bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-160: ITRI-260, a promising candidate for treatment of acute myeloid leukemia
Authors: Liu Chih-Peng , Liu Hsingjin Eugene , Lee On , Chen Chih-Hung , Huang Jui-Wen , Chen Ting-Shou , Ko Ching-Huai , Wang Ling-Mei , Chen Yen-Chun , Tseng Hsiang-Wen , Shih Ying-Chu , Chiou Shu-Jiau , Tsai Yuan-Jang , Hwang Chrong-Shiong 
Published: February 2011

Abstract
Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor characterized by an abnormal proliferation of myeloid progenitor cells, decreased rate of self-destruction and an arrest in cell differentiation. The internal tandem duplication mutations of FMS-like tyrosine kinase-3 (FLT3/ITD mutations) are common in AML and linked to poor prognosis. ITRI-260 generated from designed by computer-assisted rationale drug design and in silico prioritized approaches, was proved to be a potent cell growth inhibitor against FLT3/ITD mutated AML cells through FLT3 and c-Kit inhibition. The in vivo efficacy of ITRI-260 via oral route was demonstrated in MV4-11 xenograft mice model. Besides, two more orthotopic murine models were used to assess the in vivo therapeutic efficacy of ITRI-260. The first one is MV4-11 cell orthotopically engraft into NOD/SCID mice bone marrow and the second one is primary AML cells from AML patient engraft into NOD/SCID mice bone marrow. The results show that ITII-260 can decrease FLT3/ITD mutant leukemia blasts in peripheral blood and bone marrow in both animal models. Finally, ITRI-260 prolongs the survival in both bone marrow engraft mice models. These findings strongly suggest clinical benefits of ITRI-260 in patients with FLT3/ITD AML. Currently we are planning the bridged projects to push ITRI-260 toward IND status.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-160.
Abstract LB-164: Aurora Kinase A as a target for sensitizing glioma cells to radiation treatment
Authors: Patel Disha , Gordon Nicolaus , Shirai Katsyuki , Chakravarti Arnab 
Published: February 2011

Abstract
Purpose: Eukaryotic cells have a complex cell cycle process that is regulated by many factors. Tumors arise when cell cycle progression is deregulated. Mitosis is a well coordinated event and occurs only when proper signals allow the cell cycle machinery to proceed beyond the G2/M checkpoint. Aurora kinase A (AurKA) is a mitotic regulator involved in bipolar-spindle assembly and chromosome segregation, and also recruits other proteins and cofactors that are important for mitotic events. AurKA is upregulated in many cancers and has been shown to cause aneuploidy and induce oncogenic transformation. AurKA overexpression allows cells to surpass the G2/M checkpoint and enter mitosis prematurely, which leads to chromosomal abnormalities and genomic instability.
Experimental Design: Here we are investigating AurKA in established (ATCC) and primary glioblastoma (GBM) cell lines. Assays measuring radiosensitivity were conducted using wild-type and AurKA knockdown GBM cells. These include the clonogenic survival assay, MTS proliferation assay, cell-cycle analysis, and Annexin V apoptosis assay. Protein profiles were used to investigate pro-apoptotic, anti-apoptotic, and other downstream and upstream signaling pathways after radiation treatment.
Results and Discussion: Irradiation induces AurKA expression in both our established and primary GBM cell lines. Next we silenced AurKA using lentiviral mediated shRNA transduction. AurKA knockdown cells exhibit greater radiosensitivity when compared to cells transduced with a mock vector. AurKA and p53 interact at multiple levels. Preclinical data with AurKA inhibitors suggest p53-negative tumors may be more sensitive to AurKA inhibitors than p53-positive tumors. To investigate which subset of GBMs show greater response to AurKA silencing, we will conduct experiments using our panel of isogenic GBM cells lines. Our hypothesis is that AurKA knockdown cells will show reduced proliferation and increased apoptosis, thereby leading to cell death. The outcome of this preclinical study would be to evaluate AurKA as a potential therapeutic target for the treatment of GBM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-164.
Abstract LB-178: Characterization of estrogen responses in breast cancer cell lines highlights ERα as an LRH-1 regulated gene
Authors: Thiruchelvam Paul T.R , Hua Hui , Lai Chun Fui , Photiou Andy , Kyle Fiona , Coombes Charles , Buluwela Laki , Ali Simak 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-178.
Abstract LB-179: Enhanced resistance to tamoxifen by the c-ABL proto-oncogene in breast cancer
Authors: Zhao Hua Jun , Ou-Yang Fu , Chen I-Fen , Hou Ming-Feng , Yuan Shyng-Shiou F. , Chang Hsueh-Ling , Lee Yi-Chen , Plattner Rina , Waltz Susan , Ho Shuk-Mei , Sims Jonathan , Wang Shao-Chun 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-179.
Abstract LB-180: Prevention of NNK-induced lung cancer in mice by anti-estrogen therapy
Authors: Siegfried Jill M. , Rothstein Mary E. , Lenzner Diana , Gubish Christopher T. , Land Stephanie R. , Stabile Laura P. 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-180.
Abstract LB-194: Restoration of miR-31 function in already-established metastases elicits an anti-metastatic therapeutic response in vivo.
Authors: Valastyan Scott , Chang Amelia , Benaich Nathan , Reinhardt Ferenc , Weinberg Robert A. 
Published: February 2011

Abstract
Discussion
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-194.
Abstract LB-201: Nuclear localization of Src, androgen receptor and PSA in prostate cancer
Authors: Saxena Parmita , Wang Tao , Adams Dave S. , Gioeli Daniel , FitzGerald Thomas J. , Languino Lucia R. 
Published: February 2011

Abstract
Src signaling plays an important role in prostate cancer (PrCa) progression. Dasatinib, an oral src family kinase inhibitor, is being tested in patients with PrCa in several Phase II and III clinical trials. It has been shown that src interacts with androgen receptor (AR) and enhances AR transactivation. Although it has been shown that src promotes AR activity, the underlying pathway has not been defined.
To characterize the src-AR pathway, we first analyzed the localization of src, AR, and Prostate Specific Antigen (PSA, an AR target gene). Using sub-cellular fractionation and immunofluorescence, p-src and src were found in the nucleus, apart from their normal cytoplasmic localization, in androgen-dependent LNCaP cells upon androgen stimulation or deprivation conditions. Also, their localization was not affected by androgen stimulation. Similar to src and p-src, AR as well as pSer81-AR (an AR site indirectly phosphorylated by src) were found in the nucleus as well as in the cytoplasm. Unexpectedly, we found PSA localization in the nucleus upon androgen stimulation in LNCaP and C4-2B cells as well as in the nucleus of C4-2B cells upon androgen deprivation.
We further studied the effect of src on AR activity by transfection of dominant negative src (SrcK298M) in LNCaP and androgen-independent C4-2B cells. Transfection with SrcK298M did not affect PSA expression in LNCaP cells whereas in C4-2B cells SrcK298M transfection inhibited PSA expression.
These data show that src is required for AR activity and, consequently, PSA expression in androgen-independent prostate cancer cells, but not in androgen-dependent cells.
In conclusion, these data suggest that the nuclear co-localization of p-src, AR and PSA might allow macromolecular interactions which can further enhance AR transactivation and promote disease progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-201.
Abstract LB-208: Radiation-induced liver fibrosis is mitigated by gene therapy against transforming growth factor-ß signaling in the rat
Authors: Shi-suo Du , Zhao-Chong Zeng , Min Qiang , Zheng-Yu Zhang , Zhong-shan Liu 
Published: February 2011

Abstract
Purpose: We investigated whether blockage the Transforming growth factor (TGF)-ß signaling ameliorated established liver radiation-induced liver fibrosis (RILF).
Materials and Methods: A replication-defective adenoviral vector expressing the extracellular portion of mouse TßRII and the Fc portion of human immunoglobulin IgG fusion protein(AdT RIIFc) was produced. The entire liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdT RIIFc (1× 1011 PFU, TßRII), Control virus (1×1011 PFU, AdGFP), or saline (SALIN). Delayed radiation liver injury was assessed using histology, morphometry, and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell (HSC) activation, and hepatocyte regeneration were also analyzed.
Results: Blocking TGF-ß signaling with AdT RIIFc successfully mitigated established radiation induced liver fibrosis (RILF). Compared with RILFM or AdGFP rats, AdT RIIFc-treated mice exhibited less oxidative stress damage, less HSC activation, preserved liver function.
Conclusions: Modulation of TGF-ß with AdT RIIFc is feasible and ameliorates established radiation-induced liver fibrosis. These data confirm the putative role of TGF-ß in delayed radiation-induced liver damage.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-208.
Abstract LB-211: Identification of blood-based protein biomarker candidates for malignant glioma
Authors: Xu Baogang J. , An Qi A. , Gowda Supriya , Yan Wenwei , Abel Ty , Pierce Larry , Weaver Kyle D. , Thompson Reid C. 
Published: February 2011

Abstract
A reliable, non-invasive and convenient method for detecting malignant gliomas progression and responsiveness to treatment will significantly increase the survival of patients. A protein biomarker-based method for high-grade glioma using patients’ blood samples was investigated. Using a multiplex Luminex immunoassay, 90 proteins associated with cancer were examined in the plasma from high-grade glioma patients (N=28) and non-cancer controls (N=367). Wilcoxon rank-sum test was performed to select the differentially expressed proteins. Receiver operating characteristics (ROC) curves were constructed to determine their diagnostic accuracy. A second cohort of serum samples from different GBM patients (N=20) and non-cancer controls (N=1278) was similarly analyzed. A total of 40 and 25 proteins were found to be significantly differentially expressed between the glioma and control groups (p &lt; 0.0005) using the plasma or serum samples, respectively. With ROC analyses, 19 and 9 proteins were found with area under the curve greater than 85% using the plasma or serum samples, respectively. Five protein biomarkers with an average of 87.2% sensitivity and 87.4% specificity were similarly identified in these two different cohorts of patients. In addition, four plasma protein biomarkers were found to be significantly associated with high-grade glioma patients’ survival. Immunohistochemistry (IHC) showed that human glioblastoma tissue positively expressed the identified protein biomarkers. Differential expression levels for one of the identified protein biomarkers, MIP 1-alpha, were further investigated using human glioma tissue microarray. Compared to grade II glioma tissues (N=22), MIP 1-alpha was found to be overexpressed in grade III (N=9) and grade IV (N=41) glioma tissues (p &lt; 0.0001). Furthermore, MIP 1-alpha was found to directly promote T98G glioma cell line proliferation and migration (p&lt;0.05) using WST-1 proliferation assay and wound closure assay, respectively. Overall, a blood-based protein signature for high-grade gliomas was identified which may offer a minimally-invasive approach for diagnosing high-grade glioma and monitoring for recurrence or response to therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-211.
Abstract LB-215: Hypoxia inducible factor-1 alpha (HIF-1α) splice variants: Potential prognostic biomarkers in breast cancer
Authors: Gabert Jean A. , Beaufils Nathalie , Formisano-Tréziny Christine , Picard Christophe , Silvy Monique , Giusiano Sophie , Charpin Colette , Pauly Vanessa , Pradel Vincent , Bonnier Pascal , Dales Jean-Philippe 
Published: February 2011

Abstract
Background: Hypoxia-inducible factor-1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. HIF-1 protein is composed of two HIF-1α and HIF-1ß/ARNT subunits. Prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. The impact of HIF-1α alternative splice variants expression on breast cancer prognosis in term of metastasis risk is not well known.
Methods: With real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1α and four variants in breast specimens of a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1α splice variant levels were compared to clinicopathological parameters including tumor microvessel density and metastasis-free survival.
Results: HIF-1α isoforms containing three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1 TAG) and HIF-1 736mRNAs were found expressed at higher levels in estrogen receptor negative carcinomas compared to normal/benign tissues (p=0.009 and p=0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1 TAG mRNA levels (p=0.037). Significant statistical association was found between tumor grade and HIF-1 TAG (p=0.048), and total HIF-1 (p=0.048) mRNA levels. HIF-1 TAGmRNA levels also correlated inversely with both estrogen and progesterone receptor status (p=0.005 and p=0.033 respectively). Univariate analysis showed that high HIF-1 TAG mRNA levels correlated with shortened metastasis free survival (p=0.01).
Conclusion: Our results show for the first time that mRNA expression of HIF-1 TAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-215.
Abstract LB-22: Repression of alpha-, beta- and gamma-catenin genes by SNAI2 in human breast cancer cells
Authors: Mittal Mukul K. , Misra Smita , Bailey Charvann K. , Chaudhuri Gautam 
Published: February 2011

Abstract
SNAI2 is a transcriptional repressor protein implicated in the proliferation and metastasis of several human cancer cells. It binds to the E2-box sequence of its target gene promoters and down regulates their expressions by chromatin remodeling. While studying SNAI2-binding gene promoters in the human breast cells by ChIP-DSL technique, we found that SNAI2 binds to the promoters of the cytoskeleton proteins alpha-, beta- and gamma-catenins. These proteins help cells to maintain their epithelial phenotype and apico-basal polarity. Reduced expression of these proteins has been shown by IHC in high grade metastatic breast carcinoma. Here we report the molecular characterization of this repression. Highly invasive breast cancer cells (MDA-MB-231 and BT-549) express high levels of SNAI2 while mildly invasive (MCF 7 and MDA-MB-468) cells do not express SNAI2. Over-expression of SNAI2 in the SNAI2-negative MCF7 and MDA-MB-468 cells down regulated the mRNA and protein levels of the catenins in these cells. siRNA-mediated knock down of SNAI2 in the SNAI2-positive MDA-MB-231 and BT549 cells elevated the mRNA and protein levels of these proteins in these cells. SNAI2 over-expression induces the invasion and migration in non invasive cells, while down-regulation of the SNAI2 decreases the invasion and migration potential of highly invasive breast cancer cells. Chromatin immunoprecipitation data revealed co-recruitment of CtBP1 and HDAC1 at the catenin gene promoters in the SNAI2-expressing cells further indicating that SNAI2 represses these genes through chromatin remodeling. Our study thus adds to the mode of action of SNAI2 in mediating metastatic conversion of human breast cancer cells. Supported by the DOD-CDMRP IDEA Grant# W81XWH-06-1-0466 and the Susan G. Komen Breast Cancer Foundation grant# BCTR0707627 to GC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-22.
Abstract LB-233: IGF activation in a molecular subclass of hepatocellular carcinoma and preclinical efficacy of IGF-1R blockage
Authors: Tovar Victoria , Alsinet Clara , Villanueva Augusto , Hoshida Yujin , Chiang Derek Y. , Solé Manel , Thung Swan , Moyano Susana , Toffanin Sara , Minguez Beatriz , Cabellos Laia , Peix Judit , Schwartz Myron , Mazzaferro Vincenzo , Bruix Jordi , Llovet Josep M. 
Published: February 2011

Abstract
Background: IGF signaling contributes to proliferation and cell survival through PI3K/AKT and MAPK pathways. It has a relevant role in a variety of human malignancies.
Aims: (1) To analyze the role of IGF signaling in early hepatocellular carcinoma (HCC; BCLC class 0 or A) and (2) To asses the antitumoral activity of IGF pathway targeted therapies.
Methods: An integrative molecular dissection of the axis was performed in a cohort of 104 HCCs, including gene (quantitative PCR and Affymetrix U133 2.0® microarray) and miRNA expression (ligation-mediated amplification method), structural aberrations (Affymetrix STY Mapping Array®) and protein activation (immunohistochemistry). The therapeutic potential of a selective IGF-1R inhibitor, the monoclonal antibody A12, was assessed in vitro through viability and proliferation assays. A xenograft model of HCC was used to evaluate A12 activity in vivo.
Results: Activation of the IGF axis was observed in 21% of early HCCs. Several molecular aberrations were identified, such as overexpression of IGF2 -resulting from reactivation of fetal promoters-, IGFBP3 downregulation and allelic losses of IGF2R (25% of cases). A gene signature defining IGF-1R activation was developed. Overall, activation of IGF signaling in HCC was significantly associated with IGF2 overexpression (p=0.03), mTOR signaling (p=0.035) and was enriched in a molecularly distinct HCC subclass defined through unsupervised hierarchical clustering of the same cohort of samples (Proliferation subclass) (p=0.001). We also found an inverse correlation between IGF activation and miR-100/miR-216 levels (FDR&lt;0.05). In vitro studies showed that A12-induced abrogation of IGF-1R activation and downstream signaling significantly decreased cell viability and proliferation. In vivo, A12 treated mice exhibited delayed tumor growth and prolonged survival in comparison to control mice, a reduction in proliferation rates and induction of apoptosis was observed in treated mice tumoral samples.
Conclusions: Integrative genomic analysis showed enrichment of activation of IGF signaling in the Proliferation subclass of HCC. Effective blockage of IGF signaling with A12 provides the rationale for testing this therapy in clinical trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-233.
Abstract LB-242: Oncosomes: Large bioactive particles secreted by prostate cancer cells
Authors: Vizio Dolores Di , Morello Matteo , McNeish Brendan , Schow Peter , Lisanti Michael P. , Moses Marsha A. , Freeman Michael R. 
Published: February 2011

Abstract
Purpose of the study: Human prostate tumor cells were recently shown by our group to secrete large (0.5-10 m diameter) bioactive microvesicles capable of activating signal transduction and inducing proliferation and migration in cells in the tumor microenvironment (Di Vizio, et al. Cancer Res. 2009 69: 5601-9). These secreted particles, termed oncosomes, were shown to be vehicles for numerous signaling proteins involved in cell growth and motility. They also contain the membrane protein caveolin-1 (Cav-1), a mediator of prostate cancer (PCa) metastasis and a circulating PCa biomarker. The purpose of this study was to develop the tools to identify, isolate, sort and characterize PCa-derived oncosomes.
Experimental procedures: Secreted particles from PCa cells were ultracentrifuged at 100,000xg and the pelleted material processed on a Moflo High-Speed Cell Sorter (Beckman-Coulter) and analyzed using Summit V4.3 software (Dako Colorado, Inc.). 1, 3 and 10 m bead standards (Spherotech Inc.) were used to set size gates. To avoid capturing aggregated material, forward scatter and pulse width were set at a linear scale and only single events were gated and analyzed. Sorted particles were visualized by confocal and electron microscopy.
Results: Using the above procedure, we were able to retrieve intact particles of 1-10 m in diameter secreted by LNCaP cells overexpressing the oncoprotein MyrAkt1. The nontumorigenic prostate stromal cell line WPMY-1 secreted &gt; 10-fold fewer particles in this size range. We confirmed that these were membrane-derived particles by showing that they contained MyrAkt1, which localizes to the plasma membrane. Particles in a similar size range were also sorted after purification from LNCaP cells stably expressing a Cav-1/GFP fusion protein. Sorted particles visualized microscopically appeared to be surrounded by a lipid bilayer and to have intrinsic structure that made them resistant to collapse. Particles isolated by these methods evoked degradation of FITC-labeled collagen and contained active MMP9 and MMP2, two key proteases involved in tumor cell invasion.
Conclusions: The specific type of large bioactive particle we have isolated has not been previously described in any tumor system. Studies are ongoing to detect these particles in animal models of cancer and in human patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-242.