bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA31: Not showing up empty-handed: A multicommunity collaboration for cancer prevention and control
Authors: Tanjasiri Sora Park , Palmer Paula Healani 
Published: February 2019

Abstract
While cancer mortality is on the decline in the U.S., Pacific Islanders continue to experience high rates of cancer incidence, prevalence, and mortality due to the lack of appropriate, understandable, and accessible prevention, early detection, and treatment/survivorship information and services. California is home to the second-largest populations of Pacific Islanders, including Chamorros, Marshallese, Native Hawaiians, Samoans, and Tongans. In 2005 community and university researchers formed a multicommunity collaboration for cancer prevention and control called WINCART: Weaving an Islander Network for Cancer Awareness, Research and Training. Using a community-based participatory research (CBPR) approach, this collaboration developed decision-making processes, protocols, and MOUs that prioritized community benefits in the design and implementation of studies spanning the cancer control continuum including tobacco cessation, nutrition and physical activity promotion, colorectal screening, breast screening, Pap testing, cancer survivorship, and biospecimen collection. Specifically, this presentation will cover the elements that contributed to WINCART's successful CBPR collaborations, provide examples from selected studies, and share lessons learned for researchers interested in initiating or sustaining community-university partnerships in the future.
Citation Format: Sora Park Tanjasiri, Paula Healani Palmer. Not showing up empty-handed: A multicommunity collaboration for cancer prevention and control [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA31.
Abstract IA36: Structural and social determinants of cancer disparities
Authors: Pérez-Stable Eliseo J. , Lin-Gomez Scarlett , Lin-Gomez Scarlett , Brown Arleen 
Published: February 2019

Abstract
Biologic and behavioral factors are considered the predominant contributors to incidence of cancer from most sites, and interactions between behavior and biology are well described. Contributions from social determinants of health to cancer rates and outcomes have mostly focused on access to preventive services and screening and to quality of cancer-related health care once diagnosed. For example, presentation with advanced stages of disease is most often ascribed to inadequate early detection when screening tests are recommended or to delay in consulting for symptoms when present. Both African American and Latina women have higher breast cancer mortality after completion of treatment for early-stage disease, in part as a result of inadequate annual screening following cure. Other factors such as health literacy, limited English proficiency, and low numeracy may exacerbate race/ethnic and socioeconomic disparities in cancer clinical care based on poor or ineffective communication. Structural determinants of cancer disparities refer to the built environment, the social and political system in which the patient lives, and the geographic location of home and health care. For example, an unsafe neighborhood may interfere with medical visits, obtaining medications and tests, and maintaining health-promoting activities after cancer diagnosis. Lack of adequate transportation and geographic isolation will further exacerbate access to care barriers. Race/ethnic minorities disproportionately engage with the criminal justice system, and this may interfere with obtaining quality clinical care. On the other hand, some concentrated minority neighborhoods may have tightly-woven social networks and provide community collective efficacy that can help patients and survivors going through treatment and survivorship care. Social and structural determinants of health can impact cancer outcomes across the continuum, from risk to death. Moreover, these characteristics are often highly correlated and can interact to influence disparate cancer outcomes above and beyond their individual health effects. The intersectional approach considers the impact on health and health equity of intersecting social positions and processes. To date, the intersectional approach has primarily been applied to qualitative research. In this panel, we will discuss the social and structural determinants, and the interaction among these determinants, of cancer disparities drawing on examples from the authors' work and the published literature.
Citation Format: Eliseo J. Pérez-Stable, Scarlett Lin-Gomez, Scarlett Lin-Gomez, Arleen Brown. Structural and social determinants of cancer disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA36.
Abstract IA44: Disparate exposures of Native Americans to metal mixtures in abandoned mine waste in the West: Implications for cancer risk
Authors: Lewis Johnnye 
Published: February 2019

Abstract
More than 160,000 abandoned hard rock mines are located in the Western United States that is home to the majority of Native American lands. These mines are estimated to result in more than 500,000 discrete contamination sources. More than 600,000 Native Americans live within 10 kilometers of these mines, which are known to have contaminated at least 40% of the headwaters of western U.S. watersheds. Abandoned gold mines and uranium mines dominate the inventory in proximity to tribal lands, with more than 4,000 abandoned uranium mines associated with more than 10,000 individual waste sites. The proximity of Native populations to these sources, and their greater reliance on local resources, creates a pattern of greater than anticipated exposures to the waste through multiple pathways including ingestion of unregulated drinking water, plant and animal products raised in contaminated soils, inhalation of windblown dusts containing waste metals, and direct contact with indoor dusts. Native communities have greatly reduced access to regulated drinking water sources, creating a reliance on unregulated sources potentially contaminated by waste. These waste sites all include a combination of heavy metals geologically collocated with the primary metal of concern, and often are combined with chemicals used in the extraction process. Data compiled by Indian Health Services illustrate significant health disparities within these communities, including a shorter life expectancy and double the mortality rate for those under 44 years of age. Cancer mortality rates for the Native American population increased over the 20-year period from 1990-2009, a period during which rates for the White population have decreased. Exposure to metals such as cadmium and arsenic has been directly linked to cancer mortality in Native populations, and epidemiologic data from one community proximal to an abandoned uranium mill report 4 of every 10 residents have died of cancer. Recent work in our laboratories has shown inhibition of DNA repair as well as dysregulation of immune function to be associated with exposures to these metal mixtures, providing possible pathways underlying increased cancer risk. Disparities do not end with exposures, but continue as patients seek care. With the closest treatment options often hundreds of miles away over extremely rough roads, using gasoline significantly more expensive than in many urban areas, the impact of increased risk continues to manifest throughout diagnosis and treatment.
Citation Format: Johnnye Lewis. Disparate exposures of Native Americans to metal mixtures in abandoned mine waste in the West: Implications for cancer risk [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA44.
Abstract A24: Using single-cell RNA-seq approaches to decipher heterogeneity in autochthonous mouse models of small cell lung cancer
Authors: Marjanovic Nemanja Despot , Ng Sheng Rong , Regev Aviv , Jacks Tyler 
Published: February 2019

Abstract
Small cell lung cancer (SCLC) is one of the most aggressive cancer types, and patients in clinic usually (&gt;60% cases) present with metastasis. Current therapies for SCLC have not changed from 1980, and they include a combination therapy of cisplatin and etoposide. Most patients relapse after initial response, and the 5-year survival for extensive stage SCLC is 2%. One possible explanation for the failure of conventional and targeted therapies in cancers is the cellular heterogeneity that exists within tumors. Thus, understanding phenotypic heterogeneity at the single-cell level can be leveraged to predict mechanisms of resistance, which enables the design of effective combination therapies. In this project, we used as a model system an autochthonous mouse model of human SCLC, in which we deleted p53, RB, and p130. We collected multiple primary tumors, circulating tumor cells (CTC), and lymph node (proximal site) and liver (distant site) metastases from the same mouse, and across different mice. These samples were collected at the stage that should correspond to the limited/extensive stage of human SCLC, which is most commonly seen in clinic. Then we used single-cell RNA-seq (sc-RNAseq) methods to define and understand transcriptional heterogeneity in these samples. Furthermore, we aimed to understand the evolutionary relationships between primary tumors, CTCs, lymph node and liver metastases using different computational approaches such as diffusion maps. Further defining and functionally annotating transcriptional heterogeneity will help us better understand the disease, and find the new Achilles heel for targeting.
Note: This abstract was not presented at the conference.
Citation Format: Nemanja Despot Marjanovic, Sheng Rong Ng, Aviv Regev, Tyler Jacks. Using single-cell RNA-seq approaches to decipher heterogeneity in autochthonous mouse models of small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A24.
Abstract A36: Establishment of patient-derived xenograft models of lung adenocarcinoma with two different EGFR mutations, L858R and exon19 deletion
Authors: Kita Kenji , Fukuda Koji , Nishiyama Akihiro , Arai Sachiko , Takeuchi Shinji , Ohtsubo Koushiro , Yamashita Kaname , Tamura Masaya , Matsumoto Isao , Yano Seiji 
Published: February 2019

Abstract
Preclinical tumor models that resemble the characteristics of patients’ tumors are essential for development of novel therapy. Patient-derived tumor xenograft (PDX) models are considered to be interesting candidates. However, success rate of PDX models of lung cancer, especially adenocarcinoma, is much lower than that of other types of tumors, including colon cancer.
This study was conducted to establish clinically relevant PDX models of lung cancer. We obtained fresh surgically resected specimens from 20 NSCLC patients (10 squamous cell carcinomas, 9 adenocarcinomas, and 1 large cell carcinoma) who had submitted the written informed consent for this study, which was performed in accordance with protocols approved by the IRB of Kanazawa University. We inoculated the tumor fragments subcutaneously into immunodeficient mice, NOG mice or SCID hairless outbred (SHO) mice. The tumor take rate was 40% (8/20), with higher rates for squamous cell carcinoma (60%, 6/10) than for adenocarcinoma (22%, 2/9). Interestingly, both of two adenocarcinomas that successfully developed PDX tumors had EGFR mutations, L858R and exon 19 deletion, respectively. These PDX tumors maintained histology of adenocarcinoma and EGFR mutation even after repeated in vivo passages. Furthermore, the third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) osimertinib dramatically regressed tumors in these EGFR mutated PDX models. Osimertinib treatment is ongoing in these EGFR-mutated PDX models to obtain tumors that acquired resistance to osimertinib.
Our PDX models of lung adenocarcinoma with different EGFR mutations may be useful for investigating the mechanisms of resistance to EGFR-TKIs, including third-generation inhibitor osimertinib.
Citation Format: Kenji Kita, Koji Fukuda, Akihiro Nishiyama, Sachiko Arai, Shinji Takeuchi, Koushiro Ohtsubo, Kaname Yamashita, Masaya Tamura, Isao Matsumoto, Seiji Yano. Establishment of patient-derived xenograft models of lung adenocarcinoma with two different EGFR mutations, L858R and exon19 deletion [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A36.
Abstract B15: Increased presence of T follicular helper cells in lung adenocarcinoma is associated with mutational load
Authors: Enfield Katey S.S. , Ng Kevin W. , Marshall Erin A. , Martin Spencer D. , Lam Wan L. 
Published: February 2019

Abstract
Tertiary lymphoid organs are ectopic lymphoid formations found in inflamed tissues such as tumors, and their presence has been associated with improved patient outcome. T follicular helper cells (Tfh) reside in the germinal centre of tertiary lymphoid organs, and are required for the maturation of B cells and subsequent antibody response. Whereas the prognostic value of Tfh has been described in breast and colon tumors, they remain uncharacterized in lung tumors. We hypothesize that Tfh cells reside in lung adenocarcinomas and are associated with an increased immune response due to neoantigen exposure.
Gene expression profiles were obtained from 83 paired lung adenocarcinomas and nonmalignant lung tissues from the BC Cancer Agency, and 571 unpaired samples from The Cancer Genome Atlas. Relative proportions of 22 immune cell subsets were inferred from gene expression data using CIBERSORT, a deconvolution algorithm. Identification of tertiary lymphoid organs was achieved through multicolor immunohistochemistry (IHC) staining for T- and B-cell lineage markers (CD3 and CD79a) using whole tissue sections. Proportions of Tfh cells were correlated with tumor mutation load defined as non-silent mutations per megabase (Mann Whitney U test) and patient outcome (Cox proportional hazard model).
The proportion of Tfh cells was significantly increased in tumor tissue compared to nonmalignant lung in both cohorts. We also observed concomitant upregulation of Tfh markers PD1 and CXCR5. Multicolor IHC validated the presence of tertiary lymphoid organs in 19 out of 20 cases assessed. Intriguingly, the increase in the proportion of Tfh cells revealed by CIBERSORT was observed across all disease stages and was validated in an additional cohort of Stage I lung adenocarcinomas. The relative proportion of Tfh cells did, however, increase with increasing tumor mutation burden, suggesting their involvement in an active immune response against tumor neoantigens.
Tfh recruitment appears to be an early event in lung tumor progression and a function of neoantigen exposure, suggesting involvement in an active antitumor response rather than a passive result of chronic inflammation. Further investigation into Tfh in lung adenocarcinomas may lead to prognostic applications.
Citation Format: Katey S.S. Enfield, Kevin W. Ng, Erin A. Marshall, Spencer D. Martin, Wan L. Lam. Increased presence of T follicular helper cells in lung adenocarcinoma is associated with mutational load [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B15.
Abstract B17: Interleukin-17 and -22 expression in non-small cell lung cancer
Authors: Stump Julia , Jiang Yue , Karches Clara , Gosálvez Javier Suárez , Neumann Jens , Kobold Sebastian , Hatz Rudolf , Winter Hauke , Tufman Amanda , Huber Rudolf M. , Reu Simone 
Published: February 2019

Abstract
Background: In non-small cell lung cancer (NSCLC) the TNM staging remains standard for prognostic assessment and therapy decisions. Nevertheless, stage-specific outcomes vary significantly, indicating a need for additional prognosticators. In this retrospective study we wanted to assess the role of the mediator interleukin-22 (IL-22), as IL-22 is known to be involved in various lung diseases and to be elevated in lung cancer patients. Moreover, we evaluated interleukin-17 (IL-17), which also depicts a proinflammatory cytokine, but seems to play a dual role in antitumor immunity. We asked the question of their link to prognosis, therapy response and recurrence.
Methods: Tissue microarrays (TMAs) were generated from formalin-fixed, paraffin embedded tissue of 138 curatively resected patients with stage IA-IV NSCLC. TMAs included each three cores from the tumor center (CT) and invasive margin (IM), selected from areas with the most dense lymphocytic infiltrates. IL-22 and IL-17 expression of the tissue was analyzed by immunohistochemistry via cytoplasmic staining (double-staining: IL-22, CD3 resp. IL-17, CD3).
Results: IL-22 expression status in adeno and SCC does not seem to have a prognostic impact on survival, regardless of the localization. However, a high IL-22 CT/IM ratio in adenocarcinoma is clearly linked to longer overall survival; this cannot be seen in SCC. For IL-17 a distinct tendency is visible for adeno and SCC in the invasive margin as well as in the tumor center—interestingly, this is more clear for SCC. In SCC a high CT/IM ratio for IL-17 seems to have a positive prognostic impact on overall survival. Patient numbers will be enlarged to validate these findings.
Conclusion: The cytokines IL-22 and IL-17 seem—depending on histology and location—to have a prognostic impact on overall survival in NSCLC. In previous experiments we showed that multispectral assessment of CD8 and PD-L1 has a clear correlation with clinical outcome. Adding cytokines to this method might open novel avenues for predicting clinical outcome and therapeutic efficacy in NSCLC.
Citation Format: Julia Stump, Yue Jiang, Clara Karches, Javier Suárez Gosálvez, Jens Neumann, Sebastian Kobold, Rudolf Hatz, Hauke Winter, Amanda Tufman, Rudolf M. Huber, Simone Reu. Interleukin-17 and -22 expression in non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B17.
Abstract B21: Investigating targeted driver mutations and PD-L1 expression for improved therapy of non-small cell lung cancer
Authors: Alwithenani Akram , Forsythe Marika , Castonguay Mathieu , Greer Wenda , Flowerdew Gorden , Bethune Drew , Henteleff Harry , Plourde Madelaine , Mujoomdar Aneil , French Daniel , Johnston Micheal , Marcato Paola , Xu Zhaolin 
Published: February 2019

Abstract
Most lung cancer patients are diagnosed at an advanced stage, limiting their treatment options to chemotherapies that have very low response rate. New therapies that target driver gene mutations (e.g., EGFR, ALK, ROS1, BRAF) are being used to treat patients who have tumors with these mutations. In addition, a type of immunotherapy called immune checkpoint inhibitor is being used to treat lung cancer patients. For instance, patients with tumors that express PD-L1 are responsive to anti-PD-1/PD-L1 therapy. Thus, being able to identify the presence of driver mutations and PD-L1 will help patients to benefit from different therapies. A total of 844 cases of non-small cell lung cancer samples have been profiled for the presence of EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations by SNaPshot/sizing genotyping. Immunohistochemistry (IHC) was used to identify the protein expression of ALK and PD-L1. Histologic examination was performed to determine the pathologic type, grade, and lymphatic/vascular invasion. Statistical analysis revealed a number of correlations between the presence of the mutations, PD-L1 expression and the patient pathologic data. Specifically, it was determined that women had lung tumors with a significantly greater number of EGFR mutations than men (p value = 0.001). Examining the presence of ALK, EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations against the presence of pleural invasions yielded a p-value of 0.071, which implies evidence that different mutations are not associated with pleural invasion. However, EGFR mutations were associated with the absence of vascular and lymphatic invasions in lung cancer patients (p value = 0.001, 0.002 respectively). In addition, while the expression of PD-L1 does not associate with the patients who express KRAS mutation, it is associated with lung cancer patients who express EGFR mutation (p value = 0.002). Knowing the mutational and PD-L1 status in lung cancer patients will help patients benefit from targeted therapies and/or checkpoint inhibitors.
Citation Format: Akram Alwithenani, Marika Forsythe, Mathieu Castonguay, Wenda Greer, Gorden Flowerdew, Drew Bethune, Harry Henteleff, Madelaine Plourde, Aneil Mujoomdar, Daniel French, Micheal Johnston, Paola Marcato, Zhaolin Xu. Investigating targeted driver mutations and PD-L1 expression for improved therapy of non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr B21.