Prevention, Early Detection, and Interception最新文献_第4页

Abstract 5065: Pharmacological modulation of inflammation and p53 signaling synergize to prevents muscle invasive bladder cancerin-vivo 摘要:炎症的药理调节和p53信号的协同作用在体内预防肌肉浸润性膀胱癌

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.AM2019-5065

Venkateshwar Madka, Yuting Zhang, Nandini Kumar, Gopal Pathuri, Nicole Stratton, S. Lightfoot, A. Asch, V. Steele, Altaf Mohammed, C. Rao

{"title":"Abstract 5065: Pharmacological modulation of inflammation and p53 signaling synergize to prevents muscle invasive bladder cancerin-vivo","authors":"Venkateshwar Madka, Yuting Zhang, Nandini Kumar, Gopal Pathuri, Nicole Stratton, S. Lightfoot, A. Asch, V. Steele, Altaf Mohammed, C. Rao","doi":"10.1158/1538-7445.AM2019-5065","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-5065","url":null,"abstract":"Bladder cancer (BC) is the second most common genitourinary cancer and a leading cause of death globally. Muscle invasive BC (MIBC) has high mortality (>85% patients) leading to death within 2 years of diagnosis, if untreated. Although new treatment options were approved recently, it is still very challenging and most expensive to manage. Preventing BC is highly desirable to reduce recurrence, mortality and improve quality of life. Inactivation of p53 signaling and chronic inflammation are frequent hallmarks of MIBC. In spite of the promising chemopreventive effects of non-steroidal anti-inflammatory agents (NSAIDs), their clinical translation is hampered due to side-effects associated with their chronic intake and higher doses. Here we investigated a combinatorial approach to modulate inflammation with NSAIDs (licofelone or NO-Naproxen) and p53 signaling pathways using CP-31398 (CP) for preventing MIBC bladder in-vivo. Transgenic UPII-SV40T mice developing spontaneous MIBC were generated and fed control or experimental diets containing the licofelone (150ppm), NO-naproxen (300 ppm), CP (150ppm) alone or in combination starting at early tumor stage (6 weeks age). After 34 weeks of agent administration, mice were euthanized and urinary bladders were evaluated. Control diet fed transgenic mice developed high grade, muscle invasive, urothelial transitional cell carcinoma (TCC) leading to 3-5 fold increase in bladder weights (140.2±9.8 mg Vs 27.3±0.8 mg; p Citation Format: Venkateshwar Madka, Yuting Zhang, Nandini Kumar, Gopal Pathuri, Nicole Stratton, Stanley Lightfoot, Adam S. Asch, Vernon E. Steele, Altaf Mohammed, Chinthalapally V. Rao. Pharmacological modulation of inflammation and p53 signaling synergize to prevents muscle invasive bladder cancer in-vivo [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 5065.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86419523","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}

引用次数: 0

Abstract 1604: Modulating effects of genistein in a mouse model of conditionalBRCA1deletion and triple negative breast cancer cells 1604:染料木素在条件brca1缺失小鼠模型和三阴性乳腺癌细胞中的调节作用

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-1604

Micah G Donovan, O. Selmin, T. Doetschman, D. Romagnolo

引用次数: 0

Abstract 1603: Valproic acid and hydralazine reverse increased mammary cancer risk and upregulate Cdkn2a/p16 in mice exposed to a high fat dietin utero 摘要/ Abstract摘要:丙戊酸和肼可逆转子宫内高脂饮食小鼠乳腺癌风险升高并上调Cdkn2a/p16

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.AM2019-1603

L. Hilakivi-Clarke, F. Andrade, N. Nguyen, K. Bouker

{"title":"Abstract 1603: Valproic acid and hydralazine reverse increased mammary cancer risk and upregulate Cdkn2a/p16 in mice exposed to a high fat dietin utero","authors":"L. Hilakivi-Clarke, F. Andrade, N. Nguyen, K. Bouker","doi":"10.1158/1538-7445.AM2019-1603","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-1603","url":null,"abstract":"Maternal or paternal high fat (HF) diet that modifies the epigenome in germ cells and fetal somatic cells can program increased susceptibility to breast cancer among offspring. Resulting epigenetic changes include transgenerational upregulation of DNA methyltransferases (DNMTs). We studied here if this increased breast cancer risk can be reversed by treating HF offspring with a well-tolerated drug that inhibits DNA methyl transferase (DNMT; hydralazine), combined with a histone deacetylase (HDAC) inhibitor valproic acid (VPA). Adult C57BL/6NTac mouse offspring of dams fed either corn oil -based HF or control diet during pregnancy were treated with 5 g/kg/day VPA and 5 mg/kg/day hydralazine in drinking water, starting after mice received 7,12-dimethylbenz[a]anthracene (DMBA) to initiate mammary cancer. Treatment with VPA/hydralazine prevented the increase in mammary cancer risk associated with in utero HF diet exposure: it reduced mammary tumor multiplicity and lengthened tumor latency, compared with non-treated HF offspring. These drugs downregulated DNMT3a protein levels, and reversed down-regulation of Cdkn2a/p16 mRNA in the mammary tumors of HF offspring. p16 is a tumor suppressor that is often epigenetically silenced in human breast cancers. However, in control offspring not exposed to HF diet in utero, VPA/hydralazine increased mammary tumor incidence and burden. Further, this treatment upregulated genes involved in the unfolded protein response pathway in in utero control diet exposed animals that were already upregulated in non-VPA/hydralazine treated mammary tumors from in utero HF diet exposed animals, including HIF-1α, NFkB, PERK and SQSTM1 p62. Thus, VPA and hydralazine had opposing effects on breast cancer risk in HF and control offspring, suggesting the importance of individually tailoring breast cancer prevention strategies. Citation Format: Leena A. Hilakivi-Clarke, Fabia de Oliveira Andrade, Nguyen Nguyen, Kerrie Bouker. Valproic acid and hydralazine reverse increased mammary cancer risk and upregulate Cdkn2a/p16 in mice exposed to a high fat diet in utero [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 1603.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84376976","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}

引用次数: 0

Abstract 3330: Circulating HPV DNA as a biomarker for metastatic cervical cancer detection, genotyping and monitoring 3330:循环HPV DNA作为转移性宫颈癌检测、基因分型和监测的生物标志物

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-3330

Zhigang Kang, S. Stevanović, C. Hinrichs, Liang Cao

引用次数: 0

Abstract 3315: Workplace program that offers annual fecal immunochemical testing improves adherence to colorectal cancer screening guidelines 摘要3315:提供年度粪便免疫化学检测的工作场所项目提高了对结直肠癌筛查指南的依从性

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-3315

C. Tong, A. Satish, Maren S Fragala, L. Bare, C. Birse

引用次数: 0

Abstract 1608: Time-restricted feeding attenuates pulmonary metastasis of Lewis lung carcinoma in mice fed a high-fat diet 摘要/ Abstract摘要:限时喂养可减轻高脂饮食小鼠Lewis肺癌的肺转移

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-1608

Lin Yan, Sneha Sundaram

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Abstract 2435: Knowledge and attitudes towards anal cancer and anal cancer screening among hispanic women at increased risk of anal cancer 2435:西班牙裔肛门癌高危女性对肛门癌和肛门癌筛查的知识和态度

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-2435

A. P. Ortiz-Martínez, Sandra Camacho, J. M. R. Cartagena, Claudia Amaya Ardilla, V. C. López, J. Romaguera

引用次数: 0

Abstract 656: High resolution metabolomics of aspirin treatment in colon tissue and adenoma risk: Results from a randomized clinical trial 摘要:阿司匹林治疗在结肠组织和腺瘤风险中的高分辨率代谢组学:一项随机临床试验的结果

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-656

Elizabeth L. Barry, K. Uppal, Chunyu Ma, Dean P. Jones, J. Baron, V. Fedirko

{"title":"Abstract 656: High resolution metabolomics of aspirin treatment in colon tissue and adenoma risk: Results from a randomized clinical trial","authors":"Elizabeth L. Barry, K. Uppal, Chunyu Ma, Dean P. Jones, J. Baron, V. Fedirko","doi":"10.1158/1538-7445.SABCS18-656","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-656","url":null,"abstract":"Although substantial evidence from cell and animal studies, epidemiological studies, and clinical trials supports the chemopreventive effects of aspirin, especially for colorectal cancer, the molecular mechanisms are uncertain. Aspirin incorporates two bioactive components in one molecule, a reactive acetyl moiety and a salicylate group, and is well known for its pleotropic effects. Its best-characterized pharmacologic activity is the irreversible acetylation of the cyclooxygenases (COX-1 and COX-2). However, there is evidence for numerous COX-independent mechanisms that could also modify colorectal carcinogenesis. This study applied an untargeted, discovery-based approach (metabolomics) to elucidate the effects of aspirin on low molecular weight molecules in human colon tissue and assess their impact on colorectal carcinogenesis. We utilized normal mucosal tissue biopsies collected at colonoscopy after about 3 years of treatment from a sub-set of N=325 participants in the Aspirin/Folate Polyp Prevention Study, a randomized, placebo-controlled trial of aspirin (81 or 325 mg/day) for the prevention of colorectal adenomas. The global metabolic effects of aspirin were assessed using a high-resolution Thermo Fusion mass spectrometer coupled with dual chromatography and dual ionization (HILIC positive and C18 negative electrospray ionization). Multivariable linear regression was used to identify metabolic features associated with aspirin treatment adjusting for age, sex and race. Multivariable Poisson regression was used to assess associations with adenoma outcomes of metabolic features associated with aspirin treatment. Products of aspirin metabolism (salicylate, salicyluric acid) were identified and statistically significantly increased in post treatment compared to baseline plasma samples confirming aspirin treatment status. After quality control exclusions, N=4,879 and N=5,390 features were included in analyses from the C18 and HILIC columns, respectively, of which N=244 and N=222 were associated with aspirin treatment at a raw P Citation Format: Elizabeth L. Barry, Karan Uppal, Chunyu Ma, Dean P. Jones, John A. Baron, Veronika Fedirko. High resolution metabolomics of aspirin treatment in colon tissue and adenoma risk: Results from a randomized clinical trial [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 656.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77903944","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}

引用次数: 0

Abstract 2427: Patterns of BRCA testing by provider type based on biological and non-biological factors among a diverse sample of young breast cancer survivors 2427:在不同的年轻乳腺癌幸存者样本中，基于生物和非生物因素的提供者类型BRCA检测模式

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.SABCS18-2427

S. Reid, D. Cragun, A. Tezak, A. Weidner, I. Mayer, X. Shu, S. Vadaparampil, T. Pal

引用次数: 0

Abstract 5084: Epigenetic modifications involving reactivation of RECK inhibiting MMP-9 and MMP-2 in prostate cancer 摘要:前列腺癌中涉及rek再激活抑制MMP-9和MMP-2的表观遗传修饰

Prevention, Early Detection, and Interception Pub Date : 2019-07-01 DOI: 10.1158/1538-7445.AM2019-5084

E. Shankar, Omair Iqbal, N. Bhaskaran, Gauri Deb, G. MacLennan, P. Fu, Sanjay Gupta

{"title":"Abstract 5084: Epigenetic modifications involving reactivation of RECK inhibiting MMP-9 and MMP-2 in prostate cancer","authors":"E. Shankar, Omair Iqbal, N. Bhaskaran, Gauri Deb, G. MacLennan, P. Fu, Sanjay Gupta","doi":"10.1158/1538-7445.AM2019-5084","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-5084","url":null,"abstract":"Metastasis is responsible for more than 90% of prostate cancer-associated mortality in the United States. One of the distinctive reason for metastasis has been the imbalance of matrix metalloproteinases (MMPs) as a result of reduced expression of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs) a novel tumor suppressor. RECK has been shown to be a potent inhibitor of MMP-2 and MMP-9. Loss of RECK has been frequently identified in clinical prostate cancer specimens and prostate cancer cell lines, therefore mechanistic understanding of its loss and approaches to restore its expression would facilitate inhibition of metastasis. Green tea polyphenols (GTP) and its major constituent, epigallocatechin-3-gallate (EGCG) has been shown to suppress prostate cancer metastasis, however the mechanism has not been fully elucidated. We determined whether treatment with GTP has ability to restore induction of RECK and play a key role in suppressing invasiveness in prostate cancer. Human prostate cancer LNCaP tumor were implanted in the ventral prostate of athymic nude mice for 2 weeks followed by per-oral intake of GTP at 7.5 and 15.0 mg/kg body weight freshly prepared in 100µl PBS. Other groups were treated with DNA methyltransferase inhibitor-5-aza-29-deoxycytidine (AZA), histone deacetylase inhibitor-trichostatin A (TSA) and histone methyltransferase inhibitor-3-Deazaneplanocin A (DZNep) individually at 0.1 mg/kg body weight intraperitoneally at alternate days/week; and combination of AZA+TSA and DZNep+TSA at similar doses and times. Treatment of mice with GTP resulted in marked decrease in tumor growth and its local invasion in dose dependent manner, compared to treatment with epigenetic inhibitors and their combination after 8 weeks of intervention. GTP treatment significantly reduced serum levels of MMP-2, MMP-9 and VEGF, compared to treatment with epigenetic inhibitors alone. Combination of AZA+TSA exhibited similar effect which was equivalent to the lower dose of GTP treatment. Furthermore, GTP treatment significantly reduced EZH2 and H3K27me3 and class I HDAC protein levels in tumors. GTP partially reversed RECK hypermethylation and significantly enhanced its expression in the tumor tissue. Similar findings were noted in cell culture where treatment of PC-3 and LNCaP cells with 20µM EGCG and 10µg/mL GTP for 72 h significantly induced RECK expression at mRNA and protein levels along with decrease invasiveness in these cells. Our findings suggest that induction of RECK is a key epigenetic event reactivated by GTP/EGCG that results in suppression of MMP-2/MMP-9, matrix degradation and angiogenesis to delay prostate cancer invasion and its subsequent progression. Citation Format: Eswar Shankar, Omair Iqbal, Natarajan Bhaskaran, Gauri Deb, Gregory T. MacLennan, Pingfu Fu, Sanjay Gupta. Epigenetic modifications involving reactivation of RECK inhibiting MMP-9 and MMP-2 in prostate cancer [abstract]. In: Proceedings of the American Association ","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74969823","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}

引用次数: 0