Gene Therapy with p14/tBID Induces Selective and Synergistic Apoptosis in Mutant Ras and Mutant p53 Cancer Cells In Vitro and In Vivo.

Any gene therapy for cancer will be predicated upon its selectivity against cancer cells and non-toxicity to normal cells. Therefore, safeguards are needed to prevent its activation in normal cells. We designed a minimal p14 promoter with upstream Ap1 and E2F enhancer elements and a downstream MDR1 inhibitory element, TATA box, and a transcription initiation site (hereafter p14min).

C-Terminal p53 Palindromic Tetrapeptide Restores Full Apoptotic Function to Mutant p53 Cancer Cells In Vitro and In Vivo.

We previously demonstrated that a synthetic monomer peptide derived from the C-terminus of p53 (aa 361−382) induced preferential apoptosis in mutant p53 malignant cells, but not normal cells. The major problem with the peptide was its short half-life (half-life < 10 min.) due to a random coil topology found in 3D proton NMR spectroscopy studies.

Relative telomere length and gene expression of shelterin complex proteins among vinyl chloride monomer-exposed workers in China.

Vinyl chloride monomer (VCM) is a confirmed carcinogen. The effects of VCM on telomeres and the gene expression of telomere complex proteins, shelterin, have not been well studied but could be of potential relevance to the carcinogenic mechanism of VCM and the health surveillance of VCM-exposed workers. A group of 241 VCM-exposed workers and 101 internal controls from the same plant in Shandong, China were recruited and quantitative polymerase chain reaction was preformed to measure relative telomere length (RTL) and gene expression of shelterin proteins.

Analysis of microRNA expression and micronuclei frequency in workers exposed to vinyl chloride monomer in China.

Aim: To identify differently expressed miRNAs associated with vinyl chloride monomer (VCM) and micronuclei (MN) frequency.

Method: In discovery stage, we used microarray to detect miRNAs expression in peripheral blood lymphocytes between six low and six high VCM-exposed workers grouped by medium cumulative exposure dose. Then we validated four miRNAs using real-time quantitative reverse transcription PCR (qRT-PCR) and detected the micronuclei frequencies using cytokinesis-block micronucleus assay in 94 VCM-exposed workers and 53 healthy control subjects.

Mutations in apoptotic genes and micronucleus occurrence in vinyl chloride-exposed workers in China.

Background: Vinyl chloride is an occupational carcinogen which caused micronuclei in human directly. It has recently been demonstrated that micronuclei formation could generate a spectrum of genomic rearrangements and play a key role in the early tumorigenesis process. We aimed to investigate the association between polymorphisms in the apoptosis process related genes and micronuclei rate in vinyl chloride-exposed workers in China.

The University of Illinois at Chicago School of Public Health Doctor of Public Health program: an innovative approach to doctoral-level practice leadership development.

The University of Illinois at Chicago, School of Public Health, Doctor of Public Health degree is designed to build leadership skills and an ability to contribute to the evidence base of practice. The competency-based, distance-format, doctoral-level program for midcareer professionals features an action learning approach in which students apply leadership principles from the virtual classroom to real-world problems at their work sites. Students demonstrate mastery of the competencies and readiness to advance to the dissertation stage through completing a portfolio by using a process of systematic reflection.

Effects of DNA repair gene polymorphisms on DNA damage in human lymphocytes induced by a vinyl chloride metabolite in vitro.

Background: Epidemiologic studies suggest that variability in DNA damage from vinyl chloride monomer (VCM) may be partially mediated by genetic polymorphisms in DNA repair. This study aimed to corroborate these observations with controlled experiments in vitro using cell lines from individuals with differing DNA repair genotypes to determine damage following VCM metabolite exposure.

Methods: Matched pairs of lymphoblast cell lines (homozygous wild-type versus homozygous variant for either XRCC1 399 or XPD 751 polymorphism) were exposed to chloroacetaldehyde and analyzed by the cytokinesis-block micronucleus assay.

Polymorphisms in the p53 pathway genes and micronucleus occurrence in Chinese vinyl chloride-exposed workers.

Objectives: To investigate the association between polymorphisms in the p53 pathway genes and chromosomal damage in vinyl chloride (VC)-exposed workers.

Materials And Methods: Cytokinesis block micronucleus test was performed in 310 VC-exposed workers and 149 non-exposed workers to determine chromosomal damage. The polymerase chain reaction and restriction fragment length polymorphism technique were used to detect six SNPs in the p53 pathway genes involved in the cell cycle.

Redirecting apoptosis to aponecrosis induces selective cytotoxicity to pancreatic cancer cells through increased ROS, decline in ATP levels, and VDAC.

Pancreatic cancer cell lines with mutated ras underwent an alternative form of cell death (aponecrosis) when treated concomitantly with clinically achievable concentrations of arsenic trioxide, ascorbic acid, and disulfiram (Antabuse; AAA). AAA's major effects are mediated through generation of intracellular reactive oxygen species (ROS) and more than 50% decline in intracellular ATP. N-acetyl cysteine and a superoxide dismutase mimetic prevented aponecrosis and restored intracellular ATP levels.

Polymorphisms in BER and NER pathway genes: effects on micronucleus frequencies among vinyl chloride-exposed workers in Northern China.

In this study, a group of 317 workers occupationally exposed to vinyl chloride monomer and 166 normal, unexposed referents in Shandong province (Northern China) were examined for chromosomal damage in peripheral lymphocytes using the cytokinesis-blocked micronucleus (CB-MN) assay. The exposure group (3.47±2.

Prevalence and factors associated with 2009 to 2011 influenza vaccinations at a university medical center.

Background: Information on the rates and factors associated with influenza vaccinations, although limited, is important because it can inform the development of effective vaccination campaigns in a university medical center setting.

Methods: A study was conducted in 2011 to identify individual and organizational level barriers and facilitators to influenza vaccination among clinical and nonclinical personnel (N = 428) from a major university medical center.

Results: Seventy-one percent of clinical personnel (n = 170) reported pandemic H1N1 vaccination compared with 27% of nonclinical personnel (n = 258), even though vaccine was made widely available to all personnel at no cost.

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers.

Objective: To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM).

Materials And Methods: Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay.

Estimation of a safe level for occupational exposure to vinyl chloride using a benchmark dose method in central China.

Objectives: The aim of this study was to estimate a benchmark dose (BMD) for chromosome damage induced by vinyl chloride monomer (VCM) in VCM-exposed workers in central China and validate the published results in Shanghai.

Methods: VCM-exposed workers who had been exposed to VCM for at least one year (n=463) and matched subjects not exposed to VCM or other toxins (n=273) were asked to participate in this study. Micronucleus (MN) frequency based on the cytokinesis-block micronucleus assay (CBMN) was used as a biomarker for chromosome damage induced by VCM exposure.

Plastics and carcinogenesis: The example of vinyl chloride.

The manufacture, use and disposal of various plastics can pose numerous health risks, including the risk of cancer. A model example of carcinogenic risk from plastics is provided by polyvinyl chloride, since it is composed of the known human carcinogen vinyl chloride (VC). In recent years, much has been learned about the molecular biological pathways of VC carcinogenesis.

Estimation of benchmark dose for micronucleus occurrence in Chinese vinyl chloride-exposed workers.

In this study, we estimated the possibility of using benchmark dose (BMD) to assess the dose-response relationship between vinyl chloride monomer (VCM) exposure and chromosome damage. A group of 317 workers occupationally exposed to vinyl chloride monomer and 166 normal, unexposed control in Shandong Province northern China were examined for chromosomal damage in peripheral blood lymphocytes (PBL) using the cytokinesis-blocked micronucleus (CB-MN) assay of DNA damage. The exposed group (3.

The differing perspectives of workers and occupational medicine physicians on the ethical, legal and social issues of genetic testing in the workplace.

Genetic testing in the workplace holds the promise of improving worker health but also raises ethical, legal, and social issues. In considering such testing, it is critical to understand the perspectives of workers, who are most directly affected by it, and occupational health professionals, who are often directly involved in its implementation. Therefore, a series of focus groups of unionized workers (n=25) and occupational medicine physicians (n=23) was conducted.

Proteomic detection of cancer in asbestosis patients using SELDI-TOF discovered serum protein biomarkers.

Objectives: To identify biomarkers for cancer in asbestosis patients.

Methods: SELDI-TOF and CART were used to identify serum biomarker profiles in 35 asbestosis patients who subsequently developed cancer and 35 did not develop cancer.

Results: Three polypeptide peaks (5707.

Protein and amino acid intakes in a rural area of Bangladesh.

Background: Few studies have described protein and amino acid intakes in rural Bangladesh, a country with considerable undernutrition.

Objective: The purpose of this population-based study was to assess and describe protein and amino acid intakes in Araihazar, Bangladesh.

Methods: The study participants were 11,170 adult men and women who participated in the Health Effects of Arsenic Longitudinal Study (HEALS), which had a 98% participation rate.