1 It is a serious cause of mortality worldwide. Suicide is considered as a psychiatric emergency and the awareness of the seriousness of suicide in our society should not be overlooked. It is a significant cause of death worldwide.1 It accounts for about 30,000 deaths ...

  6. The concept of rational suicide.

    Science.gov (United States)

    Mayo, D J

    1986-05-01

    Suicide has been condemned in our culture in one way or another since Augustine offered theological arguments against it in the sixth century. More recently, theological condemnation has given way to the view that suicidal behavior must always be symptomatic of emotional disturbance and mental illness. However, suicide has not always been viewed so negatively. In other times and cultures, it has been held that circumstances might befall a person in which suicide would be a perfectly rational course of action, in the same sense that any other course of action could be rational: that it could be sensible, i.e., defensible by good reasons, or that it could be in keeping with the agent's fundamental interests. Indiscriminate use of modern life-sustaining technologies has renewed interest in the possibility of rational suicide. Today proponents of rational suicide tend to equate the rationality of suicide with the competence of the decision to commit suicide.

  7. The Crisis Treatment of Suicide

    Science.gov (United States)

    Tabachnick, Norman

    1970-01-01

    Almost all suicidal persons who consult physicians wish to live. Generally they fall into one of two groups. Interpersonal suiciders manifest frequent threats and attempts, are emotionally labile, have ill-defined suicide plans, and clear ideas as to how their crises might be resolved. Intrapersonal suiciders are less open in manifestations of suicidal drive, withdrawn rather than emotional, often have clearly-formulated suicide plans and do not have ideas (other than suicide) as to how their crises might end. The suicidal situation results from two factors: (1) the loss of some valuable person or commodity, and (2) the loss of self-esteem. What ensues is temporary character disorganization—crisis. Treatment is based on restoration or replacement of lost objects and building up of self-esteem. PMID:5429131

  8. End of Life: Suicide Grief

    Science.gov (United States)

    Healthy Lifestyle End of life A loved one's suicide can be emotionally devastating. Use healthy coping strategies — ... Clinic Staff When a loved one dies by suicide, overwhelming emotions can leave you reeling. Your grief ...

  9. Dyadic Death: Murder-Suicide.

    Science.gov (United States)

    Berman, Alan L.

    1979-01-01

    Results indicated a lower incidence for homocide-suicides than reported previously and several distinguishing characteristics of murderers who subsequently commit suicide. Presented at the 10th Annual Meeting of the American Association of Suicidology, May 1977, Boston. (Author)

  10. Effect of Tryptophan Hydroxylase-2 rs7305115 SNP on suicide attempts risk in major depression

    Directory of Open Access Journals (Sweden)

    Zhang Yuqi

    2010-08-01

    Full Text Available Abstract Background Suicide and major depressive disorders (MDD are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2 gene rs7305115 SNP may predispose to suicide attempts in MDD. Methods We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis. Results There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p p p Conclusions The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.

  11. Insertion of a nuclear factor kappa B DNA nuclear-targeting sequence potentiates suicide gene therapy efficacy in lung cancer cell lines

    DEFF Research Database (Denmark)

    Cramer, F; Christensen, C L; Poulsen, T T

    2012-01-01

    Lung cancer currently causes the majority of cancer-related deaths worldwide and new treatments are in high demand. Gene therapy could be a promising treatment but currently lacks sufficient efficiency for clinical use, primarily due to limited cellular and nuclear DNA delivery. In the present...

  12. Suicidal Behavior in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Bedriye Oncu

    2013-03-01

    Full Text Available Suicide associated mortality rates are notable for eating disorders. Crude mortality rate associated with suicide, varies between 0% and 5.3% in patients with eating disorders. Prominent risk factors for suicidal behavior among these patients are subtype of the eating disorders, comorbid psychiatric diagnosis (e.g. depression, alcohol and substance abuse, personality disorders, ultrarapid drug metabolism, history of childhood abuse and particular family dynamics. In this article, suicidal behavior and associated factors in eating disorders are briefly reviewed.

  13. Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation

    International Nuclear Information System (INIS)

    Hanafusa, Tadashi; Shinji, Toshiyuki; Shiraha, Hidenori; Nouso, Kazuhiro; Iwasaki, Yoshiaki; Yumoto, Eichiro; Ono, Toshiro; Koide, Norio

    2005-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered. In this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity. Deletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated. From these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells

  14. p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA.

    Science.gov (United States)

    Hedström, Elisabeth; Eriksson, Sofi; Zawacka-Pankau, Joanna; Arnér, Elias S J; Selivanova, Galina

    2009-11-01

    Thioredoxin reductase 1 (TrxR1) is a key regulator in many redox-dependent cellular pathways, and is often overexpressed in cancer. Several studies have identified TrxR1 as a potentially important target for anticancer therapy. The low molecular weight compound RITA (NSC 652287) binds p53 and induces p53-dependent apoptosis. Here we found that RITA also targets TrxR1 by non-covalent binding, followed by inhibition of its activity in vitro and by inhibition of TrxR activity in cancer cells. Interestingly, a novel approximately 130 kDa form of TrxR1, presumably representing a stable covalently linked dimer, and an increased generation of reactive oxygen species (ROS) were induced by RITA in cancer cells in a p53-dependent manner. Similarly, the gold-based TrxR inhibitor auranofin induced apoptosis related to oxidative stress, but independently of p53 and without apparent induction of the approximately 130 kDa form of TrxR1. In contrast to the effects observed in cancer cells, RITA did not inhibit TrxR or ROS formation in normal fibroblasts (NHDF). The inhibition of TrxR1 can sensitize tumor cells to agents that induce oxidative stress and may directly trigger cell death. Thus, our results suggest that a unique p53-dependent effect of RITA on TrxR1 in cancer cells might synergize with p53-dependent induction of pro-apoptotic genes and oxidative stress, thereby leading to a robust induction of cancer cell death, without affecting non-transformed cells.

  15. Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

    Directory of Open Access Journals (Sweden)

    Shian-Ying Sung

    Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

  16. [Suicide in Spain today].

    Science.gov (United States)

    Ruiz-Pérez, Isabel; Olry de Labry-Lima, Antonio

    2006-03-01

    Spain presents one of the lowest suicide rates (8.7 per 100,000) but, as well as Ireland, it has also experienced one of the highest rate increases both within Europe and within the world. In our country, it can be observed an increase in the suicide rates from 1975 to 1994, being this increase greater in men than in women. It can also be noted that there was a stabilisation in the following years. Social factors, specially those which have to deal with gender roles and changes in these roles, are the most common explanations. Another possible explanation for the observed increase in mortality due to suicide among young men could be the AIDS epidemic and intravenous drug addiction, that was observed in Spain during the eighties and nineties. Furthermore, we are witnessing an epidemic related to violence against children and women. Literature strongly suggests that child abuse (psychological and sexual) is associated with increased suicide risk in adolescent or adult life. Women experience violence from their intimate partners and have a greater risk of suffering from chronic pain, diverse somatisations, greater substance use like drugs and alcohol, depression and suicide attempt. The association between work precariousness and suicide seems to be due to economic and social and family support factors, which can lead to greater vulnerability to mental health problems. These factors are of great relevance, since Spain presents one of the highest unemployment and temporary employment rates in the European Union. It seems reasonable that, due to the individualism that characterises the contemporary society, its demands and the new role of women in the work market that cause, among others, a greater difficulty in combining work and family life, are factors that could explain the lack of decrease in suicide rates.

  17. Rational Suicide among the Elderly.

    Science.gov (United States)

    Humphry, Derek

    1992-01-01

    Contends that old age, in and of itself, should never need to be a cause for self-destruction. Further argues that suicide and assisted suicide carried out in the face of terminal illness causing unbearable suffering should be ethically and legally acceptable. Outlines a perspective on rational suicide among the elderly. (Author/NB)

  18. The Ethics of Assisted Suicide.

    Science.gov (United States)

    Callahan, Jay

    1994-01-01

    From social work perspective, considers ethics of assisted suicide. Discusses traditional social work value of client self-determination and identifies tensions in this ideal and conflicts with value of client well-being. Finds assisted suicide unethical, arguing that studies have shown judgment of most suicidal people to be impaired as result of…

  19. Absolutism in diaries of suicides.

    Science.gov (United States)

    Lester, David

    2006-08-01

    Two diaries, one from a completed suicide and one from an attempted suicide, were examined for the use of three words indicating absolutist thinking (perfect, always, and never). The diary of the attempted suicide had a significantly higher frequency use of "never" (2.75 per 1,000 words versus 1.73) but not the other words.

  20. Suicide Prevention for LGBT Students

    Science.gov (United States)

    Johnson, R. Bradley; Oxendine, Symphony; Taub, Deborah J.; Robertson, Jason

    2013-01-01

    Extensive media coverage of the suicide deaths of several gay and lesbian youth has highlighted lesbian, gay, bisexual, and transgender (LGBT) youth as a population at-risk for suicide. In addition, it has caused colleges and universities to address mental health and suicide behavior among this very diverse college population. One issue that…

  1. Addiction and suicide: A review.

    Science.gov (United States)

    Yuodelis-Flores, Christine; Ries, Richard K

    2015-03-01

    Addiction specialists frequently find themselves faced with suicidal behavior in their addictions patients. Although many addiction treatment programs will not accept clients with recent suicidal behavior, up to 40% of patients seeking treatment for substance dependence report a history of suicide attempt(s).(1-3) Risk factors for suicide have been studied in the general population and among people with mental illness, less is known about risk factors in those with substance use disorders and co-occurring disorders. Studies, psychological autopsies and recent reviews on risk factors for suicide and suicide attempts in patients with alcohol and drug use disorders and the relationship with co-occurring mental illness were examined. Suicidal behavior is a significant problem for people with co-occurring disorders seeking addiction treatment. Several predisposing and precipitating risk factors such as marital and interpersonal relationship disruption, occupational and financial stressors, recent heavy substance use and intoxication as well as a history of previous suicide attempts and sexual abuse combine in an additive fashion with personality traits and mental illnesses to intensify risk for suicidal behavior in addiction patients. Major depression, bipolar disorder, borderline personality disorder and post-traumatic stress disorder are especially associated with suicidal behavior in people with addictive disorders. Treatment implications of these findings are discussed. Addiction treatment providers should routinely gather information about client's suicidal histories, thoughts, and plans in order to assess risk and develop treatment plans for suicidality at various points in treatment. © American Academy of Addiction Psychiatry.

  2. Childhood Sexual Abuse and Suicide

    Science.gov (United States)

    ... and frequency of abuse increases.” 76 o Among adolescents, suicide attempters report more sexual abuse than non-attempters ... suicide attempts among junior and senior high school youth. Suicide and Life-Threatening Behavior, 25, 358-372. 1011 ...

  3. Non-Fatal Suicidal Behaviors in Adolescents

    OpenAIRE

    Jena, S.; Sidhartha, T.

    2004-01-01

    In the USA, suicide ranked as the third leading cause of death for adolescents in 1999. Non-fatal suicidal behaviours are suicidal thought, specific suicidal plan and suicide attempt. Prospective studies have emphasized the high subsequent suicide rates in clinically presenting suicide attempters. This study was planned to critically review the existing international literature on this area, and compare, if possible, with the Indian data. Both electronic and manual search for published and un...

  4. Biomarkers of suicide risk in psychosis

    OpenAIRE

    Carlborg, Andreas

    2009-01-01

    Suicide and attempted suicide are major health problems. Approximately 1400 people die from suicide every year in Sweden and ten times more attempt suicide. Patients with schizophrenia spectrum psychosis have an increased risk of suicide and suicide rates have been suggested to be as high as 10%. Important risk factors include a prior suicide attempt and depressive disorder. Low concentrations of monoamine metabolites in cerebrospinal fluid (CSF) have been related to suicida...

  5. Risk of repetition of suicide attempt, suicide or all deaths after an episode of attempted suicide

    DEFF Research Database (Denmark)

    Christiansen, Erik; Jensen, Børge Frank

    2007-01-01

    This study was undertaken in order to estimate the incidence of repetition of suicide attempt, suicide and all deaths, and to analyse the influence of psychiatric illness and socio-demographic factors on these.......This study was undertaken in order to estimate the incidence of repetition of suicide attempt, suicide and all deaths, and to analyse the influence of psychiatric illness and socio-demographic factors on these....

  6. Perceptions of Suicide Stigma.

    Science.gov (United States)

    Frey, Laura M; Hans, Jason D; Cerel, Julie

    2016-03-01

    Previous research has failed to examine perceptions of stigma experienced by individuals with a history of suicidal behavior, and few studies have examined how stigma is experienced based on whether it was perceived from treatment providers or social network members. This study examined stigma experienced by individuals with previous suicidal behavior from both treatment providers and individuals in one's social and family networks. Individuals (n = 156) with a lifetime history of suicidal behavior were recruited through the American Association of Suicidology listserv. Respondents reported the highest rates of perceived stigma with a close family member (57.1%) and emergency department personnel (56.6%). Results indicated that individuals with previous suicidal behavior were more likely to experience stigma from non-mental health providers and social network members than from mental health providers. A hierarchical regression model including both source and type of stigma accounted for more variance (R(2) = .14) in depression symptomology than a model (R(2) = .06) with only type of stigma. Prevalence of stigma perceived from social network members was the best predictor of depression symptom severity. These findings highlight the need for future research on how social network members react to suicide disclosure and potential interventions for improving interactions following disclosure.

  7. Police and Suicide Prevention.

    Science.gov (United States)

    Marzano, Lisa; Smith, Mark; Long, Matthew; Kisby, Charlotte; Hawton, Keith

    2016-05-01

    Police officers are frequently the first responders to individuals in crisis, but generally receive little training for this role. We developed and evaluated training in suicide awareness and prevention for frontline rail police in the UK. To investigate the impact of training on officers' suicide prevention attitudes, confidence, and knowledge. Fifty-three participants completed a brief questionnaire before and after undertaking training. In addition, two focus groups were conducted with 10 officers to explore in greater depth their views and experiences of the training program and the perceived impact on practice. Baseline levels of suicide prevention attitudes, confidence, and knowledge were mixed but mostly positive and improved significantly after training. Such improvements were seemingly maintained over time, but there was insufficient power to test this statistically. Feedback on the course was generally excellent, notwithstanding some criticisms and suggestions for improvement. Training in suicide prevention appears to have been well received and to have had a beneficial impact on officers' attitudes, confidence, and knowledge. Further research is needed to assess its longer-term effects on police attitudes, skills, and interactions with suicidal individuals, and to establish its relative effectiveness in the context of multilevel interventions.

  8. [Family, Suicide and Mourning].

    Science.gov (United States)

    Garciandía Imaz, José Antonio

    2013-01-01

    Death is an event that always breaks into family life in a surprising way. Of all the deaths, suicide is the one which more strongly questions the functionality of a family and increases the risk of difficulties in the mourning process. Families in which a suicide has occurred are exposed to a greater possibility of disintegration, disorganization and pathological expressions in their members. To present a reduced and circumscribed narrative revision, restricted to examine the relationship between suicide and the mourning process in the family. The suicide of a loved one is an event that may contribute to pathological grief and mental dysfunctions in surviving relatives. Death in the family is a natural phenomenon. However, death by suicide is one of the phenomena that can generate more alterations in the structure and organization of the family, due to the difficulty related to the mourning process. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  9. Adolescent suicidal ideation.

    Science.gov (United States)

    Field, T; Diego, M; Sanders, C E

    2001-01-01

    Adolescent suicidal ideation and its relationship to other variables was tapped by a self-report questionnaire administered to 88 high school seniors. Eighteen percent responded positively to the statement "sometimes I feel suicidal." Those who reported suicidal ideation were found to differ from those who did not on a number of variables, including family relationships (quality of relationship with mother, intimacy with parents, and closeness to siblings), family history of depression (maternal depression), peer relations (quality of peer relationships, popularity, and number of friends), emotional well-being (happiness, anger, and depression), drug use (cigarettes, marijuana, and cocaine), and grade point average. Stepwise regression indicated that happiness explained 46% of the variance in suicidal ideation, and number of friends, anger, and marijuana use explained an additional 20%, for a total of 66% of the variance. While 34% of the variance remained unexplained, it is suggested that the questions used to measure these four variables be included in global screenings to identify adolescents at risk for suicidal ideation.

  10. Clinical and genetic factors associated with suicide in mood disorder patients.

    Science.gov (United States)

    Antypa, Niki; Souery, Daniel; Tomasini, Mario; Albani, Diego; Fusco, Federica; Mendlewicz, Julien; Serretti, Alessandro

    2016-03-01

    Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the 'Psy Pluriel' center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.

  11. Cancer-specific binary expression system activated in mice by bacteriophage HK022 Integrase

    DEFF Research Database (Denmark)

    Elias, Amer; Spector, Itay; Sogolovsky-Bard, Ilana

    2016-01-01

    Binary systems based on site-specific recombination have been used for tumor specific transcription targeting of suicide genes in animal models. In these binary systems a site specific recombinase or integrase that is expressed from a tumor specific promoter drives tumor specific expression of a ...

  12. Effects of suicide bereavement on mental health and suicide risk

    DEFF Research Database (Denmark)

    Pitman, Alexandra; Osborn, David; King, Michael

    2014-01-01

    to psychiatric care for parents bereaved by the suicide of an offspring, increased risk of suicide in mothers bereaved by an adult child's suicide, and increased risk of depression in offspring bereaved by the suicide of a parent. Some evidence was shown for increased rejection and shame in people bereaved......Between 48 million and 500 million people are thought to experience suicide bereavement every year. Over the past decade, increased policy attention has been directed towards suicide bereavement, but with little evidence to describe the effect of exposure or to provide appropriate responses. We...... used a systematic approach to carry out a narrative review of studies of the effect of suicide bereavement on mortality, mental health, and social functioning, and compared them with effects from other bereavements. We found 57 studies that satisfied strict inclusion criteria. Results from...

  13. [Transcultural aspects of suicidal behaviour].

    Science.gov (United States)

    Calliess, I T; Machleidt, W; Ziegenbein, M; Haltenhof, H

    2007-11-01

    Due to increasing immigration in Germany the German Mental Health Care System today has to deal in a growing number with the assessment of the level of psychic functioning and the capability of self control in patients of different ethnic origin. For clinicians this is a challenge, since suicidal behaviour in terms of its frequency, meaning, motives and manner is very much dependent on the cultural context in which it occurs. Moreover, the general attitude of an individual towards suicide is embedded in the culture of origin of the immigrant. Until now there has been only little systematic research on the influence of culture on suicidal behaviour. In this review the traditions of suicidal behaviour in different cultures in their religious and historical dimensions will be reflected. The historical and cultural roots of suicidal behaviour will be put in context to a categorization of the different variants of suicide, such as institutionalized suicide versus individualized suicide. Psychodynamic aspects of suicidal ideation will be highlighted in cross-cultural perspective with a distinction between a. the wish to die, b. the wish to kill and c. the wish to be killed. It will be shown that there can be differentiated between accepted and non-accepted suicide. With respect to epidemiology there will be discussed the impact of culture on the suicide rates across cultures. The influence of culture on the psychopathology of suicidal behaviour will be summed up systematically. These aspects are of high relevance for the understanding and assessment of suicidal crisis in immigrants, since the suicidal patient even today - although subconsciously - is influenced by the deep rooted traditions of suicidal behaviour in his culture of origin.

  14. Controlling Access to Suicide Means

    Directory of Open Access Journals (Sweden)

    Miriam Iosue

    2011-12-01

    Full Text Available Background: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. Methods: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords “suicide means”, “suicide method”, “suicide prediction” or “suicide prevention” and other relevant keywords. Results: A number of factors may influence an individual’s decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing “safe rooms” in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs, as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Conclusions: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies.

  15. Association between level of suicide risk, characteristics of suicide attempts, and mental disorders among suicide attempters.

    Science.gov (United States)

    Park, Subin; Lee, Yeeun; Youn, Tak; Kim, Byung Soo; Park, Jong Ik; Kim, Haesoo; Lee, Hyo Chu; Hong, Jin Pyo

    2018-04-11

    Past attempted suicide is a strong predictor of future suicide risk, but the risk varies among suicide attempters. Hence, it is important to clarify distinguishing features of lifetime attempters with a high level of current suicide risk for efficient preventive management. We compared characteristics of suicide attempts and clinical characteristics among high-, moderate-, and low-risk attempters. Among the total of 6022 participants in the Korean Epidemiologic Catchment Area study, 193 reported a suicide attempt in their lifetime, 36 of which had high, 126 moderate, and 30 low levels of current suicide risk (1 incomplete response). High-risk suicide attempters had more past attempts compared with moderate- and low-risk suicide attempters. Suicide attempts were closely linked to a wide range of psychiatric comorbidities regardless of degree of current level of suicide risk, but the relative risk for having at least one mental disorder was the highest in high-risk attempters. Specifically, the relative risks for depressive disorder, anxiety disorders including obsessive-compulsive disorder and post-traumatic stress disorder, and substance use disorders were higher in high-risk attempters, and relative risk for somatoform disorder was higher in low-risk attempters than others. Our findings indicated that special attention is required for suicide attempters with a history of repeated attempts and current mental disorders, particularly anxiety disorders.

  16. An Integrative Suicide Prevention Program for Visitor Charcoal Burning Suicide and Suicide Pact

    Science.gov (United States)

    Wong, Paul W. C.; Liu, Patricia M. Y.; Chan, Wincy S. C.; Law, Y. W.; Law, Steven C. K.; Fu, King-Wa; Li, Hana S. H.; Tso, M. K.; Beautrais, Annette L.; Yip, Paul S. F.

    2009-01-01

    An integrative suicide prevention program was implemented to tackle an outbreak of visitor charcoal burning suicides in Cheung Chau, an island in Hong Kong, in 2002. This study evaluated the effectiveness of the program. The numbers of visitor suicides reduced from 37 deaths in the 51 months prior to program implementation to 6 deaths in the 42…

  17. Genetic association studies of suicidal behaviour: A review of the past 10 years, progress, limitations and future directions.

    Directory of Open Access Journals (Sweden)

    BOJAN MIRKOVIC

    2016-09-01

    Full Text Available Suicidal behaviours, which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in suicidal behaviour is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in suicidal behaviours including (i case-control studies, (ii family-based association studies and (iii genome-wide association studies (GWAS. Various studies on genetic associations have tended to suggest that a number of genes (e.g., tryptophan hydroxylase, serotonin receptors and transporters or brain-derived neurotrophic factors are linked to suicidal behaviours, but these findings are not consistently supported by the results obtained. Although the candidate-gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome.Association studies have addressed a wide range of SNPs in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS studies. Numerous meta-analyses of case-control studies have shown significant associations of suicidal behaviour with variants in the serotonin transporter gene (5-HTT or SLC6A4 and the tryptophane hydroxylase1 gene (TPH1, but others report contradictory results. The gene encoding brain-derived neurotrophic factor (BDNF and its receptor (NTRK2 are also promising candidates. Only two of the GWAS studies showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i sample characteristics and confounding factors; (ii statistical limits; (iii gene-gene interactions; (iv gene

  18. Middle-aged and older adults who had serious suicidal thoughts: who made suicide plans and nonfatal suicide attempts?

    Science.gov (United States)

    Choi, Namkee G; DiNitto, Diana M; Marti, C Nathan

    2015-03-01

    High suicide rates in late middle-aged and older adults are significant public health problems. Although suicide risk and protective factors are well established, more research is needed about suicide planners and attempters. Using multi-year, national epidemiologic survey data, this study identified correlates of making suicide plans and nonfatal suicide attempts among U.S. adults aged 50+ years. Data are from the 2008 to 2012 U.S. National Survey on Drug Use and Health (NSDUH). Descriptive statistics were used to examine sample characteristics by past-year serious suicidal thoughts, suicide plans, and suicide attempts. Binary logistic regression analyses were used to examine potential correlates (sociodemographic factors, health status, religiosity, psychiatric and substance use disorders (SUDs), and mental health and substance abuse treatment use) of suicide plans and suicide attempts among those who reported serious suicidal thoughts. Of the 2.5% of the study population that had serious suicidal thoughts (n = 804), 28% made suicide plans and 11.5% attempted suicide. Although 42% of those with serious suicidal thoughts had major depressive episode (MDE), MDE was not significantly associated with suicide plans or attempts in multivariate models. Being employed decreased the odds of making suicide plans, while mental health service use was associated with increased odds of suicide plans. SUDs increased the odds of suicide attempts. It is important to screen middle-aged and older adults for severe mental and SUDs and suicidal thoughts and to target interventions for likely planners and attempters.

  19. Suicide: Across the Life Span.

    Science.gov (United States)

    Ramirez, Jeffery

    2016-06-01

    Suicide remains a major public health issue. There have been more than 40,000 deaths by suicide in 2014. Understanding both the neuroscience and psychological development is key for nursing care so adequate interventions and treatment strategies are developed when working with people thinking about suicide. It is critical to assess and recognize risk and protective factors to ensure patient safety. The older adult, children, and adolescent populations remain vulnerable to suicide. A discussion regarding the psychiatric, psychosocial, and treatment considerations for these populations is included. An overview of communication, suicide assessment, and safety planning is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Tumor Immunology meets…Immunology: Modified cancer cells as professional APC for priming naïve tumor-specific CD4+ T cells.

    Science.gov (United States)

    Bou Nasser Eddine, Farah; Ramia, Elise; Tosi, Giovanna; Forlani, Greta; Accolla, Roberto S

    2017-01-01

    Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer. Here we describe emerging new strategies to increase the TH cell recognition of tumor antigens. In particular, we review recent data indicating that tumor cells themselves can act as surrogate antigen presenting cells for triggering TH response and how these findings can help in constructing immunotherapeutic protocols for anti-cancer vaccine development.

  1. [Suicide in the Elderly].

    Science.gov (United States)

    Velásquez Suarez, Juliana María

    2013-01-01

    Suicide is a public health problem worldwide, with multiple features and risk factors. It has some common and unique trends in each phase across the lifespan. To review the medical literature related to suicide in the elderly, in order to determine the current status of this problem in the world, and especially in Colombia. Literature review. There is a high volume of articles about suicide in general, even in Colombia, with many papers describing the problem in a comprehensive manner, but there is a need for more studies and publications on the scope of this problem in the elderly. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  2. Dostoevsky and suicide.

    Science.gov (United States)

    Foy, J L; Rojcewicz, S J

    1979-01-01

    Fyodor Dostoevsky has continued to grow in stature and influence among modern writers. His modernity is based, among other things, upon his psychological penetration of character and motive. Suicide received considerable attention and analysis in his novels and stories. Although dynamic psychiatry has always held Dostoevsky in high regard, practically all psychiatrists have tended to ignore Dostoevsky's valuable insights into the subject of suicide. This paper offers a total view of the author's contributions to suicidology, through a study of suicidal behavior in his fiction, journalism and in his own life experiences. Dostoevsky's writings are testimony to the continuous and brilliant interrelations between his fictional and journalistic narratives, his understanding of individual, family and group dynamics, his intellectual search for the roots of ideology, and the authentic experience and spiritual quest of his life.

  3. Male depression and suicide.

    Science.gov (United States)

    Wålinder, J; Rutzt, W

    2001-03-01

    Based on the experiences of the Gotland Study that education of general practitioners about depressive illness resulted in a statistically significant reduction in the number of female suicides, leaving the rate of male suicides almost unaffected, we propose the concept of a male depressive syndrome. This syndrome comprises a low stress tolerance, an acting-out behavior, a low impulse control, substance abuse and a hereditary loading of depressive illness, alcoholism and suicide. This notion is supported by data from The Amish study as well as the concept of van Praag of a stress-precipitated, cortisol-induced, serotonin-related and anxiety-driven depressive illness most often seen in males. In order to identify depressed males, the Gotland Male Depression Scale has been developed. Some preliminary data using the scale in a group of alcohol-dependant patients are presented.

  4. Mental Pain and Suicide

    DEFF Research Database (Denmark)

    Verrocchio, Maria Cristina; Carrozzino, Danilo; Marchetti, Daniela

    2016-01-01

    ideation than depression. Conclusion: Mental pain is a core clinical factor for understanding suicide, both in the context of mood disorders and independently from depression. Health care professionals need to be aware of the higher suicidal risk in patients reporting mental pain. In this regard......Background: Mental pain, defined as a subjective experience characterized by perception of strong negative feelings and changes in the self and its function, is no less real than other types of grief. Mental pain has been considered to be a distinct entity from depression. We have performed...... a systematic review analyzing the relationship between mental pain and suicide by providing a qualitative data synthesis of the studies. Methods: We have conducted, in accordance with PRISMA guidelines, a systematic search for the literature in PubMed, Web Of Science, and Scopus. Search terms were "mental pain...

  5. Suicide bomber detection

    Science.gov (United States)

    Alexander, Naomi; Callejero, Carlos; Fiore, Franco; Gómez, Ignacio; Gonzalo, Ramón; Enríquez de Luna, Álvaro; Ederra, Iñigo; Palacios, Inés

    2009-05-01

    The chance of suicide bomber attacks against troops in the Theatre of Operations is currently quite high. Most of the time checkpoints and compound gates are not equipped with the appropriate equipment to screen for potential suicide bombers. The ultimate solution would be to be able to perform stand-off screening under various weather conditions whilst avoiding contact between Force Protection personnel and potential suicide bombers. Radiation in the millimeterwave and the lower Terahertz range, having the useful property of being able to penetrate clothing in addition to fog and rain, makes it a clear candidate for imaging in this situation. A study has been made simulating real case scenarios to test practical detection performance and stand-off distances at a range of frequencies in this band, the results of which will be presented.

  6. Suicide in centenarians

    DEFF Research Database (Denmark)

    Shah, Ajit; Zarate-Escudero, Sofia; Bhat, Ravi

    2014-01-01

    BACKGROUND: The elderly population size is growing worldwide due increased life expectancy and decreased mortality in the elderly. This has lead to an increase in the number of centenarians, and their numbers are predicted to increase further. Little is known about suicide rates in centenarians....... METHODS: Data on the number of suicides (ICD-10 codes, X60-84) in entenarians of both gender for as many years as possible from 2000 were ascertained from three sources: colleagues, national statisics office websites and e-mail contact with the national statistics offices of as many countries as possible....... The number of centernarians for the corresponding years was estimated for each country using data provided by the United Nations website. RESULTS: Data were available from 17 countries. The suicide rate was 57 (95% confidence interval 45-69) per 100, 000 person years in men and 6.8 (95% confidence interval 5...

  7. [Suicidal poisoning with benzodiazepines].

    Science.gov (United States)

    Chodorowski, Z; Sein Anand, J

    1997-01-01

    In the period from 1987 to 1996, 103 patients with suicidal benzodiazepines poisoning were treated, including 62 women and 41 men from 16 to 79 (mean 34) years old. 23 persons were poisoned only by benzodiazepines, in 80 remaining cases intoxications were mixed eg. including benzodiazepines and alcohol, tricyclic antidepressants, barbiturates, opioids, phenothiazines. The main causes of suicides were mainly depression, drug addiction and alcoholism. Nobody died in the benzodiazepines group, while mortality rate in the group of mixed poisoning was 4%. Prescribing benzodiazepines by physicians was quite often not justified and facilitated, among others, accumulation of the dose sufficient for suicide attempt. Flumazenil was efficient for leading out from coma in 86% of cases with poisoning only by benzodiazepines and 13% of cases with mixed intoxications mainly containing benzodiazepines and alcohol or carbamazepine.

  8. An oral Salmonella-based vaccine inhibits liver metastases by promoting tumor-specific T cell-mediated immunity in celiac & portal lymph nodes. A preclinical study.

    Directory of Open Access Journals (Sweden)

    Alejandrina eVendrell

    2016-03-01

    Full Text Available Primary tumor excision is one of the therapies of cancer most widely used. However, the risk of metastases development still exists following tumor resection. The liver is a common site of metastatic disease for numerous cancers. Breast cancer is one of the most frequent source of metastases to the liver. The aim of this work was to evaluate the efficacy of the orally-administered Salmonella Typhi vaccine strain CVD 915 on the development of liver metastases in a mouse model of breast cancer. To this end, one group of BALB/c mice was immunized with CVD 915 via o.g. while another received PBS as a control. After 24 h, mice were injected with LM3 mammary adenocarcinoma cells into the spleen and subjected to splenectomy. This oral Salmonella-based vaccine produced an antitumor effect, leading to a decrease in the number and volume of liver metastases. Immunization with Salmonella induced an early cellular immune response in mice. This innate stimulation rendered a large production of IFN-γ by intrahepatic immune cells (IHIC detected within 24 h. An antitumor adaptive immunity was found in the liver and celiac & portal lymph nodes (LDLN 21 days after oral bacterial inoculation. The antitumor immune response inside the liver was associated with increased CD4+ and DC cell populations as well as with an inflammatory infiltrate located around liver metastatic nodules. Enlarged levels of inflammatory cytokines (IFN-γ and TNF were also detected in IHIC. Furthermore, a tumor-specific production of IFN-γ and TNF as well as tumor-specific IFN-γ-producing CD8 T cells (CD8+IFN-γ+ were found in the celiac & portal lymph nodes of Salmonella-treated mice. This study provides first evidence for the involvement of LDLN in the development of an efficient cellular immune response against hepatic tumors, which resulted in the elimination of liver metastases after oral Salmonella-based vaccination.

  9. TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression.

    Science.gov (United States)

    Yoon, Ho-Kyoung; Kim, Yong-Ku

    2009-04-30

    Serotonergic system-related genes can be good candidate genes for both major depressive disorder (MDD) and suicidal behavior. In this study, we aimed to investigate the association of serotonin 2A receptor gene -1438A/G SNP (HTR2A -1438A/G), tryptophan hydroxylase 2 gene -703G/T SNP (TPH2 -703G/T) and serotonin 1A receptor C-1019G (HTR1A C-1019G) with suicidal behavior. One hundred and eighty one suicidal depressed patients and 143 non-suicidal depressed patients who met DSM-IV criteria for major depressive disorder were recruited from patients who were admitted to Korea University Ansan Hospital. One hundred seventy six normal controls were healthy volunteers who were recruited by local advertisement. Patients and normal controls were genotyped for HTR2A -1438A/G, TPH2 -703G/T and 5-HT1A C-1019G. The suicidal depressed patients were evaluated by the lethality of individual suicide attempts using Weisman and Worden's risk-rescue rating (RRR) and the Lethality Suicide Attempt Rating Scale-updated (LSARS-II). In order to assess the severity of depressive symptoms of patients, Hamilton's Depression Rating Scale (HDRS) was administered. Genotype and allele frequencies were compared between groups by chi(2) statistics. Association of genotype of the candidate genes with the lethality of suicidal behavior was examined with ANOVA by comparing the mean scores of LSARS and RRR according to the genotype. There were statistically significant differences in the genotype distributions and allele frequencies of TPH2 -703G/T between the suicidal depressive group and the normal control group. The homozygous allele G (G/G genotype) frequency was significantly higher in suicidal depressed patients than in controls. However, no differences in either genotype distribution or in allele frequencies of HTR2A -1438A/G and HTR1A C-1019G were observed between the suicidal depressed patients, the non-suicidal depressed patients, and the normal controls. There were no differences in the

  10. Suicide in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Dursun Karaman

    2013-03-01

    Full Text Available Every year, almost one million people commit suicide worldwide which is approximately 1.5% of all deaths. Thus suicide is 10th leading cause of death globally and the third leading cause of death among children and adolescents ages 10 to 24 years. Little is known about the characteristics of successive attempts among individuals who survive the first suicide attempt. It is very important to identify risk factors that can be predictive of future suicide attempts. Subjects with one suicide attempt had an increased risk for a future attempt. Most children and adolescents with suicidal behavior have at least one psychiatric disorder with mood disorders being the most common. A thorough examination of risk factors, the impact of suicidal behavior on patients and on their families and communities, and recommended directions for future research are main focus of this review.

  11. Suicidal ideation among Malaysian adolescents.

    Science.gov (United States)

    Ahmad, NoorAni; Cheong, Siew Man; Ibrahim, Nurashikin; Rosman, Azriman

    2014-09-01

    Adolescence is the time of greatest risk for the first onset of suicidal behaviors. This study aimed to identify the risk and protective factors associated with suicidal ideation among Malaysian adolescents. Data from the 2012 Malaysia Global School-based Student Health Survey, a nationwide study using a 2-stage cluster sampling design, were analyzed. The survey used a self-administered validated bilingual questionnaire and the Depression Anxiety and Stress Scale. The prevalence of suicidal ideation was 7.9%. Analysis revealed that suicidal ideation was positively associated with depression, anxiety, stress, substance use, being bullied, and being abused at home, either physically or verbally. In addition, suicidal ideation was significantly higher among females and among the Indians and Chinese. Having close friends and married parents were strongly protective against suicidal ideation. Understanding the risk and protective factors is important in providing comprehensive management for suicidal ideation. © 2014 APJPH.

  12. Detecting suicidality on Twitter

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    Bridianne O'Dea

    2015-05-01

    Full Text Available Twitter is increasingly investigated as a means of detecting mental health status, including depression and suicidality, in the population. However, validated and reliable methods are not yet fully established. This study aimed to examine whether the level of concern for a suicide-related post on Twitter could be determined based solely on the content of the post, as judged by human coders and then replicated by machine learning. From 18th February 2014 to 23rd April 2014, Twitter was monitored for a series of suicide-related phrases and terms using the public Application Program Interface (API. Matching tweets were stored in a data annotation tool developed by the Commonwealth Scientific and Industrial Research Organisation (CSIRO. During this time, 14,701 suicide-related tweets were collected: 14% were randomly (n = 2000 selected and divided into two equal sets (Set A and B for coding by human researchers. Overall, 14% of suicide-related tweets were classified as ‘strongly concerning’, with the majority coded as ‘possibly concerning’ (56% and the remainder (29% considered ‘safe to ignore’. The overall agreement rate among the human coders was 76% (average κ = 0.55. Machine learning processes were subsequently applied to assess whether a ‘strongly concerning’ tweet could be identified automatically. The computer classifier correctly identified 80% of ‘strongly concerning’ tweets and showed increasing gains in accuracy; however, future improvements are necessary as a plateau was not reached as the amount of data increased. The current study demonstrated that it is possible to distinguish the level of concern among suicide-related tweets, using both human coders and an automatic machine classifier. Importantly, the machine classifier replicated the accuracy of the human coders. The findings confirmed that Twitter is used by individuals to express suicidality and that such posts evoked a level of concern that warranted

  13. Religiousness and Non-Hopeless Suicide Ideation

    Science.gov (United States)

    Simonson, Randy H.

    2008-01-01

    Individuals who think about suicide but do not feel suicidally hopeless tend to be less religious and can therefore entertain thoughts of suicide unabated by religiousness. Religiousness, suicide ideation, and hopelessness were surveyed among 279 Idaho college students, 37 (13%) of whom were non-hopeless suicide ideators. A total of only 21 (7%)…

  14. Parental affectionless control and suicidality.

    Science.gov (United States)

    Goschin, Simona; Briggs, Jessica; Blanco-Lutzen, Sally; Cohen, Lisa J; Galynker, Igor

    2013-10-01

    Although poor parental bonding is a known risk factor for suicidality, current literature is inconsistent about the relative role of low parental care and parental overprotection, as well as the combination of the two, termed "affectionless control". This review presents the current state of knowledge of the relationship between suicidality and these two aspects of parental bonding. The computerized databases Medline, PubMed, PsychINFO, PsychLit, and Google Scholar were searched using combinations of the following keywords: suicidality, suicide, suicide attempt, suicidal behavior, parental bonding, and parental bonding instrument. Using the results, we reviewed the reports on the relationship between suicidality and parental bonding as measured by validated parental bonding instruments. Twelve papers were analyzed. All of them used the parental bonding instrument (PBI) and one used both the PBI and the object representation inventory (ORI). Most reports agreed that, in mothers, either lack of maternal care and/or overprotection was associated with an increase in suicidal behavior, while in fathers only low care was consistently associated with suicidality. This lack of constancy with regard to the effect of paternal overprotection appears to be due to cultural differences in fathers' role in child rearing. With these differences acknowledged, affectionless control in both parents emerges as the parenting style most strongly associated with suicidal behavior. Common methodological problems included low numbers of subjects, inconsistent control groups, and the lack of a uniform definition of suicidality. Despite methodological limitations, current literature consistently indicates that parental affectionless control is associated with suicidal behavior. Recognizing affectionless control as a risk factor for suicide and developing early interventions aimed at modifying affectionless and overprotective parenting style in families with a history of affective disorders

  15. Adult Attachment Style and Suicidality.

    Science.gov (United States)

    Miniati, Mario; Callari, Antonio; Pini, Stefano

    2017-09-01

    There is evidence in the literature that adverse early attachment experiences and subsequent attachment insecurities during adulthood would lead to pessimism, low self-esteem, hopelessness and, ultimately, to suicide risk. This paper aims to review finding on the link between attachment style and suicidality. We searched the literature using the database of the U.S. National Center for Biotechnology Information (NCBI)-MedLine/Pubmed system from January 1992 until December 2016. We started with 1992 because, as far as we know, there are no published studies exploring the relationship between suicide and insecure attachment before that year. We considered reports published on the relationship between attachment style and suicidality. We applied several combinations of the following search terms: attachment, adult attachment style and suicidality, suicide, suicidal ideation, suicidal behavior or suicidal thoughts, and suicide attempts. We selected only English language studies. Research suggests that insecure attachment style, mostly anxious, and unresolved traumas are associated with an increased suicide risk. Few studies prospectively examined clinical course, comorbid psychiatric disorders, familial suicidality or other psychosocial factors. Further research is needed to highlight the nature of the link between attachment and suicidality. The presence of suicidal ideation and attempts might be a consequence of an underlying interaction between the emergence of psychiatrics symptoms, and the long-lasting presence of inadequate patterns of attachment. Within this context, Separation Anxiety Disorder, categorized in the DSM-5 as a condition not confined to childhood but as an anxiety disorder that may occur through the entire lifespan, might be the a key for the comprehension of this link. From a neurobiological point of view, the role of oxytocin remains unclear.

  16. Family history of suicide and exposure to interpersonal violence in childhood predict suicide in male suicide attempters.

    Science.gov (United States)

    Rajalin, Mia; Hirvikoski, Tatja; Jokinen, Jussi

    2013-05-15

    Family studies, including twin and adoption designs, have shown familial transmission of suicidal behaviors. Early environmental risk factors have an important role in the etiology of suicidal behavior. The aim of the present study was to assess the impact of family history of suicide and childhood trauma on suicide risk and on severity of suicide attempt in suicide attempters. A total of 181 suicide attempters were included. Family history of suicide was assessed with the Karolinska Suicide History Interview or through patient records. Childhood trauma was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behavior in childhood (between 6 and 14 years of age) and during adult life (15 years or older). Suicide intent was measured with the Freeman scale. Male suicide attempters with a positive family history of suicide made more serious and well planned suicide attempts and had a significantly higher suicide risk. In logistic regression, family history of suicide and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters. The information about family history of suicide and exposure to interpersonal violence as a child derives from the patients only. In the first part of the inclusion period the information was collected from patient records. The results of this study imply that suicides among those at biological risk might be prevented with the early recognition of environmental risks. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Brain-derived neurotrophic factor: role in depression and suicide

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2009-08-01

    Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

  18. Copycat Suicide Induced by Entertainment Celebrity Suicides in South Korea

    Science.gov (United States)

    Jang, Soo Ah; Sung, Ji Min; Park, Jin Young

    2016-01-01

    Objective Throughout the past several years, there have been a number of entertainment celebrity suicides in South Korea. The aim of this study was to investigate the clustering of suicides following celebrities' suicides in South Korea from 2005 to 2008, particularly according to certain characteristics. Methods Seven celebrity suicides were examined and defined using the Korean Integrated Newspaper Database System (KINDS) and from these, we considered four affected periods occurring 28 days after each celebrity's suicide. A Poisson time-series autoregression model was used to estimate the relative risk of the total suicide number for each affected period from 2005 to 2008. Logistic regression analysis was performed to investigate whether there were specific increases in the numbers of suicides in subgroups matching each celebrity. Results There were significant increases in the risk of suicide during the affected periods. Remarkable increases were found in the subgroups matching each celebrity, especially in the group in which all factors (sex, age, and method) were similar. Conclusion This study provides confirmation that a significant copycat effect was induced by these celebrities' suicides, especially among people who identified more with the celebrities. This implies that countermeasures for upright media coverage of celebrity suicides should be discussed and practiced properly in South Korea. PMID:26766949

  19. Suicidal behaviour and suicide prevention in later life.

    Science.gov (United States)

    Draper, Brian M

    2014-10-01

    Despite a general decline in late life suicide rates over the last 30 years, older people have the highest rates of suicide in most countries. In contrast, non-fatal suicidal behaviour declines with age and more closely resembles suicide than in younger age groups. There are difficulties in the detection and determination of pathological suicidal ideation in older people. Multiple factors increase suicide risk ranging from distal early and mid-life issues such as child abuse, parental death, substance misuse and traumatic life experiences to proximal precipitants in late life such as social isolation and health-related concerns. Clinical depression is the most frequently identified proximal mental health concern and in many cases is a first episode of major depression. Recent studies have identified changes on neuroimaging and neurocognitive factors that might distinguish suicidal from non-suicidal depression in older people. Strategies for suicide prevention need to be 'whole of life' and, as no single prevention strategy is likely to be successful alone, a multi-faceted, multi-layered approach is required. This should include optimal detection and management of depression and of high risk individuals as available evidence indicates that this can reduce suicidal behaviour. How best to improve the quality of depression management in primary and secondary care requires further research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Suicidality in chronic pain: predictors of suicidal ideation in fibromyalgia.

    Science.gov (United States)

    Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

    2015-04-01

    Fibromyalgia (FM) has been associated with a higher prevalence of suicidal behavior. Nevertheless, much remains unknown about suicide risk factors for this chronic pain disorder. In the present study, the relationship of suicidal ideation in FM with a number of sociodemographic, clinical, and psychological variables was analyzed. One hundred seventeen women with Fibromyalgia were assessed. The procedure included the exploration of sleep problems (Pittsburgh Sleep Quality Index), depression (Beck Depression Inventory [BDI]), health-related quality of life (SF-36 and Fibromyalgia Impact Questionnaire), the core symptoms of FM (visual analogue scales), and algometry of tender points. Suicidal ideation was evaluated by item 9 of the BDI. Patients with presence vs. absence of suicidal ideation were compared in all the variables studied. The prevalence of suicidal ideation among FM patients was 32.5%. Significant differences between patients with vs. without suicidal ideas emerged mainly for the various indices of depression. Patients with suicidal ideation also reported higher levels of anxiety, more day dysfunction due to sleepiness and more limitations due to emotional and physical problems. Logistic regression analysis revealed that cognitive depression symptoms such as BDI Self-Blame cluster are the more closely related to suicide ideation. The presence of suicidal ideation in FM patients is closely related to comorbid depression, anxiety and to a higher impact of the disease in daily life. © 2014 World Institute of Pain.

  1. The Suicidal Narrative and Its Relationship to the Suicide Crisis Syndrome and Recent Suicidal Behavior.

    Science.gov (United States)

    Cohen, Lisa Janet; Gorman, Bernard; Briggs, Jessica; Jeon, Min Eun; Ginsburg, Tal; Galynker, Igor

    2018-02-04

    In this study, we introduce the construct of the suicidal narrative, a hypothetical personal narrative linked to imminent suicide, and explore its relationship to near-term suicidal risk and the suicide crisis syndrome (SCS). Psychiatric outpatients (N = 289) were administered the Columbia Suicide-Severity Rating Scale (C-SSRS), Suicide Crisis Inventory (SCI), and Suicide Narrative Inventory (SNI), a novel instrument combining the documented risk factors of Thwarted Belongingness, Perceived Burdensomeness, Humiliation, Social Defeat, Goal Disengagement, and Goal Reengagement. Dimensional measures of past month, lifetime, and past suicidal phenomena, incorporating ideation and behavior, were calculated from the C-SSRS. Structural equation modeling was used to explore the interaction among variables. Factor analysis of the SNI yielded two orthogonal factors, termed Interpersonal and Goal Orientation. The former factor was comprised of Perceived Burdensomeness, Social Defeat, Humiliation, and Thwarted Belongingness, the latter of Goal Disengagement and Goal Reengagement. The Interpersonal factor correlated with both SCS severity and suicidal phenomena in each time frame and the Goal Orientation factor with no other variable. As hypothesized, the proposed model was significant for the past month only. Our findings support the construct of the suicidal narrative and its function as a near-term suicidal risk factor. © 2018 The American Association of Suicidology.

  2. A genome-wide association study of attempted suicide

    Science.gov (United States)

    Willour, Virginia L.; Seifuddin, Fayaz; Mahon, Pamela B.; Jancic, Dubravka; Pirooznia, Mehdi; Steele, Jo; Schweizer, Barbara; Goes, Fernando S.; Mondimore, Francis M.; MacKinnon, Dean F.; Perlis, Roy H.; Lee, Phil Hyoun; Huang, Jie; Kelsoe, John R.; Shilling, Paul D.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Purcell, Shaun; Smoller, Jordan W.; Craddock, Nicholas; DePaulo, J. Raymond; Schulze, Thomas G.; McMahon, Francis J.; Zandi, Peter P.; Potash, James B.

    2011-01-01

    The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While attempted suicide linkage regions have been identified on 2p11–12 and 6q25–26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single nucleotide polymorphism (SNP) genotypes of 1,201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1,497 BP subjects without a history of suicide attempts. 2,507 SNPs with evidence for association at p<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (p= 5.07 × 10−8). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. PMID:21423239

  3. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  4. [Autism spectrum disorder and suicidality].

    Science.gov (United States)

    Huguet, G; Contejean, Y; Doyen, C

    2015-09-01

    Most studies on suicide exclude subjects with autism spectrum disorders, yet there is a risk group. The purpose of this article is to present the data in the literature regarding the clinical and epidemiological characteristics of suicidality in subjects with autism spectrum disorders and to identify the factors that promote the transition to action. This review was carried out using the data set collected in Medline PubMed, items with "autism spectrum disorder", "pervasive developmental disorder", "Asperger's syndrome", "suicide", "suicide attempt", and "suicide behavior". In all subjects from our research on PubMed, 21.3% of subjects with autism spectrum disorder reported suicidal ideation, have attempted suicide or died by suicide (115 out of 539 subjects) and 7.7% of subjects supported for suicidal thoughts or attempted suicide exhibited an autism spectrum disorder (62 out of 806 subjects), all ages combined. Suicidal ideation and morbid preoccupation are particularly common in adolescents and young adults. Suicide attempts are accompanied by a willingness for death and can lead to suicide. They are more common in high-functioning autism and Asperger subjects. The methods used are often violent and potentially lethal or fatal in two cases published. Suicide risk depends on many factors that highlight the vulnerability of these subjects, following autistic and developmental symptoms. Vulnerability complicating the diagnosis of comorbid depressive and anxiety disorders are major factors associated with suicidality. Vulnerability but also directly related to suicidality, since the origin of physical and sexual abuse and victimization by peers assigning them the role of "scapegoat" are both responsible for acting out. Given the diversity of factors involved in the risk of suicide in this population, this does not validate "a" program of intervention, but the intervention of "customized programs". Their implementation should be as early as possible in order to treat

  5. Ecological suicide in microbes.

    Science.gov (United States)

    Ratzke, Christoph; Denk, Jonas; Gore, Jeff

    2018-05-01

    The growth and survival of organisms often depend on interactions between them. In many cases, these interactions are positive and caused by a cooperative modification of the environment. Examples are the cooperative breakdown of complex nutrients in microbes or the construction of elaborate architectures in social insects, in which the individual profits from the collective actions of her peers. However, organisms can similarly display negative interactions by changing the environment in ways that are detrimental for them, for example by resource depletion or the production of toxic byproducts. Here we find an extreme type of negative interactions, in which Paenibacillus sp. bacteria modify the environmental pH to such a degree that it leads to a rapid extinction of the whole population, a phenomenon that we call ecological suicide. Modification of the pH is more pronounced at higher population densities, and thus ecological suicide is more likely to occur with increasing bacterial density. Correspondingly, promoting bacterial growth can drive populations extinct whereas inhibiting bacterial growth by the addition of harmful substances-such as antibiotics-can rescue them. Moreover, ecological suicide can cause oscillatory dynamics, even in single-species populations. We found ecological suicide in a wide variety of microbes, suggesting that it could have an important role in microbial ecology and evolution.

  6. Stigmatization and Suicide Bereavement

    Science.gov (United States)

    Feigelman, William; Gorman, Bernard S.; Jordan, John R.

    2009-01-01

    With survey data collected primarily from peer support group participants, the authors compared stigmatization responses of 462 parents losing children to suicide with 54 other traumatic death survivors and 24 child natural death survivors. Parents who encountered harmful responses and strained relations with family members and non-kin reported…

  7. Suicide in Canada

    National Research Council Canada - National Science Library

    Leenaars, Antoon A

    1998-01-01

    ... provides long-awaited information that focuses specifically on Canada. It addresses suicide as a multidimensional problem with biological, psychological, cultural, sociological, personal, and philosophical aspects. The contributions integrate both critical analysis and personal experience. There are accounts from Inuit elders, fr...

  8. Electroconvulsive Therapy and Suicide.

    Science.gov (United States)

    Tanney, Bryan L.

    1986-01-01

    When the effectiveness and mortality-morbidity of electroconvulsive therapy (ECT) are compared with those of drug therapies, it appears that ECT is an effective and preferred treatment strategy. It remains underutilized as a modality of suicide prevention. Addresses controversies that presently limit the use of this treatment. (Author/ABB)

  9. Suicide: Neurochemical Approaches

    Directory of Open Access Journals (Sweden)

    Ritabrata Banerjee

    2013-10-01

    Full Text Available Despite the devastating effect of suicide on numerous lives, there is still a dearthof knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF and Nerve growth factor (NGF are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors trk B and trk A respectively. The present study was performed to examine whether the expression profiles of BDNF and/or trk B as well as NGF and/or trk A were altered in postmortem brain in subjects who commitsuicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed in hippocampus obtained 21 suicide subjects and 19 non-psychiatric control subjects. The protein and mRNA levels of BDNF, trk B and NGF, trk A were determined with Sandwich ELISA, Western Blot and RT PCR respectively. Given the importance of BDNFand NGF along with their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, Trk B and NGF, Trk A in both protein and mRNA levels of postmortem brain in suicide subjects suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.

  10. Psychotherapy for Suicidal Clients.

    Science.gov (United States)

    Lester, David

    1994-01-01

    Reviews various systems of psychotherapy for suitability for suicidal clients. Discusses psychoanalysis, cognitive therapy, primal therapy, transactional analysis, Gestalt therapy, reality therapy, person-centered therapy, existential analysis, and Jungian analysis in light of available treatment options. Includes 36 citations. (Author/CRR)

  11. Suicide in serial killers.

    Science.gov (United States)

    Lester, David; White, John

    2010-02-01

    In a sample of 248 killers of two victims in America from 1900 to 2005, obtained from an encyclopedia of serial killers by Newton (2006), those completing suicide did not differ in sex, race, or the motive for the killing from those who were arrested.

  12. VA Suicide Prevention Applications Network

    Science.gov (United States)

    Stephens, Brady; Morley, Sybil; Thompson, Caitlin; Kemp, Janet; Bossarte, Robert M.

    2016-01-01

    Objectives: The US Department of Veterans Affairs’ Suicide Prevention Applications Network (SPAN) is a national system for suicide event tracking and case management. The objective of this study was to assess data on suicide attempts among people using Veterans Health Administration (VHA) services. Methods: We assessed the degree of data overlap on suicide attempters reported in SPAN and the VHA’s medical records from October 1, 2010, to September 30, 2014—overall, by year, and by region. Data on suicide attempters in the VHA’s medical records consisted of diagnoses documented with E95 codes from the International Classification of Diseases, Ninth Revision. Results: Of 50 518 VHA patients who attempted suicide during the 4-year study period, data on fewer than half (41%) were reported in both SPAN and the medical records; nearly 65% of patients whose suicide attempt was recorded in SPAN had no data on attempted suicide in the VHA’s medical records. Conclusion: Evaluation of administrative data suggests that use of SPAN substantially increases the collection of data on suicide attempters as compared with the use of medical records alone, but neither SPAN nor the VHA’s medical records identify all suicide attempters. Further research is needed to better understand the strengths and limitations of both systems and how to best combine information across systems. PMID:28123228

  13. Gender differences in suicide methods.

    Science.gov (United States)

    Callanan, Valerie J; Davis, Mark S

    2012-06-01

    Gender differences in suicide completion rates have been attributed to the differences in lethality of suicide methods chosen by men and women, but few empirical studies have investigated factors other than demographic characteristics that might explain this differential. Data from the 621 suicides in Summit County, Ohio during 1997-2006 were disaggregated by gender to compare known correlates of suicide risk on three methods of suicide-firearm, hanging and drug poisoning. Compared to women, men who completed suicide with firearms were more likely to be married and committed the act at home. Unmarried men were likelier to hang themselves than married men, but unmarried women were less likely to hang themselves than married women. Men with a history of depression were more likely to suicide by hanging, but women with depression were half as likely to hang themselves compared to the women without a history of depression. Men with a history of substance abuse were more likely to suicide by poisoning than men without such history, but substance abuse history had no influence on women's use of poisoning to suicide. For both sexes, the odds of suicide by poisoning were significantly higher for those on psychiatric medications.

  14. Ethnic Differences in Suicidal Ideation and Attempts

    OpenAIRE

    Perez-Rodriguez, M. Mercedes; Baca-Garcia, Enrique; Oquendo, Maria A.; Blanco, Carlos

    2008-01-01

    Suicide is one of the leading causes of death, and suicidal ideation and attempts are a major public health problem. However, little is known about the relationship between ethnicity and suicidal behaviors.

  15. Suicide in America: Frequently Asked Questions

    Science.gov (United States)

    ... Trials? Finding Help Reprints For More Information Share Suicide in America: Frequently Asked Questions Download PDF Download ... a week. Text “HOME” to 741741. What Is Suicide? Suicide is when people direct violence at themselves ...

  16. Suicide attempts and suicides in Bolivia from 2007 to 2012

    DEFF Research Database (Denmark)

    Jørs, Erik; Christoffersen, Mette; Veirum, Nikoline Høgsgaard

    2014-01-01

    (65/77, 85.1%) among those using violent methods such as hanging and jumping compared to non-violent methods (43/84, 50.9%) such as ingesting chemicals and drugs (pdepression, and unwanted pregnancies. Many cases of suicide......BACKGROUND: Suicide attempts and suicides constitute a significant burden on communities and health systems, especially in low income countries. However, many low income countries lack epidemiological information on which to base future preventive strategies. This study reports on gender and age...... profiles as well as the likely background and means used for suicide attempts and suicides in Bolivia. METHOD: This study presents 1124 cases from four different sources of information: (i) emergency ward data with suicide attempts by poisoning from the year 2007, (ii) psychiatric ward data including...

  17. Family history of suicide and high motor impulsivity distinguish suicide attempters from suicide ideators among college students.

    Science.gov (United States)

    Wang, Yong-Guang; Chen, Shen; Xu, Zhi-Ming; Shen, Zhi-Hua; Wang, Yi-Quan; He, Xiao-Yan; Cao, Ri-Fang; Roberts, David L; Shi, Jian-Fei; Wang, Yi-Qiang

    2017-07-01

    Suicide in college students has become an important public health issue in China. The aim of this study was to identify the differences between suicide attempters and suicide ideators based on a cross-sectional survey. Our results indicate that although female gender, positive screening for psychiatric illness, positive family history of suicide, elevated overall impulsivity, and elevated motor impulsivity were correlated with suicidal ideation, only positive family history of suicide and high motor impulsivity could differentiate suicide attempters from suicidal ideators. Future research with a longitudinal and prospective study design should be conducted to confirm these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Suicide risk in schizophrenia: an analysis of 17 consecutive suicides.

    Science.gov (United States)

    Saarinen, P I; Lehtonen, J; Lönnqvist, J

    1999-01-01

    The aim of this study was to investigate interactional factors related to the recognition of suicide risk in patients with schizophrenia. The study focused on 17 schizophrenia patients who had committed suicide during the National Suicide Prevention Project in Finland between April 1, 1987, and March 31, 1988, in the province of Kuopio. Consensus case reports were assembled by using the psychological autopsy method. Study methods included structured and in-depth interviews of next of kin and interviews of health care or social services workers who had treated the suicide victims. Male and female patients with schizophrenia committed suicide in equal proportions. Most had suffered from schizophrenia for more than 15 years; all but one had been receiving psychiatric treatment at the time of suicide. Retrospective assessment indicated that 59 percent of the patients were clinically depressed at the time of suicide. In 76 percent of the cases, the mental health professionals involved in treatment had not believed that there was a risk of suicide during their last contact with the patient. In 29 percent of the cases, the patient's paranoid ideas concerning treatment personnel had increased. Patients' withdrawal from human relationships because of depression was related to loss of the treatment professionals' concern for the patients. The findings in this descriptive study suggest that withdrawal by a patient with schizophrenia and an increase in the patient's paranoid behavior should be regarded as signals of risk of suicide.

  19. Adolescent insomnia, suicide risk, and the interpersonal theory of suicide.

    Science.gov (United States)

    Zullo, Lucas; Horton, Sarah; Eaddy, Michael; King, Jessica; Hughes, Jennifer; Diederich, Andrew; Kennard, Betsy; Emslie, Graham; Stewart, Sunita

    2017-11-01

    Although insomnia has been repeatedly linked with suicide ideation, the reason for the linkage is not clear. The Interpersonal Psychological Theory of Suicide (IPTS) proposes that three core variables (thwarted belongingness, perceived burdensomeness, and acquired capability) are the final common pathway for all risk factors for suicide ideation and behavior. Recent research has suggested that insomnia may be associated with suicide ideation independently of the IPTS. We examined cross-sectional data from 151 psychiatric inpatients (ages 12-17) to determine if the association between insomnia symptoms and a continuous measure of suicide risk (measured as increasingly severe ideation and plan) was explained by the framework of the IPTS. When all IPTS variables and depressive symptoms were included in the model, insomnia symptoms did not contribute unique variance to suicide risk. Perceived burdensomeness and depressive symptoms were found to explain the relationship between insomnia symptoms and suicide risk. Our findings suggest that improved sleep might reduce suicide risk, that management of interpersonal need cognitions might reduce risk in the presence of insomnia symptoms, and reinforce the independent role of depressive symptoms in suicide risk in clinical samples of adolescents. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Health professionals' attitudes towards suicide prevention initiatives.

    Science.gov (United States)

    Brunero, S; Smith, J; Bates, E; Fairbrother, G

    2008-09-01

    Preventing suicide can depend upon the ability of a range of different health professionals to make accurate suicide risk assessments and treatment plans. The attitudes that clinicians hold towards suicide prevention initiatives may influence their suicide risk assessment and management skills. This study measures a group of non-mental health professionals' attitude towards suicide prevention initiatives. Health professionals that had attended suicide prevention education showed significantly more positive attitudes towards suicide prevention initiatives. The findings in this study further support the effectiveness of educating non-mental health professionals in suicide risk awareness and management.

  1. Suicidal ideation and suicide attempts in bipolar disorder type I: an update for the clinician

    OpenAIRE

    Abreu,Lena Nabuco de; Lafer,Beny; Baca-Garcia,Enrique; Oquendo,Maria A.

    2009-01-01

    OBJECTIVE: This article reviews the evidence for the major risk factors associated with suicidal behavior in bipolar disorder. METHOD: Review of the literature studies on bipolar disorder, suicidal behavior and suicidal ideation. RESULTS: Bipolar disorder is strongly associated with suicide ideation and suicide attempts. In clinical samples between 14-59% of the patients have suicide ideation and 25-56% present at least one suicide attempt during lifetime. Approximately 15% to 19% of patients...

  2. Military Suicide Research Consortium (MSRC)

    Science.gov (United States)

    2013-10-01

    suicide research. Suicide and Life-Threatening Behavior, 40(5), 500- 505 . doi:10.1521/suli.2010.40.5.500 Breshears, R. E., Brenner, L. A., Harwood, J...mood symptoms (Baglioni et al., 2010)—all of which may serve to mediate the relationship between insom- nia symptoms and suicidal ideation and behavior...included baseline insom- nia symptom index, MSSI, BHS, PTSD, and MCMI scores. Addi- tional analyses involved a logistic regression examining the relation of

  3. Suicide among Arab-Americans.

    Directory of Open Access Journals (Sweden)

    Abdulrahman M El-Sayed

    2011-02-01

    Full Text Available Arab-American (AA populations in the US are exposed to discrimination and acculturative stress-two factors that have been associated with higher suicide risk. However, prior work suggests that socially oriented norms and behaviors, which characterize recent immigrant ethnic groups, may be protective against suicide risk. Here we explored suicide rates and their determinants among AAs in Michigan, the state with the largest proportion of AAs in the US.ICD-9/10 underlying cause of death codes were used to identify suicide deaths from among all deaths in Michigan between 1990 and 2007. Data from the 2000 U.S. Census were collected for population denominators. Age-adjusted suicide rates among AAs and non-ethnic whites were calculated by gender using the direct method of standardization. We also stratified by residence inside or outside of Wayne County (WC, the county with the largest AA population in the state. Suicide rates were 25.10 per 100,000 per year among men and 6.40 per 100,000 per year among women in Michigan from 1990 to 2007. AA men had a 51% lower suicide rate and AA women had a 33% lower rate than non-ethnic white men and women, respectively. The suicide rate among AA men in WC was 29% lower than in all other counties, while the rate among AA women in WC was 20% lower than in all other counties. Among non-ethnic whites, the suicide rate in WC was higher compared to all other counties among both men (12% and women (16%.Suicide rates were higher among non-ethnic white men and women compared to AA men and women in both contexts. Arab ethnicity may protect against suicide in both sexes, but more so among men. Additionally, ethnic density may protect against suicide among Arab-Americans.

  4. Suicide among Arab-Americans.

    Science.gov (United States)

    El-Sayed, Abdulrahman M; Tracy, Melissa; Scarborough, Peter; Galea, Sandro

    2011-02-17

    Arab-American (AA) populations in the US are exposed to discrimination and acculturative stress-two factors that have been associated with higher suicide risk. However, prior work suggests that socially oriented norms and behaviors, which characterize recent immigrant ethnic groups, may be protective against suicide risk. Here we explored suicide rates and their determinants among AAs in Michigan, the state with the largest proportion of AAs in the US. ICD-9/10 underlying cause of death codes were used to identify suicide deaths from among all deaths in Michigan between 1990 and 2007. Data from the 2000 U.S. Census were collected for population denominators. Age-adjusted suicide rates among AAs and non-ethnic whites were calculated by gender using the direct method of standardization. We also stratified by residence inside or outside of Wayne County (WC), the county with the largest AA population in the state. Suicide rates were 25.10 per 100,000 per year among men and 6.40 per 100,000 per year among women in Michigan from 1990 to 2007. AA men had a 51% lower suicide rate and AA women had a 33% lower rate than non-ethnic white men and women, respectively. The suicide rate among AA men in WC was 29% lower than in all other counties, while the rate among AA women in WC was 20% lower than in all other counties. Among non-ethnic whites, the suicide rate in WC was higher compared to all other counties among both men (12%) and women (16%). Suicide rates were higher among non-ethnic white men and women compared to AA men and women in both contexts. Arab ethnicity may protect against suicide in both sexes, but more so among men. Additionally, ethnic density may protect against suicide among Arab-Americans.

  5. Suicide attempts in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Elsebeth Nylev; Jensen, Børge; Stenager, Maria

    2011-01-01

    The purposes of the study were (1) to estimate the risk of suicide attempts in multiple sclerosis (MS) patients in Denmark and compare the risk to the background population in the County of Funen, Denmark; (2) to estimate the risk of suicide attempts in MS patients receiving immunomodulating...... therapy compared with untreated patients. The Danish MS Registry, the Danish MS Treatment Registry and the Suicide Attempt Registry are linked and merged together using a person identification number given to all persons residing in Denmark. Among 404 MS patients, 15 patients had attempted suicide...

  6. Does Religiosity Predict Suicidal Behavior?

    Directory of Open Access Journals (Sweden)

    David Lester

    2017-10-01

    Full Text Available Research was reviewed on whether self-report measures of religiosity were a protective factor against suicidal behaviors. It was found that scores on Francis’s measure of religiosity was negatively associated with non-lethal suicidal behavior (ideation and attempts, a protective effect. Similarly, it was found that intrinsic religiosity (but not extrinsic religiosity was negatively associated with non-lethal suicidal behaviors. However, these associations were weak. Research is needed on the issue whether counselors can use their patients’ religiosity to reduce the risk of dying by suicide.

  7. Association between exposure to suicide and suicidality outcomes in youth.

    Science.gov (United States)

    Swanson, Sonja A; Colman, Ian

    2013-07-09

    Ecological studies support the hypothesis that suicide may be "contagious" (i.e., exposure to suicide may increase the risk of suicide and related outcomes). However, this association has not been adequately assessed in prospective studies. We sought to determine the association between exposure to suicide and suicidality outcomes in Canadian youth. We used baseline information from the Canadian National Longitudinal Survey of Children and Youth between 1998/99 and 2006/07 with follow-up assessments 2 years later. We included all respondents aged 12-17 years in cycles 3-7 with reported measures of exposure to suicide. We included 8766 youth aged 12-13 years, 7802 aged 14-15 years and 5496 aged 16-17 years. Exposure to a schoolmate's suicide was associated with ideation at baseline among respondents aged 12-13 years (odds ratio [OR] 5.06, 95% confidence interval [CI] 3.04-8.40), 14-15 years (OR 2.93, 95% CI 2.02-4.24) and 16-17 years (OR 2.23, 95% CI 1.43-3.48). Such exposure was associated with attempts among respondents aged 12-13 years (OR 4.57, 95% CI 2.39-8.71), 14-15 years (OR 3.99, 95% CI 2.46-6.45) and 16-17 years (OR 3.22, 95% CI 1.62-6.41). Personally knowing someone who died by suicide was associated with suicidality outcomes for all age groups. We also assessed 2-year outcomes among respondents aged 12-15 years: a schoolmate's suicide predicted suicide attempts among participants aged 12-13 years (OR 3.07, 95% CI 1.05-8.96) and 14-15 years (OR 2.72, 95% CI 1.47-5.04). Among those who reported a schoolmate's suicide, personally knowing the decedent did not alter the risk of suicidality. We found that exposure to suicide predicts suicide ideation and attempts. Our results support school-wide interventions over current targeted interventions, particularly over strategies that target interventions toward children closest to the decedent.

  8. Detection of tumor-specific cytotoxic drug activity in vitro using the fluorometric microculture cytotoxicity assay and primary cultures of tumor cells from patients.

    Science.gov (United States)

    Nygren, P; Fridborg, H; Csoka, K; Sundström, C; de la Torre, M; Kristensen, J; Bergh, J; Hagberg, H; Glimelius, B; Rastad, J

    1994-03-01

    The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was compared with known clinical response patterns, a good correspondence was observed. The results indicate that the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tumors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients.

  9. The interpersonal theory of suicide and adolescent suicidal behavior.

    Science.gov (United States)

    Barzilay, S; Feldman, D; Snir, A; Apter, A; Carli, V; Hoven, C W; Wasserman, C; Sarchiapone, M; Wasserman, D

    2015-09-01

    Joiner's interpersonal theory of suicide (IPTS) proposes that suicide results from the combination of a perception of burdening others, social alienation, and the capability for self-harm. The theory gained some empirical support, however the overall model has yet to be tested. This study aimed to test the main predictions of IPTS in a large community sample of Israeli adolescents. 1196 Israeli Jewish and Arab high-school pupils participating in the SEYLE project completed a self-report questionnaire measuring perceived burdensomeness, thwarted belongingness, health risk behaviors, and non-suicidal self-injury (risk variables), and suicidal ideation and suicide attempts (outcome measures). The data were tested in cross-sectional regression models. Consistent with IPTS, perceived burdensomeness was found to interact with thwarted belongingness, predicting suicidal ideation. Depression mediated most of the effect of thwarted belongingness and perceived burdensomeness on suicidal ideation. Acquired capability for self-harm, as measured by health risk behaviors and direct non-suicidal self-injurious behaviors, predicted suicide attempt. However, this mechanism operated independently from ideation rather than in interaction with it, at variance with IPTS-based predictions. The cross-sectional design precludes conclusions about causality and directionality. Proxy measures were used to test the interpersonal theory constructs. The findings support some of the IPTS predictions but not all, and imply two separate pathways for suicidal behavior in adolescents: one related to internalizing psychopathology and the other to self-harm behaviors. This conceptualization has clinical implications for the differential identification of adolescents at risk for suicidal behavior and for the development of prevention strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Repeated suicide attempts and suicide among individuals with a first emergency department contact for attempted suicide

    DEFF Research Database (Denmark)

    Fedyszyn, Izabela E.; Erlangsen, Annette; Hjorthoj, Carsten

    2016-01-01

    Objective: Emergency departments are important, albeit underutilized, sites for suicide prevention. Preventive strategies and interventions could benefit from a greater understanding of factors influencing the course of suicide risk after emergency department contact due to attempted suicide...... = 1.74; 95% CI, 1.22-2.49). The cumulative rates of repeated attempts and suicide deaths in the total sample were particularly high within the first week of the index attempt, reaching 3.6% and 0.1%, respectively. Conclusions: Preventive efforts need to target the period close to discharge from....... The aim of our study was 2-fold: to identify predictors of repeated suicide attempts and suicide and to investigate the timing of these events. Methods: Data from Danish nationwide, longitudinal registers were used in this prospective, population-based study of all individuals first presenting...

  11. HOMICIDE FOLLOWED BY SUICIDE

    Directory of Open Access Journals (Sweden)

    SAMANTHA DUBUGRAS

    2007-08-01

    Full Text Available Homicide followed by suicide (H/S is a complex and poorly studied phenomenon. This research aims at identifyingH/S cases occurred in Porto Alegre from 1996 throughout 2004. Information on H/S was extracted from newspapers,police reports and interviews with the informants. From the 14 identified cases, men were the killers/suicides andwomen and children their victims. The most frequently used weapons were firearms. In general, the aggressor was animpulsive, aggressive individual showing problems within its primary supporting group, possibly suffering depressionand alcohol-addicted with criminal backgrounds (violence against the family. Events were mainly triggered by jealousy,threats or the end of a love relationship.

  12. [EUTHANASIA AND ASSISTED SUICIDE].

    Science.gov (United States)

    Lantero, Caroline

    2015-07-01

    Euthanasia and assisted suicide are not part of French laws of bioethics and lack, for the time being, definition and normative framework other than their criminal prosecution. To transform them into a right, these concepts certainly call for an ethical and legal debate. This paper aims to question the ideas to be considered, the conceptual bases and normative tools that may be useful to the discussion.

  13. Prediction and prevention of suicide in patients with unipolar depression and anxiety

    Directory of Open Access Journals (Sweden)

    Kaprinis George

    2007-09-01

    Full Text Available Abstract Epidemiological data suggest that between 59 and 87% of suicide victims suffered from major depression while up to 15% of these patients will eventually commit suicide. Male gender, previous suicide attempt(s, comorbid mental disorders, adverse life-situations, acute psycho-social stressors etc. also constitute robust risk factors. Anxiety and minor depression present with a low to moderate increase in suicide risk but anxiety-depression comorbidity increases this risk dramatically Contrary to the traditional psychoanalytic approach which considers suicide as a retrospective murder or an aggression turned in-wards, more recent studies suggest that the motivations to commit suicide may vary and are often too obscure. Neurobiological data suggest that low brain serotonin activity might play a key role along with the tryptophan hydroxylase gene. Social factors include social support networks, religion etc. It is proven that most suicide victims had asked for professional help just before committing suicide, however they were either not diagnosed (particularly males or the treatment they received was inappropriate or inadequate. The conclusion is that promoting suicide prevention requires the improving of training and skills of both psychiatrists and many non-psychiatrists and especially GPs in recognizing and treating depression and anxiety. A shift of focus of attention is required in primary care to detect potentially suicidal patients presenting with psychological problems. The proper use of antidepressants, after a careful diagnostic evaluation, is important and recent studies suggest that successful acute and long-term antidepressant pharmacotherapy reduces suicide morbidity and mortality.

  14. Suicide Inside A Systematic Review of Inpatient Suicides

    NARCIS (Netherlands)

    Bowers, L.; Nijman, H.L.I.; Banda, T.

    2010-01-01

    The literature on inpatient suicides was systematically reviewed. English, German, and Dutch articles were identified by means of the electronic databases PsycInfo, Cochrane, Medline, EMBASE psychiatry, CINAHL, and British Nursing Index. In total, 98 articles covering almost 15,000 suicides were

  15. Hamlet's Suicide Soliloquy: A Case Study in Suicide Ideology.

    Science.gov (United States)

    Jenkins, Andrew P.

    This paper presents a secondary-level teaching technique that can be used in an integrated English and health education curriculum. The exercise provides students and teachers with a case study of a suicidal person for the purpose of teaching the warning signs of suicide, appropriate questioning, and referral skills. The case study uses Hamlet's…

  16. Tinnitus-Induced Suicide

    Directory of Open Access Journals (Sweden)

    Serhan Derin

    2015-04-01

    Full Text Available Tinnitus is one of the most common complaints in otolaryngology practice. Tinnitus may often be accompanied with hearing loss and vertigo. Tinnitus may impair the quality of life in advanced degrees. In very rare cases, it may cause suicide. In this report, we presented the case of a 61-year-old female patient who attempted suicide due to tinnitus. She suffered from constant tinnitus in both ears since she had undergone serous otitis media two months ago. Despite medical treatment, tinnitus did not improve, and lately, she suffered from severe insomnia. Due to severe tinnitus and insomnia, she drank hydrochloric acid. She was consequently admitted to our emergency department by her family. On physical examination, the patient’s vital signs were stable and floor of the mouth mucosa, gingiva, and hard and soft palate had widely ulcerated areas. Severe laryngeal edema and ulceration was observed on laryngoscopic examination. The eardrum was myringosclerotic on otoscopic examination. The patient was closely followed for respiratory distress; however, tracheostomy was not required. The abovementioned case suggests that patients admitted with complaints of tinnitus should be questioned for severity of depressive symptoms, considering that the presence of depressive symptoms in these patients may result in an attempt of suicide. These patients should be evaluated not only in otolaryngology clinics but also in psychiatric clinics, and subsequently receive appropriate support.

  17. Is Hinduism ambivalent about suicide?

    Science.gov (United States)

    Vijayakumar, Lakshmi; John, Sujit

    2018-05-01

    Hinduism is one of the oldest religions in the world and has over 1.1 billion adherents comprising about 16% of the global population living mainly in India and Nepal. The stand of Hinduism on suicide has been ambiguous through the ages, on one hand, condemning general suicides, while condoning religious suicides on the other. This ambiguity is reflected in contemporary India and among the Indian diaspora. To examine the stand of Hinduism as a religion in the context of suicide. A selected review of literature covering the major Hindu religious texts, cultural practices and suicide. People who follow Hinduism have a suicide rate of about 21 per 100,000 population compared to the global average of 11.4. Hindu countries have higher rates of suicide compared to Islamic and Christian countries, but these rates are lower when compared to Atheist and Buddhist countries. This is reflected in the Indian diaspora as well with reports from Fiji, the Caribbean, Malaysia and the United Kingdom, indicating that suicide was disproportionately high among those of Indian origin. However, a strong faith in Hinduism acts as protective factor. The Hindu belief in karma fosters a sense of acceptance of the vicissitudes of life with equanimity, and the belief in the cycle of births and deaths renders suicide meaningless, as one's soul continues after death. Their religious beliefs makes the Hindus tolerate and accept hardships and calamities stoically. In certain situations, the Hindu religion acts as a protective factor, whereas at other times, it may increase the risk of suicide. It is important to understand these different nuances in the Hindu religion in formulating a culturally appropriate suicide prevention strategy.

  18. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Wiebe, Leonard I.

    1997-01-01

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

  19. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  20. Predictors of Suicidal Behavior in a Sample of Turkish Suicide Attempters

    Science.gov (United States)

    Sayar, Kemal; Kose, Samet; Acar, Burcin; Ak, Ismail; Reeves, Robert A.

    2004-01-01

    In a Turkish sample, 100 suicide attempters, were compared with 60 healthy controls on measures of hopelessness, depression, and suicidal ideation. Suicide attempters were more depressive, more hopeless, and displayed greater suicidal ideation than healthy controls. Depression severity rather than hopelessness correlated with suicidal intent.…

  1. Pathways for Preparation: Locating Suicide Education in Preparing Professionals for Encounters with Suicidal Adolescents

    Science.gov (United States)

    Ranahan, Patti

    2013-01-01

    Current suicide prevention strategies often include suicide education based on the premise that education can lead to recognition of those at risk of suicide and others who are prepared can respond and potentially save lives. As suicide is a leading cause of death for young people, it is relevant to explore how suicide education is made available…

  2. Suicide Method Runs in Families: A Birth Certificate Cohort Study of Adolescent Suicide in Taiwan

    Science.gov (United States)

    Lu, Tsung-Hsueh; Chang, Wan-Ting; Lin, Jin-Jia; Li, Chung-Yi

    2011-01-01

    Suicide method used by adolescents was examined to determine if it was the same as that employed by their suicidal parents. Six hundred eighty adolescents completed suicide between 1997 and 2007, of whom 12 had parents who had previously died by suicide. The suicide method used by these adolescents was compared with that employed by their suicidal…

  3. Interventions to reduce suicides at suicide hotspots: a systematic review.

    Science.gov (United States)

    Cox, Georgina R; Owens, Christabel; Robinson, Jo; Nicholas, Angela; Lockley, Anne; Williamson, Michelle; Cheung, Yee Tak Derek; Pirkis, Jane

    2013-03-09

    'Suicide hotspots' include tall structures (for example, bridges and cliffs), railway tracks, and isolated locations (for example, rural car parks) which offer direct means for suicide or seclusion that prevents intervention. We searched Medline for studies that could inform the following question: 'What interventions are available to reduce suicides at hotspots, and are they effective?' There are four main approaches: (a) restricting access to means (through installation of physical barriers); (b) encouraging help-seeking (by placement of signs and telephones); (c) increasing the likelihood of intervention by a third party (through surveillance and staff training); and (d) encouraging responsible media reporting of suicide (through guidelines for journalists). There is relatively strong evidence that reducing access to means can avert suicides at hotspots without substitution effects. The evidence is weaker for the other approaches, although they show promise. More well-designed intervention studies are needed to strengthen this evidence base.

  4. Attempted suicide and completed suicide among young people

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The study explore risk factors associated with the onset of suicidal behavior in young people aged 15 to 24. The study survey possible risk factors and protective factors in order to evaluate if altering the conditions of children’s upbringing, structural factors, geographical segregation......, or individual resource deficits could reduce their suicidal behavior (first time suicide attempts and completed suicides). These issues are being examined using data gathered during a 10-year longitudinal study of two births cohorts of more than 145,000 young people born in 1966 or 1980. In the Nordic welfare...... model it is an ambition to level-out inequalities and give children the same opportunities despite parental income or educational resources. The paper focuses on suicidal behavior as an extreme indicator of individual disadvantage and social disintegration in order to disentangle groups of risk factors...

  5. Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

    Science.gov (United States)

    Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

    2018-02-01

    Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Latina Teen Suicide and Bullying

    Science.gov (United States)

    Romero, Andrea J.; Wiggs, Christine Bracamonte; Valencia, Celina; Bauman, Sheri

    2013-01-01

    Latina adolescents experience depression and suicidal ideations in a disproportionate manner compared to their non-Latina counterparts. We investigate suicide and depressive symptoms among a state-wide sample (N = 650) of adolescent Latina girls with a focus on bullying as a predictor. Bullying rates are higher than previous studies have found for…

  7. Suicide risk among homeless population

    Directory of Open Access Journals (Sweden)

    Fran Calvo-García

    2016-06-01

    Full Text Available There exists little scientific production on autolytic behaviour in homeless people, despite the fact that it is one of the groups that is more at risk. The aim of this study is to determine the prevalence of previous attempted suicide and suicide risk and its connection with the main risk factors. In order to do so, central tendency and dispersion measures, correlations, contingence tables, and average comparison tables according to type of variable and normality were used. The Plutchik suicide-risk test was used in order to determine the risk of suicide, and specific tests for the main risk factors analysed. The main results show a 24.7% suicide rate and 45.2% (n = 66 displayed suicide risk. The main predictive factor of the risk of suicide was the daily consumption of alcohol (OR = 1.011, p less than .001, followed by being a woman (OR = 1.381, p = .021. It is necessary to design and apply suicide prevention strategies for this population.

  8. When a Patient Commits Suicide.

    Science.gov (United States)

    Marshall, Karol A.

    1980-01-01

    Suicide is a tragic and upsetting event which sometimes occurs when a person is in some form of therapy. This paper advocates a process after a patient commits suicide which allows for a thorough and orderly working through of the event by involved treatment personnel. (Author)

  9. Suicide in Guyana: Nurses' Perspectives.

    Science.gov (United States)

    Anthony, Maureen; Groh, Carla; Gash, Jean

    Guyana, an English-speaking country on the north coast of South America, has the highest suicide rate in the world. Nurses are an integral part of the healthcare team working with patients experiencing psychological distress and are uniquely qualified to add to the discourse on factors contributing to the high suicide rate in Guyana. The purpose of this study was to explore the attitudes and experiences of nurses and nurse assistants in Guyana related to suicide. Nine registered nurses and nurse assistants who worked at a private hospital in Georgetown, Guyana, were recruited to participate in a focus group. The focus group lasted approximately 70 minutes and was recorded. The audio recordings were later transcribed word for word. Four themes emerged from the data: family issues as they relate to the high suicide rate, suicide attempts as a cry for help, lack of support, and coping mechanisms used by nurses when caring for victims of attempted suicide. Nurses are uniquely positioned to intervene with families in crisis, whether it be suicide, suicide attempts, or the underlying factors of family dysfunction, child maltreatment, poverty, or alcoholism. Establishing forensic nursing as a specialty in Guyana would validate this important role through education and certification of nurses.

  10. Toward a Biosignature for Suicide

    Science.gov (United States)

    Oquendo, Maria A.; Sullivan, Gregory M.; Sudol, Katherin; Baca-Garcia, Enrique; Stanley, Barbara H.; Sublette, M. Elizabeth; Mann, J. John

    2015-01-01

    Objective Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide. Method The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide. Results Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question. Conclusions The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors. PMID:25263730

  11. Cannabis use and suicidal ideation

    NARCIS (Netherlands)

    van Ours, J.C.; Williams, J.; Fergusson, D.; Horwood, L.J.

    2013-01-01

    Globally, suicide has emerged as the second leading cause of death among youth aged 10–24 years old. In order to better understand the causes of this phenomenon, we investigate the relationship between suicidal ideation and cannabis use. Our empirical analysis is based on a 30-year longitudinal

  12. Last Suicide Attempt before Completed Suicide in Severe Depression: An Extended Suicidal Process May Be Found in Men Rather Than Women.

    OpenAIRE

    Brådvik, Louise

    2013-01-01

    The objective of this study was to compare the time from last suicide attempt to suicide in men and women with major depressive disorder with melancholic and/or psychotic features. The case records of 100 suicide victims with severe depression were evaluated. All suicide attempts during the course of depression were noted. The time from last suicide attempt to suicide was compared as well as the occurrence of suicide attempt during the last depressive episode, by gender. Male suicide attempte...

  13. SUICIDE AMONG UNIVERSITY STUDENTS IN KENYA: CAUSES ...

    African Journals Online (AJOL)

    Suicide is against the law in Kenya. The existence of suicide phenomena in the society is a major issue that needs to be looked into with a lot of concern, and creating effective preventative measure is a matter of urgency. Knowledge concerning suicide is largely limited. The majority of people in the society treat suicide ...

  14. Suicide among Preadolescents: A Call to Action

    Science.gov (United States)

    Westefeld, John S.; Bell, Allison; Bermingham, Charles; Button, Christopher; Shaw, Kari; Skow, Christine; Stinson, Rebecca D.; Woods, Tamara

    2010-01-01

    Suicide among preadolescents is a relatively rare phenomenon. Due to the infrequency of suicide among this population, this area of study has received limited investigation relative to suicide in other age groups and populations. This article reviews research related to suicide among preadolescents, defined as children under the age of 13. The…

  15. Suicide and Its Prevention on College Campuses

    Science.gov (United States)

    Keyes, Lee

    2012-01-01

    Suicide is a significant issue facing higher education institutions. Many campuses are involved in a variety of procedures, programs, and initiatives that seek to reduce or prevent suicide and the impact of suicide-related behavior. This article offers examples of campus prevention efforts, important resources on suicide prevention for college…

  16. Children's Suicidal Thinking: An Empirical Inquiry.

    Science.gov (United States)

    Bailey, Bruce E.; And Others

    Although over 5,000 children and adolescents commit suicide annually, little is known about suicidal thinking of normal children. Due to ethical considerations, researchers must be sensitive to the possibility that they could introduce suicide as an option to a child. A methodology was developed to examine suicidal thinking through projected…

  17. Moody, Suicide and Survival: A Critical Appraisal.

    Science.gov (United States)

    Vicchio, Stephen

    1980-01-01

    The purpose of this paper is to: (1) define suicide; (2) explicate Raymond Moody's position on suicide and survival after death; (3) analyze logical connections between divine commands and moral judgments; and (4) offer constructive comments on suicide and suicide prevention. (Author/RC)

  18. Grief Experiences and Expectance of Suicide

    Science.gov (United States)

    Wojtkowiak, Joanna; Wild, Verena; Egger, Jos

    2012-01-01

    Suicide is generally viewed as an unexpected cause of death. However, some suicides might be expected to a certain extent, which needs to be further studied. The relationships between expecting suicide, feeling understanding for the suicide, and later grief experiences were explored. In total, 142 bereaved participants completed the Grief…

  19. Malignant diseases as suicidal motives

    Directory of Open Access Journals (Sweden)

    Bogdanović Ljiljana

    2007-01-01

    Full Text Available Introduction Suicide is a conscious and intentional destruction of one’s own life, which occurs as a result of mutual influence of a person’s disposition and motives (facts inspiring the commitment of suicide. It is well known that various diseases, including malignancies, could be important and in some cases the only motive for committing suicide. Objective The purpose of the study was to analyze in detail suicides of persons whose only motive was an established malignant disease. Method The analysis was performed using the autopsy material of the Institute of Forensic Medicine, School of Medicine, University of Belgrade, during the period from 1990 to 2004. The reports on performed medico-legal autopsies were used, as well as history data obtained from the family members of suicidal persons, investigation reports and the available medical documents. Results In 1931 cases there was established suicidal nature of a violent death. Neoplasms were the suicidal motive in 37 persons (1.9%. The basic characteristics of the analyzed sample were predominance of males (26:11, ratio 2.4:1, the age of over 70 years and the highest incidence of malignant lung and breast tumors. Almost all cases were the persons who underwent treatment for malignant neoplasms over a longer period of time. During 19 autopsies (51.3% out of 37, a progressive phase of malignancy was established, i.e. metastases. The data on prior oral announcement of suicide intention were obtained for 70.3% (26 cases, and on previous suicidal attempts only for 13.5% (5 cases. In the majority of cases (78.4% the place of committed suicide was the person’s home. In 16 cases (43.2% the suicide was committed with a firearm. Hanging as a manner of destroying one’s own life was chosen by 12 persons (32.4%, while other ways were less frequently used. Conclusion Although malignancies were not present with high incidence as a suicidal motive in our analyzed sample, such cases require particular

  20. Enhancement of Tumor-Specific T Cell–Mediated Immunity in Dendritic Cell–Based Vaccines by Mycobacterium tuberculosis Heat Shock Protein X

    Science.gov (United States)

    Jung, In Duk; Shin, Sung Jae; Lee, Min-Goo; Kang, Tae Heung; Han, Hee Dong; Lee, Seung Jun; Kim, Woo Sik; Kim, Hong Min; Park, Won Sun; Kim, Han Wool; Yun, Cheol-Heui; Lee, Eun Kyung; Wu, T.-C.

    2014-01-01

    Despite the potential for stimulation of robust antitumor immunity by dendritic cells (DCs), clinical applications of DC-based immunotherapy are limited by the low potency in generating tumor Ag-specific T cell responses. Therefore, optimal conditions for generating potent immunostimulatory DCs that overcome tolerance and suppression are key factors in DC-based tumor immunotherapy. In this study, we demonstrate that use of the Mycobacterium tuberculosis heat shock protein X (HspX) as an immunoadjuvant in DC-based tumor immunotherapy has significant potential in therapeutics. In particular, the treatment aids the induction of tumor-reactive T cell responses, especially tumor-specific CTLs. The HspX protein induces DC maturation and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IFN-β) through TLR4 binding partially mediated by both the MyD88 and the TRIF signaling pathways. We employed two models of tumor progression and metastasis to evaluate HspX-stimulated DCs in vivo. The administration of HspX-stimulated DCs increased the activation of naive T cells, effectively polarizing the CD4+ and CD8+ T cells to secrete IFN-γ, as well as enhanced the cytotoxicity of splenocytes against HPV-16 E7 (E7)–expressing TC-1 murine tumor cells in therapeutic experimental animals. Moreover, the metastatic capacity of B16-BL6 melanoma cancer cells toward the lungs was remarkably attenuated in mice that received HspX-stimulated DCs. In conclusion, the high therapeutic response rates with tumor-targeted Th1-type T cell immunity as a result of HspX-stimulated DCs in two models suggest that HspX harnesses the exquisite immunological power and specificity of DCs for the treatment of tumors. PMID:24990079

  1. Tissue pO2 of Orthotopic 9L and C6 Gliomas and Tumor-Specific Response to Radiotherapy and Hyperoxygenation

    International Nuclear Information System (INIS)

    Khan, Nadeem; Li Hongbin; Hou, Huagang; Lariviere, Jean P.; Gladstone, David J.; Demidenko, Eugene; Swartz, Harold M.

    2009-01-01

    Purpose: Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO 2 ) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO 2 in rats using a new and potentially widely useful method, multisite in vivo electron paramagnetic resonance oximetry. Methods and Materials: Intracerebral 9L and C6 tumors were established in the left hemisphere of syngeneic rats, and electron paramagnetic resonance oximetry was successfully used for repeated tissue pO 2 measurements after 9.3 Gy of radiation and during carbogen breathing for 5 consecutive days. Results: Intracerebral 9L gliomas had a pO 2 of 30-32 mm Hg and C6 gliomas were relatively hypoxic, with a pO 2 of 12-14 mm Hg (p 2 of the contralateral brain was 40-45 mm Hg in rats with either 9L or C6 gliomas. Irradiation resulted in a significant increase in pO 2 of the 9L gliomas only. A significant increase in the pO 2 of the 9L and C6 gliomas was observed in rats breathing carbogen, but this effect decreased during 5 days of repeated experiments in the 9L gliomas. Conclusion: These results highlight the tumor-specific effect of radiation (9.3.Gy) on tissue pO 2 and the different responses to carbogen inhalation. The ability of electron paramagnetic resonance oximetry to provide direct repeated measurements of tissue pO 2 could have a vital role in understanding the dynamics of hypoxia during therapy that could then be optimized by scheduling doses at times of improved tumor oxygenation

  2. Suicide in the military environment

    Directory of Open Access Journals (Sweden)

    Čabarkapa Milanko M.

    2004-01-01

    Full Text Available Suicide of soldiers has its own specifics, because not only it represents the tragedy for the individuals and their family, but also has great psychological effect on social environment and military unit in which it occurs. Suicide can be caused by variety of factors, as reported in the literature. The case reviewed in this article presents multilateral determination of suicide, with particular stress on the character of each individual and social interaction of soldiers. Psychological complex of basic inferiority, low educational level, family problems, and poor integration into military unit could be considered the leading determinants of this suicide. This emphasizes the importance of certain preventive measures such as more rigorous psychological selection for specific military duty, and the education of non-commissioned officers for better recognition and understanding of pre-suicidal syndrome.

  3. Risk factors for suicide in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E N; Koch-Henriksen, N; Stenager, E

    1996-01-01

    made for male and female suicides and for various groups of MS suicides according to disability status. RESULTS: The male suicide patients were characterized by a tendency to commit suicide in the age interval 40-49 years, by the use of a violent suicide method, by previous suicidal behaviour...... counselling and good information on all aspects of the disease, especially in the first stages and at time of progression, could be an instrument of prevention of suicides in MS patients. Furthermore, recognition and treatment of depression and pain is important....

  4. Books reconsidered: Emile Durkheim, Le Suicide.

    Science.gov (United States)

    Robertson, Michael

    2006-12-01

    To reappraise Emile Durkheim's taxonomy of suicide in Le Suicide in the light of recent experience. While Durkheim's scientific method and argument are fundamentally flawed, some of his concepts have instrumental value in attempting to understand the complex origins of suicidal behaviour. Durkheim's baseless dismissal of mental illness as a key determinant of suicidal behaviour weakens his thesis significantly. However, his conceptualization of anomic, egoistic and altruistic suicide provides a means of comprehending recent trends in suicidal behaviour in the former Soviet states and a possible window into the psyche of the suicides of religious and political extremists.

  5. Military and civilian media coverage of suicide.

    Science.gov (United States)

    Edwards-Stewart, Amanda; Kinn, Julie T; June, Jennifer D; Fullerton, Nicole R

    2011-01-01

    Military suicide has increased over the past decade and reports of Service Member and Veteran suicides receive media attention. Some methods of reporting suicide appear to cause a "media contagion" effect, potentially increasing suicide. This effect is explored in relation to media reports of both military and civilian suicides. To reduce possible contagion, recommendations for media reporting of suicides were adapted by the Suicide Prevention Resource Center (SPRC). We assessed 240 military and civilian newspaper reports of suicide from 15 different sources for compliance with the SPRC guidelines. Nearly all reviewed articles violated at least one guideline. Results highlighted military news articles regarding Service Members included more pejorative language and discussion of failed psychological treatment. Conversely, civilian articles romanticized the victim and provided more details regarding the suicide. Further exploration of military suicide reporting bias is discussed as a need in future research.

  6. Religion and Suicide Risk: A Systematic Review.

    Science.gov (United States)

    Lawrence, Ryan E; Oquendo, Maria A; Stanley, Barbara

    2016-01-01

    Although religion is reported to be protective against suicide, the empirical evidence is inconsistent. Research is complicated by the fact that there are many dimensions to religion (affiliation, participation, doctrine) and suicide (ideation, attempt, completion). We systematically reviewed the literature on religion and suicide over the last 10 years (89 articles) with a goal of identifying what specific dimensions of religion are associated with specific aspects of suicide. We found that religious affiliation does not necessarily protect against suicidal ideation, but does protect against suicide attempts. Whether religious affiliation protects against suicide attempts may depend on the culture-specific implications of affiliating with a particular religion, since minority religious groups can feel socially isolated. After adjusting for social support measures, religious service attendance is not especially protective against suicidal ideation, but does protect against suicide attempts, and possibly protects against suicide. Future qualitative studies might further clarify these associations.

  7. Common variations in 4p locus are related to male completed suicide.

    Science.gov (United States)

    Must, Anne; Kõks, Sulev; Vasar, Eero; Tasa, Gunnar; Lang, Aavo; Maron, Eduard; Väli, Marika

    2009-01-01

    Suicidal behavior is a multifactorial phenomenon, with a significant genetic predisposition. To assess the contribution of genes in the 4p region to suicide risk, we genotyped 36 single nucleotide polymorphisms from a 49Mb region on the chromosome arm 4p11-16 in a total of 288 male suicide victims and 327 healthy male volunteers. The nonsynonymous variants rs1383180 in EVC gene, rs6811863 in TBC1D1 gene, rs362272 in HTT gene, and rs734312 in WFS1 gene were associated to the male completed suicide. However, only EVC polymorphism remained significant after correcting for multiple comparisons (P < .05 after 10 K permutations). The function of these genes is not clear yet. WFS1 and HTT are related to the unfolded protein response and endoplasmic reticulum stress, and TBC1D1 is a GTPase activator. EVC is a protein with transmembrane and leucine zipper domains, its function has not been elucidated yet. Further studies are required in order to reveal the role of these four polymorphisms in the pathoetiology of suicide.

  8. Clinical studies of biomarkers in suicide prediction

    OpenAIRE

    Jokinen, Jussi

    2007-01-01

    Suicide is a major clinical problem in psychiatry and suicidal behaviours can be seen as a nosological entity per se. Predicting suicide is difficult due to its low base-rate and the limited specificity of clinical predictors. Prospective biological studies suggest that dysfunctions in the hypothalamo pituitary adrenal (HPA) axis and the serotonergic system have predictive power for suicide in mood disorders. Suicide attempt is the most robust clinical predictor making suici...

  9. Blood alcohol levels in suicide cases.

    OpenAIRE

    Hayward, L; Zubrick, S R; Silburn, S

    1992-01-01

    STUDY OBJECTIVE--The aim was to investigate the relationship between alcohol consumption prior to suicide and the act of suicide. DESIGN--This was a retrospective total ascertainment survey of a three year cohort of suicides in Western Australia. SETTING--Coroner's records of suicide in Western Australia between 1986 and 1988 inclusive. PARTICIPANTS--The study involved 515 consecutive suicides: 414 males and 101 females. MAIN RESULTS--Information on blood alcohol levels at time of death, pres...

  10. Clinically relevant risk factors for suicide: Comparison between clinical group with passive suicidal ideation, active suicidal ideation and without suicidal ideation

    OpenAIRE

    Miloseva, Lence; Cuijpers, Pim; Stojcev, Saso; Niklewski, Gunter; Richter, Kneginja; Jovevska, Svetlana; Arsova, Roza; Serafimov, Aleksandar

    2015-01-01

    Introduction: In recent years, researchers and clinicians do not treat passive suicidal ideation as a clinically relevant risk factor for suicide, while underestimating the strength of this desire to die, compared with making a plan for suicide in individuals having active suicidal ideation. This research study is clinically prospective, cross-sequential, but also partly retrospective because it involves also variables from the past, such as patients’ history data (number of suicidal attempts...

  11. Chronotype differences in suicidal behavior and impulsivity among suicide attempters.

    Science.gov (United States)

    Selvi, Yavuz; Aydin, Adem; Atli, Abdullah; Boysan, Murat; Selvi, Fatih; Besiroglu, Lutfullah

    2011-03-01

    Morning- and evening-type individuals differ on a number of psychological and biological variables. There has been increasing interest in the relationship between chronotype and personality traits. The aim of this study was to investigate the relationship between impulsivity and chronotype in suicide attempters. Eighty-nine suicide attempters were included in the study, and systematic information on suicide attempts was recorded. The Morningness-Eveningness Questionnaire was applied to determine chronotype, and attempter impulsivity was measured by the total score of the Barratt Impulsiveness Scale. Significant differences between chronotype and impulsivity scores were found. Evening-type subjects reported significantly higher impulsivity scores than both neither- and morning-types. A significant association between chronotype and type of suicide attempt was detected. The largest proportion of violent suicide attempters were evening-type subjects. Violent suicide attempters also reported significantly higher impulsivity scores than nonviolent attempters. Previous studies have pointed out possible relations between eveningness and impulsivity. Current findings suggest that eveningness may be a risk factor for violent suicide attempts by increasing impulsivity.

  12. Caring stress, suicidal attitude and suicide care ability among family caregivers of suicidal individuals: a path analysis.

    Science.gov (United States)

    Chiang, C-Y; Lu, C-Y; Lin, Y-H; Lin, H-Y; Sun, F-K

    2015-12-01

    What is known on the subject? Suicide is a global mental health issue. Taking care of suicidal individuals is a substantial challenge. Most studies emphasize the suicidal individual. Few studies have emphasized the family caregivers of suicidal individuals. No study has explored the relationship between family caregivers' caring stress with suicidal attitudes and suicide care ability. What this paper adds to existing knowledge? The main results indicated that the older family caregivers tended to have a more negative attitude towards suicidal individuals. Female family caregivers' stress was higher than that of male family caregivers. A mild level of caring stress would help family caregivers have a more positive attitude towards suicidal individuals. Furthermore, a positive attitude would help family caregivers improve their caring ability. What are the implications for practice? Mental health nurses could help family caregivers, especially female family caregivers, reduce their holistic caring burden by looking for support resources and enhancing their coping strategies. Mental health nurses could help family caregivers promote positive attitudes towards suicidal relatives by understanding suicidal individuals' suffering. Suicide is a global mental health issue. Family caregivers play a key role in preventing suicide attempts. The aim of this study was to examine the relationship among stress due to the family caregiver's role, suicidal attitude of the family caregiver and suicide care ability among family caregivers. Additionally, instruments of caring stress, attitudes towards suicidal relatives and caring abilities used in the study were tested to measure construct validity. A cross-sectional correlational study was conducted with 164 family caregivers of people who are suicidal. The following three questionnaires were used: the Caring Stress Scale, the Suicidal Attitudes Scale and the Suicidal Caring Ability Scale. Structural equation modelling was performed

  13. Karolinska Interpersonal Violence Scale predicts suicide in suicide attempters.

    Science.gov (United States)

    Jokinen, Jussi; Forslund, Kaj; Ahnemark, Ewa; Gustavsson, J Petter; Nordström, Peter; Asberg, Marie

    2010-08-01

    Both childhood trauma and violent behavior are important risk factors for suicidal behavior. The aim of the present study was to construct and validate a clinical rating scale that could measure both the exposure to and the expression of violence in childhood and during adult life and to study the ability of the Karolinska Interpersonal Violence Scale (KIVS) to predict ultimate suicide in suicide attempters. A total of 161 suicide attempters and 95 healthy volunteers were assessed with the KIVS measuring exposure to violence and expressed violent behavior in childhood (between 6-14 years of age) and during adult life (15 years or older). The Buss-Durkee Hostility Inventory (BDHI), "Urge to act out hostility" subscale from the Hostility and Direction of Hostility Questionnaire (HDHQ), and the Early Experience Questionnaire (EEQ) were used for validation. All patients were followed up for cause of death and a minimum of 4 years from entering in the study. Five patients who committed suicide within 4 years had significantly higher scores in exposure to violence as a child, in expressed violent behavior as an adult, and in KIVS total score compared to survivors. Suicide attempters scored significantly higher compared to healthy volunteers in 3 of the 4 KIVS subscales. There were significant correlations between the subscales measuring exposure to and expression of violent behavior during the life cycle. BDHI, Urge to act out hostility, and EEQ validated the KIVS. Exposure to violence in childhood and violent behavior in adulthood are risk factors for completed suicide in suicide attempters. Behavioral dysregulation of aggression is important to assess in clinical work. The KIVS is a valuable new tool for case detection and long-term clinical suicide prevention. Copyright 2010 Physicians Postgraduate Press, Inc.

  14. Suicide Research and Adolescent Suicide Trends in New Zealand

    Directory of Open Access Journals (Sweden)

    Said Shahtahmasebi

    2008-01-01

    Full Text Available In recent years, there have been a number of claims and counterclaims from suicide research using time series and longitudinal data; in particular, the linkage of increased antidepressant prescriptions to a decrease in suicide rates. Suicide time series appear to have a memory compounded with seasonal and cyclic effects. Failure to take into account these properties may lead to misleading conclusions, e.g., a downward blip is interpreted as the result of current knowledge and public health policies, while an upward blip is explained as suicide being complex depending on many variables requiring further research. In previous publications, I argued that this misuse of time series data is the result of an uncritical acceptance of a medical model that links mental ill-health to suicide. The consequences of such research behaviour are further increases in antidepressant prescriptions and medications to those who should not be prescribed them, with adverse effects showing across the population, e.g., the prescription of antidepressants to very young children (some under 1 year of age in New Zealand. Moreover, the New Zealand Evidence-based Health Care Bulletin recommends an authoritarian approach for every interaction with a young person to check their psychosocial well-being. When viewed holistically, this kind of human behaviour makes researchers, policy makers (politicians, treatment, and practitioners, and society in general part of the problem rather than the solution. This paper explores some dynamic aspects of suicide, using only official data with particular reference to youth suicide, and suggests that the medical model of suicide is only an attempt to treat depression without addressing suicide, and recommends the creation of a unified database through understanding the society that individuals live in. It is hoped that this paper will stimulate debate and the collaboration of international experts regardless of their school of thought.

  15. Characteristics of methods of suicide attempts in Korea: Korea National Suicide Survey (KNSS).

    Science.gov (United States)

    Kim, Bora; Ahn, Joon-Ho; Cha, Boseok; Chung, Young-Chul; Ha, Tae Hyon; Hong Jeong, Seong; Jung, Hee Yeon; Ju, Gawon; Kim, Eun-Young; Kim, Jae Min; Kim, Moon-Doo; Kim, Min-Hyuk; Kim, Soo In; Lee, Kyoung-Uk; Lee, Sang-Hyuk; Lee, Seung Jae; Lee, Yu Jin; Moon, Eunsoo; Ahn, Yong-Min

    2015-12-01

    Because the method used for a suicide attempt is an important determinant of outcome, these methods should be explored. The present study was a nationwide investigation of suicide attempts and the characteristics of suicidal behavior. To compare the suicide methods used in attempted suicides with those used in completed suicides and to examine the factors associated with each phenomenon. The present study reviewed the medical charts of subjects who had attempted suicide and subsequently visited the emergency rooms of 17 medical centers from May 1, 2013 to November 7, 2013. All subjects completed a full psychiatric interview conducted by trained psychiatric residents. Suicide-attempt methods were divided into the following six categories: drug poisoning, pesticide poisoning, gassing, cutting, hanging, and others. The associations among demographic variables, related psychiatric variables, and suicide-attempt methods were analyzed using a multinomial regression analysis. Of the 1359 suicide attempts or instrumental suicide-related behaviors with/without injuries and the 14,160 completed suicides, drug poisoning and cutting were the most common suicidal behaviors with/without injuries, but they were the least frequent method of completed suicides. In contrast, hanging and jumping from a height were less common among failed suicide attempts but resulted in a higher percentage of fatalities. Being male, age, and area of residence were associated with pesticide poisoning, whereas previous suicide attempts were associated with cutting, pesticide poisoning, and gassing. A previous suicide attempt is a risk factor for suicide; thus, assessing the characteristics of suicide attempts or instrumental suicide-related behaviors with/without injuries is necessary to prevent these attempts. The present findings showed that the methods of suicide used by individuals who only attempted suicide differed from those used by individuals who completed. Of the suicide methods, pesticide

  16. Suicidal Ideation and Distress in Family Members Bereaved by Suicide in Portugal

    OpenAIRE

    Santos, Sara; Campos, Rui; Tavares, Sofia

    2015-01-01

    The present study assessed the impact of suicide and distress on suicidal ideation in a sample of 93 Portuguese family members bereaved by suicide. A control community sample of 102 adults also participated. After controlling for educational level, those bereaved by the suicide of a family member were found to have higher levels of suicidal ideation. Forty-two percent of family members had Suicide Ideation Questionnaire scores at or above the cutoff point. General distress, dep...

  17. Association between serotonin 2A receptor genetic variations, stressful life events and suicide.

    Science.gov (United States)

    Ghasemi, Asghar; Seifi, Morteza; Baybordi, Fatemeh; Danaei, Nasim; Samadi Rad, Bahram

    2018-06-05

    Life events are series of events that disrupt a person's psychological equilibrium and may enhance the development of a disorder such as suicide. Several studies have assessed a relationship between 5-hydroxytryptamine (serotonin) 2A receptor (5-HTR2A) gene polymorphisms with an increased risk of suicide. However, there has been no study about the association between three 5-HTR2A gene polymorphisms, A1438G (rs6311), T102C (rs6313) and C1354T (rs6314), suicide, stressful life, and loss events in a same time. Relatives of 191 suicide victims were interviewed using a semi-structured questionnaire designed according to Iranian culture. Venous blood was taken from all subjects for DNA isolation. 5-HTR2A polymorphisms in a total of 191 suicide victims and 218 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-squared and Fisher's exact tests were used to compare genotype and allele frequencies between suicide and control groups. Correction for multiple comparisons was calculated using Bonferroni correction. There was a significant association between the 102 C/C genotype of 5-HTR2A gene and suicide (к 2  = 8.700, P = 0.012). Furthermore, we found that suicide victims with a 102 C/C genotype had a significantly higher number of stressful life and loss events (P suicide victims and control participants and there was no association between genotype distribution and higher number of stressful life and loss events (P > 0.05). Our results suggest that C102T (rs6313) polymorphism of 5-HTR2A gene may be involved in the susceptibility to suicide, higher number of stressful life and loss events, but A1438G (rs6311) and C1354T (rs6314) polymorphisms of 5-HTR2A gene were not associated with suicide, higher number of stressful life and loss events. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Assisted suicide and euthanasia.

    Science.gov (United States)

    van der Heide, Agnes

    2013-01-01

    Several countries have adopted laws that regulate physician assistance in dying. Such assistance may consist of providing a patient with a prescription of lethal medication that is self-administered by the patient, which is usually referred to as (physician) assistance in suicide, or of administering lethal medication to a patient, which is referred to as euthanasia. The main aim of regulating physician assistance in dying is to bring these practices into the open and to provide physicians with legal certainty. A key condition in all jurisdictions that have regulated either assistance in suicide or euthanasia is that physicians are only allowed to engage in these acts upon the explicit and voluntary request of the patient. All systems that allow physician assistance in dying have also in some way included the notion that physician assistance in dying is only accepted when it is the only means to address severe suffering from an incurable medical condition. Arguments against the legal regulation of physician assistance in dying include principled arguments, such as the wrongness of hastening death, and arguments that emphasize the negative consequences of allowing physician assistance in dying, such as a devaluation of the lives of older people, or people with chronic disease or disabilities. Opinion polls show that some form of accepting and regulating euthanasia and physician assistance in suicide is increasingly supported by the general population in most western countries. Studies in countries where physician assistance in dying is regulated suggest that practices have remained rather stable in most jurisdictions and that physicians adhere to the legal criteria in the vast majority of cases. © 2013 Elsevier B.V. All rights reserved.

  19. [Suicidal and personality characteristics of women married to men with alcohol dependence and suicidal activity].

    Science.gov (United States)

    Merinov, A V; Shustov, D I

    2011-01-01

    The effect of the suicidal activity in men with alcohol dependence on suicidal indexes, personal-codependency and psychological specifics of their wives has been studied. It has been found that women married to suicidal men with alcohol dependence significantly more frequently demonstrate suicidal activity (a phenomenon of suicidal matrimonial comorbidity) compared to wives of "non-suicidal" men. They also reveal non-suicidal behavioral patterns more frequently and prosuicidal predictors are quite common in them. This contingent of women has high suicidal potential that needs special attention during the therapeutic work.

  20. Suicide prevention through means restriction

    DEFF Research Database (Denmark)

    Knipe, Duleeka W.; Chang, Shu-Sen; Dawson, Andrew

    2017-01-01

    Objective: To investigate the effect of 3-year phased bans of the pesticides dimethoate and fenthion in 2008–2010, and paraquat in 2009–2011, on suicide mortality in Sri Lanka. Methods: Age-standardised overall, sex-specific, and method-specific suicide rates were calculated using Sri Lankan police...... data (1989–2015). Using negative binomial regression models, we estimated the change in the rate and number of suicide deaths in post-ban years (2011–15) compared to those expected based on pre-ban trends (2001–10). Findings: Overall suicide mortality dropped by 21% between 2011 and 2015, from 18.......3 to 14.3 per 100,000. The decline in pesticide suicides during this same period was larger than for overall suicides: from 8.5 to 4.2 per 100,000, a 50% reduction. This was accompanied by a smaller concurrent rise in non-pesticide suicide mortality with a 2% increase (9.9 to 10.1 per 100,000). In 2015...

  1. Internet Forums for Suicide Bereavement.

    Science.gov (United States)

    Bailey, Eleanor; Krysinska, Karolina; O'Dea, Bridianne; Robinson, Jo

    2017-11-01

    Bereavement by suicide is associated with a number of consequences including poor mental health outcomes and increased suicide risk. Despite this, the bereaved by suicide may be reluctant to seek help from friends, family, and professionals. Internet forums and social networking sites are a popular avenue of support for the bereaved, but to date there is a lack of research into their use and efficacy. To survey users of suicide bereavement Internet forums and Facebook groups regarding their help-seeking behaviors, use of forums, and perceived benefits and limitations of such use. This study employed a cross-sectional design in which users of suicide bereavement Internet forums and Facebook groups completed an anonymous online survey. Participants were 222 users of suicide bereavement Internet forums. Most participants (93.2%) had sought face-to-face help from sources other than Internet forums, but were more likely to seek help in the near future from informal rather than formal sources. Forums were perceived as highly beneficial and there were few limitations. The generalizability of these results to other internet forums may be limited. Additionally, we were not able to examine differences between forums in terms of quality or user-reported efficacy. Finally, the data reflects the subjective views of forum users, which may differ from the views of moderators or experts. Internet forums, including Facebook groups, appear to be a useful adjunct to face-to-face help-seeking for supporting those who have been bereaved by suicide.

  2. Suicide among forensic psychiatric patients.

    Science.gov (United States)

    Johnson, C; Smith, J; Crowe, C; Donovan, M

    1993-04-01

    This paper examines the problem of suicide among patients discharged from a Regional Secure Unit. The stereotype that emerges is a young man with anti-social personality traits, suffering from an affective psychosis, with a history of substance abuse and impulsive violence directed both towards himself and others, who is alienated from care staff and social supports because of his provocative and uncooperative behaviour. In contrast with the general population, forensic patients are more likely to commit suicide using a violent method and are more likely to have a suicide verdict recorded by the coroner. The implications of these findings for treatment and preventive interventions are discussed.

  3. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Tzeng Dong-Sheng

    2011-05-01

    Full Text Available Abstract Background The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide, and major depressive disorder (MDD. We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls. Methods Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared. Results The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041. Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively. Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p Conclusion The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.

  4. Suicide with 137 cesium

    International Nuclear Information System (INIS)

    Vasileva, B.

    1976-01-01

    A case report is presented of suicide by radiation exposure after a preceding attempt with potassium ferrocyanide. The subject, a 30-year-old nondestructive-testing technician, held with his right fingers and then placed in his left shirt pocket a metal-canned 5,3-Ci 137 Cs source. Despite appearance of signs of severe topical injury by day 3 after the incident and development of systemic toxicity symptoms with indications of affection of internal organs by day 16, medical aid was not sought until day 21 when efforts at management proved unable to prevent fatal outcome. A prominent distinguishing characteristic of this mode of suicide is that the deed's sequelae are delayed in coming into effect. Cases known to have occurred are extremely rare (only two have been described in the literature). This is likely to be related to a distinct unpopularity of radioactive materials as well as their limited availability to the general public. The subjects that did use them were radiation workers having access to such substances; being acquainted with the biological effects of radiation, they, nevertheless, have chosen this protracted and distressful way of taking their lives. (A.B.)

  5. Genetic and Environmental Contributions to Self-Reported Thoughts of Self-Harm and Suicide

    NARCIS (Netherlands)

    Althoff, R.R.; Hudziak, J.J.; Willemsen, G.; Hudziak, V.; Bartels, M.; Boomsma, D.I.

    2012-01-01

    Thoughts of self-harm and suicidal behavior are thought to be influenced by both genetics and environment. Molecular genetic studies are beginning to address the question of which genes may be involved and whether different genes may be expressed in men and women. We examined thoughts of self-harm

  6. Suicide: What to Do When Someone Is Suicidal

    Science.gov (United States)

    ... depressed person may not have the energy or motivation to find help. If the person doesn't ... someone who's suicidal isn't thinking logically, the emotions are real. Not respecting how the person feels ...

  7. Depressed suicide attempters with posttraumatic stress disorder.

    Science.gov (United States)

    Ramberg, Maria; Stanley, Barbara; Ystgaard, Mette; Mehlum, Lars

    2015-01-01

    Posttraumatic stress disorder and major depressive disorder are well-established risk factors for suicidal behavior. This study compared depressed suicide attempters with and without comorbid posttraumatic stress disorder with respect to additional diagnoses, global functioning, depressive symptoms, substance abuse, history of traumatic exposure, and suicidal behavior. Adult patients consecutively admitted to a general hospital after a suicide attempt were interviewed and assessed for DSM-IV diagnosis and clinical correlates. Sixty-four patients (71%) were diagnosed with depression; of them, 21 patients (32%) had posttraumatic stress disorder. There were no group differences in social adjustment, depressive symptoms, or suicidal intent. However, the group with comorbid depression and posttraumatic stress disorder had more additional Axis I diagnoses, a higher degree of childhood trauma exposure, and more often reported previous suicide attempts, non-suicidal self-harm, and vengeful suicidal motives. These findings underline the clinical importance of diagnosis and treatment of posttraumatic stress disorder in suicide attempters.

  8. Nursing students’ attitude toward suicide prevention

    Science.gov (United States)

    Nebhinani, Naresh; Mamta; Gaikwad, Achla D.; Tamphasana, L.

    2013-01-01

    Background: Preventing suicide depends upon different health professionals’ knowledge regarding suicide, attitude toward suicide attempters, skills to assess and manage suicidal risk. Objectives: This study was aimed to assess the attitude of nursing students toward suicide prevention. Materials and Methods: 308 nursing students were recruited from the two institutions through total enumeration method. Attitude toward suicide prevention scale was administered. Study design was cross-sectional. Results: Majority were single females, from urban locality, who were pursuing BSc Nursing with the mean age of 20 years. Only minority had previous exposure to suicide prevention programs or workshops. Nearly half of the subjects had positive attitude toward working with suicidal patients. Again half of the subjects considered unemployment and poverty as main causes of suicide and were quite hopeless about it and they also perceived that most of the suicidal people would not reveal their suicidal plans to others. Conclusions: Merely half of the students had positive attitude toward working with suicidal patients. Hence, there is strong need to organize more educational and training programs on suicide prevention so that these budding health professionals could be more equipped and trained to manage these suicidal patients. PMID:25013311

  9. Suicide: rationality and responsibility for life.

    Science.gov (United States)

    Ho, Angela Onkay

    2014-03-01

    Death by suicide is widely held as an undesirable outcome. Most Western countries place emphasis on patient autonomy, a concept of controversy in relation to suicide. This paper explores the tensions between patients' rights and many societies' overarching desire to prevent suicide, while clarifying the relations between mental disorders, mental capacity, and rational suicide. A literature search was conducted using search terms of suicide and ethics in the PubMed and LexisNexis Academic databases. Article titles and abstracts were reviewed and deemed relevant if the paper addressed topics of rational suicide, patient autonomy or rights, or responsibility for life. Further articles were found from reference lists and by suggestion from preliminary reviewers of this paper. Suicidal behaviour in a person cannot be reliably predicted, yet various associations and organizations have developed standards of care for managing patients exhibiting suicidal behaviour. The responsibility for preventing suicide tends to be placed on the treating clinician. In cases where a person is capable of making treatment decisions--uninfluenced by any mental disorder--there is growing interest in the concept of rational suicide. There is much debate about whether suicide can ever be rational. Designating suicide as an undesirable event that should never occur raises the debate of who is responsible for one's life and runs the risk of erroneously attributing blame for suicide. While upholding patient rights of autonomy in psychiatric care is laudable, cases of suicidality warrant a delicate consideration of clinical judgment, duty of care, and legal obligations.

  10. Nursing students' attitude toward suicide prevention.

    Science.gov (United States)

    Nebhinani, Naresh; Mamta; Gaikwad, Achla D; Tamphasana, L

    2013-07-01

    Preventing suicide depends upon different health professionals' knowledge regarding suicide, attitude toward suicide attempters, skills to assess and manage suicidal risk. This study was aimed to assess the attitude of nursing students toward suicide prevention. 308 nursing students were recruited from the two institutions through total enumeration method. Attitude toward suicide prevention scale was administered. Study design was cross-sectional. Majority were single females, from urban locality, who were pursuing BSc Nursing with the mean age of 20 years. Only minority had previous exposure to suicide prevention programs or workshops. Nearly half of the subjects had positive attitude toward working with suicidal patients. Again half of the subjects considered unemployment and poverty as main causes of suicide and were quite hopeless about it and they also perceived that most of the suicidal people would not reveal their suicidal plans to others. Merely half of the students had positive attitude toward working with suicidal patients. Hence, there is strong need to organize more educational and training programs on suicide prevention so that these budding health professionals could be more equipped and trained to manage these suicidal patients.

  11. Risk factors related to suicidal ideation and attempted suicide: comparative study of Korean and American youth.

    Science.gov (United States)

    Chung, Sung Suk; Joung, Kyoung Hwa

    2012-12-01

    Suicidal trends and related characteristics such as sociodemographic factors, psychological factors, and health behaviors can differ between countries. This study investigated the predictors of suicidal ideation and attempted suicide including health behaviors among American and Korean youth from two national representative data sets. In both countries, depression was the most predominant predictor to suicidal ideation and attempted suicide. Unique predictors of suicidal youth in each country were also found. In America, attempted suicide was predicted by poor body image, whereas in Korea attempted suicide was predicted by medical diagnosis such as asthma, concern about weight, and alcohol consumption. The value of our approach lies in the comparative analysis of analogous and unique characteristics of suicidal youths in these two huge data sets from different countries. These results should be helpful for school and mental health care providers to plan interventions for youth at risk of suicide to prevent suicidal completion in these nations.

  12. Why not Commercial Assistance for Suicide? On the Question of Argumentative Coherence of Endorsing Assisted Suicide.

    Science.gov (United States)

    Kipke, Roland

    2015-09-01

    Most people who endorse physician-assisted suicide are against commercially assisted suicide - a suicide assisted by professional non-medical providers against payment. The article questions if this position - endorsement of physician-assisted suicide on the one hand and rejection of commercially assisted suicide on the other hand - is a coherent ethical position. To this end the article first discusses some obvious advantages of commercially assisted suicide and then scrutinizes six types of argument about whether they can justify the rejection of commercially assisted suicide while simultaneously endorsing physician-assisted suicide. The conclusion is that they cannot provide this justification and that the mentioned position is not coherent. People who endorse physician-assisted suicide have to endorse commercially assisted suicide as well, or they have to revise their endorsement of physician-assisted suicide. © 2014 John Wiley & Sons Ltd.

  13. Predictors of Suicide Ideation in a Random Digit Dial Study: Exposure to Suicide Matters.

    Science.gov (United States)

    van de Venne, Judy; Cerel, Julie; Moore, Melinda; Maple, Myfanwy

    2017-07-03

    Suicide is an important public health concern requiring ongoing research to understand risk factors for suicide ideation. A dual-frame, random digit dial survey was utilized to identify demographic and suicide-related factors associated with suicide ideation in a statewide sample of 1,736 adults. The PH-Q 9 Depression scale suicide ideation question was used to assess current suicide ideation in both the full sample and suicide exposed sub-sample. Being non-married and having previous suicide exposure were separately associated with higher risks of suicide ideation in the full sample. Being male, having increased suicide exposures, and having increased perceptions of closeness to the decedent increased risks, while older age decreased risks for the suicide exposed. Implications for future screening and research are discussed.

  14. Attempted suicide in Denmark. III. Assessment of repeated suicidal behaviour

    DEFF Research Database (Denmark)

    Wang, A G; Nielsen, B; Bille-Brahe, U

    1985-01-01

    , mostly in the first year. Ten patients committed suicide, half of them in the first 3 months after the interview, shortly after discharge from hospital. The majority of the repeaters were living alone, while those that committed suicide were mostly married women aged 50-60 years. Other characteristic...... poorly due, in particular, to low specificity. Future work will focus on objective risk factors, those indicated here and others, in order to establish an up-to-date background for assessment and management....

  15. Mysore study: A study of suicide notes.

    Science.gov (United States)

    Namratha, P; Kishor, M; Sathyanarayana Rao, T S; Raman, Rajesh

    2015-01-01

    Suicide is one of the leading causes of preventable deaths. Recent data suggest South India as one of the regions with highest suicide rates in the world. In 2013, 134,799 people committed suicide in India according to the statistics released by the National Crime Records Bureau. Suicide note is one of the most important sources to understand suicide, which may be beneficial in suicide prevention. Studies on suicidal notes from this part of the world are sparse. The aim was to study the themes in suicide notes that might be useful in prevention strategies. A descriptive study of all suicide notes of those individuals who committed suicide between 2010 and 2013 available with Police Department, Mysore district was obtained and analyzed. A total of 22 suicide note were available. A majority of suicide note was in age group of 16-40 years (86%) and most were men (59%). All suicide notes were handwritten, the majority (70%) in regional language Kannada. Length of notes varied from just few words to few pages. Contents of suicide notes included apology/shame/guilt (80%), love for those left behind (55%) and instruction regarding practical affairs (23%). Most have blamed none for the act (50%). 23% mentioned that they are committing suicide to prove their innocence. 32% mentioned a last wish. The majority of suicidal note contained "guilt" which is a strong indicator of possible depression in deceased. Creating awareness about suicide among public and ensuring access to professionals trained in suicide prevention is need of the hour in this part of the world.

  16. Suicidal ideation and attempted suicide in elderly people - subjective experiences.

    Science.gov (United States)

    Gutierrez, Denise Machado Duran; Sousa, Amandia Braga Lima; Grubits, Sonia

    2015-06-01

    We discuss the subjective experiences of elderly people who show suicidal ideation and/or attempts at suicide, based on their own reports. We understand the concept of 'subjective' as referring to intra-psychic experience resulting from social, economic, relationship or biographical conditions. Although the subject is sparsely covered in the literature, it is important, because it is in the field of subjectivity that ideations of, and attempts at, suicide develop and occur until they become a concrete act. Empirical data were collected through semi-structured interviews focusing on: social characterization, portrayal and mode of life, previous mental state, atmosphere of the attempt, effects on the health of the elderly person and family. Based on the analysis of the meanings that emerge, five empirical categories were generated: (1) subject's feeling of being in a non-place; (2) absence of acceptance of losses; (3) suffering due to ingratitude of family members; (4) feeling of uselessness of, and in, life; (5) re-signification of the situations that generate suicide-related conduct. The results point to a fundamental need to incorporate knowledge about the subjective processes into programs for prevention of suicide among the elderly who have ideation of, or attempts at, suicide.

  17. Suicide Prevention: does it work?

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    2016-03-05

    Mar 5, 2016 ... suicide, family violence (including physical or sexual abuse), having guns or other ... treatment of mental and addictive disorders, restricted access to lethal means of .... therapy in manic-depressive disorders25 and addiction.

  18. Suicide by self-incineration

    DEFF Research Database (Denmark)

    Leth, Peter Mygind; Hardt-Madsen, Michael

    1997-01-01

    was 43 years, with a broad age range (20-87). Many incidents of self-incineration as a form of political protest were reported in the press especially during the 1960s and 1970s, and the press reports often inspired others to commit suicide in the same way. None of the cases in our investigation were...... victims were of Danish origin, and a religious motive played no significant role. Most of the victims were suffering from mental illness, and a majority had tried to commit suicide before. None of the victims left a suicide note. The scene was most often at home and indoors--only a minority committed...... suicide in remote areas of the countryside. Most were found dead at the scene, and the cause of death was usually heat exposure. Only a minority had a lethal carboxy-hemoglobin (CO-Hb) concentration. It is concluded that close cooperation between police, fire experts, and the forensic pathologist...

  19. Suicide Prevention Strategies for Improving Population Health.

    Science.gov (United States)

    Wilcox, Holly C; Wyman, Peter A

    2016-04-01

    Suicide is a public health problem that accounts for more than 1 million deaths annually worldwide. This article addresses evidence-based and promising youth suicide prevention approaches at the primary, secondary, and tertiary levels. Coordinated, developmentally timed, evidence-based suicide prevention approaches at all intervention levels are likely to reduce youth suicide. For most youth who die by suicide, there are opportunities for intervention before imminent risk develops. Current research in suicide prevention points to the value of investing in "upstream" universal interventions that build skills and resilience as well as policies that enable access to care and protection from lethal means. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Suicide with Shotgun: A Case Report

    Directory of Open Access Journals (Sweden)

    Ali Yildirim

    2011-03-01

    Full Text Available Suicide appears to be a major public health problem in our country and all over the World. Suicide methods will vary between the various communities the most common types of suicides are hanging, using chemicals and using firearms (pistol, shotgun. Connected with easy availability of shotguns suicide cases with using shotgun is significantly increasing in recent years. In our study, suicide with a shotgun, are evaluated in terms of shooting range and its features, originate, area of suicide, crime scene, sex and age. [J Contemp Med 2011; 1(1.000: 29-34

  1. Clinical Correlates of Planned and Unplanned Suicide Attempts.

    Science.gov (United States)

    Chaudhury, Sadia R; Singh, Tanya; Burke, Ainsley; Stanley, Barbara; Mann, J John; Grunebaum, Michael; Sublette, M Elizabeth; Oquendo, Maria A

    2016-11-01

    Suicide attempters differ in the degree of planning for their suicide attempts. The purpose of this study was to identify differences between individuals who make planned (≥3 hours of planning) and unplanned (suicide attempts. Depressed suicide attempters (n = 110) were compared based on degree of planning of their most recent suicide attempt on demographic and clinical variables. Participants who made planned suicide attempts were more likely to have family history of completed suicide, more severe and frequent suicidal ideation, greater trait impulsivity, and greater suicidal intent and more severe medical consequences for both their most recent and most serious suicide attempts. These results suggest clear clinical differences based on the degree of suicide attempt planning. Severe suicidal ideation, high suicide intent, family history of suicide completion, and high levels of motor impulsivity contribute to a phenotype that is at greater risk of planned, highly lethal suicide attempts.

  2. Suicide and ethnicity in Malaysia.

    Science.gov (United States)

    Murty, Om Prakash; Cheh, Lo Boon; Bakit, Pangie Anak; Hui, Foo Jhi; Ibrahim, Zarina Binti; Jusoh, Nazirah Binti

    2008-03-01

    This article highlights methods of ending life in different ethnic groups. This inference is drawn from analysis of data from suicidal cases from the University Malaya Medical Centre mortuary. This study also looked at sex, age, social, and employment factors. Kuala Lumpur has sizeable populations of Muslims, Chinese, Indians and Indonesian, etc. This study is based on 251 cases of suicide that were reported at the University Malaya Medical Centre from 2000 to 2004. Malaysia has a population of 22,662,365 people with 3 major ethnic groups: Malay (58%), Chinese (24%), and Indians (8%) with a minority of "others" (10%), which includes foreigners, Sabahan, and Sarawakian. This research found suicides of 164 male (65%) and 87 female (35%) victims. Their age ranged from 15 to 80 years. The age group from 21 to 30 had the highest total cases of suicide (83 of 251; 33.1%). Among ethnic groups highest rate of suicide was among Chinese with a total of 120 cases (120 of 251; 47.8%). As far as lone method of suicide is concerned, hangings accounted for the highest proportion of cases (108 of 251; 43%). Among ethnic groups, jumping from height was the commonest method used by Chinese (49 of 120; 41%), Malay (9 of 16; 56%), and others (15 of 28; 53.4%); whereas, hanging was the commonest method of committing suicide by Indians (49 of 87); Muslims showed the lowest cases of suicide (18 of 251; 7.2%). In poisoning group Indian was the highest ethnic group who used this method (20 of 37; 54.1%).

  3. Gene therapy and radionuclides targeting therapy in mammary carcinoma

    International Nuclear Information System (INIS)

    Song Jinhua

    2003-01-01

    Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

  4. [Suicide risk in somatoform disorders].

    Science.gov (United States)

    Giupponi, Giancarlo; Maniscalco, Ignazio; Mathà, Sandra; Ficco, Carlotta; Pernther, Georg; Sanna, Livia; Pompili, Maurizio; Kapfhammer, Hans-Peter; Conca, Andreas

    2018-03-01

    The somatoform disorders include a group of complex disorders consist of somatic symptoms for which there are no identifiable organic cause or pathogenetic mechanisms. Given the importance of these disorders and the need to clarify the diagnosis of somatoform disorder affecting the suicide risk, we took into consideration the scientific literature to investigate the correlation between the two conditions. We performed a bibliographic search through Medline, Embase, PsycINFO, Scopus, SciELO, ORCID, Google Scholar, DOAJ using the following terms: somatoform, somatization disorder, pain disorder AND psychological factor, suicide, parasuicide, suicidality. In all studies reported in our review, the suicidal behavior risk is high. But in the majority, the data are relatively unreliable because it takes into account the category nosographic "Neurotic, stress-related and somatoform disorders", too wide to be able to identify the clinical characteristics of patients at risk of only somatoform disorder. Several studies conclude that psychiatric comorbidity increases the suicide risk: patients with two or more psychiatric disorders are more likely to commit a suicide attempt; in particular if there is a axis I diagnosis, the risk reduplicate. The somatization disorder seems to have a significant psychiatric comorbidity in particular with anxious and affective disorders spectrum.

  5. [Active euthanasia, or assisted suicide?

    Science.gov (United States)

    Julesz, Máté

    2016-10-01

    Both active euthanasia and assisted suicide are legal in The Netherlands, Belgium, Luxemburg and, most recently, in Canada. Examination of national legislations of countries where both active euthanasia and assisted suicide are legal. The number of accomplished active euthanasia cases and that of assisted suicide cases. Analysis of national statistical data. Comparison of statistical data before and after 2010. Comparison of the related practices in the surveyed countries. The number of active euthanasia cases markedly predominates over the number of assisted suicide cases. Cancer is a main reason for active euthanasia, or assisted suicide. In countries with a larger population, the number of active euthanasia cases is higher than that in countries with a smaller population. Regarding the fact that the applicants for active euthanasia withdraw their requests in a smaller number than the applicants for assisted suicide, patients prefer the choice of active euthanasia. Since the related legislative product is too recent in Canada at present, it may be only presumed that a certain preference will also develop in the related practices in Canada. Orv. Hetil., 2016, 157(40), 1595-1600.

  6. Extended suicide with a pet.

    Science.gov (United States)

    Cooke, Brian K

    2013-01-01

    The combination of the killing of a pet and a suicide is a perplexing scenario that is largely unexplored in the literature. Many forensic psychiatrists and psychologists may be unaccustomed to considering the significance of the killing of a pet. The subject is important, however, because many people regard their pets as members of their family. A case is presented of a woman who killed her pet dog and herself by carbon monoxide poisoning. The purpose of this article is to provide an initial exploration of the topic of extended suicide with a pet. Forensic mental health evaluations may have a role in understanding the etiology of this event and in opining as to the culpability of individuals who attempt to or successfully kill a pet and then commit suicide. Because the scientific literature is lacking, there is a need to understand this act from a variety of perspectives. First, a social and anthropological perspective will be presented that summarizes the history of the practice of killing of one's pet, with a focus on the ancient Egyptians. A clinical context will examine what relationship animals have to mental illness. A vast body of existing scientific data showing the relevance of human attachment to pets suggests that conclusions from the phenomena of homicide-suicide and filicide-suicide are applicable to extended suicide with a pet. Finally, recommendations will be proposed for both clinical and forensic psychiatrists faced with similar cases.

  7. Parents bereaved by offspring suicide

    DEFF Research Database (Denmark)

    Bolton, James M; Au, Wendy; Leslie, William D

    2013-01-01

    OUTCOME MEASURES Mental and physical disorders, social factors, and treatment use. RESULTS Suicide bereavement was associated with an increased rate of depression (ARR, 2.14; 95% CI, 1.88-2.43), anxiety disorders (ARR, 1.41; 95% CI, 1.24-1.60), and marital breakup (ARR, 1.18; 95% CI, 1.13-1.23) in the 2...... years after the suicide of an offspring, as compared with the 2 years prior to the death. Suicide-bereaved and MVC-bereaved parents had very few differences on predeath to postdeath outcomes. Depression rate increases were greater for MVC-bereaved parents (19.9%) compared with suicide-bereaved parents...... (15.9%; P = .005), whereas suicide-bereaved parents had higher rate increases of hospitalization for mental illness (P = .049). Suicide-bereaved parents were more likely than their MVC-bereaved counterparts to have depression (ARR, 1.30; 95% CI, 1.06-1.61), physical disorders (ARR, 1.32; 95% CI, 1...

  8. Psychotic Depression and Suicidal Behavior.

    Science.gov (United States)

    Fredriksen, Kristin J; Schoeyen, Helle K; Johannessen, Jan O; Walby, Fredrik A; Davidson, Larry; Schaufel, Margrethe A

    2017-01-01

    This study investigated how severely depressed individuals experienced the relationship between psychotic symptoms and suicidal ideation and behavior. Semi-structured qualitative interviews were conducted with a purposive sample of nine inpatients from a psychiatric university hospital between September 2012 and May 2013 fulfilling diagnostic criteria for a psychotic depressive episode as part of a unipolar or bipolar disorder. Analysis was conducted using systematic text condensation. Participants experienced (1) being directed to perform impulsive potentially fatal actions, (2) feeling hounded to death, (3) becoming trapped in an inescapable darkness, and (4) being left bereft of mental control. They described how impulsivity directed by delusions and hallucinations resulted in unpredictable actions with only moments from decision to conduct. Suicide was seen as an escape not only from life problems but also from psychotic experiences and intense anxiety. Participants reported being in a chaotic state, unable to think rationally or anticipate the consequences of their actions. Their ability to identify and communicate psychotic symptoms and suicidal ideation and behavior was compromised, leaving them to struggle alone with these terrifying experiences. Suicide risk assessments based on verbal reports from individuals with psychotic depression may not always be valid due to potential impulsivity and underreporting of suicidal ideation. It may be important for clinicians to explore the delusional content of such patients' experiences to assess the possibility of suicide as a result of shame, guilt, remorse, or altruistic intentions to save others from harm.

  9. Predictors of Suicide Attempts in Clinically Depressed Korean Adolescents

    Science.gov (United States)

    Kwon, Ahye; Song, Jungeun; Yook, Ki-Hwan; Jon, Duk-In; Jung, Myung Hun; Hong, Narei; Hong, Hyun Ju

    2016-01-01

    We examined predictors of suicide attempts in clinically depressed adolescents in Korea and gender differences in suicidal behavior. In total, 106 adolescents diagnosed with depressive disorder were recruited in South Korea. We assessed various variables that might affect suicide attempts, and used a structured interview for the diagnosis of depression and comorbidities and to evaluate suicidality. Demographic and clinical characteristics of the subjects were compared between suicide attempt and non-suicide attempt groups and we examined significant predictors of suicide attempts. Gender differences in suicidal ideation and suicidal behavior were also analyzed. Among 106 depressed participants, 50 (47.2%) adolescents were classified in the suicide attempt group. Generally, the suicide attempt and non-suicide attempt group shared similar clinical characteristics. The suicide attempt group had more females, more major depressive disorder diagnoses, more depressive episodes, and higher suicidal ideation than the non-suicide attempt group. Suicidal ideation was the only significant predictor of suicidal attempt, regardless of gender. Higher suicidal ideation frequency scores and more non-suicidal self-injurious behaviors were shown in the female suicide attempt group than the male suicide attempt group. It is recommended that suicidal ideation be assessed regularly and managed rigorously to decrease suicide risks in depressive adolescents. PMID:27776392

  10. Antidepressants and Suicide Risk: A Comprehensive Overview

    Directory of Open Access Journals (Sweden)

    Roberto Tatarelli

    2010-08-01

    Full Text Available The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year, with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20–30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.

  11. Exposure to suicide and suicidality in Korea: differential effects across men and women?

    Science.gov (United States)

    Lee, Min-Ah; Kim, Seokho; Shim, Eun-Jung

    2013-05-01

    Little is known about whether exposure to suicide within close social networks is associated with the suicidality in exposed individuals, and potential gender differences regarding this association. This study examines the effect of exposure to suicide on the suicidality in exposed individuals. The data were drawn from the 2009 Korean General Social Survey, a nationally representative interview survey. Suicidality was measured by the suicidality module in the Mini International Neuropsychiatric Interview (MINI), with exposure to suicide being determined by asking about the experience of a failed or completed suicide attempt by a closely related person. Exposure to the suicide of someone close was significantly associated with higher suicidality in exposed individuals. While the effect of a failed attempt became non-significant after controlling for psychological factors, that of exposure to a completed act of suicide remained significant. A subsample analysis by gender indicated a significant gender difference: with control for demographic and psychological factors, exposure to a completed suicide had a significant effect on the suicidality of females only. The effect of exposure to a failed attempt became non-significant both in males and females after controlling for other factors. Findings suggest the necessity of screening for prior exposure to suicide in suicide risk assessment and the need for gender-tailored suicide-prevention strategies.

  12. Suicides and Suicide Attempts in the U.S. Military, 2008-2010

    Science.gov (United States)

    Bush, Nigel E.; Reger, Mark A.; Luxton, David D.; Skopp, Nancy A.; Kinn, Julie; Smolenski, Derek; Gahm, Gregory A.

    2013-01-01

    The Department of Defense Suicide Event Report Program collects extensive information on suicides and suicide attempts from the U.S. Air Force, Army, Marine Corps, and Navy. Data are compiled on demographics, suicide event details, behavioral health treatment history, military history, and information about other potential risk factors such as…

  13. You Can't Recover from Suicide: Perspectives on Suicide Education in MSW Programs

    Science.gov (United States)

    Ruth, Betty J.; Gianino, Mark; Muroff, Jordana; McLaughlin, Donna; Feldman, Barry N.

    2012-01-01

    Suicide is a profound worldwide public health problem that has received increased attention in recent years. The major federal response, the National Strategy for Suicide Prevention, calls for more suicide education for mental health professionals, including social workers. Little is known about the amount of suicide education in MSW curricula…

  14. Predictors of intimate partner problem-related suicides among suicide decedents in Kentucky

    Directory of Open Access Journals (Sweden)

    Ashley L. Comiford

    2016-07-01

    Full Text Available BACKGROUND: Suicide is the 10th leading cause of death in the United States. Furthermore, intimate partner problems are amid the top precipitating circumstances among suicide decedents. The aim of this study was to determine circumstantial associations of intimate partner problem-related suicides in suicide decedents in Kentucky. METHODS: All suicides that were reported to the Kentucky Violent Death Reporting System between 2005 and 2012 were eligible for this study. Multiple logistic regression was used to explore predictors (precipitating health-related problems, life stressors, and criminal/legal issues of intimate partner problem-related suicides. RESULTS: Of the 4,754 suicides, included in this study, approximately 17% had intimate partner problems prior to suicide. In the adjusted analysis, mental health issues, alcohol problems, history of suicides attempts, suicides precipitated by another crime, and other legal problems increased the odds of having an intimate partner-related suicide. However, having physical health problems, prior to the suicide, decreased the odds of intimate partner-related suicide. CONCLUSIONS: These results provide insight for the development of suicide interventions for individuals with intimate partner problems by targeting risk factors that are prevalent among this population. Moreover, these results may help marriage/relationship and/or family/divorce court representatives identify individuals with intimate partner problems more at risk for suicide and alleviate the influence these suicide risk factors have on individuals experiencing Intimate partner problems.

  15. Gratitude and Suicidal Ideation and Suicide Attempts among Chinese Adolescents: Direct, Mediated, and Moderated Effects

    Science.gov (United States)

    Li, Dongping; Zhang, Wei; Li, Xian; Li, Nini; Ye, Baojuan

    2012-01-01

    In a sample of 1252 Chinese adolescents (mean age = 15.00 years), this study examined the direct relations between gratitude and adolescents' suicidal ideation and suicide attempts. This study also examined indirect relations between gratitude and suicidal ideation and suicide attempts via two self-system beliefs--coping efficacy and self-esteem.…

  16. No-Suicide Contracts with Suicidal Youth: Mental Health Professionals' Perceptions and Current Practice

    Science.gov (United States)

    Hansen, Andrea; Heath, Melissa Allen; Williams, Marleen; Fox, Jay; Hudnall, Gregory A.; Bledsoe, Catherine

    2012-01-01

    Commonly used in clinical and medical settings, no-suicide contracts (NSCs) solicit commitment from suicidal individuals not to attempt suicide. The prevalence of community and school-based Mental Health Professionals' (MHPs) use of NSCs with suicidal youth (SY) is unknown. Additionally, minimal feedback is available regarding MHPs' current…

  17. An Application of Durkheim's Theory of Suicide to Prison Suicide Rates in the United States

    Science.gov (United States)

    Tartaro, Christine; Lester, David

    2005-01-01

    E. Durkheim (1897) suggested that the societal rate of suicide might be explained by societal factors, such as marriage, divorce, and birth rates. The current study examined male prison suicide rates and suicide rates for men in the total population in the United States and found that variables based on Durkheim's theory of suicide explained…

  18. Predicting Suicidal Ideation with the Depression Hopelessness and Suicide Screening Form (DHS)

    Science.gov (United States)

    Mills, Jeremy F.; Kroner, Daryl G.

    2008-01-01

    The current study examines a series of interactions between a prior history of suicidal behavior and cognitions permissive of suicide, and the variables of depression and hopelessness in the relationship with suicidal ideation in two samples of incarcerated offenders. Results indicate that both a prior history of suicidal behavior and cognitions…

  19. Tolerance of suicide, religion and suicide rates : an ecological and individual study in 19 Western countries

    NARCIS (Netherlands)

    Neeleman, J; Halpern, D; Leon, D; Lewis, G

    Background. Negative associations between religion and suicide, in individuals and countries, may be mediated by the degree to which suicide is tolerated. Methods. Linear regression was used to examine ecological associations between suicide tolerance, religion and suicide rates in 19 Western

  20. Personality traits as an endophenotype in genetic studies on suicidality in bipolar disorder.

    Science.gov (United States)

    Pawlak, J; Dmitrzak-Węglarz, M; Maciukiewicz, M; Kapelski, P; Czerski, P; Leszczyńska-Rodziewicz, A; Zaremba, D; Hauser, J

    2017-04-01

    Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls. The personality dimensions were assessed using the Temperament and Character Inventory (TCI). We genotyped two selected polymorphisms of the tryptophan hydroxylase 1 (TPH1) gene (rs1800532 218A>C and rs1799913 779A>C) and polymorphism in the promoter region of serotonin transporter gene (5-HTTLPR, rs25531) related to serotoninergic neurotransmission. Multiple poisson regression, logistic regression and Kruskal-Wallis tests were applied. We found numerous differences between the BP patients and the control group in terms of their TCI dimensions/subdimensions. Significant differences were found between patients with, and without, suicidal attempts in fatigability and asthenia (Ha4), as well as in harm avoidance (Ha). We also found that the interactions between TCI subdimensions (the interaction of disordiness (Ns4) and spiritual acceptance (St3), disordiness (Ns4) and integrated conscience (C5), extravagance (Ns3) and resourcefulness (Sd3)) were significantly contributing for suicidal behaviour risk. We found association between all studied genetic polymorphisms and several TCI dimensions and subdimensions. Our results confirm that personality traits are partially determined by genes. Both personality traits and the interactions between temperament and character traits, may be helpful in predicting suicidal behaviour.

  1. Internet suicide in Japan: a qualitative content analysis of a suicide bulletin board.

    Science.gov (United States)

    Ikunaga, Ai; Nath, Sanjay R; Skinner, Kenneth A

    2013-04-01

    Netto shinju, or Internet group suicide, is a contemporary form of Japanese suicide where strangers connect on the Internet and make plans to commit suicide together. In the past decade, numerous incidents have occurred whereby young Japanese make contact on the Internet, exchange tips on suicide methods, and make plans to meet offline for group/individual suicide. A systematic qualitative content/thematic analysis of online communications posted on a popular Japanese suicide bulletin board yielded a textured, thematic understanding of this phenomenon. Themes identified reflected Shneidman's theory of suicide but with an emphasis on interpersonal concerns that are embedded in Japanese culture.

  2. Suicide and mental illness in parents and risk of suicide in offspring: a birth cohort study

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Wang, August G

    2009-01-01

    BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult...... the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4...

  3. Suicide and mental illness in parents and risk of suicide in offspring : A birth cohort study

    DEFF Research Database (Denmark)

    Sørensen, Holger; Mortensen, Erik Lykke; Wang, August

    2009-01-01

    BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult...... the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4...

  4. Suicide to harass others: clues from mythology to understanding suicide bombing attacks.

    Science.gov (United States)

    Preti, Antonio

    2006-01-01

    Suicide by revenge, the Samsonic suicide, and the suicide by devotio, all described in classical mythology and also reported in the ethnographic literature, belong to the same class of suicidal behaviors as kamikaze suicide and the suicide bombing attack: suicide to harass and burden others or suicide with a hostile intent. The lack of a social dimension to share in a positive manner may lead an individual to integrate him/herself in another social structure, e.g., a military organization, which allows the individual to express his/her desires and personal identity only by destroying others and themselves. The dynamics of these forms of suicide are also likely to work in other displays of life-threatening behavior, such as family annihilation, mass murder, and spree killing. A more thorough investigation of the dynamics operating in suicide bombing attacks could, therefore, contribute to preventative strategies against violence at large.

  5. Predictive Validity of the Columbia-Suicide Severity Rating Scale for Short-Term Suicidal Behavior

    DEFF Research Database (Denmark)

    Conway, Paul Maurice; Erlangsen, Annette; Teasdale, Thomas William

    2017-01-01

    adolescents (90.6% females) who participated at follow-up (85.9%) out of the 99 (49.7%) baseline respondents. All adolescents were recruited from a specialized suicide-prevention clinic in Denmark. Through multivariate logistic regression analyses, we examined whether baseline suicidal behavior predicted......Using the Columbia-Suicide Severity Rating Scale (C-SSRS), we examined the predictive and incremental predictive validity of past-month suicidal behavior and ideation for short-term suicidal behavior among adolescents at high risk of suicide. The study was conducted in 2014 on a sample of 85...... subsequent suicidal behavior (actual attempts and suicidal behavior of any type, including preparatory acts, aborted, interrupted and actual attempts; mean follow-up of 80.8 days, SD = 52.4). Furthermore, we examined whether suicidal ideation severity and intensity incrementally predicted suicidal behavior...

  6. Suicidal Disclosures among Friends: Using Social Network Data to Understand Suicide Contagion*

    Science.gov (United States)

    Mueller, Anna S.; Abrutyn, Seth

    2015-01-01

    A robust literature suggests that suicide is socially contagious; however, we know little about how and why suicide spreads. Using network data from the National Longitudinal Study of Adolescent to Adult Health, we examine the effects of alter’s (1) disclosed and (2) undisclosed suicide attempts, (3) suicide ideation and (4) emotional distress on ego’s mental health one year later to gain insights into the emotional and cultural mechanisms that underlie suicide contagion. We find that when egos know about alter’s suicide attempt, they report significantly higher levels of emotional distress and are more likely to report suicidality, net of extensive controls; however, alter’s undisclosed suicide attempts and ideation have no significant effect on ego’s mental health. Finally, we find evidence that emotional distress is contagious in adolescence, though it does not seem to promote suicidality. We discuss the implications of our findings for suicide contagion specifically and sociology more generally. PMID:25722129

  7. Preventing Suicide in Prisons, Part I Recommendations fromthe International Association for Suicide Prevention Task Force on Suicide in Prisons

    NARCIS (Netherlands)

    Konrad, N.; Daigle, M.S.; Daniel, A.E.; Dear, G.E.; Frottier, P.; Hayes, L.M.; Kerkhof, A.J.F.M.; Liebling, A.; Sarchiapone, M.

    2007-01-01

    In 2000 the Department of Mental Health of the World Health Organization (WHO) published a guide named Preventing Suicide. A Resource for Prison Officers as part of the WHO worldwide initiative for the prevention of suicide. In 2007 there are new epidemiological data on prison suicide, a more

  8. Suicide Prevention: Critical Elements for Managing Suicidal Clients and Counselor Liability Without the Use of a No-Suicide Contract

    Science.gov (United States)

    Lee, Jeane B.; Bartlett, Mary L.

    2005-01-01

    Despite its entrenchment as a standard of practice, no-suicide contracts fail to achieve their purpose as an effective part of treatment or as an effective method of inoculating counselors against potential lawsuits should a client commit suicide. Critical elements for managing suicidal clients and counselor liability without reliance on the…

  9. Suicidal Desire and the Capability for Suicide: Tests of the Interpersonal-Psychological Theory of Suicidal Behavior among Adults

    Science.gov (United States)

    Van Orden, Kimberly A.; Witte, Tracy K.; Gordon, Kathryn H.; Bender, Theodore W.; Joiner, Thomas E., Jr.

    2008-01-01

    The interpersonal-psychological theory of suicidal behavior (T. E. Joiner, 2005) proposes that an individual will not die by suicide unless he or she has both the desire to die by suicide and the ability to do so. Three studies test the theory's hypotheses. In Study 1, the interaction of thwarted belongingness and perceived burdensomeness…

  10. Preventing adolescent suicide: a community takes action.

    Science.gov (United States)

    Pirruccello, Linda M

    2010-05-01

    Suicide is the third leading cause of death for adolescents and young people in the United States. The etiology of suicide in this population has eluded policy makers, researchers, and communities. Although many suicide prevention programs have been developed and implemented, few are evidence-based in their effectiveness in decreasing suicide rates. In one northern California community, adolescent suicide has risen above the state's average. Two nurses led an effort to develop and implement an innovative grassroots community suicide prevention project targeted at eliminating any further teen suicide. The project consisted of a Teen Resource Card, a community resource brochure targeted at teens, and education for the public and school officials to raise awareness about this issue. This article describes this project for other communities to use as a model. Risk and protective factors are described, and a comprehensive background of adolescent suicide is provided.

  11. Comparing Families of Suicide Attempters, Human

    African Journals Online (AJOL)

    Rezaei: Family process and content of suicide attempters and HIV positive patients. Annals of Medical ... the exclusion criteria (psychotic disorders, suicidal ideation, addiction, refusing ..... A review of mood disorders among juvenile offenders.

  12. Suicide in a spinal cord injured population

    DEFF Research Database (Denmark)

    Hartkopp, A; Brønnum-Hansen, Henrik; Seidenschnur, A M

    1998-01-01

    To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI).......To determine the relation between functional status and risk of suicide among individuals with spinal cord injury (SCI)....

  13. Suicide clusters among young Kenyan men.

    Science.gov (United States)

    Goodman, Michael L; Puffer, Eve S; Keiser, Philip H; Gitari, Stanley

    2017-11-01

    Suicide is a leading cause of global mortality. Suicide clusters have recently been identified among peer networks in high-income countries. This study investigates dynamics of suicide clustering within social networks of young Kenya men ( n = 532; 18-34 years). We found a strong, statistically significant association between reported number of friends who previously attempted suicide and present suicide ideation (odds ratio = 1.9; 95% confidence interval (1.42, 2.54); p self-esteem (23% of total effect). Meaning in life further mediated the association between collective self-esteem and suicide ideation. Survivors of peer suicide should be evaluated for suicide risk.

  14. Helplessness, hopelessness, and haplessness and suicidality.

    Science.gov (United States)

    Lester, D

    1998-06-01

    In a sample of 141 college students, scores on depression and suicidal ideation were best predicted by scores on hopelessness, while a history of attempted suicide was best predicated by helplessness.

  15. Tragedy prompts depression awareness, suicide prevention campaigns.

    Science.gov (United States)

    Rees, T

    1998-01-01

    The tragic suicide of Robert C. Goltz prompted associates at the integrated marketing and communications company he founded in Green Bay, Wis., to develop two multimedia campaigns, one focusing on depression awareness and the other on suicide prevention.

  16. Suicide policy in Canada: lessons from history.

    Science.gov (United States)

    Spiwak, Rae; Elias, Brenda; Bolton, James M; Martens, Patricia J; Sareen, Jitender

    2012-07-18

    In Canada, suicide has transitioned from being a criminal activity with much associated stigma, to being a public health concern that needs to be managed by governments and clinicians in a culturally sensitive manner. In Canada and worldwide, the social attitudes toward and legal interpretation of suicide have been dynamic. Much has been proposed in the development of suicide policy in Canada, however Canada is unique in that it remains one of the only industrialized countries without a national suicide prevention strategy. The current article provides a critical review of the history of suicide in Canada, as well as an appraisal of Canadian suicide prevention policies and key government and political milestones that have impacted suicide policy. Current activity regarding a national suicide prevention strategy in Canada is discussed, as well as potential options for clinician involvement.

  17. Contemplated Suicide Among Voluntary and Involuntary Retirees

    Science.gov (United States)

    Peretti, Peter O.; Wilson, Cedric

    1978-01-01

    This study explored anomic and egoistic dimensions of contemplated suicide among voluntary and involuntary retired males. Results indicated a direct relationship between anomie and egoism on the one hand, and contemplation of suicide on the other. (Author)

  18. Suicide in murderers in England and Wales.

    Science.gov (United States)

    Lester, David

    2003-06-01

    In England and Wales, the suicide rate of murderers was positively associated with the male suicide rate in the general population, and both of these rates were positively associated with the unemployment rate.

  19. Insomnia, dreams, and suicide: Connecting links

    Directory of Open Access Journals (Sweden)

    Sagar B Karia

    2016-01-01

    Full Text Available Introduction: A growing empirical literature has examined insomnia symptoms as a possible risk factor for a range of suicidal behavior. Not much literature is available in normal adolescent population. Aims: The aim is to find insomnia prevalence, studying various dream factors, and suicidality prevalence among students of various courses. To check if there is a relation between insomnia and suicidal behavior and dreams, particularly nightmares and suicide. Materials and Methods: A total of 400 students of various courses were assessed using Insomnia Severity Index and The Mannheim Dream Questionnaire and Suicide Behaviour Questionnaire. Results: Insomnia was present in 11%, 23%, 19%, and 19% and suicide behavior in 16%, 17%, 12%, and 22%, respectively, in medical, commerce, engineering, and arts students. Statistically significant correlation was found between suicide and insomnia severity and various dream factors. Conclusions: Insomnia and dreams had relation with suicidality in normal adolescent population.

  20. Lithium and suicide prevention in bipolar disorder.

    Science.gov (United States)

    Benard, V; Vaiva, G; Masson, M; Geoffroy, P A

    2016-06-01

    Bipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations. We conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: "lithium" AND "suicide" OR "suicidality" OR "suicide attempt". As confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The "impulsive-aggressive" endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/β (GSK3α and β; proteins inhibited by Li) seem to

  1. Shame-proneness in attempted suicide patients

    Directory of Open Access Journals (Sweden)

    Wiklander Maria

    2012-05-01

    Full Text Available Abstract Background It has been suggested that shame may be an important feature in suicidal behaviors. The disposition to react with shame, “shame-proneness”, has previously not been investigated in groups of attempted suicide patients. We examined shame-proneness in two groups of attempted suicide patients, one group of non-suicidal patients and one group of healthy controls. We hypothesized that the attempted suicide patients would be more shame-prone than non-suicidal patients and healthy controls. Methods The Test of Self-Conscious Affect (TOSCA, which is the most used measure of shame-proneness, was completed by attempted suicide patients (n = 175: 105 women and 3 men with borderline personality disorder [BPD], 45 women and 22 men without BPD, non-suicidal psychiatric patients (n = 162, and healthy controls (n = 161. The participants were convenience samples, with patients from three clinical research projects and healthy controls from a fourth research project. The relationship between shame-proneness and attempted suicide was studied with group comparisons and multiple regressions. Men and women were analyzed separately. Results Women were generally more shame-prone than men of the same participant group. Female suicide attempters with BPD were significantly more shame-prone than both female suicide attempters without BPD and female non-suicidal patients and controls. Male suicide attempters without BPD were significantly less shame-prone than non-suicidal male patients. In multiple regressions, shame-proneness was predicted by level of depression and BPD (but not by attempted suicide in female patients, and level of depression and non-suicidality in male patients. Conclusions Contrary to our hypothesis and related previous research, there was no general relationship between shame-proneness and attempted suicide. Shame-proneness was differentially related to attempted suicide in different groups of suicide attempters

  2. Rural and urban suicide in South Korea.

    Science.gov (United States)

    Park, B C Ben; Lester, David

    2012-10-01

    Suicide rates in 2005 in South Korea were higher in rural areas than in urban areas. Those in rural areas more often used pesticides and chemicals as a method for suicide, and there was a greater proportion of men and the elderly, both groups at higher risk for suicide in South Korea. These three factors may account for the high rural suicide rate in South Korea.

  3. Self-esteem and suicide risk

    OpenAIRE

    perrot, Clémence

    2015-01-01

    Introduction: Suicide is a major Public Health concern and self-esteem is given growing interest in our society.Objectives: To assess the correlation between self-esteem and suicidal intent, independently of depression, and to examine the relationship between the different dimensions of self-esteem (total, general, familial, professional and social). We also studied whether poor self-esteem was predictive of suicidal risk.Methods: Two studies were conducted among a Suicide Prevention Departme...

  4. Coping Strategies in People Attempting Suicide

    OpenAIRE

    Bazrafshan, Mohammad-Rafi; Jahangir, Fereidun; Mansouri, Amir; Kashfi, Seyyed Hannan

    2014-01-01

    Background: Having a set of effective coping skills can prevent suicidal behavior by increasing self-control and self-direction. This study examines coping styles used by suicidal patients. Objectives: The researchers in this study try to identify coping strategies used by suicide attempters admitted to Shiraz Shahid Faghihi Hospital emergency room. Materials and Methods: This is a analytical cross-sectional study. Participants consisted of 50 suicide-attempted people admitted to Shiraz Faghi...

  5. Insomnia, dreams, and suicide: Connecting links

    OpenAIRE

    Sagar B Karia; Nirali Mehta; Devavrat Harshe; Avinash De Sousa; Nilesh Shah

    2016-01-01

    Introduction: A growing empirical literature has examined insomnia symptoms as a possible risk factor for a range of suicidal behavior. Not much literature is available in normal adolescent population. Aims: The aim is to find insomnia prevalence, studying various dream factors, and suicidality prevalence among students of various courses. To check if there is a relation between insomnia and suicidal behavior and dreams, particularly nightmares and suicide. Materials and Methods: A total of 4...

  6. Suicide in the Early Stage of Schizophrenia

    OpenAIRE

    Ventriglio, Antonio; Gentile, Alessandro; Bonfitto, Iris; Stella, Eleonora; Mari, Massimo; Steardo, Luca; Bellomo, Antonello

    2016-01-01

    Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects w...

  7. Past suicidal ideation as an independent risk factor for suicide behaviours in patients with depression.

    Science.gov (United States)

    Park, Eun-Hee; Hong, Narei; Jon, Duk-In; Hong, Hyun Ju; Jung, Myung Hun

    2017-03-01

    As South Korea has the highest incidence of completed suicides, the present study aimed to investigate the predictive power of the variables that have been associated with suicide attempts in Korean patients diagnosed with depression. Hundred participants were divided into two groups: suicide attempters (31%) and suicide non-attempters (69%). Participants with a history of more than one suicidal attempt were assigned to the suicide attempter group. A hierarchical logistic regression analysis was performed to determine the predictive strengths of the variables that were likely to be associated with suicide attempts. After controlling for the effects of such variables as the severity of depressive symptoms, life stress events and impulsivity, the severity of past suicidal ideation was the most important predictive factor for discriminating suicide attempters from suicide non-attempters. The odds ratio for attempting suicide relative to not attempting suicide increased by a factor of 4.408 for each unit of increase in suicidal ideation. The present study suggests that the most severe suicidal ideation throughout one's entire life should not be overlooked and may be a major predictor of the risk of suicide.

  8. The Relationship between Attitudes toward Suicide and Family History of Suicide in Nagano Prefecture, Japan.

    Science.gov (United States)

    Tsukahara, Teruomi; Arai, Hiroaki; Kamijo, Tomoko; Kobayashi, Yoshikiyo; Washizuka, Shinsuke; Arito, Heihachiro; Nomiyama, Tetsuo

    2016-06-22

    Certain attitudes toward suicide may be a risk factor for suicide among the bereaved. To explore this possibility, we examined the relationship between attitudes toward suicide and family history of suicide. We focused on two specific attitudes indicating resignation in a survey: #1 "When a person chooses to die by suicide, the suicide is inevitable" (i.e., inevitability belief); and #2 "A suicide cannot be stopped by any person, because suicide is unpreventable" (i.e., unpreventable belief). The data of 5117 fully completed questionnaires were analyzed. Logistic regression analysis revealed that the two attitudes of resignation were significantly associated with a family history of suicide. The adjusted odds ratio for #1 was 1.39 (95% CI, 1.07-1.79) for individuals having experienced suicide by a family member or relative, while that for #2 was 1.57 (95% CI, 1.27-1.95) for experiencing a suicide by a family member or relative and 1.25 (95% CI, 1.05-1.49) for experiencing a suicide by a friend, business associate, partner or other. These two attitudes of resignation toward suicide were significantly associated with a family history of suicide. These attitudes might increase suicide risk among the bereaved.

  9. Gender differences in suicide and suicide attempts among US Army soldiers.

    Science.gov (United States)

    Maguen, Shira; Skopp, Nancy A; Zhang, Ying; Smolenski, Derek J

    2015-02-28

    In order to best tailor suicide prevention initiatives and programs, it is critical to gain an understanding of how service members׳ suicide risk factors may differ by gender. We aimed to better understand gender differences in suicide and suicide attempts among soldiers, including demographic, military, mental health, and other risk factors. We also examined risk factors uniquely associated with suicide and suicide attempts. We conducted a retrospective study of 1857 US Army soldiers who died by suicide or attempted suicide between 2008 and 2010 and had a Department of Defense Suicide Event Report. Female and male soldiers had more similarities than differences when examining risk factors associated with suicide. The only gender difference approaching significance was workplace difficulties, which was more strongly associated with suicide for female soldiers, compared to their male counterparts. Among suicide decedents, the most common risk factor was having a failed intimate relationship in the 90 days prior to suicide. Among those who attempted suicide, the most common risk factor was a major psychiatric diagnosis. Better understanding both gender differences and risk factors uniquely associated with suicide has critical prevention and public health implications as we work to better understand preventable mortality in our youngest generation of service members. Published by Elsevier Ireland Ltd.

  10. [Suicidal behaviour and attempted suicide occurring during assessment by the outreach psychiatric emergency service].

    Science.gov (United States)

    de Winter, R F P; de Groot, M H; van Dassen, M; Deen, M L; de Beurs, D P

    The outreach emergency psychiatric service plays an important role in recognising, arranging interventions and preventing suicide and suicidal behaviour. However, little is known about the assessments that members of the emergency team make when faced with patients showing suicidal behaviour. AIM: To describe the relationships that are revealed between patient characteristics, suicidal thoughts and attempted suicide during assessments made by the emergency psychiatric service in The Hague. METHOD: The emergency service kept a detailed record of 14,705 consultations. We compared the characteristics of patients who had suicidal thoughts with those of patients who had no such thoughts and we also compared the characteristics of patients who had attempted to commit suicide with those of patients who had not. We drew these comparisons by using logistic regression models, adjusting for clustering. RESULTS: 32.2% of the patients showed signs of suicidal behaviour and 9.2 % appeared likely to attempt suicide. Suicidal behaviour occurred most often in patients with depression. Suicidal patients were more often admitted to hospital than were non-suicidal patients and they were more likely to have been referred by a general practitioner or a general hospital. Medication was the most frequent means employed in attempts to commit suicide. CONCLUSION: In about one third of the consultations of the outreach emergency psychiatric service, the patient showed suicidal behaviour. The actions and the policy of the emergency psychiatric service with regard to suicidal behaviour were diverse and dependent on factors that could change over the course of time.

  11. Prostate-Specific and Tumor-Specific Targeting of an Oncolytic HSV-1 Amplicon/Helper Virus for Prostate Cancer Treatment

    Science.gov (United States)

    2009-11-01

    regulation HSV-1 amplicon and recombinant viruses Molecular cloning Cell culture/gene transfection Xenograft mouse model Histology 20...no herpetic lesions were seen in CMV-ICP4-143T–treated and CMV-ICP4-145T– treated animals, although some gastritis developed 28 days after the viral

  12. CROSS-CULTURAL ATTITUDES TOWARDS SUICIDE AMONG ...

    African Journals Online (AJOL)

    hi-tech

    2000-03-01

    Mar 1, 2000 ... East African Medical Journal Vol. 77 No. 3 March 2000 ... X1106, Sovenga 0727, South Africa. Request for ... pupils among three cultural groups in South Africa. Design: .... increased risk of suicidal behaviour among Asian and ... cultural transition: suicidal behaviour in South African Indian women. Suicide ...

  13. Suicide intervention training evaluation: a preliminary report.

    Science.gov (United States)

    Tierney, R J

    1994-01-01

    To date, very little work has been done on evaluating training in suicide intervention. This study developed and piloted a comprehensive method for evaluating suicide intervention training by applying three studies of immediate training effects on (a) suicide intervention abilities, (b) attitudes to suicide and suicide intervention, and (c) knowledge about suicide. The focus of the evaluation was a broadly used 2-day suicide intervention training program. Changes in suicide intervention abilities were measured by the Suicide Intervention Response Inventory (SIRI) and by performance in simulated suicide intervention situations, scored with the Suicide Intervention Protocol (SIP). Subjects consisted of 19 workshop participants in a pre-post condition and 17 participants in a post-test only condition. Results indicated significant increases in skills in suicide intervention situations. No significant effects were noted on the SIRI. Results from the attitudes and knowledge studies were very preliminary. They are reported here so that others may become aware of the methodology being used and the status of evaluation of the target program. Implications for further research are discussed.

  14. Dependent Children and Suicide of Married Parents.

    Science.gov (United States)

    Kozak, Conrad M.; Gibbs, James O.

    1979-01-01

    Single suicides and married suicides with dependent children were compared to similar groups in the general population. Married people with dependent children experienced the lowest average suicide rate, but had a larger mean number of children than the population as a whole. (Author)

  15. Continuing Bonds after Suicide Bereavement in Childhood

    Science.gov (United States)

    Wood, Lindsey; Byram, Victoria; Gosling, A. Sophie; Stokes, Julie

    2012-01-01

    It has been argued that the grieving process after suicide bereavement has unique properties (e.g., J. R. Jordan, 2001). A qualitative study was conducted to explore one aspect of the grieving process--continuing bonds--after suicide bereavement in childhood. Data were collected through semi-structured interviews with 10 suicide-bereaved children…

  16. Suicide Prevention with Diverse College Students

    Science.gov (United States)

    Shadick, Richard; Akhter, Sarah

    2014-01-01

    Because of a dearth of experience in preventing suicide in diverse student populations, Pace University developed a multicultural suicide prevention kit. This article details the process used to develop the kit. The rationale for approaching suicide prevention in a culturally competent manner is presented, and methods used to gain culture-specific…

  17. The use of technology in suicide prevention

    NARCIS (Netherlands)

    Boonstra, T.W.; Larsen, M.E.; Cummins, N.; O'Dea, B.; Tighe, J.; Nicholas, J.; Shand, F.; Epps, J.; Christensen, H.

    2015-01-01

    Suicide is one of the leading causes of death globally, and is notably a significant cause of death amongst young people. A suicide outcome is a complex combination of personal, social, and health factors, and therefore suicide prevention is a challenge, requiring a systems approach incorporating

  18. Air Force Medical Service > Resources > Suicide Prevention

    Science.gov (United States)

    Health Suicide Prevention ACE Questions Risk Factors Warning Signs Protective Factors Helping Resources Force Social Media Guide (PDF) USAF Social Media Sites Suicide Prevention Banner prevnext General . What do you need to know to effectively raise awareness about suicide prevention? Daily connections can

  19. Posttraumatic stress disorder diagnostic criteria and suicidal ...

    African Journals Online (AJOL)

    Objective: Exposure to traumatic events may precipitate suicidal ideation. Once an individual is diagnosed with PTSD, a suicide risk assessment often follows. This study explores how PTSD symptom criteria correlate with suicidal ideation in a sample of police officers. While the psychometric measures of PTSD often mirror ...

  20. Traumatic Stress as a Predictor of Suicidality

    Science.gov (United States)

    Todd, Sherry Malana

    2009-01-01

    Suicide is a deliberate act of annihilation against one's self due to a crisis of problem solving. Far too many youth are dying by their own hands resulting in suicide being the third leading cause of death for 10-19 year olds (CDC, 2005). Suicide is particularly problematic for adolescents due to the impulsivity inherent in adolescent…

  1. Sexual Orientation in Adolescents Who Commit Suicide.

    Science.gov (United States)

    Shaffer, David; And Others

    1995-01-01

    Examined relationship between suicidal behavior and homosexuality in adolescence in an unselected, matched sample. Found no evidence that suicide is a common characteristic of gay youth, or that when suicide does occur among gay teenagers, that it is a direct consequence of stigmatization or lack of support. (JBJ)

  2. Suicide Notes in Hong Kong in 2000

    Science.gov (United States)

    Wong, Paul W. C.; Yeung, April W. M.; Chan, Wincy S. C.; Yip, Paul S. F.; Tang, Arthur K. H.

    2009-01-01

    Suicide notes have been regarded as one of the most informative data sources to understand the reasons why people commit suicide. However, there is a paucity of suicide note studies, leaving researchers with an assumption that this phenomenon remains static over time. This study examines this assumption by comparing the characteristics of…

  3. The Literacy Educator's Role in Suicide Prevention

    Science.gov (United States)

    Fisher, Douglas

    2005-01-01

    Suicide, the second leading cause of death for adolescents in the United States, is preventable. Nearly 80% of individuals who commit suicide have demonstrated signs well in advance. Adolescent suicide prevention efforts require collaboration with teachers--individuals who know students well. Literacy educators have a role in suicide…

  4. Childhood Suicide and Myths Surrounding It.

    Science.gov (United States)

    Greene, Dorothea B.

    1994-01-01

    Dispels five misconceptions surrounding the suicide of children: that children under the age of six do not commit suicide; that suicide in latency years is extremely rare; that psychodynamically and developmentally true depression is not possible in childhood; that child cannot understand finality of death; and that children are cognitively and…

  5. Depression and Suicide in Schizophrenic Patients.

    Science.gov (United States)

    Salama, Aziz A.

    1988-01-01

    Identified schizophrenic patients as distinctive subgroup of patients who can suffer from major depressive illness and can commit suicide. Found 22.4 percent of 620 schizophrenics in psychiatric facility showed symptoms of major depressive episode. Seven patients committed suicide during acute phase of illness, 9 attempted suicide while…

  6. Risk Factors for Attempting Suicide in Prisoners

    Science.gov (United States)

    Sarchiapone, Marco; Carli, Vladimir; Di Giannantonio, Massimo; Roy, Alec

    2009-01-01

    We wished to examine determinants of suicidal behavior in prisoners. 903 male prisoners had a psychiatric interview which included various psychometric tests. Suicide attempters were compared with prisoners who had never attempted suicide. Significantly more of the attempters had a history of psychiatric disorder, substance abuse, a family history…

  7. A Rational Approach to Rational Suicide.

    Science.gov (United States)

    Richman, Joseph

    1992-01-01

    Describes suicide as reaction to internal and external sources of stress and the impact of life events. Notes that, in the elderly, these situations are prevalent in many who are not suicidal. Contends that much more is written about rational suicide than its alternative (rational nonsuicide). Reviews reasons for this and suggests rational…

  8. Youth Suicide Risk and Sexual Orientation.

    Science.gov (United States)

    Rutter, Philip A.; Soucar, Emil

    2002-01-01

    Study examines the relationship between sexual orientation and youth suicide risk. The suicide risk demonstrated by sexual minorities in this study was no greater than that of their heterosexual peers. Youth who reported more external support demonstrated lower overall suicide risk and, specifically, lower levels of hostility, hopelessness, and…

  9. Inpatient Suicide in a Chinese Psychiatric Hospital

    Science.gov (United States)

    Li, Jie; Ran, Mao-Sheng; Hao, Yuantao; Zhao, Zhenhuan; Guo, Yangbo; Su, Jinghua; Lu, Huixian

    2008-01-01

    Little is known about the risk factors for suicide among psychiatric inpatients in China. In this study we identified the risk factors of suicide among psychiatric inpatients at Guangzhou Psychiatric Hospital. All psychiatric inpatients who died by suicide during the 1956-2005 period were included in this study. Using a case-control design, 64…

  10. An Inquiry into Relationship Suicides and Reciprocity

    Science.gov (United States)

    Davis, Mark S.; Callanan, Valerie J.; Lester, David; Haines, Janet

    2009-01-01

    Few theories on suicide have been grounded in the norm of reciprocity. There is literature on suicide, however, describing motivations such as retaliation and retreat which can be interpreted as modes of adaptation to the norm of reciprocity. We propose a reciprocity-based theory to explain suicides associated with relationship problems. Employing…

  11. Getting Real about Suicide Prevention in Schools

    Science.gov (United States)

    Schiro, Theodora

    2018-01-01

    After her son died by suicide, Theodora Schiro vowed to raise awareness and teach others about depression and suicide. In this article, Schiro (a former teacher and principal) explains how educators can detect warning signs, devise preventative programs, and fight the stigma associated with suicide.

  12. Bullying and suicidal behavior in jails.

    NARCIS (Netherlands)

    Blaauw, E.; Winkel, F.W.; Kerkhof, A.J.F.M.

    2001-01-01

    Relationships between bullying features and suicidal behavior of inmates were examined. The files of 95 suicide victims in jails and prisons in the Netherlands were examined for reports of bullying. In addition, 221 nonsuicidal jail inmates and 53 suicidal jail inmates were interviewed. The files of

  13. Suicide in South Asia: a scoping review

    NARCIS (Netherlands)

    Jordans, Mark J D; Kaufman, Anne; Brenman, Natassia; Adhikar, Ramesh; Luitel, Nagendra; Tol, Wietse; Komproe, Ivan

    2014-01-01

    Background Globally, suicide is an important cause of mortality. In low- and middle income settings, it is difficult to find unequivocal data to establish suicide rates. The objective of this review is to synthesize the reporting of suicide incidence in six south Asian countries. Methods We

  14. College Students' Reasons for Concealing Suicidal Ideation

    Science.gov (United States)

    Burton Denmark, Adryon; Hess, Elaine; Becker, Martin Swanbrow

    2012-01-01

    Self-reported reasons for concealing suicidal ideation were explored using data from a national survey of undergraduate and graduate students: 558 students indicated that they seriously considered attempting suicide during the previous year and did not tell anyone about their suicidal thoughts. Content analysis of students' qualitative responses…

  15. Suicidal Ideation in Anxiety-Disordered Youth

    Science.gov (United States)

    O'Neil, Kelly A.; Puleo, Connor M.; Benjamin, Courtney L.; Podell, Jennifer L.; Kendall, Philip C.

    2012-01-01

    Evidence is mixed regarding an independent association between anxiety and suicidality in youth. Study 1 examined suicidal ideation in treatment-referred, anxiety-disordered youth (N = 312, aged 7-17). Forty-one percent of anxiety-disordered youth endorsed suicidal ideation. Anxiety disorder severity, global impairment, and current depressive…

  16. Associations between the neuron-specific glucocorticoid receptor (NR3C1) Bcl-1 polymorphisms and suicide in cancer patients within the first year of diagnosis.

    Science.gov (United States)

    Park, Subin; Hong, Jin Pyo; Lee, Jong-Keuk; Park, Young-Mi; Park, Yangsoon; Jeon, Juri; Ahn, Myeong Hee; Yoon, Se Chang

    2016-07-11

    Cancer diagnosis is associated with an increased suicide risk, particularly within the first 1 year after diagnosis of cancer. Abnormal function of the hypothalamic-pituitary-adrenal axis has been implicated in the pathophysiology of depression and suicide. We examined genetic associations of the functional Bcl-1 polymorphism of (rs41423247) neuron-specific glucocorticoid receptor (NR3C1) gene, with death by suicide in cancer patients. Suicides occurring within a year of cancer diagnosis ('early suicide') were considered separately from those suicides during the second or subsequent year ('late suicide') after cancer diagnosis. The subjects consisted of 343 cancer patients admitted to a general hospital in Seoul, South Korea from 1996 to 2009, of which 182 had died by suicide and 161 were alive on December 31, 2009. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sample of patients with cancer. We conducted a case-control association analysis of Bcl-1 polymorphism of NR3C1 gene. Subjects carrying the GG genotype of Bcl-1 polymorphism were at increased risk of early suicide when compared to those carrying the CC genotype (OR 3.80, 95 % CI 1.02-14.16, p = .047). Similarly, those individuals carrying the GG genotype (recessive mode) had an increased risk of early suicide relative to the CC or CG genotype (OR 3.71, 95 % CI 1.03-13.43, p = .045). However, there were no differences in the genotype distributions of the NR3C1 Bcl-1 polymorphism between late suicide cases and controls. Our findings suggest that the NR3C1 Bcl-1 polymorphisms may be involved in the susceptibility to suicide within the first year after cancer diagnosis among cancer patients in Korean population.

  17. The Evolutionary Puzzle of Suicide

    Directory of Open Access Journals (Sweden)

    Henri-Jean Aubin

    2013-12-01

    Full Text Available Mechanisms of self-destruction are difficult to reconcile with evolution’s first rule of thumb: survive and reproduce. However, evolutionary success ultimately depends on inclusive fitness. The altruistic suicide hypothesis posits that the presence of low reproductive potential and burdensomeness toward kin can increase the inclusive fitness payoff of self-removal. The bargaining hypothesis assumes that suicide attempts could function as an honest signal of need. The payoff may be positive if the suicidal person has a low reproductive potential. The parasite manipulation hypothesis is founded on the rodent—Toxoplasma gondii host-parasite model, in which the parasite induces a “suicidal” feline attraction that allows the parasite to complete its life cycle. Interestingly, latent infection by T. gondii has been shown to cause behavioral alterations in humans, including increased suicide attempts. Finally, we discuss how suicide risk factors can be understood as nonadaptive byproducts of evolved mechanisms that malfunction. Although most of the mechanisms proposed in this article are largely speculative, the hypotheses that we raise accept self-destructive behavior within the framework of evolutionary theory.

  18. The Impact of BDNF Polymorphisms on Suicidality in Treatment-Resistant Major Depressive Disorder: A European Multicenter Study.

    Science.gov (United States)

    Schosser, Alexandra; Carlberg, Laura; Calati, Raffaella; Serretti, Alessandro; Massat, Isabel; Spindelegger, Christoph; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

    2017-10-01

    Numerous studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders, including suicidal behavior, although with conflicting results. A total of 250 major depressive disorder patients were collected in the context of a European multicenter resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression, and treatment response using the HAM-D. Genotyping was performed for the functional Val66Met polymorphism (rs6265) and 7 additional tagging single nucleotide polymorphisms within the BDNF gene. Neither BDNF single markers nor haplotypes were found to be associated with suicide risk and lifetime history of suicide attempts. Gender-specific analyses revealed nonsignificant single marker (rs908867) and haplotypic association with suicide risk in males after multiple testing correction. Analyzing treatment response phenotypes, the functional Val66Met polymorphism as well as rs10501087 showed significant genotypic and haplotypic association with suicide risk in remitters (n=34, 13.6%). Considering the sample size, the present findings need to be replicated in larger samples to confirm or refute a role of BDNF in the investigated suicidal behavior phenotypes. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  19. Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment.

    Science.gov (United States)

    Levey, D F; Niculescu, E M; Le-Niculescu, H; Dainton, H L; Phalen, P L; Ladd, T B; Weber, H; Belanger, E; Graham, D L; Khan, F N; Vanipenta, N P; Stage, E C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R; Niculescu, A B

    2016-06-01

    Women are under-represented in research on suicidality to date. Although women have a lower rate of suicide completion than men, due in part to the less-violent methods used, they have a higher rate of suicide attempts. Our group has previously identified genomic (blood gene expression biomarkers) and clinical information (apps) predictors for suicidality in men. We now describe pilot studies in women. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation (no SI) and high suicidal ideation (high SI) states (n=12 participants out of a cohort of 51 women psychiatric participants followed longitudinally, with diagnoses of bipolar disorder, depression, schizoaffective disorder and schizophrenia). We then used a Convergent Functional Genomics (CFG) approach to prioritize the candidate biomarkers identified in the discovery step by using all the prior evidence in the field. Next, we validated for suicidal behavior the top-ranked biomarkers for SI, in a demographically matched cohort of women suicide completers from the coroner's office (n=6), by assessing which markers were stepwise changed from no SI to high SI to suicide completers. We then tested the 50 biomarkers that survived Bonferroni correction in the validation step, as well as top increased and decreased biomarkers from the discovery and prioritization steps, in a completely independent test cohort of women psychiatric disorder participants for prediction of SI (n=33) and in a future follow-up cohort of psychiatric disorder participants for prediction of psychiatric hospitalizations due to suicidality (n=24). Additionally, we examined how two clinical instruments in the form of apps, Convergent Functional Information for Suicidality (CFI-S) and Simplified Affective State Scale (SASS), previously tested in men, perform in women. The top CFI-S item distinguishing high SI from no SI states was the chronic stress of social isolation. We

  20. Proximal risk factors and suicide methods among suicide completers from national suicide mortality data 2004-2006 in Korea.

    Science.gov (United States)

    Im, Jeong-Soo; Choi, Soon Ho; Hong, Duho; Seo, Hwa Jeong; Park, Subin; Hong, Jin Pyo

    2011-01-01

    This study was conducted to examine differences in proximal risk factors and suicide methods by sex and age in the national suicide mortality data in Korea. Data were collected from the National Police Agency and the National Statistical Office of Korea on suicide completers from 2004 to 2006. The 31,711 suicide case records were used to analyze suicide rates, methods, and proximal risk factors by sex and age. Suicide rate increased with age, especially in men. The most common proximal risk factor for suicide was medical illness in both sexes. The most common proximal risk factor for subjects younger than 30 years was found to be a conflict in relationships with family members, partner, or friends. Medical illness was found to increase in prevalence as a risk factor with age. Hanging/Suffocation was the most common suicide method used by both sexes. The use of drug/pesticide poisoning to suicide increased with age. A fall from height or hanging/suffocation was more popular in the younger age groups. Because proximal risk factors and suicide methods varied with sex and age, different suicide prevention measures are required after consideration of both of these parameters. Copyright © 2011 Elsevier Inc. All rights reserved.