bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1152: MUC1: A metabolic regulator in triple-negative breast cancer
Authors: Goode Gennifer D. , Chaika Nina , Purohit Vinee , Gunda Venugopal , Singh Pankaj 
Published: July 2016

Abstract
Breast cancer, the second leading cause of cancer deaths in women, is the most common cancer among North American women, accounting for nearly 1 in 3 cancer cases diagnosed in the U.S. women. Triple negative breast cancer (TNBC) subtype accounts for approximately 15-25% of all breast cancer cases and has an increased incidence of metastasis, high recurrence within 1-3 years and a high mortality rate. Therefore, identifying factors that facilitate tumor growth and metastases have the potential to serve as novel molecular targets for breast cancer therapy. Mucin1 (MUC1), a glycoprotein associated with chemoresistance, is aberrantly overexpressed in TNBC and facilitates growth and metastasis of TNBC cells. This occurrence can be partially attributed to MUC1 interaction with hypoxia-inducible factor alpha (HIF1α), a key regulator of glycolysis. As metastasis is the leading cause of cancer related deaths, this process relies on the ability of tumor cells to adapt to the changing nutrient levels in the surrounding stroma. In the present study we examined how signaling through MUC1 facilitates metabolic phenotype in TNBC; thus facilitating tumor growth and metastasis. Our results indicate that MUC1 expression facilitates glucose and glutamine uptake in a panel of TNBC cell lines. Furthermore, metabolomic analysis through liquid chromatography-coupled tandem mass spectrometry approach revealed that MUC1 expression modulates metabolite levels in glycolysis, pentose phosphate pathway and TCA cycle in TNBC cells. Thus, our results support the notion that MUC1 serves as a metabolic regulator in TNBC, facilitating metabolic reprogramming that influences growth of TNBC.
Citation Format: Gennifer D. Goode, Nina Chaika, Vinee Purohit, Venugopal Gunda, Pankaj Singh. MUC1: A metabolic regulator in triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1152.
Abstract 1156: Downregulation of glycine decarboxylase contributes to paclitaxel resistance in ovarian cancer cells
Authors: Kim Jin Young , Shin Sojin , HA Eunyoung , Cha Soondo , Cho Chi-Heum 
Published: July 2016

Abstract
Glycine decarboxylase (GLDC) is a metabolic oncogene that links glycine metabolism with tumorigenesis. In humans, GLDC is part of a multienzyme complex that couples the decarboxylation of glycine to the biosynthesis of serine. The role of GLDC in relation to chemoresistance is unclear. We designed this study to determine the role of GLDC in chemoresistance in ovarian cancer cells. First, we found GLDC is downregulated in paclitaxel resistant ovarian cancer cells (OVCAR3/PTX). Prompted by decreased glucose transport in OVCAR3/PTX cells, we transplanted OVCAR3 and OVCAR3/PTX onto the back of the NOD-scid IL2Rgammanull mice and found that the OVCAR3/PTX tumor grew less rapidly than paclitaxel sensitive ovarian cancer cells (OVCAR3). We also found that GLDC is downregulated in OVCAR3/PTX tumor. In vitro study revealed that the inhibitory effect of siGLDC on proliferation was significantly greater in OVCAR3 than in OVCAR3/PTX. We also found that knockdown of GLDC in OVCAR3 cells rendered ovarian cancer cells PTX-resistant. Finally, we determined GLDC expressions in patients with chemosensitive and chemoresistant serous type ovarian cancer and found that GLDC expression was markedly downregulated in chemoresistant cancer patients. These results suggest GLDC is associated with ovarian cancer chemoresistance.
Citation Format: Jin Young Kim, Sojin Shin, Eunyoung HA, Soondo Cha, Chi-Heum Cho. Downregulation of glycine decarboxylase contributes to paclitaxel resistance in ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1156.
Abstract 1170: EphA3 maintains radioresistance in head and neck cancers
Authors: Han Myung Woul , Kim Song Hee , Chang Hyo Won , Nam Hae Yun , Lee Myungjin , Kim Gui Chul , Lee Yoon sun , Kim Mi Ra 
Published: July 2016

Abstract
Radiotherapy is a well-established therapeutic modality used in treatment of many cancers. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after treatment by radiation. Thus, special emphasis has been given to the discovery of effective radiosensitizers. EphA3 receptors functions contribute to tumor development, modulating cell-cell adhesion, invasion, neo-angiogenesis, tumor growth and metastasis. However, the role of EphA3 in radioresistance remains to be elucidated. Here, we established the stable radioresistant head and neck cancer cell line (AMC HN3R cell line) and identified that EphA3 was overexpressed predominantly in the AMC HN3R cancer cell line through DNA microarray, real time PCR and Western blotting. Additionally, we identified that EphA3 was overexpressed in recurred laryngeal cancer specimen after radiation therapy. And we found that EphA3 mediated the tumor invasiveness and migration and EMT (epithelial mesenchymal transition) related protein expression in AMC HN3R cancer cell line. To investigate the role of EphA3 in modulating the radiosensitivity, we observed the change of survival fraction after transfection EphA3 siRNA. And we found that inhibition of EphA3 enhances radiosensitivity in AMC HN 3R cell line. In conclusion, these results suggest that EphA3 is overexpressed in radioresistant head and neck cancer and can play a crucial role in development radioresistance in head and neck cancers through regulation of EMT pathway.
Citation Format: Myung Woul Han, Song Hee Kim, Hyo Won Chang, Hae Yun Nam, Myungjin Lee, Gui Chul Kim, Yoon sun Lee, Mi Ra Kim. EphA3 maintains radioresistance in head and neck cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1170.
Abstract 1172: Expression of notch1, numb, and musashi1 in non-small cell lung cancer
Authors: Kikuchi Hajime , Sakakibara-Konishi Jun , Ikezawa Yasuyuki , Takashina Taichi , Mizugaki Hidenori , Kikuchi Eiki , Kikuchi Junko , Shinagawa Naofumi , Oizumi Satoshi , Hida Yasuhiro , Kaga Kichizo , Kinoshita Ichiro , Dosaka-Akita Hirotoshi , Nishimura Masaharu 
Published: July 2016

Abstract
Background: Deregulation of Notch pathway is associated with carcinogenesis, and Notch signaling is identified as tumor activator in non-small cell lung cancer(NSCLC). The function of Musashi1 has been found to activate Notch signaling through the translational repression of Numb, which represses an intracellular Notch signaling. In NSCLC, the association between Numb or Musashi1 expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1, Numb, and Musashi1 in NSCLC. Methods: A total of 135 surgically resected NSCLCs were immunohistochemically assessed for Notch1, Numb, and Musashi1 expression. Only cytoplasm and nuclear staining was considered in the evaluation of activated Notch1 expression. The immunoscores were determined, and then its correlation with either the clinicopathological variables or the survival outcomes was analyzed. Results: Immunohistochemical reactivity for Numb, and Musashi1 was detected in the cytoplasm and nuclear of the tumor cells. Notch1 expression was associated with several clinicopathological factors, including pathological histology (p = 0.002), and differentiation of tumor (p = 0.024). Numb expression was also associated with several clinicopathological factors, including sex (p = 0.037), smoking habit (p = 0.033), pathological histology (p = 0.002), and differentiation of tumor (p = 0.015). No correlations were noted between Musashi1 expression and any of the variables. Analysis of cellular biological expression demonstrated a link between low Numb expression and high Notch expression. Multivariate Cox regression analysis showed that positive Numb expression was an independent favorable prognostic factor. Conclusions: We demonstrate that Numb expression was associated with better prognosis in NSCLC. Numb might have the function as tumor suppressor in NSCLC.
Citation Format: Hajime Kikuchi, Jun Sakakibara-Konishi, Yasuyuki Ikezawa, Taichi Takashina, Hidenori Mizugaki, Eiki Kikuchi, Junko Kikuchi, Naofumi Shinagawa, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Masaharu Nishimura. Expression of notch1, numb, and musashi1 in non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1172.
Abstract 1176: The role of KIF3A in the suppression of canonical Wnt signaling through the KIF3A and β-arrestin complex, independent of the ciliary mechanism, in non-small cell lung cancer (NSCLC)
Authors: Kim Minsuh , Suh Yong-Ah , Oh Ju-hee , Lee Bo Ra , Kim Joon , Jang Se Jin 
Published: July 2016

Abstract
Aberrant Wnt/β-catenin signaling is implicated in the progression of several human cancers, including non-small-cell lung cancer (NSCLC). However, mutations in Wnt/β-catenin pathway com-ponents are uncommon in NSCLC, and epigenetic mechanisms controlling the Wnt/β-catenin path-way remain unclear. Here, we show that KIF3A, a member of the kinesin-2 motor family, plays a key role in suppressing Wnt/β-catenin signaling in NSCLC cells. Knockdown of KIF3A increases both β-catenin levels and transcriptional activity, with a concomitant promotion of malignant phenotypes, such as enhanced proliferation and migration, and upregulation of stemness markers. KIF3A binds to β-arrestin, and KIF3A depletion allows β-arrestin to form a complex with DVL2 and AXIN, result-ing in β-catenin stabilization. Although primary cilia, of which the biogenesis requires KIF3A, are thought to restrain the Wnt response, pharmacological inhibition of ciliogenesis does not enhance β-catenin activity in NSCLC cells. A correlation between KIF3A loss and worse NSCLC prognosis as well as upregulation of β-catenin and Cyclin D1 further suggests that KIF3A is a suppressor of Wnt/β-catenin signaling and tumorigenesis in NSCLC.
Citation Format: Minsuh Kim, Yong-Ah Suh, Ju-hee Oh, Bo Ra Lee, Joon Kim, Se Jin Jang. The role of KIF3A in the suppression of canonical Wnt signaling through the KIF3A and β-arrestin complex, independent of the ciliary mechanism, in non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1176.
Abstract 1193: Treatment of breast cancer xenografts with paclitaxel enriches for cancer stem cells that can be targeted by a ROR1-specific antibody
Authors: Zhang Suping , Liu Grace , Lai Sam H. , Zhang Han , Ghia Emanuela M. , Cui Bing , Wu Rongrong , Widhopf George , Yu Jian , Schwab Richard , Messer Karen , Parker Barbara , Kipps Thomas J. 
Published: July 2016

Abstract
Although initially responsive to hormone therapy and chemotherapy, many patients with metastatic breast cancer develop resistant and potentially fatal disease. One of the mechanisms of resistance is the emergence of post-treatment survival of a small number of breast cancer stem cells (CSC), which are relatively resistant to chemotherapy, have self-renewal capacity, and can repopulate the tumor and spread to distal sites. New therapies are required to eliminate breast CSC that could be used alone or in combination with standard therapy to mitigate the risk of developing relapsed disease.
In this study, treatment of immune-deficient mice bearing breast-cancer patient-derived xenografts (PDX) with paclitaxel reduced tumor volumes, but enhanced the proportion of tumor cells that expressed ROR1, an RTK-like orphan receptor that is ordinarily expressed during embryogenesis. We found that breast cancer tumors with high levels of ROR1 expression were enriched for stem-cell gene-expression signatures. Moreover, cells isolated from breast cancer PDX that were positive for CSC markers such as aldehyde dehydrogenase 1 (ALDH1) were enriched for ROR1 expression, and ROR1+-cells isolated from breast cancer PDX had a greater capacity to form spheroids in vitro or re-engraft immune-deficient mice, than did ROR1-negative (ROR1Neg) cells isolated from the same tumor population. Treatment of breast cancer cells with a humanized anti-ROR1 mAb, UC-961, suppressed expression of the polycomb-ring-finger oncogene Bmi-1, and genes encoding proteins implicated in the epithelial-mesenchymal transition. UC-961 also impaired the capacity of breast-cancer cells to form spheroids or to re-engraft immune-deficient mice. Finally, combined therapy with UC-961 and paclitaxel appeared more effective in reducing re-engraftment potential than either agent alone (Table1). Collectively, this study implies that patients with advanced breast cancer may benefit from anti-CSC therapy, either alone or in combination with conventional anti-cancer drugs.
Citation Format: Suping Zhang, Grace Liu, Sam H. Lai, Han Zhang, Emanuela M. Ghia, Bing Cui, Rongrong Wu, George Widhopf, Jian Yu, Richard Schwab, Karen Messer, Barbara Parker, Thomas J. Kipps. Treatment of breast cancer xenografts with paclitaxel enriches for cancer stem cells that can be targeted by a ROR1-specific antibody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1193.
Abstract 1212: Effect of metformin and insulin-/IGF1-receptor inhibitor combination drug therapy in triple negative breast cancer
Authors: Xue Lei , Camacho Laura , Kothapalli Sushma , Jiralerspong Sao 
Published: July 2016

Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor survival outcomes. Chemotherapy is the only approved treatment, as there are no targeted therapies. Metformin is an anti-diabetic drug for Type 2 Diabetes. It has been shown to have anti-tumor effects by lowering serum levels of the mitogen insulin, and by pleiotropic effects on cancer cell signaling pathways. BMS-754807 is a potent and reversible inhibitor of the insulin receptor (IR)/insulin-like growth factor 1 receptor (IGF-1R) family kinases that has been shown to have activity in a subset of TNBC. The aim of this study is to evaluate the hypothesis that the combination of metformin and BMS-754807 is more effective than single drug treatment in TNBC.
Experimental design and methods: We treated TNBC cell lines with metformin and BMS-754807 alone and in combination and tested cell viability using MTS assays. Then we used CompuSyn software to analyze the dose-effect of drug combinations for additivity, synergism, or antagonism. We also examined the mechanism by performing Western blots of candidate pathways.
Results: 5 out of the 9 cell lines tested (56%) showed synergism of metformin and BMS-754807 in the drug combination assays. Western blots showed significant inhibition of IR/IGF-1R and PI3K/Akt pathways with the drug combination.
Conclusion: We conclude that the combination of metformin and BMS-754807 is more effective than single drug in a significant proportion of triple negative breast cancer cell lines. This combination may represent effective targeted therapy for a subset of TNBC. Further studies to evaluate this possibility are underway.
Citation Format: Lei Xue, Laura Camacho, Sushma Kothapalli, Sao Jiralerspong. Effect of metformin and insulin-/IGF1-receptor inhibitor combination drug therapy in triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1212.
Abstract 1213: Thymidine kinase 1 is on the cell surface of prostate cancer cells
Authors: Weagel Evita G. , Chu Roger P. , Meng Wei , Brog Rachel A. , Townsend Michelle H. , Robison Richard A. , O’Neill. Kim L. 
Published: July 2016

Abstract
Thymidine Kinase 1 (TK1) is a salvage pathway enzyme that assists in DNA repair and is characteristically expressed in the cytosol, but it also presents at an abnormally high level in the serum of cancer patients. We developed a unique mouse-anti-human TK1 antibody (A72), and used it in conjunction with Flow Cytometry, Scanning Electron Microscopy (SEM), and Confocal Microscopy, to explore the presence of TK1 on the cell surface of two prostate cancer cell lines, namely PC3 and DU145. Flow Cytometry was performed using a standard protocol. Briefly, cells were stained with A72 conjugated to FITC. Anti-NF-κB-FITC and a non-specific IgG-FITC were used as negative controls. Anti-Na+/K+-ATPase-FITC was used as positive control. Cells were then analyzed using a Flow Cytometer. SEM was carried out by first incubating cells with anti-Na+/K+-ATPase and anti-TK1 conjugated to biotin. After probing with streptavidin-gold solution, cells were imaged to examine the presence of gold particles on cell surface. Our data demonstrated TK1-positive populations after flow cytometry analysis, and the presence of gold particles on the membrane of prostate cancer cells. The presence of TK1 on plasma membrane of PC3 and DU145 was further confirmed by Confocal Microscopy. Cells were first stained with A72-FITC and a red plasma membrane stain, then consecutively imaged with a Confocal Microscope. Results showed that A72-FITC associate with the cells in the same region that the membrane had been stained red, concluding that the A72 binds to the cell membrane. These data strongly suggest that TK1 is located on the surface of prostate cancer cells, and indicate that TK1 may be used as a new immunotherapy target for prostate cancer treatment.
Citation Format: Evita G. Weagel, Roger P. Chu, Wei Meng, Rachel A. Brog, Michelle H. Townsend, Richard A. Robison, Kim L. O’Neill. Thymidine kinase 1 is on the cell surface of prostate cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1213.
Abstract 1214: Development of anti-5T4 antibody-drug conjugates, ZV05-ADCs for targeted cancer therapy in different type of cancers
Authors: Li Zhaohui , Xie Zhangming , Zhang Qian , Fang Jie , Wu Liqin , Fang Hedi , Zhang Hong , Zhu Tong , Chen Gang , Miao David , Cao Sheldon 
Published: July 2016

Abstract
5T4 is an N-glycosylated transmembrane 72 kDa glycoprotein expressed in a number of carcinomas, and has been explored as a target for cancer therapy in different type of cancers, including NSCLC, RCC, colorectal, ovarian, pancreatic and gastric cancers. The expression of 5T4 in normal tissue is very limited, but widespread in malignant tumors throughout their development, making it an attractive target for antibody-drug conjugate (ADC). In this aspect, a 5T4-MMAF ADC from Pfizer is under clinical investigation in phase I/II trials.
We have developed novel anti-5T4 ADCs, using our proprietary conjugation technologies. A highly potent anti-5T4 antibody ZV05 was conjugated to a variety of internally developed linkers and toxins and purified to populations containing defined DAR (Drug-Antibody Ratio) numbers. The ADCs were studied both in vitro and in vivo for their activity against a variety of tumors. The results showed that the lead ZV05 ADCs were potent towards a bunch of cancer cell lines that express 5T4, and also dramatically inhibited tumor growth in several models in vivo. In the xenograft studies, a single dose of the lead ZV05 ADCs completely wiped out the tumors and kept the tumor volume down for the whole period of studies. ZV05 ADCs are currently under further evaluation to select a candidate for clinical treatment of 5T4-positive cancers.
Citation Format: Zhaohui Li, Zhangming Xie, Qian Zhang, Jie Fang, Liqin Wu, Hedi Fang, Hong Zhang, Tong Zhu, Gang Chen, David Miao, Sheldon Cao. Development of anti-5T4 antibody-drug conjugates, ZV05-ADCs for targeted cancer therapy in different type of cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1214.
Abstract 1216: Assays for the selection and functional characterization of antibody-drug conjugates at the National Research Council of Canada
Authors: Jaramillo Maria L. , Meury Luc , Jolicoeur Normand , Banville Myriam , Tao Limei , O’Connor McCourt. Maureen 
Published: July 2016

Abstract
One of the most promising and fastest growing classes of cancer therapeutics builds on the molecular targeting abilities of antibodies by combining them with drugs to generate highly specific antibody-drug conjugates (ADCs). However, the development of ADCs requires time-consuming selection of the antibody for every target and cancer type. Screening technologies based on the use of conjugated secondary antibodies provide a fast and efficient surrogate assay from which to identify which antibodies are best internalized and suitable for immunoconjugate development into ADCs.
As part of its integrated antibody development initiative, NRC has isolated and characterized anti- mouse Fc and anti-human Fc monoclonal antibodies to serve as very selective detective reagents for various IgG isoforms. We have shown that these secondary antibodies are species specific, selective and of high affinity. Furthermore, they exhibit high specific potency and low background toxicity after conjugating them to drugs (DM1, MMAE) or immunotoxins(saporin) in cell viability studies. By combining this methodology with our proprietary mRNA and DNA expression database for the selection of appropriate cell lines, we plan on screening thousands of NRC antibodies generated against variety of cancer associated cell surface targets for ADC development.
In addition to secondary conjugate cytotoxicity assays, we have developed a suite of assays based on cellular accumulation, endosomal routing and activation (intracellular drug release) of antibody drug conjugates. These assays can all contribute to our mechanistic understanding of ADCs under development. Combined with our strength in biologic production and characterization, this expertise promotes the integration and advancement of NRC's capabilities and strengths in the area of Antibody-Drug Conjugates (ADCs), and can be used to establish strategic collaborations with other Canadian or international partners to develop external or internal NRC antibodies into novel ADC biologics.
Citation Format: Maria L. Jaramillo, Luc Meury, Normand Jolicoeur, Myriam Banville, Limei Tao, Maureen O’Connor McCourt. Assays for the selection and functional characterization of antibody-drug conjugates at the National Research Council of Canada. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1216.