bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-06-07: StemScreen®, an innovative platform technology for the identification of novel cancer stem cell-directed compounds
Authors: Chen Janice , Li Hai , Glicksman Marcie A , Karan Charles , Brooks Christopher , Rowinsky Eric K 
Published: May 2015

Abstract
Cancer stem cells (CSCs) are thought to play significant roles in breast cancer initiation and progression. Conventional therapeutic agents target tumor bulk but spare CSCs, leading to tumor recurrence and relapse. Therefore, drugs that eliminate both tumor bulk and CSCs may represent the most effective treatment strategy for breast cancer. We have developed a proprietary cell-based screen called StemScreen® that permits the rapid testing and identification of novel CSC-directed compounds in a high-throughput manner. StemScreen® takes advantage of a landmark discovery that many cancer cell lines harbor stable populations of CSCs. Our initial studies utilized a breast cancer cell line transfected with a unique expression vector that is only active in the 1-5% putative CSC population. The StemScreen® platform is unique because it allows for screening of compounds within the context of the CSCs’ natural microniche environment and has advantages over traditional drug discovery methods that have been designed to identify compounds that only target tumor bulk, but not CSCs.
In an effort to increase the throughput and make the assay compatible with existing compound libraries, we miniaturized the platform to a 384-well format and optimized the line for high-content screening. A series of compound hits identified from screening these cells against smaller libraries of known active compounds as well as larger and more diverse compound libraries will be presented. We are also currently expanding this technology into other tumor types. We believe that this approach represents a major technological advance in oncology drug discovery and that this platform will be instrumental in the discovery of unique new therapies that have a dual effect on CSCs and non-CSC tumor bulk.
Citation Format: Janice Chen, Hai Li, Marcie A Glicksman, Charles Karan, Christopher Brooks, Eric K Rowinsky. StemScreen®, an innovative platform technology for the identification of novel cancer stem cell-directed compounds [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 P2-06-07.
Abstract P2-07-01: EMT activates PERK-eIF2α signaling and sensitizes cells to perturbations in endoplasmic reticulum function
Authors: Feng Yuxiong , Sokol Ethan S , Del Vecchio Catherine A , Sanduja Sandhya , Claessen Jasper HL , Proia Theresa A , Jin Dexter X , Reinhardt Ferenc , Ploegh Hidde L , Wang Qiu , Gupta Piyush B 
Published: May 2015

Abstract
Epithelial-to-mesenchymal transition (EMT) plays an important role in cancer progression. By undergoing an EMT, cancer cells acquire a spectrum of malignant properties, including invasiveness, multi-drug resistance and stem-like traits. Although they play an important role in tumor progression and resistance, few vulnerabilities of EMT cancer cells have been reported to date. To identify specific vulnerabilities of EMT cells, Using small molecule and RNAi screens, we have discovered that induction of EMT greatly sensitizes cells to agents that perturb endoplasmic reticulum (ER) function. This unexpected sensitivity to ER stress is mainly due to the expression and secretion of large amount of extracellular matrix (ECM) proteins by cells that have undergone an EMT. In line with their increased secretory load, EMT cells display a branched ER morphology and constitutively activate the PERK-eIF2α branch of the unfolded protein response (UPR). Using a PERK-specific inhibitor, we found that PERK activation is also required for EMT cells to invade and metastasize. In human tumor tissues, EMT gene expression correlates strongly with both ECM and PERK-eIF2α genes. In summary, our findings identify a novel vulnerability of cells that have undergone an EMT, and demonstrate that the PERK branch of the UPR is required for their malignancy.
Citation Format: Yuxiong Feng, Ethan S Sokol, Catherine A Del Vecchio, Sandhya Sanduja, Jasper HL Claessen, Theresa A Proia, Dexter X Jin, Ferenc Reinhardt, Hidde L Ploegh, Qiu Wang, Piyush B Gupta. EMT activates PERK-eIF2α signaling and sensitizes cells to perturbations in endoplasmic reticulum function [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 P2-07-01.
Abstract P2-07-07: Prostaglandin E receptor 2 (EP2) regulates breast cancer stem-cell like property and promotes epithelial-mesenchymal transition
Authors: Shin Vivian Y , Siu Man T , Ho John C , Cheuk Isabella , Chen Jiawei , Kwong Ava 
Published: May 2015

Abstract
Background: Presence of cancer stem-like cells (CSCs) is the main obstacle for poor treatment response and mortality in breast cancer patients. Prostaglandin E receptors have been reported to play a role in epithelial-mesenchymal transition (EMT) and metastasis, however, the contribution on cancer stem cell compartment remains unstudied.
Methods: Human xenograft breast cancer model was used to study the expression of EP receptors during cancer development. Construction of stable EP2-expression cells was used to study tumorigenesis and characterization of EP2 receptor. Functional role of EP2 receptor on cell proliferation, flow cyometry, invasion and EMT gene expression array were performed in transfected cells. Expression of EP2 receptor was compared in primary tumor tissues by immunostaining and real-time PCR.
Results: EP2 receptor was predominantly expressed in animal tissues during cancer development, as well as in human primary tumor tissues. In mouse xenograft model, MB-231-EP2 clone developed a more aggressive tumor with a larger tumor size and showed a significant increase in cancer stem cell marker aldehyde hydrogenase (ALDH1) expression. In vitro study, MB-231-EP2 clone increased colony formation capacity and S-phase entry by the regulation of E-cadherin, TWIST1 and ALDH1. Importantly, we found that Twist1 expression level was higher in breast cancer patients than healthy controls and was associated with ALDH1 expression.
Conclusions: These findings implicated that EP2 receptor was crucial to nurture CSC phenotype and promote tumorigenesis in breast cancer. Blocking of EP2 might be a potential therapeutic strategy to improve treatment response for breast cancer patients.
Citation Format: Vivian Y Shin, Man T Siu, John C Ho, Isabella Cheuk, Jiawei Chen, Ava Kwong. Prostaglandin E receptor 2 (EP2) regulates breast cancer stem-cell like property and promotes epithelial-mesenchymal transition [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 P2-07-07.
Abstract P2-08-01: Autoimmunity in breast carcinogenesis. A new paradigm
Authors: Fernández Madrid Félix , Maroun Marie-Claire , Lipovich Leonard , Tait Larry , Stark Azadeh , Zarbo Richard , Polin Lisa , Chitale Dhananjay 
Published: May 2015

Abstract
The B cell response in breast cancer [BC] may have a tumor-promoting effect. The objective of this work was to demonstrate that TAAs and cytokines inflict autoimmune damage to the breast creating a chronic inflammatory milieu that promotes BC progression
Methods: The DCIS.com nude mouse xenograft model of BC was treated with rituximab and dexamethasone. Immunoscreening of a cDNA library, PCR, and sequence determination. Immunohistochemistry [IHC] for inflammatory cytokines, immunoglobulins and complement and the TUNEL assay.
Results: Deposition of immunoglobulins and complement was shown on breast epithelial and stromal cells and the involvement of IL-4, IL-6, IL-17, TNF-alpha and NFkB was demonstrated by IHC staining. We identified autoantibodies recognizing multiple human breast epithelial and stromal antigens and the Fc and V regions of immunoglobulins. Rituximab and dexamethasone treatment markedly modified the macroscopic and microscopic appearance of BC and the pattern of cytokine deposition, induced increase in vascularity, marked stromal hypertrophy and massive debulking of the tumor by drastically reducing the tumor mass through apoptosis.
Conclusions: These results suggest that autoantibody- and cytokine-mediated autoimmune damage, triggered by TAAs creates a chronic inflammatory milieu with generation of pro-inflammatory and tumor promoting signals supporting BC progression. The dramatic results of the treatment of the xenograft model with rituximab and dexamethasone illustrate the potential of treating BC as a chronic rheumatic autoimmune disease. The demonstration of a major role of autoimmunity in BC progression may have a transformative impact on prevention, diagnosis and treatment of BC.
Citation Format: Félix Fernández Madrid, Marie-Claire Maroun, Leonard Lipovich, Larry Tait, Azadeh Stark, Richard Zarbo, Lisa Polin, Dhananjay Chitale. Autoimmunity in breast carcinogenesis. A new paradigm [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 P2-08-01.
Abstract P2-08-02: Autoimmunity to centrosomal and proteasome proteins in breast cancer. A link to chromosome instability?
Authors: Maroun Marie-Claire , Olivero Ofelia , Abrams Judith , Chen Wei , Stark Azadeh , Peebles Carol , Tait Larry , Chitale Dhanajay , Fernández Madrid Félix 
Published: May 2015

Abstract
BACKGROUND. Perturbation of centrosomal or centrosome-associated proteins has been observed in nearly all human solid tumors and has been implicated in the origin of chromosomal instability. Ubiquitin-proteasome degradation is highly dependent on the organizing capabilities of the centrosomes. Here we report that autoantibodies in breast cancer [BC] sera target centrosomal proteins as well as important proteins involved in proteasome protein degradation.
METHODS. We immunoscreened a T7 cDNA library of BC proteins and the association of the cloned autoantigens with BC was studied by autoantigen microarray analysis. We used immunohistochemistry [IHC] to investigate the expression of the centrosome and centrosome-associated autoantigens identified.
RESULTS. Immunoscreening with BC sera led to the identification of autoantibodies recognizing epitopes developing in a family of proteins located on the centrosomes such as NIMA-related kinase 7, dynein heavy chain domain 3, peri-centriolar material-1, isomorph CRA, and stathmin-1, the ubiquitin-conjugating enzyme E2, the proteasome 26S subunit and the SUMO/sentrin peptidase. Antibody reactivity to these proteins which are associated with centrosome assembly, microtubule function and protein degradation were highly associated with the diagnosis of BC. IHC staining of paraffin-embedded BC sections with specific antibodies showed that aurora and stathmin-1 and other centrosome antigens are expressed in BC.
CONCLUSIONS. The discovery of autoantibodies targeting important centrosome and proteasome proteins associated with BC suggests that this immune reactivity could be related to autoimmunity developing in BC. Our findings indicate that these autoantibodies might be biomarkers of early BC and suggest the possibility of a link with chromosomal instability in BC.
Citation Format: Marie-Claire Maroun, Ofelia Olivero, Judith Abrams, Wei Chen, Azadeh Stark, Carol Peebles, Larry Tait, Dhanajay Chitale, Félix Fernández Madrid. Autoimmunity to centrosomal and proteasome proteins in breast cancer. A link to chromosome instability? [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 P2-08-02.
Abstract P2-09-04: Measurements of advocate participation in and contributions to the Mayo Clinic breast cancer SPORE
Authors: Chauhan Cynthia , Eppard Wayland , Denison Lori , Gearhart Debra , Holmes Lawanna , Kraft Ruth , Miller Linda , Sitta Mary A , Smith Mary L , Ingle James , Goetz Matthew 
Published: May 2015

Abstract
[Background] Patient advocates bring a unique, valuable perspective and presence to SPOREs. However, although patient advocates are recommended members of SPORE grants, guidelines are not given on the role of advocates or on measurement of the performance of advocates.
[Methods] The Mayo Clinic Breast Cancer SPORE Patient Advocate Advisory Committee has developed a participation measurement tool. This tool will underpin and augment evaluations of the individual advocate contributions by the program PI and the SPORE project leaders. The Advocate Advisory Committee Chair will review the evaluations with the individual advocates. Annually, the advocate committee will review the performance of the group by the standard of the metrics.
[Results] Advocates kept a log of their SPORE activities for four months then worked with a statistician to discern patterns of measurable, evaluable behaviors. The determined evaluable areas are training, scientific activity, meeting attendance, communication. Currently, those metrics are being tracked. Advocates developed the metrics together and report activities at the monthly advocate meetings. Currently, activities are simply tracked and categorized. No minimum standards are set. This will be the third step in the development of the metrics.
[Conclusions] This approach is the first step in the development of meaningful evaluation of advocate SPORE activities. It quantifies the participation of advocates in the SPORE and provides the basis for developing a qualitative performance evaluation. The SPORE PI and the Committee Chair will use the evaluations to interpret the involvement of advocates in SPORE research and activities and to plan interventions to strengthen the advocate contributions to the SPORE.
Citation Format: Cynthia Chauhan, Wayland Eppard, Lori Denison, Debra Gearhart, Lawanna Holmes, Ruth Kraft, Linda Miller, Mary A Sitta, Mary L Smith, James Ingle, Matthew Goetz. Measurements of advocate participation in and contributions to the Mayo Clinic breast cancer SPORE [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 P2-09-04.
Abstract P2-10-08: Understanding potential gaps in treatment discussions between caregivers/patients with advanced breast cancer and oncologists
Authors: Mayer Musa , Coons Helen L , Jones Stephen , Percassi Deana 
Published: May 2015

Abstract
Approximately 232,670 cases of breast cancer will be diagnosed in the US in 2014, of which 86,088 (37%) cases will involve cancer that has spread regionally or metastasized. The 2013 Global Count Us, Know Us, Join Us survey found that 53% of women with advanced breast cancer (ABC; breast cancer that has spread to distant parts of the body) surveyed in the US wish they had more time to discuss their needs during clinic visits, and 60% believe their cancer treatment options are limited. To better understand unmet patient needs and potential communication gaps in treatment discussions with physicians, surveys were developed for women with ABC, their caregivers, and oncologists.
The Make Your Dialogue Count survey will be conducted online, by paper, and by telephone in the US from June through August 2014. Survey respondents must be (1) women ≥21 years of age diagnosed with ABC; (2) their caregivers who attend at least half the clinic visits; or (3) licensed US medical oncologists who treat ≥5 women with ABC per month. Patient and caregiver data were not weighted. Oncologist data regarding geographic region and years in practice by gender were weighted to align with actual proportions in the population.
Final results of the full survey are expected by September 30, 2014. The Make Your Dialogue Count survey will explore issues such as the emotional impact of diagnosis of ABC; the doctor-patient relationship, including the quality of communications and information exchange during clinic visits; and the effect of side effects on treatment choice and satisfaction, from the perspectives of patients, their caregivers, and oncologists.
Findings from the Make Your Dialogue Count survey will provide insight into the doctor-patient relationship from multiple perspectives. Comparing responses given by patients, caregivers, and oncologists can identify potential communication gaps that could be affecting the quality of care provided. Considering the number of women living with ABC, our findings could help oncologists to meet the emotional and informational needs of their patients, and provide patients with the supportive treatment environment they seek and the most relevant disease and treatment information possible.
Citation Format: Musa Mayer, Helen L Coons, Stephen Jones, Deana Percassi. Understanding potential gaps in treatment discussions between caregivers/patients with advanced breast cancer and oncologists [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 P2-10-08.
Abstract P2-12-15: Perception of women after undergoing microbiopsy following a positive breast cander screening
Authors: Carly Birgit , Aimont Mireille , Beauloye Nicolas , Liebens Fabienne 
Published: May 2015

Abstract
Background: Some authors have challenged the benefit of breast cancer mammographic screening due to high prevalence of overdiagnosis and overtreatment.
Purpose: To assess the anxiety and stress of women undergoing a microbiopsy following a false positive breast cancer screening and to evaluate whether this experience refrains them from continuing breast cancer screening.
Methods: 296 patients underwent breast microbiopsy for positive breast cancer screening B1, B2 and B3 lesions in our Breast Center between 2011 and 2013. Patients undergoing microbiopsy for B4 and B5 lesions were excluded from the study. The patients were thereafter interviewed by our two psychologists by phone within a time range of 6 to 18 months following the biopsy.
Results: 201 women answered the questionnaire (68% response). 5.5% had a breast lesion at risk and 75% had a benign lesion. Half of the women rated their anxiety as high (7-8 on a scalebetween 0 – 10) and 15% as very high (9-10/10) before the biopsy. While waiting for the result, 42% rated their anxiety as high (7-8/10) and nearly a third as very high (9-10/10). But 80% accepted to continue breast cancer screening and 90% would accept to undergo again a microbiopsy if necessary.
Conclusion: microbiopsy provides high stress in most patients undergoing it. Nevertheless, 90% of those who had a false positive results accept it and are willing to undergo a biopsy again if necessary.
Citation Format: Birgit Carly, Mireille Aimont, Nicolas Beauloye, Fabienne Liebens. Perception of women after undergoing microbiopsy following a positive breast cander screening [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 P2-12-15.
Abstract P2-13-10: Assessment of diagnostic and therapeutic value of ductoscopy biopsy in single intraductal papillary lesion compared with open surgery
Authors: Xu Zheli , Xing Wanying , Li Qiang , Xing Deli , Gu Yiqi 
Published: May 2015

Abstract
Purpose
Papillary lesions (PL) account for 1–2 % of all breast neoplasms and fiberoptic ductoscopy is a practical and direct method compared with open biopsy in diagnosis and treatment of intraductal papillary lesions. This study aimed to assess efficacy of ductoscopy in the diagnosis and management of single intraductal papillary lesion.
Methods
A total of 232 patients at China-Japan Union Hospital of Jilin University who were diagnosed with single intraductal papillary lesion by fiberoptic ductoscopy were enrolled from March 2011 to November 2013. All patients underwent ductoscopic papillomectomy before open surgery. The final pathologic diagnoses were made by using specimen from both ductoscopic papillomectomy and surgeries. Any intraductal papillomatous lesion or surface abnormalities were considered as positive findings during ductoscopy.
Results
Histopathologic investigations of surgically excised or ductoscopically removed lesions revealed that 217 out of 232 cases were positive. In 187 cases pathological changes were only found in ductoscopic papillomectomy specimen, while the number of cases which was only found in open biopsy was 24. In 6 cases ductoscopic papillomectomy and surgeries specimen both showed positive.
Conclusions
The accuracy of ductoscopy biopsy in diagnosis was 88.9% (193/217) and specificity was 100%. In 187 out of 217 cases (86.2%) ductoscopic papillomectomy alone could completely remove the lesion. Ductoscopy is an effective tool for diagnosis and treatment of single intraductal papillary lesion.
Citation Format: Zheli Xu, Wanying Xing, Qiang Li, Deli Xing, Yiqi Gu. Assessment of diagnostic and therapeutic value of ductoscopy biopsy in single intraductal papillary lesion compared with open surgery [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 P2-13-10.