bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 358: Nf1 inactivation in NG2-cells is not sufficient for murine optic glioma formation.
Authors: Solga Anne C. , Gianino Scott M. , Gutmann David H. 
Published: August 2014

Abstract
Individuals with the tumor predisposition syndrome, neurofibromatosis 1 (NF1), are prone to development of low-grade astrocytomas (gliomas). These tumors frequently include optic pathway gliomas predominantly arising in young children. We have previously developed several Nf1 genetically-engineered mouse (GEM) strains that form optic gliomas similar to those that occur in children with NF1. However, in the optic nerve, there are two types of potential neuroglial progenitors, GFAP+ and NG2+ cells. This latter population has been shown to represent a potential cell of origin for rat malignant gliomas, suggesting that NG2+ progenitors may represent the initiating cell for Nf1 optic glioma. In this study, we employed a complementary series of in vitro and in vivo approaches to determine whether NG2+ cells could give rise to Nf1 optic glioma. First, we demonstrate that Nf1 loss in NG2+ cells does not increase glial cell proliferation in vitro. Second, NG2-Cre-expressing cells give rise to all three macroglial lineages (astrocytes, NG2+ cells, and oligodendrocytes) in vivo, similar to GFAP-Cre-expressing cells that drive Nf1 optic glioma formation. Third, in striking contrast to the GFAP-Cre strain, Nf1 loss in NG2+ progenitor cells in vivo is insufficient for optic gliomagenesis. Together, these data exclude NG2+ cells as the likely cell of origin for NF1-associated optic glioma and establish a model of gliomagenesis in which Nf1 loss occurs in specific neuroglial progenitors during embryonic development.
Citation Format: Anne C. Solga, Scott M. Gianino, David H. Gutmann. Nf1 inactivation in NG2-cells is not sufficient for murine optic glioma formation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 358. doi:10.1158/1538-7445.AM2013-358
Abstract 3581: Impact of Nrf2 on the development of ethyl carbamate/ butylated hydroxytoluene-induced lung tumorigenesis in mice.
Authors: Wu Tien-Yuan , Khor Tin Oo , Cheung Ka-Lung , Kong Ah-Ng 
Published: August 2014

Abstract
Chronic inflammation has been linked to the development of various types of cancers and has been recently recognized as the seventh hallmark of cancer. Accumulating evidence suggests that Nrf2 plays a pivotal role in protection against oxidative tissue damage and inflammation. Previous findings from ours as well as other laboratories have demonstrated that Nrf2 possesses the protection effects in the inflammation-associated carcinogenesis in preclinical models. The aim of the present study is to investigate the role of Nrf2 in butylated hydroxytoluene (BHT)-induced pulmonary inflammation and BHT-urethane/ethyl carbamate (EC) induced two-stage lung carcinogenesis. Nrf2 deficient mice showed an increased susceptibility to BHT-induced pulmonary inflammation, whereas Nrf2 WT mice have higher antioxidant proteins level and lower pro-inflammatory markers. Although lung inflammation was slightly more severe in Nrf2KO mice as compared to their wildtype counterpart, the tumor incidence and tumor multiplicity were found to be significantly lower in Nrf2KO mice treated with EC-BHT. Tumor multiplicity was also lower in Nrf2KO mice treated with EC alone. In summary, on one hand, Nrf2 is required to dampen inflammation, but Nrf2 may be disadvantage in EC or BHT-EC mediated lung tumorigenesis.
Citation Format: Tien-Yuan Wu, Tin Oo Khor, Ka-Lung Cheung, Ah-Ng Kong. Impact of Nrf2 on the development of ethyl carbamate/ butylated hydroxytoluene-induced lung tumorigenesis in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3581. doi:10.1158/1538-7445.AM2013-3581
Abstract 3584: Ethanol and aging promote pathogenesis of hepatocellular carcinoma in mice.
Authors: George Joseph , Tsuchishima Mutsumi , Toshikuni Nobuyuki , Saito Takashi , Tsutsumi Mikihiro 
Published: August 2014

Abstract
Background & Aims: Chronic intake of alcohol increases the risk of gastrointestinal and hepatic carcinogenesis. The present study was focused to investigate the incidence and mechanism of pathogenesis of hepatocellular carcinoma (HCC) during aging and chronic ingestion of alcohol without any additional hepatic injury.
Methods: Ethanol was administered to ICR male mice through drinking water for 70 weeks at concentrations of 5% (first week), 10% (next 8 weeks), and 15% thereafter. The animals were sacrificed at 60 weeks and 70 weeks, the livers were examined for hepatic tumors, and evaluated for foci of cellular alteration. Immunohistochemical staining was performed in the liver sections for cytochrome P4502E1 (CYP2E1), 4-hydroxy-nonenal, and proto-oncogene, c-Myc
Results: At 60th week, 40% of mice in the ethanol group had visible white nodules (5-10 mm) in the liver, but not in control mice. At 70th week, several larger nodules (5-22 mm) were present in the livers of 50% mice in ethanol group. In control group, one mouse developed a single nodule. All nodules were histologically trabecular HCC composed of eosinophilic and vacuolated cells. In the livers of both control and ethanol group, several foci with cellular alteration were present, which were significantly higher in ethanol group. Staining for CYP2E1, 4-hydroxy-nonenal and c-Myc depicted marked upregulation of all these molecules in the foci of cellular alteration.
Conclusions: Our data demonstrated that upregulation of CYP2E1 and subsequent production of reactive oxygen species along with the persistent expression of c-Myc play a significant role in the pathogenesis of HCC during chronic ingestion of ethanol. Furthermore, aging is also a risk factor for development of HCC.
* Presenting author
Citation Format: Joseph George, Mutsumi Tsuchishima, Nobuyuki Toshikuni, Takashi Saito, Mikihiro Tsutsumi. Ethanol and aging promote pathogenesis of hepatocellular carcinoma in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3584. doi:10.1158/1538-7445.AM2013-3584
Abstract 3586: Benzopyrene diol epoxide attenuates p34cdc2 and inhibits cell growth: role of p53.
Authors: Mukherjee Jagat J. , Kumar Subodh 
Published: August 2014

Abstract
Our previous findings demonstrated that DNA damage by polynuclear aromatic hydrocarbons (PAHs) triggers cellular protective response of cell growth inhibition (G1-S cell cycle arrest and inhibition of DNA synthesis) in human fibroblast associated with accumulation of p53 protein, a known cell growth inhibitory transcription factor. Here we report that in different cell lines BPDE treatment (ultimate carcinogenic metabolite of the PAH benzo[a]pyrene) triggers variable extent of cell growth inhibition which do not correspond to the extent of increased p53 accumulation as we observed. We also observed that BPDE treatment of cells significantly down-regulates expression of p34cdc2, a known cell cycle activating protein. Although the role of cdc2 down-regulation in inhibition of cell cycle progression is well known, to the best of our knowledge cdc2 down-regulation in response to cellular insult by PAHs has not been reported. Unlike p53 accumulation there is correspondence between extent of cell growth inhibition and the extent of cdc2 down-regulation by BPDE in different cell lines. Interestingly, BPDE-induced cdc2 down-regulation is observed to be p53 dependent although there is lack of correspondence between the extent of p53 accumulation and cdc2 down-regulation. However, extent of BPDE induced cdc2 down-regulation was observed to have correspondence with the extent of accumulation of cell cycle inhibitor protein p21 (transactivation product of p53) in different cell lines. These findings may have an implication that cell growth inhibition in response to DNA damaging PAHs may involve down-regulation of cdc2 protein mediated by p53 activation (transactivation ability), and the extent of p53 accumulation is not the determining factor in this regard.
Citation Format: Jagat J. Mukherjee, Subodh Kumar. Benzopyrene diol epoxide attenuates p34cdc2 and inhibits cell growth: role of p53. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3586. doi:10.1158/1538-7445.AM2013-3586
Abstract 3588: Common and different effects induced in primary human mesothelial cells and mice exposed to chrysotile or crocidolite asbestos.
Authors: Qi Fang , Okimoto Gordon , Jube Sandro , Pass Harvey I. , Laczko Rozalia , DeMay Richard M. , Khan Ghazal , Tiirikainen Maarit , Yang Haining , Gaudino Giovanni , Carbone Michele 
Published: August 2014

Abstract
Crocidolite is considered the most oncogenic asbestos type. Chrysotile accounts for &gt;90% of asbestos used worldwide, however its capacity to induce MM is still debated. We linked crocidolite carcinogenesis to the release of High-Mobility Group Box-1 protein (HMGB1) and activation of downstream genes (TNF-α and NF-κB). We compared the carcinogenicity of crocidolite and chrysotile in primary human mesothelial cells (HM). Microarray analyses of HM exposed to crocidolite or chrysotile identified 57 genes that were significantly induced or repressed. Forty-eight hours after exposure we observed induction of HMGB1 and NF-κB targeted genes and E-cadherin and SFRP4 down-regulation. In vitro, both crocidolite and chrysotile induced HMGB1 and TNF-α secretion, induced β-catenin nuclear translocation and caused HM death and epithelial-mesenchymal transition in surviving cells. Five weeks from exposure these effects were sustained in HM exposed to crocidolite; the expression of these genes had returned to normal in HM exposed to chrysotile. Soon after injection, serum HMGB1 levels were elevated in mice injected with either crocidolite or chrysotile, and remained elevated 10 weeks post-injection only in mice injected with crocidolite. Our results show that chrysotile induces the same intracellular signaling elicited by crocidolite, however these effects are transient. Accordingly, HM exposure to chrysotile in the presence of TNF-α or in co-culture with macrophages, induced foci formation with a lower transforming efficiency compared to crocidolite.
Citation Format: Fang Qi, Gordon Okimoto, Sandro Jube, Harvey I. Pass, Rozalia Laczko, Richard M. DeMay, Ghazal Khan, Maarit Tiirikainen, Haining Yang, Giovanni Gaudino, Michele Carbone. Common and different effects induced in primary human mesothelial cells and mice exposed to chrysotile or crocidolite asbestos. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3588. doi:10.1158/1538-7445.AM2013-3588
Abstract 3589: Microbiomic analysis of colon cancer tumors and their matched normal reveals distinct gut floras.
Authors: Brim Hassan , Yooseph Shibu , Torralba Manolito , Lee Edward , Nelson Karen , Ashktorab Hassan 
Published: August 2014

Abstract
Background: The gut flora has long been suspected to play a role in colon carcinogenesis either through their secreted toxins or through their processing of ingested nutrients leading to the production of carcinogenic products. We previously have shown that stool samples flora from patients with pre-neoplastic colon lesions differ from those from healthy individuals. However, bacteria in stool samples are not representative of the colon adherent bacteria that are more prone to affect colon mucosa homeostasis. Here we analyzed the microbiota composition in 10 colon tumors and their matched normal tissue from 10 African American patients.
Materials & Methods: DNA extracts from 10 pairs of colon tumors and matched normal tissue, was used to amplify the V1-V3 regions of the 16S rRNA gene. The PCR primers included the A and B adaptor sequences for 454 pyrosequencing as well as a unique 12 bp barcode incorporated onto the reverse primer such that each sample receives its own unique barcode. The amplicons were purified, quantified, normalized, and then pooled in preparation for emulsion PCR followed by 454 sequencing using Titanium chemistry. After deconvolution and trimming, the sequences were put through chimera checking (using chimera slayer). Those sequences of length &gt;=100 bp that were not labeled as chimeras were then processed using RDP's classifier.
Results: Overall, each tumor sample microbiota was the closest to its matched normal based on the general bacterial profile. Bacteroidetes and Firmicutes were the dominant bacterial groups in all analyzed samples. Using a Principal Component Analysis at the genus level with bacterial genera that are represented at least 5% in one sample revealed two distinctly separated healthy tissue groups, one defined primarily by Bacteroides and the second defined by Prevotella bacteria. No tumor sample was within these two groups. It is noteworthy that Fusobacteria, that was shown by other similar studies as primarily abundant in tumors, was not defining any tumor group in our study.
Conclusion: Our study reveals the presence of significant microbiota changes between tumor samples and matched normal tissue even though our analysis were done only at the genus level. Further analysis at the Operational Taxonomic Units (sub-genus level) for each pair of samples are underway and will further dissect the observed differences.
Citation Format: Hassan Brim, Shibu Yooseph, Manolito Torralba, Edward Lee, Karen Nelson, Hassan Ashktorab. Microbiomic analysis of colon cancer tumors and their matched normal reveals distinct gut floras. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3589. doi:10.1158/1538-7445.AM2013-3589
Abstract 359: Systematic manipulation of brain tumor diversity using piggybac transposon mediated transgenesis approach in rat.
Authors: Chen Fuyi , Becker Albert , LoTurco Joseph 
Published: August 2014

Abstract
Animal models are important for interrogating the native biology of tumor formation, invasiveness, and may lead to novel therapeutic approaches. Here we describe the development of a rat glioma model which provides a fast and convenient approach to reproducibly induce brain tumors of different type in rat. We utilize a piggybac transposon system delivered by in utero electroporation (PB-IUE) to express oncogenic HRasV12 in different cell types in CNS. When expression of HRasV12 was driven by ubiquitous CAG promoter in radial glia cells, glioblastoma multiforme (GBM) was induced. When we specifically express HRasV12 in astrocytes using a mouse GFAP promoter, malignant astroglioma resembling GBM was induced in rat brains. In contrast, anaplastic oligoastrocytoma was induced when HRasV12 were expressed in oligodendrocytes under the control a rat MBP promoter. Surprisingly when co-expressing a basic helix loop helix protein Neurogenin2 (Ngn2) with HRasV12 both driven by CAG promoter, primitive neuroectodermal tumor (PNET) like tumors were generated. Molecular classification of tumors induced by CAG and GFAP HRasV12 matched mesenchymal GBM subtypes. Our data demonstrate the induction of different tumor types using a non-viral piggyBac transposon mediated transgenesis approach. The binary plasmid system we developed provides a method to direct different oncogenetic signals to different cell types. The models generated with this system should facilitate our understanding of the sources of tumor diversity.
Citation Format: Fuyi Chen, Albert Becker, Joseph LoTurco. Systematic manipulation of brain tumor diversity using piggybac transposon mediated transgenesis approach in rat. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 359. doi:10.1158/1538-7445.AM2013-359
Abstract 360: Erlotinib inhibits growth of a patient derived chordoma tumor xenograft.
Authors: Siu I-Mei , Burger Peter C. , Zhao Qi , Ruzevick Jacob , Connis Nick , Hann Christine L. , Gallia Gary L. 
Published: August 2014

Abstract
Chordomas are rare primary bone tumors that occur along the neuraxis. Current treatment includes surgical resection and often postoperative radiotherapy. Despite treatment, local recurrence occurs in the majority of patients and metastasis is frequent. Treatment options for patients with recurrence is limited and, notably, there are no FDA approved chemotherapeutic agents. Median survival is approximately 7 years. The lack of treatment options is in part due to the paucity of preclinical model systems for this tumor. We have previously established a serially transplantable animal model directly from human chordoma tissue. Further analysis of this patient derived xenograft demonstrates that subsequent passages continue to resemble the original patient tumor histologically and immunohistochemically and maintain nuclear expression of brachyury, a marker for chordoma. Genome wide variation between the patient's tumor and xenografts continues to be more than 99% concordant. To further characterize this model, a receptor tyrosine kinase screen of more than 70 kinases was evaluated and epidermal growth factor receptor (EGFR) was found to be the most activated kinase. In vitro studies demonstrate that EGFR inhibitors, such as erlotinib and gefitinib, inhibit growth of a validated human chordoma cell line, U-CH1. In vivo studies demonstrate that erlotinib significantly inhibits growth of this patient derived chordoma xenograft. Evaluation of tumors post-treatment reveals that erlotinib reduces tumor proliferation and phosphorylation of EGFR. Taken together, these findings demonstrate targeting EGFR can inhibit chordoma growth in vivo and support further clinical evaluation of EGFR inhibitors in the treatment of this disease.
Citation Format: I-Mei Siu, Peter C. Burger, Qi Zhao, Jacob Ruzevick, Nick Connis, Christine L. Hann, Gary L. Gallia. Erlotinib inhibits growth of a patient derived chordoma tumor xenograft. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 360. doi:10.1158/1538-7445.AM2013-360
Abstract 3602: Effect of alcohol on DB[a,l]P, an environmental pollutant and a tobacco smoke constituent, on DNA adduct formation in mouse oral tissues.
Authors: Zhang Shang-Min , Chen Kun-Ming , Richie John R. , Calcagnotto Ana , Aliaga Cesar , Berg Arthur , Sun Yuan-Wan , Sharma Arun K. , Amin Shantu , El-Bayoumy Karam 
Published: August 2014

Abstract
Alcohol acts synergistically with tobacco smoke to greatly increase the risk of oral squamous cell carcinoma (OSCC) up to 20-fold; the mechanisms of this synergism remain unknown. Research in this area has been hampered by the lack of appropriate animal models that would mimic chronic simultaneous human exposure to alcohol and representative carcinogens in tobacco or tobacco smoke as a whole. Recently, we developed a more relevant animal model (Int. J. Cancer, 2012, 2783-90) and showed that dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and a tobacco smoke component, induces SCC in oral tissues of mice. We also showed that its diol epoxide metabolite, (±)-anti-DB[a,l]PDE, is a potent and specific carcinogen in tongue and other oral tissues in mice. We hypothesize that chronic alcohol consumption will increase the carcinogenic potency of DB[a,l]P in the mouse oral cavity by multiple mechanisms including the depletion of glutathione (GSH) and increasing levels of covalent DB[a,l]PDE-DNA adducts.
As an initial study to test our hypothesis, mice were fed Isocaloric Lieber-DeCarli-type liquid diets formulated by BioServ (Frenchtown, N.J.) with or without ethanol (35% of total calories, increased gradually from 0, 11, 22 to 35%). After 3 weeks, mice were treated with 2 daily doses of DB[a,l]P (240 nmol each) and/or tobacco smoke particulates (TSP, 2R4F, 2.5 mg/mouse). Mice were sacrificed 24 hrs later and DB[a,l]PDE-DNA adduct levels were quantified by our recently developed LC-MS/MS method (Chem. Res. Toxicol. 2011, 1297-303). We showed that alcohol consumption significantly increased the levels of (-)-anti-trans-DB[a,l]P-dA in the absence of TSP (25%) or in the presence of TSP (75%). We also demonstrated that GSH levels in buccal mucosa were decreased (38%) in mice fed with liquid diet (35% calories from ethanol) compared with mice fed with control diet (0.89±0.13 μmol/g vs 1.23±0.17 μmol/g). Collectively, our preliminary results support our hypothesis that alcohol consumption will increase the carcinogenic potency of DB[a,l]P by altering the metabolic detoxification via depleting GSH and increasing DNA damage in oral tissues of mice.
Citation Format: Shang-Min Zhang, Kun-Ming Chen, John R. Richie, Ana Calcagnotto, Cesar Aliaga, Arthur Berg, Yuan-Wan Sun, Arun K. Sharma, Shantu Amin, Karam El-Bayoumy. Effect of alcohol on DB[a,l]P, an environmental pollutant and a tobacco smoke constituent, on DNA adduct formation in mouse oral tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3602. doi:10.1158/1538-7445.AM2013-3602