Prevention, Early Detection, and Interception最新文献

{"title":"Abstract 5080: Decursinol intercepts LNCaP human prostate cancer xenograft growth bypassing androgen receptor-prostate specific antigen axis","authors":"Sangyub Kim, Chongtao Qin, Deepkamal N. Karelia, Arati Sharma, Cheng Jiang, Junxuan Lu","doi":"10.1158/1538-7445.SABCS18-5080","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-5080","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"113 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91454401","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 5083: BSCHL-2046, a lead chalcone derivative from a newly synthesized library, is a potent neddylation inhibitor against the growth of prostate cancer cell lines","authors":"Matthew Tippin, Dongjun Fu, Liankun Song, Victor Pham, Xaolin Zi","doi":"10.1158/1538-7445.SABCS18-5083","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-5083","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88518614","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 3318: Development of a cfDNA based trans-omics approach for early cancer detection","authors":"Yuying Wang, Heng Zhao, Kaijian Ling, Jianchao Zheng, Zhilong Li, Shuangshuang Chen, Jia Li, Chichuan Liu, Guanghui Yang, Hongpo Zhou, Jiaxi Peng, Lili Ye, Liuhong Zeng, Jianlong Sun, Ruijingfang Jiang, L. Deng, Yanzhou Wang, Kezhong Chen, Zhiqing Liang, Fan Yang, T. Shi, M. Ye","doi":"10.1158/1538-7445.SABCS18-3318","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-3318","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87983255","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 LB-251: The cancer clinical trial landscape in the EU and the Nordic countries","authors":"J. Pouwels, S. Soidinsalo, Heidi M. Haikala, P. Jaakola, T. Jalava, H. Joensuu, M. Mustonen, P. Korhonen, P. Kovanen, A. Lehtonen, J. Mattson, O. Monni, J. Westermarck, J. Klefström","doi":"10.1158/1538-7445.SABCS18-LB-251","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-LB-251","url":null,"abstract":"Background. Cancer clinical trials seek to determine the safety and efficacy of new treatment modalities. Due to the impact of cancer clinical trials on health care, economic activity and cancer research, many large-scale efforts have been undertaken around the world to create clinical trial-facilitating environments. The Nordic countries (Norway, Sweden, Denmark, Iceland and Finland) are among the countries with the highest 5-year net survival for cancer patients, which is a testimony to their high standard of early diagnosis, cancer care and functional public health care system. However, the contribution of the Nordic countries to the international cancer clinical trial landscape has remained largely unexplored. Methods. We mined www.clinicaltrials.gov for cancer clinical trials starting between the 1st of January 2000 and the 31st of December 2017. Trials were designated Cancer Clinical Trials if the trial indication contained one of 17 cancer-specific words (e.g. “cancer”, “neoplasia”, “malignancy”). The trial databases of all European Free Trade Association (EFTA; the EU, Switzerland, Norway, Iceland and Liechtenstein) countries was downloaded and subsequently mined for specific terms, i.e. cancer indication, study location and intervention type. A trial was counted for every country with a study center and thus the same trial can be counted for multiple countries. Results. Here, we present an analysis of the cancer clinical trial landscape in the EFTA and the Nordic countries. While in the EFTA the number of cancer clinical trials strongly increased from 2000-2014, that number has not grown between 2014 and 2017, unlike in the USA or China. Comparison of the number of cancer clinical trials in different EFTA countries showed strong variation, and indicated that Sweden, Finland and Norway have been involved in far fewer cancer clinical trials than expected for countries of their economic size or socio-economic status. Denmark is the only Nordic country to perform much better than the EFTA average. Discussion. We show that despite a high standard of care, most Nordic countries are lagging behind in cancer clinical trials compared to countries of similar socio-economic stature. This low number of cancer clinical trials may slow down uptake of new cancer drugs to routine care, prevent patients from receiving state-of-the-art therapies, increase health care costs, and inhibit scientific progress and commercial activity. We provide recommended actions to increase the number of cancer clinical trials, with special focus on Finland as part of the national growth strategy in the health sector. Note: This abstract was not presented at the meeting. Citation Format: Jeroen Pouwels, Sebastian Soidinsalo, Heidi Haikala, Panu Jaakola, Tarja Jalava, Heikki Joensuu, Mika Mustonen, Pasi Korhonen, Panu Kovanen, Anne Lehtonen, Johanna Mattson, Outi Monni, Jukka Westermarck, Juha Klefstrom. The cancer clinical trial landscape in the EU and the Nordic countries ","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87335491","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 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 3993A: Real-world utilization of PD-L1 IHC testing and results across multiple tumor types","authors":"G. Krigsfeld, Emily A. Prince, K. Zerba, V. Chizhevsky, J. W. Ragheb, James White","doi":"10.1158/1538-7445.AM2019-3993A","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-3993A","url":null,"abstract":"Background: A number of programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) diagnostic (Dx) tests have been approved by the FDA to guide treatment (Tx) with programmed death-1/PD-L1 inhibitors. Here, we evaluate the utilization of the Dako PD-L1 IHC 28-8 and 22C3 pharmDx and Ventana PD-L1 (SP142) assays on real-world samples across multiple tumor types, characterize PD-L1 testing practices among physicians who order a PD-L1 test, and investigate how PD-L1 test results impact physicians’ Tx decision-making and use of immuno-oncology (I-O) Tx. Methods: 55,652 samples with clinical characteristics were provided by Symphony Health Solutions. NeoGenomics Laboratories, Inc assessed PD-L1 expression between October 2015–April 2018, according to manufacturers’ protocols at time of study. Clinical characteristics were matched to PD-L1 test results using unique identifiers for the 4714 patients (pts) whose diagnoses and treatment could be determined. Results: Across tumor types, 56% of pts received a test prior to first-line (1L) Tx. Most lung cancer (57%) or melanoma (MEL; 65%) pts had a PD-L1 test prior to 1L Tx, while most squamous cell carcinoma of the head and neck (70%) or urothelial carcinoma (73%) pts had a PD-L1 test after Tx initiation, in line with drug and complementary Dx approvals for these tumor types during the testing period. The percentage of lung cancer pts whose PD-L1 expression was tested prior to 1L Tx rose from 32% during Q4 2015–Q3 2016 to 63% during Q4 2016–Q1 2018, in line with FDA approval of a companion PD-L1 IHC Dx for non-small cell lung cancer. Regardless of PD-L1 test used, most lung cancer (73%) or MEL (93%) pts received I-O Tx, defined as nivolumab (NIVO; + ipilimumab [IPI] for MEL only), pembrolizumab (pembro) ± chemotherapy, atezolizumab, or IPI alone. Moreover, the majority of lung cancer pts who had ≥1% PD-L1 expression or MEL regardless of PD-L1 expression received 1L I-O Tx irrespective of the PD-L1 test used. Analysis of PD-L1 expression, Dx test used, and Tx received showed that, for MEL pts tested with 22C3, 28%, 17%, and 0% of pts received NIVO or IPI, while 28%, 43%, and 43% received NIVO+IPI, at the expression cutoffs of 0%, 1–49%, and ≥50%, respectively. Lung cancer pts with 1–49% PD-L1 expression, as determined by a 22C3 test, received NIVO or pembro monotherapy at similar rates (12–18%). Of those who had ≥50% PD-L1 expression, as determined by the 28-8 test only, 52% received pembro monotherapy vs other Tx. Conclusions: Since FDA approval of the first PD-L1 IHC Dx in 2015, analyses of PD-L1 testing practices and physicians’ Tx decision behavior at a US national reference laboratory have shown that physicians’ adoption of PD-L1 testing is responsive to FDA approvals and that most testing for lung cancer and MEL occurs before 1L Tx initiation. In lung cancer or MEL pts who had a PD-L1 test result available, Tx decisions do not appear to be tied to the specific intended use of the PD-L1 assay that was ","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82832491","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 644: Ancestral paternal obesity: Systemic versus local effects on offspring mammary tissue development and tumorigenesis","authors":"C. C. Fontelles, A. Wärri, R. S. D. Cruz, M. I. Cruz, Ersilia Barin, S. Assis","doi":"10.1158/1538-7445.AM2019-644","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-644","url":null,"abstract":"Background: Obesity and overweight are risk factors for breast cancer, particularly in the post-menopausal years. We recently reported that having a history of ancestral overweight from the paternal lineage is enough to increase breast cancer susceptibility in daughters. Using a mouse model, we demonstrated that paternal consumption of an obesity inducing diet (OID) altered mammary gland development, increased mammary carcinogenesis and disrupted metabolic parameters in the female offspring, compared to the female offspring of fathers who consumed only control (CO) diet. Given both the systemic and local the mammary tissue alterations observed, we aimed to investigate in more details why daughters of overweight fathers are at increased risk for breast cancer. More specifically, we used mammary gland transplantation experiments to study whether this ancestrally-induced breast cancer predisposition is linked to systemic factors and/or mammary tissue confined changes in daughters. Material and methods: Male mice were exposed either to a control (CO) or to high-fat (OID) diet. CO and OID male mice were then mated with female mice fed CO diet exclusively. Female offspring of both CO and OID male mice underwent a mammary gland transplantation surgery. Briefly, female offspring had their mammary fat pad area between the nipple and the proximal lymph node excised. Afterwards, mammary tissue fragments (1 mm3) of a donor mouse, either CO or OID female offspring, were implanted into a pocket made in the cleared fat pad. The transplantations were performed from CO female offspring donors to both CO [CO(CO)] and OID [OID(CO)] female offspring hosts, as well as from OID female offspring donors to both CO [CO(OID)] and OID [OID(OID)] female offspring hosts. Approximately 10 weeks post-surgery, the mammary glands were collected, photographed and analyzed using ImageJ software to determine branching density, epithelial elongation and number of Terminal End Buds. Cell proliferation was assessed by ki-67 and cell apoptosis was measured on ImageJ software. Results: Our preliminary data shows that CO(OID) had more (p≤0.05) articulated mammary branching morphogenesis than CO(CO). OID(CO) displayed marginal increase (p≤0.09) in the mammary gland area, as well as in the mammary ductal elongation, compared to CO(OID). Additionally, the number of apoptotic cells within mammary ducts and lobules is higher in CO(OID) compared to OID(CO). In contrast, the number of proliferating cells is higher in OID(CO) mammary gland compared to CO(OID). Conclusion: Altogether, our findings suggest that daughters of overweight fathers have both systemic and mammary gland confined factors alterations that ultimately lead to higher breast cancer risk in adulthood. However, further data is needed to corroborate this hypothesis. Our ongoing mammary tumor transplantation studies should provide further insight. Citation Format: Camile C. Fontelles, Anni Warri, Raquel S. Da Cruz, Maria I. Cruz, E","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83211633","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 645: Pregnancy inhibits mammary carcinogenesis by altering the mammary epithelial and stromal interactions","authors":"R. S. Reddy, Adriana Galvez, D. Pedroza, A. Chatterjee, Courtney L Perry, Elizabeth Penner, R. Lakshmanaswamy","doi":"10.1158/1538-7445.SABCS18-645","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-645","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77600130","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}