bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3178: Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation
Authors: Zhang Jinhui , Zhu Feng , Li Xiang , Xu Yanming , Peng Cong , Li Shengqing , Cho Yong-Yeon , Yao Ke , Zykova Tatyana A. , Bode Ann M. , Dong Zigang 
Published: May 2015

Abstract
The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. We show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 plays a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N- terminus by JNKs or other kinases.
Citation Format: Jinhui Zhang, Feng Zhu, Xiang Li, Yanming Xu, Cong Peng, Shengqing Li, Yong-Yeon Cho, Ke Yao, Tatyana A. Zykova, Ann M. Bode, Zigang Dong. Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3178. doi:10.1158/1538-7445.AM2014-3178
Abstract 3179: Redox signaling to nuclear respiratory factor-1 proteins by reactive oxygen species contributes to the estrogen-induced breast tumor development
Authors: Roy Deodutta , Felty Quentin , Okoh Victor 
Published: May 2015

Abstract
We have investigated the molecular mechanisms by which reactive oxygen species (ROS)-mediated redox signaling regulates estrogen-dependent growth of breast tumorigenesis and prospects for targeting these signaling pathways for therapeutic prevention and control of tumor growth. We present here for the first time that ROS generated by E2 exposure were responsible for in vitro MCF-7 cell tumor formation. This is evident from the inhibition of E2-induced ROS formation by ROS scavengers. H2O2 and O2•− seem to play important role in estrogen-mediated tumor growth redox signaling by inactivation of PTPs, such as, CDC25A, PTEN to prolong signaling through kinases, such as ERK and AKT. We observed a novel link between ROS-generated by estrogen, redox regulation of ERK and AKT-mediated signaling to nuclear regulatory protein, nuclear respiratory factor-1 (NRF-1) and ERα responsive gene expression in breast cancer cells and their involvement in the growth of estrogen-dependent breast tumor. NRF-1 serves as a nucleating factor to recruit signaling proteins involved in regulating estrogen-responsive cell cycle genes, and oxidative stress regulatable proteins. Findings of this study not only identify the new redox signaling pathway critical to the estrogen-dependent growth of breast tumors; but also provides important information for the design of redox signaling based therapeutic agents for the prevention and treatment of breast cancer.
Citation Format: Deodutta Roy, Quentin Felty, Victor Okoh. Redox signaling to nuclear respiratory factor-1 proteins by reactive oxygen species contributes to the estrogen-induced breast tumor development. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3179. doi:10.1158/1538-7445.AM2014-3179
Abstract 318: Specific role of Mieap α in Mieap-induced vacuole generation through an interaction with UVRAG
Authors: Nakamura Yasuyuki , Kamino Hiroki , Saito Yuri , Kitamura Noriaki , Sano Hitoya , Arakawa Hirofumi 
Published: May 2015

Abstract
Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria via Mieap-induced accumulation of lysosome-like organelles within mitochondria (MALM) or Mieap-induced vacuole (MIV), respectively (1-4). BNIP3 and NIX are essential mediators of MALM. MIV generation is closely related to the endocytic pathway. However, the mechanism of MALM and MIV function and of their selection and regulation remains unclear. UVRAG was identified as a Mieap-interacting protein. UVRAG plays a role in canonical autophagy through the endocytic pathway. Interestingly, Mieap α, but not Mieap β, specifically interacts with UVRAG. Knockdown of UVRAG severely inhibited MIV generation induced by Mieap α. On the other hand, endogenous Mieap β, but not Mieap α, accumulated at and within mitochondria during the MALM process. These results, taken together, suggest that Mieap α has a specific role in MIV generation through an interaction with UVRAG by regulating the endocytic pathway. In addition, UVRAG and Mieap are inactivated in human cancers including colorectal cancer patients, suggesting that the MIV regulated by the interaction of Mieap and UVRAG may play a role in tumor suppression. In this paper, we discuss several possible mechanisms for the selection of MALM or MIV and the role of Mieap/UVRAG in tumorigenesis on the basis of our recent data.
1. Miyamoto Y et al. PLoS ONE 6: e16054, 2011
2. Kitamura N et al. PLoS ONE 6: e16060, 2011
3. Nakamura Y et al. PLoS ONE 7: e30767, 2012
4. Miyamoto T et al. Sci Rep 2: 379, 2012
Citation Format: Yasuyuki Nakamura, Hiroki Kamino, Yuri Saito, Noriaki Kitamura, Hitoya Sano, Hirofumi Arakawa. Specific role of Mieap α in Mieap-induced vacuole generation through an interaction with UVRAG. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 318. doi:10.1158/1538-7445.AM2014-318
Abstract 3180: Gastrokine 1 inhibits Helicobacter pylori CagA-induced gastric carcinogenesis
Authors: Yoon Junghwan , Park WonSang , Choi Won Seok 
Published: May 2015

Abstract
Helicobacter pylori CagA directly injected by the bacterium into epithelial cells via a type IV secretion system, leads to cellular changes such as morphology, apoptosis, proliferation and cell mortality, and stimulates gastric carcinogenesis. We investigated the effects of CagA and GKN1 on cell proliferation, apoptosis, ROS production, epithelial-mesenchymal transition (EMT) and cell migration in CagA or GKN1 transfected gastric epithelial cells and tissues from humans and mice infected with H. pylori. We studied whether H. pylori CagA regulates gene copy number and expression of GKN1 in gastric cells and tissues of both humans and mice. On a molecular level, H. pylori CagA induced increased cell proliferation, ROS production, anti-apoptotic activity, and cell migration and invasion, and activation of NF-κB and PI3K/Akt signaling pathways and epithelial mesenchymal transition-related proteins. In addition, H. pylori CagA reduced GKN1 gene copy number and expression in gastric cells and tissues of humans and mice. However, GKN1 overexpression successfully suppressed these carcinogenic effects through directly binding to CagA. These study identifies GKN1 as pharmacological target that inhibits the development and progression of gastric cancers via suppression of H. pylori CagA-induced carcinogenic potential. Additionally, we propose that GKN1 is a potential diagnostic biomarker for H. pylori CagA status, gastritis and gastric cancers.
Citation Format: Junghwan Yoon, WonSang Park, Won Seok Choi. Gastrokine 1 inhibits Helicobacter pylori CagA-induced gastric carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3180. doi:10.1158/1538-7445.AM2014-3180
Abstract 3182: Tobacco smoke induces pulmonary neuroendocrine alterations in vivo
Authors: Xie Wei , Liang Zhaofeng , Yin Ying , Xie Chunfeng , Geng Hao , Zhao Li , Wu Rui , Li Xiaoting , Deng Feifei , Wu Jieshu , Geng Shanshan , Zhu Mingming , Zhu Jianyun , Zhu Weiwei , Huang Cong , Zhong Caiyun 
Published: May 2015

Abstract
Tobacco smoke is the leading cause of lung cancer. High-grade malignant pulmonary neuroendocrine tumors, including small cell lung cancers (SCLCs) and large cell neuroendocrine carcinomas (LCNECs), are almost exclusively associated with tobacco smoking. Unanalogous to most of other lung tumors such as squamous cell carcinomas, adenocarcinoma, adenosquamous carcinoma or carcinoid, no precursor lesions for high-grade lung neuroendocrine tumors have so far been identified. The purpose of the present study was to investigate the effects of tobacco smoke on pulmonary neuroendocrine alterations in phenotypically normal cells in vivo. Male BALB/c mice were exposed to tobacco smoke for 6h/day, 7days/week for 12 weeks. Pulmonary histology, neuroendocrine differentiation as well as MAPK/AP-1 activation were examined in lung tissues. Exposure to tobacco smoke significantly induced expression of neuroendocrine differentiation markers such as chromogranin A, neural cell adhesion molecule/(CD56), synaptophysin, and neuron specific enolase, as demonstrated by immunohistochemistry, Western blotting and real-time PCR. The expression levels of epithelial markers, including E-cadherin, zona ocludens-1, cytokeratin 5 and involucrin, were downregulated by tobacco smoke. Moreover, tobacco smoke significantly increased levels of p-ERK1/2, p-JNK and p-p38, while it suppressed p-ERK5 level. Expression of Jun and Fos proteins were differentially regulated by tobacco smoke. Taken together, the present study provides experimental evidence for the first time that tobacco smoke induces pulmonary neuroendocrine differentiation, shedding new light on the carcinogenic process of pulmonary neuroendocrine tumors.
Citation Format: Wei Xie, Zhaofeng Liang, Ying Yin, Chunfeng Xie, Hao Geng, Li Zhao, Rui Wu, Xiaoting Li, Feifei Deng, Jieshu Wu, Shanshan Geng, Mingming Zhu, Jianyun Zhu, Weiwei Zhu, Cong Huang, Caiyun Zhong. Tobacco smoke induces pulmonary neuroendocrine alterations in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3182. doi:10.1158/1538-7445.AM2014-3182
Abstract 3183: Modulation of NLRP3 by chemotherapeutics: Potential application in mesothelioma treatment
Authors: Shukla Arti , Westbom Catherine , Thompson Joyce , MacPherson Maximilian , Beuschel Stacie 
Published: May 2015

Abstract
Malignant mesothelioma (MM) is a deadly cancer and inflammation plays an important role in this carcinogenesis. In about 80% of cases, asbestos is the cause of MM development. We have previously shown that asbestos-induced NLRP3 priming and activation plays a significant role in MM development. We have also demonstrated that MM cells and tumor tissues show decreased levels of NLRP3 and caspase-1 activity as compared to normal mesothelial cells or tissue. Here using various human MM lines and two chemotherapeutic agents, doxorubicin and cisplatin, we show that chemotherapeutic agents can prime and activate NLRP3 in various MM cell lines, resulting in caspase-1 activation which may help in reducing drug resistance and increase tumor toxicity. The process of NLRP3 priming/activation was in part based on reactive oxygen species generated by these chemotherapeutic agents, as N-acetyl cysteine (NAC) was able to block these responses partly but significantly. The process of NLRP3 activation by these drugs also resulted in the release of pro-inflammatory cytokine IL-1β and IL-18. Our current studies are focused on blocking IL-1 receptor by an antagonist to find out if this can attenuate the release of IL-1-related cytokines like IL-6, IL-8 and VEGF. If successful, the combination of chemotherapeutic drugs and IL-1 receptor antagonists may have potential in MM treatment. This work is supported by NIH RO1 grant and a fellowship from the Department of Pathology, UVM.
Citation Format: Arti Shukla, Catherine Westbom, Joyce Thompson, Maximilian MacPherson, Stacie Beuschel. Modulation of NLRP3 by chemotherapeutics: Potential application in mesothelioma treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3183. doi:10.1158/1538-7445.AM2014-3183
Abstract 3186: Transplacental arsenic exposure modifies the number of hair follicle keratinocytes stem cells and alters their cell-cycle control
Authors: Marval Paula L. Miliani de , Kim Sun Hye , Rodriguez-Puebla Marcelo L. 
Published: May 2015

Abstract
Drinking water contamination with arsenic is a worldwide problem and a concern in some areas of the United States, especially in the West (California, Nevada, Alaska and Utah) and small areas of New England. Inorganic arsenic is considered a human carcinogen with many target tissues such as the skin, urinary bladder and lung; and characterizing its mechanisms of action is key to designing methods of intervention. Arsenic has transplacental carcinogenic activity, and since their fetal abundance, stem cells (SCs) seem to be a main target of arsenic exposure during gestation. We have established that fetal arsenic exposure via the maternal drinking water, leads to a decrease number of keratinocyte's stem cells (KSC) in mouse epidermis of the offspring. Biochemical analysis of these KSCs shows increased mRNA levels of the cell-cycle regulators cyclin D1 and CDK4. Supporting this observation, overexpression of CDK4 in KSCs mimics arsenic exposure as demonstrated by the reduced number of KSCs, and the decreased number of benign skin tumors, and severe rise in the rate of malignant conversion to squamus cell carcinomas.
We expect that these studies will enable to determine the consequence of in utero arsenic exposure on the proliferative potential of KSCs and the impact on the selection of KSCs that give origin to skin tumors with high risk of malignant conversion. Therefore, these studies will contribute to understanding how early alterations of somatic stem cells results in functional changes that impact a late stage of tumorigenesis such as malignant progression.
Citation Format: Paula L. Miliani de Marval, Sun Hye Kim, Marcelo L. Rodriguez-Puebla. Transplacental arsenic exposure modifies the number of hair follicle keratinocytes stem cells and alters their cell-cycle control. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3186. doi:10.1158/1538-7445.AM2014-3186
Abstract 3187: Genomic abnormalities in air pollution-related lung cancer
Authors: Zhou Guang-Biao , Yu Xian-Jun , Wu Li-Chuan , Huang Yun-Chao , Li Gao-Feng , Wen Zhe-Sheng , Chen Sai-Juan , Cao Yi , Wang Sheng-Yue , Yang Min-Jun , Chen Zhu 
Published: May 2015

Abstract
The lung cancer incidence in Xuanwei (XW) City and Fuyuan (FY) County in Yunnan Province of China is among the highest in China, owing to high levels of air pollution produced by combustion of smoky coal. This epidemiology profile provides a unique opportunity for identifying the carcinogenic mechanism underlying air pollution. Here, we analyze the genome sequences of 14 XW/FY non-small-cell lung cancers and their paired normal tissues, and report a mean of 289 somatic exonic mutations and 71 genomic rearrangements/tumor. Among the recurring mutated genes, calcium signaling and ion channel genes are the most frequently altered gene category. Higher mutation rate in calcium signaling genes is confirmed by genomic resequencing in 65 XW/FY patients and 85 patients from control regions. Small interfering RNA mediated silencing shows that inactivation of calcium channel leads to inhibition of lung cancer cells, suggesting a role for calcium signaling molecules in air pollution-related carcinogenesis leading to lung cancer.
Citation Format: Guang-Biao Zhou, Xian-Jun Yu, Li-Chuan Wu, Yun-Chao Huang, Gao-Feng Li, Zhe-Sheng Wen, Sai-Juan Chen, Yi Cao, Sheng-Yue Wang, Min-Jun Yang, Zhu Chen. Genomic abnormalities in air pollution-related lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3187. doi:10.1158/1538-7445.AM2014-3187
Abstract 3188: Evaluation of clonal origin of malignant mesothelioma/polyclonal origin of malignant mesothelioma
Authors: Comertpay Sabahattin , Mezzapelle Rosanna , Tanji Mika , Strianese Oriana , Pass Harvey I. , Weigel Tracey , Friedberg Joseph , Sugarbaker Paul , Krausz Thomas , Wang Ena , Gaudino Giovanni , Yang Haining , Powers Amy , Parsons Barbara , Pastorino Sandra , Carbone Michele 
Published: May 2015

Abstract
Tumors are generally thought to be monoclonal in origin, although this paradigm stemmed decades ago mostly from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma, a deadly cancer resistant to the current therapies, has never been investigated before. We used the HUMARA (human androgen receptor) assay to examine the pattern of clonality in 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 14 were informative and nearly all (13/14) revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, in that an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.
Citation Format: Sabahattin Comertpay, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Harvey I. Pass, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Giovanni Gaudino, Haining Yang, Amy Powers, Barbara Parsons, Sandra Pastorino, Michele Carbone. Evaluation of clonal origin of malignant mesothelioma/polyclonal origin of malignant mesothelioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3188. doi:10.1158/1538-7445.AM2014-3188
Abstract 3189: Morphological and molecular study of cell-chrysotile interaction in two different cell lines
Authors: Ricardi Luana R. , Rezende-Teixeira Paula , Souza Marcelo Medina de , Machado-Santelli Glaucia M. 
Published: May 2015

Abstract
Chrysotile accounts for more than 90% of the asbestos used worldwide. This type of fiber is considered the least oncogenic among the asbestos fibers, mainly based on the fiber dimension and biopersistence inside the lung. It is associated with respiratory diseases and lung cancer and identified as human carcinogen by the International Agency for Research on Cancer. However the mechanism and potential of different fibers to cause cancer is still a matter of debate. The present study focuses the interaction of fibers with different cell types, analyzing their ability and mechanism of fiber internalization. After short chrysotile small fibers exposure time (4-8hrs) both non-small cell lung carcinoma and monocytic cell lines were able of fiber internalization. Transmission electron microscope (TEM) analyses showed fibers involved or not by membrane into the cytoplasm and sometimes seemed to be associated with the chromatin. Cytoskeleton elements were observed to be concentrated around the fibers and they were identified as intermediate filaments according to their diameter. Immunofluorescent preparations imaged by laser scanning confocal microscope and submitted to localization analyses showed that both vimentin and cytokeratin may participate in this process. The data suggest that the internalization of fibers may occur through endocytosis and/or by physical perforation of the plasma membrane.
Since the scavenger receptors are responsible for recognition and internalization of dust particles by macrophages in lung, and some of them are linked to silica-containing particles recognition we evaluated their expression level of mRNA by using quantitative RT-PCR. The scavenger receptors appear to interfere with the internalization of chrysotile fibers process. SR-A and SCARA5 change their relative expression of mRNA after cell exposure to chrysotile fibers, such as SR-A and SCARA5. Furthermore, our study was the first to find the relationship between the SCARA5 receptor and chrysotile fibers. To check if features of the chrysotile internalization by epithelial and monocytic cells would be related with fibers shape or chemical composition, the cells were exposed to single walled carbon nanotubes in similar conditions.
Financial support: FAPESP, CAPES and CNPq)
Citation Format: Luana R. Ricardi, Paula Rezende-Teixeira, Marcelo Medina de Souza, Glaucia M. Machado-Santelli. Morphological and molecular study of cell-chrysotile interaction in two different cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3189. doi:10.1158/1538-7445.AM2014-3189
Abstract 3191: Elevation of tumor-promoting cytokines in mice exposed to the environmental contaminant tributyltin
Authors: Lawrence Shanieek , Pellom Samuel Troy , Hurd-Brown Tasia , Shanker Anil , Whalen Margaret 
Published: May 2015

Abstract
Cytokines are important regulators of immune responsiveness. Alterations of cytokine secretion from immune cells would have the potential to disrupt both immune destruction of cancer cells and to alter the proliferation and invasiveness of tumor cells due to their capacity to act as growth factors, angiogenic factors, and inducers of epithelial-mesenchymal transition. Tributyltin (TBT) is a widespread environmental contaminant having been used in a variety of industrial applications and is found in human blood at levels ranging as high as 261 nM. Studies in human immune cells have shown that secretion of tumor necrosis factor alpha (TNFα) is altered by exposures to TBT. There have been no in vivo studies of the effects of exposure to TBT on the cytokine communication network. As it is not possible to examine alterations of this network in exposed humans, we examined the effects of TBT exposure in a mouse model using Milliplex mouse cytokine/chemokine magnetic bead premixed 32 plex kit. Serum and spleens of TBT-exposed mice were analyzed for changes in cytokine secretion/levels. TBT increased the levels of IL13 in the serum of non-tumor-bearing mice and increased IL1β, IL6, KC, and M-CSF in tumor-bearing mice. The spleens of both non-tumor-bearing and tumor-bearing mice showed increases in Eotaxin when exposed to TBT. Of significant interest is the fact that the presence of tumor causes increases in Eotaxin, IL12p40, M-CSF, and TNFα and exposure to TBT alone can cause increases in these same cytokines. Tumors are known to increase levels of cytokines that enhance their ability to survive. The results showing that TBT can amplify the levels of several cytokines that are increased by tumor suggest that TBT may have tumor-promoting abilities by modulating tumor growth and/or invasiveness. Experiments are under way to dissect cytokine signaling pathways that are affected by TBT. The findings will allow identification of molecular targets that are necessary to intercept the tumor promoting signaling following TBT exposure.
Supported by: NIH grant 5U54CA163066-03
Citation Format: Shanieek Lawrence, Samuel Troy Pellom, Tasia Hurd-Brown, Anil Shanker, Margaret Whalen. Elevation of tumor-promoting cytokines in mice exposed to the environmental contaminant tributyltin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3191. doi:10.1158/1538-7445.AM2014-3191