bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-01-14: Dissection of the Abl interactor 1 signaling in metastatic breast cancer cells
Authors: Jiang P , Tang H , Hogan H , Tate S , Ryan W , Paul L , Liu X , Zonghan D 
Published: March 2017

Abstract
Abl interactor 1 (Abi1) is a key component of WAVE regulatory complex (WRC) that regulates actin cytoskeleton reorganization, membrane receptor signaling, and intracellular trafficking. Recent in vitro and in vivo studies as well as the studies of human patient samples suggest that Abi1 may play an important role in breast cancer (BC) metastasis. To determine if Abi1 is deregulated in metastatic breast cancer cells, we compared the expression of Abi1 in a panel of human breast cancer cell lines exhibiting distinct metastatic properties. In comparison with low-metastatic ER+/PR+ BC lines MCF-7 and T47D and a non-transforming mammary epithelial cell line MCF-10A, two ER-BC lines CN34 and MDA 231 and their sublines selected by high metastatic potential to bone (231Bo), brain (231Br and CN34Br), and lung (231LM2) show significantly reduced Abi1 protein levels, with greater reduction found in highly metastatic sublines. It is unlikely that the down-regulation of Abi1 expression in these metastatic BC cells occurs at mRNA level, because RT-PCR analysis shows no significant difference in Abi1 mRNA levels among the cells analyzed. Interestingly, despite a reduction in protein level, the tyrosine phosphorylation of Abi1 was increased in CN34, MDA231, and their metastatic sublines compared to low-metastatic BC cells. The tyrosine phosphorylation of Abi1 is stimulated by epidermal growth factor (EGF) in these cells and Abi1 is recruited to EGF receptor (EGFR) upon EGF stimulation. The deregulation of Abi1 in metastatic BC cells is mediated by Abl tyrosine kinases, as the inhibition of Abl family kinases by imatinib not only attenuates EGF-stimulated Abi1 tyrosine phosphorylation but also rescue the down-regulation of Abi1 protein in metastatic BC cells.
These findings are consistent with a role of the EGFR-Abl-Abi1 signaling in BC metastasis. The studies suggest that this pathway may serve as a biomarker for diagnosis and/or prognosis of metastatic breast cancer. We have identified the tyrosine 213 in Abi1 as a major phosphorylation site stimulated by Abl kinases and have generated a unique conditional Abi1 depletion/re-expression system to dissect how the deregulation of the Abi1 signaling contributes to BC metastasis.
Citation Format: Jiang P, Tang H, Hogan H, Tate S, Ryan W, Paul L, Liu X, Zonghan D. Dissection of the Abl interactor 1 signaling in metastatic breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-14.
Abstract P6-01-15: Novel regulation of breast cancer cell aggressiveness by cancer testis antigen
Authors: Kannan A , Wells RM , Ikebe M , Dasgupta S 
Published: March 2017

Abstract
We recently demonstrated that a vesicular endocytosis associated protein SH3GL2, attenuates spontaneous metastases of breast cancer cells by inducing a mesenchymal to epithelial differentiation and the onset of the intrinsic apoptotic pathway. The present study aims to understand the molecular mechanism behind the SH3Gl2 mediated reduction of spontaneous metastasis of the breast cancer cells.
We employed a cDNA microarray analysis of the SH3GL2-overexpressing breast cancer cells exhibiting reduced pulmonary metastasis and identified a 12.1 fold downregulation of SPANXB1, a cancer-testis antigen that regulates sperm motility. A limited number of studies reported an association between increased SPANXB1 expression and progression of melanoma and hepatocellular carcinoma. Augmented SPANXB1 mRNA and protein expression was evident in primary breast tumors and its upregulation was associated with pulmonary metastasis of breast cancer cells. However, the expression pattern of SPANXB1 and its role in BCa development and progression is unknown. By immunohistochemical analysis, we detected high expression (p=0.002) of SPANXB1 in 78% (18/23) of the primary breast cancer tissues and corresponding lymph node metastases compared to the matched normal breast tissues. A couple of non-tumorigenic human breast epithelial cell lines were stably transformed with SPANXB1 to understand its effect on cellular growth and progression. The SPANXB1-transformed cells exhibited increased invasion (p=0.0001) and epithelial to mesenchymal transition accompanied by an augmented expression ratio of Vimentin/E-Cadherin, molecules regulating differentiation and metastasis. The SPANXB1-transformed cells also exhibited a markedly reduced expression of SH3GL2, implicating a SPANXB1:SH3GL2 crosstalk accompanied by an enhanced production of lactate (p=0.004). Our investigation identifies new breast cancer promoting role of a cancer testis antigen, which bears potential for biomarker and targeted therapeutic development.
Citation Format: Kannan A, Wells RM, Ikebe M, Dasgupta S. Novel regulation of breast cancer cell aggressiveness by cancer testis antigen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-15.
Abstract P6-01-20: Effects of local and radiation enhanced TGFβ on the invasive nature of inflammatory breast cancer cells
Authors: Barkataki S , van Golen K 
Published: March 2017

Abstract
Inflammatory Breast Cancer (IBC) is the deadliest form of epithelial breast cancer, accounting for ~10% of breast cancer deaths in the United States. A hallmark of IBC is the formation intralymphatic emboli that are known to be chemotherapy and radiation resistant and contribute to rapid metastasis. This form of breast cancer progresses very quickly, expressing aggressive behavior. IBC and melanoma share a number of similarities in disease presentation and progression. Both spread via dermal lymphatics, form intralymphatic emboli and have a propensity to form cutaneous metastases. Melanoma can also present as “inflammatory melanoma”, which resembles IBC phenotypically. Thus, new leads for studying cutaneous metastasis can be gathered from the melanoma literature. Studies demonstrate a role for transforming growth factor beta (TGFβ) in the etiology of melanoma cutaneous metastasis. TGFβ promotes tumor cell invasion and its expression can be induced in the stroma by radiation treatment. Recently, our lab has demonstrated low expression of TGFβ in IBC patients, which we believe promotes cohesive invasion of IBC cells. Stimulation of IBC cells with 2ng/ml of TGFβ causes altered tumor cell behavior such as stimulating single cell invasion. The invasion of KPL4, SUM149 and MDA-MB231 cell lines were significantly higher in TGFβ stimulated cells compared to non-stimulated cells. As in melanoma cells we hypothesize that radiation enhanced local TGFβ production in the stroma. We radiated normal human epidermal fibroblasts cells with 0gy, 0.5gy, 1.0gy, 2.5gy and 5.0gy intensity and observed that the invasion was significantly higher in 1.0gy, 2.5gy and 5.0gy. We have also looked at the levels of TGFβ-1 in different conditioned medium. ELISA results don't show significant level of increase in TGFβ-1. Since there are two more TGFβ receptors in the TGFβ pathway (TGFβ -2 TGFβ -3), next I will look at the level of TGFβ-2 and 3 on the different intensity of radiation-conditioned medium. Our prediction is that the increase in the invasion of IBC cells is because of TGFβ, which alters the cohesive nature of IBC cells, and enhance single cell invasion. Moreover, radiation increases TGFβ levels in the stroma, which is responsible for rapid metastasis of IBC cells to the skin.
Citation Format: Barkataki S, van Golen K. Effects of local and radiation enhanced TGFβ on the invasive nature of inflammatory breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-01-20.
Abstract P6-02-06: Metabolomic profiling of breast cancer and adjacent tissue
Authors: Santos JR , Brentanni MM , Tortelli T , Dale I , Waitzberg A , Waitzberg D , Ravacci G 
Published: March 2017

Abstract
Breast cancer (BC) is the most common cause of death among women worldwide. Nowadays, research directed toward the discovery of cancer molecular characteristics has extended into various biological aspects, from early investigations of cancer genomics and proteomics to recent efforts in cancer metabolomics. We consider that breast cancer cells display significantly altered cellular processes, and thus metabolites, compared to normal cells. In this regard, the application of metabolomics towards cancer research can led to the discovery of metabolite cancer biomarkers and the identification of target therapeutics. Methods: Metabolomics signature was extracted from primary BC and adjacent tissue samples from a cohort of 182 breast cancer patients from the Institut Gustave-Roussy and Institute Curie – Paris, University of Debrecen – Hungary, and University of Tartu – Estonia. The Biocrates Life Science® company, performed the metabolomics analysis using the Absolute IDQ p180 kit. Statistical analysis was performed by MetaboAnalyst 3.0 software (p &lt;0.05). Results: We observed 99 differential metabolites between breast tumor and adjacent tissues (p&lt;0,05). In the tumor tissue we observed an increase of glycolysis, glutamine uptake and synthesis, glutamate production, intermediates for redox homeostasis, as well reduction in tricarboxylic acid cycle and β –oxidation impairment. Together, these pathways, favor lipogenesis with a consequent increase in saturated fatty acids and cholesterol synthesis for the formation of membranes and lipid rafts in tumors. The increase in rafts in tumors maintains proliferation signaling via membrane receptors, making them important biomarkers. Conclusion: Metabolomics analysis is useful in identifying differential metabolites between breast cancer and adjacent tissue. In this scenario, cancer cells may be dependent on some metabolites for its development, making them therapeutically valuable biomarkers.
Citation Format: Santos JR, Brentanni MM, Tortelli T, Dale I, Waitzberg A, Waitzberg D, Ravacci G. Metabolomic profiling of breast cancer and adjacent tissue [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-02-06.
Abstract P6-05-05: The expression of lysyl oxidase and fibrotic focus is related to inflammation in breast cancer
Authors: Park SH , Jeong YJ , Bong JG , Oh HK 
Published: March 2017

Abstract
Background: Lysyl oxidase (LOX) is an extracellular matrix enzyme that catalyzes the
cross-linking of collagens or elastin. Our hypothesis is that LOX contributes to the formation
of a fibrotic focus (FF), which is related to inflammation in breast carcinogenesis.
In this study, we analyzed the association between the expression LOXs and FF, and
investigated prognostic significance in breast cancer.
Methods: Tissue microarrarys were constructed from the specimens of 444 patients
with primary invasive breast cancer. Immunohistochemical staining for LOX, LOXlike
(LOXL)-, LOXL-2 and LOXL-3 was performed. The status of FF within the tumor
was assessed. The number of CD4+ T cells, CD8+ T cells, CD68+ macrophages was
counted, and intratumoral and peritumoral lymphocyte infiltration were evaluated.
The clinicopathologic characteristics of the patients were analyzed.
Result: The percentage of positive FF was 39.2% and positive rate of LOX expression
was 50% in primary breast cancer tissues. FF was found to be significantly associated
with intratumoral and peritumoral inflammation, lymph node metastasis, high histologic
grade, larger tumor size. LOX was associated with intratumoral and peritumoral
inflammation, CD8+ T cells and menopausal status. LOXL-3 was significantly associated
with positive expression of ER and PR, and molecular subtype.
Conclusions: FF and the expression of LOX were associated with inflammation in
breast cancer in this study. Our results suggest that LOXs may contribute to the formation
of a FF indirectly in relation with inflammation in breast cancer. Further studies
are needed to clarify the role of LOXs, FF and inflammation in tumorigenesis and
prognostic value of them in breast cancer.
Citation Format: Park SH, Jeong YJ, Bong JG, Oh HK. The expression of lysyl oxidase and fibrotic focus is related to inflammation in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-05-05.
Abstract P6-07-30: Identifying novel glycosylation markers in Her2+ breast cancer using MALDI mass spectrometry
Authors: Scott DA , Angel P , Xu H , Drake R , Yeh E 
Published: March 2017

Abstract
Breast cancer characterized by human epidermal growth factor receptor 2 (HER2) overexpression represents approximately 25-30% of all breast cancer cases. Many patients acquire resistance to current chemotherapies, leading to a more aggressive disease state with severe clinical outcomes. Lapatinib, a first generation tyrosine kinase inhibitor of HER2 and EGFR (epidermal growth factor receptor), is commonly used to treat HER2+ breast cancer. Resistance to lapatinib is steadily increasing among HER2+ patients, highlighting the need for therapy development. Identifying markers that predict treatment response or potential drug targets could enhance treatment efficacy and patient survival. To investigate this, we have used MALDI mass spectrometry to identify N-linked glycans specific to human breast cancer cell lines with known resistance and sensitivity to lapatinib treatment, JIMT-1 (resistant) HER2+ and BT474 (sensitive) HER2+. After different lapatinib dose and time course experiments, N-linked glycans were isolated and comparatively profiled by high resolution MALDI mass spectrometry. Differences in the levels of fucosylation and sialylation of glycans from sensitive and resistant cell lines, before and after treatment, were evaluated. In addition, mouse xenograft tumor tissues derived from the same cell lines treated with and without lapatinib were processed for on-tissue imaging of N-glycans using a MALDI imaging mass spectrometry approach. Tissues from HER2+ human breast tumors were also imaged with the same MALDI imaging approach. Cumulatively, these preliminary studies have identified novel glycosylation patterns associated with lapatinib treatment sensitivity and resistance.
Citation Format: Scott DA, Angel P, Xu H, Drake R, Yeh E. Identifying novel glycosylation markers in Her2+ breast cancer using MALDI mass spectrometry [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-30.
Abstract P6-09-38: Interaction between body mass index and hormone receptor status as a prognostic factor in node-positive breast cancer
Authors: Chung IY , Lee JW , Lee JS , Park YR , Lee Y , Lee SB , Kim HJ , Ko BS , Son BH , Ahn SH 
Published: March 2017

Abstract
Purpose: The aim of this study was to investigate the interaction between BMI at breast cancer diagnosis and the various factors including hormone-receptor, menopausal and nodal status, and to find a specific subgroup where BMI has an effect on breast cancer prognosis.
Methods: We retrospectively analyzed the data of 8,763 non-metastatic invasive breast cancer patients from the Asan Medical Center's research database. Overall survival (OS) and breast cancer-specific survival (BCSS) among BMI groups were compared using the Kaplan-Meier method and Cox proportional hazard model with interaction term.
Results: Only in node-positive breast cancer, there was a significant interaction between obesity (BMI ≥ 30.0 kg/m2) at diagnosis and positive hormone receptor which showed worse overall survival (OS) and breast cancer specific survival (BCSS) than normal weight patients (adjusted hazard ratio [HR] = 1.65, 95% confidence interval [CI] = 1.01 to 2.69 and HR = 1.90, 95% CI = 1.15 to 3.15, respectively). Underweight (BMI&lt;18.50 kg/m2) which interacted with negative hormone receptor status in node-positive breast cancer was associated with decreased OS (HR = 2.01, 95% CI = 1.02 to 3.98) and BCSS (HR = 2.15, 95% CI = 1.08 to 4.26). There was no significant interaction between BMI and hormone receptor status in node-negative setting and BMI did not interact with menopausal status in any population.
Conclusions: BMI interacts with hormone receptor status in node positive setting, thereby playing a role in the breast cancer prognosis.
Citation Format: Chung IY, Lee JW, Lee JS, Park YR, Lee Y, Lee SB, Kim HJ, Ko BS, Son BH, Ahn SH. Interaction between body mass index and hormone receptor status as a prognostic factor in node-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-38.
Abstract P6-09-47: The development of personalized diagnostic tests and therapeutic strategies in breast cancer
Authors: Kutasovic JR , Rozali E , Miranda M , Lakhani SR , Al-Ejeh F 
Published: March 2017

Abstract
Despite some improvement in the overall survival rates of breast cancer, it remains as a leading cause of cancer-related deaths in women. Currently, we are unable to accurately predict patients' response to therapies and their long-term outcome. We developed and patented a 275-gene signature based on in silico meta-analysis of global transcriptome profiles (approximately 10,000 cases) that can predict which patients suffer from aggressive disease and succumb to their disease within 5 years of diagnosis. This test, the integrated Breast Cancer Recurrence (iBCR) score outperformed every clinicopathological indicator available in three independent, large cohorts of breast cancer. The iBCR can also predict the likelihood of response to standard treatments and which emerging targeted therapies should be added to an individual's treatment regime to improve outcomes. In addition, 21 of the genes in this signature are novel potential drug targets that have not previously been described in aggressive breast tumours. We performed a pilot study using the NanoString nCounter Dx platform to measure the expression of the top 125 genes within the signature in a cohort of 48 patients. We have validated with 100% accuracy the prognostic power of the iBCR in the Queensland Follow Up (QFU) cohort with 25 years of follow up (p&lt;0.0001), irrespective of clinicopathological features. Our pilot study using the Nanostring platform successfully counted mRNA molecules from samples that averaged 26.8 years of age (range 24 – 29 years), with an average RNA Integrity (RIN) score of 2.4. Future work will expand this test to the full 275-gene set across 500 patients from the QFU cohort. In vitro siRNA screening of the 21 novel genes revealed that at least 10 of these genes are required for breast cancer cell survival. We have started validation of the top 4 hits and these studies confirm the requirement of these genes in breast cancer progression. These data will pave the way towards the study of these genes as new drug targets. Collectively, our test addresses the significant issue of heterogeneous responses to breast cancer treatment. The iBCR platform aims to improve both patients' clinical outcome and quality of life by directing more appropriate treatment with greater likelihood of success, and preventing overtreatment for those with a less aggressive tumor type.
Citation Format: Kutasovic JR, Rozali E, Miranda M, Lakhani SR, Al-Ejeh F. The development of personalized diagnostic tests and therapeutic strategies in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-47.
Abstract P6-11-14: Src homology 2 domain containing transforming protein 1 and steroid receptor coactivator-3 as novel targets for triple-negative breast cancer
Authors: Chang Y-F , Wang Y , Greene GL 
Published: March 2017

Abstract
Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases and is more prevalent among young women and African American women. Metastasis and chemoresistance remain significant challenges in TNBC. The development of targeted therapies for TNBC may dramatically improve the survival of patients and the quality of life. An adaptor protein, Src Homology 2 Domain Containing Transforming Protein 1 (SHC1) and steroid receptor coactivator-3 (NCOA3) are found to be overexpressed in breast cancers and important in the regulation of tumor progression and metastasis and drug resistance in ER+ breast cancer. The elevated SHC1 or NCOA3 correlates with poor prognosis in breast cancer patients. However, the biological significance of SHC1 and NCOA3 in TNBC is not well known. In this study, we performed siRNA-mediated knockdown to determine the importance of SHC1 and NCOA3 in the cell proliferation and death of TNBC. The effect of siSHC1 or siNCOA3 on the invasion and chemoresistance was also assayed in vitro. We found that although SHC1 and NCOA3 knockdown slightly inhibited the tumor growth of TNBC cells (MDA-MB-231, BT549, and HS578T), siSHC1 + paclitaxel and siNCOA3 + paclitaxel significantly decreased cell proliferation and increased caspase-3/7 activity in vitro, compared to drug alone. In vivo studies using MDA-MB-231 xenografts and a TNBC PDX model also showed that siSHC1 and siNCOA3 significantly augmented paclitaxel-induced tumor shrinkage. In invasion assays, SHC1 and NCOA3 knockdown significantly decreased the invasion of TNBC cells. These results suggest that targeting SHC1 and NCOA3 is worth investigating for the treatment of TNBC.
Citation Format: Chang Y-F, Wang Y, Greene GL. Src homology 2 domain containing transforming protein 1 and steroid receptor coactivator-3 as novel targets for triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-14.