bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3384: Characterization of the tumor microenvironment and liquid biopsy in head and neck and non-small cell lung cancer
Authors: Kulasinghe Arutha , Kapeleris Joanna , Kenny Liz , Hughes Brett , Warkiani Majid , Vela Ian , Thiery Jean-Paul , O'Byrne Ken , Punyadeera Chamindie 
Published: September 2020

Abstract
Metastasis in cancer patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of cancer patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in a number of solid tumor types.
Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. Head and Neck cancer (n=350) and lung cancer (n=150) patients were recruited to investigate the prognostic role of CTCs. In parallel, a subset of HNC tumors were profiled using the NanoString GeoMx Digital Spatial Profiling (DSP) technology using a 44-plex antibody cocktail. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, Spiral, Straight and novel microfluidic chip technology) using matched patient samples which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification, ALK-translocations). In HNC, the presence of CTC clusters associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression free survival (Hazard ratio [HR]: 4.946; 95% [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof of principle study, we were able to demonstrate for the first time, short-term patient derived CTC cultures outside the patient's body and exome sequencing of CTCs cultures confirmed the presence of mutational signatures consistent with The Cancer Genome Atlas (TCGA). Spatial characterization of the tumor microenvironment revealed immune subsets predictive of outcome to immunotherapy. Comprehensive characterization of the tumor microenvironment and liquid biopsy allows for the recapitulation of the molecular diversity present within the tumor, understanding of the disease progression and testing of therapies.
Citation Format: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Brett Hughes, Majid Warkiani, Ian Vela, Jean-Paul Thiery, Ken O'Byrne, Chamindie Punyadeera. Characterization of the tumor microenvironment and liquid biopsy in head and neck and non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3384.
Abstract 3449: A novel rapid zebrafish model for validation of potential therapies for fatal pediatric brain tumors
Authors: Kaur Harpreet , Guo Huizi , Emmerich Kevin , White David , Green Peter , Hector Alara Michelle , Akhtarkhavari Sepehr , Bhargava Anukriti , Martin Allison , Shah Smit , Eberhart Charles G. , Mumm Jeffrey , Raabe Eric H. 
Published: September 2020

Abstract
Diffuse intrinsic pontine glioma (DIPG) and atypical teratoid/rhabdoid tumors (AT/RT) are deadly pediatric brain tumors. There is an urgent need of better therapeutics for improving survival and quality of life for these patients. Additionally, we need improved animal models to accelerate identification of novel therapeutics and improve through-put. In line with our long-term interests of validating therapies and developing model systems for pediatric brain tumors, we tested a repurposed drug quinacrine as a potential therapy using a new and faster model system in zebrafish. Quinacrine is a safe and widely used treatment for pediatric malaria and parasitic infections. We hypothesized that quinacrine will increase tumor cell death and decrease tumorigenicity of DIPG and ATRT. We used quinacrine in six patient-derived cell lines: three AT/RT (BT37, CHLA-05, CHLA-266) and three DIPG (JHHDIPG1, SUDIPGXIII, SF7761). In all tumor cell lines, quinacrine caused a dose-dependent reduction in proliferation (BrdU) and increase in apoptosis (cleaved caspase-3 and cleaved PARP) compared to vehicle-treated cells (P&lt;0.01). Quinacrine had no effect on growth of normal hindbrain neural stem and progenitor cells. Using quinacrine fluorescence as a surrogate, we achieved micromolar concentration of quinacrine in the mouse and zebrafish brain without overt toxicity. Treatment of mice bearing ATRT flank tumors with quinacrine resulted in decreased tumor volume compared to vehicle-treated mice (P&lt;0.05). To validate quinacrine orthotopically in DIPG, we developed a novel model in zebrafish wherein we injected fluorescent DIPG cells into the developing zebrafish blastula. Two days post injection, DIPG cells had homed to the zebrafish brain. Treatment of xenografted zebrafish with quinacrine for 72 hours decreased DIPG growth by 40% as measured by fluorescence, suggesting that minor groove binding drugs like quinacrine are a viable treatment strategy for these tumors. Using this new system, we were able to validate a potential therapeutic in 7 days versus 7 months in mice. Future studies are aimed at investigating the mechanism of quinacrine in these tumors and optimizing our zebrafish model for high-throughput screening of potential drugs.
Citation Format: Harpreet Kaur, Huizi Guo, Kevin Emmerich, David White, Peter Green, Alara Michelle Hector, Sepehr Akhtarkhavari, Anukriti Bhargava, Allison Martin, Smit Shah, Charles G. Eberhart, Jeffrey Mumm, Eric H. Raabe. A novel rapid zebrafish model for validation of potential therapies for fatal pediatric brain tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3449.
Abstract 3457: Plasma metabolomic changes in mice with time restricted feeding-attenuated pulmonary metastasis of Lewis lung carcinoma
Authors: Yan Lin , Rust Bret M. , Picklo Matthew J. 
Published: September 2020

Abstract
Erratic eating behavior disrupts diurnal rhythms of metabolism and may contribute to obesity. Time-restricted feeding (TRF), in which food is available in the active period of the day (the dark phase for nocturnal animals), restores metabolic homeostasis in mice. In a mouse model of Lewis lung carcinoma (LLC), we found that TRF (12 hours, dark phase) attenuates obesity-enhanced spontaneous metastasis to the lungs in a study that compared differences in the extent of metastasis among four dietary groups: non-LLC-bearing mice fed the standard AIN93G diet and LLC-bearing mice fed the AIN93G, an obesogenic high-fat diet (HFD) or TRF with the HFD. With the goal of determining potential plasma fingerprints underlying TRF efficacy, we performed untargeted metabolomic analysis upon the plasma samples from this study. Using gas chromatography time-of-flight mass spectrometry, we identified 152 compounds of which 24 differed among the four groups. Ten analytes that were the most influential in treatment separation were alpha-tocopherol, phenylalanine, isoleucine, leucine, pyruvic acid, dihydrocholestrol, arachidonic acid (ARA), docosahexaenoic acid (DHA), lactic acid, and cholesterol. In mice fed the AIN93G diet, compared to non-LLC-bearing mice LLC elevated alpha-tocopherol, ARA, isoleucine, phenylalanine, cholesterol, lauric acid, and 4-hydroxybenzoate and decreased lactic acid, lactamide, and pyruvic acid. In LLC-bearing mice, compared to the AIN93G diet the HFD elevated asparagine, leucine, phenylalanine, dehydrocholesterol, p-cresol sulfate, and hexuronic acid and decreased 1,5-anhydroglucitol, palmitoleic acid, myristic acid, lauric acid, and 4-hydrobenzoate. Compared to the HFD, TRF elevated linoleic acid and 2-hydroxyhexanoic acid and decreased alpha-tocopherol, asparagine, isoleucine, leucine, phenylalanine, dihydrocholesterol, p-cresol sulfate, hexuronic acid, and DHA. This study showed that LLC metastatic growth and an increase in dietary fat consumption disrupted metabolic homeostasis, as reflected in plasma analyte changes compared to their respective controls. TRF, through its temporal regulation of food intake, restored HFD-mediated metabolic disruption and may have contributed to its inhibition of obesity-enhanced LLC metastasis.
Citation Format: Lin Yan, Bret M. Rust, Matthew J. Picklo. Plasma metabolomic changes in mice with time restricted feeding-attenuated pulmonary metastasis of Lewis lung carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3457.
Abstract 3462: Gender differences in dietary behavior and urinary gallic acid concentrations in racial minorities in New York City
Authors: Zambrano Cristina , Lu Wenyue , Johnson Cicely , Beeber Maayan , Panitz April , Ibrahim Safa , Fraser Marilyn , Ma Grace , Navder Khursheed , Yeh Ming-Chin , Ogunwobi Olorunseun 
Published: September 2020

Abstract
Nutrition is important for cancer prevention. Previous research has found that socioeconomic factors may affect access to a healthy diet, which may impact the risk of cancer. To investigate this association, we assessed dietary behavior and the urinary concentrations of gallic acid, an antioxidant found in various fruits and vegetables, in racial minorities in New York City. Ninety-one (91) participants were recruited from a senior center in East Harlem, New York City, a racially diverse and underserved community. A National Institute of Health (NIH) - validated diet survey questionnaire was used to collect dietary behavior data. Demographic and cancer information were also collected. All 91 participants completed the survey and forty-five (45) participants provided urine samples for gallic acid analysis. Associations between demographic factors and the intake of certain foods were assessed. Gender differences were significantly associated with dietary behavior and urinary gallic acid concentrations. Female participants had a higher daily intake of fruits compared to male participants (p&lt;0.05). Additionally, female participants had significantly higher urinary gallic acid concentrations compared to male participants (p&lt;0.05). Other associations were also observed. Age was negatively associated with the quantity of french fries/fried potatoes and white potatoes intake (p&lt;0.05), while positively associated with frequency of fruit intake (p&lt;0.05). Furthermore, Asian race was associated with a higher frequency of fruit intake (p&lt;0.05), compared to other races. Among all recruited participants, we collected information on three cancer cases. Compared to non-cancer cases, participants with cancer reported a significantly lower fruit intake quantity (p&lt;0.05). In a multivariate analysis, we observed a significant association between fruit intake quantity and urinary gallic acid concentration (p&lt;0.05) after controlling for income. Our findings suggest that gender differences in dietary behavior and urinary gallic acid concentration may explain some of the gender differences in cancer incidence and prevalence observed in racial minority groups.
Citation Format: Cristina Zambrano, Wenyue Lu, Cicely Johnson, Maayan Beeber, April Panitz, Safa Ibrahim, Marilyn Fraser, Grace Ma, Khursheed Navder, Ming-Chin Yeh, Olorunseun Ogunwobi. Gender differences in dietary behavior and urinary gallic acid concentrations in racial minorities in New York City [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3462.
Abstract 3475: CYP3A5 inhibitor bergamottin present in grape fruit extract blocks prostate cancer cell growth
Authors: Vetrichelvan Opalina , Gorjala Priyatham , Goodman Oscar , Mitra Ranjana 
Published: September 2020

Abstract
Background: Previous research has revealed that the androgen receptor (AR), which upon activation goes to the nucleus, is the driving force of prostate cancer growth. Once activated, AR promotes transcription of genes responsible for promoting cancer growth. Previous studies have shown that inhibition of CYP3A5 blocks the activation process of the AR. CYP3A5 is a liver enzyme and together with CYP3A4 processes 50% of all commonly prescribed drugs. CYP3A5 is the extrahepatic form expressed in both normal and malignant prostate. Bergamottin, a compound found in grapefruit juice, is a known CYP3A4/5 inhibitor. Based on CYP3A5's ability to regulate AR activation, we tested the effects of bergamottin on AR activation to see if the compound can be utilized as a dietary supplement to reduce prostate cancer growth.
Methods: Western blotting, cell fractionation, and immunofluorescence were used to observe the effects of bergamottin on AR, amount of AR in nucleus/cytoplasm, and cellular localization of AR, respectively. MTT based cell growth measurement was used to see how prostate cancer cell growth was affected by bergamottin.
Results: Cell growth assay revealed that bergamottin reduced prostate cancer cell growth. The IC50 for LNCaP cells was observed to be 2.4 μM. Growth of RWPE1 cells (non transformed prostate epithelium) was not effected at the same concentration of bergamottin. Western blot analysis showed that total AR protein expression was downregulated in the bergamottin treated LNCaP and MDAPCa2b cells. Cell fractionation assay revealed that bergamottin significantly reduced nuclear AR after DHT induction compared to non-treated cells. Immunofluorescence assay confirmed reduced nuclear AR in the bergamottin treated LNCaP and MDAPCa2b cells. Furthermore, bergamottin reduced PSA levels both inside the cells and in the growth media indicating that it inhibits AR downstream signaling.
Conclusion: Our results concluded that bergamottin successfully blocked AR activation and downstream signaling, and consequently slowed down prostate cancer cell growth. The implication of this experiment is the potential use of bergamottin as a food supplement alongside other prostate cancer treatments in order to aid in blocking prostate cancer growth.
Citation Format: Opalina Vetrichelvan, Priyatham Gorjala, Oscar Goodman Jr, Ranjana Mitra. CYP3A5 inhibitor bergamottin present in grape fruit extract blocks prostate cancer cell growth [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3475.
Abstract 3491: COX-2 inhibitor use and risk of skin cancer: three prospective cohort studies
Authors: Yen Hsuan , Yen Hsi , Drucker Aaron , Han Jiali , Li Wen-Qing , Li Tricia , Qureshi Abrar , Cho Eunyoung 
Published: September 2020

Abstract
Skin cancer is the most commonly diagnosed type of cancer, with continually rising incidence rates. Cyclooxygenase-2 (COX-2) inhibitor use has been associated with lower risk of several cancers, though epidemiological studies on skin cancer risk have been limited and inconclusive. To evaluate whether COX-2 inhibitor use is associated with decreased risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, we analyzed COX-2 inhibitor use and risk of skin cancer based on three prospective cohorts–the Nurses' Health Study (NHS, 2000-2012), NHS II (2001-2011), and the Health Professionals Follow-up Study (HPFS, 2002-2012). COX-2 inhibitor use and duration were assessed by biennial questionnaires, with cSCC and melanoma cases verified by pathological records. Over 1.54 million person-years of follow-up, 16,098 BCC, 1,973 cSCC, and 625 invasive melanoma cases were documented. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of COX-2 inhibitor use with risk of BCC, cSCC, and melanoma were estimated using Cox proportional hazards models. We pooled the results between the three cohorts using a fixed effects model. For ever vs. never users, COX-2 inhibitor use was associated with a modestly increased risk of BCC (multivariable HR 1.10, 95% CI 1.06–1.15) and cSCC (multivariable HR 1.12, 95% CI 1.00–1.27). The effect estimate was similar for melanoma, but was non-significant (multivariable HR 1.10, 95% CI 0.89–1.38). In conclusion, COX-2 inhibitor use was not associated with decreased skin cancer risk and instead was associated with modestly increased risk of BCC and cSCC. Further investigation is necessary to replicate these results.
Citation Format: Hsuan Yen, Hsi Yen, Aaron Drucker, Jiali Han, Wen-Qing Li, Tricia Li, Abrar Qureshi, Eunyoung Cho. COX-2 inhibitor use and risk of skin cancer: three prospective cohort studies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3491.
Abstract 3497: The physical activity paradox in lung cancer: A systematic review and meta-analysis
Authors: Rana Benny , Hu Liang , Harper Andrew , Cao Chao , Peters Cheryl , Brenner Darren , Yang Lin 
Published: September 2020

Abstract
Objective: To deliver a systematic review of the literature synthesizing data on the association of occupational physical activity with lung cancer risk in observational studies.
Design: Systematic review with meta-analysis.
Data Source: A literature search was performed in electronic databases of PubMed/Medline and Embase.
Eligibility criteria for selecting studies: We screened for peer-reviewed articles from prospective cohort and case-control studies assessing the association of occupational physical activity with lung cancer risk. A sex-specific meta-analysis assessed the association of high (compared to low) level occupational physical activity with lung cancer risk, estimating the relative risk (RR) and odds ratio (OR) with a 95% confidence interval (CI).
Results: The systematic search identified 2065 articles, among which, 13 journal articles met the inclusion criteria. The meta-analysis adjusted for age, status and/or intensity of smoking, with a pooled sample size of 623,741 participants (men: 263,530; women: 358,589). A random-effect model of four prospective and four case-control studies indicated that men who engage in high-level occupational physical activity had a 16% higher risk (OR 1.16, 95% CI 1.00 to 1.35) of lung cancer than those engaging in low-level occupational physical activity. There was no association observed among women (RR=1.05, 95% CI 0.81 to 1.36) based on three available studies (prospective cohort: n=2; case-control: n=1).
Conclusions: Findings from the review suggest a higher risk of lung cancer among men reported high-level occupational physical activity. Further prospective studies incorporating rigorous measures of domain-specific physical activity and other occupational exposures are needed to elucidate this association.
Citation Format: Benny Rana, Liang Hu, Andrew Harper, Chao Cao, Cheryl Peters, Darren Brenner, Lin Yang. The physical activity paradox in lung cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3497.
Abstract 3543: Facile genome-wide detection of genomic fusions and other somatic chromosomal abnormalities through Bionano Whole Genome Imaging
Authors: Hastie Alex , Pang Andy W. , Lee Joyce , Lam Ernest T. , Anantharaman Thomas , Sadowski Henry , Oldakowski Mark 
Published: September 2020

Abstract
Genome instability is a key hallmark of cancer. Instability is important because it allows the genome to acquire growth advantage by amplifying or creating oncogenes by fusing otherwise non-pathogenic genes and by deleting/inactivating tumor suppressor genes. Several gene fusions have been discovered and some have been exploited for therapies as they produce fusion proteins that can be targeted by chemotherapeutics such as tyrosine-kinase inhibitors targeting BCR-ABL used to treat CML. In addition, other genomic fusions serve as diagnostic or prognostic indicators important for cancer management. Clinically, fusions are generally detected through targeted assays like NGS panels, PCR and FISH, or through karyotyping. High resolution, whole genome approaches to detect fusions are needed as current approaches have innate limitations, such as karyotyping (low resolution) and whole genome sequencing (blind in the ~66% of the genome containing repeats). Bionano whole genome imaging is able fill in the gaps, providing high resolution (~2kbp breakpoint precision) and ability to span complicated genomic repeats.
Here we demonstrate an easy, fluid, largely automated workflow for whole genome detection of fusions and other somatic variants. The Bionano workflow involves a novel rapid isolation protocol for extremely high molecular weight DNA, labeling the DNA to create a barcode across the genome and automated data collection using the Bionano Saphyr system. The assay is inexpensive and the whole workflow can be accomplished from cells/tissue to variant calls within 4 days turnaround time. Because this approach is whole genome and not masked/hidden by repeat elements, we are able to detect novel fusions that have not previously been detected. In a standard assay, whole genome imaging can detect variants at 5% allele fraction and with increased coverage fusions down to 1% allele fraction can be efficiently detected. Whole genome imaging for novel fusion detection and genome instability studies will likely play an increasing role as a complementary genomics tool in cancer research going forward.
Citation Format: Alex Hastie, Andy W. Pang, Joyce Lee, Ernest T. Lam, Thomas Anantharaman, Henry Sadowski, Mark Oldakowski. Facile genome-wide detection of genomic fusions and other somatic chromosomal abnormalities through Bionano Whole Genome Imaging [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3543.