Genes that act inside the cell to negatively regulate proliferation are of great interest because of their implications for such processes as development and cancer, but these genes have been difficult to clone. This report details the cloning and analysis of cDNA for prohibitin, a novel mammalian antiproliferative protein. Microinjection of synthetic prohibitin mRNA blocks entry into S phase in both normal fibroblasts and HeLa cells. Microinjection of an antisense oligonucleotide stimulates entry into S phase. By sequence comparison, the prohibitin gene appears to be the mammalian analog of Cc, a Drosophila gene that is vital for normal development.

Transducing and distributing a vector throughout a tumor mass are presently insufficient for effective cancer gene therapy. To overcome these difficulties an adenoviral vector was designed that would replicate specifically in tumor cells. This tumor-specific replication-restricted adenoviral (TSRRA) vector was constructed by requiring that the essential E1A gene be expressed from a tumor-specific promoter, namely, the alpha-fetoprotein (AFP) gene promoter. This promoter was chosen since the AFP gene is highly expressed in 70-80% of patients with hepatocellular carcinoma (HCC) but not in normal adults. HCC is one of the major worldwide causes of cancer death. A vector was constructed (AvE1a04i) and demonstrated to replicate in human AFP-producing HCC cell lines. However, little replication was observed in seven other, non-AFP-producing human cell lines, as well as primary cultures of normal human lung epithelial and endothelial cells. In addition, AvE1a04i was shown to prevent tumor growth of an ex vivo-transduced AFP-expressing HCC cell line but not a non-AFP-expressing cell line. Finally, in situ administration of AvE1a04i into preestablished tumors resulted in a greater than 50% long-term survival rate. This novel TSRRA vector for HCC demonstrated both specificity and efficacy in vitro and in vivo.

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Abstract:Excessive gambling is recognized with dopamine agonist therapy, but the prevalence is unknown. We assessed the prevalence of excess gambling by specific prospective enquiry in Parkinson's disease patients attending six West Scotland movement disorder clinics. Of 388 patients taking anti-Parkinson medication, 17 (4.4%) developed pathological gambling, all of whom were prescribed dopamine agonists. Thus, 8% of patients taking dopamine agonists had pathological gambling. Pathological gambling is not uncommon, and patients should be made aware of this potential adverse effect. © 2006 Movement Disorder Society Key words: Parkinson's disease; dopamine agonists; pathological gambling Pathological gambling associated with anti-Parkinson therapy is considered rare. 1,2 Estimates of prevalence vary between 0.05% of 1,884 patients from a retrospective database review 3 to approximately 7% of 200 cases from face-to-face interview. 4 Systematic prospective review analyzing drug class and dosages has been suggested, in particular to assess relative risk among antiParkinson agents and was the purpose of the present study. PATIENTS AND METHODSConsecutive patients with a clinical diagnosis of idiopathic Parkinson's disease (PD) in six West Scotland movement disorder clinics were asked over a 3-month period about their interest in gambling. Patients were excluded if such enquiry was deemed inappropriate, e.g., in the presence of advanced dementia. Demographic data, anti-Parkinson medication, and gambling behavior (classed as pathological when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were fulfilled) were recorded by semistructured interview. Type of gambling (e.g., lottery, Internet, horse racing) and weekly expenditure were also registered. Daily doses were recorded, using salt for pramipexole. Statistical analysis used GraphPad Prism (GraphPad Software, San Diego, CA) and Statistica (StatSoft, Tulsa, OK). Groups were compared by unmatched t tests for continuous parametric variables, Mann-Whitney tests for nonparametric data, and 2 tests for categorical variables. RESULTSOf 424 patients, 10 with advanced dementia were excluded. Of the remaining 414, mean age was 69 years (standard deviation [SD] 11; range, 35-93 years) and 61% were men. Twenty-six patients were diagnosed recently and not yet prescribed anti-Parkinson medication. Of the 388 prescribed anti-Parkinson therapy, 66 cases (17%) were taking dopamine agonists either as monotherapy (n ϭ 57; 15%) or with an adjunct (n ϭ 9; 2.3%); 174 (45%) were on levodopa-based treatment as monotherapy (n ϭ 128; 33%) or with an adjunct (n ϭ 46; 12%); 146 (38%) had a combination of dopamine agonist and L-dopa (with adjunct n ϭ 71; 18%), and 2 (0.5%) were on selegiline only. Of those 388 patients, 17 (4.4%) reported problematic excessive gambling that began after starting anti-Parkinson therapy. None of these cases had prior pathological gambling. The mean age of these 17 cases was 56 years (SD 7; range,, which was significantly younger than n...

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