ABSTRACT
Numerous studies have attempted to restore the function of the tumour suppressor p53 as an anti-cancer strategy through gene delivery. However, most studies employed non-bacterial vectors to deliver p53. Various facultative and obligate anaerobic bacteria have been proposed as vectors because of their intrinsic tumour targeting ability and anti-tumour activity. Salmonella enterica Typhimurium is the most studied bacterial vector in anti-cancer therapy. We used the previously designed χ11218 strain of S. enterica Typhimurium, displaying regulated delayed lysis, as a vector for delivering p53 to human bladder carcinoma cells, restoring wild-type p53 protein function. We cloned p53 into pYA4545 (containing a eukaryotic expression system) to generate the χ11218 pYA4545p53 strain. Cloning of p53 did not affect the growth or interfere with the invasive and replicative capacity of χ11218 bacteria in tumour cells. Human bladder carcinoma cells (expressing mutated p53) transfected with pYA4545p53 showed a significant increase in the expression of p53 protein. We demonstrated that p53 supplied by χ11218 significantly decreased the viability of human bladder cancer cells in a dose-dependent manner. This study demonstrates the applicability of the attenuated χ11218 strain as a vector for DNA plasmids expressing tumour suppressor genes.
Subject(s)
Carcinoma , Urinary Bladder Neoplasms , Carcinoma/genetics , Cell Death , Genes, p53 , Humans , Salmonella typhimurium/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Urinary Bladder , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapyABSTRACT
Neurosyphilis follows a more aggressive and different clinical course in HIV-infected patients compared to patients with normal immunity. Two historical series of patients with a diagnosis of neurosyphilis between 1995 and 2008 were compared: they included a group of 15 patients with y and 28 patients without HIV infection. Probability of neurosyphilis in patients with positive serum VDRL was increased in patients infected with HIV compared to HIV negative patients (OR: 62.37 IC:95% (32.1-119.1) p value:< 0,001). Predominant clinical manifestations in neurosyphilis in the HIV negative group were ocular abnormality, vascular encephalic and spinal cord lesions. In the HIV positive group, they were fever, ocular abnormalities and headache. There were no differences in cerebrospinal fluid characteristics between both groups. Neurosyphilis was diagnosed even in patients with blood VDRL of < 1:32, that happened in 17.8% of the HIV positive patients with blood and in 60% of t he HIV negative patients. Penicillin sodium given at dose >or= than 18.000.000 IU/day IV during 14 days was the most common treatment. In patients with clinical neurosyphilis, 93% of HIV negative group, and 54.2% of HIV positive group had persistent neurological after-effects. Three HIV positive patients died due to causes not related to neurosyphilis.
