bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1888: Target sequencing of papillary renal cell carcinoma, type 2, using custom-made kidney cancer panel
Authors: Kim Ji-Yeon , Lee Se-Hoon , Kim Jong-Il , Shin Jong-Yeon , Heo Dae seog 
Published: May 2015

Abstract
Purpose: Papillary renal cell carcinoma type2 (PRCC2) is 2nd most common kidney malignancy followed by clear cell renal cell carcinoma (CCRCC). PRCC2 has poor prognosis, treatment strategy is not established and the genetic alteration is poorly understood. We sequenced PRCC2 samples using custom-made kidney cancer panel to figure out genetic alterations of PRCC2.
Methods: We have reviewed publications about the genetics of kidney cancer including all subtypes and selected 55 candidate genes. This cancer panel consisted of 1022 regions by Agilent SureSelect Target Enrichment. We sequenced 12 PRCC2 tumor samples along with 6 paired normal tissue samples. The patients' age were ranged from 26 to 82 year-old, and 3 patients were female (25%). Genomic DNA was isolated from dissected tumor tissue samples (6 fresh, frozen and 6 formalin-fixed, paraffin-embedded) and normal tissue samples. Sequencing was performed by Illumina platform and aligned to H. sapiens, hg19, GRCh37. Total probe number was 4103 and size was 283.494 kbp. Presumed germline variants, which were present in matched normal tissue, were filtered out, and manual curation was performed for each area of variants.
Results: Fifty-four of 55 target genes had 100% coverage, in spite of 92.7% coverage of one target gene. We found two novel FH mutations (one single nucleotide variant and one 5bp indel) and one novel NFE2L2 mutation. Two out of 12 samples (17%) were altered in NRF2 pathway (1 NFE2L2 and 1 KEAP) which was already well-known as driver in PRCC2. Novel PBRM1 mutation in two samples and SETD2 mutation in one sample were identified. In addition, PTEN, TSC1, KDM5C and AKT1 mutation are observed in one case, respectively. No VHL mutation in PRCC2 was revealed.
Conclusions: We analyzed somatic mutation of PRCC2 with custom-made kidney cancer panel. We found several candidate driver mutations of PRCC2. Our result reveals that the genetics of PRCC2 is heterogeneous, therefore, the approach using kidney cancer panel could be used to characterize individual PRCC2.
The gene list of RCC panelABCB1BRAFERBB2MDM2NUDT11SDHBTP53ABL1CNTNAP4FHMDM4PBRM1SDHCTSC1AKR1B10CR1FLCNMETPCDHGA8SDHDTSC2AKT1CUL3HIF1AMTORPIK3CASTED2VEGFAALKDACH2KANK3MYCPOTECSIRT1VHLANKRD36EBPLKEAP1NBPF10PTENSPAM1WDR52ARID1AEGFRKRASNFE2L2RETSTAG3L2TSC1BAP1EPAS1KRT1NPNTROS1TERT
Citation Format: Ji-Yeon Kim, Se-Hoon Lee, Jong-Il Kim, Jong-Yeon Shin, Dae seog Heo. Target sequencing of papillary renal cell carcinoma, type 2, using custom-made kidney cancer panel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1888. doi:10.1158/1538-7445.AM2014-1888
Abstract 1897: Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices for diagnosis of pancreatic neoplasms
Authors: Yonezawa Suguru , Yokoyama Seiya , Higashi Michiyo 
Published: May 2015

Abstract
Mucins play crucial roles in diagnostic and prognostic prediction and in carcinogenesis and tumor invasion. In our clinicopathological investigation for mucin expression in human pancreatic ductal adenocarcinomas (PDACs) and intraductal papillary mucinous neoplasms (IPMNs), we had reported that MUC1 (pan-epithelial membrane mucin) or MUC4 (tracheobronchial mambrane mucin) expression is related with the aggressive behavior and a poor outcome of the patients, whereas MUC2 (intestinal secretory mucin) expression tends to be related with the indolent behavior and a favorable outcome of the patients. We investigated the mechanism of mucin genes expression from the DNA methylation standpoint in human cancer cell lines using the mapping of methylated cytosines by the quantitative MassARRAY analysis, followed by the confirmation with MSP analysis and a novel DNA methylation analysis method ‘methylation specific electrophoresis (MSE, international patent open: WO 2011/132798)’, and compared the results with expression levels of mucin core protein and mRNA in the cancer cells. The results obtained showed that MUC1, MUC2 and MUC4 expression is regulated by DNA methylation at their proximal 5′ flanking regions in the cancer cells. The MSE method greatly decreases the amount of input DNA, although conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. The lower detection limit for distinguishing different methylation status is under 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We applied the MSE method to human pancreatic juices from 45 patients with various pancreatic lesions. The analyses for DNA methylation status of MUC1, MUC2 and MUC4 combined with image data were useful for differential diagnosis of various human pancreatic neoplasms. The examination of 45 samples of human pancreatic juices by the MSE method combined with the image examination showed the following specificity and sensitivity by quadratic discrimination analysis: PDAC, 87% and 80%; gastric-type IPMN (safe type), 88% and 77%; intestinal-type IPMN (dangerous type), 100% and 88%; respectively. The MSE analysis of human pancreatic juices may give us very useful informations for the selection of the treatment methods for pancreatic neoplasms.
Citation Format: Suguru Yonezawa, Seiya Yokoyama, Michiyo Higashi. Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices for diagnosis of pancreatic neoplasms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1897. doi:10.1158/1538-7445.AM2014-1897
Abstract 1898: The combination of gemcitabine/nab-paclitaxel and anti-DLL4 (demcizumab) produces synergistic growth inhibition, delays tumor recurrence and reduces tumor initiating cells in pancreatic cancer
Authors: Yen Wan-Ching , Fischer Marcus , Lewicki John , Gurney Austin , Hoey Timothy 
Published: May 2015

Abstract
Clinical management of pancreatic cancer is challenging and this disease remains the fourth most common cause of cancer-related death. Conventional chemotherapeutic agents, including gemcitabine, commonly used in the treatment of pancreatic cancer, have low response rates and limited effects on improving patient survival. A recent Phase III clinical trial has demonstrated that nab-paclitaxel (Abraxane, a protein-bound paclitaxel) in combination with gemcitabine significantly improved response rate and overall survival compared to patients receiving gemcitabine alone. We previously demonstrated that targeting Notch signaling by anti-DLL4 (demcizumab) inhibits tumor growth, reduces tumor initiating cell frequency and induces differentiation in patient-derived pancreatic xenograft tumors. To further explore the utility of demcizumab in the setting of pancreatic cancer, we evaluated anti-DLL4 combination with gemcitabine/ nab-paclitaxel in a panel of pancreatic xenograft models. We found that anti-DLL4 in combination with gemcitabine plus nab-paclitaxel resulted in striking tumor regression, whereas tumors treated with chemotherapeutic agents alone grew continuously. The effect of the triple combination in some tumors was quite durable and persisted after both antibody and chemotherapeutic treatments were discontinued. The significant growth inhibitory effect by the combination of anti-DLL4 with gemcitabine/nab-paclitaxel was associated with a decrease in cancer stem cell frequency and an increase in apoptosis and tumor cell differentiation. The triple combination of anti-DLL4, gemcitabine and nab-paclitaxel was generally more efficacious compared with anti-DLL4 plus gemcitabine alone. Notably, in a xenograft established from a patient that previously did not respond to demcizumab plus gemcitabine, the triple combination was highly effective. We are currently evaluating demcizumab in combination with gemcitabine plus nab-paclitaxel in a Phase 1b clinical trial in pancreatic cancer.
Citation Format: Wan-Ching Yen, Marcus Fischer, John Lewicki, Austin Gurney, Timothy Hoey. The combination of gemcitabine/nab-paclitaxel and anti-DLL4 (demcizumab) produces synergistic growth inhibition, delays tumor recurrence and reduces tumor initiating cells in pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1898. doi:10.1158/1538-7445.AM2014-1898
Abstract 1901: Detection of EML4-ALK fusion gene expression in circulating tumor cells (CTCs) captured from non-small cell lung cancer (NSCLC) patients
Authors: Park Joo Kyung , Ryu Ji Kon , Lee Se-Hoon , Kim Eun-Hye , Kim Byung-Chul 
Published: May 2015

Abstract
Background & Aims: Detection of unique genomic profile such as EML4-ALK rearrangement in CTCs can be directly implicated to the course of treatment in patients with NSCLC. The aims of this study were to determine 1) if CTC could reliably be identified using microfabricated porous filter platform in advanced NSCLC; 2) feasibility of RT-PCR as a useful tool in detection of EML4-ALK rearrangement from CTCs.
Method: Lung cancer cell lines with EML4-ALK rearrangement (NCI-H3122, NCI-H2228) were spiked into 5 ml of blood and were passed through the CTC platform. Twenty-five patients (19 FISH-proven ALK positive and 6 ALK negative in tissue) were prospectively enrolled in this study. Peripheral blood samples were drawn from the study patients and processed through CTC platform. Captured cells were characterized by IF staining; DAPI (nucleated cell marker), cancer cells by EpCAM and WBCs by CD45. RNA was extracted from the captured CTCs and RT-PCR was used to detect EML4-ALK fusion gene.
Results: EpCAM expression was evaluated qualitatively and quantitatively in NSCLC cell lines by FACS analysis. Surprisingly, 100% of NSCLC cells expressed EpCAM, most at very high levels (165,000 ∼ 215,274 EpCAM antigens/cell). EpCAM was uniformly expressed throughout the population. The capture yield of ALK positive lung cancer cells were varied in spiking experiments (41-59%). There were 25 stage IV NSCLC patients whose clinical situations were variable in the aspect of previous cytotoxic chemotherapies and ALK-targeted tyrosine kinase inhibitors. CTCs were detected in 41% and EML4-ALK expressions were detected by RT-PCR in 58% of initially EML4-ALK positive NSCLC patients. Sequencing of PCR products identified the expression of EML4-ALK fusion gene. The sensitivity and the specificity of RT-PCR in detection of EML4-ALK fusion gene expression from the CTCs of NSCLCs were 58% and 100%, respectively.
Conclusion
We have proved the existence of EML4-ALK positive CTCs using RT-PCR after the enrichment of CTCs from the peripheral blood of NSCLC patients. Being able to reliably capture and molecularly characterize CTC may not only allow us to characterize a patient's cancer from a simple blood draw but investigation of genomic profile from CTCs may give us insights into the genetics and biology of tumor cell dissemination with further investigation.
Citation Format: Joo Kyung Park, Ji Kon Ryu, Se-Hoon Lee, Eun-Hye Kim, Byung-Chul Kim. Detection of EML4-ALK fusion gene expression in circulating tumor cells (CTCs) captured from non-small cell lung cancer (NSCLC) patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1901. doi:10.1158/1538-7445.AM2014-1901
Abstract 1907: Wnt pathway antagonist OMP-54F28 (FZD8-Fc) inhibits tumor growth and reduces tumor-initiating cell frequency in patient-derived hepatocellular carcinoma and ovarian cancer xenograft models
Authors: Yeung Pete , Beviglia Lucia , Cancilla Belinda , Dee-Hoskins Cristina , Evans James W. , Fischer Marcus M. , Yen Wan-Ching , Gurney Austin , Lewicki John , Hoey Timothy , Kapoun Ann M. 
Published: May 2015

Abstract
The Wnt/beta-catenin pathway, which signals through the Frizzled (FZD) receptor family and several co-receptors, has long been implicated in cancer. We have developed OMP-54F28, a recombinant fusion protein consisting of the ligand-binding domain of FZD8 and a human IgG1 Fc fragment. OMP-54F28 acts as a decoy receptor in sequestering Wnts and preventing them from binding to FZD receptors and thereby inhibiting Wnt signaling. The Wnt pathway is important for stem cell self renewal, differentiation, tumorigenicity, and epithelial-mesenchymal transition (EMT). Using minimally passaged human patient-derived xenograft tumors, we demonstrate that OMP-54F28 is efficacious as a single agent and in combination with standard of care in four hepatocellular carcinoma (HCC) and two ovarian cancer models. In the HCC models, OMP-54F28 shows tumor growth inhibition (TGI) as a single agent (average of 46%, p&lt;0.05 vs. control) and displays additive TGI in combination with Sorafenib (average of 78%, p&lt;0.05; 48% Sorafenib alone). Also, in the ovarian cancer models, treatment with OMP-54F28 results in TGI as a single agent (average of 32% vs. control) and shows additive TGI in combination with Paclitaxel (average of 78%, p&lt;0.05; 48% with Paclitaxel alone). We also performed in vivo serial transplantation assays and found that OMP-54F28 as a single agent and in combination with standard of care reduces tumor-initiating cell frequency in both HCC and ovarian cancer xenografts. The anti-tumor effect was associated with a decrease in cell proliferation, induction of cell differentiation, and modulation of target Wnt pathway genes. Our data demonstrate the potential therapeutic benefit of targeting Wnt signaling in HCC and ovarian cancer. OMP-54F28 is being tested in Phase 1b clinical studies in these indications.
Citation Format: Pete Yeung, Lucia Beviglia, Belinda Cancilla, Cristina Dee-Hoskins, James W. Evans, Marcus M. Fischer, Wan-Ching Yen, Austin Gurney, John Lewicki, Timothy Hoey, Ann M. Kapoun. Wnt pathway antagonist OMP-54F28 (FZD8-Fc) inhibits tumor growth and reduces tumor-initiating cell frequency in patient-derived hepatocellular carcinoma and ovarian cancer xenograft models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1907. doi:10.1158/1538-7445.AM2014-1907
Abstract 1909: Identification and characterization of microRNA-134 as a novel receptor tyrosine kinase-regulated tumor suppressive hub in glioblastoma
Authors: Zhang Ying , Kim Jungeun , Mueller Adam C. , Dey Bijan , Yang Yanzhi , Lee Daehee , Hachmann Jan , Finderle Sanjo , Park Deric M. , Christensen James , Schiff David , Purow Benjamin , Dutta Anindya , Abounader Roger 
Published: May 2015

Abstract
Receptor tyrosine kinases (RTKs) are co-deregulated in a majority of glioblastoma (GBM), the most common and most deadly brain tumor. In this study, we uncovered microRNA-134 (miR-134) as a novel tumor suppressive hub that is co-regulated by multiple RTKs via MAPK and KLF4 and that acts via regulation of KRAS and STAT5B expressions. Using microRNA microarrays and qRT-PCR, we screened for microRNAs that are co-regulated by multiple RTKs in GBM. We found that miR-134 was one such microRNA that is downregulated by the activation of MET, EGFR, and PDGFR, the three most commonly deregulated RTKs in GBM. Using a combination of pharmacology, promoter analysis, transcription factor functional and rescue approaches and ChIP/qPCR, we uncovered the MAPK pathway and the transcriptional repressor KLF4 as mediators of the effects of RTKs on miR-134 repression. We then measured the expression of miR-134 and found that it was downregulated in human GBM tumors and GBM stem cells (GSCs) and that it inversely correlated with the activation levels of MET, EGFR, and PDGFR in the tumors. We demonstrated that miR-134 inhibits GBM cell and GSC proliferation, survival, and in vivo xenograft growth, as well as GSC self-renewal and stemness. We uncovered the oncogenes KRAS and STAT5B as direct targets of miR-134 with immunoblots and 3′UTR reporter assays, and showed with rescue experiments that they mediate miR-134 tumor suppressive effects. Thereafter, using a series of molecular and functional assays we established direct links and dependencies between RTKs, KLF4, miR-134, KRAS/STAT5B and malignancy in vitro and in vivo. Importantly, we also found that miR-134 induction is required for the anti-tumor effects of small molecule RTK inhibitors. Altogether, our extensive study identified miR-134 as a novel RTK-regulated tumor-suppressive hub that mediates RTK and RTK-inhibitor effects on GBM malignancy by controlling KRAS and STAT5B. These findings shed new light onto the molecular and functional interactions between RTKs and microRNAs and uncover opportunities for exploiting these interactions for therapeutic purposes.
Citation Format: Ying Zhang, Jungeun Kim, Adam C. Mueller, Bijan Dey, Yanzhi Yang, Daehee Lee, Jan Hachmann, Sanjo Finderle, Deric M. Park, James Christensen, David Schiff, Benjamin Purow, Anindya Dutta, Roger Abounader. Identification and characterization of microRNA-134 as a novel receptor tyrosine kinase-regulated tumor suppressive hub in glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1909. doi:10.1158/1538-7445.AM2014-1909
Abstract 1916: β3 integrin/KRAS/RalB complex drives tumor stemness and resistance to EGFR inhibition
Authors: Seguin Laetitia Jocelyne , Kato Shumei , Franovic Aleksandra , Camargo Maria Fernanda , Elliott Katrhyn , Yebra Mayra , Lesperance Jacqueline , Mielgo Ainhoa , Desgrosellier Jay , Anand Sudarshan , Weis Sara , Cheresh David 
Published: May 2015

Abstract
Integrin αvβ3 expression is a marker of tumor progression for a wide range of histologically distinct cancers, yet the molecular mechanism by which αvβ3 influences the growth and malignancy of cancer is poorly understood. Here, we reveal that integrin αvβ3, in the unligated state on lung, breast and pancreatic cancer cells, recruits KRAS and RalB to the plasma membrane, leading to the activation of TBK-1/c-Rel. These events are both necessary and sufficient to promote tumor initiation, anchorage-independence, self-renewal, as well as resistance to nutrient deprivation and treatment with receptor tyrosine kinase (RTK) inhibitors such as erlotinib. Genetic or pharmacological inhibition of RalB or its effectors suppress tumor initiation, self-renewal, and re-sensitizes tumors to RTK inhibition. These findings not only identify ανβ3 as a marker/driver of tumor stemness but also provide a strategy to overcome tumor resistance to RTK Inhibition.
Citation Format: Laetitia Jocelyne Seguin, Shumei Kato, Aleksandra Franovic, Maria Fernanda Camargo, Katrhyn Elliott, Mayra Yebra, Jacqueline Lesperance, Ainhoa Mielgo, Jay Desgrosellier, Sudarshan Anand, Sara Weis, David Cheresh. β3 integrin/KRAS/RalB complex drives tumor stemness and resistance to EGFR inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1916. doi:10.1158/1538-7445.AM2014-1916
Abstract 1919: Profiling of cancer cell lines demonstrates a dynamic relationship between epithelial, mesenchymal and cancer stem states
Authors: Hernandez James R. , Mooney Steven M. , Shiraishi Takumi , Verdone James E. , Harberg Calvin A. , Vindivich Donald , Pienta Kenneth J. 
Published: May 2015

Abstract
Our previous work has demonstrated that exposure of M2 - Tumor Associated Macrophages M2-TAMs) to epithelial cancer cells can induce an Epithelial to Mesenchymal Transition (EMT). The resulting mesenchymal cancer cells exhibit a more aggressive phenotype, which places patients at a higher risk of relapse and death. Although most patients are cured by radical prostatectomy or radiation, it has been demonstrated that the majority of patients have disseminated tumor cells in their bone marrow at the time of primary treatment and approximately 10-15% of these men will eventually suffer a relapse after a period of dormancy. Further characterization of these disseminated cells both at the time of primary treatment and over time, is needed. It is unclear if these cells, especially those destined to eventually proliferate, are “mesenchymal”, “epithelial”, or “cancer stem” cells (CSCs). In this work, we investigate the CSC molecular and gene expression profile across multiple cancer cell lines and cell phenotypes. In part, this was done by utilizing various culturing conditions, such as 3D growth in stem cell media in order to generate sphere-like cultures known as tumorspheres. Flow cytometric analysis was performed based on ALDH, CD44 variant and CD133 expression. This was followed by gene expression analysis and characterization of the resulting tumorspheres and standard 2D cultures. The results demonstrate that there may be a level of plasticity that allows these cancer cells to alter gene expression and shift towards a CSC state and/or that there is a common CSC progenitor that exists within the population which can give rise to both epithelial and mesenchymal cell types. Therefore, furthering our understanding of the dynamic relationship between CSCs, EMT, and the converse mesenchymal to epithelial transition, is critical in developing novel therapeutics and prognostic tools in the field of cancer medicine.
Citation Format: James R. Hernandez, Steven M. Mooney, Takumi Shiraishi, James E. Verdone, Calvin A. Harberg, Donald Vindivich, Kenneth J. Pienta. Profiling of cancer cell lines demonstrates a dynamic relationship between epithelial, mesenchymal and cancer stem states. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1919. doi:10.1158/1538-7445.AM2014-1919