S. Sharad, Z. Sztupinszki, Z. Szallasi, S. Srivastava, A. Srinivasan, A. Dobi, Hua Li
{"title":"Abstract 2526: PMEPA1 gene isoforms indicated aggressive disease progression in non-prostate solid tumors","authors":"S. Sharad, Z. Sztupinszki, Z. Szallasi, S. Srivastava, A. Srinivasan, A. Dobi, Hua Li","doi":"10.1158/1538-7445.AM2021-2526","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2526","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86581123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atieh Hajirahimkhan, Caitlin E. Howell, Shao-Nong Chen, S. Clare, G. Pauli, J. Bolton, B. Dietz, S. Khan
{"title":"Abstract 2566: The potential role of licorice and its bioactive compounds in promoting a tumor preventive environment in the postmenopausal breast","authors":"Atieh Hajirahimkhan, Caitlin E. Howell, Shao-Nong Chen, S. Clare, G. Pauli, J. Bolton, B. Dietz, S. Khan","doi":"10.1158/1538-7445.AM2021-2566","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2566","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89575645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Zaidi, K. Shetty, Herbert Yu, Linda Wong, Shuyun Rao, W. Jogunoori, R. Amdur, Shulin Li, P. Latham, B. Nguyen, L. Mishra
{"title":"Abstract 2544: TGF-β receptors 1 and 2 are functional biomarkers that stratify risk of hepatocellular cancer (HCC). Artificial intelligence based validation at three centers","authors":"S. Zaidi, K. Shetty, Herbert Yu, Linda Wong, Shuyun Rao, W. Jogunoori, R. Amdur, Shulin Li, P. Latham, B. Nguyen, L. Mishra","doi":"10.1158/1538-7445.AM2021-2544","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2544","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80715595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Slava Katerov, A. Vaccaro, Jacquelyn Hennek, J. Carlson, W. Taylor, D. Mahoney, J. Kisiel, H. Allawi
{"title":"Abstract 111: Accurate multi-cancer detection using methylated DNA markers and proteins in plasma","authors":"Slava Katerov, A. Vaccaro, Jacquelyn Hennek, J. Carlson, W. Taylor, D. Mahoney, J. Kisiel, H. Allawi","doi":"10.1158/1538-7445.AM2021-111","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-111","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76918688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amanda Cox, Ana C. Martini, Eunkyung Lee, R. Moroose, A. Khaled, A. Khaled
{"title":"Abstract 2601: Using chaperonin containing TCP1 as a marker to track clinically relevant circulating tumor cells","authors":"Amanda Cox, Ana C. Martini, Eunkyung Lee, R. Moroose, A. Khaled, A. Khaled","doi":"10.1158/1538-7445.AM2021-2601","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2601","url":null,"abstract":"Current methods for assessing circulating tumor cells (CTC) in blood focus on capture and enumeration with epithelial markers that provide little information about the aggressive and invasive potential of CTC. As a result, valuable knowledge that improves monitoring of cancer recurrence and metastasis is lacking. To provide actionable information on CTC, we developed a CTC identification method based on detection of the second subunit of Chaperonin Containing TCP1 (CCT2). CCT is a macromolecular protein folding complex composed of eight subunits (CCT1-8) that drives expression of many tumorigenic factors. Bioinformatic analysis in multiple cancers, such as breast cancer, revealed increased gene expression in tumor tissue compared to normal tissue for CCT1-8 (p Citation Format: Amanda Cox, Ana Martini, Eunkyung Lee, Rebecca Moroose, Amr Khaled, Annette R. Khaled. Using chaperonin containing TCP1 as a marker to track clinically relevant circulating tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2601.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80804420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiffany J. Gilliard, J. Pérez-Morales, M. Schabath, M. Haver
{"title":"Abstract LB219: Methods to improve representation of racial and ethnic minorities in lung cancer screening programs: A systematic review","authors":"Tiffany J. Gilliard, J. Pérez-Morales, M. Schabath, M. Haver","doi":"10.1158/1538-7445.AM2021-LB219","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB219","url":null,"abstract":"Background: Most lung cancer screening trials to date and current screening guidelines overlook vulnerable populations with disproportionate lung cancer burden such as racial and ethnic minorities. Given the barriers, perceptions, and socioeconomic burden of these underserved populations, uptake of lung cancer screening has minimal. To develop and implement better methods of recruitment underserved populations, concerted efforts to understand the barriers and perceptions of these population are needed. Objective: Conduct a systematic review of methods for recruitment of racial and ethnic minorities into lung cancer screening trials or programs. Methods: We searched for studies that reported methods of recruitment and racial and ethnic minorities into lung cancer screening from 2010 to June 2020, using Ovid MEDLINE and Embase databases. Full-text screening and data extraction were completed independently by two reviewers and adjudication was performed by a third, independent reviewer. We compared referral rates of the recruitment modalities by racial/ethnic subgroups and by sex. Results: We identified 525 studies of which 25 were included in the systematic review corresponding to 291,329 patients. The most frequent methods of recruitment were referral, physical mail, community-based strategies, targeted strategies, phone, advertisement, and social media. Referral (n=7; 2,510 patients) was the most effective method of recruitment with response rates ranging from 31% to 97%. Direct mail (n=8 studies; 189,799 patients) was the second most extensively used recruitment method with response rates of 28% to 79%. Direct mail to Hispanic patients (2,995 total) for lung cancer screening programs was more effective than other methods of recruitment. Direct mail was more effective in recruiting African American patients (8,331 total) compared to referral (1,083 total). Conclusion: This review identified recruitment modalities that were more successful and less unsuccessful in recruiting racial and ethnic minorities into lung cancer screening trials and programs. This work highlights priorities and next steps required to improve recruitment of racial and ethnic minorities in lung cancer screening. There is a need to develop culturally relevant lung cancer screening interventions for Hispanics/Latino patients and to create targeted intervention for African American patients. Citation Format: Tiffany J. Gilliard, Jaileene Perez-Morales, Matthew Schabath, Mary Katherine Haver. Methods to improve representation of racial and ethnic minorities in lung cancer screening programs: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB219.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79332198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Psarianos, Camilla Giovino, Sangeetha Paramathas, N. Patel, Rajesh Gupta, Ran Kafri, D. Malkin
{"title":"Abstract 2591: Characterizing the metabolic landscape of dermal fibroblasts in Li-Fraumeni Syndrome for the prediction of cancer risk and drug response","authors":"P. Psarianos, Camilla Giovino, Sangeetha Paramathas, N. Patel, Rajesh Gupta, Ran Kafri, D. Malkin","doi":"10.1158/1538-7445.AM2021-2591","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2591","url":null,"abstract":"Purpose: Li-Fraumeni Syndrome (LFS) is a genetic disorder associated with a significant risk of early-onset cancer. This condition affects 1 in 5000 individuals and is largely driven by germline mutations in the TP53 tumor suppressor gene, which has a broad spectrum of functions including metabolic regulation. While LFS is highly penetrant, there is a wide degree of variability in clinical phenotype, including age of onset and tumor type. This variability suggests a role for patient-specific genetic factors, such as the type of TP53 mutation, which may define each individual9s cancer risk and response to therapy. There remains a significant clinical need for better prognostication of LFS patients to predict disease outcomes and improve treatment options. An emerging body of literature is focused on the identification of non-invasive biomarkers to stratify patient populations. To this end, dermal skin fibroblasts (DSFs) have been shown to contain patient-specific disease correlates in a variety of conditions. Importantly, it has been shown that different TP53 mutations may underlie differential metabolic patterns in LFS fibroblasts; hence, we hypothesize that the metabolic signatures of DSFs from LFS patients can be utilized as prognostic biomarkers of cancer risk and response to treatment. Methods and Results: To understand the phenotypic diversity of LFS fibroblasts, our lab created a mouse xenograft model and co-cultured human LFS-derived DSFs with a sarcoma cancer cell line. LFS fibroblasts initiated earlier tumor onset in the mice compared to DSFs from healthy individuals, suggesting that these fibroblasts may secrete tumorigenic factors. Moreover, this effect was abrogated by exposure to rapamycin, an inhibitor of the mTORC1 protein kinase, suggesting that mTORC1 activity may govern the paracrine activity of these divergent fibroblast phenotypes. Next, to explore the role of mTORC1 in LFS, we used inducible expression of mutant p53 in DSFs. p53 mutants promoted mTORC1 hyperactivation, leading to increased anabolic activity, basal respiration and ATP production, suggesting that mTORC1 may alter fibroblast metabolism in a p53-dependent manner. Overall, these data provide evidence for divergent metabolic profiles of LFS skin fibroblasts which may reflect LFS phenotype variability. Ongoing work in our lab aims to further characterize the metabolic profiles of LFS fibroblasts through RNA sequencing and metabolomic profiling. Machine learning techniques will then be employed to identify molecular signatures correlating with clinical features such as age of tumor onset. Significance: This work will advance our understanding of how metabolism may underpin the clinical heterogeneity of LFS. The discovery of metabolic biomarkers will provide prognostic information with the potential to improve the early detection and treatment of cancers in LFS patients. Citation Format: Pamela Psarianos, Camilla Giovino, Sangeetha Paramathas, Nish Patel, Rajesh Gupta","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81100827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lin Yan, Sneha Sundaram, Bret M. Rust, M. Picklo, M. Bukowski
{"title":"Abstract 2561: Tumorigenic and metabolomic impacts of adipose-derived monocyte chemotactic protein-1 in a model of obesity-enhanced, male breast cancer","authors":"Lin Yan, Sneha Sundaram, Bret M. Rust, M. Picklo, M. Bukowski","doi":"10.1158/1538-7445.AM2021-2561","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2561","url":null,"abstract":"Breast cancer is a rare but aggressive disease in men. Approximately, 90% of all breast cancer in men are invasive carcinomas, 25% of which have distant metastasis at the time of clinical presentation. Obesity is a risk factor for breast cancer. Monocyte chemotactic protein-1 (MCP-1) is an adipose-derived cytokine whose concentrations are elevated by obesity. This study tested the hypothesis that adipose-derived MCP-1 contributes to male breast cancer. In a 2x2 design, male MMTV-PyMT mice with or without adipose specific Mcp-1 knockdown [designated as Mcp-1-/- or wild-type (WT)] were fed the standard AIN93G diet or an obesogenic, high-fat diet (HFD) for 25 weeks. The AIN93G diet and HFD contained 16% and 45% of energy from soybean oil, respectively. Mcp-1-/- mice had lower adipose Mcp-1 expression than WT mice. Adipose Mcp-1 deficiency reduced plasma concentrations of MCP-1 in mice fed the HFD. Mice fed the HFD had a greater tumor progression rate than mice fed the AIN93G diet (4679% vs 2430%), regardless of genotype. Mcp-1-/- mice, compared to WT mice, had a longer tumor latency (25.2 weeks vs 18.0 weeks) and lower tumor incidence (19% vs 56%), tumor progression rate (2317% vs 4792%), and tumor weights (0.23 g vs 0.64 g). Metabolomic analysis of plasma identified 87 metabolites, 56 of which differed among the four groups, including 24 that differed between the diets and 22 that differed between the genotypes. Sparse partial least squares-discriminant analysis identified 10 major metabolites that were altered the most among the four groups. These included amino acids (alanine, isoleucine, leucine, phenylalanine, threonine, and valine) and carbohydrate metabolites (fumaric acid, glucuronic acid, hexuronic acid, and malic acid). The integrated pathway analysis of the 87 identified metabolites showed that protein biosynthesis and carbohydrate metabolism pathways are the most disturbed in MMTV-PyMT mice. In conclusion, adipose-derived MCP-1 contributes to mammary tumorigenesis and alters metabolism in male MMTV-PyMT mice. Citation Format: Lin Yan, Sneha Sundaram, Bret M. Rust, Matthew J. Picklo, Michael R. Bukowski. Tumorigenic and metabolomic impacts of adipose-derived monocyte chemotactic protein-1 in a model of obesity-enhanced, male breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2561.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79312150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstract 2569: miR520a inhibits Fzd9 in bronchial epithelial cells and NSCLC","authors":"Alex J. Smith, Paulina Do, K. Sompel, A. Elango","doi":"10.1158/1538-7445.AM2021-2569","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2569","url":null,"abstract":"Non-small cell lung cancer (NSCLC) continues to be the most diagnosed cancer type worldwide and has the highest mortality rate. Treatment is highly researched, but 5 year survival remains around 20%. Chemoprevention could combat the development of lung cancer in individuals who are at high risk, such as former cigarette smokers. Iloprost is a prostacyclin analogue demonstrated to reduce the presence of endobronchial dysplasia in former smokers. Increased Frizzled-9 (Fzd9) expression is induced by Iloprost, resulting in activation of peroxisome proliferator activated receptor γ (PPARγ) and inhibition of transformed growth. The goal of this study is to elucidate the relationship of cigarette smoke, NSCLC, and miRNA regulation of Fzd9 expression. We hypothesized that miRNA regulate Fzd9 expression when NSCLC cells are exposed to both cigarette smoke condensate (CSC) and Iloprost. miR520a5p was predicted in silico to bind Fzd9 and we validated binding with a miR520a5p mimic and Fzd9 39UTR luciferase in an immortalized human bronchial epithelial cell line (HBEC) and NSCLC cell lines. A549 and H322 NSCLC cells and HBEC were exposed to cigarette smoke condensate (CSC) and Iloprost. CSC increased miR520a expression, while the opposite was observed in Iloprost treated cells. We also measured Fzd9 39UTR activity and demonstrated that CSC decreases both Fzd9 39UTR and PPRE activity, while Iloprost does the opposite. We investigated the effect of miR520a5p on targets downstream of Fzd9, including PPARγ response element (PPRE), a direct measure of PPARγ activity, and epithelial to mesenchymal transition (EMT) gene expression, including Cox2, E-cadherin, and CRB3. We found that when Fzd9 is inhibited by miR520a5p, PPRE activity and epithelial gene expression are inhibited, while mesenchymal gene expression is stimulated. Rescue experiments combining CSC with a miR520a5p inhibitor or iloprost with a miR520a5p mimic supported a role for miR-520a-5p in inhibition of Fzd9 in a CSC carcinogenic pathway in lung epithelial cells that is reversed with iloprost treatment. Overall, these findings suggest a mechanism for miRNA regulation of Fzd9 in lung epithelial cells exposed to cigarette smoke and a potential chemoprevention target. Citation Format: Alex J. Smith, Paulina Do, Kayla M. Sompel, Alamelu Elango. miR520a inhibits Fzd9 in bronchial epithelial cells and NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2569.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82221739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren Palluth, B. Harlow, Bryan McCellan, C. Jolly, Molly S. Bray, Linda A. Degraffenried
{"title":"Abstract 106: Assessing the impact of staggered light exposure on breast cancer risk and metabolism","authors":"Lauren Palluth, B. Harlow, Bryan McCellan, C. Jolly, Molly S. Bray, Linda A. Degraffenried","doi":"10.1158/1538-7445.AM2021-106","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-106","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73762944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}