bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5093: Nucleolin phosphorylation profiling under normal and cellular stress conditions
Authors: Ng Kenneth , Rodriguez Allana , Saxena Anjana D. 
Published: May 2015

Abstract
Nucleolin (NCL) is a ubiquitous nucleolar phosphoprotein that integrates critical cellular processes, from cell growth (ribosome biogenesis) and cell proliferation to cell cycle arrest and cell death. Deregulation of these processes often lead to different pathological conditions including cancer and heightened levels of nucleolin are often found in a variety of tumors. Nucleolin is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2) and mitotic cyclin-dependent kinase 1 (Cdk1). Although increased nucleolin phosphorylation by CK2 is finely regulated in exponentially dividing cells, the role of nucleolin phosphorylation in regulating cell cycle remains largely unexplored. The high content of acidic stretches in the N-terminus of nucleolin protein limits the effective use of mass-spectrophotometry as well as our ability to generate various phosphorylation-specific nucleolin antibodies. In this study, we used novel phosphate-binding tag to analyze nucleolin phosphorylation in human osteosarcoma cells. With phosphate affinity gel electrophoresis and subsequent western analyses, we have enabled the detection and quantification of different phosphorylation states of nucleolin during interphase as well as in mitosis. CK2 phosphorylated nucleolin (as in interphase) has multiple bands that migrate slower when bound to phos-tag as compared to hypo-phosphorylated nucleolin mutant (6/S*A, where six consensus CK2 sites were modified from serine to alanine and hence defective in undergoing phosphorylation). In contrast, a single hyper-phosphorylated nuclolin band was predominant in mitotic arrested cells. Furthermore, we elucidated nucleolin phosphorylation patterns under various cellular stresses e.g. DNA damage (UV, CPT) as well as kinase stimulation (e.g. arachidonic acid) or inhibition by CK2-specific inhibitor CX4945. Our data provide for the first time informative nucleolin phosphorylation patterns during different cellular conditions. This profiling of nucleolin phosphoprotein is essential in understanding the role of nucleolin phosphorylation in various cellular processes as well as during cellular response to stress. This work is supported by grants PSC/CUNY 66740-00 44 and CA175794.
Citation Format: Kenneth Ng, Allana Rodriguez, Anjana D. Saxena. Nucleolin phosphorylation profiling under normal and cellular stress conditions. [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 5093. doi:10.1158/1538-7445.AM2014-5093
Abstract 51: Elevated levels of E2F1, EZH2 and SUZ12 lead to invasive progression of superficial bladder cancers
Authors: Lee Se-Ra , Roh Yun-Gil , Kim Won-Tae , Kim Seon-Kyu , Heo Jeonghoon , Chu In-Sun , Leem Sun-Hee 
Published: May 2015

Abstract
Bladder cancer is increasing a rate of occurrence in aging societies. A superficial bladder cancer is noninvasive that is presented as a good prognosis after receiving treatment. However, about 20∼50% of superficial bladder cancer patients progressed to invasive tumor which represent the poor survival rates within 5 years. In previous study, we addressed if the transcriptional characteristics of the superficial bladder cancer could be used as predictive biomarkers for the progression of superficial tumors to invasive ones. Using gene expression data from 165 bladder cancer patients, we identified a gene expression signature that could predict the likelihood of progression to invasive tumors. Gene network analyses of the signature revealed that E2F1 and its downstream effectors EZH2 and SUZ12 could be important mediators for the invasive and metastatic progression of superficial tumors. In this study, we investigated how these genes may affect the invasive and metastatic progression of superficial tumors. For confirmation of the expression of E2F1, EZH2 and SUZ12 in two groups of bladder cancer cells, we performed quantitative RT-PCR and western blot assay. Both of mRNA and protein expression of E2F1, EZH2 and SUZ12 in superficial bladder cancer were significantly lower than invasive bladder cancer cells (p&lt; 0.0001). Next, we performed an invasion and migration assay. The overexpression of E2F1, EZH2 and SUZ12 presented an increase of invasiveness and migratory in UC9 superficial bladder cancer. On the other hand, the silencing of gene expression in EJ invasive cell was shown a significantly decreasing of invasiveness and migratory ability. Also, we determine the effect of proliferation and colony formation in superficial and invasive bladder cancer. The depletion of E2F1, EZH2 and SUZ12 in EJ and 5637 invasive bladder cancer cells that significantly decreasing of forming colonies on soft agar. Furthermore, we founded the reduction of tumor size when injected cells depleted E2F1, EZH2 and SUZ12 than control by xenograft assay. Together, our findings reveal that the estimating the roles of E2F1, EZH2 and SUZ12 for the invasive and metastatic progression in superficial bladder cancer.
Citation Format: Se-Ra Lee, Yun-Gil Roh, Won-Tae Kim, Seon-Kyu Kim, Jeonghoon Heo, In-Sun Chu, Sun-Hee Leem. Elevated levels of E2F1, EZH2 and SUZ12 lead to invasive progression of superficial bladder cancers. [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 51. doi:10.1158/1538-7445.AM2014-51
Abstract 5105: A novel metabolite from an extremophile Streptomyces with apoptosis regulator function
Authors: Moazami Nasrin , Hakami Fatoulah , Ofoghi Hamideh , Ghaffarpour Massoud 
Published: May 2015

Abstract
Apoptosis or programmed cell death is essential for the normal functioning and survival of most multi-cellular organisms. The morphological and biochemical characteristics of apoptosis are highly conserved during the evolution. Therapeutic strategies based on exogenous delivery of the native form of superoxide dismutase (SOD), a free radical scavenger, are limited because of its short half-life (approximately 6 min) in vivo and poor permeability across the blood barrier and cell membrane. In this study, the spectrum of in vivo anti cancer activity of a Streptomyces SOD with a carrier protein designated Kavir-48by apoptotic function was assessed. Two xenograft models including LXFl 529 and LXFL H460 lung cancer cells were used. Purified protein complex was administrated through intra- peritoneal injection (ip) for 4 weeks. The results showed that treatment with 300 mg/kg of kavir-48 significantly reduced the growth of xenografted tumor with a tumor growth inhibition (TGI) of 70 % for LXFI 529 cell line. In addition, no adverse effects were observed based on general appearance, weight loss or reduction in weight gain. Finally, Kavir-48, demonstrated a highly anti-tumor efficacy in vivo and a tolerability profile amenable to intra peritoneal administration. It acts as a promising therapeutic target against cancer.Further analysis on this antitumor metabolite on gene expression profiles involved in regulation of apoptosis and oxidative stress pathways in different cancer cells in progress.
Note: This abstract was not presented at the meeting.
Citation Format: Nasrin Moazami, Fatoulah Hakami, Hamideh Ofoghi, Massoud Ghaffarpour. A novel metabolite from an extremophile Streptomyces with apoptosis regulator function. [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 5105. doi:10.1158/1538-7445.AM2014-5105
Abstract 5106: Induction of reactive oxygen species-dependent mitotic arrest and apoptosis by sulforaphane in human bladder cancer 5637 cells
Authors: Choi Yung Hyun 
Published: May 2015

Abstract
The present study was undertaken to determine whether sulforaphane-derived reactive oxygen species (ROS) might cause growth arrest and apoptosis in human bladder cancer 5637 cells. Our results show that the reduced viability of 5637 cells by sulforaphane is due to mitotic arrest, but not the G2 phase. The sulforaphane-induced mitotic arrest correlated with an induction of cyclin B1 and phosphorylation of Cdk1, as well as a concomitant increased complex between cyclin B1 and Cdk1. Sulforaphane-induced apoptosis was associated with the activation of caspase-8 and -9, the initiators caspases of the extrinsic and intrinsic apoptotic pathways, respectively, and activation of effector caspase-3 and cleavage of PAPR. However, blockage of caspase activation inhibited apoptosis and abrogated growth inhibition in sulforaphane-treated 5637 cells. This study further investigated the roles of ROS with respect to mitotic arrest and the apoptotic effect of sulforaphane, and the maximum level of ROS accumulation was observed at 30 min after sulforaphane treatment. However, a ROS scavenger, N-acetyl L-cysteine, notably attenuated sulforaphane-mediated apoptosis as well as mitotic arrest. Overall, these results suggest that sulforaphane induces mitotic arrest and apoptosis of 5637 cells via a ROS-dependent pathway.
Citation Format: Yung Hyun Choi. Induction of reactive oxygen species-dependent mitotic arrest and apoptosis by sulforaphane in human bladder cancer 5637 cells. [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 5106. doi:10.1158/1538-7445.AM2014-5106
Abstract 5111: Nitric oxide and its role in photodynamic therapy
Authors: Monroy Marco , Tipgunlakant Pooncharas , Simonis Ursula , Esquerra Raymond 
Published: May 2015

Abstract
Porphyrinic pigments are used as photosensitizers (PS) in photodynamic detection (PDD) and therapy (PDT) that is a minimally invasive modality in the fight against cancer. When the PS is activated by visible light at a given wavelength, reactive oxygen species (ROS) are generated, which cause cancer cells to undergo cell death. Despite significant advances, drawbacks of the PSs in clinical use include their non-selectivity in cellular-targeting causing cell death by necrosis leading to tissue inflammation. Nitric oxide (NO) has been shown to play a key role in modulating apoptotic cell death pathways and to react with reactive oxygen species to form additional lethal reactive nitrogen species (RNS). In our efforts to enhance the effectiveness of PDT, we set out to investigate the role of NO in PDT. We hypothesized that NO delivered to cancer cells at the time that the PS was administered would enhance the efficacy of PDT by promoting mitochondria-mediated apoptosis. To this end, we incubated androgen-sensitive human prostate adenocarcinoma (LNCaP) cells with both a PS and an NO releasing agent that was most effective in NO release as was spectrophotometrically determined by its oxidation of hemoglobin. Phototoxicity experiments were carried out at 37 OC with a noncoherent light source. Cell viability, damage and death were assessed in both illuminated and non-illuminated cells and were quantified by MTT staining as well as trypan blue and propidium iodide exclusion. To corroborate the cell viability results, we assayed clonogenic recovery in response to PDT in pigmented cells both in the presence and absence of NO. Our results indicate that the effectiveness of PDT in causing cell death depends on the NO concentration. PDT with NO alone was toxic to the cancer cells at high concentration of NO, whereas at low NO concentration no significant cell damage was observed after light illumination. PDT with the PS alone was not as effective in promoting cell death as PDT in the presence of both NO and the PS. Depending on the concentrations of the PS and NO, we observed that either necrosis or apoptosis were the prevailing modes of cell death after PDT. Our results indicate that the phototoxicity of the compounds is mainly determined by their intracellular concentration. Thus, understanding the combined effects of NO and the PSs in enhancing cell phototoxicity will aid in determining the roles that NO plays in improving the efficacy of PDT and may provide an alternate regimen to enhance PDT efficacy.
Citation Format: Marco Monroy, Pooncharas Tipgunlakant, Ursula Simonis, Raymond Esquerra. Nitric oxide and its role in photodynamic therapy. [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 5111. doi:10.1158/1538-7445.AM2014-5111
Abstract 5117: Cytotoxic effects of hypericum extracts on breast and colorectal tumors
Authors: Gibbs Carla , Duggans Johnette S. , Malone Erin , Myles Elbert L. 
Published: May 2015

Abstract
The risk of acquiring certain types of cancers has many causes which include age, environment and genetics. There have been advances in the primary treatment options available, which include surgery, radiation therapy, and chemotherapy. However, the survival prognosis for many cancer patients remains low. Cancer treatments may involve chemotherapy, which often cause harsh side effects. The Plant kingdom may provide alternative therapy that may have less side effects and possibly more effective. Hypericum perforatum possesses hypericin, which has been been shown to have antitumor effects with invitro studies on specific cell lines. In other Hypericum species, hypericin makes up a smaller percentage of the extract. However, these species contain other phytochemical compounds that may also exert an antitumor effect. The objective of the present study was to assess the cytotoxic potential of H. perforatum cv. topas, H. olympicum, and H. calycinum on breast and colorectal adenocarcinoma cell lines. MCF7, SW480, and SW620 cells were treated with varying concentrations dosages of methanolic crude extracts from the plant species. Cytotoxicity was determine by measuring the reduction of Alamar Blue after a 24 hour exposure period of 10,000 cells in 96 well fluorescent plates. The reduction was determine using the Molecular Devices fluorescent spectrophotometer. At the lowest comparable concentrations, H. perforatum cv. topas had a greater reduction in tumor growth than MCF7 and SW40 cells lines. Whereas, H. olympicum demonstrated a greater decrease in SW620 cell growth at the lowest comparable concentration. These results suggest a difference in the phytochemical composition of these plants, which should be evaluated in order to determine what metabolite(s) are having the antitumor effect and their target.
Citation Format: Carla Gibbs, Johnette S. Duggans, Erin Malone, Elbert L. Myles. Cytotoxic effects of hypericum extracts on breast and colorectal tumors. [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 5117. doi:10.1158/1538-7445.AM2014-5117
Abstract 5118: Decursin synergistically enhances TRAIL-induced apoptosis through CHOP dependent DR5 signaling in TRAIL resistant lung cancer cells
Authors: Kwang Kim Jae 
Published: May 2015

Abstract
Targeting the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has been clinically established for anticancer therapy, is the attractive strategy to specifically kill cancer cells through the death receptors. Nonetheless, its therapeutic potential is limited due to the resistance in cancer cells. Thus, in the present study, we evaluated the therapeutic potential of Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root as a TRAIL sensitizer in a variety of resistant lung cancer cells. Co-treatment of Decursin with TRAIL synergistically induced apoptosis in TRAIL resistant lung cancer cells, A545, H1299, H596 and Calu-1. This synergistic effect through the induction of DR5 in Decursin treated cells was also confirmed by immunoblotting and immunoanalysis of endogeneous and surface expression of DR5, respectively. In contrast, in DR knockdown cells, combination treatment Decursin and TRAIL did not induce apoptosis at all. Furthermore, we found that DR5 induction by Decursin was mediated by ER-stress and its byproduct CHOP. Depletion of CHOP via siRNA transfection completely blocked Decusin induced apoptosis cell death in TRAIL resistant lung cancer cells. Taken together, induction of the DR5 via upregulation of CHOP and its inducer, ER stress, by Decursin leads to synergistically increase the TRAIL mediated cell death in TRAIL resistant lung cancer cells. Our results indicate that Decursin is a useful therapeutic strategy for overcoming TRAIL resistance in lung tumor treatment.
Key words: Decursin, DR-5, ER stress, CHOP, Trail resistant, Lung cancer
Conflict of Interests: The authors disclose no potential conflicts of interest.
Acknowledgment: This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MEST) (no. 2012-0005755).
Citation Format: Kim Jae Kwang. Decursin synergistically enhances TRAIL-induced apoptosis through CHOP dependent DR5 signaling in TRAIL resistant lung cancer cells. [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 5118. doi:10.1158/1538-7445.AM2014-5118
Abstract 5121: Omega-3 polyunsaturated fatty acids induce apoptotic and autophagic cell death through inhibition of Akt/mTOR pathway in human oral cancer cells
Authors: Lim Kyu , Shin Soyeon , Hong Tae-Hwa , Jing Kaipeng , Jeong Soyeon , Kim Soyeon , Kweon Gi-Ryang , Park Seung-Kiel , Park Jong-Il 
Published: May 2015

Abstract
Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effect in oral cancer remains unclear. This study was designed to examine the impact of ω3-PUFAs on oral cancer and the molecular mechanism of their action using in vitro and in vivo models. Exposure SCC4 and SCC9 human oral cancer cells to the ω3-PUFA docosahexaenoic acid (DHA) reduced cell viability in a dose- and time-dependent manner. The increase in cell death was due in part to apoptosis, since cells incubated with DHA exhibited elevated levels of apoptotic markers including cleaved PARP expression, subG1 DNA portion and TUNEL-positive nuclei. DHA treatment also led to autophagic vesicle formation and an increase in autophagic flux, indicating the involvement of both apoptosis and autophagy in the cytotoxic effect of ω3-PUFAs on oral cancer cells. Further experiments revealed that the concurrent activation of apoptosis and autophagy induced by DHA was linked to reactive oxygen species (ROS) overproduction and inhibition of Akt/mTOR signaling molecules. Moreover, stable SCC9 cell lines expressing the ω3-desaturase gene (SCC9-fsc) or control vector (SCC9-csc) were generated, and the effect of endogenous high level of ω3-PUFAs was investigated. The growth rate and colony-forming capacity of SCC9-fsc were remarkably decreased compared to those of SCC9-csc. Likewise, tumor size and volume of SCC9-fsc implanted into nude mice were also significantly inhibited with increases in the cell death index. Taken together, these results indicate that ω3-PUFAs induce apoptosis- and autophagy-associated cell death through ROS and Akt/mTOR signaling pathways in oral cancer cells. Thus, utilization of ω3-PUFAs may represent a promising therapeutic approach for chemoprevention and treatment of human oral cancer. [This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0013263 and 2007-0054932).]
Citation Format: Kyu Lim, Soyeon Shin, Tae-Hwa Hong, Kaipeng Jing, Soyeon Jeong, Soyeon Kim, Gi-Ryang Kweon, Seung-Kiel Park, Jong-Il Park. Omega-3 polyunsaturated fatty acids induce apoptotic and autophagic cell death through inhibition of Akt/mTOR pathway in human oral cancer cells. [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 5121. doi:10.1158/1538-7445.AM2014-5121
Abstract 5127: Reprogramming of EMT and stemness by human recombinant CCN5 in triple negative breast cancer cells
Authors: Das Amlan , De Archana , Banerjee Snigdha , Banerjee Sushanta K. 
Published: May 2015

Abstract
Epithelial to Mesenchymal transition (EMT) is an important and coordinated series of events associated with tumor metastasis and invasion. Recent studies from our group had shown the importance of CCN5/ WISP-2 in the suppression of breast and pancreatic cancer progression through the regulation of the invasive phenotypes. In our study we have observed that exposure of triple negative human breast cancer cells (TNBC), MDA-MB-231 and HCC-70 to recombinant CCN5 (hrCCN5), resulted in a dose-dependent inhibition of cell-proliferation through the induction of apoptotic cell death. Anchorage-independent growth and colony forming ability of MDA-MB-231 cells were also found to be drastically inhibited in the presence of hrCCN5. Distinct up regulation of the epithelial markers such as CD24, and cytokeratin19 and down regulation of the mesenchymal markers such as Notch-1, vimentin, and CD44 were observed in CCN5 treated TNBC cells. CCN5 treatment also resulted in the significant reduction of stemness of these cells, as confirmed by mammosphere assay. Collectively, the studies indicate CCN5 could be a re-programmer of EMT and stemness and thus hrCCN5 can be considered as a potential therapeutic agent for TNBC.
Note: This abstract was not presented at the meeting.
Citation Format: Amlan Das, Archana De, Snigdha Banerjee, Sushanta K. Banerjee. Reprogramming of EMT and stemness by human recombinant CCN5 in triple negative breast cancer cells. [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 5127. doi:10.1158/1538-7445.AM2014-5127