bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2353: Fibulin-3, an extracellular matrix protein, regulates Notch signaling and promotes brain tumor cell invasion and survival
Authors: Hu Bin , Agudelo Paula A. , Saldivar Joshua C. , Sim Hosung , Dolan Claire E. , Mora Maria E. , Nuovo Gerard J. , Cole Susan E. , Viapiano Mariano S. 
Published: June 2012

Abstract
Malignant gliomas are the most common primary brain tumors and have extremely poor prognosis. Glioma cell infiltrate into normal neural tissue, escaping conventional chemo-radiotherapy and making tumor relapse almost unavoidable. We have recently characterized a novel extracellular matrix (ECM) protein named fibulin-3, which is highly expressed in gliomas but is absent in normal brain and rarely expressed in other solid tumors. We demonstrated that fibulin-3 regulates the expression of metalloproteases and promotes glioma cell invasion. In addition, this ECM protein increases the resistance of glioma cells to pro-apoptotic treatments, including starvation, oxidative stress and treatment with temozolomide. To further understand the mechanisms of fibulin-3 in gliomas, we investigated several candidate pathways but found no activation of EGFR, MAPK or Akt signaling. Interestingly, fibulin-3 bears significant homology with the Notch ligands from the Delta-like family, which prompted us to study the possible activation of this pathway, which is a critical anti-apoptotic pathway in cancer cells. Surprisingly, we found that fibulin-3 increased cleavage of endogenous Notch-1 in glioma cells as well as activation of a Notch-dependent reporter. In agreement, fibulin-3 expression regulated the levels of the Notch effector Hes-1 both in vitro and in vivo. Moreover, the pro-invasive effect of fibulin-3 in glioma cells was inhibited by pharmacological inhibition of Notch signaling or knockdown of Notch-1. This is potentially a novel mechanism by which tumor-associated ECM molecules can activate Notch signaling and modulate this key pro-tumoral pathway in gliomas. These results underscore the potential of fibulin-3 as a glioma-specific target in the tumor microenvironment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2353. doi:10.1158/1538-7445.AM2011-2353
Abstract 2365: Actopaxin: A novel regulator of cell migration and invasion in human hepatocellular carcinoma
Authors: Ng Lui , Poon Ronnie , Wong BCY , Pang Roberta 
Published: June 2012

Abstract
Background: The mortality rate of hepatocellular carcinoma (HCC) is high due to tumor recurrence and development of metastasis, involving cell spreading, lamellipodia formation and cell migration. Formation of focal adhesions is a key regulator of cell motility and cell invasion. Actopaxin, a focal adhesion and cytoskeleton-associated protein, is required for such processes. The aim of this study was to examine the role of Actopaxin in HCC cell migration, invasion and development of metastasis.
Methods: The expression of Actopaxin in primary and metastatic liver cancer cell-lines was examined by western blot and RT-PCR. The functional and molecular effects of Actopaxin expression were studied by transient as well as stable enforced expression or down-regulation in HCC cell-lines. Immunofluorescence staining for actin cytoskeleton and focal adhesion was performed to examine the effect of Actopaxin expression on cell shape, stress fiber organization, and focal adhesion. The clinicopathological significance of Actopaxin expression in tumorous tissues of 119 HCC patients was also investigated.
Results: High protein level of Actopaxin was found in the metastatic HCC cell-lines compared with other non-metastatic HCC cell-lines. Expression of a shorter form of Actopaxin was also detected in some of these cell-lines. Comparing to Actopaxin (LF-Actopaxin), the unreported short form (SF-Actopaxin) lacks a fragment in the C-terminal and hence results in an incomplete 2nd CH domain which consists binding sites for its downstream activation targets. Expression of LF-Actopaxin but not SF-Actopaxin in HCC cell-lines was positively correlated with their migration and invasion potential in vitro, accompanied by altered expressions of several focal adhesion proteins as well as EMT proteins. Study in clinical samples showed that LF-Actopaxin expression was positively correlated with tumor size (p&lt;0.05) while SF-Actopaxin expression was lower in HCC tumor compared with corresponding nontumorous liver (p&lt;0.001) and lower in HCC with metastasis compared with HCC without metastasis (p&lt;0.05).
Conclusion: This study demonstrated for the first time the pro-migratory effects of Actopaxin in human HCC, and the existence of SF-Actopaxin which displays different expression pattern as well as functional and molecular effects.
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Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2365. doi:10.1158/1538-7445.AM2011-2365
Abstract 2366: Impact of EWS-FLI induced changes in gene expression and cell behavior on metastatic potential
Authors: Chaturvedi Aashi P. , Welm Alana , Lessnick Stephen , Beckerle Mary 
Published: June 2012

Abstract
Ewing's sarcoma (ES) is frequently metastatic at presentation, a condition that is associated with poor prognosis. ES is caused by the oncogenic fusion of the EWSR1 and FLI1 genes to encode a chimeric EWS/FLI protein product that results in an altered transcriptional program. Because the metastatic potential of ES appears to develop at an early stage, we have explored whether the oncogene-driven misregulation of gene expression might contribute directly to promotion of metastasis. Metastasis is a complex process involving sequential and interrelated steps. In this study, we have examined the impact of EWS/FLI expression on cell migration, cell adhesion, and cytoarchitecture of ES cells by comparing the behavior of A673 ES cells with that of A673 cells in which we knocked down expression of EWS/FLI by RNA-interference. In contrast with what one might expect for a critical oncogene, we found that EWS/FLI expression reduced in vitro migration and Matrigel invasion. Consistent with these findings, expression of EWS/FLI abrogated cell adhesion and spreading. An in vivo mouse lung colonization assay revealed that ES cells treated with EWS/FLI RNAi adhere and colonize better in the lung tissue compared to ES cells, further supporting the in vitro adhesion results. At the cellular level, adhesion strength is correlated with the capacity of cells to form focal contacts and stress fibers. Knockdown of EWS/FLI expression in ES cells resulted in a striking remodeling of the actin cytoskeleton, with establishment of robust stress fibers and focal adhesions. Gene expression profiles, Western immunoblot analysis, and immunofluorescence staining confirmed that EWS/FLI expression is associated with reduced levels of focal adhesion proteins, including zyxin, a key regulator of actin assembly. Introduction of a zyxin cDNA expression construct into A673 ES cells was sufficient to restore the integrity of the actin cytoskeleton and focal adhesions, and to partially restore cell adhesion, both in vitro and in vivo, demonstrating a central role for zyxin in regulation of ES phenotype. Since release of cells from the primary tumor site is a critical initial step in metastasis, the profound impact of EWS/FLI expression on cytoarchitecture and cell adhesion may contribute to the metastatic phenotype in a unique, yet fundamental, way. Based on these data, we hypothesize that EWS/FLI-induced changes in gene expression simultaneously promotes both oncogenic transformation and tumor cell dissemination.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2366. doi:10.1158/1538-7445.AM2011-2366
Abstract 2371: Comparison of repeated minor liver resection and major resection on lung metastasis growth in mice
Authors: Momiyama Masashi , Suetsugu Atsushi , Tome Yasunori , Bouvet Michael , Chishima Takashi , Endo Itaru , Hoffman Robert M. 
Published: June 2012

Abstract
Liver resection has traditionally been the first choice treatment for patients presenting with primary and metastatic liver tumor. Many of the factors up-regulated during liver regeneration after a liver resection have been implicated in tumor growth and the extent of the up-regulation of these factors correlate with the degree of liver resection. However, the effects of a major liver resection compared to repeated minor resections on the growth of malignant tumor are unknown. This study examines the effects of liver regeneration on the growth of the lung metastatic tumors in an established mouse model, after major (70%) and repeated minor (35%+35%) liver resection. Experimental lung metastases were established by tail vein injection with the Colon 26 murine adenocarcinoma cell line expressing green fluorescent protein (GFP). Three days after cancer cell injection, groups of mice underwent liver resection (35%+35% vs. 70%). Lung tumor growth was measured by fluorescence imaging with the Olympus OV100 Small Animal Imaging System. Although, major and repeated minor resection removed the same volume of liver parenchyma, the two procedures had very different effects on lung metastases growth: Major resection stimulated lung metastatic growth. In contrast to major resection, repeated minor resection significantly inhibited the growth of metastatic lung tumors. There was no significant difference in liver regeneration between the two groups. These results show that repeated minor resection of liver is much safer regarding tumor stimulation than major resection. The results of this study indicate that when liver resection is necessary, repeated minor liver resection is superior to major liver resection, since repeated minor resection inhibits lung metastasis and major resection stimulates lung metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2371. doi:10.1158/1538-7445.AM2011-2371
Abstract 2374: First time identification of circulating tumor cellsin murine models of human non-small cell lung cancer
Authors: Mordant Pierre , Loriot Yohann , Decraene Charles , Lahon Benoit , Castier Yves , Soria Jean-Charles , Deutsch Eric 
Published: June 2012

Abstract
Background. Circulating tumor cells (CTCs) have been found in up to 40% of patients with either localized or metastatic non-small cell lung cancer (NSCLC). However, level of CTCs has never been established in preclinical murine models of human NSCLC. We sought to determine the levels of CTCs in subcutaneous and orthotopic murine models of human non-small cell lung cancer.
Material and Methods. We used athymic nude mice and luciferase-positive A549 lung adenocarcinoma cell line (A549-luc, Xenogen Corp, USA). In group 1, animals underwent subcutaneous injection of cells in both flank (n=6). In group 2, animals underwent general anesthesia, chest wall incision, and transpleural injection of cells in the parenchyma of the left lung (n=15). After 2 weeks, bioluminescent in vivo imaging (IVIS) was performed after intra peritoneal injection of luciferine, and xenograft implantation rates were calculated. During the third week, tumor-bearing animals were anesthetized, 1-mL venous blood was punctured from the cavernous sinus, mixed with 7-mL of healthy human blood, and tested using the Cellsearch assay (Veridex LLC, USA). Animals were then humanely killed.
Results. Xenograft implantation rates were 100% in group 1 (n=6) and 60% (n=9) in group 2. Among the 6 blood tubes collected from the first group, none were clotted, 6 tubes underwent successful Cellsearch assay, and 5 assays were positive for CTCs detection (CTCs level range 2-5, mean 2.5, sd 1.76). Among the 9 blood tubes collected from the second group, 3 tubes were clotted and impossible to analyze, 6 tubes underwent successful Cellsearch assay, and 5 assays were positive for CTCs detection (CTCs level range 2-21, mean 9.5, sd 9.35). When comparing groups, the difference in CTC levels show a trend toward statistical significance (student test, p=0.058).
Conclusions. Two weeks after tumor implantation, CTCs are detected in 83% of nude mice bearing either subcutaneous or orthotopic NSCLC tumors. Evolution of CTCs level should be established, but this model could be of interest to study oncogenesis and to assess new treatments.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2374. doi:10.1158/1538-7445.AM2011-2374
Abstract 238: Inhibition of SHP2 abolishes mammary tumorigenesis in mice
Authors: Matalka Fatimah , Hartman Zachary , Agazie Yehenew M. 
Published: June 2012

Abstract
The Src homology phosphotyrosyl phosphatase 2 (SHP2) plays a positive role in receptor tyrosine kinase-induced mitogenic and cell survival signaling. In addition, SHP2 mediates cell transformation induced by oncogenic tyrosine kinases. Here, we provide evidence that show that the SHP2 protein is overexpressed in basal-type/triple-negative breast cancer (BTBC) with strong correlation to higher tumor grade, metastasis and elevated expression of the epidermal growth factor. We further show that SHP2 plays an essential role in the tumorigenesis and metastasis of BTBC cells (MDA-MB-231 and MDA-MB-468) transplanted into the mammary glands of NOD/SCID mice. These results suggest that SHP2 can be used for targeted therapy in BTBC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 238. doi:10.1158/1538-7445.AM2011-238
Abstract 2381: Preclinical molecular targeting therapy of pancreatic cancer using a genetically engineered mouse model
Authors: Miyabayashi Koji , Ijichi Hideaki , Mohri Dai , Tada Motohisa , Asaoka Yoshinari , Ikenoue Tsuneo , Omata Masao , Moses Harold L. , Koike Kazuhiko 
Published: June 2012

Abstract
Patients with pancreatic ductal adenocarcinoma have a poor prognosis. New therapeutic approaches to improve the prognosis are expected. We generated pancreas-specific Tgfbr2 knockout mice in the context of Kras activation, which recapitulated clinical and histopathological manifestations of human pancreatic cancer. Using this model we investigated the anti-tumor effects of gemcitabine and molecular targeted drugs.
We treated the mice with EGFR inhibitor elrotinib or VEGFR inhibitor axitinib in combination with gemcitabine. Median survival times were 45, 60, 77, and 74 days for control, gemcitabine alone, gemcitabine + axitinib, and gemcitabine + erlotinib, respectively.
In vitro assays, elrotinib inhibited phosphorylation of EGFR and both drugs also inhibited proliferation of human pancreatic cancer cell lines in vitro.This mouse model also recapitulated chemosensitivity of human pancreatic cancer and suggested erlotinib and axitinib in combination with gemcitabine can be superior to gemcitabine alone. This mouse model helps us to investigate the mechanism of the action of drugs and chemoresistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2381. doi:10.1158/1538-7445.AM2011-2381
Abstract 2389: Efficacy of ABT-737 against c-Myc-induced mammary adenocarcinomas in transgenic and syngrafted mouse tumor models
Authors: Eskelinen Vilja , Saarikoski Sirkku T. , Nieminen Anni I. , Haapakorva Elias , Marques Elsa , Klefström Juha 
Published: June 2012

Abstract
Traditional preclinical discovery methods and models only poorly predict drug efficacy in clinical trials. It has been reasoned that present cultured tumor cell line and xenotransplantation-based in vivo models are too reductionist, failing to recapitulate tumour heterogeneity, tumor-microenvironment interactions and tumor microevolutionary trajectories. The genetically engineered mouse models (GEMMs) hold promise as next generation preclinical models, but the caveat is that GEMMs are not straightforward suitable for preclinical cohort studies. Here we hypothesized that mammary tumors from tumor-prone WAP-Myc mice retain their molecular characteristics and authentic drug responses when recreated as syngrafts in the mammary fat pads of recipient mouse. This platform would allow rapid and non-laborious pilot cohort studies with GEMM tumors. We are testing the hypothesis by determining tumor markers and apoptotic efficacy of BH3-mimetic ABT-737 against c-Myc-induced mammary adenocarcinomas and pulmonary metastases in both transgenic and syngraft models. In the WAP-Myc mice c-Myc is induced in the luminal mammary epithelial cells during late pregnancy resulting in development of endogeneous mammary adenocarcinomas in nearly 100% of multiparous animals. We observe that the tumors are transplantable as cells suspensions (25 000 cells/gland) with approximately 90% success rate. While the transgenic WAP-Myc tumors develop with an average of 3.5 months latency, the syngrafted tumors develop within 3-4 weeks post-transplantation. However, in contrast to 20% rate of pulmonary metastases in the transgenic WAP-Myc mice, syngrafted animals need to be sacrificed prior to metastasis formation. Our preliminary results suggest that the tumor histopathology does not significantly change and the tumor heterogeneity is preserved in the syngrafted tumors. To investigate the response of tumors to ABT-737, animals bearing either endogenous or transplanted tumors were treated with 100mg/kg of ABT-737 for 21 days. ABT-737 reduced primary tumor growth and lung metastases as well as enhanced caspase-3 activity in the transgenic WAP-Myc tumors. Also the syngrafted tumors respond to ABT-737 and the data comparing effects in transgenic versus syngrafted tumors will be presented. Our results demonstrating feasibility of the syngraft platform may help to alleviate many shortcomings of GEMMs in preclinical studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2389. doi:10.1158/1538-7445.AM2011-2389
Abstract 239: Biomarker profiling and combination studies of receptor tyrosine kinase inhibitors of EGFR, ERBB2, IGFR-1, FGFR and PDGFR
Authors: O'Day Christine L. , Ovechkina Yulia , Marcoe Karen , Keyser Robert , Chesnut-Speelman Jessica , Hnilo James 
Published: June 2012

Abstract
Targeting Receptor Tyrosine Kinases (RTKs) for therapeutic efficacy has been a promising approach for modern oncological agents. However, not all cancers respond to these agents and understanding of the feedback and resistance mechanisms is not complete. We have used an In vitro cellular profiling of 240 genetically characterized tumor human cell lines to help understand genotypes that convey sensitivity and resistance to these agents. While most of the sensitive cell lines were unique to a given RTK inhibitor, many of the resistant cell lines had similar genotypes. We have investigated downstream genes for mutations, over-expression and phosphorylation status. Phosphorylation levels pAKT, pERK, and pJNK, and as well as basal levels of p27KIP, EGFR and ERBB2 protein levels were analyzed. Many of the downstream mutations or activated genes confer resistance to the RTK inhibitors such as AKT, PTEN and PI3K mutations.
In addition to downstream activation, we have found that overexpressed RTKs often seem to confer resistance to other RTK inhibitors. For example, EGFR over-expressed cell lines disproportionately populated the group of cell lines resistant to an IGFR-1 receptor agonist. We have investigated cross talk between these various RTKs. Both EGFR and IGFR-1 inhibitors were tested in a combinatorial approach through 60 cell lines for synergy and antagonism. We evaluate synergy calculations through combination index and bliss analysis across 60 cell lines. Other combinations are also in the process of being tested for synergy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 239. doi:10.1158/1538-7445.AM2011-239
Abstract 2399: Simvastatin inhibits advanced prostate cancer in TRAMP mice
Authors: Drenkhahn Sara K. , Jackson Glenn A. , Huber Christal D. , Browning Jim D. , Fritsche Kevin L. , Wiedmeyer Charles E. , Besch-Williford Cynthia L. , Lubahn Dennis B. 
Published: June 2012

Abstract
Controversial literature suggests the potential off-label benefit of statins in the prevention of breast and prostate cancers. As millions of Americans are currently taking statins to lower cholesterol and prevent heart disease, we wanted to test if simvastatin could inhibit prostate carcinogenesis in the TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate) model. We hypothesized that simvastatin would inhibit the most aggressive form of cancer in the model, poorly differentiated carcinoma (PDC), similar to what has been seen in epidemiological studies. Mice were fed a Western Diet to mimic the high-fat diet common among men in the United States (n=25 per group). Two additional groups were fed the Western diet supplemented with either 0.025% or 0.050% w/w simvastatin. The control mice on the Western diet had an increase of PDC when compared to a low-fat AIN93 casein based diet (48% vs. 32%). While the 0.025% simvastatin Western diet reduced PDC incidence from 48% to 38%, the 0.050% simvastatin Western diet drastically reduced PDC incidence from 48% to 16% when compared to Western controls (p=0.0153 by Chi square analysis). Changes in serum profiles analyzing total cholesterol, LDL, HDL, and triglycerides did not correlate to the reduction in PDC incidence. In conclusion, our results show that simvastatin can reduce the most aggressive stage of prostate cancer in the TRAMP model and supports the observation that simvastatin reduces the risk of developing advanced prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2399. doi:10.1158/1538-7445.AM2011-2399