Identifying Food Insecurity and Increasing Access to Nutrition in Brandon, VT

Food insecurity is a significant problem in Vermont affecting over 10% of the population in 2016. Access to nutrition is an important social determinant of health with long term implications for our communities. In order to increase awareness of existing infrastructure to reduce food insecurity in Rutland County, a resource guide was created with information about local food pantries, community dinners, and assistance obtaining 3SquaresVT benefits.https://scholarworks.uvm.edu/fmclerk/1394/thumbnail.jp

Asthma in Vermont Dairy Farmers

Introduction. Although 5.4% of the Vermont population participates in agriculture as an occupation, little data exists on the prevalence of asthma in Vermont dairy farmers, due to inadequate sample sizes. Previous studies have shown dairy farmers are at risk of respiratory illness due to unique exposures intrinsic to their occupation. We conducted a study to assess the prevalence of asthma in dairy farmers in Vermont, to understand rates among this population and potential occupational risks.Methods. We distributed a paper survey modeled after previously-validated surveys, such as the BRFSS, to farmers at Vermont Farmer Bureau meetings, farmers markets, and individual farmers through Cabot Creamery. Out of 309 distributed surveys, we received 176 completed surveys for a response rate of 57%.Results. Self-reported asthma rate in dairy farmers was 21% (22% in dairy only farmers), with 90% of these cases reported as confirmed by a doctor. Of non-dairy farmers, 11% self-reported experiencing asthma. Farming activities associated with exacerbation of asthma symptoms were milking, prepping or cleaning bedding, and haying. 31% of dairy-only farmers reported symptom exacerbations due to these occupational triggers.Conclusions. The prevalence of asthma in Vermont dairy farmers is one of the highest reported rates in any Vermont occupation. Our data suggest that certain occupational exposures may increase risk of asthma and warrant further study; certain farming practices were associated with exacerbation of respiratory symptoms in farmers diagnosed with asthma. These findings and further research can assist in development of health care and preventive health measures for farmers.https://scholarworks.uvm.edu/comphp_gallery/1238/thumbnail.jp

Co-Clinical Trials Demonstrate Superiority of Crizotinib to Chemotherapy in ALK-Rearranged Non-Small Cell Lung Cancer and Predict Strategies to Overcome Resistance

To extend the results of a phase III trial in non-small cell lung cancer patients with adenocarcinomas harboring EML4-ALK fusion

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non-small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically-engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor JQEZ5 that promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a subset of lung cancer

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition

Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non-small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically-engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways leading to epigenetic transformation independent from canonical growth factor pathway activation. As such, tumors feature a transcriptional program distinct from KRAS- and EGFR-mutant mouse lung cancers, but shared with human lung adenocarcinomas exhibiting high EZH2 expression. To target EZH2-dependent cancers, we developed a novel and potent EZH2 inhibitor JQEZ5 that promoted the regression of EZH2-driven tumors in vivo, confirming oncogenic addiction to EZH2 in established tumors and providing the rationale for epigenetic therapy in a subset of lung cancer