Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2526
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":"21 1","pages":""},"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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2566
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":"27 1","pages":""},"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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2544
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":"159 1","pages":""},"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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-111
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":"1 1","pages":""},"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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2601
Amanda Cox, Ana C. Martini, Eunkyung Lee, R. Moroose, A. Khaled, A. Khaled
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.
目前评估血液中循环肿瘤细胞(CTC)的方法主要集中在上皮标记物的捕获和计数上,这些标记物很少提供关于CTC侵袭性和侵袭性潜力的信息。因此,缺乏改善癌症复发和转移监测的宝贵知识。为了提供可操作的CTC信息,我们开发了一种基于检测含有TCP1的伴侣蛋白第二亚基(CCT2)的CTC鉴定方法。CCT是一种由8个亚基(CCT1-8)组成的大分子蛋白质折叠复合物,它驱动许多致瘤因子的表达。生物信息学分析显示,在乳腺癌等多种癌症中,与正常组织相比,肿瘤组织中CCT1-8的基因表达增加(p引文格式:Amanda Cox, Ana Martini, Eunkyung Lee, Rebecca Moroose, Amr Khaled, Annette R. Khaled)。利用含有TCP1的伴侣蛋白作为标志物跟踪临床相关循环肿瘤细胞[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2601。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-LB219
Tiffany J. Gilliard, J. Pérez-Morales, M. Schabath, M. Haver
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.
背景:迄今为止,大多数肺癌筛查试验和目前的筛查指南忽视了具有不成比例肺癌负担的弱势人群,如种族和少数民族。鉴于这些服务不足人群的障碍、观念和社会经济负担,接受肺癌筛查的人数很少。为了制定和执行更好的征聘服务不足人口的方法,需要共同努力了解这些人口的障碍和看法。目的:对招募少数民族参与肺癌筛查试验或项目的方法进行系统综述。方法:我们使用Ovid MEDLINE和Embase数据库检索2010年至2020年6月期间报道招募方法和种族和少数民族用于肺癌筛查的研究。全文筛选和数据提取由两名审稿人独立完成,评审由第三名独立审稿人完成。我们比较了按种族/民族亚组和按性别招募方式的转诊率。结果:我们确定了525项研究,其中25项纳入系统评价,对应291,329例患者。最常见的招聘方法是推荐、实体邮件、社区策略、目标策略、电话、广告和社交媒体。推荐(n = 7;2510例患者)是最有效的招募方法,有效率从31%到97%不等。直接邮件(n=8项研究;189,799例患者)是第二大最广泛使用的招募方法,有效率为28%至79%。直接邮寄给西班牙裔患者(总共2995人)进行肺癌筛查项目比其他招募方法更有效。在招募非裔美国患者(共8331人)方面,直接邮寄比转诊(共1083人)更有效。结论:本综述确定了在肺癌筛查试验和项目中招募少数族裔更成功和更少不成功的招募模式。这项工作强调了在肺癌筛查中改善种族和少数民族招募的优先事项和下一步需要采取的步骤。有必要为西班牙裔/拉丁裔患者制定与文化相关的肺癌筛查干预措施,并为非洲裔美国患者制定有针对性的干预措施。引文格式:Tiffany J. Gilliard, Jaileene Perez-Morales, Matthew Schabath, Mary Katherine Haver。提高少数民族和种族在肺癌筛查项目中的代表性的方法:一项系统综述。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要nr LB219。
{"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":"83 1","pages":""},"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}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2591
P. Psarianos, Camilla Giovino, Sangeetha Paramathas, N. Patel, Rajesh Gupta, Ran Kafri, D. Malkin
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
目的:Li-Fraumeni综合征(LFS)是一种与早发性癌症显著风险相关的遗传性疾病。这种情况每5000人中就有1人患病,主要是由肿瘤抑制基因TP53的种系突变引起的,该基因具有广泛的功能,包括代谢调节。虽然LFS具有高渗透性,但其临床表型(包括发病年龄和肿瘤类型)存在很大程度的可变性。这种差异表明了患者特异性遗传因素的作用,如TP53突变的类型,这可能决定了每个人的癌症风险和对治疗的反应。临床仍然需要更好地预测LFS患者的预后,以预测疾病结局并改进治疗方案。一个新兴的文献集中在非侵入性生物标志物的识别,以分层患者群体。为此,真皮皮肤成纤维细胞(dsf)已被证明在各种情况下含有患者特异性疾病相关因子。重要的是,研究表明,不同的TP53突变可能是LFS成纤维细胞代谢模式差异的基础;因此,我们假设LFS患者的dsf代谢特征可以用作癌症风险和治疗反应的预后生物标志物。方法和结果:为了了解LFS成纤维细胞的表型多样性,我们实验室建立了小鼠异种移植模型,并将人LFS衍生的DSFs与肉瘤癌细胞系共培养。与健康个体的DSFs相比,LFS成纤维细胞在小鼠中更早地引发肿瘤发作,这表明这些成纤维细胞可能分泌致瘤因子。此外,这种作用被暴露于雷帕霉素(mTORC1蛋白激酶的抑制剂)所消除,这表明mTORC1活性可能控制这些不同成纤维细胞表型的旁分泌活性。接下来,为了探索mTORC1在LFS中的作用,我们在DSFs中诱导表达突变型p53。p53突变体促进mTORC1过度活化,导致合成代谢活性、基础呼吸和ATP产生增加,表明mTORC1可能以p53依赖的方式改变成纤维细胞代谢。总的来说,这些数据为LFS皮肤成纤维细胞的不同代谢谱提供了证据,这可能反映了LFS表型的变异性。我们实验室正在进行的工作旨在通过RNA测序和代谢组学分析进一步表征LFS成纤维细胞的代谢谱。然后,机器学习技术将用于识别与临床特征(如肿瘤发病年龄)相关的分子特征。意义:这项工作将促进我们对代谢如何支持LFS临床异质性的理解。代谢生物标志物的发现将提供预后信息,有可能改善LFS患者癌症的早期发现和治疗。引文格式:Pamela Psarianos, Camilla Giovino, Sangeetha Paramathas, Nish Patel, Rajesh Gupta, Ran Kafri, David Malkin。表征Li-Fraumeni综合征真皮成纤维细胞的代谢景观,以预测癌症风险和药物反应[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2591。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2561
Lin Yan, Sneha Sundaram, Bret M. Rust, M. Picklo, M. Bukowski
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.
乳腺癌是一种罕见但侵袭性的男性疾病。大约90%的男性乳腺癌为浸润性癌,其中25%在临床表现时有远处转移。肥胖是患乳腺癌的一个危险因素。单核细胞趋化蛋白-1 (MCP-1)是一种脂肪来源的细胞因子,其浓度因肥胖而升高。这项研究验证了脂肪来源的MCP-1与男性乳腺癌有关的假设。在2x2设计中,有或没有脂肪特异性Mcp-1基因敲低的雄性MMTV-PyMT小鼠[被称为Mcp-1-/-或野生型(WT)]被喂食标准AIN93G饮食或致肥性高脂肪饮食(HFD) 25周。AIN93G日粮和HFD分别含有16%和45%的大豆油能量。Mcp-1-/-小鼠脂肪Mcp-1表达低于WT小鼠。脂肪Mcp-1缺乏降低了喂食HFD的小鼠血浆Mcp-1浓度。无论基因型如何,喂食HFD的小鼠肿瘤进展率高于喂食AIN93G的小鼠(4679% vs 2430%)。与WT小鼠相比,Mcp-1-/-小鼠具有更长的肿瘤潜伏期(25.2周对18.0周),更低的肿瘤发病率(19%对56%),肿瘤进展率(2317%对472%)和肿瘤重量(0.23 g对0.64 g)。血浆代谢组学分析鉴定出87种代谢物,其中56种代谢物在四组中不同,其中24种在饮食中不同,22种在基因型中不同。稀疏偏最小二乘判别分析确定了四组中变化最大的10个主要代谢物。这些包括氨基酸(丙氨酸、异亮氨酸、亮氨酸、苯丙氨酸、苏氨酸和缬氨酸)和碳水化合物代谢物(富马酸、葡萄糖醛酸、己糖醛酸和苹果酸)。对鉴定的87种代谢物的综合通路分析表明,蛋白质生物合成和碳水化合物代谢途径在MMTV-PyMT小鼠中受到的干扰最大。总之,脂肪来源的MCP-1有助于乳腺肿瘤的发生,并改变雄性MMTV-PyMT小鼠的代谢。引文格式:林岩,Sneha Sundaram, Bret M. Rust, Matthew J. Picklo, Michael R. Bukowski。脂肪来源的单核细胞趋化蛋白-1在肥胖增强的男性乳腺癌模型中的致瘤性和代谢组学影响[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2561。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2569
Alex J. Smith, Paulina Do, K. Sompel, A. Elango
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.
非小细胞肺癌(NSCLC)仍然是世界上诊断最多的癌症类型,死亡率最高。治疗方法已得到高度研究,但5年生存率仍在20%左右。化学预防可以对抗肺癌高危人群的发展,比如前吸烟者。伊洛前列素是一种前列环素类似物,被证明可以减少前吸烟者支气管内发育不良的存在。Iloprost诱导卷曲蛋白9 (Fzd9)表达增加,导致过氧化物酶体增殖物激活受体γ (PPARγ)的激活和转化生长的抑制。本研究的目的是阐明吸烟、非小细胞肺癌和miRNA调控Fzd9表达的关系。我们假设,当非小细胞肺癌细胞暴露于香烟烟雾冷凝物(CSC)和Iloprost时,miRNA调节Fzd9的表达。通过计算机预测miR520a5p与Fzd9结合,并在永生化人支气管上皮细胞系(HBEC)和非小细胞肺癌细胞系中验证了miR520a5p模拟物与Fzd9 39UTR荧光素酶的结合。A549和H322 NSCLC细胞和HBEC暴露于香烟烟雾冷凝物(CSC)和伊洛前列素。CSC增加了miR520a的表达,而在Iloprost处理的细胞中则相反。我们还测量了Fzd9 39UTR活性,并证明CSC降低了Fzd9 39UTR和PPRE活性,而Iloprost则相反。我们研究了miR520a5p对Fzd9下游靶标的影响,包括PPARγ反应元件(PPRE), PPARγ活性的直接测量,以及上皮到间充质转化(EMT)基因表达,包括Cox2, E-cadherin和CRB3。我们发现当Fzd9被miR520a5p抑制时,PPRE活性和上皮基因表达受到抑制,而间充质基因表达受到刺激。将CSC与miR520a5p抑制剂或伊洛前列素与miR520a5p模拟物联合进行的拯救实验支持了miR-520a-5p在肺上皮细胞CSC致癌途径中抑制Fzd9的作用,这一作用被伊洛前列素治疗逆转。总的来说,这些发现提示了暴露于香烟烟雾的肺上皮细胞中miRNA调控Fzd9的机制和潜在的化学预防靶点。引文格式:Alex J. Smith, Paulina Do, Kayla M. Sompel, Alamelu Elango。miR520a在支气管上皮细胞和NSCLC中抑制Fzd9[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要第2569期。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-106
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":"130 1","pages":""},"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}