bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2215: Cancer awareness, tobacco use and cessation among Malayali tribes, Yelagiri Hills, Tamil Nadu, India
Authors: Francis Delfin Lovelina 
Published: June 2022

Abstract
BACKGROUND: Health is a state of complete wellbeing free from any discomfort and pain. Despite remarkable world-wide progress in the field of diagnostic, curative and preventive medicine, still there are large populations of people living in isolation in natural and unpolluted surroundings far away from civilization, maintaining their traditional values, customs, beliefs and myths. India has the second largest tribal population of the world next to the African countries. The present study was conducted to assess the cancer awareness, tobacco use, and its effect on health among Malayali tribes, Yelagiri Hills, Tamil Nadu, India.
METHODOLOGY: After a study among this population of 660 in 2010, an extended research was carried out in 2018 among 2185 participants. The inhabitants of the 14 villages of the Yelagiri hills, who were willing to participate in the study were included. Data was collected from a cross-sectional survey, using a Survey Proforma, clinical examination and a pre-tested questionnaire which included Demographic data, tobacco habits. A brief tobacco cessation counseling was given to all the users. SPSS version 21 was used for statistical analysis.
RESULTS: Results showed that among 2185 study population, 47% had no formal education. Of those who had the habit of smoking, 29% smoked beedi, 31% smoked cigarette, 39% chewed raw tobacco, 33% chewed Hans and 12% had a combination of smoking and smokeless tobacco usage. Prevalence of oral mucosal lesions 47% and 7% oral cancer in the study population was due to tobacco usage and lack of awareness regarding the deleterious effects of the products used.
CONCLUSION: From the results of this study it may be concluded that the Malayali tribes were characterized by a lack of awareness about oral health, deep rooted dental beliefs, high prevalence of tobacco use and limited access to health services.
Citation Format: Delfin Lovelina Francis. Cancer awareness, tobacco use and cessation among Malayali tribes, Yelagiri Hills, Tamil Nadu, India [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2215.
Abstract 2270: Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking
Authors: Han Hyun Ho , Sung Jin Sol , Song Dong Wook , Park Cheol Keun , Cho Nam Hoon , Choi Young Deuk , Ko Woo Jin 
Published: June 2022

Abstract
Introduction: Hyperlipidemia has been associated with increased risk of advanced stage and high Gleason grade prostate cancer (PCa), yet the underlying mechanism is not completely understood. Quaking (QKI) is an RNA-binding protein (RBP) that regulate lipid metabolism. For PCa, QKI overexpression has been associated with increased chance of metastatic recurrence.
Method: We performed RNA sequencing of prostate cancer tissues of hyperlipidemia (n = 12) and normolipidemia (n=32). Tissue samples were acquired by MRI-US fusion targeted biopsy. DESeq2 and GSEA was used to identify differently expressed genes and enriched genesets. A web-based RBP motif screening tool TRANSITE was utilized to identify active RBPs in hyperlipidemia-associated PCa.
Results: PCa samples of hyperlipidemia patients exhibited poorer histology than normolipidemia PCA. RNA sequencing found that hyperlipidemia-associated PCa is enriched of Myc-regulated genes as well as interferon or innate immunity-associated genes. Interestingly, hyperlipidemia-associated PCa gene expression signature identified PCa samples devoid of common PCa genetic alterations - TMPRSS2-ERG fusion and PTEN deletion/mutation. RBP motif screening found QKI as one of the top enriched RBP in hyperlipidemia-associated PCa transcriptome. In a separate a consecutive radical prostatectomy series (n=190), we found that QKI-high (immunohistochemistry staining score 2-3) tumors had significantly higher serum cholesterol than QKI-low (score 0-1) tumors. Overexpression and knockdown experiments proved that QKI is responsible of rapid cell proliferation and interferon-related inflammatory gene expressions, In silico analysis predicted QKI overexpressing cancer cells are susceptive to stain-mediated ferroptosis-like cell death. Mechanistically, QKI regulates expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which dictates the sensitivity of QKI overexpressing cells to ferroptosis.
Conclusion: Hyperlipidemia was associated with aggressive pathologic characteristics of PCa without TMPRSS2-ERG fusion or PTEN deletion/mutation, and high tissue expression of QKI, an RNA-binding protein. QKI overexpression in PCa increased sensitivity to ACSL4-mediated ferroptosis by statins. This explains the epidemiological associations between hyperlipidemia and PCa, and will guide molecular subtype-driven drug repurposing studies.
Citation Format: Hyun Ho Han, Jin Sol Sung, Dong Wook Song, Cheol Keun Park, Nam Hoon Cho, Young Deuk Choi, Woo Jin Ko. Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2270.
Abstract 2272: Integration of multi-omics data reveals molecular features of Hispanic hepatocellular carcinoma
Authors: Das Debodipta , Wang Xiaojing , Chiu Yu-Chiao , Bouamar Hakim , Chen Yidong , Zheng Siyuan , Cigarroa Francisco G. , Sun Lu-Zhe 
Published: June 2022

Abstract
Hepatocellular carcinoma (HCC) is the major type of liver cancer and one of the few cancers with a steady increase in incidence and mortality rate over the past several decades in the USA. It disproportionately affects Hispanics in the USA with an incidence and mortality rate about two to three times higher in Hispanics than in non-Hispanic whites. To identify molecular features associated with the Hispanic HCC we have generated genome-wide sequencing (i.e., exome-seq, RNA-seq) data and mass spectrometry-based proteomics data from HCC tumor and matched blood and/or adjacent normal tissues of Hispanic patients based in South Texas. The landscape of somatic mutation in HCC tumors revealed the aflatoxin-induced mutational signature (COSMIC) in some patients indicating an association of aflatoxin mediated toxicity in them. Similar to The Cancer Genome Atlas (TCGA) study, with predominant non-Hispanic HCC tumors, we could identify the most frequent somatic mutations in CTNNB1 and TP53. Other frequently (&gt;10%) mutated genes in our patients appear to be mutated at relatively lower rate in the TCGA patients. Mutation(s) in some of the frequently mutated genes might contribute to the significant enrichment of cellular signaling pathways observed from the Gene Set Enrichment Analysis (GSEA) using paired RNA-seq data. Single sample GSEA (ssGSEA) of our RNA-seq and proteomic data sets revealed two clusters of HCC tumors, denoted as H1 and H2 clusters, with striking differences in various signaling pathways and cellular functions. Patients from the H1 cluster and two sub-clusters within the H2 cluster showed a significant difference in their survival rate based on overall survival information from the TCGA study. The transcriptomic data from Hispanic & non-Hispanic HCC identified activated immune evasion mechanisms in H1 patients. Sorafenib treatment was found to be associated with a lower hazard ratio for overall survival in patients from the H1 cluster compared to the H2 cluster. In sum, we have identified genes more frequently mutated in Hispanic HCC than in non-Hispanic HCC, and cellular and tissue functions significantly enriched only in the Hispanic HCC. We also report a novel classification of HCC tumors with significant differences in various cellular signaling pathways and overall survival. Our findings might be used as biomarkers for the early prediction and better therapeutic management of HCC.
Citation Format: Debodipta Das, Xiaojing Wang, Yu-Chiao Chiu, Hakim Bouamar, Yidong Chen, Siyuan Zheng, Francisco G. Cigarroa, Lu-Zhe Sun. Integration of multi-omics data reveals molecular features of Hispanic hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2272.
Abstract 2306: BLU-222, an investigational, potent, and selective CDK2 inhibitor, demonstrated robust antitumor activity in CCNE1-amplified ovarian cancer models
Authors: Brown Victoria , Ramsden Phil , House Nealia , Vargas Richard , Guo Jian , Wang Ruduan , Lobbardi Riadh , Chen Maxine , Wilson Douglas , Kim Joseph , Bifulco Neil , Maynard Michelle , Perola Emanuele , Zhang Dean , Wenglowsky Steve , Choi Yoon Jong 
Published: June 2022

Abstract
Background: Cyclin-dependent kinases (CDK) are a class of enzymes that, along with their regulatory cyclin binding partners, drive cell cycle progression. Cell cycle dysregulation is a hallmark of cancer and targeting its genetic drivers can confer therapeutic benefits. Cyclin E1 (CCNE1) gene alterations are common in patients with ovarian cancer and can be found in ~20% of high-grade serous ovarian cancer cases, which tend to be platinum therapy resistant and therefore represent a high medical need. Cyclin E1 is the canonical binding partner of CDK2, which becomes constitutively active when CCNE1 is amplified and overexpressed. Selectively inhibiting CDK2 is an attractive therapeutic option for CCNE1-amplified tumors and may limit off-target CDK-driven toxicities. Here we report preclinical validation studies leading to the development of an orally available CDK2 inhibitor, BLU-222, for the treatment of ovarian cancer harboring a CCNE1 amplification.
Methods: BLU-222 selectivity was measured by enzyme assays, cellular target engagement assays (NanoBRET), and proliferation assays in a panel of ovarian cancer cell lines. In vitro cellular potency was assessed by phospho-Rb levels. In vivo antitumor activity of BLU-222 as a single agent or in combination with carboplatin was measured in an OVCAR-3 cell line-derived xenograft (CDX) tumor model harboring a CCNE1 amplification.
Results: BLU-222 demonstrated selectivity, both biochemically and in cells, with low nanomolar potency for CDK2 vs other CDK family members (CDK1, -4, -6, -7, and -9). In a panel of ovarian cancer cell lines, those with CCNE1 amplifications were highly sensitive to BLU-222. Consistent with the in vitro profiling, BLU-222 exhibited significant antitumor activity in the OVCAR-3 CDX model. While administration of single-agent carboplatin led to stasis in vivo, the combination of BLU-222 + carboplatin induced durable tumor regression even after treatment cessation.
Conclusions: These data provide a strong rationale for advancing BLU-222 towards clinical development in patients with CCNE1-amplified ovarian cancer.
Citation Format: Victoria Brown, Phil Ramsden, Nealia House, Richard Vargas, Jian Guo, Ruduan Wang, Riadh Lobbardi, Maxine Chen, Douglas Wilson, Joseph Kim, Neil Bifulco, Michelle Maynard, Emanuele Perola, Dean Zhang, Steve Wenglowsky, Yoon Jong Choi. BLU-222, an investigational, potent, and selective CDK2 inhibitor, demonstrated robust antitumor activity in CCNE1-amplified ovarian cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2306.
Abstract 2323: A bioenergetic functional screening assay workflow to identify, validate, and characterize anti-cancer compounds
Authors: Kam Yoonseok , Winer Lisa , Romero Natalia 
Published: June 2022

Abstract
As bioenergetic metabolism is recognized as a critical activity supporting cell proliferation, differentiation, and even death, many proposed targets for cancer therapy are functionally linked to cellular bioenergetic metabolism. Here, we introduce an assay workflow for screening and analyzing potential anticancer drugs affecting cellular metabolism using extracellular flux analysis. The Agilent Seahorse XF Real-Time ATP rate assay can be used as a starting point to identify therapeutic compounds that induce a perturbation in metabolic phenotype. It provides a quantitative comparison of basal mitochondrial and glycolytic activities using the universal unit of ATP production rate. Through this initial comparative screening, the effect of different compounds on basal energetic state and pathway-specific metabolic perturbations can be identified providing information that cannot be assessed by intracellular ATP level measurements or cytotoxicity assays. A more comprehensive functional analysis can then be applied to validate the target mode of action through pathway-specific analysis tools such as the XF Cell Mito Stress Test and the XF Glycolytic Rate Assay. In this study, we tested the proposed workflow in three different NSCLC cell lines with different genetic backgrounds using a mock panel of known metabolic modulators including thiosemicarbazones, EGFR inhibitors, KRAS inhibitors, a glutaminase inhibitor, a Glut1 inhibitor, a chemotherapy drug, and a radiotherapy sensitizer candidate. The ATP production rate data from lung cancer cell lines exposed for 1 hour or 24 hours to the compounds, successfully identified the effects of metabolic pathway-specific modulation as well as metabolic phenotypic switching. In addition, dose-response studies using cell lines with different genetic backgrounds demonstrated differential susceptibility to the tested compounds. The workflow was then applied using a broader panel of 72 potential mitochondrial toxicants compounds. The assay could identify potent mitochondrial and glycolytic suppressor compounds effective on A549, a lung cancer cell line. A more comprehensive XF analysis then validated the mode of action for the identified metabolic suppressors. These results demonstrate the benefit of using the XF Real-Time ATP rate assay as an initial assay to uncover novel metabolic targets in early drug discovery research, guiding further research toward functional validation with the appropriate comprehensive XF assays.
Citation Format: Yoonseok Kam, Lisa Winer, Natalia Romero. A bioenergetic functional screening assay workflow to identify, validate, and characterize anti-cancer compounds [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2323.
Abstract 2381: Interleukin-4 receptor signaling induces glycolysis in triple negative breast cancer
Authors: Williams Demond , Bindeman Wendy , Hargrove-Wiley Ebony , Fingleton Barbara 
Published: June 2022

Abstract
In the context of cancer biology Th2 cytokines such as IL4 and IL13 are most studied for their effects on immune cells such as macrophages. IL-4 receptor is established to cause polarization of macrophages to a pro-tumor M2 phenotype. While much is known about the signaling effects of IL-4 in immune cells there is relatively little known about its effects in cancer cells that express the receptor. Our lab has established a role of signaling in IL4 receptor expressing cancer cells for promoting metastasis. Many of the effects of IL-4 signaling in immune cells are accompanied by metabolic changes. Thus, we aimed to study the effects of IL-4 signaling on metabolism in breast cancer to better understand how these metabolic changes might induce metastatic phenotypes associated with IL-4 stimulation. IL-4 increased glucose uptake in multiple human TNBC cell lines assessed via NBDG uptake assay. Production of lactate was also significantly increased as assessed by colorimetric assay. We then became interested in possible alterations in metabolism downstream of increased glucose uptake. By Seahorse assay we found that IL-4 significantly increased glycolysis, as well as mitochondrial metabolism when assessed by ATP Rate assay. By metabolic flux using C13 labeled glucose we found that IL-4 increased incorporation of carbon from glucose into lactate while not having a significant effect on TCA cycle intermediates. This led us to question whether IL-4 may affect other arms of metabolism that feed into TCA cycle and mitochondrial metabolism. We looked at how IL4 impacts glutaminolysis and found that IL-4 stimulation leads to increased expression of glutamine transporter ASCT2, as well as increased glutamine uptake. We have begun to examine whether these metabolic changes affect epigenetic regulation. Initial data indicates that IL4 treatment leads to increased histone acetylation in TNBC cell lines.
Citation Format: Demond Williams, Wendy Bindeman, Ebony Hargrove-Wiley, Barbara Fingleton. Interleukin-4 receptor signaling induces glycolysis in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2381.
Abstract 2382: Aberrant glycogen accumulation alters gene expression and promotes lung tumor progression in vivo
Authors: Lamb Jessica Faith , Conroy Lindsey R. , James Alexis N. , Buoncristiani Michael D. , Relich Eric R. , Young Lindsay E. , Branson Christine F. , Sun Ramon C. 
Published: June 2022

Abstract
Lung cancer is one of the most prevalent cancers worldwide, accounting for nearly two million new cases each year. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and is the leading cause of cancer related mortalities worldwide. LUAD has an extremely poor five-year survival rate, which is likely due to cases being diagnosed at advanced stages and thus being more difficult to treat the metastatic disease. Identifying the molecular processes that contribute to disease progression is a critical goal in lung cancer research that could lead to predictive biomarkers and novel therapies. Glycogen is the primary form of carbohydrate storage in mammalian cells, and its degradation product, Glucose 6-Phosphate (G6P) feeds directly into glycolysis, making glycogen intimately connected to central carbon metabolism. Recently, aberrant glycogen accumulation in lung tumors has been reported to promote lung cancer progression, driven by largely unknown mechanisms. We recently generated a transgenic KRASG12D/p53-/- LUAD mouse model that also lacks the glycogen phosphatase laforin (LKO). This model develops increased glycogen accumulation in the lungs and displays accelerated tumor growth compared to the KRASG12D/p53-/- control (WT), as measured by Ki67 staining. To identify potential biological processes perturbed by LUAD-glycogen, we performed RNA-seq on lung tumors resected from WT and LKO mice. We identified over 300 genes that are differentially expressed between WT and LKO lung tumors. Specifically, gene set enrichment analysis (GSEA) revealed genes that were upregulated in LKO lung tumors were involved in extracellular matrix remodeling, cell-to-cell communication, and cell proliferation. All of these processes are implicated in tumor growth, which supports our initial observation that LKO mice have increased tumor burden and disease progression. Our findings ultimately highlight several potential mechanisms by which LUAD-glycogen promotes LUAD tumor progression, which can be further investigated to identify novel biomarkers and therapeutic targets.
Citation Format: Jessica Faith Lamb, Lindsey R. Conroy, Alexis N. James, Michael D. Buoncristiani, Eric R. Relich, Lindsay E. Young, Christine F. Branson, Ramon C. Sun. Aberrant glycogen accumulation alters gene expression and promotes lung tumor progression in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2382.
Abstract 2385: A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary cancer
Authors: Farhat Zeinab , Freedman Neal D. , Sampson Joshua N. , Falk Roni T. , Koshiol Jill , Weinstein Stephanie J. , Albanes Demetrius , Sinha Rashmi , Loftfield Erikka 
Published: June 2022

Abstract
Abstract Background: Laboratory and emerging epidemiologic data suggest that bile acids (BAs), major regulators of the gut microbiota, play an important role in liver disease and cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and either liver endpoints or biliary cancer.
Methods: In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, we designed 1:1 matched nested case-control studies of primary liver cancer (n=247 cases), fatal liver disease (n=261 cases), and primary biliary cancer (n=92 cases). Using baseline serum collected ≤30 years prior to diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography tandem mass spectrometry. We used multivariable conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between BAs and each endpoint, accounting for multiple comparisons.
Results: Comparing the highest to the lowest quartile, ten BAs were positively associated with liver cancer risk, including taurocholic (OR =4.70, 95% CI=2.51-8.78; Q-trend&lt;0.0001), taurochenodeoxycholic (OR =4.61, 95% CI=2.38-8.91; Q-trend&lt;0.0001), and glycocholic acid OR =4.11, 95% CI=2.11-7.99; Q-trend&lt;0.0001), and 11 were positively associated with fatal liver disease risk, including taurochenodeoxycholic acid (OR =9.65, 95% CI=4.41-21.14; Q-trend&lt;0.0001), taurocholic OR =7.45, 95% CI=3.70-14.97; Q-trend&lt;0.0001), taurochenodeoxycholic (OR =9.05, 95% CI=4.04-20.32; Q-trend&lt;0.0001), and glycocholic acid OR=6.12, 95% CI=2.84-13.77; Q-trend&lt;0.0001). No significant associations were observed between BAs and biliary cancer though ORs were consistently &gt;1.
Conclusion: Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between the gut microbiota, BA signaling pathways, and liver cancer or death from liver disease.
Citation Format: Zeinab Farhat, Neal D. Freedman, Joshua N. Sampson, Roni T. Falk, Jill Koshiol, Stephanie J. Weinstein, Demetrius Albanes, Rashmi Sinha, Erikka Loftfield. A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2385.