Prevention, Early Detection, and Interception最新文献

{"title":"Abstract 2434: Characterizing age-of-onset of multiple primary cancers and specific cancer types in families with Li-Fraumeni syndrome","authors":"S. Shin, Elissa B. Dodd, G. Peng, J. Bojadzieva, Jingxiao Chen, J. Ning, P. Mai, S. Savage, M. Ballinger, David M. Thomas, Ying Yuan, L. Strong, Wenyi Wang","doi":"10.1158/1538-7445.SABCS18-2434","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-2434","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74009698","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 5069: Breast cancer prevention by triterpenoids from allspice","authors":"Jie Gao, K. Mamouni, G. Kallifatidis, S. Panda, M. Thangaraju, B. L. Lokeshwar","doi":"10.1158/1538-7445.SABCS18-5069","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-5069","url":null,"abstract":"Breast cancer ranks second as a lethal cancer in women. Although survival following initial diagnosis is ~ 100% in first five years, cancer progression and mortality is imminent in subsequent years. The slow progression to the lethal form of breast cancer has prompted development of multiple avenues to delay the progression, metastasis and mortality using potent prevention strategies, including the use of nutraceuticals. Oleanolic acid (OA) and ursolic acid (UA) are two triterpenoids found in edible plant parts-fruits and seeds with potent cancer preventive, and selective cytotoxic activities against multiple cancers including breast cancer. We conducted cytotoxic assays of the combination of OA and UA. We found the combination has enhanced efficacy as compared to OA or UA alone. The combination of OA and UA and UA alone caused cell death by increased autophagy but not apoptosis in both MCF7 and MB231 human breast cancer cells. Further analysis revealed increased autopagosomes and autophagic flux, inhibition of either process reduced cytotoxicity, indicating cytotoxic autophagy is the primary mechanism of their action. Therefore, a combination of OA and UA with conventional therapies could enhance their therapeutic efficacy while limiting systemic toxicities of existing therapies. Citation Format: Jie Gao, Kenza Mamouni, Georgios Kallifatidis, Siva Panda, Muthusamy Thangaraju, Bal L. Lokeshwar. Breast cancer prevention by triterpenoids from allspice [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 5069.","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":"74730690","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 1624: Antigen-independentde novoprediction of cancer-associated TCR repertoire","authors":"Bo Li","doi":"10.1158/1538-7445.am2019-1624","DOIUrl":"https://doi.org/10.1158/1538-7445.am2019-1624","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79940127","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 663: Diagnostic screen for lung cancer using high throughput metabolomics screen","authors":"R. Plumb, L. Gethings, A. Peck","doi":"10.1158/1538-7445.AM2019-663","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-663","url":null,"abstract":"Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States, cigarette smoking being leading cause of lung cancer. There are two main types of lung cancer small cell and non-small cell lung cancer (NSCLC). The most common type being NSCLC which accounts for 80-85% of all reported cases. The ability to rapidly detect / diagnose lung cancer at an early stage is critical to successful treatment selection and patient survival. The use of metabolic profiling in biomedical applications metabolic profiling is being deployed as a method for finding novel, mechanistic, biomarkers of disease with obvious potential for improving diagnosis, and patient stratification. Here we present a rapid, simple and reliable high throughput targeted LC/MS single platform, for the quantification/monitoring of small molecule metabolites, lipids and peptides. The methodology employs a single set of LC/MS conditions which facilitate TCA cycle, bile acids, biogenic amine, free fatty acids, acyl carnitines, lipids and 100 protein panel without need for user intervention. Plasma from pilot cohort of lung cancer a health control samples were evaluated using this new methodology. The methodology showed excellent reproducibility and accuracy. The peptide analysis showed that 10 peptides were shown to be markers of lung cancer, these are listed in Table 1. Acylcarnitines were quantified over a range of 5 - 625ng/mL data showed that the C14:2 tetradecadienoyl carnitine and C16:1 palmitoleoyl carnitine were elevated in lung cancer samples whereas the C8:1 octenoyl carnitine level was reduced in the lung cancer samples . Although deoxycholic acid and chendeoxycholic acid appeared to be reduced in the lung cancer samples this was determined to be not statistically relevant. A total of 29 amino acids were measured during the analysis. Using t-test with p-value FDR cutoff adjusted to 0.01 the data clearly showed that sarcosine was highly over-expressed in lung cancer samples. Note: This abstract was not presented at the meeting. Citation Format: Robert S. Plumb, Lee Gethings, Andrew Peck. Diagnostic screen for lung cancer using high throughput metabolomics screen [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 663.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76722618","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 665: Cancer neoantigen and autoantibody discovery with PEP functional proteomics platform","authors":"Xing Wang, T. Landon","doi":"10.1158/1538-7445.SABCS18-665","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-665","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84061462","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-243: Curcumin suppresses oncogenicity of human colon cancer cells through covalent modification of oncogenic SIRT1","authors":"Yeon-Hwa Lee, Na-Young Song, Do-Hee Kim, H. Na, Y. Surh","doi":"10.1158/1538-7445.AM2019-LB-243","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-LB-243","url":null,"abstract":"Silent mating type information regulator 2 homolog 1 (SIRT1), an NAD+-dependent histone/protein deacetylase, has multifaceted functions in various biological events such as inflammation, aging and energy metabolism. The role of SIRT1 in carcinogenesis, however, is still under debate. Recent studies have indicated that aberrant overexpression of SIRT1 is correlated with metastasis and poor prognosis in several types of cancer, suggesting that it may act as a tumor promoter. In our present study, 27 out of 35 human colorectal cancer specimens exhibit significantly elevated expression of SIRT1 compared with corresponding adjacent normal tissues. siRNA knock down of SIRT1 in human colon cancer (HCT-116) cells significantly reduced the volume and the weight of the xenograft tumors when these cells were injected subcutaneously into the flanks of BALB/c nude mice. Curcumin (diferuloymethane), a substance present in the spice turmeric (Curcuma longa L., Zingiberaceae) has been known to possess the beneficial effects on pathological conditions such as inflammation and cancer. Curcumin abrogated migration and colony forming capability of HCT-116 cells. This prompted us to investigate the effect of curcumin on the expression of SIRT1 and underlying molecular mechanisms. When HCT-116 cells were treated with curcumin, the protein expression of SIRT1 was significantly reduced, but the level of its mRNA transcript remained unchanged. Notably, the ubiquitination of SIRT1 was elevated by curcumin treatment. Nano-LC-ESI-MS/MS analysis revealed the modification of the SIRT1 cysteine 67 residue by curcumin. In line with this observation, the protein stability of a mutant SIRT1 in which cysteine 67 was replaced by alanine (SIRT1-C67A) was unaffected by curcumin treatment. Furthermore, migration and anchorage-independent growth of cells expressing SIRT1-C67A were affected by curcumin to a lesser extent than those of cells expressing wild-type SIRT1. It has been reported that c-Jun N-terminal kinases 2 (JNK2) phosphorylates SIRT1 at the serine 27 residue, thereby enhancing the protein stability of SIRT1 in HCT-116 cells. Based on these report, we speculated that binding of curcumin to SIRT1 at cysteine 67 may disrupt the interaction between JNK and SIRT1, leading to blockade of the phosphorylation-dependent stabilization of SIRT1. Binding of phosphorylated JNK to SIRT1 in cells expressing SIRT1-C67A was barely inhibited by curcumin compared with that in cells harbouring wild-type SIRT1, lending support to the above supposition. Taken together, cysteine 67 modification of SIRT1 by curcumin is a prerequisite for proteasomal degradation of oncogenic SIRT1, which accounts for anti-cancer effects of curcumin. Supported by the Global Core Research Center (GCRC) grant (No. 2011-0030001) from the National Research Foundation (NRF) of Republic of Korea. Citation Format: Yeon-Hwa Lee, Na-Young Song, Do-Hee Kim, Hye-Kyung Na, Young-Joon Surh. Curcumin suppresses oncogenicity of h","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87665380","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 5077: Proteomic profiling reveals chemopreventive targets in esophageal adenocarcinoma","authors":"Katherine M. Weh, Connor L. Howard, A. Howell, J. Clarke, L. Kresty","doi":"10.1158/1538-7445.SABCS18-5077","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-5077","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84811985","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 659: Expression patterns of NF-κB in inflammatory oral potentially malignant lesions","authors":"I. Lin, Lewei Zhang, M. Rosin, Leigha D. Rock, D. Laronde","doi":"10.1158/1538-7445.SABCS18-659","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-659","url":null,"abstract":"Introduction: Oral lichen planus (OLP), a common chronic autoimmune inflammatory condition, is recognized as a potentially malignant condition by the World Health Organization. However, some argue that only OLP with epithelial dysplasia - termed lichenoid dysplasia (LD) - have malignant potential. As research continues to characterize the immune microenvironment of OLP, there is a need to elucidate factors favorable for malignant change. Recent research has demonstrated that activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is key to cancer development. This transcription factor has been extensively explored in inflammation-associated cancers, such as colon and gastric cancers. There is a need to investigate these factors in oral potentially malignant lesions (OPML), including OPL. In this study, we aim to compare clinical and risk habit differences between OLP and LD, and determine if NF-κB expression is associated with histological and clinical features of OPML indicative of cancer risk. Methods: Clinical, demographic, and histological data have been collected from the Oral Cancer Prediction Longitudinal (OCPL) study and the CoPath Vancouver Coastal Health Database. Patients with a primary diagnosis of OLP or low-grade LD were eligible to participate. Patients with previous history of head and neck cancer, or who have less than one year of follow-up are excluded from enrollment. Demographic, risk habit and clinical information was collected.For completed cases, immunohistochemistry (IHC) has been performed on formalin-fixed and paraffin-embedded tissue. Nuclear reactivity of NF-κB in the epithelium was counted in 10 high-power fields, and cytoplasmic positivity classified into 4 categories. Chi-squared tests were performed on categorical demographic and risk habit data. Results: To date, 51 participants have been recruited into this ongoing study: 37 with OLP and 14 cases of LD. There is no significant difference in gender and age between groups (p=0.297, p=0.120, respectively). Ever smokers and lesion location at a high-risk site were significantly associated with a diagnosis of LD compared to OLP (p=0.002, p Conclusion: Patients with LD were more apt to be smokers, and more often presented with lesions at a high-risk site compared to those with OLP. Strong NF‐κB cytoplasmic positivity in OLP, especially adjacent to areas with intense cytotoxic inflammatory infiltrate, reinforces the prominent role of NF-κB in inflammation. Citation Format: Iris Lin, Lewei Zhang, Miriam Rosin, Leigha Rock, Denise Laronde. Expression patterns of NF-κB in inflammatory oral potentially malignant lesions [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 659.","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"142 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83522790","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 5079: Targeting cholecystokinin-2 receptor (CCK2R) for pancreatic ductal adenocarcinoma prevention in p48Cre/+-LSL-KrasG12D/+mice model","authors":"Altaf Mohammed, N. Janakiram, C. Suen, Nicole Stratton, S. Lightfoot, Anil Singh, Gopal Pathuri, Rebekah L. Ritchie, Venkateshwar Madka, C. Rao","doi":"10.1158/1538-7445.SABCS18-5079","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-5079","url":null,"abstract":"","PeriodicalId":20357,"journal":{"name":"Prevention, Early Detection, and Interception","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84001245","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 2733: Novel mouse model carryingAPCandPIK3CAmutations in colorectal cancer","authors":"N. Khan, Farah Jajeh, Emily L. Eberhardt, Devon D Miller, Dawn M. Albrecht, R. Doorn, Melissa D. Hruby, Morgan E. Maresh, L. Clipson, H. Mukhtar, R. Halberg","doi":"10.1158/1538-7445.AM2019-2733","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-2733","url":null,"abstract":"Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States, despite substantial development in its early diagnosis and treatment. The animal models of CRC have been immensely useful for understanding CRC pathogenesis, investigating the effects of genetic modifications on CRC, and for the development of new chemopreventive/chemotherapeutic drugs. Most (>80%) CRC carry mutations in the APC gene and many (15-20%) carry mutations in the PIK3CA gene, encoding the p110 catalytic subunit of the PI3K kinase. We sought to better understand the interaction between APC and PIK3CA mutations in the mammalian intestine. To examine the effect of mutations in APC and PIK3CA on tumorigenesis, Min mice were crossed with the FC13K1 (FC13K1ApcMin/+). This cross resulted in a murine model with the loss of one allele of Apc throughout the intestine and the expression of a dominant active PI3K (3K1) in the distal small intestine and colon due to the expression of Cre under the control of the rat fatty acid binding protein-1 promoter (FC1). There was increased tumor multiplicity, size and a more aggressive and poorly differentiated phenotype as a consequence of synergy between APC and PIK3CA mutations. Tumors form as adenomas, but quickly progress to invasive adenocarcinomas that eventually metastasize to regional lymph nodes. Using this mouse model, we have recently shown that fisetin, a dietary flavonoid could be used as a preventive agent and an adjuvant with 5-fluorouracil (FU) for the treatment of PIK3CA-mutant CRC. Tumor incidence was markedly lower in fisetin-treated FC13K1ApcMin/+ mice in distal small intestine and colon, as compared to control animals, indicating that fisetin is a strong preventive agent. In addition, the combination of fisetin and 5-FU also reduced the total number of intestinal tumors. We extended our work by demonstrating that the effect of drugs on tumorigenesis was impacted by the mutation profile of the tumor and intratumoral heterogeneity. We developed the mouse model in which intestinal tumors were composed entirely of PIK3CA wild-type cells, entirely of PIK3CA-mutant cells, or a mixture of both. We demonstrated that low dose aspirin blocked the development of heterogeneous tumors composed of PIK3CA wild-type and PIK3CA-mutant cells but not the development of homogenous tumors composed entirely of PIK3CA wild-type cells. Thus, this new model of CRC recapitulates the effect of aspirin that was observed in humans. Sustained exposure to low dose aspirin reduced the recurrence the PIK3CA-mutant CRC cancers in humans. This aggressive murine model is an exciting model of human CRC that has the potential to be instrumental in the development of targeted chemoprevention and therapeutics. Citation Format: Naghma Khan, Farah Jajeh, Emily L. Eberhardt, Devon D. Miller, Dawn M. Albrecht, Rachel Van Doorn, Melissa D. Hruby, Morgan E. Maresh, Linda Clipson, Hasan Mukhtar, Richard B. Halberg. Novel mouse model car","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":"88909965","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}