Prevention Research最新文献

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}