Prevention Research最新文献

{"title":"Abstract 107: Identifying the role of fibrocytes in obesity-induced mammary gland fibrosis","authors":"G. Kuziel, Lisa M. Arendt","doi":"10.1158/1538-7445.AM2021-107","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-107","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85927673","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 2565: Detection of ETV1 expression in human prostate tissue specimens using a novel and highly specific rabbit monoclonal antibody","authors":"Shyh-Han Tan, D. Young, S. Elsamanoudi, J. Kagan, S. Srivastava, A. Dobi, G. Petrovics, I. Sesterhenn, Gregory T. Chesnut","doi":"10.1158/1538-7445.AM2021-2565","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2565","url":null,"abstract":"Introduction: ETV1 is frequently involved in genomic fusions and translocation events that lead to its overexpression in multiple cancers. These events occur in approximately 5% of prostate cancers, which are mutually exclusive from tumors harboring TMPRSS2-ERG fusion or PTEN deletion. Studies suggest a correlation between strong ETV1 protein expression and poor outcome in prostate cancer. ETV1 has been reported to synergistically cooperate with KIT as a lineage survival factor in gastrointestinal stromal tumors. The expression of ETV1 in a subset of sarcomas that harbor CICrearrangements or CIC-DUX4 gene fusions presents a reliable molecular signature for the diagnosis of this cancer. Our understanding of the role that ETV1 plays in the activation of prostate cancer has been limited by the lack of ETV1 specific antibodies. Methods: A novel ETV1 monoclonal antibody (MAb) was raised by immunization of ETV1 peptides in rabbit followed by screening of hybridomas by ELISA and immunoblot assays. Further screening using exogenously expressed ETV1, ETV4, ETV5, ERG, SPDEF, and FLI1 proteins identified the clone with the most reactive MAb. Purified MAb was used to evaluate ETV1 expression on a tissue micro-array (TMA) constructed from radical prostatectomies of 50 African American (AA) and 50 Caucasian American (CA) patients by immunohistochemistry (IHC). Key residues required for Mab binding were mapped by ELISA using overlapping peptides and alanine scanning. Results: IHC evaluation using the ETV1 specific rabbit Mab on a prostate cancer TMA derived from 100 patients identified five ETV1 positive cases, of whom four were CA. The index tumors for these five ETV1 cases were ERG negative. One patient harbored both ERG positive and ERG negative tumor foci, and as expected, the ETV1 positive tumor focus was ERG negative, and vice versa. Conclusions: We developed a novel rabbit monoclonal ETV1 antibody that is suitable for IHC assay in human prostate tissue. An evaluation of prostate cancer specimens confirmed the reported frequency of ETV1 alteration. Further evaluation using tissue specimens from larger cohorts to establish the sensitivity and specificity of this antibody and validate the utility of ETV1 detection in improving the diagnosis and stratification of prostate and other cancers are in progress. Citation Format: Shyh-Han Tan, Denise Young, Sally Elsamanoudi, Jacob Kagan, Sudhir Srivastava, Albert Dobi, Gyorgy Petrovics, Isabell A. Sesterhenn, Gregory T. Chesnut. Detection of ETV1 expression in human prostate tissue specimens using a novel and highly specific rabbit monoclonal antibody [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 2565.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85369363","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 2595: Cancer cachexia is mediated by the suppression of PGC1-alpha expression in the skeletal muscle vasculature","authors":"Young-Mee Kim, Georgina Mancinelli, P. Grippo, J. Rehman","doi":"10.1158/1538-7445.AM2021-2595","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2595","url":null,"abstract":"Background: Cancer patients experience cachexia which is characterized by extensive skeletal muscle wasting that worsens the quality of life and increases mortality. However, there are no approved treatments that can effectively counteract cancer cachexia. Prior research has focused on the changes within the muscle tissue but little is known about the role of the muscle vasculature in mediating cancer cachexia. Vascular endothelial cells (ECs) are essential for maintaining tissue perfusion, nutrient supply and preventing inappropriate transmigration of immune cells into the tissue. We therefore hypothesized that endothelial dysfunction in the skeletal muscle results in the development of cachexia in cancer. The transcriptional co-activator PGC1α (peroxisome proliferation activator receptor-γ coactivator1-α) regulates endothelial health. Methods and Results: To evaluate whether skeletal muscle EC-PGC1α is modulated in the setting of malignancy, we isolated muscle ECs from control and melanoma bearing mice at 1, 2, and 3 weeks after melanoma implantation. PGC1α expression was significantly decreased in mECs of melanoma bearing mice from early stage (1 week) compared with control mice. Thus, we generated an EC-specific inducible PGC1α deletion mouse model (ECΔPGC1α) to investigate the mechanistic role of EC-PGC1α in cancer cachexia in vivo. Interestingly, vascular density and muscle area were significantly decreased in the gastrocnemius (GC) of ECΔPGC1α mice compared with ECWT mice using an innovative tissue clearing and high-resolution 3D-tissue imaging system. Tumor bearing ECWT mice had decreased GC mass and weight compared with no tumor mice by enhancing cachexia marker genes, MuRF1 and Atrogin1. The tumor bearing ECΔPGC1α mice had further decreased muscle mass and weight, and grip strength than tumor bearing ECWT mice. We assessed the role of EC-PGC1α in the regulation of capillary function in vivo, and observed that ECΔPGC1α mice demonstrated significantly greater vascular leak than ECWT mice. Conclusion: These data suggest that the presence of melanoma suppresses PGC1α expression in the skeletal muscle endothelium. Endothelial PGC1α, in turn, is essential for maintaining the integrity of the skeletal muscle vascular barrier. Our study suggests that restoring muscle endothelial dysfunction could be a novel therapeutic approach to prevent or reverse cancer cachexia. Citation Format: Young-Mee Kim, Georgina Mancinelli, Paul Grippo, Jalees Rehman. Cancer cachexia is mediated by the suppression of PGC1-alpha expression in the skeletal muscle vasculature [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 2595.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85403089","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 LB225: Colon cancer preventive efficacy of licofelone and its analogue LFA-9 in PIRC rat model of FAP","authors":"Venkateshwar Madka, N. Yarla, Gopal Pathuri, Yuting Zhang, Anh Bao, Nicole Stratton, Anil Singh, D. Mccormick, Altaf Mohammed, S. Sei, J. Fox, C. Rao","doi":"10.1158/1538-7445.AM2021-LB225","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB225","url":null,"abstract":"Inflammation is a key hallmark of many cancers and potent target for chemoprevention. Experimental and clinical intervention studies indicate strong cancer preventive efficacy of cyclooxygenase (COX)-2 inhibitors. Their use for chemoprevention is limited due to increased cardiovascular (CV) toxicities. Selective COX-2 inhibition diverts arachidonic acid to the 5-lipoxygenase (5-LOX) pathway resulting in accumulation of prothrombotic leukotrienes while depleting antithrombotic prostaglandin (PG)I2, leading to increased risk of CV events. To overcome side effects, balanced dual inhibitors targeting COX-2/5-LOX or microsomal PGE synthase (mPGES)-1/5-LOX enzymes are being developed for chemoprevention. In this study, the clinically advanced dual COX-2/5-LOX inhibitor, licofelone, and its glycine analogue (LFA-9), the mPGES-1/5-LOX dual inhibitor, were evaluated for colon cancer preventive efficacy in the FAP relevant PIRC rat model. In preclinical dose range finding and preliminary toxicity studies in F344 rats, dietary administration of licofelone Citation Format: Venkateshwar Madka, Nagendra S. Yarla, Gopal Pathuri, Yuting Zhang, Anh Bao, Nicole C. Stratton, Anil Singh, David L. McCormick, Altaf Mohammed, Shizuko Sei, Jennifer Fox, Chinthalapally V. Rao. Colon cancer preventive efficacy of licofelone and its analogue LFA-9 in PIRC rat model of FAP [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 LB225.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88046206","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 2608: Lung cancer prevention and an early detection educational intervention in minority and underserved communities","authors":"S. J. Sojourner, Marlo M. Vernon, Ghadeer Albashir, J. Moore, S. Looney, M. Tingen","doi":"10.1158/1538-7445.AM2021-2608","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2608","url":null,"abstract":"Purpose: Lung cancer is the leading cause of cancer death in African Americans (AAs). The 5-year relative survival rate for localized lung cancer among AAs is 52%; however, only 16% of lung cancer cases are detected at this early stage. Even when lung cancer is diagnosed early, AAs are less likely than whites to receive life-saving surgery. Procedures: An educational intervention was delivered in 16 sites across the CSRA: 12 AA churches, three Federally-Qualified Health Centers, and one Community Center serving low-income and minority families. Community Health Workers at each site were selected and trained to deliver the educational content in four (4) 90-minute weekly sessions to participants in their congregation/facility. Content included cancer risk factors, the health consequences of tobacco use, tobacco cessation for current smokers, and the benefits of low-dose computed tomography (LDCT) screening for lung cancer. Pre- and post-intervention “site surveys” were administered to individuals who were members/visitors of the intervention sites (i.e. members of the church, patients at the FQHC, and visitors of the Community Center) to assess community changes in knowledge, attitudes and beliefs regarding lung cancer following the intervention. This report is on the surveys completed anonymously by the people at the sites, not on those enrolled in the study. Results: Data were collected from 2136 participants (n=1404 baseline and 732 follow-up). Baseline and follow-up surveys were independent observations. Approximately 70.1% of respondents were female, 29.9% male, and 91.9% AA. There was significant improvement in the self-reported frequency of exercise among respondents, with 41.5% reporting 2-3 days of exercise at follow-up compared to 34.2% at baseline (p=0.006). Other significant findings include: current smoking status decreased from 13.5% at baseline to 8.0% at follow-up (p=0.001); knowledge of the recommended screening test for lung cancer increased from 35.2% at baseline to 43.4% at follow-up (p=0.002); men who have had a Prostate Specific Antigen (PSA) blood test within the last year increased from 54.4% at baseline to 72.2% at follow-up (p=0.006); and women answering whether they had ever had a mammogram increased from 78.0% at baseline to 86.6% at follow-up (p Conclusion: AAs are at greater risk for lung cancer incidence and mortality due to low access to quality healthcare, education, and prevention efforts. This project demonstrates that education and prevention efforts can be used to increase community knowledge about lung cancer and cancer risk factors, provide resources to decrease risk factors (smoking cessation) and increase access to screening for early detection. These efforts are promising for reducing cancer incidence and increasing early detection, and decreasing mortality rates among AAs who suffer disproportionate cancer health disparities. Citation Format: Samantha J. Sojourner, Marlo M. Vernon, Ghadeer Albashir, Justi","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88090577","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 2597: Non-clinical studies of systemic delivery of oncolytic virus arms with IL-12 and anti-PD-1 antibody","authors":"Yanxin Zheng, Runbin Yan, Yuxin Tang, Borui Zhan, Yue Huang, Dongyao Ni, Xiaoqing Chen, G. Zhou","doi":"10.1158/1538-7445.AM2021-2597","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2597","url":null,"abstract":"Background: Limited success has been reported with intravenous delivery of oncolytic viruses because of dilution of viruses in the blood volume, rapid clearance of viral particles and sequestration in non-target organs. We have reported construction of MVR-T3011, a recombinant oncolytic herpes virus embodies immunotherapeutic genes encoding IL-12 and anti-PD-1 antibody. Intratumoral Injection of MVR-T3011 has entered into clinical stage for the study of its safety and preliminary efficacy. Here we propose systemic delivery of MVR-T3011 by intravenous (IV) injection to treat tumor types that are not easily accessible by local injection. Methods: The pharmacological activity, safety and biodistribution of MVR-T3011 by intravenous injection have been studied in immune deficient and competent mouse model. Results: (i) In immune deficient mice, MVR-T3011 is enriched in tumor following tail vein injection. MVR-T3011 inhibits tumor growth of A549 xenograft. (ii) In immune competent mice, MVR-T1013L, the virus backbone carries a reporter gene encodes luciferase was enriched in upper abdomen and thorax 24hr following IV injection. (iii) IV administration of mouse surrogate oncolytic virus MVR-T3855 extended survival of mice in B16-F10 mouse melanoma lung metastasis model, LLC mouse orthotopic lung cancer model and H22 mouse orthotopic hepatocarcinoma model significantly. (iv) IV administration of MVR-T3855 delayed the onset of peritoneal effusion in H22 mouse hepatocarcinoma model significantly. (v) The biodistribution studies showed: following IV injection, tumor viral DNA reached peak level at 24hr, and dropped to baseline at 48hr; Subsequent injection showed similar patterns with lower peak levels. Consistent virus DNA level in the blood was detected without spike of viral DNA in other tissues probably due to non-complete virus genome circulating following virus clearance. Both IL-12 and anti-PD-1 antibody were detected in tissue and/or blood with low level 24hr following injection. Conclusions: MVR-T3011 is a suitable herpes oncolytic virus agent for intravenous injection through studies of pharmacological activity, safety and biodistribution. The significant finding reported in this article is clinical potential of herpes oncolytic virus for extensive metastatic tumors. Citation Format: Yanxin Zheng, Runbin Yan, Yuxin Tang, Borui Zhan, Yue Huang, Dongyao Ni, Xiaoqing Chen, Grace Zhou. Non-clinical studies of systemic delivery of oncolytic virus arms with IL-12 and anti-PD-1 antibody [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 2597.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89012672","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 2570: Evaluation of aspirin use with cancer incidence and survival among older adults in the prostate, lung, colorectal, and ovarian cancer screening trial","authors":"Holli A. Loomans-Kropp, P. Pinsky, A. Umar","doi":"10.1158/1538-7445.AM2021-2570","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2570","url":null,"abstract":"Many studies have evaluated the long-term benefits of aspirin use, however the association between aspirin use and cancer incidence and survival in older individuals remains uncertain. Additional epidemiologic evidence of this association is necessary to better understand any possible protective effects of aspirin in older adults. We performed a post-hoc retrospective analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, investigating the association of aspirin use with the risk of cancer incidence and survival from bladder, breast, esophageal, gastric, pancreatic, and uterine cancers among individuals age 65 and older. PLCO participants were included in the current study if (1) they were age 65 or over at baseline or survived to at least age 65 after enrollment and (2) had a valid baseline questionnaire with completed aspirin use information. Incident cancers were defined as first cancers diagnosed during cohort follow-up. Follow-up time began at the time of randomization or when the participant turned 65, whichever occurred first, and continued until the date of the cancer diagnosis, participant death, or the end of the study follow-up. Among participants diagnosed with the above incident cancers, the association of aspirin use prior to diagnosis with subsequent cancer-specific survival was evaluated. Follow-up for this analysis began at the time of diagnosis and ended at death or end of study follow-up. A total of 154,897 individuals were enrolled in the PLCO Trial. Of these, 139,896 individuals (mean [SD] age at baseline, 66.4 [2.4] years; 71,884 [51.4%] women; 123,824 white non-Hispanic [88.5%]) were included in the current analysis. During the study period, 32,580 incident cancers (including 1,751 bladder, 4,552 breast, 332 esophageal, 397 gastric, 878 pancreatic, 716 uterine cancers) were reported. Neither any aspirin nor aspirin use ≥3 times/week was associated with incidence of any of the investigated cancer types. However, multivariable regression analyses demonstrated that aspirin use ≥3 times/week was associated with increased bladder (HR, 0.67; 95% CI, 0.51-0.88) and breast (HR, 0.75; 95% CI, 0.59-0.96), but not esophageal, gastric, pancreatic, or uterine, cancer-specific survival. A similar association with bladder (HR, 0.75; 95% CI, 0.58, 0.98) and breast (HR, 0.79; 95% CI, 0.63, 0.99) cancer survival was observed with any aspirin use. In conclusion, any aspirin use and aspirin use ≥3 times/week was associated with improved bladder and breast cancer survival. The results of the current study provide suggestive observational evidence of the potential of aspirin use to improve bladder and breast cancer survival, however additional, follow-up studies are warranted. Citation Format: Holli A. Loomans-Kropp, Paul Pinsky, Asad Umar. Evaluation of aspirin use with cancer incidence and survival among older adults in the prostate, lung, colorectal, and ovarian cancer screening trial [abstract]. In: Proceeding","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88467056","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 2572: γ-Tocotrienol inhibition of androgen receptor (AR) expression and activation in triple negative breast cancer (TNBC) MBA-MB-231 and MDA-MB-453 cells is associated with a reduction in proliferation, migration and epithelial-to-mesenchymal transition (EMT)","authors":"T. Sultana, Nayef Aldabaan, P. Sylvester","doi":"10.1158/1538-7445.AM2021-2572","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2572","url":null,"abstract":"Triple negative breast cancer (TNBC) is an aggressive invasive malignancy with the lowest 5-years survival rate. Gene expression profiling indicates that TNBC is a heterogeneous disease and at present, there is no targeted therapy available for treatment. Approximately one third of TNBC expressed androgen receptor (AR) and evaluation of AR positive TNBC primary tumors shows nuclear localization of AR, an indication of transcriptionally active receptors. AR levels are most abundant in the luminal AR (LAR) molecular subtype of TNBC, but other non-LAR molecular TNBC subtypes also display high levels of AR expression and activity. Previous studies have shown that AR inhibition or AR knockdown significantly reduces baseline proliferation, anchorage-independent growth, migration and invasion and increase apoptosis in different TNBC cell lines. γ-Tocotrienol is a natural isoform of vitamin E that displays potent anticancer activity. Studies were conducted to determine if γ-tocotrienol effects on AR levels and activity play a role in mediating γ-tocotrienol induced inhibition of TNBC cell proliferation, migration and epithelial-to-mesenchymal transition (EMT). In vitro studies showed that treatment with 0-12 μM γ-tocotrienol induced a dose-responsive significant decrease in TNBC MDA-MB-231 and MDA-MB-453 cell proliferation and viability. Treatment with 35 nM dihydrotestosterone (DHT) resulted in an increase of AR expression and corresponding increase in the growth of both TNBC cell lines. Treatment of MDA-MB-231 and MDA MB-453 cells with γ-tocotrienol (5 μM and 7 μM, respectively), significantly inhibited DHT-induced proliferation of both TNBC cell lines. Western blot analysis showed that γ-tocotrienol treatment significantly reduced DHT-induced cytoplasmic and nuclear AR expression in MDA-MB-453 cells, but induced only a slight and insignificant reduction in AR expression in MDA-MB-231 cells. Immunocytochemistry studies confirmed that γ-tocotrienol treatment induced a decrease in cytoplasmic and nuclear AR expression in both TNBC cell lines, but this decrease was only found to be significant in MDA-MB-453 cells. Other studies showed that γ-tocotrienol treatment significantly reduced cancer cell migration and this finding was associated with an increased expression in cytokeratin 8 (an epithelial cell biomarker) and decrease in vimentin (a mesenchymal cell biomarker) in both TNBC cell lines, and is an indication of a reversal in EMT. In summary, these results demonstrated that γ-tocotrienol treatment inhibits AR expression as well as DHT-dependent cell proliferation, migration and EMT in TNBC. These findings also suggest that AR may be a potential therapeutic target for the treatment of both LAR and non-LAR TNBC subtypes. Citation Format: Tasmin A. Sultana, Nayef Aldabaan, Paul W. Sylvester. γ-Tocotrienol inhibition of androgen receptor (AR) expression and activation in triple negative breast cancer (TNBC) MBA-MB-231 and MDA-MB-453 cells is associated wi","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89495366","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 2577: Metaboendocrine and inflammatory correlates of tumor growth following caloric restriction and vertical sleeve gastrectomy in a mouse model of breast cancer","authors":"Tori L. McFarlane, Kristina K Camp, Elaine M Glenny, Erika T Rezeli, Michael F. Coleman, S. Hursting","doi":"10.1158/1538-7445.AM2021-2577","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2577","url":null,"abstract":"Breast cancer is the second leading cause of cancer-related deaths in women living in the United States, and obesity is a well-established breast cancer risk and progression factor. Identifying interventions that effectively break the obesity-cancer link is therefore of great importance. This preclinical project aims to compare circulating cytokine and metaboendocrine hormone levels in formerly obese mice following dietary and surgical weight loss to identify serum markers potentially contributing to differential tumor mass outcomes. 20 control female C57BL/6 mice were maintained on a 10 kcal% fat diet throughout the study. All other mice were placed on a 60 kcal% diet for 15 weeks to promote diet-induced obesity (DIO), then randomized to receive either: a) vertical sleeve gastrectomy (VSG) with concurrent switch to control diet (16 mice); b) sham surgery and continuation of DIO regimen (18 mice); c) sham surgery with switch to a chronic calorie restricted (CCR; 30% daily calorie reduction) regimen (16 mice); or d) sham surgery with switch to an intermittent calorie restricted (ICR; 14% calorie reduction 5 days per week, 70% calorie reduction 2 non-consecutive days per week) regimen (19 mice). Following 10 weeks of weight loss interventions, serum from fasted animals was collected, and glucose (by glucometer), cytokines (by BioRad Mouse Cytokine 23-plex panel on a BioRad MAGPIX Instrument), and hormones (BioRad Mouse Diabetes 8-plex panel) were analyzed to characterize the systemic metaboendocrine and inflammatory environment immediately prior to orthotopic transplantation of E0771 mammary cancer cells. Surgical or dietary weight loss reduced serum cytokines that are classically induced by obesity, including interleukin 6 (IL-6), interleukin 2 (IL-2), and tumor necrosis factor alpha (TNFα), compared with DIO mice. Compared with VSG mice, only circulating chemokine ligand 13 (CXCL13) was significantly lower in serum from both CCR and ICR mice. Moreover, CCR and ICR mice displayed significantly lower fasting blood glucose levels and circulating plasminogen activator inhibitor-1 (PAI-1) compared with VSG mice. Therefore, these data suggest that decreased circulating CXCL13, PAI-1 and/or decreased fasted blood glucose may contribute to the superior antitumor effects of CCR and ICR versus VSG. This research was supported by R35CA197627 to S. Hursting. Citation Format: Tori L. McFarlane, Kristina Kalevas Camp, Elaine M. Glenny, Erika Rezeli, Michael F. Coleman, Stephen D. Hursting. Metaboendocrine and inflammatory correlates of tumor growth following caloric restriction and vertical sleeve gastrectomy in a mouse model of breast cancer [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 2577.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80743227","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 2573: The anticancer effects of the vitamin E isoform, γ-tocotrienol, and vitamin D3 act synergistically to inhibit MDA-MB-231 triple negative breast cancer (TNBC) cell proliferation and viabilityin vitro","authors":"M. R. Anwar, A. Hossian, Georgios Matthaiolampakis, P. Sylvester","doi":"10.1158/1538-7445.AM2021-2573","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2573","url":null,"abstract":"Epidemiological studies suggest that dietary intake of some natural products may be effective in reducing the risk of breast cancer. Furthermore, various phytochemicals have been shown to interfere with cell signaling pathways involved in regulating breast cancer cell proliferation and viability. γ-Tocotrienol is a natural isoform of vitamin E that displays potent anticancer activity against a variety of cancer cell types at treatment doses that have little or no effect on normal cell growth or viability. Vitamin D3 is an abundant phytochemical which also displays potent antiproliferative and antiangiogenic activity against human breast cancer cells. Studies were conducted to examine the effects of γ-tocotrienol and vitamin D3 given alone or in combination on MDA-MB-231 triple negative breast cancer (TNBC) cellular proliferation, migration, colony formation, invasion, cell cycle progression, and apoptosis. Results showed that combined treatment with subeffective doses of γ-tocotrienol (8 μM) and vitamin D3 (10 nM) synergistically inhibited the growth of MDA-MB-231 cells, as determined by the MTT assay and isobologram analysis. Additional studies indicated that this combination treatment resulted in a significant inhibition in cancer cell migration and a significant reduction in cancer cell colony formation. Studies using the Matrigel invasion assay showed that combined treatment with subeffective doses of γ-tocotrienol and vitamin D3, significantly inhibited MDA-MB-231 invasiveness. Flow cytometry analysis showed that similar combined treatment of γ-tocotrienol and vitamin D3 significantly increased the percentage of cells found in G0/G1 phase, as compared to cells in the vehicle-treated control group. After 4 days of combined treatment with subeffective doses of γ-tocotrienol and vitamin D3, the percentage of cells in the G0/G1 phase of the cell cycle increased to 55% (p Citation Format: Md. R. Anwar, A.K.M.N. Hossian, Georgios Matthaiolampakis, Paul W. Sylvester. The anticancer effects of the vitamin E isoform, γ-tocotrienol, and vitamin D3 act synergistically to inhibit MDA-MB-231 triple negative breast cancer (TNBC) cell proliferation and viability in vitro [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 2573.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77849108","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}