bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3784: Expression of estrogen receptor specific signaling transcriptome in epithelial cell adhesion molecule (EpCAM) captured circulating tumor cells from patients with breast cancer
Authors: Singh Ashok , Sperger Jamie M. , Schehr Jennifer , Witkowski Tessa , Weaver Beth A. , Burkard Mark E. , Lang Joshua M. 
Published: July 2017

Abstract
Background: Breast cancer (BC) is the second leading cause of cancer related death in American women. There is a critical need for new biomarkers to evaluate treatment response and emerging mechanisms of resistance. The identification and characterization of new biomarkers such as Circulating Tumor Cells (CTCs) may be helpful tools for these purposes as well as understanding the biology of metastatic BC.
Methods: Blood samples were processed with a Ficoll gradient to isolate nucleated cells. CTCs were isolated from these samples using an exclusion-based sample preparation technology known as the VERSA (Versatile Exclusion-based Rare Sample Analysis) platform. EpCAM positive CTCs were captured in the VERSA followed by mRNA extraction for gene expression profiling for the estrogen receptor (ER) and other breast cancer relevant targets. CTCs were defined as Hoechst positive, CD45/CD11b/CD14 negative, and cytokeratin positive. Captured CTCs were evaluated for ER protein staining intensity and localization.
Results: The VERSA platform was validated to capture and enumerate CTCs from patients with breast cancer using EpCAM capture and immunofluorescent staining for intact nucleus, ER, and cytokeratin while negative for multiple immune markers (CD45, CD11b, CD14). The VERSA can capture cells with &gt;90% capture efficiency with EpCAM antibody in MCF7 and T47D cell lines. ER specific transcriptome analysis in BC patient CTCs and cell lines was performed. We evaluated expression of ER signaling pathway, prognostic, metastatic/EMT; stemness; epithelial markers with concordant expression of RPLPO and HPRT1. We identified expression of ER in 6 out of 7 BC samples. Expression of PR and HER2 in a subset of samples confirms capture of breast cancer cells for further molecular interrogation.
Conclusion: In conclusion, we report the expression profiles of ER signaling genes in EpCAM captured CTCs from BC patients. These tools will be used to compare subpopulations of CTCs from patients with BC as predictive and pharmacodynamic biomarkers of response to targeted therapies or chemotherapies.
Citation Format: Ashok Singh, Jamie M. Sperger, Jennifer Schehr, Tessa Witkowski, Beth A. Weaver, Mark E. Burkard, Joshua M. Lang. Expression of estrogen receptor specific signaling transcriptome in epithelial cell adhesion molecule (EpCAM) captured circulating tumor cells from patients with breast cancer [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 3784. doi:10.1158/1538-7445.AM2017-3784
Abstract 3789: Simultaneous visual assessment of RNA and protein expression in circulating tumor cells using the AccuCyte-Cytefinder system
Authors: Ramirez Arturo B. , Crist Sarah B. , Yeats Tyler , Werbin Jeffrey L. , Stilwell Jackie L. , Kaldjian Eric P. 
Published: July 2017

Abstract
Background. Circulating tumor cells (CTCs) provide real-time information regarding patient tumor phenotype, including RNA expression. This information may be valuable in guiding care of cancer patients. Simultaneous RNA and protein assessment has been reported previously in large populations of cells. Here, we describe methods to simultaneously evaluate RNA and protein expression on rare single CTCs using the AccuCyte – CyteFinder system (RareCyte).
Methods. To establish RNA detection in model CTCs (mCTCs), we used SkBr3 cells spiked into blood and the isolated buffy coat was processed by AccuCyte onto microscope slides. RNAscope® in-situ hybridization (ISH, Advanced Cell Diagnostics) was performed to detect Her2, UBC (positive control) and dapB (negative control) expression in mCTCs. A process to simultaneously stain for RNA and protein was then developed to allow identification of mCTCs by protein expression of cytokeratin (CK) and EpCAM and measurement of gene expression with RNAscope. Various blood collection tubes were tested to measure gene expression, protein expression, and cell recovery up to 48 hours after blood draw. Image analysis software was developed to automatically analyze and count RNA dot number from 40x z-stack images of mCTCs. Finally, clinical samples were stained with the combined RNA/protein assay.
Results. Using RNAscope, Her2 and UBC expression could be detected in all SkBr3 cells and was negative in surrounding white blood cells (WBC). Using blood collected into EDTA tubes and processed immediately after spike-in, there were an average of 29 Her2 mRNA dots and 20 UBC dots/cell; negative control dapB gave 1 dot/cell. Using CK and EpCAM expression for mCTCs identification, recovery of mCTCs was over 95%. The RNA/protein assay was compared using blood collected and stored in EDTA, CellSave®, Cell-Free DNA®, Cell-Free RNA®, Cyto-Chex®, and RareCyte BCT tubes. At 48 hours, Cell-Free RNA tubes had the highest number of RNA dots/cell – about half as many dots/cell compared to fresh EDTA samples. Clinical samples were successfully stained with the RNA/protein assay.
Conclusions. We have developed a protocol that identifies rare mCTCs using protein staining, and measures RNA expression by RNAscope ISH. This assay may be a useful clinical tool for the real-time investigation of CTC gene expression in cancer patients.
Citation Format: Arturo B. Ramirez, Sarah B. Crist, Tyler Yeats, Jeffrey L. Werbin, Jackie L. Stilwell, Eric P. Kaldjian. Simultaneous visual assessment of RNA and protein expression in circulating tumor cells using the AccuCyte-Cytefinder system [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 3789. doi:10.1158/1538-7445.AM2017-3789
Abstract 3809: SWI/SNF aberrations sensitize pancreatic cancer cells to DNA crosslinking agents
Authors: Shen Zhewei , Davidson Jean , Pollack Jonathan 
Published: July 2017

Abstract
While gemcitabine has been the mainstay therapy for advanced pancreatic cancer, newer combination regimens (e.g. FOLFIRINOX) have extended patient survival, though carry greater toxicity. Biomarkers are needed to better stratify patients for appropriate therapy. Previously, we reported that one-third of pancreatic cancers harbor deletions or deleterious mutations in key subunits of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. The SWI/SNF complex mobilizes nucleosomes on DNA, and plays a key role in modulating DNA transcription and repair. Thus, we hypothesized that pancreatic cancers with SWI/SNF aberrations might exhibit compromised DNA repair, and show increased sensitivity to DNA damaging agents. Here, we studied pancreatic cancer cell lines with deficient (or else exogenously reconstituted) SWI/SNF subunits, as well as normal pancreatic epithelial cells (HPDE) following SWI/SNF subunit knockdown. Cells were challenged with DNA damaging agents, including those used in current combination regimens, and then cell viability assayed. We found that pancreatic cells with SWI/SNF dysfunction showed markedly increased sensitivity to DNA damaging agents, and in particular DNA crosslinking agents (cisplatin and oxaliplatin). Assaying clearance of γH2AX foci confirmed that SWI/SNF dysfunction impaired DNA damage response/repair. Finally, by analyzing pancreatic cancer patient data (TCGA), we found that pancreatic cancers with SWI/SNF deficiency (subunit mutation and/or decreased expression) showed a strong trend towards extended survival with platinum containing chemo regimens. Thus, SWI/SNF dysfunction sensitizes pancreatic cancer cells to DNA crosslinking agents, and SWI/SNF mutation status may provide a useful biomarker to predict which patients are likely to benefit from platinum-containing chemotherapy regimens.
Citation Format: Zhewei Shen, Jean Davidson, Jonathan Pollack. SWI/SNF aberrations sensitize pancreatic cancer cells to DNA crosslinking agents [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 3809. doi:10.1158/1538-7445.AM2017-3809
Abstract 381: Genomic alterations in mucins in cancer
Authors: King Ryan J. , Yu Fang , Singh Pankaj K. 
Published: July 2017

Abstract
Mucins promote the growth, aggressiveness, and invasiveness of various cancer types. Changes in the expression or localization of mucins can significantly alter patient survival. Due to their predominance in multiple cancers, biomarkers and therapeutic agents have been developed to improve patient care. However, an extensive investigation across multiple cancer subtypes examining the genomic status of the cohort of mucins has not been performed and could yield significant leads into new roles of mucins in different cancers. Utilizing The Cancer Genome Atlas, the cancers of 11 mucin expressing tissues were examined for the genomic alterations in mutations, mRNA expression levels, copy numbers, methylation status, and the impact on patient survival due to these genomic features. It was discovered that different mucins across multiple tissue origins and cancer subtypes might have a different rate, pattern, and survival impact. MUC1 was not mutated in the majority of cancers; however, we did observe a frequent T112P mutation in pancreatic tumors that was also present in other cancers. MUC4 was frequently mutated at H4205 and MUC4 mutations were seen to have survival differences. Multiple significant differences were discovered in mRNA expression, which varied distinctly between cohorts. One such pattern was observed with de novo expression of MUC21 in colorectal cancers, in which mRNA expression was suddenly induced in cancer and increased in a stage dependent manner. Copy number alterations were seen for only a few cancer subtypes and mucins, including MUC4 in lung squamous cell carcinomas. Global promoter demethylation was generally observed across the cancers. MUC15 in renal cancers was seen to be one of the most demethylated mucins, in which mRNA was seen to be substantially decreased or expunged. This extensive study investigated the status of multiple mucins in multiple cancer settings and highlights a few noticeable mucins that are suggested to be further studied for roles in biomarkers, survival, and etiology for cancer progression.
Citation Format: Ryan J. King, Fang Yu, Pankaj K. Singh. Genomic alterations in mucins in cancer [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 381. doi:10.1158/1538-7445.AM2017-381
Abstract 3815: The clinical impact of c-MET over-expression in advanced biliary tract cancers
Authors: Heo Mi Hwa , Kim Seung Tae , Park Young Suk , Park Joon Oh , Lee Hansang 
Published: July 2017

Abstract
Background: c-MET is a proto-oncogene that encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF). Activation of HGF-c-MET signaling involves cell invasiveness and evokes metastasis through direct involvement of tumor angiogenesis. However, the value of c-MET overexpression is still unknown in metastatic BTC.
Methods: We analyzed the incidence and clinicopathologic characteristics of c-MET overexpression in advanced BTC. Moreover, we investigated the value of c-MET overexpression in predicting response to gemicitabine plus cisplatin (GC), a first line standard regimen, and as a prognostic marker in metastatic BTC.
Results: The BTC subtype distribution (N=44) was as follows: intrahepatic cholangiocarcinoma (IHCC, n=7), extrahepatic cholangiocarcinoma (EHCC, n=25) and gallbladder cancer (GBC, n=12). Liver (52.3%) was the predominant metastatic site, followed by lymph nodes (36.4%) and bone (15.9%). Among the 44 patients analyzed for c-MET expression, 15 (34.1%) exhibited c-MET overexpression in tumor tissues. There was no significant difference in the prevalence of c-MET overexpression among primary sites in EHCC (7/25, 28.0%), IHCC (3/7, 42.9%), and GBC (5/12, 41.7%). There was also no significant correlation between specific clinicopathological variables and c-MET expression. Comparing the tumor-response to GC according to c-MET expression (overexpression vs. non-overexpression), there was no significant difference in either RR or DCR (p=0.394 and 1.000, respectively). PFS for all 44 patients was 9.00 months (95%CI, 7.47-10.53 months) and there was no significant difference for PFS between patients with c-MET overexpression and those without (p=0.917). The median OS was 14.4 months (95% CI, 12.8-19.2). There was a significant difference in OS between patients with c-MET overexpression compared to those without (13.7 vs. 14.4 months, respectively; p=0.708).
Conclusions: c-MET overexpression was detected in 34.1% of advanced BTC patients irrespective of tumor location. c-MET overexpression did not predict response to GC or survival. Further studies are needed to fully elucidate the value of c-MET overexpression as a novel biomarker in these patients.
Citation Format: Mi Hwa Heo, Seung Tae Kim, Young Suk Park, Joon Oh Park, Hansang Lee. The clinical impact of c-MET over-expression in advanced biliary tract cancers [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 3815. doi:10.1158/1538-7445.AM2017-3815
Abstract 3816: Mutations of the lim protein ajuba mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell cycle inhibitors
Authors: Zhang Ming , Ratnakar Singh , Peng Shaohua , Tuhina Mazumdar , Li Shen , Tong Pan , Pickering Curtis , Myers Jeffrey N. , Wang Jing , Johnson Faye M. 
Published: July 2017

Abstract
The genomic alterations identified in head and neck squamous cell carcinoma (HNSCC) tumors have not resulted in any changes in clinical care, making the development of biomarker-driven targeted therapy for HNSCC a major translational gap in knowledge. To fill this gap, we used 59 molecularly characterized HNSCC cell lines and found that mutations of AJUBA,SMAD4 and RAS predicted sensitivity and resistance to treatment with inhibitors of polo-like kinase 1 (PLK1), checkpoint kinases 1 and 2, and WEE1. Inhibition or knockdown of PLK1 led to cell-cycle arrest at the G2/M transition and apoptosis in sensitive cell lines and decreased tumor growth in an orthotopic AJUBA-mutant HNSCC mouse model. AJUBA protein expression was undetectable in most AJUBA-mutant HNSCC cell lines, and total PLK1 protein expression was increased in cell lines wild-type for AJUBA. Exogenous expression of wild-type AJUBA in an AJUBA-mutant cell line partially rescued the phenotype of PLK1 inhibitor-induced apoptosis and decreased PLK1 substrate inhibition, suggesting a threshold effect in which higher drug doses are required to affect PLK1 substrate inhibition. PLK1 inhibition was an effective therapy for HNSCC in vitro and in vivo. However, biomarkers to guide such therapy are lacking. We identified AJUBA, SMAD4 and RAS mutations as potential candidate biomarkers of response of HNSCC to treatment with these mitotic inhibitors.
Citation Format: Ming Zhang, Singh Ratnakar, Shaohua Peng, Mazumdar Tuhina, Shen Li, Pan Tong, Curtis Pickering, Jeffrey N. Myers, Jing Wang, Faye M. Johnson. Mutations of the lim protein ajuba mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell cycle inhibitors [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 3816. doi:10.1158/1538-7445.AM2017-3816
Abstract 3837: Primary tumor cell lines derived from gastric PDX tumors displays differences in chemosensitivity
Authors: Ge Xiaomei , Qiang Fulin , Zhang Yixin , Liu Jibing , Yang Lei , Qu Yingying , Xie Fubo , Li Xueting , Gu Ying , Zhou He 
Published: July 2017

Abstract
Gastric cancer is a multifactorial and fatal disease with limited effective therapeutic options. Its overall mortality ranked third among cancer-related deaths worldwide. Patient-derived-xenograft (PDX) models have been widely used in the biomedical research. They recapitulate the genomic diversity/heterogeneity of patient tumors, maintain a lot of the characteristics of the original tumors and showed much better correlation with clinical outcome comparing to traditional cell line derived xenograft models. However, the relatively low throughput and time-consuming nature of PDX studies prevent them from being used in large scale screening or mechanistic studies. To facilitate drug development in gastric cancer, different cancer cell lines have been developed in our laboratory from gastric PDX tumors. We performed STR analyses to validate their identity and RNAseq data also showed high similarities to their parental PDX tumors. These primary gastric tumor cell lines displayed differences from each other in their chemo-sensitivities in vitro and in vivo. They also differ in their protein expression such as the HER-2 expression level. Pharmacology studies using different compounds showed similar drug responses of these cell lines in tissue culture, xenografts using these cell lines and the original PDX models. Our data demonstrated the high fidelity of these cell lines to their parental PDX tumors and serve as a bridge between the high-throughput drug screening and highly clinical relevant PDX models and will greatly facilitate the drug development in gastric cancer.
Citation Format: Xiaomei Ge, Fulin Qiang, Yixin Zhang, Jibing Liu, Lei Yang, Yingying Qu, Fubo Xie, Xueting Li, Ying Gu, He Zhou. Primary tumor cell lines derived from gastric PDX tumors displays differences in chemosensitivity [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 3837. doi:10.1158/1538-7445.AM2017-3837
Abstract 3839: MLN8237 treatment in an orthoxenograft rodent model for malignant peripheral nerve sheath tumors
Authors: Mrowczynski Oliver 
Published: July 2017

Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerves and often occur in the extremities. MPNSTs arise sporadically or in the neurofibromatosis type one (NF1). NF1 is an autosomal-dominant disorder characterized by neurofibromas, cutaneous hyperpigmentation, and intellectual deficits affecting 1 in 3000 births. The lifetime risk of a person with NF1 developing MPNSTs ranges between 8-13%. MPNSTs have increased expression of the oncogene Aurora kinase A. This leads to enhanced cell proliferation, making MPNSTs extremely aggressive, with high potential for metastasis, and devastating prognosis, with five year survival estimates ranging from a dismal 15-60%. MPNSTs are currently treated with surgical resection, sometimes requiring limb amputation, as well as chemoradiation, all of which demonstrate limited effectiveness, and highlight the necessity for novel therapies. To evaluate the effectiveness of new treatments, a translationally accurate, robust, and cost-effective model is crucial. A major goal of this study was to produce an orthotopic xenograft murine MPNST model for evaluation of novel therapies, which we created by intra-neural injection of luciferase transfected MPNST cells into the mice sciatic nerve. Our model circumvents drawbacks of previous in vivo models by producing a robust tumor in the physiologically relevant microenvironment of the nerve that allows for accurate tumor burden quantification through luciferin fluorescence. Another goal of this study was to demonstrate the effectiveness of MLN8237 for MPNST treatment. MLN8237 is an aurora kinase A inhibitor that we demonstrate to decrease MPNST burden and increase survival significantly. This study provides a robust and reproducible MPNST model, allowing for the advancement of MPNST therapy. This study also demonstrates the effectiveness of MLN8237 for MPNST treatment. Together, our data has major implications on the future of MPNST research by providing a robust murine model as well providing evidence that MLN8237 is an effective treatment for MPNSTs.
Note: This abstract was not presented at the meeting.
Citation Format: Oliver Mrowczynski. MLN8237 treatment in an orthoxenograft rodent model for malignant peripheral nerve sheath tumors [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 3839. doi:10.1158/1538-7445.AM2017-3839
Abstract 3850: Establishment of patient derived model of high-risk endometrial cancer for pre-clinical combined carboplatin and decitabine therapy
Authors: Feng Weiwei , Zhu Menghan , Yu Yinhua , Jiang Wei 
Published: July 2017

Abstract
Objective: The high risk endometrial cancers (EC), including high grade EC, serous carcinoma (SC), clear cell carcinoma (CC) and carcinosarcoma, account for 50% of death. Therapies for them are limited and patient derived tumor xenograft (PDX) model become useful tools to predict response to treatment. Here we compared the two methods of establishment of PDX models and evaluated the efficacy of carboplatin and decitabine in two high grade EC PDX models.
Methods: Fresh tumor tissues collected from 11 primary high risk EC patients (6 high grade ECs, 4 SCs, 1 CC and 1 carcinosarcoma) were engrafted subcutaneously and in subrenal capsule in SCID mice. For those subcutaneous models, tumors were then orthotopic transplanted into uterine cavity. Histology, vimentin, cytokeratin, ER, PR, P53 expression were evaluated, together with mutation profiles by next generation sequencing for 500 cancer-panel genes. The efficacy of carboplatin and decitabine were evaluated in two high grade EC models.
Results: The total tumor take rate was 81.8% (9 /11), without regard to engraft methods. The tumor take rate was higher in subrenal capsule models than subcutaneous models (70% vs 54.5%, respectively). The time for tumor formation (from transplantation to 1 cm in diameter) varies greatly from 4 weeks to 5 months. We observed good similarity between primary tumors and corresponding different passage of xenografts. One high grade EC model was sensitive to carboplatin and decitabine treatment whereas another was drug resistant. Two models harbor different genetic mutation profiles.
Conclusion: The high tumor take rate ensures the establishment of the high risk EC biobank which provides a powerful resource for pre-clinical drug-sensitive tests as well as identification of biomarkers of response or resistance.
Note: This abstract was not presented at the meeting.
Citation Format: Weiwei Feng, Menghan Zhu, Yinhua Yu, Wei Jiang. Establishment of patient derived model of high-risk endometrial cancer for pre-clinical combined carboplatin and decitabine therapy [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 3850. doi:10.1158/1538-7445.AM2017-3850