bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2626: Characterization of the invading cells in glioblastoma using a syngeneic intracranial transplant tumor model.
Authors: Zhang Nailing , Song Yurong , Jansen Sanaz , Adhikari Amit , Wang Sophie , Lu Lucy , Sullivan Teresa , Van Dyke Terry 
Published: August 2014

Abstract
Local and distant invasion is a hallmark property of glioblastoma (GBM) that prevents curative surgical resection, and may be the key reason for GBM recurrence. Although cancer stem cells (CSCs) have been suggested to cause tumor recurrence based on their resistance to radiotherapy and chemotherapy, it is not clear whether CSCs are also involved in GBM invasiveness. We hypothesize that the invading cells in GBM have stem-like properties. To test our hypothesis, we propose to characterize cells at the invasive front of GBM using a syngeneic intracranial transplant tumor model.
Three core regulatory networks are dysregulated in most human GBMs, including the RTK/RAS/PI3K/PTEN, INK/Cyclin D/CDK/RB, and ARF/p53 pathways. We have previously generated a genetically engineered mouse (GEM) model for GBM development via adult-inducible astrocyte-specific perturbation of RB, K-RAS and PTEN. These mice develop astrocytomas that progress to high grade GBM, and faithfully recapitulate the histopathology and molecular characteristics of most human GBMs. We have isolated primary tumor cells from these mice that are maintained in serum-free neural stem cell culture medium and expanded as neurospheres. These primary and low-passage cultures contain a mixed population of cancer stem cells and progenitor cells, and are highly invasive in vitro by matrigel invasion assay. With &gt; 90% penetrance, intracranial injection of 25,000 cells leads to invasive GBM formation and a 32-day median survival in syngeneic host mice. Thus, the model provides an efficient approach for dissecting GBM cell invasion mechanisms in vivo. We will further trace the migration/invasion of GBM cells in the host brain after labeling with lentiviral-expressed mCherry. Host blood vessels are labeled with YFP via Tie2-Cre endothelial expression of a Rosa26-YFP allele. A time course analysis of stem cell marker expression will be used to assess properties of invading cells at the diffusive tumor margin. Laser capture microdissection will be used for invasive rim-cell and non-invasive core-cell isolation, and RNA samples will be compared by unbiased transcriptome studies. Results will provide hypotheses for invasion mechanisms and may identify potential biomarkers for invasive cells.
Citation Format: Nailing Zhang, Yurong Song, Sanaz Jansen, Amit Adhikari, Sophie Wang, Lucy Lu, Teresa Sullivan, Terry Van Dyke. Characterization of the invading cells in glioblastoma using a syngeneic intracranial transplant tumor model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2626. doi:10.1158/1538-7445.AM2013-2626
Abstract 264: Mesenchymal stem cells mediate epithelial-to-mesenchymal transition (EMT) and stemness regulation in pancreatic cancer via Notch signal.
Authors: Kabashima-Niibe Ayano , Higuchi Hajime , Matsuzaki Yumi , Mabuchi Yo , Funakoshi Shinsuke , Adachi Masayuki , Hamamoto Yasuo , Takaishi Hiromasa , Hibi Toshifumi 
Published: August 2014

Abstract
Cancer associate fibroblasts (CAFs), one of the major components of the cancer stroma, are prominently involved in tumor progression including epithelial to mesenchymal transition (EMT). Recently, bone marrow derived mesenchymal stem cells (MSCs) have been suggested as candidate for the source of tumor-promoting CAFs. We previously demonstrated that side population (SP) cells, which are enriched with so-called tumor initiating stem cell like cells (TISCs), play a pivotal role of local invasion and liver metastasis in pancreatic cancer (Int-J-Cancer 124:2771, 2009). Therefore, we formulated the hypothesis that MSCs regulate SP cells EMT and TISC-like properties such as tumor formation/progression. The AIM of the present study was to examine whether bone marrow-derived MSCs have ability to mediate EMT and/or tumor progression in pancreatic cancer SP cells. METHODS: MSCs were pre-treated with TGF-beta for 3 days. SP or non-SP cells were co-cultured in the presence or absence of TGF-beta-pretreated MSCs (Tb-MSCs) for 3 days. Real-time PCR experiments were performed to quantitate mRNA levels of EMT associated genes as well as so-called stemness related genes. PANC-1 derived SP or non-SP cells were co-injected with Tb-MSCs into NOD/SCID mice, and their tumorigenesity was evaluated. RESULTS: Co-culturing with Tb-MSCs dramatically induced EMT-associated mRNA alterations including suppression of E-cadherin and induction of slug in PANC-1 SP cells. In SP cells but not in non-SP cells, levels of stemness genes including CD133, Oct4, LGR5, were enhanced by co-culturing with Tb-MSCs. Tb-MSCs enhanced in vitro sphere forming activity as well as in vivo tumor formation in SP cells. These alterations including EMT-associated gene modifications and enhanced sphere formation were suppressed by Notch signal inhibition, suggested MSCs-associated regulation of EMT and TISC-like properties are mediated by Notch-signaling. In CONCLUSION, MSCs regulate EMT and they maintain TISC-like properties in pancreatic cancer SP cells via Notch signal-dependent mechanisms. Targeting Notch signaling would appear to be attractive to prevent MSCs and/or stromal cell-associated cancer progression.
Citation Format: Ayano Kabashima-Niibe, Hajime Higuchi, Yumi Matsuzaki, Yo Mabuchi, Shinsuke Funakoshi, Masayuki Adachi, Yasuo Hamamoto, Hiromasa Takaishi, Toshifumi Hibi. Mesenchymal stem cells mediate epithelial-to-mesenchymal transition (EMT) and stemness regulation in pancreatic cancer via Notch signal. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 264. doi:10.1158/1538-7445.AM2013-264
Abstract 2657: The role of NR5A2 in pancreas development and oncogenesis.
Authors: Nissim Sahar , Wucherpfennig Julia , Wang Xiao-Xu , Kimmelman Alec , Goessling Wolfram 
Published: August 2014

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers today. A recent genome-wide association study (GWAS) has implicated the nuclear receptor NR5A2 in modulating risk for pancreatic cancer. While a role for this gene in pancreatic cancer has not been previously recognized, it is known to have an important role in stem cell pluripotency and metabolism. Using the zebrafish model organism, we demonstrate that knockdown of nr5a2 results in absence of exocrine pancreas, while leaving endocrine pancreas unaffected, indicating an essential role in pancreas organ formation. Further, we localize expression of nr5a2 to the endodermal bud that gives rise to the exocrine pancreas, consistent with a role for nr5a2 in regulating differentiation of pancreas progenitors. In resected human PDAC specimens and in vitro cell lines, we find that NR5A2 is overexpressed compared to normal ductal epithelium. Moreover, shRNA knockdown of NR5A2 dramatically slows proliferation of PDAC cell lines, supporting the hypothesis that NR5A2 is involved in pancreatic carcinogenesis. These data support a model that NR5A2 regulates the proliferation and differentiation of exocrine pancreas progenitor cells during development. We postulate that aberrant expression of NR5A2 results in dysregulation of these processes in the adult pancreas by driving ductal epithelial cells to acquire properties of progenitor cells, and therefore may be an important step in pancreas oncogenesis.
Citation Format: Sahar Nissim, Julia Wucherpfennig, Xiao-Xu Wang, Alec Kimmelman, Wolfram Goessling. The role of NR5A2 in pancreas development and oncogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2657. doi:10.1158/1538-7445.AM2013-2657
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2662: Effects of chemotherapy on tumor hypoxia measured with 18-F-FAZA PET/CT and compared to FDG-PET/CT in advanced non-small-cell lung cancer (NSCLC).
Authors: Kerner Gerald S.M.A. , Bollineni Vikram R. , Hiltermann Thijo J.N. , Pruim Jan , Groen Harry J.M. 
Published: August 2014

Abstract
Introduction
Hypoxia in tumors is associated with resistance to chemotherapy. 18-F-FAZA is a PET tracer developed to characterize intratumoral hypoxic regions. Tumor metabolism is measured with 18-F-FDG PET. Goal of this study is to investigate hypoxic changes in relation to metabolic alterations in patients with advanced NSCLC during chemotherapy.
Methods
PET-CT with 18-F-FDG and 18-F-FAZA tracers were used prior to the first cycle and after the second cycle of chemotherapy. Volumes of interest were manually drawn on visual inspection. For FAZA, mean and maximum (max) tumor to background (FAZAT/B) ratios, and for FDG, SUVmax and SUVmean, were calculated. Measurements were corrected for partial volume using a NEMA image quality phantom. The fractional hypoxic volume, defined as the tumor fraction with a T/B ratio above 1.2 was calculated. The hypoxic and metabolic distribution within the primary tumor was studied with skewness and kurtosis. Differences between baseline and second measurement were calculated with the Wilcoxon signed rank test.
Results
FDG and FAZA scans were performed in 9 patients. Median FAZAT/Bmax was 2.8 (1.9-4.7) at baseline and 3.3 (1.3-5.5) and after 2 cycles, respectively, while SUVmax was 14.8 (5.8-32.5) at baseline and 14.6 (1.9-24.9) after 2 cycles. Fractional hypoxic volume was 78% (17-100%) at baseline and 74% (0-100%) after 2 cycles of therapy. No significant changes in hypoxia or metabolism were observed during chemotherapy. Hypoxic and metabolic heterogeneity within the primary tumor remained unchanged. At baseline skewness was different between FDG and FAZA (p=0.02). After 2 cycles this difference did not persist (p=0.31). There was no difference at baseline or after 2 cycles in kurtosis between FDG and FAZA. Tumor response measured with CT was 2 PR, 5 SD and 2 PD.
Conclusion
In this exploratory study the fractional hypoxic volume and the heterogeneity of hypoxic and metabolic areas remained unchanged during chemotherapy. The intratumoral difference in FAZA and FDG distribution changed from baseline to that after 2 cycles of chemotherapy.
Citation Format: Gerald S.M.A. Kerner, Vikram R. Bollineni, Thijo J.N. Hiltermann, Jan Pruim, Harry J.M. Groen. Effects of chemotherapy on tumor hypoxia measured with 18-F-FAZA PET/CT and compared to FDG-PET/CT in advanced non-small-cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2013-2662
Abstract 2691: Chemokine expression profile in prostate cancer cell lines: Association with metastatic potential.
Authors: Reyes Niradiz , Bettin Alfonso , Rebollo Juan , Correa Oscar , Geliebter Jan 
Published: August 2014

Abstract
Background: Metastatic spread poses the greatest challenge for the management of Prostate Cancer (PCa). Although its frequency at diagnosis of PCa cases is only 4%, it is associated with poor prognosis, with five year survival rates of only 30%. Molecular mechanisms involved in metastatic progression are not completely understood; however, it has been noted that chemokines and their receptors play a key role in the establishment of metastatic lesions.
Objective: To compare the mRNA expression profiles of chemokines and their receptors in two human PCa cell lines with different metastatic phenotypes (LNCaP, PC-3) and in a control, normal prostate epithelial cell line (PWR-1E).
Methods: We evaluated the expression profiles at the transcript level of chemokines and their receptors in LNCaP, PC-3 and PWR-1E human cell lines using a commercial primer panel (Chemokines SensiMix qPCR Primers Panel©,Origene Technologies), as well as a custom primer panel. The relative quantification of gene expression was determined using the ΔΔCt method with the normal PWR-1E cell line as the reference cell line and normalizing the expression to β-actin, HPRT1 and GAPDH housekeeping genes.
Results: Sixteen gene transcripts were overexpressed in PC-3, 13 of which were exclusively overexpressed in this cell line and 3 other genes were up-regulated in both PC-3 and LNCaP cell lines. Of the 13 genes overexpressed in PC-3, 12 were found under-expressed in LNCaP cell line, compared to PWR-1E (CCL2, CCL26, CCL28, CXCL2, CXCL3, CXCL4, CXCL4V1, CXCL6, IL8, CXCL12, CCR10, and CCRL2). Chemokine transcript under-expression was more frequently found in LNCaP than in PC-3 (11 vs 8) and transcripts for genes CCL3, CCL3L1, CCL3L3, CCL27 and DARC were underexpressed in both cell lines.
Discussion: Here we describe the differential chemokine expression profile between PCa cell lines with different metastatic potentials. In addition to chemokines/receptors known to play a role in PCa, we have identified the differential expression of chemokine gene transcripts not previously associated with PCa.
Conclusions: Differential chemokine expression at the mRNA level was found in association with metastatic phenotypes of PCa cell lines. Additional research is needed to determine mechanisms involved in genic regulation of this profiles and to determine their roles in tumorigenesis and cancer progression in the prostate.
Financial support: Colciencias Contract #462-2008
Citation Format: Niradiz Reyes, Alfonso Bettin, Juan Rebollo, Oscar Correa, Jan Geliebter. Chemokine expression profile in prostate cancer cell lines: Association with metastatic potential. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2691. doi:10.1158/1538-7445.AM2013-2691
Abstract 2698: Alternative expression of E2F1, EZH2 and SUZ12 response for the invasive progression of superficial bladder cancers.
Authors: Lee Se-Ra , Roh Yun-Gil , Chu In-Sun , Yeom Young Il , Leem Sun-Hee 
Published: August 2014

Abstract
A superficial bladder cancer is a noninvasive cancer that is presented as a good prognosis after receiving treatment, and noninvasive. However, about 20∼50% of superficial bladder cancer patients progressed to invasive tumor which represent the poor survival rates within 5 years. In previous study, we addressed if the transcriptional characteristics of the superficial bladder cancer could be used as predictive biomarkers for the progression of superficial tumors to invasive ones. Using gene expression data from 165 bladder cancer patients, we identified a gene expression signature that could predict the likelihood of progression to invasive tumors. Gene network analyses of the signature revealed that E2F1 and its downstream effectors EZH2 and SUZ12 could be important mediators for the invasive and metastatic progression of superficial tumors. In this study, we investigated how these genes may affect the invasive and metastatic progression of superficial tumors. We investigated the invasive ability by these genes in two groups of bladder cancer cell lines: One group (UC5 and UC9) has a superficial signature of bladder cancer, and the other group (EJ and 5637) has an invasive signature of bladder cancer. We examined the effects of overexpression or siRNA inhibition of these genes on cell growth, migration and invasion in bladder cancer cell lines. We will report the results estimating the roles of these genes for the invasive and metastatic progression in bladder cancer cell lines.
Citation Format: Se-Ra Lee, Yun-Gil Roh, In-Sun Chu, Young Il Yeom, Sun-Hee Leem. Alternative expression of E2F1, EZH2 and SUZ12 response for the invasive progression of superficial bladder cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2698. doi:10.1158/1538-7445.AM2013-2698
Abstract 270: Cell assay on a chip to study tumor initiating cells’ heterogeneity and treatment resistance.
Authors: Zhang Weijia , Qin Lidong 
Published: August 2014

Abstract
Recent investigations from both animal models and clinical samples have continuously supported that Tumor Initiating Cell (TIC) does exist and plays an important role in tumor metastasis and recurrence. However, TICs have a few intrinsic properties leading to their complexity in molecular targeting and inhibition. TICs are 1) heterogeneous, 2) dynamically changing states, 3) often rare and 4) lack robust biomarker combinations, thereby challenging conventional bulk in vitro experimental tools and complicating the prediction and explanation of animal study results. High throughput, in situ, and cell-by-cell measurement on TICs is a way to fully decipher TIC's molecular signature and signaling pathways. We believe such measurement can lead to 1) revolutionary implementation of TIC models; 2) identification of new therapeutic targets; and 3) reduction of breast cancer recurrence and metastasis. Microfluidics technology (1) is a candidate to serve as such type of high throughput single-cell characterization.
We started pursuing such measurements a few years ago and demonstrated high throughput single-cell protein profiling on both cell lines and clinical samples. The technology, called single-cell barcode chip (SCBC), is facilitated by state-of-the-art Polydimethylsiloxane (PDMS) microfluidics protocols. The SCBC consists of down to nanoliter chambers that concentrate proteins from individual cells to a level even higher than cell culture media in conventional dish technology and contains extremely miniaturized antibody arrays to capture proteins produced by cells in these chambers. Further utilization of our SCBC platform to TICs is expected to characterize protein expression from individual breast TIC and lead to new discoveries in TIC filed.
Citation Format: Weijia Zhang, Lidong Qin. Cell assay on a chip to study tumor initiating cells’ heterogeneity and treatment resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 270. doi:10.1158/1538-7445.AM2013-270
Abstract 2703: A direct regulation of Twist1 by FOXQ1 promotes colorectal cancer metastasis.
Authors: Abba Mohammed , Patil Nitin , Rasheed Kabeer , Nelson Laura D. , Mudduluru Giridhar , Leupold Jörg H. , Allgayer Heike 
Published: August 2014

Abstract
Abstract
Malignant cell transformation, invasion and metastasis are dependent on the coordinated rewiring of gene expression. A major component in the scaffold of these reprogramming events is one in which epithelial cells lose intercellular connections and polarity and adopt a motile mesenchymal phenotype, one that is largely supported by a robust transcriptional machinery consisting mostly of developmental transcription factors.
We investigated the winged helix transcription factor, FOXQ1, identified from an oligonucleotide microarray expression analysis, as being concomitantly deregulated in both epithelial and stromal compartments. We found that FOXQ1 contributes to epithelial to mesenchymal transition (EMT), in part by directly affecting the transcription of Twist1, itself a key mediator of metastasis that transcriptionally regulates the expression of important molecules involved in EMT. Reporter gene assays and chromatin immunoprecipitation experiments showed that FOXQ1 regulated and directly interacted with the Twist1 promoter, leading to a suppression of E-cadherin and increased expression of mesenchymal markers. Forced expression and RNAi mediated silencing of FOXQ1 led to increased and decreased levels of Twist1 mRNA and protein levels, respectively, with concomitant effects on migration, invasion and in vivo metastasis of colorectal cancer cells. Moreover, FOXQ1 mRNA and protein expression correlated in a series of resected patient samples. Conclusively our results show that FOXQ1 is a novel mediator of colorectal cancer metastasis and joins the network of transcription factors that orchestrate EMT.
Citation Format: Mohammed Abba, Nitin Patil, Kabeer Rasheed, Laura D. Nelson, Giridhar Mudduluru, Jörg H. Leupold, Heike Allgayer. A direct regulation of Twist1 by FOXQ1 promotes colorectal cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2703. doi:10.1158/1538-7445.AM2013-2703
Abstract 2711: BART9, an EBV encoded miRNA, regulates E-cadherin and metastasis.
Authors: Chung Yuan Hsu 
Published: August 2014

Abstract
EBV is a casual agent of NPC and products of EBV genome are believed to be involved in the pathogenesis of NPC. EBV is the first human virus found to express microRNAs (miRNAs). EBV has been found encoded more than forty miRNAs, the functions of which remain largely unknown. In this study, We discovered that BART9 was expressed at high levels in NPC tissues examined. In addition, the level of BART9 was higher than the best documented human oncogenic miR-21. Next, we investigated the role and mechanism of BART9 in NPC cells, and found that exogenous expression of BART9 enhanced the migration and invasion but not proliferation of EBV negative-NPC cells in vitro. Further, depletion of endogenous BART9 suppressed migration and invasion of EBV-positive NPC cells. We further demonstrated that BART9 directly targeted CDH1-3’-UTR and repressed the expression of CDH1, a metastasis suppressor. In addition, restoring of BART9-resistant CDH1 expression in BART9 over-expression cells recovered the migratory and invasive ability of BART9. More importantly, ectopic expression of BART9 triggered spontaneous metastasis of NPC cells in vivo. Finally, in situ hybridization for BART9 showed strong positive staining in paraffin-embedded nasopharyngeal carcinoma tissues and the CDH1 protein levels have an inverse correlation with BART9 expression. Collectively, our findings indicate that BART9 promoted migration, invasion and metastasis in NPC. It is the first case reported that EBV encodes an BART miRNA has effect on motility of infected cells, suggesting a novel mechanism by which Epstein-Barr virus induces the metastasis and recurrence of NPC.
Citation Format: Hsu Chung Yuan. BART9, an EBV encoded miRNA, regulates E-cadherin and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2711. doi:10.1158/1538-7445.AM2013-2711