{"status":"ok","message-type":"work-list","message-version":"1.0.0","message":{"facets":{},"total-results":151227,"items":[{"indexed":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T09:40:08Z","timestamp":1745314808863,"version":"3.40.4"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"8_Supplement_1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2025,4,21]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n EZH2, a core subunit of the Polycomb Repressive Complex 2 (PRC2), is significantly upregulated in advanced Prostate Cancer (PCa), especially in Castration-Resistant Prostate Cancer (CRPC). However, enzymatic inhibitors of EZH2, such as EPZ-6438, have shown limited efficacy in PCa, while EZH2 knockdown has previously shown to lead to cellular senescence and major growth suppression, warranting the development of Proteolysis Targeting Chimera (PROTAC) to degrade all EZH2 proteins.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Medicinal chemistry was utilized to develop a plethora of EZH2 PROTACs. Mass spectrometry and western blotting were used to assess target protein levels. RNA-seq and H3K27me3 ChIP-seq analyses were performed in PCA cells to evaluate transcriptional and histone modification changes. Senescence staining and flow cytometry were used to evaluate cellular senescence and analyze cell cycle progression. Cell proliferation was assessed in vitro using CellTiter-Glo and live-cell proliferation assays. In vivo efficacy was evaluated using 22Rv1 and VCaP xenograft mouse models.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Among several EZH2 PROTAC degraders, 6272 was chosen as the lead candidate due to its high specificity and efficiency in degrading EZH2. We showed that 6272 significantly inhibited 22Rv1 and VCaP cell proliferation compared to EPZ-6438, although this effect was not observed in LNCaP cells. RNA-seq analysis revealed that 6272 readily induced cellular senescence pathways, such as CDKN1A (p21) expression, in 22Rv1 and VCaP, but not LNCaP cells. Further, ChIP-seq showed no changes in H3K27me3 at the CDKN1A gene locus, indicating that 6272 regulates these genes in a catalytic function-independent manner. Lastly, we confirmed that 6272 also significantly reduced 22Rv1 and VCaP xenograft tumor growth.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n In this study, we developed a novel EZH2 PROTAC with superior efficacy compared to EPZ-6438 in suppressing some prostate cancer cells via rapidly promoting cellular senescence.<\/jats:p>\n <\/jats:sec>\n \n Citation Format:<\/jats:title>\n Qi Chu, Wanqing Xie, Galina Gritsina, Xiaodong Lu, Ka Wing Fong, Zhiquan Lei, Hongshun Shi, Lourdes Brea, Jonathan Zhao, Gary Schiltz, Jindan Yu. Targeting EZH2 in castration-resistance prostate cancer using a novel PROTAC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7215.<\/jats:p>\n <\/jats:sec>","DOI":"10.1158\/1538-7445.am2025-7215","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T22:10:32Z","timestamp":1745273432000},"page":"7215-7215","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 7215: Targeting EZH2 in castration-resistance prostate cancer using a novel PROTAC"],"prefix":"10.1158","volume":"85","author":[{"given":"Qi","family":"Chu","sequence":"first","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanqing","family":"Xie","sequence":"additional","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Gritsina","sequence":"additional","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Lu","sequence":"additional","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ka Wing","family":"Fong","sequence":"additional","affiliation":[{"name":"2Northwestern University, Chicago, IL;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiquan","family":"Lei","sequence":"additional","affiliation":[{"name":"2Northwestern University, Chicago, IL;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongshun","family":"Shi","sequence":"additional","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Brea","sequence":"additional","affiliation":[{"name":"2Northwestern University, Chicago, IL;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Schiltz","sequence":"additional","affiliation":[{"name":"3Northwestern University, Evanston, IL."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jindan","family":"Yu","sequence":"additional","affiliation":[{"name":"1Emory University, Atlanta, GA;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/7215\/760282\/Abstract-7215-Targeting-EZH2-in-castration","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/7215\/760282\/Abstract-7215-Targeting-EZH2-in-castration","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T09:10:58Z","timestamp":1745313058000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/7215\/760282\/Abstract-7215-Targeting-EZH2-in-castration"}},"issued":{"date-parts":[[2025,4,21]]},"references-count":0,"journal-issue":{"issue":"8_Supplement_1","published-print":{"date-parts":[[2025,4,21]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2025-7215","ISSN":["0008-5472","1538-7445"],"issn-type":[{"type":"print","value":"0008-5472"},{"type":"electronic","value":"1538-7445"}],"published":{"date-parts":[[2025,4,21]]}},{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T15:41:05Z","timestamp":1715960465177},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"24_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2013,12,15]]},"abstract":"Abstract<\/jats:title>\n There is considerable controversy regarding the appropriate surgical procedure and its timing for evaluating the status of the axillary nodes in the neoadjuvant setting. Sentinel lymph node (SLN) surgery following initial chemotherapy avoids an axillary dissection and its associated morbidity in clinical N0 patients who have pathologic negative SLN. SLN identification and false negative rates (FNR) have been acceptable in these women and axillary recurrence rates without radiation directed to the axilla are \u00a31%. For clinical N1 disease, 2 recent studies (SENTINA, ACOSOG 1071) reported SLN identification rates of 80% and 91%, FNR of 12.8 and 14% and ypN0 rates of 52% and 40% respectively. The SLN was the only positive node(s) in 58% and 40% of the ypN1 patients. Several studies have evaluated the role of regional node (RN) irradiation in clinical N1 patients who are ypN0 following neoadjuvant chemotherapy and have found no improvement in local-regional disease free survival. RN failure rates are low as reported by the NSABP B18 and 27 trials in the absence of post mastectomy radiation or with breast only radiation. The question of RN radiation is being addressed by an NRG (NSABP-RTOG) randomized trial. For women with clinical N1 disease who remain ypN1, axillary radiation may substitute for axillary dissection. Axillary radiation has been shown in randomized trials to be equivalent to axillary dissection in the adjuvant setting for clinical N0 women (NSABP B04) including those with positive SLN (Dutch Mirror, IBCSG 23-01, AMAROS). The Alliance trial will address this question. The potential advantage of neoadjuvant chemotherapy is the ability to adjust surgical and radiation treatment based on pathologic response and thereby minimize the morbidity of combined therapy. Various clinical scenarios will be presented with treatment options.<\/jats:p>\n Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr CS01-2.<\/jats:p>","DOI":"10.1158\/0008-5472.sabcs13-cs01-2","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T22:26:43Z","timestamp":1408055203000},"page":"CS01-2-CS01-2","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract CS01-2: The role of radiation in the treatment of the axilla in the setting of neoadjuvant chemotherapy"],"prefix":"10.1158","volume":"73","author":[{"given":"B","family":"Fowble","sequence":"first","affiliation":[{"name":"University California San Francisco, San Francisco, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/24_Supplement\/CS01-2\/584899\/Abstract-CS01-2-The-role-of-radiation-in-the","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/24_Supplement\/CS01-2\/584899\/Abstract-CS01-2-The-role-of-radiation-in-the","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T08:30:05Z","timestamp":1656577805000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/24_Supplement\/CS01-2\/584899\/Abstract-CS01-2-The-role-of-radiation-in-the"}},"issued":{"date-parts":[[2013,12,15]]},"references-count":0,"journal-issue":{"issue":"24_Supplement","published-print":{"date-parts":[[2013,12,15]]}},"URL":"https:\/\/doi.org\/10.1158\/0008-5472.sabcs13-cs01-2","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2013,12,15]]}},{"indexed":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T04:13:12Z","timestamp":1745381592428,"version":"3.40.4"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"8_Supplement_1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2025,4,21]]},"abstract":"Abstract<\/jats:title>\n Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with poor survival outcomes. Transcriptomic profiling has identified distinct PDAC subtypes associated with survival, highlighting their clinical relevance. However, reliance on RNA sequencing for subtype classification is not feasible in routine clinical practice, underscoring the need for surrogate biomarkers that are both effective and practical for predicting patient outcomes. This study evaluated GATA6 and KRT17 as multiplex immunohistochemistry (IHC) biomarkers to develop a prognostic model for PDAC subtype classification. Using a tissue microarray (TMA) comprising 130 patient-derived xenografts (PDXs), we quantified cell IHC positivity and stratified samples into subtypes based on GATA6 and KRT17 expression. Whole-slide staining of representative patient tumors validated the consistency of subtype classifications between PDXs and corresponding patient tumors. Patient TMAs (224 cores from 82 tumors) were subsequently analyzed to refine the classification system, incorporating GATA6 and KRT17 positive cell percentages, staining intensity (H-scores), and clinical variables into a comprehensive prognostic model. Initial classification based on PDX models demonstrated non-significant distinct survival trends (p=0.14), likely due to sample size limitations. However, a refined model applied to patient TMAs that incorporated additional parameters effectively stratified patients into prognostic groups with significantly different overall survival (p=0.042). These findings highlight the utility of GATA6 and KRT17 as surrogate classifiers for PDAC subtype classification and prognostication, offering a practical alternative to transcriptomic sequencing in HR-proficient PDAC.<\/jats:p>\n \n Citation Format:<\/jats:title>\n Ruomeng Fang, Joan Miguel Romero, Yifan Wang, Alicia Gomez Mendez, Adeline Cuggia, George Zogopoulos. Evaluation of GATA6 and KRT17 immunostaining for subtype classification in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3339.<\/jats:p>\n <\/jats:sec>","DOI":"10.1158\/1538-7445.am2025-3339","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T15:59:32Z","timestamp":1745251172000},"page":"3339-3339","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 3339: Evaluation of GATA6 and KRT17 immunostaining for subtype classification in pancreatic ductal adenocarcinoma"],"prefix":"10.1158","volume":"85","author":[{"given":"Ruomeng","family":"Fang","sequence":"first","affiliation":[{"name":"1McGill University, Montreal, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan Miguel","family":"Romero","sequence":"additional","affiliation":[{"name":"1McGill University, Montreal, Quebec, Canada;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[{"name":"2MD Anderson Cancer Center, Houston, TX;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia Gomez","family":"Mendez","sequence":"additional","affiliation":[{"name":"3Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeline","family":"Cuggia","sequence":"additional","affiliation":[{"name":"3Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Zogopoulos","sequence":"additional","affiliation":[{"name":"3Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/3339\/758309\/Abstract-3339-Evaluation-of-GATA6-and-KRT17","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/3339\/758309\/Abstract-3339-Evaluation-of-GATA6-and-KRT17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T07:38:01Z","timestamp":1745307481000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/3339\/758309\/Abstract-3339-Evaluation-of-GATA6-and-KRT17"}},"issued":{"date-parts":[[2025,4,21]]},"references-count":0,"journal-issue":{"issue":"8_Supplement_1","published-print":{"date-parts":[[2025,4,21]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2025-3339","ISSN":["0008-5472","1538-7445"],"issn-type":[{"type":"print","value":"0008-5472"},{"type":"electronic","value":"1538-7445"}],"published":{"date-parts":[[2025,4,21]]}},{"indexed":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T04:12:17Z","timestamp":1745381537855,"version":"3.40.4"},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"8_Supplement_1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2025,4,21]]},"abstract":"Abstract<\/jats:title>\n \n Background:<\/jats:title>\n While inflammation and gonadotropin levels are hypothesized to contribute to ovarian cancer initiation, specific proteomic pathways and other potential mechanisms are unclear. Thus, we aimed to identify novel blood-based non-invasive proteomic risk biomarkers for invasive epithelial ovarian cancer.<\/jats:p>\n <\/jats:sec>\n \n Method:<\/jats:title>\n We measured 7, 310 pre-diagnostic plasma proteins using SomaScan v4.1 in 169 incident ovarian cancer cases [140 high-grade serous (HGS) cases] and 169 matched controls nested within the Nurses\u2019 Health Studies. We excluded proteins with coefficient of variation \u2265 25% and influenced by delayed processing, resulting in 3, 131 proteins included in this analysis. We transformed protein levels to probit scores to achieve normality and used conditional logistic regression modeling to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) per one standard deviation increase in protein levels. We used Gene Set Enrichment Analysis to identify biological pathways and STRING to conduct protein-protein interaction network and functional enrichment analysis. We also conducted analyses restricted to HGS histotype.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n All ovarian cancer cases included in the current analysis had blood samples collected years prior to diagnosis (median=14 years). Average age at blood collection was 56.3 years in both ovarian cancer cases and controls. When examining individual proteins associated with ovarian cancer risk, 94 proteins were significantly associated with ovarian cancer risk with nominal p-value&lt;0.05. Biological pathway analysis revealed complement cascade (NES=2.0; FDR p=0.049) and innate immune system (NES=1.5; FDR p=0.049) pathways being upregulated in ovarian cancer cases compared to controls. STRING analysis showed protein-protein interactions were enriched in pathways such as tissue remodeling (e.g., COL6A1, COL18A1, IGFBP2), lipid metabolism (e.g., NCOA2, ME1), and B cell function (e.g., IGLL5, MZB1) in ovarian cancer cases compared to controls. Similar results were observed for HGS ovarian cancer.<\/jats:p>\n <\/jats:sec>\n \n Discussion:<\/jats:title>\n We conducted a comprehensive examination of the plasma proteins associated with ovarian cancer risk in a prospective cohort study and observed upregulation of pathways related to innate immune system and complement cascade being associated with ovarian cancer risk.<\/jats:p>\n <\/jats:sec>\n \n Citation Format:<\/jats:title>\n Nan Lin, Allison F. Vitonis, Simon T. Dillion, Ngo Long, Shelley S. Tworoger, Towia A. Libermann, Kathryn L. Terry, Naoko Sasamoto. Plasma proteomics associated with ovarian cancer risk in the Nurses' Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2338.<\/jats:p>\n <\/jats:sec>","DOI":"10.1158\/1538-7445.am2025-2338","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T12:17:33Z","timestamp":1745237853000},"page":"2338-2338","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 2338: Plasma proteomics associated with ovarian cancer risk in the Nurses' Health Studies"],"prefix":"10.1158","volume":"85","author":[{"given":"Nan","family":"Lin","sequence":"first","affiliation":[{"name":"1Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison F.","family":"Vitonis","sequence":"additional","affiliation":[{"name":"1Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon T.","family":"Dillion","sequence":"additional","affiliation":[{"name":"2Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ngo","family":"Long","sequence":"additional","affiliation":[{"name":"2Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelley S.","family":"Tworoger","sequence":"additional","affiliation":[{"name":"3Knight Cancer Institute, Oregon Health & Science University, Portland, OR."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Towia A.","family":"Libermann","sequence":"additional","affiliation":[{"name":"2Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn L.","family":"Terry","sequence":"additional","affiliation":[{"name":"1Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Sasamoto","sequence":"additional","affiliation":[{"name":"1Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/2338\/756095\/Abstract-2338-Plasma-proteomics-associated-with","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/2338\/756095\/Abstract-2338-Plasma-proteomics-associated-with","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T05:39:50Z","timestamp":1745300390000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/85\/8_Supplement_1\/2338\/756095\/Abstract-2338-Plasma-proteomics-associated-with"}},"issued":{"date-parts":[[2025,4,21]]},"references-count":0,"journal-issue":{"issue":"8_Supplement_1","published-print":{"date-parts":[[2025,4,21]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2025-2338","ISSN":["0008-5472","1538-7445"],"issn-type":[{"type":"print","value":"0008-5472"},{"type":"electronic","value":"1538-7445"}],"published":{"date-parts":[[2025,4,21]]}},{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T15:32:04Z","timestamp":1715959924392},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"24_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2013,12,15]]},"abstract":"Abstract<\/jats:title>\n Introduction<\/jats:p>\n Peptide-based cancer vaccines require presentation by a specific HLA molecule. HLA-A2 is the most common class I allele in the US (40-50% of the population) and, therefore, the most commonly targeted. Our group has been investigating HER2-derived peptide vaccines administered in the adjuvant setting to high risk breast cancer patients in order to prevent disease recurrence. This study was undertaken to compare known prognostic factors and disease-free survival (DFS) in control HLA-A2+ and HLA-A2- patients in order to better define these populations for future trial design.<\/jats:p>\n Methods<\/jats:p>\n Our group is currently enrolling patients in a phase II trial evaluating the HER2-derived peptide vaccines, AE37 (MHC Class II, HLA-non-restricted epitope) and GP2 (MHC Class I, HLA-A2+ restricted epitope). The studies are enrolling high-risk, disease-free breast cancer patients with any level of HER2 expression (IHC 1+, 2+ or 3+) after completion of standard of care therapy. Patients are HLA-typed. HLA-A2+ patients are randomized to GP2+GM-CSF or GM-CSF alone. HLA-A2- patients are randomized to AE37+GM-CSF or GM-CSF alone. Demographics between groups are compared using chi squared or fisher exact as appropriate. DFS is compared using log rank.<\/jats:p>\n Results<\/jats:p>\n Thus far, 407 patients have been enrolled to the study (181 HLA-A2+ and 226 HLA-A2-). Demographics are shown in Table 1.<\/jats:p>\n Table 1. Demographics (all)\u00a0A2+A2-pn181226\u00a0Age (median)51500.47Node Positive62%66%0.46Grade 354%54%0.99Tumor &gt;\/ = 2 cm59%64%0.23ER\/PR Negative36%38%0.59HER2 Overexpression55%51%0.39Triple Negative13%15%0.52<\/jats:p>\n There are no differences between groups with respect to age, node positivity, grade, tumor size, ER\/PR status, HER2 over-expression, or triple negative breast cancer. Of those enrolled, 83 HLA-A2+ patients and 109 HLA-A2- patients have been randomized to the control groups. Within the control group, there are no differences between the HLA-A2+ and HLA-A2- patients regarding age, node positivity, grade, tumor size, ER\/PR status, HER2 over-expression, or triple negative breast cancer (Table 2).<\/jats:p>\n With a median follow-up of 30 months, DFS is similar between A2+ and A2- control patients (83% v. 80%, p = 0.93).<\/jats:p>\n Conclusions<\/jats:p>\n Baseline clinico-pathologic factors are similar between HLA-A2+ and HLA-A2- breast cancer patients with no correlations to known prognostic factors. Well-matched blinded control patients treated only with GM-CSF demonstrate no differences in DFS between HLA-A2+ and HLA-A2- patients. Therefore, it does not appear that HLA-A2 status is a prognostic factor in breast cancer, and HLA-A2+ and HLA-A2- patients should be comparable in peptide-based breast cancer vaccine trials.<\/jats:p>\n Table 2. Demographics (Control Group Only)\u00a0A2+A2-pn83109\u00a0Age (median)51510.75Node Positive65%64%0.99Grade 359%57%0.76Tumor &gt;\/ =59%71%0.08ER\/PR Negative36%38%0.84HER2 Overexpression55%46%0.19Triple Negative11%16%0.34<\/jats:p>\n Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-13-05.<\/jats:p>","DOI":"10.1158\/0008-5472.sabcs13-p4-13-05","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T22:26:43Z","timestamp":1408055203000},"page":"P4-13-05-P4-13-05","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Abstract P4-13-05: HLA-A2 is not a prognostic indicator in breast cancer: Implications for cancer vaccine trials"],"prefix":"10.1158","volume":"73","author":[{"given":"AF","family":"Trappey","sequence":"first","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JS","family":"Berry","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"TJ","family":"Vreeland","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CT","family":"Guy","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HF","family":"Diane","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SK","family":"Alan","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SJ","family":"Erika","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Ferrise","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"NM","family":"Shumway","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Papamichail","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SA","family":"Perez","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Ponniah","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EA","family":"Mittendorf","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GE","family":"Peoples","sequence":"additional","affiliation":[{"name":"San Antonio Military Medical Center, San Antonio, TX; Blanchfield Army Community Hospital, Fort Campbell, KY; Cancer Vaccine Development Lab, Bethesda, MD; Cancer Immunology and Immunotherapy Center, St. Savas Hospital, Greece; MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/24_Supplement\/P4-13-05\/585746\/Abstract-P4-13-05-HLA-A2-is-not-a-prognostic","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/24_Supplement\/P4-13-05\/585746\/Abstract-P4-13-05-HLA-A2-is-not-a-prognostic","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T09:04:12Z","timestamp":1656579852000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/24_Supplement\/P4-13-05\/585746\/Abstract-P4-13-05-HLA-A2-is-not-a-prognostic"}},"issued":{"date-parts":[[2013,12,15]]},"references-count":0,"journal-issue":{"issue":"24_Supplement","published-print":{"date-parts":[[2013,12,15]]}},"URL":"https:\/\/doi.org\/10.1158\/0008-5472.sabcs13-p4-13-05","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2013,12,15]]}},{"indexed":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T17:18:59Z","timestamp":1720113539758},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"15_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2015,8,1]]},"abstract":"Abstract<\/jats:title>\n Estrogen signaling has been shown to play a large role in the development and progression of breast tumors that express the estrogen receptor (ER\u03b1). Thus, endocrine therapies that either inhibit ER\u03b1 action (tamoxifen or fulvestrant) or inhibit estrogen synthesis (aromatase inhibitors) have been increasingly valuable for the management of ER+ breast cancer. A frequent obstacle, however, is acquired resistance to endocrine therapies, often characterized by aberrant ER\u03b1 expression and heightened growth factor signaling. Another aspect of acquired endocrine resistance that is now being examined is the role of microRNA (miRNA). miRNAs are 18-22 base pair RNA molecules whose primary role is to inhibit expression of mRNA targets by inhibition of translation or by degradation of the mRNA. Here, we have conducted next generation sequencing of the miRNA from three breast cancer cell lines - one ER+ line that is estrogen-dependent and AI-sensitive (MCF-7), and two ER+ long-term estrogen deprived (LTED) models of AI resistance (MCF-7:5C and MCF-7:2A). We found that in LTED\/AI-resistant MCF-7:5C and MCF-7:2A cells there were over 330 and 240 miRNAs differentially expressed, respectively, compared to AI-sensitive MCF-7 breast cancer cells. Initially, we used qPCR to validate the expression of miRNAs that that were differentially expressed in both LTED cell lines vs. MCF-7. Notably, LTED cell lines had upregulated miR-181a (&gt; 4 to 8-fold) and downregulated miR-221\/222 expression compared to MCF-7. Elevated miR-181a has been shown to be associated with more aggressive breast cancers whereas miR-221\/222 play a role in tamoxifen resistance through targeting ER\u03b1. Further bioinformatic analysis also revealed that the LTED cells had very unique expression profiles compared to one another, indicating that they have adapted to an estrogen-depleted environment through potentially different mechanisms. In MCF-7:5C cells, which have lost expression of the progesterone receptor (PR), a miRNA cluster on chromosome 14 is upregulated. This upregulated cluster, which encodes miR-127, miR-654, miR-889 and others, has been shown to be associated with Luminal B (ER+\/PR-) breast cancer, consistent with the hormone receptor status of the MCF-7:5C cells. The oncogenic, estrogen-responsive miR-17\/92 cluster on chromosome 13 is upregulated in the MCF-7:2A cells and these miRNAs target proteins including PTEN, p21, and Bim. Overall, these findings reveal altered expression of miRNAs in AI-resistant breast cancer cells and they suggest that targeting these miRNAs might be an effective strategy to reverse AI resistance in breast cancer patients.<\/jats:p>\n Citation Format: Erin L. Hayes, Jennifer Knapp, Joan Lewis-Wambi. MicroRNA analysis of aromatase inhibitor-resistant breast cancer cells reveals upregulation of a unique miRNA cluster on chromosome 14. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3993. doi:10.1158\/1538-7445.AM2015-3993<\/jats:p>","DOI":"10.1158\/1538-7445.am2015-3993","type":"journal-article","created":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T18:10:52Z","timestamp":1438798252000},"page":"3993-3993","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Abstract 3993: MicroRNA analysis of aromatase inhibitor-resistant breast cancer cells reveals upregulation of a unique miRNA cluster on chromosome 14"],"prefix":"10.1158","volume":"75","author":[{"given":"Erin L.","family":"Hayes","sequence":"first","affiliation":[{"name":"University of Kansas Medical Center, Kansas City, KS."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Knapp","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City, KS."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Lewis-Wambi","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center, Kansas City, KS."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/15_Supplement\/3993\/602963\/Abstract-3993-MicroRNA-analysis-of-aromatase","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/15_Supplement\/3993\/602963\/Abstract-3993-MicroRNA-analysis-of-aromatase","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:11:24Z","timestamp":1656367884000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/15_Supplement\/3993\/602963\/Abstract-3993-MicroRNA-analysis-of-aromatase"}},"issued":{"date-parts":[[2015,8,1]]},"references-count":0,"journal-issue":{"issue":"15_Supplement","published-print":{"date-parts":[[2015,8,1]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2015-3993","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2015,8,1]]}},{"indexed":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T11:14:13Z","timestamp":1656587653000},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"8_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2013,4,15]]},"abstract":"Abstract<\/jats:title>\n Embryonic transcription factors (ETFs) of the Snail, Zeb and Twist families are essential mediators of EMT programs (Epithelial to Mesenchymal Transition) and play central roles in cell determination and cell plasticity. The aberrant expression of ETFs is frequently observed in various cancer types, particularly in carcinomas, and is associated with poor prognosis and high risk of metastasis. We and others have demonstrated that their oncogenic potential relies on their ability to enable escape from oncogene-induced failsafe programs, senescence and apoptosis. Therefore, EMT-resembling processes initiated by ETFs contribute to neoplastic transformation in vitro and accelerate tumor progression in vivo in an epithelial context. We now unveil a completely different scenario in melanoma, a highly metastatic neural crest-derived cancer. Consistent with their role in melanoblasts determination, SNAIL2 and ZEB2 are already expressed in melanocytes and naevi, but their expression is down-regulated in primary melanoma. In contrast, TWIST1 and ZEB1 are aberrantly reactivated in primary and metastatic melanoma. Interestingly, this switch in ETFs expression represents a novel independent factor of poor prognosis in patients with malignant melanoma. We further demonstrate that BRAF activation, the most frequent driving event in melanoma, induces a drastic upregulation of TWIST1 and ZEB1 at the expense of SNAIL2 and ZEB2 in murine and human melanocytes. This reversible switch, orchestrated by the FRA1 transcription factor, is determinant for BRAF-driven melanocyte transformation in vitro and in a xenograft model. As a whole, while TWIST1 and ZEB1 cooperate with oncogenic BRAF to induce neoplastic transformation, SNAIL2 and ZEB2 rather behave as oncosuppressive proteins in melanoma. Gene expression profiles analyses further show that this oncogenic reprogramming of ETFs regulates the expression of the MITF master regulator, with an inhibition of MITF-regulated differentiation program and an activation of TGF\u03b2- and invasion-associated gene expression signatures. Collectively, these data highlight yet unexpected antagonistic properties of ETFs in tumor progression, and place the ETF network as a master regulator of MITF-dependent phenotype switching during melanomagenesis.<\/jats:p>\n Citation Format: Julie Caramel, Eftychios Papadogeorgakis, Louise Hill, Gareth J. Browne, Geoffrey Richard, Anne Wierinckx, Gerald Saldanha, Peter Hutchinson, James H. Pringle, Alain Puisieux, Eugene Tulchinsky, Stephane Ansieau. Antagonistic functions of EMT-inducing transcription factors during melanoma development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 285. doi:10.1158\/1538-7445.AM2013-285<\/jats:p>","DOI":"10.1158\/1538-7445.am2013-285","type":"journal-article","created":{"date-parts":[[2014,8,14]],"date-time":"2014-08-14T22:46:55Z","timestamp":1408056415000},"page":"285-285","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 285: Antagonistic functions of EMT-inducing transcription factors during melanoma development."],"prefix":"10.1158","volume":"73","author":[{"given":"Julie","family":"Caramel","sequence":"first","affiliation":[{"name":"1Centre Le\u0301on-Be\u0301rard - Centre de Recherche en Cance\u0301rologie de Lyon, Lyon, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eftychios","family":"Papadogeorgakis","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Hill","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth J.","family":"Browne","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Richard","sequence":"additional","affiliation":[{"name":"1Centre Le\u0301on-Be\u0301rard - Centre de Recherche en Cance\u0301rologie de Lyon, Lyon, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Wierinckx","sequence":"additional","affiliation":[{"name":"3ProfilXpert, Lyon, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Saldanha","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"Pringle","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Puisieux","sequence":"additional","affiliation":[{"name":"1Centre Le\u0301on-Be\u0301rard - Centre de Recherche en Cance\u0301rologie de Lyon, Lyon, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Tulchinsky","sequence":"additional","affiliation":[{"name":"2University of Leicester, Leicester, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephane","family":"Ansieau","sequence":"additional","affiliation":[{"name":"1Centre Le\u0301on-Be\u0301rard - Centre de Recherche en Cance\u0301rologie de Lyon, Lyon, France;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/8_Supplement\/285\/588495\/Abstract-285-Antagonistic-functions-of-EMT","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/8_Supplement\/285\/588495\/Abstract-285-Antagonistic-functions-of-EMT","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T10:57:00Z","timestamp":1656586620000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/73\/8_Supplement\/285\/588495\/Abstract-285-Antagonistic-functions-of-EMT"}},"issued":{"date-parts":[[2013,4]]},"references-count":0,"journal-issue":{"issue":"8_Supplement","published-print":{"date-parts":[[2013,4,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2013-285","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published-other":{"date-parts":[[2013,4]]},"published":{"date-parts":[[2013,4]]}},{"indexed":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T06:01:12Z","timestamp":1674108072670},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"2_Supplement_1","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2023,1,15]]},"abstract":"Abstract<\/jats:title>\n Patients 65 and older account for 69% of all new cancer diagnoses. Melanoma is a deadly disease, with chances of survival for patients with stage IV disease totaling only 27%. Age-related changes- both secreted and biophysical- drive metastasis, immune cell recruitment, and changes in the vasculature. Age-related changes also impact the ability of tumor cells to respond to targeted therapy, and new data from our lab indicate this may be sex specific. Our recent studies also show that age-related changes in the lung microenvironment facilitate a permissive niche for efficient outgrowth of disseminated dormant tumor cells, in contrast to the aged skin, where age-related changes suppress melanoma growth but drive dissemination. We now show that age-induced changes in distal metastatic microenvironments promote efficient reactivation of dormant melanoma cells in the lung due to changes in Wnt signaling pathways. Overall, our studies argue for placing mechanistic studies of cancer biology into the context of aging.<\/jats:p>\n Citation Format: Ashani Weeraratna. Age against the machine: How the aging microenvironment drives tumor progression [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA023.<\/jats:p>","DOI":"10.1158\/1538-7445.agca22-ia023","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T06:13:47Z","timestamp":1674022427000},"page":"IA023-IA023","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract IA023: Age against the machine: How the aging microenvironment drives tumor progression"],"prefix":"10.1158","volume":"83","author":[{"given":"Ashani","family":"Weeraratna","sequence":"first","affiliation":[{"name":"1Johns Hopkins, Baltimore, MD."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/83\/2_Supplement_1\/IA023\/712500\/Abstract-IA023-Age-against-the-machine-How-the","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/83\/2_Supplement_1\/IA023\/712500\/Abstract-IA023-Age-against-the-machine-How-the","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T06:13:47Z","timestamp":1674022427000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/83\/2_Supplement_1\/IA023\/712500\/Abstract-IA023-Age-against-the-machine-How-the"}},"issued":{"date-parts":[[2023,1,15]]},"references-count":0,"journal-issue":{"issue":"2_Supplement_1","published-print":{"date-parts":[[2023,1,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.agca22-ia023","ISSN":["1538-7445"],"issn-type":[{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2023,1,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T05:41:19Z","timestamp":1655876479411},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Small molecule imipridone ONC201 is a selective, mixed competitive and non-competitive antagonist of dopamine receptor D2 (DRD2), a GPCR that is overexpressed in a broad range of malignancies (Madhukar et al, Nature Communications, 2019). ONC201 was recently found to also act as an allosteric agonist of the mitochondrial protease ClpP that degrades members of the electron transport chain and other mitochondrial substrates (Ishizawa et al, Cancer Cell 2019). ONC201 is currently being tested in several Phase II clinical trials with evidence of clinical activity in DRD2-dysregulated tumor types, including high-grade glioma, endometrial cancer, mantle cell lymphoma and adrenal tumors. Previously, we reported that DRD2 and DRD5 expression correlates with ONC201 efficacy in the NCI60 and GDSC panels (&gt;1000 cancer cell lines) (Prabhu et al, Clinical Cancer Research, 2019). In this study, we explored additional predictive biomarkers of response for ONC201, including ClpP and known downstream effects of ONC201 across the NCI60 and GDSC cancer cell line panels. Elevated ClpP expression emerged as a top predictive biomarker for ONC201 anti-cancer efficacy (low IC50) in the NCI60 and GDSC (p = 0.0066 and p = 0.00071, respectively) panels. Upregulation of HIF1 expression is known to drive cancer cells toward glycolysis; conversely, its loss shunts cellular energetics toward oxidative phosphorylation as the primary mechanism of ATP generation (Clark et al, Cell, 2019) that is inhibited by ONC201 via ClpP activation. Accordingly, decreased HIF1a expression correlated with increased anti-cancer efficacy in the NCI60 (p = 0.058) and GDSC (p = 0.0021) panels. ONC201 is known to cause downstream activation of the integrated stress response pathway, triggering induction of ATF4 (Ishizawa et al, Science signaling, 2016). High baseline ATF4 expression correlated with lower ONC201 IC50s in the GDSC panel (p = 0.027). Proteasomal degradation of c-myc by ONC201 has been reported in association with DRD2 antagonism and inhibition of oxidative phosphorylation in GBM (Ishida et al Clinical Cancer Research, 2018). High c-myc expression correlated with lower ONC201 IC50s in the GDSC panel (p = 2.5e-6). Ongoing studies are investigating biomarker combinations and identifying tumor types that are enriched for these predictive biomarkers. In conclusion, a series of target and downstream signaling biomarkers can be used to predict innate ONC201 tumor cell sensitivity that may provide guidance for patient and tumor type selection in future ONC201 clinical trials.<\/jats:p>\n Citation Format: Sara Morrow, Varun Vijay Prabhu, Joshua E. Allen, Wolfgang Oster. Predictive biomarker evaluation for the anti-cancer imipridone ONC201 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3173.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-3173","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:35:04Z","timestamp":1599183304000},"page":"3173-3173","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 3173: Predictive biomarker evaluation for the anti-cancer imipridone ONC201"],"prefix":"10.1158","volume":"80","author":[{"given":"Sara","family":"Morrow","sequence":"first","affiliation":[{"name":"Oncoceutics, Inc., Philadelphia, PA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varun Vijay","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Oncoceutics, Inc., Philadelphia, PA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Oncoceutics, Inc., Philadelphia, PA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Oster","sequence":"additional","affiliation":[{"name":"Oncoceutics, Inc., Philadelphia, PA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/3173\/642594\/Abstract-3173-Predictive-biomarker-evaluation-for","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/3173\/642594\/Abstract-3173-Predictive-biomarker-evaluation-for","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T05:06:01Z","timestamp":1655874361000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/3173\/642594\/Abstract-3173-Predictive-biomarker-evaluation-for"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-3173","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T05:11:43Z","timestamp":1655874703835},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Purpose of the study: The NCCN guidelines state that adjuvant radiotherapy (RT) can be omitted in older women with estrogen receptor (ER)-positive, node-negative early-stage (i.e., Tis and T1) breast cancer (ESBC). However, there is no specific algorithm to select a subgroup of women who can safely forgo RT. Older women commonly present with multiple comorbid conditions with different levels of functional limitations and health-related quality of life (HRQOL), which challenge the RT-decision process. This study aimed to understand pre-diagnosis comorbidity burdens in this patient group and to examine its relationship with HRQOL and treatment selection in a retrospective cohort study design.<\/jats:p>\n Methods: From the SEER-MHOS database, we included 985 older women who were diagnosed at age \u2265 70 years, with ER-positive, node-negative ESBC between 1998 and 2013. SEER provides primary treatments (surgery and radiation), and MHOS provides self-reported comorbidity, functionality, and HRQOL. We used latent class analysis (LCA) to identify clinically distinct comorbidity burden classes. The associations between the comorbidity burdens with HRQOL and treatment selection (lumpectomy only, lumpectomy + RT, mastectomy, mastectomy + RT) were examined using generalized linear models.<\/jats:p>\n Results: A mean age at diagnosis was 77 years, 81 % of patients were whites, and 43 % were married. A majority had stage I disease (80 %) with 20 % stage 0. About one fourth (26 %) had \u2264 1 comorbid condition, whereas 28 % had \u2265 4 comorbidities. LCA identified four distinct comorbidity burden classes; healthy (n=577, 58 %), low comorbidity with limited functionality (n=64, 7 %), moderate comorbidity with symptoms (n=247, n=25 %), and high comorbidity with highly limited functionality and symptoms (n=97, 10 %). Classes were distinguished by the presence or absence of comorbid conditions and functional limitations as well as symptoms. Comorbidity burdens were independently associated with HRQOL mental component summary (MCS-12) score (p &lt; .0001) and physical component summary (PCS-12) score (p &lt; .0001) but not with treatment selection (p = 0.096). In stage 0, age (p=0.025) and education level (p=0.024) were the independent predictors of treatment selection while age (p&lt;.0001), education level (p=0.0013), income (p=0.044), and obesity (p=0.026) determined the treatment selection in stage I.<\/jats:p>\n Conclusions: Older women with ESBC can be described by four distinct comorbidity burdens that are independent predictors of HRQOL. However, it seems that the comorbidity burdens were not considered in the treatment selection process. Future studies need to address treatment outcomes (such as changes in HRQOL and survival) by comorbidity burdens to better guide treatment decisions.<\/jats:p>\n Citation Format: Eunkyung Lee, Jianbin Zhu, Robert Hines, Eunji Nam, Cassie Odahowski. Pre-diagnosis comorbidity class, health-related quality of life, and treatment selection among older women with breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4631.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-4631","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:37:42Z","timestamp":1599183462000},"page":"4631-4631","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 4631: Pre-diagnosis comorbidity class, health-related quality of life, and treatment selection among older women with breast cancer"],"prefix":"10.1158","volume":"80","author":[{"given":"Eunkyung","family":"Lee","sequence":"first","affiliation":[{"name":"University of Central Florida, Orlando, FL."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianbin","family":"Zhu","sequence":"additional","affiliation":[{"name":"University of Central Florida, Orlando, FL."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Hines","sequence":"additional","affiliation":[{"name":"University of Central Florida, Orlando, FL."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunji","family":"Nam","sequence":"additional","affiliation":[{"name":"University of Central Florida, Orlando, FL."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassie","family":"Odahowski","sequence":"additional","affiliation":[{"name":"University of Central Florida, Orlando, FL."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/4631\/643459\/Abstract-4631-Pre-diagnosis-comorbidity-class","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/4631\/643459\/Abstract-4631-Pre-diagnosis-comorbidity-class","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:38:18Z","timestamp":1655872698000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/4631\/643459\/Abstract-4631-Pre-diagnosis-comorbidity-class"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-4631","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T05:11:46Z","timestamp":1655874706891},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Introduction:Small cell lung cancer (SCLC) exhibits high-grade neuroendocrine features and recent genomic analyses revealed that aberrant expression of bacic helix loop helix transcription factors such as neurogenic differentiation 1 (NEUROD1) as well as achaete-scute homolog 1(ASCL1) have also been observed in SCLC. NEUROD1 plays important role for the development, maturation in several nerve system and formation of distal lung of neuroendocrine morphology. Previous report showed that mRNA expression as well as target genes of NEUROD1 are largely distinct from those of ASCL1 in human SCLC cell lines, however, protein level and expression patterns of these transcription factors in SCLC clinical tumor samples as well as its relation to clinicopathological characteristics have not been fully elucidated.<\/jats:p>\n Method: We retrospectively analyzed specimens from 95 SCLC patients between June 1988 and December 2017, and immunohistochemical (IHC) staining of NEUROD1 as well as ASCL1 was performed. Furthermore, we examined the effect of gain or loss of NEUROD1 function on proliferation and migration by transfection in SCLC cell lines.<\/jats:p>\n Result:Dual high staining score of ASCL1 and NEUROD1 was present in SCLC samples (32\/95: 34%) and IHC score of NEUROD1 was higher in extensive disease (ED) samples than those in limited disease (LD) samples (median score 160 vs 80 ; P = 0.0389).Overall survival did not significantly differ between SCLC patients with high or low score of NEUROD1 or ASCL1. Next, our vitro data showed that upregulation of NEUROD1 in SCLC cell lines promoted transwell migration whereas downregulation of NEUROD1 reduced cell migration.<\/jats:p>\n Conclusion: Our results from clinical and in vitro experimental data collectively indicate that NEUROD1 expression increases in extensive SCLC by promoting migration and metastasis of SCLC cells.<\/jats:p>\n Citation Format: Yuki Ikematsu, Kentaro Tanaka, Nobuhisa Ando, Kayo Ijichi, Yasuto Yoneshima, Hiroyuki Inoue, Goji Toyokawa, Tetsuzo Tagawa, Yoichi Nakanishi, Isamu Okamoto. NEUROD1 is highly expressed in extensive small cell lung cancer by promoting migration [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4922.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-4922","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:37:42Z","timestamp":1599183462000},"page":"4922-4922","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 4922: NEUROD1 is highly expressed in extensive small cell lung cancer by promoting migration"],"prefix":"10.1158","volume":"80","author":[{"given":"Yuki","family":"Ikematsu","sequence":"first","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhisa","family":"Ando","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayo","family":"Ijichi","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuto","family":"Yoneshima","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goji","family":"Toyokawa","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuzo","family":"Tagawa","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isamu","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/4922\/643619\/Abstract-4922-NEUROD1-is-highly-expressed-in","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/4922\/643619\/Abstract-4922-NEUROD1-is-highly-expressed-in","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:45:02Z","timestamp":1655873102000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/4922\/643619\/Abstract-4922-NEUROD1-is-highly-expressed-in"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-4922","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T05:11:46Z","timestamp":1655874706831},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies. The persistence of quiescent OC stem cells (OCSCs) not eliminated by chemotherapy plays a key role in tumor relapse and metastasis. In the current study, we tested the hypothesis that targeting DAB2IP will inhibit OCSCs and prevent disease recurrence. Subpopulations of CSC and non-CSC were isolated from OC cell lines by fluorescence-activated cell sorting (FACS) based on aldehyde dehydrogenase (ALDH) activity, a consistent CSC marker. Expression of DAB2IP in ALDH(+) cells was lower (P&lt;0.05) compared to non-CSC ALDH(-) cells. Chromatin immunoprecipitation (ChIP) analysis demonstrated enrichment (P&lt;0.05) of H3K27me3 at DAB2IP promoter loci in CSC compared to non-CSC. Furthermore, inhibiting EZH2 decreased H3K27me3 and increased (P&lt;0.05) DAB2IP expression in OC cells, demonstrating that DAB2IP downregulation in CSC was due to EZH2. Knocking out DAB2IP using CRISPR\/Cas9 system in OC cell lines upregulated (P&lt;0.05) expression of stemness-related genes. Enforced overexpression of DAB2IP decreased (P&lt;0.05) the number of ALDH(+) cells and inhibited (P&lt;0.05) spheroid formation. Transcriptome analysis revealed that DAB2IP overexpression significantly (FDR &lt; 0.05, fold change &gt; 2) altered expression of 449 genes, including down-regulation of ALDH1A1, LGR5, PROM1 and TWIST1, markers strongly associated with CSC phenotypes. Ingenuity Pathway Analysis for upstream regulators of differentially expressed genes revealed WNT-signaling as a dominant pathway mediating the anti-OCSC effects of DAB2IP. Based on RNA-seq analysis, WNT5B expression decreased (P&lt;0.05) by 3.83 fold, indicating that DAB2IP may negatively regulate Wnt signaling pathway by repressing WNT5B. Furthermore, WNT5B recombinant protein significantly increased (P&lt;0.05) the OCSC population, and Reverse Phase Protein Array (RPPA) analysis demonstrated activation of non-canonical WNT signaling via C-JUN as a possible downstream target of WNT5B. Collectively, our data revealed that EZH2-regulated DAB2IP is a critical tumor suppressor regulating cancer stemness-related phenotypes, via inhibiting WNT5B-induced C-JUN activation, which could be abolished by RAC1 inhibitor. Based on these novel findings, we are testing novel combination treatment strategies targeting OCSCs, with the goal of inhibiting tumor relapse and overcoming chemoresistance. Importantly, we showed that co-administration of EZH2 inhibitor and RAC1 inhibitor inhibits OCSC survival in vitro, impedes tumor growth and augments chemoresponse in vivo. These findings establish that targeting EZH2\/DAB2IP\/C-JUN axis could be considered as adjuvant therapy for platinum-based chemotherapy to prevent OC recurrence.<\/jats:p>\n Citation Format: Xingyue Zong, Ali Ozes, Weini Wang, Fang Fang, Kenneth P. Nephew. Targeting EZH2\/DAB2IP\/C-JUN axis in ovarian cancer stem cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 498.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-498","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:37:42Z","timestamp":1599183462000},"page":"498-498","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 498: Targeting EZH2\/DAB2IP\/C-JUN axis in ovarian cancer stem cells"],"prefix":"10.1158","volume":"80","author":[{"given":"Xingyue","family":"Zong","sequence":"first","affiliation":[{"name":"Indiana University, Bloomington, IN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Ozes","sequence":"additional","affiliation":[{"name":"Indiana University, Bloomington, IN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weini","family":"Wang","sequence":"additional","affiliation":[{"name":"Indiana University, Bloomington, IN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Fang","sequence":"additional","affiliation":[{"name":"Indiana University, Bloomington, IN."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth P.","family":"Nephew","sequence":"additional","affiliation":[{"name":"Indiana University, Bloomington, IN."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/498\/643615\/Abstract-498-Targeting-EZH2-DAB2IP-C-JUN-axis-in","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/498\/643615\/Abstract-498-Targeting-EZH2-DAB2IP-C-JUN-axis-in","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T04:44:54Z","timestamp":1655873094000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/498\/643615\/Abstract-498-Targeting-EZH2-DAB2IP-C-JUN-axis-in"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-498","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T07:40:43Z","timestamp":1655883643707},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"4_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,2,15]]},"abstract":"Abstract<\/jats:title>\n Background: In breast oncology, the increasing number of oral drug therapies pose great challenges for patient management. Numerous studies demonstrate that well-informed patients develop higher confidence in their treatment and a greater sense of disease control, resulting in increased adherence and persistence as well as potentially better outcome. Patients need knowledge, skills and confidence to actively participate in their own care. Moreover, such skills also contribute to reduction of planned and unplanned visits and of accompanying a time expenditure of the practice staff, thus lowering the costs of the whole treatment. Enhanced quality of life also affects financial resources by reducing sick leaves at work. The electronic Patient Reported Outcome (ePRO) tool CANKADO is designed to help oncologists to bridge the gap between good, personalized care and a time and resource-saving treatment for cancer patients. CANKADO helps patients and their physicians regarding therapy management by a standardized documentation procedure and, if needed, direct feedback to patients by the integrated Pro-React system. Methods: Aim of GERA is to assess the economic impact of an ePRO tool in breast cancer care. It is a prospective, single arm, non-interventional trial, based on questionnaires that answered by patients via the CANKADO Patient App. All patients undergoing systemic therapy for breast cancer with access to CANKADO will be included in the evaluation. This study will take place in 10 German centers and 337 patients will be included in the study. The enrollment phase of patients will last 6 months, while the individual patient observation and accompaniment phase through CANKADO will continue for 3 months. Primary objective is to gain knowledge on the health economic impact of CANKADO resource utilization in breast cancer care including the evaluation of physicians\u2019 time and patient experience. As secondary objectives, exploratory analysis of all collected information is planned. This includes the socio-demographic patient information, clinical characteristics, quality-of life and patient documentation behavior. Results: The GERA trial is ongoing. Results will be presented at the conference. Conflict of interest: None declared<\/jats:p>\n Citation Format: Tanja Eggersmann, Christoph Riese, Claudia Wenzel, Timo Schinkoethe, Tom Degenhardt, Rachel Wuerstlein, Nadia Harbeck, Manfred Welslau. GERA: A health economic trial to analyze the impact of ehealth in breast cancer care [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-14-01.<\/jats:p>","DOI":"10.1158\/1538-7445.sabcs19-ot3-14-01","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T21:14:22Z","timestamp":1585257262000},"page":"OT3-14-01-OT3-14-01","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract OT3-14-01: GERA: A health economic trial to analyze the impact of ehealth in breast cancer care"],"prefix":"10.1158","volume":"80","author":[{"given":"Tanja","family":"Eggersmann","sequence":"first","affiliation":[{"name":"1Breast Center, Department of Gynecology and Obstetrics and CCC Munich, University of Munich (LMU), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Riese","sequence":"additional","affiliation":[{"name":"2CANKADO, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Wenzel","sequence":"additional","affiliation":[{"name":"2CANKADO, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Schinkoethe","sequence":"additional","affiliation":[{"name":"2CANKADO, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Degenhardt","sequence":"additional","affiliation":[{"name":"1Breast Center, Department of Gynecology and Obstetrics and CCC Munich, University of Munich (LMU), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Wuerstlein","sequence":"additional","affiliation":[{"name":"1Breast Center, Department of Gynecology and Obstetrics and CCC Munich, University of Munich (LMU), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Harbeck","sequence":"additional","affiliation":[{"name":"1Breast Center, Department of Gynecology and Obstetrics and CCC Munich, University of Munich (LMU), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Welslau","sequence":"additional","affiliation":[{"name":"3Hematological-Oncological Practice, Hospital Aschaffenburg, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/4_Supplement\/OT3-14-01\/646149\/Abstract-OT3-14-01-GERA-A-health-economic-trial-to","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/4_Supplement\/OT3-14-01\/646149\/Abstract-OT3-14-01-GERA-A-health-economic-trial-to","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T07:19:20Z","timestamp":1655882360000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/4_Supplement\/OT3-14-01\/646149\/Abstract-OT3-14-01-GERA-A-health-economic-trial-to"}},"issued":{"date-parts":[[2020,2,15]]},"references-count":0,"journal-issue":{"issue":"4_Supplement","published-print":{"date-parts":[[2020,2,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.sabcs19-ot3-14-01","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,2,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T07:14:38Z","timestamp":1655882078664},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Introduction: About one-third of prostate cancer (PCa) patients will experience rising prostate specific antigen levels, a condition known as biochemical recurrence. INO-5150 is a DNA-based immunotherapy targeting PSA and PSMA previously tested with or without plasmid-encoded cytokine adjuvant IL-12 (INO-9012) in a phase 1\/2, open-label, multi-center study. Treatment was well-tolerated and safe, with no treatment-related serious adverse events. Here we sought to characterize the T cell receptor (TCR) repertoire of treated patients before and after INO-5150. Experimental Procedures: 62 post-prostatectomy\/radiation therapy patients with rising PSA were enrolled in the trial. INO-5150\u00b1INO-9012 was administered IM followed by electroporation with the CELLECTRA\u00ae device on day 0, weeks 3, 12 and 24. Peripheral blood mononuclear cells (PBMCs) were collected before and after treatment from a subset of patients (n=19) and stimulated with PSA or PSMA peptides, negative or positive controls. After 5 days the Complementary Determining Region 3 (CDR3) of the TCR beta chain was sequenced. Results: TCR sequences that expanded after PSA or PSMA stimulation only were considered antigen specific sequences. On average, &gt;70% of antigen specific TCR sequences were expanded following treatment with INO-5150 +\/- INO-9012, including fold increases of up to 327 fold for PSA and 471 fold for PSMA over pretreatment frequencies. All treated patients had a Shannon's entropy (H) index &gt;3.5 for TCR diversity. Previous examination of these patients using flow cytometry suggested that half of them demonstrated expansion of a PSA\/PSMA specific CD8+ T cell subset harboring lytic potential (CD38+PD1+Prf+). TCR analysis performed by grouping patients based on the presence or absence of these cells suggested PSA\/PSMA specific TCR expansion occurred for both groups. Deeper analysis suggested differences in the degree of expansion, as 56% of patients with the CD38+PD1+Prf+ phenotype were found to have at least 150 TCRs with a 10 fold expansion over baseline, whereas only 20% of patients without this cell population met this criteria. Conclusions: Treatment with INO-5150 +\/- INO-9012 in PCa patients drove the expansion of a diverse pool of antigen specific T cells with a high Shannon's Entropy value suggesting high TCR diversity. Patients with immune reactivity by flow cytometry were more likely to have a higher frequency of PSA\/PSMA specific TCRs that expanded &gt;10 fold over their pre-treatment value; however patients without immune reactivity also demonstrated expansion in TCRs. These data suggest that INO-5150 induced PSA\/PSMA specific T cells and that TCR sequencing is a valuable tool for assessment of immune responses induced by immunotherapy that does not bias towards a specific T cell function.<\/jats:p>\n Citation Format: Kimberly A. Kraynyak, Matthew P. Morrow, Albert J. Sylvester, Snehal Wani, Jean Boyer, Kamal Bhatt, Trevor McMullan, Jessica Lee, Brian Sacchetta, Samantha Rosencranz, Jeffrey Skolnik, Neal Shore. Immunotherapy targeting PSA and PSMA in patients with biochemically recurrent prostate cancer expands antigen-specific T cell receptor repertoire in a PhI\/II trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-144.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-lb-144","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:41:01Z","timestamp":1599183661000},"page":"LB-144-LB-144","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract LB-144: Immunotherapy targeting PSA and PSMA in patients with biochemically recurrent prostate cancer expands antigen-specific T cell receptor repertoire in a PhI\/II trial"],"prefix":"10.1158","volume":"80","author":[{"given":"Kimberly A.","family":"Kraynyak","sequence":"first","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew P.","family":"Morrow","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert J.","family":"Sylvester","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snehal","family":"Wani","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Boyer","sequence":"additional","affiliation":[{"name":"2Inovio Pharmaceuticals, San Diego, CA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal","family":"Bhatt","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor","family":"McMullan","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Lee","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Sacchetta","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Rosencranz","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Skolnik","sequence":"additional","affiliation":[{"name":"1Inovio Pharmaceuticals, Plymouth Meeting, PA;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal","family":"Shore","sequence":"additional","affiliation":[{"name":"3Carolina Urologic Research Center, Myrtle Beach, SC."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/LB-144\/645269\/Abstract-LB-144-Immunotherapy-targeting-PSA-and","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/LB-144\/645269\/Abstract-LB-144-Immunotherapy-targeting-PSA-and","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T06:57:50Z","timestamp":1655881070000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/LB-144\/645269\/Abstract-LB-144-Immunotherapy-targeting-PSA-and"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-lb-144","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T07:14:57Z","timestamp":1655882097220},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Stomach cancer is the third most common cause of cancer mortality worldwide. Most are adenocarcinomas. Adenocarcinomas of the stomach fall into two obvious groups based on site of origin; those arising in the area of the gastroesophageal junction (GEJ) and those arising from a more distal location, which we term gastric in this study. Adenocarcinomas of the stomach fall into four obvious groups based on a combination of genomic, molecular biologic, clinical and histopathologic characteristics (Nagara A, Kikuchi O, Bass AJ, Cancer Discovery 2019; DOI: 10.1158\/2159-8290.CD-19-0487). We are reporting herein a study of 99 patients with adenocarcinoma of the stomach. This study evaluates the location of the tumor, the histopathologic features of the tumor, the immunohistochemically determined nuclear and cytoplasmic expression of P21 activated kinase (Pak 1), Transforming Growth Factor \u03b1 (TGF\u03b1), and Ki67, a marker of cell proliferation. This study correlates these findings with patient survival. The study reveals:<\/jats:p>\n 1. significantly lower survival in patients with diffuse type adenocarcinoma compared to intestinal type, in both GEJ and gastric locations.<\/jats:p>\n 2. both GEJ and gastric adenocarcinomas had a poor prognosis.<\/jats:p>\n 3. increased expression of both TGF\u03b1 and Pak1 in GEJ adenocarcinomas.<\/jats:p>\n 4. Ki67 expression is significantly less in diffuse type than the intestinal type (p=0.01 for GEJ and 0.03 for gastric).<\/jats:p>\n 5. cytoplasmic Pak1 and cytoplasmic TGF\u03b1 were highly positively correlated (p=0.0001).<\/jats:p>\n 6. Ki67 expression was significantly inversely correlated with both nuclear Pak1 (p=0.04) and nuclear TGF\u03b1 (p=0.02).<\/jats:p>\n 7. significantly increased expression of nuclear Pak1 in gastric diffuse type compared with gastric intestinal (p=0.0002) and GEJ intestinal (p=0.0001).<\/jats:p>\n These data suggest that Pak1 and TGF\u03b1 might serve as diagnostic biomarkers of subtypes of adenocarcinomas of the stomach and gastroesophogeal junction.<\/jats:p>\n Citation Format: Larry E. Douglass, Michael Parritt, Adam Neltner, Mariah Dooley, Michelle Robillard, Molly Frydl, Leah Focke, Kyle Damen, James A. Deddens, Julia H. Carter. Pak1, TGF\u03b1, Ki 67 and survival in human gastric and gastroesophageal junction adenocarcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 747.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-747","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:40:31Z","timestamp":1599183631000},"page":"747-747","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 747: Pak1, TGF\u03b1, Ki 67 and survival in human gastric and gastroesophageal junction adenocarcinomas"],"prefix":"10.1158","volume":"80","author":[{"given":"Larry E.","family":"Douglass","sequence":"first","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Parritt","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Neltner","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariah","family":"Dooley","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Robillard","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly","family":"Frydl","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah","family":"Focke","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle","family":"Damen","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Deddens","sequence":"additional","affiliation":[{"name":"2University of Cincinnati, Cincinnati, OH."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia H.","family":"Carter","sequence":"additional","affiliation":[{"name":"1Wood Hudson Cancer Research Lab., Newport, KY;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/747\/644785\/Abstract-747-Pak1-TGF-Ki-67-and-survival-in-human","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/747\/644785\/Abstract-747-Pak1-TGF-Ki-67-and-survival-in-human","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T06:45:29Z","timestamp":1655880329000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/747\/644785\/Abstract-747-Pak1-TGF-Ki-67-and-survival-in-human"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-747","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T07:14:56Z","timestamp":1655882096780},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"16_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2020,8,15]]},"abstract":"Abstract<\/jats:title>\n Introduction: Prostate carcinoma (PCa) is the most common cancer in men. The therapeutic effect of approved compounds, such as docetaxel, is limited due to the development of therapy resistance, making new treatment options essential. Artesunate (ART), used in Traditional Chinese Medicine, has shown anti-tumor activity in several tumor types. However, little is known about the efficacy of ART on therapy-resistant PCa. Therefore, the impact of ART on docetaxel-resistant PCa cells was investigated.<\/jats:p>\n Material and Methods: Parental (=sensitive) and docetaxel-resistant PCa cell lines, PC3, DU145, and LNCaP, were exposed to ART [1-100 \u00b5M] for 24, 48, or 72 hours. Cells not exposed to ART served as controls. Tumor cell growth, proliferation, cell cycling, and the expression of cell cycle regulating proteins were assessed. Apoptotic, ferroptotic, and necrotic effects were also evaluated.<\/jats:p>\n Results: Exposure to ART significantly reduced tumor cell growth and proliferation of parental and docetaxel-resistant PCa cells in a time- and dose-dependent manner. Cell cycle arrest in the G0\/G1 phase after 48h exposure to 37.5 \u00b5M ART was observed in parental LNCaP and in all three resistant cell lines. The observed changes in cell growth and cell cycle phases were accompanied by marked modulation of cell cycle regulating proteins. Significant apoptotic effects were observed in parental PC3 and both parental and resistant LNCaP, whereas ferroptosis was apparent in parental and resistant DU145 after exposure to ART. Necrotic events were not detectable in the PCa cells after ART exposure.<\/jats:p>\n Conclusion: ART induced anti-tumor effects, though differing according to the cell line, were apparent in not only parental but also in docetaxel-resistant PCa cells. Thus, adding ART to standard therapies might be a promising treatment strategy for patients with advanced prostate cancer. Further investigations are necessary to verify our findings.<\/jats:p>\n Citation Format: Vitus Braeunig, Patricia Schupp, Sascha Markowitsch, Olesya Vakhrusheva, Holger Erb, Thomas Efferth, Axel Haferkamp, Eva Juengel. Artesunate reduces tumor growth and induces different kinds of cell death in docetaxel-resistant prostate carcinoma cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6327.<\/jats:p>","DOI":"10.1158\/1538-7445.am2020-6327","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:39:20Z","timestamp":1599183560000},"page":"6327-6327","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 6327: Artesunate reduces tumor growth and induces different kinds of cell death in docetaxel-resistant prostate carcinoma cells"],"prefix":"10.1158","volume":"80","author":[{"given":"Vitus","family":"Braeunig","sequence":"first","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Schupp","sequence":"additional","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Markowitsch","sequence":"additional","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olesya","family":"Vakhrusheva","sequence":"additional","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Erb","sequence":"additional","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"2Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Haferkamp","sequence":"additional","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Juengel","sequence":"additional","affiliation":[{"name":"1University Medical Center Mainz, Mainz, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/6327\/644760\/Abstract-6327-Artesunate-reduces-tumor-growth-and","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/6327\/644760\/Abstract-6327-Artesunate-reduces-tumor-growth-and","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T06:44:51Z","timestamp":1655880291000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/80\/16_Supplement\/6327\/644760\/Abstract-6327-Artesunate-reduces-tumor-growth-and"}},"issued":{"date-parts":[[2020,8,15]]},"references-count":0,"journal-issue":{"issue":"16_Supplement","published-print":{"date-parts":[[2020,8,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2020-6327","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2020,8,15]]}},{"indexed":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T02:11:30Z","timestamp":1655863890171},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"4_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2019,2,15]]},"abstract":"Abstract<\/jats:title>\n The concept that leukocytes are critical components of solid tumors is now generally accepted, however, their role(s) in regulating aspects of cancer progression, and\/or response to cytotoxic, targeted and\/or immune therapy is only beginning to be understood. Utilizing de novo mouse models of mammary tumor development, we now appreciate that CD4+ T lymphocytes differentially regulate myeloid cell recruitment, activation and effector function, and in turn, activated tumor-infiltrating myeloid cells foster malignancy and repress anti-tumor immunity by a diversity of mechanisms. Treatment of tumor-bearing mice with therapeutic agents disrupting lymphocyte-myeloid interactions, myeloid activation, or myeloid functionality generally slow primary tumor growth kinetics when combined with cytotoxic therapy; however, their impact on metastases is variable. Similar to organ-specific regulatory programs co-opted to foster primary tumor growth, regulation of metastatic seeding and outgrowth is also regulated by tissue- and organ-specific mechanisms. Based on this, it stands to reason that therapeutic strategies may not be efficacious in both primary and metastatic locations. To be presented will be our recent insights into organ-specific regulation of primary and metastatic mammary cancer development by adaptive and innate immune cells regulating pro- and\/or anti-tumor immunity, and new studies evaluating how attenuating protumor properties of select lymphoid and myeloid cells can be exploited to enhance therapeutic responses to cytotoxic and immune-based therapy.<\/jats:p>\n LMC acknowledges generous support from the NIH \/ NCI, the Department of Defense Breast Cancer Research Program Era of Hope Scholar Expansion Award, Susan G. Komen Foundation, the Breast Cancer Research Foundation, the Brenden-Colson Center for Pancreatic Health, and a Stand Up To Cancer \u2013 Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant.<\/jats:p>\n Citation Format: Coussens L. Modeling Immune Response: Lessons Learned from Mouse Models of Cancer Development [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BL1.<\/jats:p>","DOI":"10.1158\/1538-7445.sabcs18-bl1","type":"journal-article","created":{"date-parts":[[2019,5,11]],"date-time":"2019-05-11T19:13:55Z","timestamp":1557602035000},"page":"BL1-BL1","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract BL1: Modeling Immune Response: Lessons Learned from Mouse Models of Cancer Development"],"prefix":"10.1158","volume":"79","author":[{"given":"L","family":"Coussens","sequence":"first","affiliation":[{"name":"Oregon Health & Sciences University, Portland, OR"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/79\/4_Supplement\/BL1\/638627\/Abstract-BL1-Modeling-Immune-Response-Lessons","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/79\/4_Supplement\/BL1\/638627\/Abstract-BL1-Modeling-Immune-Response-Lessons","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T01:39:59Z","timestamp":1655861999000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/79\/4_Supplement\/BL1\/638627\/Abstract-BL1-Modeling-Immune-Response-Lessons"}},"issued":{"date-parts":[[2019,2,15]]},"references-count":0,"journal-issue":{"issue":"4_Supplement","published-print":{"date-parts":[[2019,2,15]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.sabcs18-bl1","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2019,2,15]]}},{"indexed":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T16:10:44Z","timestamp":1656346244924},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"19_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2014,10,1]]},"abstract":"Abstract<\/jats:title>\n Despite comprising up to 10% of pediatric CNS tumors, an animal model of intracranial germinoma has not been previously established. Standard of case for germinoma is radiation therapy, with recent evidence that neo-adjuvant chemotherapy may allow reduction of radiation dose, but concern for neuro-cognitive toxicity remains despite the reduction of radiation. A clinically relevant animal model of germinoma would facilitate investigation and discovery of novel agents which may obviate the need for radiation in the future. To develop xenograft mouse models, we implanted germinoma tumor cells from two children with metastatic disease, one from a surgical specimen of a cervical metastatic tumor and the second from disseminated tumor cells in the CSF, directly into the right cerebral hemispheres of NOD-SCID mice. Both patient tumor samples have undergone whole exome sequencing; one of the two models has a germinoma-associated mutation in c-kit. The tumors have been serially passaged in xenografts for 3-5 times, with each passaged tumor maintaining the ability to generate tumors, suggestive of the persistence of viable tumorigenic\/tumor stem cells. Data from additional tumor models established by our lab have confirmed molecular and genetic fidelity between xenograft-initiating human brain tumors and their corresponding murine models. The orthotopic location in the mouse brain of the xenograft model should also reasonably replicate the human germinoma tumor microenvironment. Cultured cells are currently growing from both tumor models in order to establish germinoma cell lines. In summary, our orthotopic xenograft murine models of two metastatic pediatric germinomas are the first to be established for this tumor type. These models will allow much needed pre-clinical drug testing of chemotherapeutics and combination therapies as well as further biologic characterization of pediatric germinomas.<\/jats:p>\n Citation Format: Holly B. Lindsay, Mari Kogiso, Lin Qi, Teo Wan Yee, Yulun Huang, Hua Mao, Frank Lin, Patricia Baxter, Jack M. Su, Keita Terashima, Laszlo Perlaky, Ching C. Lau, Donald W. Parsons, Murali Chintagumpala, Xiao-Nan Li. Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1193. doi:10.1158\/1538-7445.AM2014-1193<\/jats:p>","DOI":"10.1158\/1538-7445.am2014-1193","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T21:52:08Z","timestamp":1430517128000},"page":"1193-1193","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 1193: Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma"],"prefix":"10.1158","volume":"74","author":[{"given":"Holly B.","family":"Lindsay","sequence":"first","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Kogiso","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Qi","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teo Wan","family":"Yee","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulun","family":"Huang","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Mao","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Lin","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Baxter","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack M.","family":"Su","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Terashima","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laszlo","family":"Perlaky","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching C.","family":"Lau","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald W.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murali","family":"Chintagumpala","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, TX."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/74\/19_Supplement\/1193\/593038\/Abstract-1193-Establishment-of-patient-tumor","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/74\/19_Supplement\/1193\/593038\/Abstract-1193-Establishment-of-patient-tumor","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T15:32:49Z","timestamp":1656343969000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/74\/19_Supplement\/1193\/593038\/Abstract-1193-Establishment-of-patient-tumor"}},"issued":{"date-parts":[[2014,10,1]]},"references-count":0,"journal-issue":{"issue":"19_Supplement","published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2014-1193","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2014,10,1]]}},{"indexed":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T20:12:05Z","timestamp":1656360725813},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"15_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2015,8,1]]},"abstract":"Abstract<\/jats:title>\n Aim: Although minimal invasive treatment is accepted for gastric cancer, we still do not have any appropriate risk markers to detect residual neoplasia and recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of neoplasia. Our goal is to find some candidate genes as a treatment marker using genome wide DNA methylation analysis for early gastric cancer (EGC). Methods and Results: We studied Methylated CpG Island Amplification Microarray (MCAM) analysis using 12 gastric washes (each 6 before (Pre) and after (Post) endoscopic treatment in same patients). One of them is BARHL2. We examined the DNA methylation status of BARHL2 in a validation set consisting of 128 washes samples (Pre, 64: Post, 64) at EGC. We next identified functional studies about BARHL2 as a putative tumor suppressor gene. Treating GCa cells that lacked BARHL2 expression with a methyltransferase inhibitor, 5-aza-2\u2032-deoxycytidine, restored the gene's expression. Introduction of exogenous BARHL2 into silenced cells suppressed colony formation. Moreover, BARHL2 showed significantly differential methylation between before and after treatment in EGC patient (BARHL2, p&lt;0.0001). Discussion: Our data suggest that silencing of BARHL2 occurs frequently in EGC and may play a key role in development and progression of the disease.<\/jats:p>\n Citation Format: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh. Hypermethylation of BARHL2 gene is useful as a molecular marker in early stage of gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1062. doi:10.1158\/1538-7445.AM2015-1062<\/jats:p>","DOI":"10.1158\/1538-7445.am2015-1062","type":"journal-article","created":{"date-parts":[[2015,8,5]],"date-time":"2015-08-05T18:10:41Z","timestamp":1438798241000},"page":"1062-1062","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract 1062: Hypermethylation of BARHL2 gene is useful as a molecular marker in early stage of gastric cancer"],"prefix":"10.1158","volume":"75","author":[{"given":"Yoshiyuki","family":"Watanabe","sequence":"first","affiliation":[{"name":"St. Marianna Univ. School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritsuko","family":"Oikawa","sequence":"additional","affiliation":[{"name":"St. Marianna Univ. School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"St. Marianna Univ. School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumio","family":"Itoh","sequence":"additional","affiliation":[{"name":"St. Marianna Univ. School of Medicine, Kawasaki, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/15_Supplement\/1062\/599843\/Abstract-1062-Hypermethylation-of-BARHL2-gene-is","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/15_Supplement\/1062\/599843\/Abstract-1062-Hypermethylation-of-BARHL2-gene-is","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T19:44:39Z","timestamp":1656359079000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/15_Supplement\/1062\/599843\/Abstract-1062-Hypermethylation-of-BARHL2-gene-is"}},"issued":{"date-parts":[[2015,8,1]]},"references-count":0,"journal-issue":{"issue":"15_Supplement","published-print":{"date-parts":[[2015,8,1]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.am2015-1062","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2015,8,1]]}},{"indexed":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T01:40:28Z","timestamp":1656380428380},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"9_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"published-print":{"date-parts":[[2015,5,1]]},"abstract":"Abstract<\/jats:title>\n Background: Breast cancer (BC) among young women is an emerging public health issue in Mexico, as the proportion of incident cases and deaths has been reported to be greater in women aged &lt;40 years compared to high-income regions. However, there is scarce information in Hispanic populations regarding the presentation and outcome of this subgroup of patients. The purpose of our study was to compare the distribution of BC subtypes between age subgroups and to determine the prognostic significance of young age stratified by molecular subtype based on ER, PR, and HER2 status.<\/jats:p>\n Methods: This study included all consecutive patients with BC diagnosed at the National Cancer Institute in Mexico in the year 2007. A panel of ER, PR, and HER2 was used as a means of classifying BC into three molecular subtypes: (a) Hormone-receptor (HR) positive and HER2-negative, (b) Triple-negative, and (c) HER2-positive. The Chi-square test was used to compare the distribution of baseline characteristics among groups according to age (\u226440 years vs. &gt;40 years). Cox proportional hazard analysis was applied to assess the association of clinical and pathological factors with recurrence free survival with follow-up through 2013.<\/jats:p>\n Results: Of the 696 analyzed patients, 134 (19.3%) were \u226440 years. For the whole group, locally advanced BC accounted for the majority of the cases (61%), and there was no difference regarding clinical stage of presentation between age subgroups. The BC subtype distribution differed among age subgroups (HR-pos\/HER2-neg: 42% vs. 52%, triple-negative: 30% vs. 21%, HER2-pos: 24% vs. 23%, for young vs. non-young respectively). After a median follow-up of 74.6 months, 48% of young patients experienced a recurrence compared to 39% of women &gt;40 years. After subtype and clinical stage stratification, young age remained a significant independent predictor of recurrence in patients with HR-pos\/HER2-neg tumors (hazard ratio 1.71; 95% CI:1.09-2.69; P = 0.019), but was not found to be a predictor of recurrence for patients with HER2-pos and triple negative subtypes.<\/jats:p>\n Conclusions: The results of our present study suggest that the poor survival associated with young age is not only driven by a high proportion of triple-negative BC, but also by poor prognosis in the most prevalent HR-pos\/HER2-neg subgroups. Possible explanations for this finding are a greater proportion of Luminal B BC subtype and\/or tamoxifen resistance in the young age group. Further characterization of HR-pos BC should be pursued and aggressive therapeutic strategies must be considered for treatment of young women with high-risk features.<\/jats:p>\n It is critical to note the extremely high prevalence of BC among young women in our Institution, which comprised 19% of the total population. To address this unmet, growing burden, we adopt the model of a specialized program for the care of young women with BC, the first in Latin America, at the National Cancer Institute in Mexico. The goals of our program include optimizing complex clinical care and supporting needs for young women and their families; promoting medical, biomedical, and social research; and educating women and health professionals to promote early cancer detection and improved multidisciplinary management.<\/jats:p>\n Citation Format: Cynthia Villarreal-Garza, Nancy Reynoso-Noveron, Claudia Arce-Salinas, Fernando Lara-Medina, Enrique Bargallo, Leticia Mendoza-Galindo, Federico Lasa, Maria Teresa Ramirez, Alejandro Mohar. High triple-negative breast cancer prevalence and poor outcome of hormone receptor positive breast cancer among young Mexican women [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-55.<\/jats:p>","DOI":"10.1158\/1538-7445.sabcs14-p6-08-55","type":"journal-article","created":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T19:00:05Z","timestamp":1430766005000},"page":"P6-08-55-P6-08-55","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Abstract P6-08-55: High triple-negative breast cancer prevalence and poor outcome of hormone receptor positive breast cancer among young Mexican women"],"prefix":"10.1158","volume":"75","author":[{"given":"Cynthia","family":"Villarreal-Garza","sequence":"first","affiliation":[{"name":"1Instituto Nacional de Cancerologia"},{"name":"2Tecnologico de Monterrey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Reynoso-Noveron","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Arce-Salinas","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Lara-Medina","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Bargallo","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia","family":"Mendoza-Galindo","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Lasa","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Ramirez","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Mohar","sequence":"additional","affiliation":[{"name":"1Instituto Nacional de Cancerologia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1086","container-title":["Cancer Research"],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/9_Supplement\/P6-08-55\/607818\/Abstract-P6-08-55-High-triple-negative-breast","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/9_Supplement\/P6-08-55\/607818\/Abstract-P6-08-55-High-triple-negative-breast","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T01:14:34Z","timestamp":1656378874000},"score":0.0,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/75\/9_Supplement\/P6-08-55\/607818\/Abstract-P6-08-55-High-triple-negative-breast"}},"issued":{"date-parts":[[2015,5,1]]},"references-count":0,"journal-issue":{"issue":"9_Supplement","published-print":{"date-parts":[[2015,5,1]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.sabcs14-p6-08-55","ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"published":{"date-parts":[[2015,5,1]]}}],"items-per-page":20,"query":{"start-index":0,"search-terms":null}}}