Adolescent suicide risk factors and the integration of socialemotional skills in school-based prevention programs

Adolescents are considered one of the most vulnerable groups affected by suicide.Rapid changes in adolescents’physical and mental states,as well as in their lives,significantly and undeniably increase the risk of suicide.Psychological,social,family,individual,and environmental factors are important risk factors for suicidal behavior among teenagers and may contribute to suicide risk through various direct,indirect,or combined pathways.Social-emotional learning is considered a powerful intervention measure for addressing the crisis of adolescent suicide.When deliberately cultivated,fostered,and enhanced,selfawareness,self-management,social awareness,interpersonal skills,and responsible decision-making,as the five core competencies of social-emotional learning,can be used to effectively target various risk factors for adolescent suicide and provide necessary mental and interpersonal support.Among numerous suicide intervention methods,school-based interventions based on social-emotional competence have shown great potential in preventing and addressing suicide risk factors in adolescents.The characteristics of school-based interventions based on social-emotional competence,including their appropriateness,necessity,cost-effectiveness,comprehensiveness,and effectiveness,make these interventions an important means of addressing the crisis of adolescent suicide.To further determine the potential of school-based interventions based on social-emotional competence and better address the issue of adolescent suicide,additional financial support should be provided,the combination of socialemotional learning and other suicide prevention programs within schools should be fully leveraged,and cooperation between schools and families,society,and other environments should be maximized.These efforts should be considered future research directions.

Suicide risk in juvenile open angle glaucoma patients

AIM:To investigate the association between juvenile open angle glaucoma(JOAG)and mental health among Koreans.METHODS:This study used nationally representative data from the 8th Korea National Health and Nutrition Examination Survey(KNHANES)2021.Glaucoma diagnosis followed the International Society of Geographical and Epidemiological Ophthalmology criteria based on glaucomatous structural defects,visual field defects,corrected vision,and intraocular pressure.As outcomes,suicidal behaviors,psychiatric counseling,and depression were evaluated through mental health questionnaires.Odds ratios(ORs)with 95%confidence intervals(CIs)were estimated using logistic regression models,adjusting for covariates.RESULTS:Among 7090 participants,3446 met the inclusion criteria for analysis,and 88(2.6%)were diagnosed with open angle glaucoma(OAG).After adjusting for age,sex,and best-corrected visual acuity(VA),participants with OAG were revealed to have significantly higher odds of suicidal behaviors(i.e.,ideation,planning,or attempts)compared with those without OAG(OR:2.70;95%CI:1.12-6.54;P=0.028).This association remained significant after further adjustments for socioeconomic status,lifestyle factors,and presence of chronic conditions(P=0.031 and 0.035,respectively).However,there was no significant difference for the other two outcomes,psychiatric counseling and depression.An age-stratified analysis revealed a stronger association between OAG and suicidal behaviors in younger JOAG participants(<40y)than in older OAG participants(≥40y;OR:3.80 vs 2.22;95%CI:0.79-18.22 vs 0.56-8.80,respectively).CONCLUSION:OAG patients show a higher risk of suicidal behaviors than those without glaucoma particularly in JOAG patients.

Suicide Ideation and Its Associated Factors among Men in Selected Compounds of Lusaka, Zambia

Background: Globally, it is estimated that more than 800,000 individuals die by suicide each year, making suicide one of the biggest causes of death worldwide. Additionally, suicide kills far more males than women, more so in developing regions that are characterized by economic distress due to low income. Although the number of suicide cases has been seen to increase from 2013 to date, limited studies provide information on the factors influencing the trend. Therefore, this study aimed at investigating the prevalence of suicidal ideation and factors associated with suicide in males in selected compounds of Lusaka. Methods: The study used an analytical quantitative cross- sectional study design that involved 367 men in Mtendere and Kaunda Square townships in Lusaka district, Zambia. A structured questionnaire was used to collect data from participants, which was analyzed using Statistical Package for Social Sciences (SPSS) version 26.0. The Chi-square, Fisher’s exact test and Wilcoxon rank sum tests were used to test relationships among variables at a five percent level of significance. Ethical approval and clearance was obtained from the National Health Research Authority. Results: Participants had a median age of 29 years (IQR, 27 - 32 years), 216 (58.9%) were single and 278 (75.8%) attained tertiary education. Under a quarter, 75 (20.4%) reported suicide ideations, and 97 (26.4%) reported low social support. For most participants, 347 (94.7%) experienced at least one stressful life event, and 359 (97.8%) experienced severe levels of stress. Under half, 170 (46.3%) were alcohol dependent, while 54 (14.7%) used alcohol harmfully. Suicide ideation was significantly associated with marital status (p Conclusion: Suicide ideation is relatively high among men in Mtendere and Kaunda Square townships, mainly influenced by marital status, education level, social support, stressful events alcohol abuse. Efforts must be channeled towards suicide awareness campaigns, and establishment of supportive environments in health facilities which can make it easy for men to open up about their struggles.

Lethal means and suicide prevention among military veterans

Dear Editor,Suicide amongst the military veteran population is a significant publichealthproblemintheUnitedStates.TheNational VeteranSuicidePreventionAnnualReportrevealedthat6261 died by suicide in 2019[1]. The lingering effects of the coronavirus disease 2019 (COVID-19) pandemic may account for an increase in veteran suicide rates[1].

Mental health implications of suicide rates in South Africa

Mental health challenges are a severe issue that could lead to suicide if not properly addressed.South Africa has a significant burden of mental health issues,which contributes to the soaring rate of suicide.Adequate mental health-care provision could reduce the high suicide rate in South Africa.Since the apartheid regime,the country has made a series of efforts to improve mental health.This study aimed to review and examine available literature on mental health and suicide issues in South Africa and demonstrate the policy implications.This study adopted a narrative review approach.Electronic databases(PubMed,Scilit,Google Scholar and Semantic Scholar)were used to identify published articles in the English language with crucial search terms that included mental health,South African mental health policy,South Africa,suicide and policy.Literature suggests that at the provincial level,there are no adequate mental health policies,and the implementation of the country’s mental health policy is faced with many challenges,such as a shortage of professionals and finances.The review also showed that task sharing and counselling have been pilot-tested and shown to be effective methods for the prevention of mental illness and promotion of positive mental health.This study concludes that the mental health treatment gap still exists in South Africa,and this needs to be tackled using effective,multi-level counselling interventions and policy initiatives.Adequate mental health-care provision and effective implementation of mental health policy could reduce the high rate of suicide in South Africa.

Suicide Attempts in a General Hospital: A Case-Control

Objective: This study aims is to conduct a comparative analysis of the clinical and sociodemographic profiles of individuals referred to Consultation-Liaison Psychiatry (CLP) at a tertiary general hospital, specifically focusing on those seeking assistance due to suicide attempts (TS) versus CLP requests for other reasons (non-TS) between the years 2010 and 2020. Additionally, we aim to assess factors associated with suicide attempts. Method: This retrospective controlled study involves a thorough examination of medical records encompassing 3913 patients who received CLP services at the Hospital de Base (HB) and the Children and Maternity Hospital (HCM) of São José do Rio Preto Medical School Foundation (Funfarme) from June 2010 to June 2020. The patient cohort is categorized into two groups: those with requests for SA (n = 677) and those with requests for other reasons. Results: In the SA group, as opposed to the non SA group, statistically significant differences were observed for gender (predominantly female), employment status (employed), marital status (single), and age (younger). Notably, a higher prevalence of psychiatric antecedents (88.7%, n = 555 vs. 73.6% n = 2018) was found in the SA group, indicating a significant association. The frequency of SA requests remained stable over the years. Among the SA group, mood disorders were the most prevalent (39%, n = 372), followed by disorders related to substance use (21.2%, n = 202), and personality disorders (16%, n = 152). A history of previous suicide attempts emerged as a crucial factor for the recurrence of SA (p-value ≤ 0.001). Exogenous intoxication emerged as the most frequently employed method in attempts (79.6%, n = 539), particularly prevalent among patients diagnosed with mood disorders (41%, n = 314). A significant association was observed between the method of attempt and the nosological psychiatric diagnosis (χ2 = 42.277;p ≤ 0.001). Regarding outcomes, the majority of patients were referred for outpatient follow-up (23%, n = 336) in specialized mental health services or at the Primary Healthcare Unit, highlighting the general hospital’s pivotal role in integrating patients into the broader healthcare network. Conclusion: Variables such as gender (female), age group (young adults), and psychiatric history exhibited stronger associations with suicide attempts compared to the group assisted by CLP for other reasons. Furthermore, a noteworthy correlation between the method employed and the psychiatric diagnosis was identified.

The Utility of Artificial Intelligence for Mood Analysis,Depression Detection,and Suicide Risk Management

Mood disorders are often an indication or a sign of depression,and individuals suffering from mood swings may face higher probability and increased suicidal tendencies.Depression-also called“clinical depression”or a“depressive disorder”-is a mood disorder that adversely impacts how an individual feels,thinks,and handles daily activities,such as sleeping,eating,or working.To be diagnosed with depression,symptoms must be present most of the time,nearly every day for at least minimum of 2 to 3 weeks.Feeling sad or having low emotional energy may be common among people.For most,however,these feelings are transitory and can be managed by changing daily life routines.But for some,prolonged mood disorders can lead to depression and foster suicidal tendencies.Suicide is a major public health concern.Over 47,000 people died by suicide in the United States in 2017.It is the 10th leading cause of death overall according to NIMH(National Institute of Mental Health).Suicide is complicated and tragic,but it is often preventable.Identifying the warning signs for suicide and how to get help can be a major mitigating factor.In this short communication,we are reviewing the promise and limitations of AI(artificial intelligence)with its integrated tools such as ML(machine learning)and DL(deep learning)for mood analysis as a means for detecting early signs of depression and increased suicidal tendencies for possible suicide risk management.

Suicide in Digestive System Cancers: A Scoping Review

Digestive system cancers are important causes of morbidity and mortality worldwide.Cancer patients are more likely to commit suicide.The objective of this scoping review is to provide a comprehensive and updated summary of the existing literature on suicide among patients with digestive system cancers to identify the incidence and risk factors relevant to suicide in these populations.The PRISMA-Scr(Preferred Reporting Items for Systematic reviews and Meta-Analyses extension protocol for scoping reviews)protocol was used.The review was based on relevant articles published prior to January 2022 in databases of Web of Science and PubMed.The authors identified 21 records that met the criteria for inclusion.Among the 21 articles,18(n=85.7%)reported suicide risk factors,21(n=100%)evaluated the incidence of suicide and 16(n=76.2%)involved the variation in suicide rates.Only one study comprehensively reported that the suicide rate for this population was 32.8 per 100,000 years and the standardized mortality ratio(SMR)was 1.91.Most suicides occurred in patients with pancreatic,esophageal,and gastric cancers.The factors associated with suicide in digestive system cancers included male gender,older age,the white race,single status,advanced stage of disease,and cancer metastasis.The most critical time for suicide was in the early post-diagnostic period.It is indispensable to identify suicide in these cancer patients,especially those with high-risk factors.In the future,more prospective research may be needed to provide more reliable support and care to prevent suicide.

Multidimensional Approach to Suicide Prevention in Jails and Prisons: The Best Defense against Liability Lawsuits

Inmates in jails and prisons are a high-risk group for suicide. Often, legal claims of medical negligence and §1983 based on deliberate indifference by the correctional officials follow. Unique stable and dynamic factors and circumstances and their interaction explain most suicides. A systematic suicide screening using a well-designed suicide screening questionnaire that captures known risk factors will identify most inmates at risk if adequately used. Identification and subsequent mental health assessment set the stage for preventive intervention, monitoring, and treatment of the inmates. A multidimensional suicide prevention program saves not only lives but also the best defense against a liability lawsuit.

Understanding the Unique Characteristics of Suicide in China: National Psychological Autopsy Study

Objective To compare the characteristics of suicides in the four main demographic groups： urban males, urban females, rural males and rural females in order to help clarify the demographic pattern of suicides in China. Methods A detailed psychological autopsy survey instrument was independently administered to 895 suicide victims in family members and close associates from 23 geographically representative locations from around the country. Results Pesticide ingestion accounted for 58% （519） of all suicides and 61% （3181519） of deaths were due to unsuccessful medical resuscitation. A substantial proportion （37%） of suicide victims did not have a mental illness. Among the 563 victims with mental illness, only 13% （76/563） received psychiatric treatment. Compared to other demographic groups, young rural females who died from suicide had the highest rate of pesticide ingestion （79%）, the lowest prevalence of mental illness （39%）, and the highest acute stress from precipitating life events just prior to the suicide. Contusion Many suicides in China are impulsive acts of deliberate self-harm following acute interpersonal crises. Prevention of suicides in China must focus on improving awareness of psychological problems, improving mental health services, providing alternative social support networks for managing acute interpersonal conflicts, limiting access to pesticides, and improving the resuscitation skills of primary care providers.

Prevalence and associated factors of suicide among hospitalized schizophrenic patients

BACKGROUND Previous studies found several factors associated with suicide in schizophrenic patients,such as age,sex,education level,history of suicide attempts,psychotic symptoms,social factors,and substance abuse.However,there might be some additional factors that were not considered in previous studies but may be correlated with a greater likelihood of suicide attempts,such as medication and treatment.AIM To investigate the prevalence of suicide attempts and identify the risk of suicidality in hospitalized schizophrenia patients.METHODS This is a cross-sectional study of schizophrenic patients admitted to a psychiatric hospital who were 18 years of age or more.The outcomes and possible suicide risk factors in these patients were collated.The current suicide risk was evaluated using the mini-international neuropsychiatric interview module for suicidality and categorized as none(0 points),mild(1-8 points),moderate(9-16 points),or severe(17 or more points).This study used ordinal logistic regression to assess the association of potential risk factors with the current suicide risk in schizophrenic patients.RESULTS Of 228 hospitalized schizophrenia patients,214(93.9%)were included in this study.The majority(79.0%)of patients were males.Females appeared to have a slightly higher suicidality risk than males,with borderline significance.With regard to the current suicide risk assessed with the mini-international neuropsychiatric interview,172(80.4%)schizophrenic patients scored zero,20(9.4%)had a mild risk,8(3.7%)had a moderate risk,and 14(6.5%)had a severe risk.The total prevalence of current suicide risk in these schizophrenic patients was 19.6%.Based on multivariable ordinal logistic regression analysis with backward elimination,it was found that younger age,a current major depressive episode,receiving fluoxetine or lithium carbonate in the previous month,or a relatively higher Charlson comorbidity index score were all significantly and independently associated with a higher level of suicide risk.CONCLUSION The prevalence rate of suicide attempts in schizophrenia is high.Considering risk factors in routine clinical assessments,environmental manipulations and adequate treatment might prevent or decrease suicide in these patients.

Newspaper Reporting of Suicide Impact on Rate of Suicide in the Contemporary Society in Sri Lanka

Suicide has been largely investigated by many researchers in a variety of perspectives. The objective of this study is to identify the relationship between the rate of suicide in contemporary society and how it can be affected by the way of suicide reporting at the same time. Qualitative method is used to analysis the data capturing from observation, interviews and textual analysis. Special attention has been paid to the news reporting in the suicide in Sri Lankan newspapers. Sinhala medium newspapers： Lankadeepa, Diwaina, Lakbima, Silumina, Dinamina, Rivira, were used as the major sample of this study. Time period is located from January 2000 to January 2010. In conclusion, Suicide has been reporting in Sri Lanka as a heroic and sensational action for the target of maximum selling and the financial benefit of media institutions. Use of Language in suicide reporting and the placement of the story in the newspaper have been two major factors that cause to glamorize the incident. Suicide reporting is highly sensational and rhetorically made by the ownership of the media and non-ethical consideration of the journalism in Sri Lanka. Victims and vulnerable are encouraged to get in to suicide and they are generally encouraged to their action for faith. Suicide should be reported in the newspaper as a problem of mental health and attention should be drawn to well inform the public on the issue. Human incidents should not be reported in media for cheap commercial purposes that indirectly chance to gain much financial profit through the highest selling and expansion. This study suggest to take necessary action to immediately make a frame of ethics of media reporting that avoids such unethical reporting in the practice of suicide reporting in Sri Lanka.

Mental Health, Religion and Suicide

Suicide is one of the most common yet serious concerns, and a worldwide subject that individuals have debated from the past to the present. Suicidal ideation affects and disrupts the functionality of a human being regardless of age, gender, ethnicity, or even religion. This article aims to discuss suicide in general and from an Islamic perspective in specific, as research has shown that an Islamically oriented approach and intervention works better with the Muslim population in general. The paper also aims to have a broader view of how Islam categorized suicide classically and its modern implications, which also lets us explore the similarities, and differences between the Islamic perspective and different religions about suicide and related mental health concerns. A collection of both classic and modern sources was used to extract information and provide a scope of definitions to clarify suicide and religiosity concerning the teachings and opinion of Islam about the meaning of life, afterlife, and soul. It was found that the Muslim population showed a lower rate of suicide in comparison to individuals from other religions, and religious individuals showed faster recovery from suicidal ideation. Yet, Muslims are not immune to mental health conditions that would result in suicide. Therefore, further studies and research need to be conducted to understand the huge stigma around Muslim about mental health and suicide in the Muslim communities, to compare the effectiveness among the religious and the non-religious Muslims, and lastly to fill the gap as to why the Muslim population tends to be hesitant in seeking help regarding their psychological problems.

Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

Trends in Suicide by Poisoning in China 2000-2006: Age, Gender, Method, and Geography

Objective This study analyzed patterns of suicide and suicide attempts by poisoning as reported through a national poison control system for the purpose of improving intervention and prevention. Methods During the period of 2000 to 2006, 6440 cases of poisoning suicide were reported to the telephone consultation service system of The National Center for Poisoning Control （Chinese Center for Disease Control and Prevention）. Among these records, 4728 cases had completed data for this analysis in terms of age, sex, trend of time and location, and type of poisons. Results There were 60.6% female cases with the age from 10 to 90 years old. The age of cases from 20 to 39 years accounted for 54.5% of all age groups. Both the numbers and percentage in record related to poisoning consultation of oral poisoning suicide showed an increasing tendency during the 7 years. In particular, there was a drastic increase from 2004 to 2006. In addition, the high frequency of cases occurred from May to October. Hebei, Shandong, Henan, and Anhui Provinces had the highest number of cases. Pesticide poisonings were the most common method in these cases of consultation for suicide and suicide attempts. Conclusion This study describes epidemiological characteristics in the oral poisoning suicide cases and provides scientific basis for suicide prevention interventions.

Influence of Connexin43 on the Bystander Effect Induced by Double Suicide Genes System in Vitro and in Vivo

Objective： To observe the influence of connexin 43 （Cx43） on the bystander effect induced by cytosine deaminase （CD） and herpes simplex virus thymidine kinase （HSV-tk） coexpression suicide genes system in human cholangiocarcinoma QBC939 cells and transplantation tumors in nude mice. Methods： In vitro, the CD＋tk＋ and CD＋tk＋Cx＋ cells were respectively treated with 5-fluorocytosine （5-Fc） and Ganciclovir （GCV）. The cytotoxic effect was evaluated by MTT method. In order to investigate the influence of Cx43 on the bystander effect, the size of transplantation tumors of the CD＋tk＋ and CD＋tk＋Cx＋ cells was measured before and after application of 5-Fc and GCV. Results： CD and tk genes were stably expressed in transfected QBC939 cells. The increased expression of Cx43 was determined by testing for the presence of Cx43 mRNA by RT-PCR and the presence of Cx43 protein by Western Blot in CD＋tk＋Cx＋ cells. The killing effect of 5-Fc and GCV on CD＋tk＋Cx＋ cells was more effective than that on CD＋tk＋ cells both in vitro and in vivo. Conclusion： Double suicide genes system CD/5-Fc＋tk/GCV could induce remarkable killing effect on cholangiocarcinoma cells in vitro and transplantation tumors in vivo. The cotransfection of Cx43 gene could enhance the bystander effect and hence the inhibition of carcinoma cells.

A qualitative study on nurses'reactions to inpatient suicide in a general hospital

Aims:To explore the impact of inpatient suicides on nurses working in front-line,the patterns of regulation and their needs for support.Methods:Data were collected through purposive sampling by conducting semi-structured and individual in-depth interviews in a tertiary referral hospital in China.Colaizzi's sevenstep phenomenological method was simultaneously used by two interviewers.Results:Reactions to inpatient suicides revealed three central themes:(1)inpatients were highly likely to commit suicide,(2)inpatient suicide was difficult to prevent,and(3)nurses lacked the necessary suicide prevention skills.Psychological responses mainly included shock and panic,self-accusation or guilt,sense of fear,and frustration.The impacts on practice were stress,excessive vigilance,and burnout.Avoidance and sharing of feelings played key roles in the regulation patterns of nurses.Conclusions:Nurses who experienced inpatient suicide became stressed.Effective interventions must be implemented to improve the coping mechanisms of nurses against the negative consequences of inpatient suicide.The findings of this study will allow administrators to gain insight into the impacts of inpatient suicides on nurses in general hospitals.Such information can be used to develop effective strategies and provide individual support and ongoing education.Consequently,nurses will acquire suicide prevention skills and help patients achieve swift recovery.

Inter-relationships between isotretinoin treatment and psychiatric disorders: Depression, bipolar disorder, anxiety, psychosis and suicide risks

Isotretinoin(Accutane) is a treatment for severe acne that is resistant to other forms of treatment, including antibiotics and topical treatments. The prescription of this drug has been controversial ever since its initial marketing in 1982. It is the only non-psychotropic drug in the Food and Drug Administration top 10 drugs found to be associated with depression. Recently, Bremner et al published an extensive review(until 2010) of the evidence for the association of retinoic acid(RA) with depression and suicide. Some patients who are admitted in psychiatric hospitals report a history of present or past treatment with isotretinoin. Then, the imputability of the molecule in the occurrence of disorders represents necessarily an important question for both professionals and their patients. This paper aims to specify the links between the drug and specific psychiatric disorders. A review of the literature related to isotretinoin, RA, vitamin A, depression, suicide, anxiety, bipolar disorder, psychosis, schizophrenia was performed. Many studies demonstrated an increased risk of depression, attempted suicide and suicide following isotretinoin treatment. However, isotretinoin may have an antidepressant impact, according to some dermatological papers. They consider treating acne with this efficient treatment could improve selfimage and make the patient feel better. Several studies showed that patients with bipolar disorder had an increased risk for a clinical exacerbation of symptoms undergoing treatment with isotretinoin. A few studies also seem to suggest a possible link between isotretinoin and psychosis. Nonetheless, studies point out a link between retinoid dysregulation and schizophrenia through modulation of dopamine receptors. From this review, we propose guidelines for isotretinoin prescription to healthcare professionals.

Evaluation of miR-122-regulated suicide gene therapy for hepatocellular carcinoma in an orthotopic mouse model

Objective： Intratumoral administration of adenoviral vector encoding herpes simplex virus （HSV） thymidine kinase （TK） gene （Ad-TK） followed by systemic ganciclovir （GCV） is an effective approach in treating experimental hepatocellular carcinoma （HCC）. However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy, miR-122 is an abundant, liver-specific microRNA whose expression is decreased in human primary HCC and HCC-derived cell lines. These different expression profiles provide an opportunity to induce tumor-specific gene expression by miR-122 regulation. Methods： By inserting miR-122 target sequences （miR-122T） in the 3＇ untranslated region （UTR） ofTK gene, we constructed adenovirus （Ad） vectors expressing miR-122-regulated TK （Ad-TK-122T） and report genes. After intratumoral administration of Ad vectors into an orthotopic miR-122-deficient HCC mouse model, we observed the miR-122-regulated transgene expression and assessed the antitumor activity and safety of Ad-TK-122T. Results： Insertion of miR-122T specifically down-regulated transgene expression in vitro and selectively protected the miR-122-positive cells from killing by TK/GCV treatment. Insertion of miR-122T led to significant reduction of tansgene expression in the liver without inhibition of its expression in tumors in vivo, resulting in an 11-fold improvement of tumor-specific transgene expression. Intratumoral injection of Ad vectors mediated TK/GCV system led to a vector dosage-dependent regression of tumor. The insertion of miR-122T does not influence the antitumor effects of suicide gene therapy. Whereas mice administrated with Ad-TK showed severe lethal hepatotoxicity at the effective therapeutic dose, no liver damage was found in Ad-TK-122T group. Conclusions： miR-122-regulated TK expression achieved effective anti-tumor effects and increased the safety of intratumoral delivery of adenovirus-mediated TK/GCV gene therapy for miR-122-deficient HCC.

Kinase domain insert containing receptor promoter controlled suicide gene system selectively kills human umbilical vein endothelial cells

AIM： To study the selective killing of human umbilical vein endothelial cells （HUVECs） by a double suicide gene under the regulation of a kinase domain insert containing receptor （KDR） promoter and mediated by an adenoviral gene vector. METHODS： Human KDR promoter was cloned by polymerase chain reaction （PCR）, and two recombinant adenoviral plasmids pAdKDR-CdgIyTK, pAdCMV-CDglyTK were constructed according to a two-step transformation protocol. These two newly constructed plasmids were then transfected into 293 packaging cells to grow adenovirus, which were further multiplied and purified. HUVECs and LoVo cells were infected with either of the two resultant recombinant adenoviruses （AdKDR-CDglyTK and AdCMV-CDglyTK） respectively, and the infection rates were estimated by detection of green fluorescent protein （GFP） expression. Infected cells were cultured in culture media containing different concentrations of 5-fiuoroo/tosine （5-FC） and ganciclovir （GCV）, and the killing effects were measured. RESULTS： The two recombinant adenoviral plasmids pAdKDR-CdglyTK, pAdCMV-CDglyTK were successfully constructed and transfected into 293 cells. The resultant recombinant adenoviruses infected cells caused similar infection rates; and the infected cells exhibited different sensitivity to the prodrugs： HUVECs infected with AdCMV-CDglyTK and LoVo cells infected with AdCMVo CDglyTK were highly sensitive to the prodrugs, and HUVECs infected with AdKDR-CDglyTK were similarly sensitive but significantly more sensitive than the LoVo cells infected with AdKDR-CdglyTK （P 〈 0.001）. CONCLUSION： Selective killing of HUVECs may be achieved by gene transfer of double suicide gene under the regulation of the KDR promoter. This finding may provide an optional way to target gene therapy of malignant tumors by abrogation of tumor blood vessels.