bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C18: Interpreting the cancer genome using the Mouse Tumor Biology (MTB) Database
Authors: Krupke Debra M. , Begley Dale A. , Neuhauser Steven B. , Richardson Joel E. , Sundberg John P. , Bult Carol J. , Eppig Janan T. 
Published: August 2014

Abstract
For over a century cancer biologists have utilized the laboratory mouse in the study of cancer biology. Many mouse models recapitulate the genetic abnormalities observed in human cancers. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) provides multiple tools to explore and interpret the cancer genome. These tools include the ability to search MTB using mouse or human gene symbols, a mouse cancer quantitative trait loci (QTL) viewer, links to gene expression data for a variety of mouse models of human cancer, and access to public genomic data from the emerging Jackson Laboratory (JAX; http://www.jax.org) Patient-Derived Xenograft (PDX) program.
MTB was established in 1997 and provides freely available access to data on spontaneous and induced tumors from genetically defined mice (inbred, hybrid, mutant, and genetically engineered strains). These data include standardized tumor names and classifications, pathology reports and images, mouse genes and QTL associated with cancers, genomic and cytogenetic changes occurring in the tumor, strain names, tumor frequency and latency, and literature citations. Although the primary source for data represented in MTB is peer-reviewed scientific literature an increasing amount of data are derived from large systematic programs (e.g. JAX Aging Resource, PDX Program) and laboratory or consortia contributions. MTB includes annotated histopathology images and cytogenetic assay images for mouse tumors where these data are available. MTB encourages direct submission of mouse tumor data and images from the cancer research community and provides investigators with a web-accessible tool for image submission and annotation.
MTB is supported by NCI grant CA089713.
Citation Format: Debra M. Krupke, Dale A. Begley, Steven B. Neuhauser, Joel E. Richardson, John P. Sundberg, Carol J. Bult, Janan T. Eppig. Interpreting the cancer genome using the Mouse Tumor Biology (MTB) Database. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C18.
Abstract C31: Characterization of malignant melanoma growth triggered by the brain microenvironment in experimental metastasis models
Authors: Nygaard Vigdis , Prasmickaite Lina , Vasiliauskaite Kotryna , Clancy Trevor , Hovig Eivind 
Published: August 2014

Abstract
Melanomas are particularly renowned for their plasticity in response to microenvironmental signals. The brain offers a unique microenvironment to which malignant melanoma frequently spreads leading to dismal prognosis for the patients. The aim of our study was to reveal characteristics of metastatic growth of melanoma in the brain by in vivo imaging, cellular characterization and molecular approaches. The study was based on experimental metastasis models in vivo established from the melanoma cell lines, Melmet 1 and Melmet 5 with opposing phenotypes (invasive/proliferative, respectively) in the in vitro setting and distinct metastatic patterns in vivo. Gene expression profiling of brain metastatic cells isolated from different growth phases revealed the dynamic and opportunistic nature of melanoma in this context. We detected transitioning from the invasive phenotype to the proliferative phenotype, as the brain metastases passed from early to late growth phase. We also identified the existence of a neuron-like phenotype which included synaptic characteristics and a neurotransmission-like circuit involving glutamate receptors. This brain-adaptive phenotype was more prominent in the earlier metastatic growth phases compared to a later phase. To uncover microenvironmental factors that could play a role in melanoma cell colonization of the brain, we analyzed gene expression in host stroma. Genes implicated in immune-/inflammatory-responses were up-regulated and cellular characterization of metastatic brain tissue revealed the emergence and accumulation of cells of bone-marrow origin like microglia (F4/80+, CD11b+) that correlated with “active growth” phase initiation. Altogether, this suggests that acquisition of the brain-adaptive phenotype in a cooperative inflammatory environment might be critical for the establishment of metastatic growth in the brain microenvironment. Global network modeling and functional annotation analysis revealed that several of the central molecular factors and pathways mediating melanoma brain metastasis in this study, are also central to other pathological diseases, in particular neurodegenerative diseases. The identification of essential molecular networks that operate to promote the brain-adaptive phenotype is of clinical relevance, as they represent leads to urgently needed therapeutic targets.
Citation Format: Vigdis Nygaard, Lina Prasmickaite, Kotryna Vasiliauskaite, Trevor Clancy, Eivind Hovig. Characterization of malignant melanoma growth triggered by the brain microenvironment in experimental metastasis models. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C31.
Abstract C40: Amyloid precursor protein (APP) synchronizes cell cycle progression and the rate of global protein synthesis in dividing cells
Authors: Sobol Anna , Galluzzo Paola , Liang Shuang , Rambo Brittany , Skucha Sylvia , Weber Megan , Bocchetta Maurizio 
Published: August 2014

Abstract
In previous studies we targeted hypoxic Non-Small Cell Lung Cancer (NSCLC) tumor tissue using gamma-secretase inhibitors (GSI) in a preclinical model of advanced NSCLC. GSI treatment of mice suggested reactivation of mTORC-1 in otherwise quiescent hypoxic NSCLC tissue.
Methods included immunohistochemistry and cytochemistry, immunoblotting, immunoprecipitation, siRNA-mediated gene knockdown, nucleotide and amino acid analogs incorporation, FACS analysis, various imaging techniques, Q-PCR, gene transfection, cap binding assays, RNA and antibodies arrays.
GSI treatment of mice showed a re-induced phosphorylation of 4E-BP1 at T37/46 in hypoxic tumor masses. In vitro studies indicated a role for APP in this phenomenon. APP downregulation caused a rearrangement in 4E-BP1's phosphorylation pattern at residues T37/46, S65 and T70, reversed by overexpression of the APP C-terminal domain. Increased recruitment of eIF4A on the mRNA cap was observed. These events coincided with a drastic increase in the rate of global protein synthesis, an event that appeared to be mTOR-independent.
Meanwhile, NSCLC cells with depleted APP were arrested in G0/G1 through a cyclin C-mediated mechanism. Cells arrested in G0/G1 with augmented rate of global protein synthesis (both cap- and IRES-dependent) increased their size and underwent a substantial necrotic cell death due to cell membrane permeabilization.
These results indicate a novel role for APP in synchronizing the rate of protein synthesis and cell cycle progression, raising questions on how these processes interact in malignant transformation.
The data presented here suggest that cells of different origin, including NSCLC cells, have developed some mechanisms to couple cell growth with cell cycle progression independent of overlapping signals which derive, among others, from the PI3-K pathway. APP seems to play a central role in this synchronization, and its loss of function causes cell size abnormalities and death.
Citation Format: Anna Sobol, Paola Galluzzo, Shuang Liang, Brittany Rambo, Sylvia Skucha, Megan Weber, Maurizio Bocchetta. Amyloid precursor protein (APP) synchronizes cell cycle progression and the rate of global protein synthesis in dividing cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C40.
Abstract C46: The pharmacokinetics and pharmacodynamics study of honokiol in Sprague-Dawley rats and colorectal tumor-bearing mice
Authors: Tsai Yung-Jen , Tsai Pei-Yi , Hung Le-Mei , Su Mei-Yin , Lin Min-Hui , Kuan Lung-Yu , Tsai Yih-Chiao , Chen Hui-Ling , Chang Jia-Ming 
Published: August 2014

Abstract
Honokiol, a small-molecule pharmacological bioactive constituent of the bark of Magnolia plants, has shown anti-tumor effect in a variety of human cancer xenograft models through the induction of apoptosis. Additionally, honokiol could enhance the cytotoxicity in combination of oxaliplatin in colon cancer cells.
To investigate the anti-tumor effect and the pharmacokinetics (PK) of honokiol, honokiol was tested for anti-tumor activity in a colorectal cancer xenograft mice model and oral-bioavailability of honokiol was assayed in Sprague-Dawley rats.
The pharmacokinetic results of 5.0 mg/kg honokiol after intravenous injection showed that the elimination half time was about 0.79 ± 0.03 hours, the Cmax was about 752.67 ± 58.36 ng/mL, and the mean residence time (MRT) was about 0.85 ± 0.05 hours.
In vivo study for testing anti-cancer activity of honokiol is underwent and expected that honokiol would inhibit the tumor growth in colorectal tumor-bearing mice. In conclusion, honokiol may be developed be as therapeutic agent for cancer treatment in combination with PK and pharmacodynamics (PD) data.
Citation Format: Yung-Jen Tsai, Pei-Yi Tsai, Le-Mei Hung, Mei-Yin Su, Min-Hui Lin, Lung-Yu Kuan, Yih-Chiao Tsai, Hui-Ling Chen, Jia-Ming Chang. The pharmacokinetics and pharmacodynamics study of honokiol in Sprague-Dawley rats and colorectal tumor-bearing mice. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C46.
Abstract C52: Induction of homologous recombination by DNA nicks
Authors: Vriend Lianne E.M. , Krawczyk Przemek M. , Jasin Maria 
Published: August 2014

Abstract
Homologous recombination (HR) is a major mechanism of DNA repair, such that mutations in HR genes are associated with tumor susceptibility. We have used a recently adapted system for genome engineering to study HR mechanisms in mammalian cells. Clustered regularly-interspaced short palindromic repeats (CRISPR) are prokaryotic adaptive immune systems that specifically cleave nucleic acids of invading pathogens. The effector phase of CRISPR system in Staphylococcus pyogenes consists of two main components, the endonuclease Cas9 and RNA strands that dictate the recognition sequence cleaved by Cas9. The activity of Cas9 resides in 2 nucleolytic domains, HNH-like and RuvC1-like, such that mutating the active site of either of these domains turns Cas9 into a DNA nicking enzyme.
Here we applied the commonly used DR-GFP HR reporter to investigate the repair of both DNA double-strand breaks (DSBs) and nicks induced by Cas9 in human cells. We show that a DSB, introduced by wild-type (wt) Cas9 and a guide RNA (gRNA) directed to the I-SceI site of the DR-GFP reporter, induces HR at levels similar to the I-SceI endonuclease, demonstrating the robustness of the system and confirming the potential of the CRISPR system as a genome engineering tool. Cas9 with mutations in either of the nucleolytic domains also stimulates HR, albeit at much lower levels, suggesting that a nick can also be repaired by HR. Stimulation of HR by DNA nicks is not reduced by PARP inhibition and has the same genetic requirements as DSB-induced HR. Given that SSBs are induced by endogenous DNA metabolic processes as well as by many anti-cancer treatments, our results may advance the understanding of mechanisms responsible for repair of these abundant DNA lesions.
Citation Format: Lianne E.M. Vriend, Przemek M. Krawczyk, Maria Jasin. Induction of homologous recombination by DNA nicks. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C52.
Abstract C55: Investigating mechanisms of gastrointestinal polyposis and osteoblastic tumor formation induced by mesenchymal Lkb1 deficiency
Authors: Laajanen Kaisa , Ollila Saara , Wong Iris PL , Vaahtomeri Kari , Leone Gustavo , Viollet Benoit , Tomi Makela P. 
Published: August 2014

Abstract
Lkb1 has emerged as an important tumor suppressor gene in both sporadic and hereditary cancer. Inactivating germline mutations in the LKB1 gene underlie familial Peutz-Jeghers Syndrome (PJS), a cancer-prone disorder characterized by predisposition to gastrointestinal polyposis. Targeted disruption of Lkb1 in mesenchymal smooth muscle cells was sufficient to recapitulate PJS-type polyposis in mice (Katajisto et al, 2008) and Lkb1 heterozygous mice develop osteoblastic tumors (Robinson et al, 2008). To investigate the mechanism(s) by which Lkb1 loss in mesenchymal tissues drives tumorigenesis, we deleted Lkb1 using two mesenchymal deletors (Fsp1-Cre and Twist2-Cre) expressed in mesenchymal progenitors. Heterozygous deletion of Lkb1 with either Fsp1-Cre (Lkb1flox/+;Fsp1-Cre) or Twist2-Cre (Lkb1flox/+;Twist2-Cre) results in both polyposis and osteoblastic tumor. Homozygous Lkb1 deletion using Fsp1-Cre (Lkb1flox/flox;Fsp1-Cre) leads to rapid polyposis and osteoblastic tumors with complete penetrance, indicating that complete loss of Lkb1 is advantageous for tumorigenesis. AMPK, a key substrate of Lkb1 connected to several other tumor suppressors, has been proposed to mediate Lkb1 tumor suppressive function. However, homozygous deletion of both AMPKα1 and AMPKα2 using Fsp1-Cre does not lead to tumorigenesis. These results implicate other Lkb1 substrate kinases in tumor suppression and suggest Lkb1 loss in a common progenitor underlies mesenchymal tumorigenesis.
Katajisto P, et al., (2008) LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis. Nat Genet, 40(4): p. 455-9
Robinson J, et al., (2008) Osteogenic tumours in Lkb1-deficient mice. Exp Mol Pathol, 85(3): p. 223-6
Citation Format: Kaisa Laajanen, Saara Ollila, Iris PL Wong, Kari Vaahtomeri, Gustavo Leone, Benoit Viollet, Makela P. Tomi. Investigating mechanisms of gastrointestinal polyposis and osteoblastic tumor formation induced by mesenchymal Lkb1 deficiency. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C55.
Abstract C58: The transglutaminase 2 (TG2) as a new target of p53
Authors: Yeo Shi Yun 
Published: August 2014

Abstract
The transglutaminase type 2 (TG2) is a multifunctional protein that has been found previously to be upregulated in lung and breast cancer cells in response to DNA damage. Since the tumor suppressor p53 stabilizes and accumulates in the nucleus upon DNA damage, we investigated the relationship of TG2 and p53 in this study. We demonstrated that TG2 is a downstream target of p53. Knockdown of p53 down-regulated the expression of TG2 mRNA and protein. Similarly, over-expression of p53 upregulated the level of TG2 under normal cell culture condition and also with doxorubicin treatment. More importantly, we found that loss of TG2 enables the transformation of primary mammary epithelial cells in a sensitized colony forming assay. In this system, we used primary human mammary epithelial cells (HMECs) that over-express hTERT, SV40 Small T and RasV12; these cells depend only on the loss of p53 activity for full transformation. Interestingly, we observed a synergy in colony formation when both p21 and TG2 were knock-down, and this effect is even more pronounced when there is a deprivation of growth factors. We discovered that insulin and EGF can overcome the effects of p53 in colony formation and the combined loss of TG2 and p21 can replace the absence of insulin in the transformation of HMECs, similar to that of p53 knock-down. This suggests that loss of TG2 potentiates insulin signaling that could be important in cell transformation. Indeed, we showed that loss of TG2 increase the phosphorylation of 4EBP1 at Thr37/46. Our findings indicate that TG2 functions like a tumor suppressor and is an important target of p53. The loss of TG2 results in cell transformation by mimicking insulin signaling.
Citation Format: Shi Yun Yeo. The transglutaminase 2 (TG2) as a new target of p53. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C58.
Abstract C59: Estradiol and mTORC2 orchestrate to enhance prostaglandin biosynthesis andtumorigenesis in tuberous sclerosis complex
Authors: Li Chenggang , Lee Po-Shun , Gu Xiaoxiao , Sun Yang , Zhang Erik , Csibi Alfredo , Li Jing , Priolo Carmen , Guo Yanan , Wu Chin-Lee , Blenis John , Xu Kai-Feng , Henske Elizabeth Petri , Levy Bruce , Kwiatkowski David , Yu Jane J. 
Published: August 2014

Abstract
Lymphangioleiomyomatosis (LAM) is a female predominant progressive and neoplastic disorder that leads to lung destruction and respiratory failure primarily in women. LAM is typically due to TSC2 mutations resulting in mTORC1 activation in proliferative smooth muscle-like cells in the lung. The female predominance of LAM suggests that estradiol contributes to disease development. Metabolomic profiling identified estradiol-enhanced prostaglandin biosynthesis signature in Tsc2-deficient cells, both in vitro and in vivo. Estradiol increased the expression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin biosynthesis, which was increased at baseline in TSC2-deficient cells, and was not affected by rapamycin treatment, but decreased by Torin 1 treatment and Rictor knockdown, associated with reduction of levels phospho-Akt (S473). Prostaglandin production was also increased in TSC2-deficient cells. In preclinical models, Celecoxib or aspirin treatment suppressed tumor progression. LAM patients had significantly higher
serum prostaglandin levels than healthy women. 15-epi-lipoxin-A4 was identified in exhaled breath condensate from LAM subjects and was increased by aspirin treatment, indicative of functional COX-2 expression in the LAM airway. Targeting COX-2 and prostaglandin pathways may have therapeutic value in LAM and TSC-related diseases, and possibly in other conditions associated with mTOR-hyperactivation.
Citation Format: Chenggang Li, Po-Shun Lee, Xiaoxiao Gu, Yang Sun, Erik Zhang, Alfredo Csibi, Jing Li, Carmen Priolo, Yanan Guo, Chin-Lee Wu, John Blenis, Kai-Feng Xu, Elizabeth Petri Henske, Bruce Levy, David Kwiatkowski, Jane J. Yu. Estradiol and mTORC2 orchestrate to enhance prostaglandin biosynthesis andtumorigenesis in tuberous sclerosis complex. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C59.
Abstract C66: MUC1-C oncoprotein induces aldehyde dehydrogenase expression and activity in breast cancer cells
Authors: Ahmad Rehan , Alam Maroof , Rajabi Hasan , Kharbanda Akriti , Kufe Donald 
Published: August 2014

Abstract
Aldehyde dehydrogenase 1A1 (ALDH1A1) activity is used as a marker of breast cancer stem cells; however, little is known about the regulation of ALDH1A1 expression. Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly overexpressed in about 90% of human breast cancers. The present studies have been performed on breast cancer cells that were stably silenced for MUC1 expression or overexpress the oncogenic MUC1-C subunit. We demonstrate that MUC1-C is sufficient for induction of MEK-ERK signaling and that treatment with a MUC1-C inhibitor suppresses ERK activation. In turn, MUC1-C induces ERK-mediated phosphorylation and activation of the CCAAT/enhancer-binding protein β (C/EBPβ) transcription factor. The results further show that MUC1-C and C/EBPβ form a complex on the ALDH1A1 gene promoter and activate ALDH1A1 gene transcription. Importantly, MUC1-C-induced upregulation of ALDH1A1 expression is associated with marked increases in ALDH activity as detected by the aldefluor assay. These findings demonstrate that MUC1-C (i) activates a previously unrecognized ERK-C/EBPβ-ALDH1A1 pathway, and (ii) promotes the induction of ALDH activity in breast cancer cells.
Note: This abstract was not presented at the conference.
Citation Format: Rehan Ahmad, Maroof Alam, Hasan Rajabi, Akriti Kharbanda, Donald Kufe. MUC1-C oncoprotein induces aldehyde dehydrogenase expression and activity in breast cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C66.
Abstract IA18: Activities of wild-type and mutant p53
Authors: Vousden Karen H. 
Published: August 2014

Abstract
The p53 tumor suppressor protein restrains malignant progression through a number of mechanisms, and most cancers show loss of the normal functions of p53. In many cancers this is due to mutations in the p53 gene, leading to the expression of mutant p53 proteins that have lost wild type activity and acquired an oncogenic function that can promote metastasis. We have found that mutant p53 can promote the activation of integrin and cell surface receptor trafficking that depends on Rab-coupling protein (RCP) and which results in constitutive activation of signaling though the EGFR, MET and integrin. Simultaneous loss of p53 and p63 recapitulates the phenotype of mutant p53 both in cells and in vivo, and this function of mutant p53 reflects, at least in part, the inhibition of the p53 family member p63 . Interestingly, the tumor-associated point mutations induce conformational instability of the p53 protein, and the misfolding of p53 correlates with loss of wild type and gain of mutant activity. We have found that folding of wild type p53 is promoted by an interaction with the chaperonin CCT. Intriguingly, p53 proteins mutated to prevent the interaction with CCT show conformational instability, and acquire an ability to promote invasion and random motility that is similar to the activity of tumor derived p53 mutants. Our data therefore suggest that both growth suppression and cell invasion may be differentially regulated functions of wild type p53.
Citation Format: Karen H. Vousden. Activities of wild-type and mutant p53. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr IA18.