Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2558
M. Wilson, Jake J. Reske, R. Chandler
{"title":"Abstract 2558: Understanding the shared roles of obesity and genetic mutation in the development of endometrial cancer","authors":"M. Wilson, Jake J. Reske, R. Chandler","doi":"10.1158/1538-7445.AM2021-2558","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2558","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79979480","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.AM2021-2589
A. Bhardwaj, Z. Ju, Matthew D Embury, Jing Wang, I. Bedrosian
Introduction: Cholesterol biosynthesis pathway is highly regulated and inhibition of the pathway with statins is known to cause restorative upregulation of several genes in the pathway. The goal of this study is to investigate if the statin mediated upregulation in the cholesterol biosynthesis pathway genes associates with the resistance to fluvastatin in a model of hormonally insensitive breast cancer Methods: A published gene signature of statin resistance was validated 1) a cell line based model of breast cancer progression consisting of inherently fluvastatin sensitive and inherently fluvastatin resistant cell lines and also compared to our experimentally derived acquired signature of fluvastatin resistance using 2) an isogenic set of cell lines consisting of a fluvastatin sensitive cell line (MCF10.AT1), and an acquired resistant cell line (MCF10.AT- R) and lastly validated using 3) SV40 C3 tag, a mouse model of hormone receptor negative breast cancer. Clariom RNA profiling were processed and mined by IPA analysis to identify the fluvastatin resistance signature that were validated by qPCR. Fluvastatin resistance was determined in vitro by colony formation assay and in vivo in a mouse model of breast cancer. Results: We found more than 75% of the published 17 gene panel fluvastatin resistance gene signature (consisting of cholesterol biosynthesis pathway genes) to be significantly upregulated in an inherently resistant cell line, DCIS cell line, relative to fluvastatin sensitive preneoplastic, MCF10.AT1 cell line. We found this inherent statin resistance gene signature to be also relevant in the MCF10.AT-R resistant cells as we found 13 of these genes to map to top 3 upregulated pathways that are steroid biosynthesis, steroid hormone biosynthesis and terpenoid backbone biosynthesis pathway. Next, we tested if 17 gene statin resistance signature associates with presence of tumors in the mammary glands of fluvastatin treated mice and found upregulation of more than 50% of the genes in the resistance signature in the tumor bearing mammary glands. Lastly, we studied if a 10-day period of fluvastatin treatment to SV40C3 Tag mice, a spontaneous mouse model of breast cancer, can also trigger the upregulation of these cholesterol biosynthesis pathway genes and provide an early signal of statin resistance. These experiments showed that a 10-day period is not long enough to cause a feedback upregulation in steroid biosynthesis pathway genes and thus can9t be used a surrogate timepoint to detect resistance to fluvastatin. Conclusions: Upregulation of multiple steroid biosynthesis pathway genes after fluvastatin treatment suggests an opportunity of dual targeting of the cholesterol biosynthesis pathway in order to sensitize the fluvastatin resistant breast cancer cells. Citation Format: Anjana Bhardwaj, Zhenlin Ju, Matthew Embury, Jing Wang, Isabelle Bedrosian. Gene signature of fluvastatin resistance for prevention of breast cancer and predicting resis
{"title":"Abstract 2589: Gene signature of fluvastatin resistance for prevention of breast cancer and predicting resistance to statins","authors":"A. Bhardwaj, Z. Ju, Matthew D Embury, Jing Wang, I. Bedrosian","doi":"10.1158/1538-7445.AM2021-2589","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2589","url":null,"abstract":"Introduction: Cholesterol biosynthesis pathway is highly regulated and inhibition of the pathway with statins is known to cause restorative upregulation of several genes in the pathway. The goal of this study is to investigate if the statin mediated upregulation in the cholesterol biosynthesis pathway genes associates with the resistance to fluvastatin in a model of hormonally insensitive breast cancer Methods: A published gene signature of statin resistance was validated 1) a cell line based model of breast cancer progression consisting of inherently fluvastatin sensitive and inherently fluvastatin resistant cell lines and also compared to our experimentally derived acquired signature of fluvastatin resistance using 2) an isogenic set of cell lines consisting of a fluvastatin sensitive cell line (MCF10.AT1), and an acquired resistant cell line (MCF10.AT- R) and lastly validated using 3) SV40 C3 tag, a mouse model of hormone receptor negative breast cancer. Clariom RNA profiling were processed and mined by IPA analysis to identify the fluvastatin resistance signature that were validated by qPCR. Fluvastatin resistance was determined in vitro by colony formation assay and in vivo in a mouse model of breast cancer. Results: We found more than 75% of the published 17 gene panel fluvastatin resistance gene signature (consisting of cholesterol biosynthesis pathway genes) to be significantly upregulated in an inherently resistant cell line, DCIS cell line, relative to fluvastatin sensitive preneoplastic, MCF10.AT1 cell line. We found this inherent statin resistance gene signature to be also relevant in the MCF10.AT-R resistant cells as we found 13 of these genes to map to top 3 upregulated pathways that are steroid biosynthesis, steroid hormone biosynthesis and terpenoid backbone biosynthesis pathway. Next, we tested if 17 gene statin resistance signature associates with presence of tumors in the mammary glands of fluvastatin treated mice and found upregulation of more than 50% of the genes in the resistance signature in the tumor bearing mammary glands. Lastly, we studied if a 10-day period of fluvastatin treatment to SV40C3 Tag mice, a spontaneous mouse model of breast cancer, can also trigger the upregulation of these cholesterol biosynthesis pathway genes and provide an early signal of statin resistance. These experiments showed that a 10-day period is not long enough to cause a feedback upregulation in steroid biosynthesis pathway genes and thus can9t be used a surrogate timepoint to detect resistance to fluvastatin. Conclusions: Upregulation of multiple steroid biosynthesis pathway genes after fluvastatin treatment suggests an opportunity of dual targeting of the cholesterol biosynthesis pathway in order to sensitize the fluvastatin resistant breast cancer cells. Citation Format: Anjana Bhardwaj, Zhenlin Ju, Matthew Embury, Jing Wang, Isabelle Bedrosian. Gene signature of fluvastatin resistance for prevention of breast cancer and predicting resis","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77052818","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.AM2021-2522
Xiu Liu, Xuan Zhang, K. Ou, Chelong Lu, Dong-Huan Zheng, Jun Liu, Qiang Xu, Lin Yang
{"title":"Abstract 2522: Exploring the prognostic and predictive value of circulating tumor DNA in patients with advanced colorectal cancer and chemotherapy","authors":"Xiu Liu, Xuan Zhang, K. Ou, Chelong Lu, Dong-Huan Zheng, Jun Liu, Qiang Xu, Lin Yang","doi":"10.1158/1538-7445.AM2021-2522","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2522","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":"83204896","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.AM2021-109
Jill P. Smith, H. Cao, B. Kallakury, T. Phillips, L. Sutton, A. Cato
{"title":"Abstract 109: Vaccination with Polyclonal Antibody Stimulator (PAS) prevents pancreatic carcinogenesis in the KRAS mouse model","authors":"Jill P. Smith, H. Cao, B. Kallakury, T. Phillips, L. Sutton, A. Cato","doi":"10.1158/1538-7445.AM2021-109","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-109","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88693535","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-LB222
Louise Wang, H. Desai, A. Le, R. Hausler, S. Verma, A. Verma, R. Judy, A. Doucette, P. Gabriel, S. Damrauer, M. Ritchie, Daniel Rader, R. Kember, K. Maxwell
Background: Genome wide association studies (GWAS) have identified hundreds of common, low risk genetic variants significantly associated with a number of gastrointestinal cancers, but the predictive ability of individual variants or a polygenic risk score (PRS) derived from multiple variants is still unclear especially among minorities. Specific Aims: To evaluate the discriminatory ability of PRS models to differentiate cancer cases vs. controls in patients of European (EUR) and African (AFR) ancestry in an academic biobank. Methods: We identified 445 cases of esophageal, colon, and pancreatic cancers and 12,565 cancer-free controls. Genome-wide significant variants were selected for each of the cancers, and Plink 1.9 was used to generate a PRS, an effect size weighted sum of specific cancer associated alleles for each population. To determine the discriminatory ability of PRS, we performed multivariate logistic regressions in R controlling for age, sex, and the first 10 principal components. Results: There were 285 cases of colon (48.4% AFR), 63 cases of esophageal (34.9% AFR), and 97 cases of pancreatic cancer (51.5% AFR) vs. 12,565 controls (48.5% AFR). Among the EUR individuals, the PRScolon was significantly associated with colon cancer [OR 1.25 (1.06-4.48, p=0.007)] (Table 1). The discriminatory ability of the model comprised of age, gender and principal components was 0.680-0.732 in the respective cancer cancers and the AUC minimally increased to 0.688-0.747 after inclusion of the PRS in the model. Among AFR individuals, the discriminatory ability was overall higher in the full model (AUC 0.755-0.812) but PRS increased the AUC less in AFR vs. EUR. Conclusion: Colon, esophageal, and pancreatic cancer PRS models have a moderate discriminatory ability to identify cases. However, the individual contribution of PRS to the model was small. Further studies are needed to determine additional genetic predictors of cancer risk and how best to incorporate PRS into gastrointestinal cancer risk prediction models. Citation Format: Louise Wang, Heena Desai, Anh Le, Ryan Hausler, Shefali Verma, Anurag Verma, Renae Judy, Abigail Doucette, Peter Gabriel, Scott Damrauer, Marylyn Ritchie, Daniel Rader, Rachel Kember, Kara Maxwell. Performance of polygenic risk scores for GI cancer prediction in an academic biobank [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 LB222.
背景:全基因组关联研究(GWAS)已经确定了数百种常见的低风险遗传变异与许多胃肠道癌症显著相关，但个体变异或多基因风险评分(PRS)的预测能力仍不清楚，特别是在少数民族中。具体目的:评估PRS模型在学术生物库中区分欧洲(EUR)和非洲(AFR)血统患者的癌症病例与对照组的区别能力。方法:我们确定了445例食管癌、结肠癌和胰腺癌以及12565例无癌对照。为每种癌症选择全基因组显著变异，并使用Plink 1.9生成PRS，即每个人群的特定癌症相关等位基因的效应大小加权总和。为了确定PRS的区分能力，我们对年龄、性别和前10个主成分进行了多变量logistic回归。结果:结肠癌285例(48.4%)，食管癌63例(34.9%)，胰腺癌97例(51.5%)，对照组12565例(48.5%)。在EUR个体中，PRScolon与结肠癌显著相关[OR 1.25 (1.06-4.48, p=0.007)](表1)。由年龄、性别和主成分组成的模型在各自癌症中的区分能力为0.680-0.732，将PRS纳入模型后，AUC最低增加到0.688-0.747。在AFR个体中，在完整模型中，歧视能力总体上更高(AUC 0.755-0.812)，但与欧元相比，PRS对AFR个体的AUC增加较少。结论:结肠癌、食管癌和胰腺癌PRS模型具有中等的鉴别能力。然而，PRS对模型的个人贡献很小。需要进一步的研究来确定癌症风险的其他遗传预测因子，以及如何最好地将PRS纳入胃肠道癌症风险预测模型。引文格式:Louise Wang, Heena Desai, Anh Le, Ryan Hausler, Shefali Verma, Anurag Verma, Renae Judy, Abigail Doucette, Peter Gabriel, Scott Damrauer, marilyn Ritchie, Daniel Rader, Rachel Kember, Kara Maxwell。多基因风险评分在学术生物库中预测胃肠道癌症的表现[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nr LB222。
{"title":"Abstract LB222: Performance of polygenic risk scores for GI cancer prediction in an academic biobank","authors":"Louise Wang, H. Desai, A. Le, R. Hausler, S. Verma, A. Verma, R. Judy, A. Doucette, P. Gabriel, S. Damrauer, M. Ritchie, Daniel Rader, R. Kember, K. Maxwell","doi":"10.1158/1538-7445.AM2021-LB222","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB222","url":null,"abstract":"Background: Genome wide association studies (GWAS) have identified hundreds of common, low risk genetic variants significantly associated with a number of gastrointestinal cancers, but the predictive ability of individual variants or a polygenic risk score (PRS) derived from multiple variants is still unclear especially among minorities. Specific Aims: To evaluate the discriminatory ability of PRS models to differentiate cancer cases vs. controls in patients of European (EUR) and African (AFR) ancestry in an academic biobank. Methods: We identified 445 cases of esophageal, colon, and pancreatic cancers and 12,565 cancer-free controls. Genome-wide significant variants were selected for each of the cancers, and Plink 1.9 was used to generate a PRS, an effect size weighted sum of specific cancer associated alleles for each population. To determine the discriminatory ability of PRS, we performed multivariate logistic regressions in R controlling for age, sex, and the first 10 principal components. Results: There were 285 cases of colon (48.4% AFR), 63 cases of esophageal (34.9% AFR), and 97 cases of pancreatic cancer (51.5% AFR) vs. 12,565 controls (48.5% AFR). Among the EUR individuals, the PRScolon was significantly associated with colon cancer [OR 1.25 (1.06-4.48, p=0.007)] (Table 1). The discriminatory ability of the model comprised of age, gender and principal components was 0.680-0.732 in the respective cancer cancers and the AUC minimally increased to 0.688-0.747 after inclusion of the PRS in the model. Among AFR individuals, the discriminatory ability was overall higher in the full model (AUC 0.755-0.812) but PRS increased the AUC less in AFR vs. EUR. Conclusion: Colon, esophageal, and pancreatic cancer PRS models have a moderate discriminatory ability to identify cases. However, the individual contribution of PRS to the model was small. Further studies are needed to determine additional genetic predictors of cancer risk and how best to incorporate PRS into gastrointestinal cancer risk prediction models. Citation Format: Louise Wang, Heena Desai, Anh Le, Ryan Hausler, Shefali Verma, Anurag Verma, Renae Judy, Abigail Doucette, Peter Gabriel, Scott Damrauer, Marylyn Ritchie, Daniel Rader, Rachel Kember, Kara Maxwell. Performance of polygenic risk scores for GI cancer prediction in an academic biobank [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 LB222.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87140927","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.AM2021-2587
A. Benmoussa, L. Levasseur, Shuxia Coté-Sergerie, V. Bélanger, E. Levy, C. Laverdière, A. Stintzi, D. Sinnett, V. Marcil
{"title":"Abstract 2587: Investigating the impact of chemotherapy on gut microbiota and microbiota-derived metabolites and their link to inflammation and cardiometabolic disorders in children with cancer","authors":"A. Benmoussa, L. Levasseur, Shuxia Coté-Sergerie, V. Bélanger, E. Levy, C. Laverdière, A. Stintzi, D. Sinnett, V. Marcil","doi":"10.1158/1538-7445.AM2021-2587","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2587","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90627887","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.AM2021-2599
A. G. Theakstone, Paul M. Brennan, M. Baker
This study focuses on investigating the link between brain tumor volume and the spectroscopic classification between patients with known gliomas and healthy controls. Discrimination of brain cancer vs. non-cancer patients using serum-based ATR-FTIR diagnostics was first developed by Hands et al. achieving sensitivity and specificity values of 92.8% and 91.5% respectively. Cameron et al. then went on to stratifying between specific brain tumor types and was successful in providing a sensitivity of 90.1% and a specificity of 86.3%. Expanding on these studies, it is vital to determine if the size of a tumor has a direct effect on the sensitivity and specificity and whether or not it was only the larger tumors that were being identified as cancerous. A cohort of 90 patients whose tumor volumes were calculated using their MRI images (either T1-weighted contrast enhanced, T2-weighted or FLAIR images), including patients with high-grade glioblastoma multiforme (GBM), and low-grade gliomas such as anaplastic astrocytoma, astrocytoma, oligoastrocytoma and oligodendroglioma, were used for investigation. Utilizing ATR-FTIR spectroscopy coupled with machine learning algorithms these tumor patients were stratified against 87 healthy controls and were classified as either cancer or non-cancer. From these initial findings9 sensitivities, specificities and balanced accuracies were greater than 88% and cancer patients with tumor volumes as small as 0.2 cubic cm were correctly identified, demonstrating that classifications are not affected by tumor volume. Both small and low-grade gliomas were identified which shows great promise for this technique to be used as a screening tool or in diagnostics for early detection of brain tumors. Citation Format: Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker. Does tumor volume effect the spectroscopic classification of brain cancer patients [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 2599.
本研究的重点是研究已知胶质瘤患者和健康对照者之间脑肿瘤体积和光谱分类之间的联系。使用基于血清的ATR-FTIR诊断方法区分脑癌与非脑癌患者是由Hands等人首先开发的，其灵敏度和特异性分别为92.8%和91.5%。Cameron等人随后继续在特定脑肿瘤类型之间进行分层，并成功地提供了90.1%的敏感性和86.3%的特异性。在这些研究的基础上，至关重要的是要确定肿瘤的大小是否对敏感性和特异性有直接影响，以及是否只有较大的肿瘤才被确定为癌症。通过MRI图像(t1加权增强，t2加权或FLAIR图像)计算肿瘤体积的90例患者，包括高级别多形性胶质母细胞瘤(GBM)和低级别胶质瘤(如间变性星形细胞瘤，星形细胞瘤，少星形细胞瘤和少突胶质细胞瘤)患者，用于研究。利用ATR-FTIR光谱结合机器学习算法，将这些肿瘤患者与87名健康对照者进行分层，并将其分类为癌症或非癌症。从这些初步发现来看，敏感性、特异性和平衡准确性均大于88%，并且肿瘤体积小至0.2立方厘米的癌症患者也能被正确识别，这表明分类不受肿瘤体积的影响。小胶质瘤和低级别胶质瘤都被发现，这显示了这项技术作为筛查工具或早期发现脑肿瘤的诊断的巨大希望。引用格式:Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker。肿瘤体积是否影响脑癌患者的光谱分类?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):2599。
{"title":"Abstract 2599: Does tumor volume effect the spectroscopic classification of brain cancer patients","authors":"A. G. Theakstone, Paul M. Brennan, M. Baker","doi":"10.1158/1538-7445.AM2021-2599","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2599","url":null,"abstract":"This study focuses on investigating the link between brain tumor volume and the spectroscopic classification between patients with known gliomas and healthy controls. Discrimination of brain cancer vs. non-cancer patients using serum-based ATR-FTIR diagnostics was first developed by Hands et al. achieving sensitivity and specificity values of 92.8% and 91.5% respectively. Cameron et al. then went on to stratifying between specific brain tumor types and was successful in providing a sensitivity of 90.1% and a specificity of 86.3%. Expanding on these studies, it is vital to determine if the size of a tumor has a direct effect on the sensitivity and specificity and whether or not it was only the larger tumors that were being identified as cancerous. A cohort of 90 patients whose tumor volumes were calculated using their MRI images (either T1-weighted contrast enhanced, T2-weighted or FLAIR images), including patients with high-grade glioblastoma multiforme (GBM), and low-grade gliomas such as anaplastic astrocytoma, astrocytoma, oligoastrocytoma and oligodendroglioma, were used for investigation. Utilizing ATR-FTIR spectroscopy coupled with machine learning algorithms these tumor patients were stratified against 87 healthy controls and were classified as either cancer or non-cancer. From these initial findings9 sensitivities, specificities and balanced accuracies were greater than 88% and cancer patients with tumor volumes as small as 0.2 cubic cm were correctly identified, demonstrating that classifications are not affected by tumor volume. Both small and low-grade gliomas were identified which shows great promise for this technique to be used as a screening tool or in diagnostics for early detection of brain tumors. Citation Format: Ashton G. Theakstone, Paul M. Brennan, Matthew J. Baker. Does tumor volume effect the spectroscopic classification of brain cancer patients [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 2599.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76359647","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-LB224
A. Meirovitz, Daniela Nahmias, E. Hermano, O. Maimon, T. Peretz, M. Elkin
Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients. Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [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 LB224.
{"title":"Abstract LB224: The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients.","authors":"A. Meirovitz, Daniela Nahmias, E. Hermano, O. Maimon, T. Peretz, M. Elkin","doi":"10.1158/1538-7445.AM2021-LB224","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB224","url":null,"abstract":"Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients. Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [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 LB224.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78672855","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.AM2021-2584
John W R Kincaid, Annie E. Hill-Baskin, N. Berger
Human leukemias have been reported to show sexual dimorphism in both incidence and behavior. However, few studies of this observation have been conducted in animal models. We used the C57BL/6J mouse, genetically engineered to contain the PML-RARA fusion gene at the mouse cathepsin G (mCG) locus, as a model (B6.mCG-PML-RARα) of acute promyelocytic leukemia (APL) to interrogate the impact of sex and diet variation on disease latency as measured by leukemia-free survival. At 30 days of age, control (WT) and mutant (mCG+/PR) mice were separated by sex and provided with high fat (HF) [57% coconut oil fat] or low fat (LF) [10% coconut oil fat] diets. Mice were followed with serial blood collections and sacrificed when peripheral blood revealed signs of leukemia development including elevated granulocytes (WBC >20 K/μL), anemia (Hb 425 days was observed. In contrast, male mCG+/PR mice fed LF diets showed a reduced MLFS of 360 days of age, indicating a difference in latency of 65 days, thereby demonstrating sexual dimorphism in the appearance of APL. HF diet accelerated the appearance of APL in both female (MLFS = 277 days of age) and male mCG+/PR mice (MLFS = 277 days of age), which also displayed a difference in latency of 65 days. Thus, HF diet accelerated appearance of APL by 148 days in male and 148 days in female mCG+/PR mice. There were no signs of leukemia development in WT mice on either HF or LF diets. There was no splenomegaly observed in WT mice on either HF or LF diets. Thus, although HF diet and obesity accelerate the onset of APL in B6.mCG-PML-RARα mice, sexual dimorphism remains, with females showing extended latency compared to males under conditions of both HF and LF diets. Overall, our studies provide a robust mouse model to study the mechanisms by which sex impacts leukemia latency, as well as demonstrate that obesity accelerates leukemia development without affecting sexual dimorphism. Citation Format: John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger. Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity [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 2584.
据报道，人类白血病在发病率和行为上都表现出性别二态性。然而，很少在动物模型中进行这一观察的研究。我们使用C57BL/6J小鼠，通过基因工程在小鼠组织蛋白酶G (mCG)位点含有PML-RARA融合基因，作为急性早幼粒细胞白血病(APL)的模型(b6 .mCG- PML-RARA α)，研究性别和饮食变化对疾病潜伏期的影响。30日龄时，对照(WT)和突变(mCG+/PR)小鼠按性别分开，分别饲喂高脂(HF)[57%椰子油脂肪]或低脂(LF)[10%椰子油脂肪]日粮。小鼠连续采血，当外周血出现粒细胞升高(WBC >20 K/μL)、贫血(Hb 425 d)等白血病发展迹象时处死。相比之下，饲喂LF的雄性mCG+/PR小鼠在360日龄时MLFS减少，潜伏期差异为65天，从而显示APL外观的性别二态性。HF饮食加速了雌性(MLFS = 277日龄)和雄性mCG+/PR小鼠(MLFS = 277日龄)APL的出现，其潜伏期也有65天的差异。由此可见，HF饮食使mCG+/PR小鼠APL的出现在雄性小鼠和雌性小鼠中分别提前了148天和148天。无论是HF还是LF饮食，WT小鼠都没有白血病发展的迹象。无论是HF还是LF饮食，WT小鼠均未观察到脾肿大。因此，尽管HF饮食和肥胖加速了B6患者APL的发病。mCG-PML-RARα小鼠的性别二态性仍然存在，在HF和LF饮食条件下，雌性小鼠比雄性小鼠表现出更长的潜伏期。总之，我们的研究提供了一个强大的小鼠模型来研究性别影响白血病潜伏期的机制，并证明肥胖在不影响性别二态性的情况下加速了白血病的发展。引文格式:John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger。mCG-PML-RARα小鼠模型的白血病潜伏期受性别和肥胖的影响[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):2584。
{"title":"Abstract 2584: Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity","authors":"John W R Kincaid, Annie E. Hill-Baskin, N. Berger","doi":"10.1158/1538-7445.AM2021-2584","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2584","url":null,"abstract":"Human leukemias have been reported to show sexual dimorphism in both incidence and behavior. However, few studies of this observation have been conducted in animal models. We used the C57BL/6J mouse, genetically engineered to contain the PML-RARA fusion gene at the mouse cathepsin G (mCG) locus, as a model (B6.mCG-PML-RARα) of acute promyelocytic leukemia (APL) to interrogate the impact of sex and diet variation on disease latency as measured by leukemia-free survival. At 30 days of age, control (WT) and mutant (mCG+/PR) mice were separated by sex and provided with high fat (HF) [57% coconut oil fat] or low fat (LF) [10% coconut oil fat] diets. Mice were followed with serial blood collections and sacrificed when peripheral blood revealed signs of leukemia development including elevated granulocytes (WBC >20 K/μL), anemia (Hb 425 days was observed. In contrast, male mCG+/PR mice fed LF diets showed a reduced MLFS of 360 days of age, indicating a difference in latency of 65 days, thereby demonstrating sexual dimorphism in the appearance of APL. HF diet accelerated the appearance of APL in both female (MLFS = 277 days of age) and male mCG+/PR mice (MLFS = 277 days of age), which also displayed a difference in latency of 65 days. Thus, HF diet accelerated appearance of APL by 148 days in male and 148 days in female mCG+/PR mice. There were no signs of leukemia development in WT mice on either HF or LF diets. There was no splenomegaly observed in WT mice on either HF or LF diets. Thus, although HF diet and obesity accelerate the onset of APL in B6.mCG-PML-RARα mice, sexual dimorphism remains, with females showing extended latency compared to males under conditions of both HF and LF diets. Overall, our studies provide a robust mouse model to study the mechanisms by which sex impacts leukemia latency, as well as demonstrate that obesity accelerates leukemia development without affecting sexual dimorphism. Citation Format: John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger. Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity [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 2584.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85752377","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.AM2021-2536
S. J. Rahman, Shilin Zhao, Shih-Kai Chu, Y. Zou, A. Hui, T. Stricker, Chen Heidi, M. Diehn, P. Massion
{"title":"Abstract 2536: Mutational landscape of the bronchial epithelium of individuals at high risk for lung cancer","authors":"S. J. Rahman, Shilin Zhao, Shih-Kai Chu, Y. Zou, A. Hui, T. Stricker, Chen Heidi, M. Diehn, P. Massion","doi":"10.1158/1538-7445.AM2021-2536","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2536","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79871807","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：