bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-05-06: Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer
Authors: Soni M , Patel Y , Shealy R , Chen H 
Published: May 2019

Abstract
Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer.
Mithil Soni1,2, Yogin Patel1,2,3, Ryann Shealy1, Hexin Chen1,2,4.
1Dept. of Biological Sciences, University of South Carolina, 2Center for colon cancer research, 3current location, National cancer institute, surgery branch, 4corrosponding author.
Approximately 75% of diagnosed breast cancer tumors are Estrogen receptor positive tumors and are associated with better prognosis due to response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. Identification of novel molecular targets is necessary to combat such resistant tumors. In the current study, using microarray, qRT-PCR, western blot, luciferase reporter assay and immunofluorescence, we found that miR-489 is an estrogen regulated miRNA that negatively regulates estrogen signaling. Depletion of miR-489 using Anti-miR-489 siRNA or CRISPR-Cas9 significantly increased estrogen induced proliferation, colony formation ability and stem like cell population. Loss of miR-489 also induced estrogen independent proliferation. Mechanistically we found that depletion of miR-489 enhanced nuclear localization of estrogen receptor while restoration of miR-489 increased cytosolic ER and inhibited estrogen induced transcription. Furthermore, we found that miR-489 depletion also increases estrogen independent growth through activation of MAPK and PI3K-AKT pathway. We also observed loss of miR-489 in tamoxifen resistance breast cancer cell line and found increased resistance to tamoxifen upon miR-489 inhibition while miR-489 restoration sensitized Tamoxifen resistant cell lines. Clinical analysis of estrogen receptor positive breast cancer patient showed that ER+ve breast cancers with low miR-489 expression represents aggressive cancers with significant reduction in survival time. In summary, these results indicate potential role of miR-489 as a biomarker to predict aggressiveness of ER+ve breast cancer and response to tamoxifen therapy and can potentially be used as a therapeutic agent to treat or sensitize tamoxifen resistant tumors.
Citation Format: Soni M, Patel Y, Shealy R, Chen H. Estrogen induced miR-489 acts as a negative feedback to confine uncontrolled estrogen signaling and cell proliferation in breast cancer [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 P6-05-06.
Abstract P6-05-10: MicroRNA-137 inhibits cancer progression by targeting DEL-1 in triple negative breast cancer cells, MDA-MB-231
Authors: Chae YS , Baek DW , Lee IH , Lee SJ , Lee RK , Lee J , Jung J , Park H , Jeong J-H , Kang J , Park J 
Published: May 2019

Abstract
Background: This study aimed to investigate the function of microRNA-137 in Del-1 expression in triple negative breast cancer (TNBC) cells and tissues.
Methods: The Del-1 mRNA and microRNA levels were measured using a qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 20 patients with TNBC. The effects of miR-137 on cell proliferation, migration, and invasion were determined using MTT, wound healing, and Matrigel Transwell assays.
Results: microRNA-137 (miR-137) levels were remarkably low and Del-1 mRNA expression was higher in MDA-MB-231 cells as compared to other breast cancer cell lines. The luciferase reporter assay revealed that miR-137 binds directly at the 3¢-UTR of Del-1 and that Del-1 expression was downregulated by miR-137 mimics and rescued by its inhibitors. Furthermore, miR-137 inhibited the cell proliferation, migration, and invasion of MDA-MB-231 cells. Moreover, among the 30 TNBC specimens, miR-137 was downregulated (p &lt;0.0001) and the level of Del-1 in plasma was significantly elevated as compared to normal controls (p &lt; 0.0001).
Conclusions: In conclusion, miR-137 regulates Del-1 expression in TNBC via directly binding to the Del-1 gene, and thereby affects cancer progression. This suggests that miR-137 may be a new therapeutic biomarker for patients with TNBC.
Keywords: Del-1, triple negative breast cancer, miR-137, biomarker
Citation Format: Chae YS, Baek DW, Lee IH, Lee SJ, Lee RK, Lee J, Jung J, Park H, Jeong J-H, Kang J, Park J. MicroRNA-137 inhibits cancer progression by targeting DEL-1 in triple negative breast cancer cells, MDA-MB-231 [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 P6-05-10.
Abstract P6-05-11: Not presented
Authors: Chu J , Li Y , Fu Z , Tang J , Yin Y 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Chu J, Li Y, Fu Z, Tang J, Yin Y. Not presented [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 P6-05-11.
Abstract P6-17-35: Withdrawn
Authors: Hamilton EP , Barve M , Bardia A , Beeram M , Edenfield WJ , Noonan A , Tolcher A , Bendell J , Mosher R , Xu J , Hailman E , Burris III H , Soliman HH 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Hamilton EP, Barve M, Bardia A, Beeram M, Edenfield WJ, Noonan A, Tolcher A, Bendell J, Mosher R, Xu J, Hailman E, Burris III H, Soliman HH. Withdrawn [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 P6-17-35.
Abstract P6-20-06: Withdrawn
Authors: Dann S , Chionis J , Eisele K , Zhang Q , Liu C , Yuan J , Miller N , Murray B , Xu M , Solowiej J , Wei P , Weinrich S , Sutton S , Behenna D , Ninkovic S , Hoffman R , Freeman-Cook K , Jessen B , Huser N , Zhang C , Visswanathan R , Boras B , VanArsdale T , White MA 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Dann S, Chionis J, Eisele K, Zhang Q, Liu C, Yuan J, Miller N, Murray B, Xu M, Solowiej J, Wei P, Weinrich S, Sutton S, Behenna D, Ninkovic S, Hoffman R, Freeman-Cook K, Jessen B, Huser N, Zhang C, Visswanathan R, Boras B, VanArsdale T, White MA. Withdrawn [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 P6-20-06.
Abstract P6-20-16: BAT8003, a potent anti-Trop-2 antibody-drug conjugate, for the treatment of triple negative breast cancer
Authors: Tang W , Huang X , Ou Z , Yan H , Gan J , Dong Q , Tan B , Yang Y , Guo Y , Li S , Thomas B , Yu J-C 
Published: May 2019

Abstract
Trophoblast cell surface antigen 2 (Trop-2) is overexpressed on many epithelial carcinomas, yet is expressed at much lower level on normal tissue. Overexpression of Trop-2 has been correlated with poor prognosis in several solid tumors. These two characteristics make Trop-2 a potential drug target. An antibody-drug conjugate (ADC) targeting Trop-2, IMMU-132, has recently been demonstrated to be effective in treating triple negative breast cancer (TNBC) and gastric cancer patients. Here we present a Trop-2 ADC, BAT8003, which contains an uncleavable linker and a maytansine derivative as the payload. An A114C mutation on antibody heavy chain was introduced to BAT8003 for site-specific conjugation, in order to generate a more homogeneous product for a better pharmacokinetics profile. BAT8003 is also completely devoid of fucose modification, to allow for enhanced ADCC effect. We show that BAT8003 is effectively internalized upon binding to Trop-2, and inhibits proliferation of Trop2-overexpressed tumor cells with IC50s of ˜1 nM. In a TNBC (MDA-MB-468 cell) mouse xenograft model, BAT8003 strongly inhibits tumor growth at a dose level as low as 5 mg/kg. BAT8003 also demonstrates potent activity in another TNBC (MX-1 cell) mouse tumor model, in which it shows the same inhibition activity as the naked antibody conjugated heterogeneously with almost two fold payload (DAR 3.5), suggesting the effect caused by site-specific conjugation. We are currently developing BAT8003 for clinical evaluation in TNBC and other cancer indications.
Citation Format: Tang W, Huang X, Ou Z, Yan H, Gan J, Dong Q, Tan B, Yang Y, Guo Y, Li S, Thomas B, Yu J-C. BAT8003, a potent anti-Trop-2 antibody-drug conjugate, for the treatment of triple negative breast cancer [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 P6-20-16.
Abstract P6-21-02: Withdrawn
Authors: Minichsdorfer C , Bergen E , Steger GG , Pfeiler G , Frantal S , Greil R , Fohler H , Egle D , Balic M , Fitzal F , Wette V , Exner R , Bartsch RA , Gnant M 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Minichsdorfer C, Bergen E, Steger GG, Pfeiler G, Frantal S, Greil R, Fohler H, Egle D, Balic M, Fitzal F, Wette V, Exner R, Bartsch RA, Gnant M. Withdrawn [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 P6-21-02.
Abstract P6-21-06: Target N-Ras for degradation by flunarizine to treat basal-like breast cancer
Authors: Zheng Z-Y , Li J , Li F , Zhu Y , Cui K , Wong ST , Chang EC , Liao Y-h 
Published: May 2019

Abstract
Background:Basal-like breast cancer (BLBC) is an aggressive form of breast cancer that are usually triple negative for ER, PR, and HER2. There is no effective targeted therapy for BLBC due to the lack of a druggable driver. Ras GTPases are powerful drivers for tumorigenesis. We have shown that wild type N-Ras, but not K- or H-Ras, is overexpressed in BLBC and driving itsgrowth and transforming activities. However, there is currently no treatment that directly target Ras. This study thus screened existing pharmacologically active and approved compounds for the new ability to induce N-Ras degradation in BLBC.
Methods:Compounds in the LOPAC library were screened by an automated microscopy system for the ability to reduce GFP-N-Ras signals in the cells. Isolated compounds were then examined to identify those that can degrade endogenous N-Ras in BLBC cells without impacting levels of other Ras proteins. Final candidate compounds were further examined to determine by which proteolytic pathway N-Ras is induced to be degraded. The potentials of the identified compound to treat BLBC were assessed by examining cell growth and soft agar colony formation in vitroand tumor growth in vivo.
Results:We identified flunarizine (FLN), previously approved for treating migraine and epilepsy. The FLN-induced N-Ras degradation was not affected by a 26S-proteasome inhibitor. Rather, it was blocked by autophagy inhibitors. Furthermore, N-Ras can be seen co-localized with active autophagosomes upon FLN treatment, suggesting that FLN alters the autophagy pathway to degrade N-Ras. Importantly, FLN treatment recapitulated the effect of N-RASsilencingin vitroby selectively inhibiting the growth of BLBC cells, but not that of breast cancer cells of other subtypes. In addition, in vivoFLN inhibited tumor growth of a BLBC xenograft model.
Conclusion:This proof-of-principle study presents evidence that the autophagy pathway can be coerced by small molecule inhibitors, such as FLN, to degrade Ras as a strategy to treat cancer. FLN has low toxicity and should be further investigated to enrich the toolbox of cancer therapeutics against BLBC.
Citation Format: Zheng Z-Y, Li J, Li F, Zhu Y, Cui K, Wong ST, Chang EC, Liao Y-h. Target N-Ras for degradation by flunarizine to treat basal-like breast cancer [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 P6-21-06.
Abstract PD6-11: Withdrawn
Authors: Cronin-Fenton DP , Falstie-Jensen AM , Kjaersgaard A , Dupont Jensen J , Lorenzen EL , Reinertsen KV , Dekkers OM , Ewertz M 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Cronin-Fenton DP, Falstie-Jensen AM, Kjaersgaard A, Dupont Jensen J, Lorenzen EL, Reinertsen KV, Dekkers OM, Ewertz M. Withdrawn [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 PD6-11.
Abstract PD8-05: POSNOC - Positive sentinel node: Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy
Authors: Goyal A , Mann B , Thompson AM 
Published: May 2019

Abstract
Background: Role of additional axillary treatment (AxT) (axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) in women with ≤2 macrometastases and undergoing systemic therapy remains unclear. Z11 included both micro and macrometastases (around 40% micrometastases) and showed that ALND may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and receiving whole breast RT. Paradoxically, NCIC MA20, demonstrated improved DFS following the addition of regional RT. 51.8% (949/1832) had 1 or 2 positive nodes. 98.9% (1812/1832) had T1/T2 tumours. A post-Z11 survey shows that most US radiation oncologists treat the undissected axilla in women with macrometastases with ART rather than omitting AxT. Therefore, a confirmatory study is needed to clarify the role of additional AxT in women with ≤2 macrometastases undergoing BCS and other subgroups that were not included in Z11 e.g. mastectomy, microscopic extranodal invasion and sentinel node biopsy (SNB) before neoadjuvant chemotherapy.
Methods: Primary objective is to assess whether for women with ≤2 macrometastases at SNB, systemic therapy alone is non-inferior to systemic therapy plus AxT in terms of axillary recurrence at 5 years. Secondary objectives are arm morbidity assessed by LBCQ and QuickDASH questionnaires; QoL assessed by FACT-B+4 questionnaire; anxiety assessed by STAI; loco-regional recurrence; distant metastasis; time to axillary recurrence; axillary recurrence-free survival; DFS; OS; contralateral breast cancer; non-breast malignancy; and economic evaluation. Eligibility criteria include: ≥18 y, uni or multifocal invasive cancer, T1/T2, 1 or 2 macrometastases, with or without extranodal invasion. Target sample size is 1900 with a projected drop-out and non-compliance with treatment allocation rate of 10%. Primary analysis will be per protocol. The following pre-specified subgroup analyses shall be performed: number of macrometastases (1, 2), age (&lt;50, ≥50), breast surgery (mastectomy, BCS), ER (positive, negative), tumour grade (1 or 2, 3), SN assessment technique (OSNA, non-OSNA), extranodal invasion (present, absent). POSNOC opened to recruitment in July 2014. To date 1100 women have been recruited at 82 sites in the UK and 18 sites in Australia and New Zealand. Clinicaltrials.gov NCT02401685.
Citation Format: Goyal A, Mann B, Thompson AM. POSNOC - Positive sentinel node: Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy [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 PD8-05.
Abstract A01: Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of pro-metastatic tumor-associated macrophages
Authors: Rabe Daniel C. , Frankenberger Casey , Bainer Russell , Sankarasharma Devipriya , Chada Kiran , Krausz Thomas , Gilad Yoav , Becker Lev , Rosner Marsha Rich 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR02) of the Conference Proceedings.
Citation Format: Daniel C. Rabe, Casey Frankenberger, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker, Marsha Rich Rosner. Metastasis suppressors regulate the tumor microenvironment by blocking recruitment of pro-metastatic tumor-associated macrophages. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A01.
Abstract A03: Lymphocytes lead to circulating tumor cell death from 4D model seeded with non-metastatic lung cancer cell line
Authors: Mishra Dhruva K. , Juarez Humberto , Thrall Michael J. , Kim Min P. 
Published: May 2019

Abstract
Objective: Mouse lung cancer cell lines 393P and 344SQ are derived from KrasLA1/+ p53R172HΔG mice and have different metastatic potential in immunocompetent mice. 393P cells have local primary tumor growth but do not form metastatic lesions when injected into the subcutaneous space of 129sv mice. However, 344SQ cells form a primary tumor and metastatic lesions when injected into the subcutaneous space. Our aim is to determine if lymphocytes play a role in this differential metastatic lung cancer formation between the two cell lines.
Methods: Both 393P and 344SQ cells were grown in the ex vivo 4D lung cancer model. We determined the amount of primary tumor growth, the number of circulating tumor cells (CTCs), and metastatic lesion formation. The CTCs from the 4D model seeded with either cells were injected into the tail veins of immunocompetent 129sv mice (wt) or immunodeficient mice (nu/nu). We calculated the Kaplan Meier survival curve. Next, we added lymphocytes derived from a 129sv mouse spleen to an ex vivo 4D lung cancer model seeded with 393P or 344SQ and isolated the CTCs. We plated the CTCs on a petri dish and compared the survival of these cells.
Results: Both 393P and 344SQ cells grew in the 4D model. There were no significant differences in the primary tumor growth and circulating tumor cell formation between the two cell lines. There were no significant differences in the number of metastatic lesion formation between the two cell lines (p=0.5). When CTCs from the 4D model seeded with 344SQ were injected into the tail vein of nu/nu mice or wt mice, there were no differences in the survival rates between the two types of mice (p=0.3). However, nu/nu mice that were injected with CTC from the 4D model seeded with 393P were less likely to survive compared to the wt mice (p=0.002). No metastatic lesions formed in the wt mice injected with 393P CTC for 8 months. The CTC from the 4D model seeded with 344SQ and treated with lymphocytes had no significant difference in cell growth when cultured on a petri dish compared to the control group (p=0.9). However, the CTC from the 4D model seeded with 393P treated with lymphocytes had significantly less live cells compared to the control group (p=0.01).
Conclusions: Lymphocytes inhibit metastatic lesion formation in 393P cell lines but not 344SQ cell lines. The ex vivo 4D lung cancer model allows for the identification of the cell type that is responsible for inhibition of metastasis. The model can be used to study the role of different components of a tumor's microenvironment in tumor metastasis.
Citation Format: Dhruva K. Mishra, Humberto Juarez, Michael J. Thrall, Min P. Kim. Lymphocytes lead to circulating tumor cell death from 4D model seeded with non-metastatic lung cancer cell line. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A03.
Abstract A31: A novel 3D osteoblastic niche assay is useful to study the characteristics of bone metastatic cancers
Authors: Lim Seunghwan , Pareek Tej , Palassery Rasmi , Letterio John 
Published: May 2019

Abstract
(Background) Many patients with metastatic cancer (i.e. Prostate, breast, lung, kidney, and melanoma) struggle with skeletal metastases which is frequently causing cancer-related death. Thus, there is an imminent demand for a better understanding of how bone-homing cancers communicate and physically interact with the bone microenvironment. It is known that cancer-stromal cell interaction in bone marrow is a pivotal step in determining bone metastasis and tumor behavior and is seen in the events of competition with HSC for the osteoblastic niche, entering dormant status, and enhanced tumor growth. However, the lack of biologically relevant assay platforms has hampered interrogation of the mechanism of cancer-bone interaction as well as the development of bone-targeted anti-metastatic drugs. (Methods) Here, we present a novel method that can measure the bone-homing ability of cancers by co-culturing 3D osteoblastic niche (3D-ObN) spheroids derived from human mesenchymal stem cells along with reporter cell lines carrying hypoxia response element (HRE)-regulated reporter genes (pGF-HRE4-GFP/SecNLuc). First, the migration ability of metastatic cancers into the 3D-ObN was examined by analyses of O.C.T. frozen section images using confocal microscopy. Next, the metastatic ability of highly metastatic cancers were compared to normal epithelial cells and assessed by using either fluorescent microscopy (IncuCyte) or a luminometer. (Results) The HRE-driven reporter was activated in a 3D-ObN spheroid-specific manner in response to the nature of the hypoxia gradient within the spheroid. While the 3D-ObN provided signals that suppressed cancer cell proliferation, highly metastatic cancer cells displayed higher homing ability in the 3D-ObN assay relative to the normal epithelial cells. Prostate cancer cells expressing putative cancer stem cell markers (CD44/CD133high) showed higher homing ability compared to CD44/CD133low populations. (Conclusion) This assay platform is the first of its kind through the fact that it mimics cancer-osteoblastic niche interactions and allows for quantification of the ability of cancer cells including cancer stem-like cells to invade and anchor in osteoblastic niche. Furthermore, this assay system can be readily amended to an efficient and effective high throughput screening system useful for identifying molecules potentially preventive to critical process of bone metastases.
Citation Format: Seunghwan Lim, Tej Pareek, Rasmi Palassery, John Letterio. A novel 3D osteoblastic niche assay is useful to study the characteristics of bone metastatic cancers. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A31.