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Successful cancer gene therapy requires a vector that systemically and specifically targets tumor cells throughout the body. Although several vectors have been developed to express cytotoxic genes via tumor-specific promoters or to selectively replicate in tumor cells, most are taken up and expressed by just a few targeted tumor cells. By contrast, we show here that blood-borne Sindbis viral vectors systemically and specifically infect tumor cells. A single intraperitoneal treatment allows the vectors to target most tumor cells, as demonstrated by immunohistochemistry, without infecting normal cells. Further, Sindbis infection is sufficient to induce complete tumor regression. We demonstrate systemic vector targeting of tumors growing subcutaneously, intrapancreatically, intraperitoneally and in the lungs. The vectors can also target syngeneic and spontaneous tumors in immune-competent mice. We document the anti-tumor specificity of a vector that systemically targets and eradicates tumor cells throughout the body without adverse effects.

Ras activation is critical for T-cell development and function, but the specific roles of the different Ras isoforms in T-

NANOG is a pluripotency transcription factor in embryonic stem cells; however, its role in adult tissues remains largely unexplored. Here we show that mouse NANOG is selectively expressed in stratified epithelia, most notably in the oesophagus where the Nanog promoter is hypomethylated. Interestingly, inducible ubiquitous overexpression of NANOG in mice causes hyperplasia selectively in the oesophagus, in association with increased cell proliferation. NANOG transcriptionally activates the mitotic programme, including Aurora A kinase (Aurka), in stratified epithelia, and endogenous NANOG directly binds to the Aurka promoter in primary keratinocytes. Interestingly, overexpression of Nanog or Aurka in mice increased proliferation and aneuploidy in the oesophageal basal epithelium. Finally, inactivation of NANOG in cell lines from oesophageal or head and neck squamous cell carcinomas (ESCCs or HNSCCs, respectively) results in lower levels of AURKA and decreased proliferation, and NANOG and AURKA expression are positively correlated in HNSCCs. Together, these results indicate that NANOG has a lineage-restricted mitogenic function in stratified epithelia.

In the original Figure 8B, the authors failed to indicate that the four lanes showing the expression of miR-203 (top part of the panel) were rearranged to correspond with the samples shown in the lower part of the panel. All four lanes come from the same agarose gel, and this reorganization does not affect the data or the conclusions. The authors regret this error and apologize for any confusion that it may have caused. This has now been corrected in the figure below.

Psychiatric comorbidity is common among pathological gamblers and is associated with greater severity of clinical problems. The DRD(2) gene could be a liability genetic factor for psychiatric comorbidity in pathological gambling.

This study was conducted to detect a possible association of MAOA and/or MAOB genes with pathological gambling (PG). DNA polymorphisms in MAOA and MAOB genes were screened by molecular analysis in 68 individuals (47 males and 21 females) meeting ICD-10 and DSM-IV criteria for pathological gambling and 68 healthy comparison controls matched for age and sex. There were no significant differences between pathological gamblers and healthy volunteers in overall allele distribution at the MAOA gene polymorphism. However there was a significant association between allele distribution and the subgroup of severe male gamblers (n = 31) compared to the males in the group of healthy volunteers ( 2 = 5246; df = 1; P Ͻ 0.05 [Bonferroni corrected]). No association was found between the MAOB polymorphic marker and PG. Allele variants at the MAOA, but not the MAOB gene may be a genetic liability factor in PG, at least in severe male gamblers. Molecular Psychiatry (2000) 5, 105-109.Pathological gambling is an impulse control disorder and it has also been proposed as a model of addiction without substance. 1 As defined by DSM-IV its essential feature is a persistent and recurrent maladaptive gambling behaviour. It is a progressive, chronic and highly disabling disorder that is poorly understood and often underdiagnosed despite affecting 1-3% of the adult population. 2 At present, little is known about the biological correlates of pathological gambling. A growing literature suggests the involvement of genetic factors in behavioral disorders related to pathological gambling such as alcoholism, substance abuse, attention-deficithyperactivity disorder, and smoking. 3 An increased incidence of about 20% of pathological gambling in first-degree relatives within clinical samples of pathological gamblers has been reported 4,5 and it has led to consideration of the possible role of a genetic component in the development of this disorder. Moreover, there is evidence for genetic influence derived from a large twin study performed on 3359 twin pairs in United States. This study revealed that inherited factors explained 62% of the diagnosis of pathological gambling disorder. 6 Recently, a positive association has been reported between pathological gambling and DNA polymorphism at the D2 and D4 receptor genes. 7,8 Monoamine oxidases A (MAOA) and B (MAOB) play a critical role in the degradation of several neurotransmitters which could be involved in the pathogenesis of pathological gambling. Decreased platelet MAOB activity has been reported in pathological gambling 9,10 and other impulse control disorders. 11,12 Although MAOA activity has never been studied in pathological gambling, previous research suggests that abnormal MAOA activity may play a role in the pathophysiology of disorders with impaired impulse control. 13 Decreased MAOA activity was associated with impulsive behaviors in several affected males from a large Dutch family with a mutation in that locus. 14 Differences in MAOA activity have been associated with specific alleles of th...

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