Addressing the burden of gastric cancer disparities in low-income New York City Chinese American immigrants [Meeting Abstract]
Background: Gastric cancer is the third most common cause of cancer death worldwide. In the US, gastric cancer incidence for Chinese Americans is nearly twice that for non-Hispanic whites. Cancer is the leading cause of death among Chinese New Yorkers who experience higher mortality for gastric cancer than other New Yorkers overall. The bacterium Helicobacter pylori (H. pylori) is the strongest risk factor for gastric cancer, and eradication of H. pylori through triple antibiotic therapy is the most effective prevention strategy for gastric cancer. Despite the elevated burden, there are no culturally and linguistically tailored evidence-based intervention strategies to address H. pylori medication adherence and gastric cancer prevention for Chinese Americans in NYC, a largely foreign-born (72%), limited English proficient (61%), and low-income (21% living in poverty) population.
Objective(s): The study objective was to develop and pilot a community health worker (CHW)-delivered linguistically and culturally adapted gastric cancer prevention intervention to improve H. pylori treatment adherence and address modifiable cancer prevention risk factors, including improved nutrition for low-income, LEP, Chinese American immigrants.
Method(s): We used a mixed methods and community-engaged research approach to develop and pilot the intervention curriculum and materials. Methods included: 1) a comprehensive scoping review of the peer-reviewed and grey literature on gastric cancer prevention programs and strategies targeting Chinese Americans; 2) 15 key informant interviews with gatekeepers and stakeholders serving the New York Chinese immigrant community to assess the knowledge and perception of H. pylori infection and gastric cancer among Chinese New Yorkers; and 3) pilot implementation of the collaboratively developed intervention with H. pylori-infected LEP Chinese immigrant participants (n=7).
Result(s): Study process findings and pilot results will be presented. Preliminary results indicate high patient- and community-level need and acceptability for the intervention. Baseline and 1-month post-treatment outcomes and survey data, qualitative data analysis of the CHW session notes, and key informant interviews will be presented.
Conclusion(s): Findings suggest that a CHW-delivered culturally adapted gastric cancer prevention intervention can result in meaningful health information and treatment adherence for at-risk, low-income Chinese immigrant communities. Study findings are being applied to inform a randomized controlled trial being implemented in safety net hospital settings
Implementing electronic health records-based intervention tools in a large NYC healthcare system to facilitate H. pylori eradication strategies for gastric cancer prevention for at-risk Chinese American immigrant patients [Meeting Abstract]
Alteration at translational but not transcriptional level of transferrin receptor expression following manganese exposure at the blood-CSF barrier in vitro
Manganese exposure alters iron homeostasis in blood and cerebrospinal fluid (CSF), possibly by acting on iron transport mechanisms localized at the blood-brain barrier and/or blood-CSF barrier. This study was designed to test the hypothesis that manganese exposure may change the binding affinity of iron regulatory proteins (IRPs) to mRNAs encoding transferrin receptor (TfR), thereby influencing iron transport at the blood-CSF barrier. A primary culture of choroidal epithelial cells was adapted to grow on a permeable membrane sandwiched between two culture chambers to mimic blood-CSF barrier. Trace (59)Fe was used to determine the transepithelial transport of iron. Following manganese treatment (100 microM for 24 h), the initial flux rate constant (K(i)) of iron was increased by 34%, whereas the storage of iron in cells was reduced by 58%, as compared to controls. A gel shift assay demonstrated that manganese exposure increased the binding of IRP1 and IRP2 to the stem loop-containing mRNAs. Consequently, the cellular concentrations of TfR proteins were increased by 84% in comparison to controls. Assays utilizing RT-PCR, quantitative real-time reverse transcriptase-PCR, and nuclear run off techniques showed that manganese treatment did not affect the level of heterogeneous nuclear RNA (hnRNA) encoding TfR, nor did it affect the level of nascent TfR mRNA. However, manganese exposure resulted in a significantly increased level of TfR mRNA and reduced levels of ferritin mRNA. Taken together, these results suggest that manganese exposure increases iron transport at the blood-CSF barrier; the effect is likely due to manganese action on translational events relevant to the production of TfR, but not due to its action on transcriptional, gene expression of TfR. The disrupted protein-TfR mRNA interaction in the choroidal epithelial cells may explain the toxicity of manganese at the blood-CSF barrier.
In vitro activity of doripenem (S-4661) against multidrug-resistant gram-negative bacilli isolated from patients with cystic fibrosis
Doripenem 50% inhibitory concentrations (MIC50) and 90% inhibitory concentrations (MIC90) for multidrug-resistant strains of mucoid Pseudomonas aeruginosa (n=200 strains), nonmucoid P. aeruginosa (n=200), and Burkholderia cepacia complex (n=200) isolated from patients with cystic fibrosis were 8 and 32, 8 and 64, and 8 and 32 microg/ml, respectively. Doripenem had somewhat better activity than established antimicrobial agents.
Establishment and characterization of an immortalized Z310 choroidal epithelial cell line from murine choroid plexus
The choroid plexus plays a wide range of roles in brain development, maturation, aging process, endocrine regulation, and pathogenesis of certain neurodegenerative diseases. To facilitate in vitro study, we have used a gene transfection technique to immortalize murine choroidal epithelial cells. A viral plasmid (pSV3neo) was inserted into the host genome of primary choroidal epithelia by calcium phosphate precipitation. The transfected epithelial cells, i.e., Z310 cells, that survived from cytotoxic selection expressed SV40 large-T antigen throughout the life span, suggesting a successful gene transfection. The cells displayed the same polygonal epithelial morphology as the starting cells by light microscopy. Immunocytochemical studies demonstrate the presence of transthyretin (TTR), a thyroxine transport protein known to be exclusively produced by the choroidal epithelia in the CNS, in both transfected and starting cells. Western blot analyses further confirm the production and secretion of TTR by these cells. The mRNAs encoding transferrin receptor (TfR) were identified by Northern blot analyses. The cells grow at a steady rate, currently in the 110th passage with a population doubling time of 20-22 h in the established culture. When Z310 cells were cultured onto a Trans-well apparatus, the cells formed an epithelial monolayer similar to primary choroidal cells, possessing features such as an uneven fluid level between inner and outer chambers and an electrical resistance approximately 150-200 omega-cm(2). These results indicate that immortalized Z310 cells possess the characteristics of choroidal epithelia and may have the potential for application in blood-CSF barrier (BCB) research.
The blood-CSF barrier in culture. Development of a primary culture and transepithelial transport model from choroidal epithelial cells