Prevention, Early Detection, and Interception最新文献

{"title":"Abstract 648: Effects of bazedoxifene and lapatinib in the prevention of estrogen receptor positive (ER+) and negative (ER-) mammary cancers","authors":"C. Grubbs, Altaf Mohammed, S. Sei, R. Shoemaker","doi":"10.1158/1538-7445.SABCS18-648","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-648","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90368849","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 5088: Silibinin inhibits UVB-induced promotion and progression of microscopic basal cell carcinoma formation via targeting bone morphogenic protein 2","authors":"Cynthia M. Rigby, G. Deep, A. Jain, D. Orlicky, C. Agarwal, K. Raina, R. Agarwal","doi":"10.1158/1538-7445.AM2019-5088","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-5088","url":null,"abstract":"Non-melanoma skin cancers (NMSCs) account for about half of all malignancies diagnosed annually in the United States. Around 80% of NMSCs are basal cell carcinoma (BCC) and 20% are squamous cell carcinoma (SCC). Whereas the efficacy of several chemopreventive agents has been examined and reported against both BCC and SCC, a majority of these studies have focused on the test agent’s activity in a long-term setting to determine the amount of tumors formed. Notably, the studies evaluating the efficacy of chemopreventive agents during early stage/s of BCC development are lacking. Accordingly, utilizing the well-established patched (Ptch)+/- mouse model of UVB-induced BCC formation, we excised skin samples from UVB exposed mice prior to tumor formation to study the promotion/progression of BCC and to determine the target/s of silibinin, a well-known skin cancer (SCC) chemopreventive agent, in tumor growth inhibition. Ptch+/- and Ptch+/+ mice were irradiated with UVB 240mJ/cm2 3 times per week with or without topically applied silibinin 5 times per week. As early as one month, we found that UVB exposure significantly increased the number of mast cells in Ptch+/- mice by about 48% (P Citation Format: Cynthia M. Rigby, Gagan Deep, Anil K. Jain, David J. Orlicky, Chapla Agarwal, Komal Raina, Rajesh Agarwal. Silibinin inhibits UVB-induced promotion and progression of microscopic basal cell carcinoma formation via targeting bone morphogenic protein 2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5088.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75099680","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 4225: Is biomarker-driven precision medicine possible by using high dimensional augmented intelligence assisted analysis of cancer immune responses","authors":"C. Krieg, L. Cardenas, S. Guglietta, John M. Wrangle, M. Rubinstein, M. Robinson","doi":"10.1158/1538-7445.AM2019-4225","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-4225","url":null,"abstract":"Checkpoint inhibitors have significantly accelerated cancer treatment but still a majority of patients do not respond. Biomarker driven patient stratification early to the right immunotherapeutic might enhance response and patient survival. Here we used high-dimensional mass cytometry (CyTOF) combined with machine-learning bioinformatics for the in-depth characterization of immune responses before and during anti-PD-1 immunotherapy. CyTOF allows us to monitor protein expression of 34 markers on a single cell while running 20 samples simultaneously. The analysis is data driven, can be adapted to high throughput approaches and can model arbitrary trial designs such as batch effects and paired designs and is quantitative over millions of events. Using CyTOF as a precision medicine tool we could predict response to anti-PD-1 using liquid blood biopsies. Biobanked peripheral blood mononuclear cells (PBMCs) from 51 patients with stage IV melanoma before and after 12 weeks of anti-PD-1 therapy was analyzed. We observed a clear T cell response on therapy. The most evident difference in responders before therapy was an enhanced frequency of CD14+ CD16+HLA-DRhi classical monocytes. We validated our results using conventional flow and found a clear correlation of enhanced monocyte frequencies before therapy initiation with clinical response such as lower hazard and extended progression-free and overall survival. In a second study we used CyTOF to monitor immune response in 21 non small cell lung cancer (NSCLC) patients that initially responded and then progressed under anti-PD-1 to a novel combination immunotherapy of anti-PD-1 plus an IL-15 super-agonist (ALT-803). In this phase Ib clinical study a response in the CD8+ T cell compartment was observed. Unexpected our high dimensional unbiased analysis was able to detect and characterize a strong expansion of innate tumor-reactive effector NK cells starting around day 4 of therapy. Taken together, our unbiased artificial intelligence driven immune workflow might support patient selection prior to therapy, and serve as a novel tool for precision medicine to select the right drug combination and identify new drug-able cell populations. Citation Format: Carsten Krieg, Luis Cardenas, Silvia Guglietta, John Wrangle, Mark Rubinstein, Mark Robinson. Is biomarker-driven precision medicine possible by using high dimensional augmented intelligence assisted analysis of cancer immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4225.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73812895","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 660: The molecular characterization of a murine lung premalignancy model for lung cancer interception","authors":"S. Mazzilli, Kahkeshan Hijazi, R. Pihl, A. Belkina, Xiaohui Zhang, Gang Liu, M. Lenburg, Christopher S. Stevenson, A. Spira, J. Beane","doi":"10.1158/1538-7445.SABCS18-660","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-660","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83480864","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 653: Ovarian cancer persister cells: 2D and 3D in-depth characterization and analysis","authors":"Kathrin Boepple, M. Dong, Andrea Gaissler, Bernd Winkler, M. Kleih, F. Essmann, W. Aulitzky","doi":"10.1158/1538-7445.SABCS18-653","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-653","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86353919","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 650: Gut microbiota population may be used to predict chemotherapeutic responsiveness in triple negative breast cancer","authors":"Alaa Bawaneh, Adam S. Wilson, Kenysha Y. J. Clear, A. Chiba, K. Cook","doi":"10.1158/1538-7445.AM2019-650","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-650","url":null,"abstract":"Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and predominately affects young and minority women. TNBC is characterized by a high recurrence rate, with about 34% of TNBC patients relapsing around 2.6 years. This type of breast cancer lacks targeted therapy options and is limited to chemotherapy treatment options. The purpose of our study was to determine whether gut microbiota populations correlate with chemotherapeutic responsiveness and may be a predictive biomarker of outcome. Moreover, we want to determine the impact of targeting the microbiome on chemotherapy efficacy. In this study, 8-week old female BALB/c mice were injected with TNBC 4T1-luciferase cells into their L4/5 mammary fat pad. Once tumors developed, mice were either untreated (control group), treated with 1 x weekly 2.5 mg/kg IV doxorubicin (DOX), or treated with doxorubicin + antibiotics (mixture of streptomycin, ampicillin, and colistin in the drinking water to ablate host bacterial populations). Tumors were collected at the end of the study. Fecal samples were collected at time point 0 weeks (T0; before therapy when tumors were approximately 100 mm3) and time point 4 weeks (T4; after treatment). We subdivided the doxorubicin treated group into DOX-responders (tumors stopped growing or shrank) or DOX-nonresponders (tumors continued to grow on treatment). Tumors from the DOX-responders and DOX + antibiotics groups were significantly smaller and mice from these groups displayed reduced lung weight, suggesting decreased lung metastatic burden. 16S-bacterial sequencing analysis was performed on breast tumor tissue and feces. We demonstrate that at T0, elevated fecal Ruminococcus correlates with DOX-nonresponsiveness. Furthermore, at T4, we show increased fecal abundance of Oscillospira and Bacteroidales are associated with better therapeutic outcome. Protein analysis of primary 4T1 breast tumor tissue indicate a significant elevation of apoptosis (cleaved caspase-3 protein levels) in DOX-responders and DOX + antibiotic treated mice. We also stained breast tumor tissue and lung tissue for bacteria to confirm presence of microbiota by immunohistochemistry. Taken together our data demonstrates that chemotherapy efficacy is modulated by the microbiome. Moreover, fecal microbiota populations could be used as a predictive biomarker of chemotherapeutic responsiveness and suggests that modulation of the gut microbiome through dietary or probiotic interventions may affect therapeutic outcomes. Citation Format: Alaa Bawaneh, Adam S. Wilson, Kenysha YJ Clear, Akiko Chiba, Katherine L. Cook. Gut microbiota population may be used to predict chemotherapeutic responsiveness in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 650.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81170116","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 5073:mPGES-1deficiency impairs self-renewal properties of colon cancer stem cells","authors":"M. Nakanishi, D. Rosenberg","doi":"10.1158/1538-7445.AM2019-5073","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-5073","url":null,"abstract":"Dysregulation of prostaglandin E2 (PGE2) signaling is a hallmark of many cancers, including colorectal cancer (CRC). Direct suppression of inducible PGE2 synthesis by genetic deletion of Ptges1 (mPGES-1) affords dramatic cancer protection to the colon. However, the precise mechanisms by which this effect occurs remain incompletely understood. Recent evidence points to a fundamental role of PGE2 signaling in the expansion of cancer stem cells. In the present study, using an organoid system established from Apc mutant mice, we have evaluated the influence of PGE2 and related prostanoids on the viability of cancer stem cells in the colon. To establish cancer organoids, colon tumors were harvested from 16 week-old ApcΔ14/+ mice with or without mPGES-1 (D14:WT and D14:KO). Colon tumor multiplicity in D14:KO mice is approximately half the number of tumors in D14:WT mice. Tumor tissues were digested with collagenase and dispase, and cultured in Matrigel with complete organoid media. Organoid growth was scored daily over a one-week time period, and passaged. Tumor organoids generated from D14:WT and D14:KO mice showed no obvious differences in their growth characteristics nor morphological features during the first week of ex-vivo growth. After the first passage, however, the growth rate of D14:KO organoids was significantly reduced (175% vs. 80%, WT and KO, respectively), and by the second passage, D14:KO organoids failed to maintain cell viability. Immunohistochemical analysis of the organoids showed strong nuclear localization of s-catenin and loss of Apc expression regardless of mPGES-1 genotype, indicating intact Wnt-driven cancer growth mechanisms that were independent of inducible PGE2 signaling. These observations indicate that alternative mechanisms are contributing to the compromised stem cell expansion observed in the D14:KO organoids. Since mPGES-1 is expressed within the tumor stroma, we postulated that the inactivation of mPGES-1 would cause a marked microenvironmental change. To test this possibility, we used GC-MS/MS to measure a panel of prostanoids within the tumor tissue. Targeted lipidomic analysis showed significant metabolite redirection of tissue prostanoids, with a significant increase (2-fold) in PGD2in the D14:KO mice. Interestingly, administration of PGD2 was recently shown to reduce the growth and regeneration potential of stem cells within a hair follicle organ culture system. Given new evidence that PGD2 may have a direct influence on ‘stem cell-ness9 in other organ systems, we propose that the colon tumor microenvironment, deficient in inducible PGE2, may undergo permanent molecular changes that directly influence the growth characteristics and viability of cancer stem cells as reflected in our organoid culture system. New data is presented to define the long-lasting influence of eicosanoid metabolic changes on cancer-derived stem cell viability and proliferative capacity. Citation Format: Masako Nakanishi, Daniel W. Rosenb","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84447019","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 1614: Coconut kernel extract as a novel chemopreventive agent that target cancer stemness","authors":"Sandhya Sorra, Joyeeta Talukdar, G. Gogoi, Hong Li, D. Baishya, Bikul Das","doi":"10.1158/1538-7445.SABCS18-1614","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-1614","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79763040","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 3313: Plasma levels of MMP7 are significantly increased in patients with colorectal cancer compared to benign disease colon pathology","authors":"H. S. Kumara, D. N. Gamage, N. Mitra, Carl S Winkler, Sandhu K. Jaspreet, Xiaohong Yan, V. Cekic, H. Miyagaki, N. Gandhi, R. Whelan","doi":"10.1158/1538-7445.SABCS18-3313","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-3313","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80042377","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 1606: The ethyl ester forms of the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid decrease the proliferation, invasion, and matrixmetalloproteinase activity of colorectal cancer cells","authors":"Eric Pfister, M. Lane","doi":"10.1158/1538-7445.SABCS18-1606","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-1606","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82483011","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}