bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1931: The first circulating tumor cell detection technique from frozen PBMCs
Authors: Li Heming , Batth Izhar Singh , Xia Xueqing , Hsu Frank J. , Somaiah Neeta , Torres Keila Enitt , Wang Ruoyu , Li Shulin 
Published: July 2017

Abstract
Circulating tumor cells (CTCs) enter the vasculature or lymphatic system after shedding from the primary tumor. CTCs may serve as “seed” cells for tumor metastasis. The utility of CTCs in clinical application is not fully investigated, partly due to the necessity for fresh blood samples and the lack of CTC specific antibody. Of note, there is no CTC detection tool for pediatric tumors. To overcome these drawbacks, we developed a protocol for CTC capture from frozen peripheral blood mononuclear cells (PBMCs) based on the cell-surface vimentin (CSV) antibody 84-1. CSV is a unique marker compared to others such as EpCAM because it is only specific to tumor cells and has been demonstrated to be a viable target for isolation and enumeration of CTCs across tumor types. In this study, we report the first CTC isolation technology from frozen PBMCs of osteosarcoma patients using the CSV antibody 84-1. The CTCs captured using this new protocol were validated by single cell gene sequencing analysis and mesenchymal marker α-SMA staining. Moreover, spiking analysis was also performed to ensure the specificity and sensitivity of this unique CTC capture analysis. Linear regression analysis yielded a positive correlation between the number of detected sarcoma cells and the number of sarcoma cells spiked in both fresh and frozen PBMCs. In summary, our results demonstrate for the first time, a technology to specifically detect and isolate mesenchymal origin CTCs from frozen PBMCs. This technology can be easily expanded to other types of cancers including pediatric tumors because the antibody used is universal and CTC specific. Such a technology will boost the feasibility and utility of CTC-based diagnosis and therapeutic treatment monitoring in a centralized laboratory.
Citation Format: Heming Li, Izhar Singh Batth, Xueqing Xia, Frank J. Hsu, Neeta Somaiah, Keila Enitt Torres, Ruoyu Wang, Shulin Li. The first circulating tumor cell detection technique from frozen PBMCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1931. doi:10.1158/1538-7445.AM2017-1931
Abstract 1933: Discovery of first-in-class small molecule CD99 inhibitors for targeted therapy of Ewing sarcoma
Authors: Celik Haydar , Sciandra Marika , Flashner Bess , Gelmez Elif , Kayraklıoğlu Neslihan , Allegakoen David V. , Petro Jeff R. , Conn Erin J. , Hour Sarah , Han Jenny , Oktay Lalehan , Tiwari Purushottam B. , Hayran Mutlu , Manara Maria Cristina , Toretsky Jeffrey A. , Scotlandi Katia , Uren Aykut 
Published: July 2017

Abstract
Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that affects predominantly children and adolescents with a high propensity to metastasize and poor prognosis. CD99 is a transmembrane cell surface protein that is highly expressed on ES cells, and routinely used as a marker for histological diagnosis of ES. We screened small molecule libraries for their binding to recombinant CD99 protein and subsequent selective inhibition of ES cell growth. We identified two structurally similar FDA-approved nucleoside analogues, clofarabine and cladribine that selectively inhibited the growth of ES cells in a panel of 14 ES vs. 28 non-ES cell lines. A significant negative correlation was found in human cell lines between CD99 expression and IC50 values for clofarabine and cladribine. Both drugs inhibited CD99 dimerization and its interaction with downstream signaling components cyclophilin A and PKA-RIIα as well as led to reduced ROCK2 protein expression and migration in ES cells. A membrane-impermeable analog of clofarabine showed similar cytotoxicity in ES cells, suggesting that it can function through inhibiting CD99 alone without any effect on DNA metabolism. Clofarabine and cladribine led to a significant increase in hypodiploid DNA content of ES cells, which was diminished by suppression of CD99 expression. Both drugs drastically inhibited anchorage-independent growth of ES cells, but clofarabine was more effective in inhibiting ES xenografts. Finally, the screening of a set of chemotherapy drugs revealed a synergy for the combination of anti-CD99 drugs and dasatinib in ES cells, which may translate into increased survival and reduced toxicity. Overall, our findings suggest that clofarabine is a good candidate for early phase clinical trials in children with ES.
Citation Format: Haydar Celik, Marika Sciandra, Bess Flashner, Elif Gelmez, Neslihan Kayraklıoğlu, David V. Allegakoen, Jeff R. Petro, Erin J. Conn, Sarah Hour, Jenny Han, Lalehan Oktay, Purushottam B. Tiwari, Mutlu Hayran, Maria Cristina Manara, Jeffrey A. Toretsky, Katia Scotlandi, Aykut Uren. Discovery of first-in-class small molecule CD99 inhibitors for targeted therapy of Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1933. doi:10.1158/1538-7445.AM2017-1933
Abstract 1949: Salvage pathway enzyme HPRT as a molecular marker for Burkitt’s Lymphoma
Authors: Townsend Michelle H. , Lattin John Ellis , Anderson Michael D. , Felsted Abigail , Velazquez Edwin , Weagel Evita , Robison Richard , O'Neill Kim L. 
Published: July 2017

Abstract
The aim of this study is to investigate the potential of Hypoxanthine phosphoribosyltransferase (HPRT) as a surface biomarker and target for future immunotherapies in Burkitt’s B-cell Lymphoma. B-cell malignancies are the most common type of childhood cancer. Development of immunotherapies could improve current treatment. HPRT is a cytosolic transferase involved in nucleotide production via the purine salvage pathway. Altered expression of TK1, a salvage pathway enzyme, is an indicator of prognosis and diagnosis in multiple cancer types due to active proliferation of cells and the resulting elevated nucleotide demand. It has previously been reported that some salvage pathway enzymes are found on the surface of Burkitt’s Lymphoma cells. HPRT presence on the surface of this B-cell lymphoma subtype could provide a target for adoptive cell transfer and other immunotherapies. The potential surface presentation of HPRT was assessed using flow cytometry, scanning electron microscopy (SEM), and cytoplasmic staining on both healthy lymphocytes and Burkitt’s Lymphoma cells (Raji). Flow cytometry experiments with HPRT antibodies and fluorescent-labeled secondary antibodies show that Raji cells exhibit an 81.4% (p-value .0001) positive fluorescence shift when compared to IgG controls (1.5%). Healthy lymphocytes had a fluorescence shift of 2.38% (p-value .9787). The presence of HPRT on the surface of both Raji cells and healthy lymphocytes was further confirmed using gold-labeled antibodies. Utilizing a scanning electron microscope, the presence of the protein on the surface was evaluated and quantified via increases in gold weight percentage of the sample. When treated with antibodies against HPRT, there was a significant increase in gold binding along with an increase in gold weight percentage. These results suggest a direct relationship between HPRT and the surface of Burkitt’s lymphoma cells, indicating HPRT as a potential target for future immunotherapeutic treatment in Burkitt’s B-cell lymphoma pediatric patients.
Citation Format: Michelle H. Townsend, John Ellis Lattin, Michael D. Anderson, Abigail Felsted, Edwin Velazquez, Evita Weagel, Richard Robison, Kim L. O'Neill. Salvage pathway enzyme HPRT as a molecular marker for Burkitt’s Lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1949. doi:10.1158/1538-7445.AM2017-1949
Abstract 1961: Downregulation of proteasome activity promotes epithelial-mesenchymal transition
Authors: Garcia Daniel A. , Banno Asoka , Baarsel Eric D. Van , Metz Patrick J. , Widjaja Christella E. , Kim Stephanie H. , Bui Jack D. , Yang Jing , Chang John T. 
Published: July 2017

Abstract
The epithelial-mesenchymal transition (EMT) is a developmental program that is aberrantly activated in cancer cells, producing an invasive phenotype that can lead to metastases. Inducers of EMT are largely known and have been widely studied. However, the mechanisms that regulate the link between extracellular stimuli and EMT phenotypes remain poorly understood. Preliminary evidence from our laboratory suggests that downregulation of proteasome activity may be responsible, in part, for driving EMT. Using immortalized human mammary epithelial (HMLE) cells as a model, we show that (1) EMT is associated with decreased proteasome activity and increased polyubiquitinated substrates, (2) pharmacologic inhibition of proteasome activity leads to increased EMT phenotypes and functionality, and (3) pharmacologic inhibition of proteasome activity leads to increased EMT via stabilization of the TGF-β signaling pathway. Together, these data suggest that proteasome activity may be an unappreciated regulator of EMT.
Citation Format: Daniel A. Garcia, Asoka Banno, Eric D. Van Baarsel, Patrick J. Metz, Christella E. Widjaja, Stephanie H. Kim, Jack D. Bui, Jing Yang, John T. Chang. Downregulation of proteasome activity promotes epithelial-mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1961. doi:10.1158/1538-7445.AM2017-1961
Abstract 1970: Glucose-regulated protein 94 is the novel progression biomarker in esophageal squamous cell carcinoma
Authors: Chang Yu-Jia , Huang Chien-Yu 
Published: July 2017

Abstract
Background
Esophageal cancer is a worldwide health problem with a very poor prognosis as most patients present very late when the disease is advanced and difficult to cure. It is urgent to figure out a diagnostic and therapeutic strategy. Glucose-regulated protein 94 (GRP94) has been found highly correlation with cancer progression. However, the role of GRP94 in the progression and metastasis of esophageal squamous cell carcinoma (ESCC) is still unclear.
Methods: We investigated the GRP94 expression level of ESCC cells and generated GRP94-KD cells by shRNA technique. The proliferation assay, migration, invasion assay were performed. The tissue array was performed to see the correlation of GRP94 and clinical outcome on ESCC. Mitochondrial bioenergetics were assessed using a Seahorse XF24 flux analyzer. The Transmission Electron microscopy was applied to see the structure of mitochondria.
Results: We found that ESCC specimen that expressed higher GRP94 showed the lower overall survival in tissue array results. The ESCC cells expressed high level of GRP94. Silencing GRP94 reduced the proliferation, migratory and invasion activity. Transmission Electron microscopy revealed the impaired mitochondrial in GRP94-KD cells. GRP94-KD cells also displayed reduced basal respiration, spare of respiratory capacity and ATP production. GRP94-KD caused the accumulation of oxidative damage. In molecular mechanism, we found that silencing GRP94 may cause a decrease COX2 expression and alter EMT expression pattern.
Conclusion
We found that silencing GRP94 in ESCC cells suppressed cancer growth and metastasis ability through COX-2 and EMT molecules expression. In addition, GRP94 may mediate the functional mitochondria in ESCC. GRP94 may be a new target to develop the therapeutic strategy for ESCC.
Citation Format: Yu-Jia Chang, Chien-Yu Huang. Glucose-regulated protein 94 is the novel progression biomarker in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1970. doi:10.1158/1538-7445.AM2017-1970
Abstract 1980: Fusion of cancer and stromal cells imaged by color -coded imaging of metasasis
Authors: Nakamura Miki , Suetsugu Atsushi , Hasegawa Kousuke , Matsumoto Takuro , Aoki Hitomi , Kunisada Takahiro , Shimizu Masahito , Saji Shigetoyo , Moriwaki Hisataka , Hoffman Robert M. 
Published: July 2017

Abstract
We report here imaging of stroma during the metastatic process. RFP-EL4 lymphoma cells were injected subcutaneously in C57/BL6 GFP transgenic mice. Subcutaneous tumors were resected and immediately transplanted to the abdominal cavity of BALB/c nude mice. Metastases to the liver, perigastric lymph node, ascites, bone marrow and as well as the primary tumor were imaged. Metastases expressed GFP at low magnification. At higher magnification, yellow-remaining cancer cells resulting from fusion of GFP stromal cells and RFP cancer cells were observed. Metastasis contained fusion of caner and stromal cells which may be a feature of metastasis.
Citation Format: Miki Nakamura, Atsushi Suetsugu, Kousuke Hasegawa, Takuro Matsumoto, Hitomi Aoki, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M. Hoffman. Fusion of cancer and stromal cells imaged by color -coded imaging of metasasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1980. doi:10.1158/1538-7445.AM2017-1980
Abstract 1986: Determining the signaling pathway of epithelial-IKKα deletion-mediated symbiotic bacterial and fungal infection in carcinogenesis
Authors: Song Na-Young , Willette-Brown Jami , Zhu Feng , Hu Yinling 
Published: July 2017

Abstract
Bacteria and fungi, two major components of the microbiota, generally share niches and develop both antagonistic and symbiotic relationships, regulating the pathological impacts on the host. The epithelium is where the bacterial-fungal interaction occurs most abundantly, but the relationship between the epithelium, bacteria, and fungi on the pathogenesis, particularly tumorigenesis, is poorly understood. IKKα is one of the crucial factors regulating the homeostasis of squamous epithelial tissues. Recently, our lab has established a mouse model that develops esophageal squamous cell carcinomas associated with IKKα reduction, inflammation and chronic fungal infection. Cladosporium cladosporioides was a major type of fungi identified in this mouse model. Because IKKα deletion in the keratinocytes causes impaired skin barrier, we hypothesized that loss of epithelial IKKα may control fungal colonization through regulating the barrier integrity and inflammation. We generated IKKαf/f mice with inducible K15.Cre (IKKαf/f/K15.Cre) specifically expressed in keratinocytes in hair follicles which is considered as skin stem cells. After deleting IKKα in K15 cells in oral mucosa and skin, IKKαf/f/K15.Cre mice were orally inoculated with Cladosporium cladosporioides. We found that epithelial IKKα deletion increased bacterial colonization in oral mucosa and skin. Moreover, Cladosporium infection further promoted bacterial and fungal colonization in oral cavity and development of skin tumors. Taken together, our data suggest that loss of epithelial IKKα induces the bacterial-fungal symbiosis in oral mucosa, promoting skin tumors. This study will shed light on the importance of the epithelial-bacterial-fungal interaction in the pathogenesis, proposing epithelial IKKα as a novel regulator of the bacterial-fungal interaction.
Citation Format: Na-Young Song, Jami Willette-Brown, Feng Zhu, Yinling Hu. Determining the signaling pathway of epithelial-IKKα deletion-mediated symbiotic bacterial and fungal infection in carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1986. doi:10.1158/1538-7445.AM2017-1986
Abstract 1991: Enhanced role of the extracellular matrix in ovarian cancer recurrence
Authors: Huang Zhiqing , Foster Brad , Grenier Carole , Sfakianos Gregory , Whitaker Regina , Berchuck Andrew , Murphy Susan K. 
Published: July 2017

Abstract
Purpose: Despite improvements in care and advancements in the understanding of ovarian cancer (OC) pathobiology and genetic alterations, the survival rate is disappointingly low when compared to that of other types of cancer. One factor contributing to the poor survival rate is the development of chemotherapeutic resistance and a high rate of recurrent tumor growth in the months and years following primary OC treatment. Our objective was to identify potential new therapeutic targets for prevention of recurrence through examination of changes in gene regulation that occur in recurrent versus matched primary tumors.
Procedures: We used 16 primary-recurrent tumor pairs from patients with stage III/IV serous epithelial OC from the Duke Gynecologic Oncology Tissue Bank. Illumina Infinium HumanMethylation450 BeadChips and Affymetrix Human Genome U133A arrays were used to quantify methylation and gene expression, respectively. Expression and methylation of POSTN and COL11A1 were analyzed using an independent OC dataset comprising 38 women with &lt;3 years survival and 26 women with &gt;7 years survival, 3 normal ovarian surface epithelium (OSE) and 2 fallopian tube fimbriae epithelium (FTFE) samples. siRNA knockdown of POSTN and COL11A1 in OC cells was followed by expression and proliferation assays.
Results: Paired student t tests showed a &gt;2-fold difference for 13 of the 1,569 significantly differentially expressed genes, seven with increased expression in recurrent OC (POSTN, COL11A1, MMP1, MMP13, TNC, ASPN, and EPYC), and six with decreased expression (GATA6, PEG3, SST, MAOB, TSPAN8, and C7). Interestingly, all seven up-regulated genes are involved in extracellular matrix (ECM) functions, an important component of the tumor microenvironment. With an independent OC microarray dataset, we found elevated COL11A1 mRNA in OCs as compared to OSE and FTFE tissues (p&lt;0.05). There are inverse correlations between COL11A1 expression and methylation at five promoter CG sites (R=-0.58 to -0.65, p&lt;0.05). Immunohistochemistry showed higher expression of POSTN and COL11A1 in recurrent OC. Knockdown of POSTN and COL11A1 in OC cell lines led to significantly reduced proliferation (p&lt;0.05).
Conclusion: Our findings indicate that the genes involved in extracellular matrix function that contribute to the composition and regulation of the tumor microenvironment play critical roles in OC recurrence, and may offer new therapeutic opportunities.
Citation Format: Zhiqing Huang, Brad Foster, Carole Grenier, Gregory Sfakianos, Regina Whitaker, Andrew Berchuck, Susan K. Murphy. Enhanced role of the extracellular matrix in ovarian cancer recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1991. doi:10.1158/1538-7445.AM2017-1991
Abstract 1993: Acidic tumor microenvironment stimulation of GPR4 alters cytoskeletal dynamics and migration of vascular endothelial cells
Authors: Krewson Elizabeth A. , Yang Li V. , Dong Lixue 
Published: July 2017

Abstract
The acidic tumor microenvironment results from aberrant vasculature, insufficient oxygen delivery and aerobic glycolysis of cancer cells. As cancer progresses, the acidic microenvironment can lead to structural changes of endothelial cells (ECs) resulting in increased vascular permeability which may increase metastasis. Extracellular acidification can activate cellular signaling molecules, including G-protein coupled receptor 4 (GPR4), which is prominently expressed in ECs. We have previously reported that acidic activation of GPR4 induces the transcription of several pro-inflammatory and ER-stress related genes in ECs. The purpose of the study is to identify the functional response of acidosis-induced GPR4 activity using Human Umbilical Vein Endothelial Cells (HUVECs) as a model system. The expression of GPR4 was overexpressed (HUVEC/GPR4) or knocked down (GPR4 shRNA) using several genetic constructs. HUVECs were treated with media buffered to pH 6.4 or to physiological pH 7.4. Permeability of a HUVEC cell monolayer was assessed by quantifying gap formation as one indicator. Cell migration was assessed through wound-healing assays. Cytoskeletal dynamics were also investigated using Rhodamine Phalloidin to investigate actin stress fiber formation and immunocytochemistry to investigate focal adhesion dynamics. Our results showed acidic pH induced GPR4 activation changed the cytoskeletal phenotype, decreased cellular migration, and proliferation in HUVECs compared to the physiological pH treatment. There was also a further increase in gap area of a HUVEC/GPR4 monolayer and formation of actin stress fibers in response to acidic conditions. Additionally, altering expression of phosphorylated paxillin and focal adhesion kinase were observed under acidosis/GPR4 mediated stress. In conclusion, the proton sensor GPR4 induces cytoskeletal variations, reduces cellular migration, and proliferation in response to an acidic tumor microenvironment.
Citation Format: Elizabeth A. Krewson, Li V. Yang, Lixue Dong. Acidic tumor microenvironment stimulation of GPR4 alters cytoskeletal dynamics and migration of vascular endothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1993. doi:10.1158/1538-7445.AM2017-1993