bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3948: Proteome analysis of ovarian cancer cell lines under hypoxic conditon by two-dimensional difference gel electrophoresis (2D-DIGE)
Authors: Kikuchi Ryoko , Iwaya Kei-ichi , Matsubara Osamu 
Published: August 2012

Abstract
The cancer cells which survived hypoxia are known to have aggressive properties and can easily metastasize to other regions, however, the molecular basis of hypoxia-induced changes of cancer cells is not clear. We used a proteomic approach to identify the hypoxia-responsive proteins in 3 ovarian cancer cell lines, KFr13, RMUG-S and ES-2. The cell lines were incubated under lower oxygen concentration (5%) and under normal oxygen concentration (20%) in 48 hours. Even in lower oxygen concentration, the cells survived and increased in number in these 48 hours. The total proteins from the cells were extracted and analysed by 2D-DIGE and MALDI-TOF-MS. We identified the protein, HRP1, whose molecular weight is 71KDa, that all 3 cell lines showed decreased expression under lower oxygen condition compared with normal condition. HRP1 secretion is a growth arrest signal for rat mammary adenocarcionma cells. HRP1 is one of the new candidates for hypoxia-related proteins in ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3948. doi:1538-7445.AM2012-3948
Abstract 3953: Senescence induced of smooth muscel protein 22-alpha (SM22) and Radiation patients change human-link genes expression level
Authors: Kim Myeong Ok , Kim Younjoo , Ko Younmi 
Published: August 2012

Abstract
P53 and RB protein is famous for its capacity to suppress tumor senescence pathway member. Senescence is a leading cause of cancer-related death, considerable uncertainty still remains about their effectiveness. However, each marker in an increased risk that experience genomic data with a cancer-specific mutations. So, senescence marker that techniques can't develop patient-specific treatment for particular about experimental study-conditions and result-analysis. This study was undertaken to evaluate the sm22 (smooth muscel protein 22-alpha) protein relation of senescence marker and changes condition of the radiation at human-link senescence marker genes. We were determined the expression of senescence-associated β-galactosidase and western-blot assay. It was performed in colon cancers that were 17 patients each of normal and adenoma, 16 patients each of normal and adenocarcinoma. To conformed enzyme efficiency is β-galactosidase, senescence pathway using of p16, p21 and p53. On the other hand, sm22 use of senescence marker in study. we have decided to micro-array analysis that 3 patients each of normal and adenoma, 2 patients each of normal and adenocarcinoma, 2 patients each of normal and irradiation-adenocarcinoma (2 weeks after) available miRNA sequences on the Agilent Human whole genome 8x60K array chip. Gene expression levels were calculated with Feature Extraction v10.7.3.1 (Agilent technologies, CA) Relative signal intensities for each gene were generated using the Robust Multi-Array Average algorithm. Senescence induced p16 expression in dependent β-galactosidase assay results, sm22 protein suppressed cellular senescence levels as well as p16 protein. The expression of p16 and sm22 was analyzed that not involved each normals, adenomas and adenocarcinomas tissue by western blot analysis. In addition, it found that these results were similar to those of micro array. The three groups (adenoma, adeno-carcinoma and irradiation-adeno-carcinoma) can be compared in terms of total 2-fold changed gene (least 200% of controls for up-regulated and lower than 50% of controls for down-regulated genes). We found this integrative data analysis tool to the LCN2, LYPD5 and LOC100132051 genes as well as CDKN2 (p16) and TAGLN2 (sm22) gene expression. Irradiation groups was much less than the adenoma (45.3 %) and adenocarcinoma (71.1 %) 2-fold changed gene expression. The LCN2, LYPD5 and LOC100132051 genes lower than adeno-carcinoma group level. Our observations suggest that shared gene and protein expression profiles may contribute to sm22 and p16 of senescence marker, irradiation induces cellular senescence of colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3953. doi:1538-7445.AM2012-3953
Abstract 3954: mTOR inhibitor increases radiation sensitivity in a radiation-resistance cancer cells through induction of cellular senescence
Authors: Nam Hae Yun , Lee Yoon Sun , Lee Hyang Ju , Kwak Jihye , Jung Ji Young , Kim Seong Who , Kim Sang Yoon 
Published: August 2012

Abstract
Autophagy is frequently activated in cancer cells resistant to ionizing radiation and is considered to limit the efficacy of radiotherapy as a prosurvival mechanism. In autophagy signaling, mTOR is an important target for enhancing the therapeutic effect of radiation since inhibiting mTOR limits cell growth and decreases cell proliferation, while increasing autophagy. However, the mode of these actions has remained poorly understood. Here, using radioresistant carcinoma cells, we investigated the mechanism by which the enhanced autophagy flux through the mTOR inhibition overcomes radioresistance of cancer cells subjected to irradiation. AMC-HN-9 cells triggered robust cellular proliferation, and induced cell arrest and autophagy activation in an irradiation dose-dependent manner, showing that adoption of an autophagy mode serves as a survival strategy against radiation. Interestingly, however, the potentiation of radiation-induced autophagy by concomitant inhibition of mTOR activity with mTOR inhibitors (rapamycin or PP242) reduced rather than enhanced cell survival and cell proliferation. Notably, mTOR inhibition in radiation-exposed cells was accompanied by senescence features, including the increased senescence-associated β-galactosidase (SA α-gal) activity and heterochromatin formation and irreversible growth arrest. Stress-induced senescence was associated with suppression of Rb-mediated E2F target genes. The results of this study show that the mTOR-dependent induction of autophagy can maintain a growth-arrested state in radioresistant cancer cells and increase radiosensitivity. It indicates that cellular senescence induced by mTOR inhibitor is a promising interventional strategy for enhancing the therapeutic efficacy in cancer cells refractory to irradiation
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3954. doi:1538-7445.AM2012-3954
Abstract 3955: Overexpression of the 58-kDa microspherule protein (MSP58) triggers cellular senescence via the p53-p21 signaling axis
Authors: Hsu Che-Chia 
Published: August 2012

Abstract
The nucleolar protein 58-kDa microspherule protein (MSP58) is a candidate oncogene implicated in modulating cellular proliferation. In our studies, acute depletion of MSP58 expression using short hairpin (sh)RNA synthesis led to aneuploidy and apoptosis, whereas ectopic expression of MSP58 regulated cell proliferation in a context-dependent manner. Remarkably, ectopic expression of MSP58 in HT1080, NIH3T3, normal human fibroblasts, and mammary epithelial cell lines resulted in induction of premature senescence, caused large and flattened cell morphology, and increased senescence-associated β-galactosidase activity. This phenotype was accompanied by hypophosphorylated Rb, elevation of p53 and p21 protein expressions, activation of p53-mediated transcription, accumulation of phosphorylated forms of ATM/ATR and Chk1/Chk2 kinases, and formation of γH2AX and RPA70 foci, indicating that MSP58 activates the DNA damage response (DDR) and p53/p21 signaling pathways. Furthermore, we identified the SWI/SNF chromatin remodeling subunit, BRG1, as a critical mediator of MSP58-induced senescence. MSP58, BRG1, and p53 form a ternary complex on the p21 promoter, and collaborate to activate p21. This study revealed novel links among MSP58, p53, and cellular senescence in human tumors and normal cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3955. doi:1538-7445.AM2012-3955
Abstract 3958: Multi-Reg: An integrative parallel approach to uncover drivers of cancer
Authors: Akavia Uri David , Danussi Carla , Sanchez-Garcia Felix , Iavarone Antonio , Pe'er Dana 
Published: August 2012

Abstract
Tumor samples harbor a vast number of genomic alterations of various kinds, and it is difficult to distinguish driver alterations that contribute to oncogenesis from passenger alterations. Most computational methods identify driver genes by focusing on the most frequent copy number alterations. Previous work in our lab has led to the development of CONEXIC, a Bayesian algorithm that identifies candidate driver genes in cancer and links them to gene expression signatures they govern by integrating copy number and gene expression (Akavia et al, Cell, 2010). This algorithm was applied to data from melanoma cell lines, where it correctly identified known drivers, such as MITF and KLF6, and connected them to their known targets. In addition, it predicted novel tumor dependencies not previously implicated in melanoma, which were validated experimentally. Drivers may act concurrently, where not only the strongest one is important. For example, either PTEN deletion or AKT activation can lead to a similar expression signature and phenotype. Therefore, we developed a new algorithm, based on the same principles as CONEXIC, with multiple improvements. The new algorithm - Multi-Reg - is capable of detecting multiple candidate regulators that can all act in parallel to regulate an expression signature, and is also capable of integrating mutations in addition to copy number and gene expression data. We applied Multi-Reg to glioblastoma data from The Cancer Genome Atlas (TCGA). This data includes copy number, gene expression and mutations for hundreds of primary tumor samples. Multi-Reg has identified putative drivers that were missed by CONEXIC, such as the known genes PDGFRA and NF1, in addition to EGFR & ERB2 (identified by CONEXIC). Additionally, since Multi-Reg candidate drivers act in parallel, we can group them by shared targets. For example, EGFR & ERRB2 induce the same genes, which represent the Mesenchymal subtype of glibolastoma. These same genes are repressed by PDGFRA & NF1. This matches the known behavior of glioblastoma subtypes, where EGFR & PDGFRA characterize the Mesenchymal and Proneural subtypes, respectively. Thus, our results correctly identify known drivers of glioblastoma. Additionally, Multi-Reg results identified RHPN2 as a novel oncogenic factor controlling a gene expression signature related to adhesion. Validation has shown that while RHPN2 has no effect on cell proliferation it induces invasiveness in glioblastoma cell lines. This shows that Multi-Reg cannot only discover drivers, but can link them to the oncogenic phenomena they controls, and suggest the appropriate biological validation for it.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3958. doi:1538-7445.AM2012-3958
Abstract 3961: Computational modeling of pancreatic cancer reveals growth and dissemination kinetics and suggests optimum treatment strategies
Authors: Haeno Hiroshi , Gonen Mithat , Davis Meghan B. , Herman Joseph M. , Iacobuzio-Donahue Christine A. , Michor Franziska 
Published: August 2012

Abstract
Pancreatic cancer is a leading cause of cancer-related death, largely due to metastatic dissemination. We investigated pancreatic cancer progression by utilizing a mathematical framework of metastasis formation together with comprehensive data of 228 patients, 101 of whom had autopsies. We found that pancreatic cancer growth is initially exponential. After estimating the rates of pancreatic cancer growth and dissemination, we determined that patients likely harbor metastases at diagnosis and predicted the number and size distribution of metastases as well as patient survival. These findings were validated in an independent database. Finally, we analyzed the effects of different treatment modalities, finding that therapies which efficiently reduce the growth rate of cells earlier in the course of treatment appear to be superior to upfront tumor resection. These predictions can be validated in the clinic. Our interdisciplinary approach provides insights into the dynamics of pancreatic cancer metastasis and identifies optimum therapeutic interventions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3961. doi:1538-7445.AM2012-3961
Abstract 3962: Mathematical models for cellular pharmacodynamics of fractionated radiation and radiochemotherapy
Authors: El-Kareh Ardith W. , Jones Leslie Braziel , Secomb Timothy W. 
Published: August 2012

Abstract
Cellular response to radiation is generally described by the linear-quadratic equation, but the extension to complicated fractionated schedules, and to combined exposure with chemotherapeutic drugs is not well-established. Mathematical models for cellular response are needed for predictive quantitative modeling of treatment. Here, such models are formulated using the previously developed concepts of peak damage models and additive damage, which in prior studies proved successful in describing cellular pharmacodynamics of single-agent and combination chemotherapy. The exponential form of the linear-quadratic equation is replaced by Hill or cumulative lognormal functions of the peak value over time of a quantity termed “cellular damage.” Damage is a saturating function of radiation dose. Cell survival depends on whether the peak value of cellular damage ever exceeds a threshold value during treatment. This model is tested for a range of data sets for single-dose radiation, and compares favorably with the linear-quadratic. In one data set (Park et al 2008) the dose range was sufficiently wide to show the significant overestimation of cell kill by the linear-quadratic model at high doses; the Hill/lognormal formulation behaves more satisfactorily in this limit. The model is then extended to the case of fractionated radiation through the assumption that damage decays between treatments according to first-order kinetics, and damage from different cycles is additive. The model gives a satisfactory fit to literature data with multiple fractionation schedules for the same drug and cell line. Finally, the principle of additive damage is applied to model cellular response to radiochemotherapy, with damage as a linear superposition of terms from radiation and drug. Overall, the peak cellular damage model with additive damage was found to fit in vitro dose-response data well, and provides a tool for understanding and predicting response as schedule and dose are varied in combination treatments. It is expected that these models will have application in assessment of preclinical cellular pharmacodynamics data, as well as computational simulations of treatment response.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3962. doi:1538-7445.AM2012-3962
Abstract 3964: Inference of robust tumor phylogenetic markers from multi-sample data
Authors: Subramanian Ayshwarya , Schwartz Russell , Shackney Stanley 
Published: August 2012

Abstract
Computational cancer phylogenetics can play an important role in delineating possible tumor progression pathways and identifying molecular subtypes and mechanisms of action. We previously developed a pipeline for constructing tumor phylogenies from recurring cell types computationally inferred from whole genome copy number data. The accuracy and detail of these tumor phylogenies, however, depends on the identification of accurate and high-resolution molecular markers of progression, i.e., reproducible regions of copy number variation that can be used to robustly differentiate different subtypes and stages of progression. Here we present a new method for the problem using hidden Markov models (HMMs) to derive robust, high resolution progression markers from sets of tumor samples. We demonstrate our method on a publicly available array comparative genome hybridization (aCGH) dataset (NCBI GEO GSE16672, Navin et al., 2010) from sectioned primary ductal breast tumors. Our method uses an HMM, a class of probabilistic models, to classify sets of aCGH data into a partitioning of samples into normal (diploid) or amplified at each copy number probe. It differs from other similar HMM methods primarily in seeking a parsimonious set of combinations of amplification states able to explain all aCGH profiles simultaneously in order to identify robust markers of progression across samples. The model learns frequencies with which different combinations of amplifications are observed across the samples by modeling individual probes as Gaussian random variables with either normal or tetraploid means, with data more consistent with tetraploid being classified as amplified and those more consistent with diploid classified as normal. To handle a combinatorial explosion in combinations of amplification states with increasing numbers of samples, the method introduces a Gibbs sampling algorithm to learn a parsimonious model of the most frequently occurring combinations of amplification states. We applied our methods to a previously constructed set of inferred cell types derived from the Navin et al. data (Tolliver et al., 2010) and to a comparison set of 9 random samples from the raw aCGH data. We validated our model relative to manual labeling of amplicons on the same data. In both experiments, the HMM method was able to pick up significantly larger numbers of robustly amplified segments per chromosome than did prior methods or manual analysis. The resulting segments can be directly fed into downstream analysis routines for phylogeny inference or other predictions. In future work, the HMM method may be improved by fine-tuning the underlying model for copy number variation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3964. doi:1538-7445.AM2012-3964
Abstract 425: Targeting embryonic signaling pathways in melanoma
Authors: OReilly Kathryn E. , Poliseno Laura , de Miera Eleazar Vega-Saenz , Friedman Erica , Hernando Eva , Osman Iman 
Published: August 2012

Abstract
Melanoma incidence is quickly rising and the average survival for a patient with metastatic disease is less than one year. Novel targeted therapies, such as B-Raf mutant kinase inhibitors, have shown dramatic initial responses, but resistance to single agent therapy inevitably ensues. We hypothesize that melanoma stem-like cells may be important in melanoma progression and may play a role in chemoresistance to targeted therapy. We have profiled melanoma cell lines as well as metastatic melanoma tissue for activation of embryonic stem cell pathways via microarray and quantitative RT-PCR. We observed upregulation of the Hedgehog pathway in a subset of cell lines and in human melanoma tissue and found that Smoothened (SMO) expression was associated with significantly shorter recurrence-free survival in metastatic melanoma patients. We also found that small molecule inhibition or genetic silencing of Smoothened (SMO) decreased melanoma cell proliferation and migration in vitro and identified overexpression of GLI2 as a marker of resistance to SMO inhibition. These findings suggest that inhibitors of hedgehog pathway signaling, already in clinical trials in other tumor types, may be a novel strategy for advanced melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 425. doi:1538-7445.AM2012-425
Abstract 4252: Activated ALK collaborates with MYCN in neuroblastoma pathogenesis
Authors: Zhu Shizhen , Lee Jeong-Soo , Guo Feng , Shin Jimann , Perez-Atayde Antonio R. , Kutok Jeffery L. , Rodig Scott J. , Neuberg Donna S. , Helman Daniel , Feng Hui , Stewart Rodney A. , Wang Wenchao , George Rani E. , Kanki John , Look A Thomas 
Published: August 2012

Abstract
Neuroblastoma is a developmental tumor that arises in the peripheral sympathetic nervous system and accounts for 10% of all cancer-related deaths in children. The anaplastic lymphoma kinase (ALK) gene is mutationally activated in a subset of primary neuroblastomas, including those with MYCN gene amplification, suggesting pathogenic cooperation. Because the mechanism underlying this cooperation is unclear, we generated a novel transgenic zebrafish model that overexpresses human MYCN and activated ALK in the peripheral sympathetic nervous system to analyze their interaction. The expression of MYCN in this model induces neuroblastomas in the inter-renal gland, the zebrafish analogue of the adrenal medulla, which is the site of origin observed in approximately half of childhood neuroblastomas. Furthermore, the tumors resemble human neuroblastomas histologically, immunohistochemically and ultrastructurally. Concomitant expression of activated ALK with MYCN in this model profoundly accelerates the onset of neuroblastoma and markedly increases disease penetrance. Detailed in vivo analyses show that MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts. Taken together, these findings provide a mechanism for the synergistic interplay of MYCN with activated ALK in neuroblastoma pathogenesis and demonstrate the utility of the zebrafish model in understanding human disease processes that may aid the development of improved therapeutic strategies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4252. doi:1538-7445.AM2012-4252