bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-03-10: Circulating exosomal microRNA profiling to depict mechanisms of chemotherapy resistance among triple negative breast cancer
Authors: He Y , Tang J 
Published: May 2019

Abstract
Background: Chemotherapeutic resistance leads to high mortality among triple negative breast cancer (TNBC) and underlying mechanisms are poorly understood. Exosomes have been new member of liquid biophsy. MicroRNAs (miRNAs), as the most important inclusions in exosomes, making them ideal candidate biomarkers and therapeutical targets.
Methods: We isolated exosomes and analyzed exosome-carried miRNAs signatures in several TNBC cells lines sensitive or resistant to adariamycin, docetaxel or cisplatin. The resistance transfer capacity was determined by flow cytometry after sensitive cells incubated 48 hours with exosomes from drug resistant cells. Locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH) was performed to detect exosomal miRNA molecules transfer. Animal mode was constructed to evaluate treatment feasibility using miRNA modified exosomes. Serum exosomes from 40 TNBC stage IV patients underwent chemotherapy before or after progress disease (PD) status were isolated to analyze miRNA profiling for potential biomarkers identification.
Results: We successfully isolated and identified exosomes from several drug sensitive and resistant TNBC cell lines and patients. Exosomal miR-222, miR-4443, miR-100, miR-17, miR-210 were found significantly upregulated from chemotherapy resistance cells. Incubation of exosomes from the resistant cells with the sensitive cells resulted in increasing resistant capacity among sensitive cells. Exosomal miRNA molecules transfer were detected using LNA-ELF-FISH. Transfection of synthesized miRNAs competitors into exosomes increased drug sensitivity in vivo. Exosomal miR-222, miR-4443, miR-100, miR-17, miR-210 were also found upregulated significantly from serums of patients after PD status. These five miRNAs were able to differentiate patients with PD status from those with CR or PR status with at least 89% accuracy.
Conclusion: Exosomes from chemotherapy resistant TNBC cells could transfer drug resistance to sensitive cells via exosomal miRNAs. A circulating exosomal microRNA profiling was estabilished for potential biomarkers and therapeutical targets identification.
Citation Format: He Y, Tang J. Circulating exosomal microRNA profiling to depict mechanisms of chemotherapy resistance among 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 P5-03-10.
Abstract P5-03-14: Not presented
Authors: Xu Z , Tang J 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Xu Z, Tang J. 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 P5-03-14.
Abstract P5-04-04: Withdrawn
Authors: Das GM , Kulkarni S , Oturkar C , Edge SB , Wilton JH , Wang J , Swetzig WM , Adjei AA , Bies R , Hutson AD , Morrison CD , Kaipparettu BA , Groman A , Kumar S , Capuccino H 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Das GM, Kulkarni S, Oturkar C, Edge SB, Wilton JH, Wang J, Swetzig WM, Adjei AA, Bies R, Hutson AD, Morrison CD, Kaipparettu BA, Groman A, Kumar S, Capuccino H. 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 P5-04-04.
Abstract P5-04-06: Withdrawn
Authors: Katzenellenbogen JA , Min J , Kim SH , Laws MJ , Zhao Y , Ziegler Y , Nelson ER , Shahoei SH , Chu D , Park BH , Katzenellenbogen BS 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Katzenellenbogen JA, Min J, Kim SH, Laws MJ, Zhao Y, Ziegler Y, Nelson ER, Shahoei SH, Chu D, Park BH, Katzenellenbogen BS. 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 P5-04-06.
Abstract P5-04-12: Withdrawn
Authors: Charmsaz S , Doherty B , Cocchiglia S , Bolger J , Vareslija D , McCartan D , Hill A , Young L 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Charmsaz S, Doherty B, Cocchiglia S, Bolger J, Vareslija D, McCartan D, Hill A, Young L. 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 P5-04-12.
Abstract P5-04-22: Withdrawn
Authors: Treuner K , Hayes M , Schnabel CA , Heinz S 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Treuner K, Hayes M, Schnabel CA, Heinz S. 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 P5-04-22.
Abstract P5-04-27: Investigating the incidence of ESR1 gene amplification in breast cancers resistant to multiple endocrine agents
Authors: Turnbull AK , Martinez-Perez C , Mok S , Tanioka M , Fernando A , Renshaw L , Keys J , Wheless A , Garrett A , Parker J , He X , Sims AH , Carey LA , Perou CM , Dixon JM 
Published: May 2019

Abstract
Background: Around 70% of all breast cancers (BCs) are estrogen receptor positive (ER+), but some do not respond to endocrine therapy (ET) and many eventually develop resistance. ESR amplification (ESRA) linked to an increase in ESR1 gene expression is known to occur in some cancers that are endocrine resistant. However, the incidence of ESRA has been the object of debate and its clinical significance remains unclear. This study aimed to investigate the incidence of ESRA in BCs resistant to multiple sequential ETs and optimise a fluorescence in-situ hybridisation (FISH) methodology to robustly detect ESRA.
Methods: Two unique cohorts have been studied:
(A) 20 post-menopausal women with ER+ BC with acquired resistance to letrozole, subsequently treated with up to 4 different lines of ET. Serial RNA and DNA from 3-5 cancer samples per patient (58 samples from 20 patients) were analysed by Ribo0-RNAseq and DNA exome sequencing;
(B) 18 post-menopausal women who developed ER+ BC recurrences on 1st line adjuvant letrozole, then on 2nd line tamoxifen and subsequently on 3rd line exemestane. Tissues were collected at the time of each surgery.
We have optimised a FISH method to assess ESRA in these tissues.
Results: In cohort A, 6/20 patients developed ESR1 gene amplification (ESRA) at some point during treatment. In 5 of these cases, ESRA was only found while on 2nd or 3rd line exemestane but was not present on acquired resistance to previous letrozole or tamoxifen. 1 patient had ESRA at the time of first recurrence on letrozole.
The FISH method showed concordance with the genomic analysis. This suggests that ESRA may be associated with BCs that are treated with and then become resistant to exemestane.
ESRA is also evident in samples from Cohort B, which includes 18 exemestane resistant cases. The complete analysis is ongoing.
Conclusions:
· ESRA can be seen in ER+ recurrent BCs.
· ESRA may be associated with BCs treated with 2nd or 3rd line exemestane.
· The frequency of ESRA in endocrine and exemestane resistance can now be ascertained using an optimised FISH-based method, which is more cost-effective than alternative genomic and biochemical methods.
Citation Format: Turnbull AK, Martinez-Perez C, Mok S, Tanioka M, Fernando A, Renshaw L, Keys J, Wheless A, Garrett A, Parker J, He X, Sims AH, Carey LA, Perou CM, Dixon JM. Investigating the incidence of ESR1 gene amplification in breast cancers resistant to multiple endocrine agents [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 P5-04-27.
Abstract P5-05-13: Quantitative combinatory indexed ChIP-seq reveals distinct transcriptional complexes containing estrogen receptor and GREB1 at chromatin in breast cancer cells
Authors: Sun J , Lippman ME 
Published: May 2019

Abstract
GREB1 is an estrogen-activated gene in estrogen receptor a (ER)-positive breast cancer cells. GREB1 is also required for estrogen-stimulated breast cancer cell growth and its level is highly correlated to ER level in breast cancer cells and tumor samples. In endocrine resistant diseases, GREB1 is often dysregulated. GREB1 has been shown to interact with ER and bind to the same ER binding sites throughout the genome. There is no identified functional domain in GREB1 and it is not completely known how GREB1 exerts its function to regulate the transcription of ER target genes. In order to demonstrate whether GREB1 is present in the ER-containing transcriptional complex at chromatin, we have adapted and developed a quantitative combinatory indexed ChIP-seq assay suitable for dissecting components in a transcriptional cofactor complex in a genome-wide scale. In ER-positive MCF-7 breast cancer cells, we found that almost all GREB1 binding sites are the same sites bound by ER or its bona fide coactivator SRC-3. We further found that GREB1 and SRC-3 are both present in the same ER-containing complex at chromatin. Thus, both GREB1 and SRC-3 are integral members of the ER transcriptional complex at chromatin. Moreover, we discovered that only a portion of GREB1 at chromatin is present in the ER complex while the other portion of GREB1 is present in a different complex lacking ER or SRC-3 at the same genomic loci. Thus, two distinct GREB1-containing complexes are identified in equilibrium at chromatin: one contains ER/SRC-3 and the other one lacks ER/SRC-3. Our results suggest a non-traditional role of GREB1 in transcriptional regulation of ER target genes. The method used in our study can be widely applied for probing components of transcriptional complexes at chromatin.
Citation Format: Sun J, Lippman ME. Quantitative combinatory indexed ChIP-seq reveals distinct transcriptional complexes containing estrogen receptor and GREB1 at chromatin in breast cancer cells [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 P5-05-13.
Abstract P5-07-02: Not presented
Authors: Chatterjee S , Berdnikov A , Buchel E , Safneck J , Marshall AJ , Murphy LC , Raouf A 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Chatterjee S, Berdnikov A, Buchel E, Safneck J, Marshall AJ, Murphy LC, Raouf A. 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 P5-07-02.
Abstract P5-07-07: The immune microenvironment of ductal carcinoma in situ of the breast
Authors: Yamashita N , Hisamatsu Y , Shigechi T , Tokunaga E , Saeki H , Oki E , Maehara Y 
Published: May 2019

Abstract
Background: The importance of tumor-infiltrating lymphocytes (TIL) in invasive breast carcinoma for tumor development and therapeutic response is widely accepted. However, the immune microenvironment of breast ductal carcinoma in situ (DCIS) has not been fully elucidated. Evasion of immune surveillance is a necessary step in tumor evolution. In DCIS, the tumor cells are relatively protected from the immune system due to an myoepithelial cell layer and basement membrane, and intraductal immune cells are rarely detected. In contrast, in invasive disease, cancer cells and immune cells are often intermingled. Thus, understanding the immune microenviroment of in situ to invasive carcinoma transition might be particularly important to identify novel targets for early stage of tumor invasion.
Aims: The aim of this study is to evaluate the clinical importance of TILs in DCIS.
Methods: TILs were assessed in 133 DCIS samples with or without microinvasive disease according to the proposed method from the International Immuno-Oncology Working Group on Breast Cancer. In addition, the relationship between TILs in DCIS and clinicopathological features was evaluated.
Results: TILs are present in most DCIS in varying levels. The median proportion of TILs in DCIS was 14%. Only a minority of DCIS showed &gt;50% TILs, which represented only 12.8% of all cases. High TILs in DCIS was significantly associated with comedo necrosis (p&lt;0.0001), high nuclear grade (p=0.0030), ER negativity (p&lt;0.0001), PR negativity (p&lt;0.0001), HER2 positivity (p=0.0030). Triple negative DCIS and HER2 positive DCIS had significantly higher level of TILs (p=0.0008). No correlation was demonstrated between TILs and recurrence risk.
Conclusions: High TILs in DCIS was significantly associated with adverse histopathologic features. Further characterization of immune environment of DCIS may be essential for immunotherapy and breast cancer prevention.
Citation Format: Yamashita N, Hisamatsu Y, Shigechi T, Tokunaga E, Saeki H, Oki E, Maehara Y. The immune microenvironment of ductal carcinoma in situ of the breast [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 P5-07-07.
Abstract P5-07-08: Withdrawn
Authors: Persson E , Gregersson P , Fitzpatrick P , Ståhlberg A , Landberg G 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Persson E, Gregersson P, Fitzpatrick P, Ståhlberg A, Landberg G. 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 P5-07-08.
Abstract P5-07-11: Transcriptome alteration of breast cancer cells in the process of tumor-associated macrophages-promoted metastasis
Authors: Long M , Yang M , An J , Su H , Liu R 
Published: May 2019

Abstract
Introduction: Tumor-associated macrophages (TAMs) play an important role in the process of tumor metastasis. Previous studies have shown that TAMs induce breast cancer cells undergo epithelial-mesenchymal transition (EMT) by secreting CCL18. Reciprocally, the induced mesenchymal-like breast cancer cells activate macrophages into a TAM-like phenotype via secreting the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), forming a positive feedback loop that is essential to breast cancer metastasis.
Methods: To better understand the underlying mechanism that links this positive feedback loop to breast cancer metastasis, a TAMs-induced EMT cell model (MCF-7) was used. RNA-seq was used to compare the transcriptome of MCF-7 cells which were cocultured with TAMs and those with or without monocyte-derived macrophages (MDMs). Results were further verified by qRT-PCR.
Results: Among 811 known protein-coding genes with reliable readouts, 42 were significantly changed between groups (P&lt;0.001). Further analysis using KEGG, Reactome and Wikipathways databases found that these 42 genes were enriched in 15 signal pathways (P&lt;0.01). According to their biological function, these pathways can be divided into 5 functional groups: SUMOylation related, virus related, immune related, interferon related and cytokine related. The last 3 groups demonstrated that our model were representative and able to provide some real and useful information, while SUMOylation and virus related signal pathways have never been reported to be involved in TAMs induced breast cancer metastasis.
Conclusion: We investigated the transcriptome alteration of MCF-7 cells in the process of TAMs-promoted metastasis. Results from bioinformatic analysis indicated SUMOylation and virus related signal pathways in the process of TAMs induced breast cancer metastasis, which are yet to be confirmed.
Citation Format: Long M, Yang M, An J, Su H, Liu R. Transcriptome alteration of breast cancer cells in the process of tumor-associated macrophages-promoted metastasis [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 P5-07-11.
Abstract P5-07-14: CCL18 signaling from breast tumor-associated macrophages fosters the activation of fibroblasts into a chemoresistance-inducing phenotype
Authors: Song E , Su S , Chen J 
Published: May 2019

Abstract
Carcinoma-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in tumor microenvironment critically involved in cancer progression. Our recent study identified a specific CAFs subset by two cell-surface molecules, CD10 and GPR77. We proved that CD10+GPR77+ CAFs could promote tumor formation and chemoresistance by providing a survival niche for cancer stem cells (CSCs). However, their origin and underlying activating initiation mechanism are unclear. Tumor-associated macrophages (TAMs) are the most abundant immune-related stromal cells and the important source of inflammatory cytokine. Here, we demonstrated that CCL18 secreted by TAMs could induces the activation of normal breast fibroblasts into a CD10+GPR77+ CAFs phenotype, which are not only resistant to chemotherapy themselves, but also can induce chemoresistance in cancer cells by abundantly producing IL-8 and IL-6 and enriching the population of cancer stem cells. In conclusion, our studies have identified an inflammatory signaling network in the interaction of different kind of stroma cells in tumor microenvironment and highlighted its potential values as predictive markers and therapeutic targets to abrogate tumor formation and improve chemotherapeutic efficacy.
Citation Format: Song E, Su S, Chen J. CCL18 signaling from breast tumor-associated macrophages fosters the activation of fibroblasts into a chemoresistance-inducing phenotype [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 P5-07-14.
Abstract P5-08-06: Differential effects of eribulin on key transcription factors snail and slug
Authors: Kaul R , Risinger AL , Mooberry SL 
Published: May 2019

Abstract
Microtubule targeting agents (MTAs) are a mainstay in the treatment of breast cancer and a growing body of evidence demonstrates that they have non-mitotic effects that contribute to their anticancer actions. Even after decades of clinical use, there is much to still be learned about the mechanisms of action these drugs, and differences among them, for optimal utility. MTAs rapidly alter microtubule dynamics, often within minutes, leading to significant changes in oncogenic cellular signaling. We evaluated the early effects of eribulin on key oncogenic signaling pathways following a 2 h incubation using clinically relevant concentrations and compared the effects to those initiated by other MTAs. These studies led to the identification of novel mechanisms by which MTAs disrupt oncogenic signaling and contribute to the reversal of epithelial to mesenchymal transition (EMT), including unanticipated differences among drugs.
The TGF-β-mediated expression of the Snail transcription factor is a key driver pathway of EMT in breast cancer. The effects of eribulin and other MTAs on TGF-β-induced, Smad-dependent expression of Snail were evaluated. Our results show that eribulin and vinorelbine, but not paclitaxel or ixabepilone, inhibit the ability of TGF-β to promote the transcriptional induction of Snail by impeding the nuclear transport of Smad2/3 proteins in 4 triple-negative breast cancer cell lines. This study begins to explain how microtubule disruption might contribute to the eribulin-mediated EMT reversal observed in vitro, in vivo, and in patients.
Slug is another member of the Snail family of transcription factors that plays a central role in breast cancer EMT. Although Snail and Slug are often grouped together due to functional similarities, it is becoming increasingly clear that Slug has an independent role in regulating stemness and cancer cell survival during partial EMT. In contrast to our findings with Snail, eribulin and vinorelbine, but not paclitaxel or ixabepilone, induced Slug expression independent of TGF-β stimulation in a subset of triple-negative breast cancer cell lines. Studies are ongoing to identify the molecular pathways and consequences of eribulin and vinorelbine-induced Slug induction, which might begin to identify biomarkers of patient response to different MTAs. This work highlights the multifaceted nature of MTA-mediated effects on EMT-associated signaling pathways in breast cancer cells and prompts a reevaluation of their differential efficacy in tumors with distinct molecular profiles. These studies are supported by Eisai Inc.
Citation Format: Kaul R, Risinger AL, Mooberry SL. Differential effects of eribulin on key transcription factors snail and slug [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 P5-08-06.
Abstract P5-08-08: Not presented
Authors: Zhao Y , Sun H , Jin W 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Zhao Y, Sun H, Jin W. 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 P5-08-08.