To generate vector Ad.Tyr-E1A, which is cytolytic for tyrosinase-positive melanoma cells, we replaced the adenoviral E1A promoter with a human tyrosinase enhancer/promoter. To overcome the low transduction efficiency in populations of melanoma cells that exhibit a low level of the coxsackievirus-adenovirus receptor (CAR), we inserted an RGD-4C peptide into the HI loop of the fiber knob domain of the Ad.Tyr-E1A vector. The resulting vector was named Ad.Tyr-E1A(RGD). As a result of these changes, the transduction efficiency of the RGD-modified vector was increased both in vitro and in vivo. Western blot analysis proved that infection of cells with the Ad.Tyr-E1A(RGD) vector led to expression of the E1A gene selectively in tyrosinase-positive melanoma cell lines, but not in tyrosinase-negative cell lines. The Ad.Tyr-E1A(RGD) vector was as potent in its cytotoxic effect as a tumor nonselective vector (Ad.CMV-E1A) in tyrosinase-positive melanoma cell lines. The Ad.Tyr-E1A(RGD) vector produced a higher vector particle yield in tumor cells than did the Ad.Tyr-E1A vector. Intratumoral injection of the Ad.Tyr-E1A(RGD) vector into xenotransplanted human melanoma tumors led to tumor regression in vivo. The combination of tumor-specific replication and enhanced infectivity generates a more potent CRAD vector for gene therapy of melanoma.
Background
Various explanations account for suicide incidents, and some patients continue to attempt afterwards and others never again. The suicide mortality rate increases with the number of serious attempts. The prevention of secondary attempt of suicide should be an important approach to reduce suicide mortality. However, the characteristics of the targeted population of repeated suicide attempters are understudied.
Methods
This was a cross-sectional data collection from hospital emergency room from patients who had either attempted suicide for the first time (n=721) or for two or more times (n=70). The subjects were between 14–53 years old and comprised 293 males and 498 females. In-depth interview was conducted for each suicide attempter with a semi-structural protocol. Demographic and social-psychological characteristics were compared between the two groups of suicide attempters. Logistic regression was used to identify independent predictors of multiple attempts.
Findings
The two groups only differed in religion factor among demographic characteristics and multiple suicide attempters group have a higher percentage of subjects who reported to have a religion affiliation than first time suicide attempters. Multiple attempters were more likely to have family suicide history, physical illness, mental disorder, higher scores on Beck Hopelessness Scale (BHS) and Suicide Intent Scale (SIS) and lower scores on Duke Social Support Scale (DSSI). In the final regression model, family history of suicide, mental disorder, hopelessness and social support emerged as significant predictors of multiple suicide attempts.
Conclusion
Suicide attempters that have mental disorder, family history of suicide, higher level of hopelessness and lower level of social support are more likely to re-attempt suicide again. Social and clinical interventions may have to also focus on this sub-group of patients with these characteristics to effectively reduce suicide mortality rate.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.