bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1003: Cancer-associated myofibroblast may stimulate vimentin expression of gastric cancer cells
Authors: Yuhiko Fuyuhiro , Yashiro Masakazu , Noda Satoru , Doi Yosuke , Kato Yukihiro , Kashiwagi Shinichiro , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Inoue Toru , Yamada Nobuya , Ohira Masaichi , Hirakawa Kosei 
Published: February 2011

Abstract
Introduction: Epithelial-mesenchymal transition (EMT) is a process in which cells undergo a developmental switch from an epithelial to a mesenchymal phenotype. During the EMT, epithelial cells seem to acquire malignant properties, with changes in cell morphology, invasion, and migration capacity. Vimentin is one of EMT markers for cancer cells, and vimentin expression of epithelial cells has been reported to be associated with the malignant phenotype of cancer cells in vitro. Fibroblasts, especially cancer-associated myofibroblasts which express α-smooth muscle actin, may affect the malignant phenotype of cancer cells. Then, we examined the effect of fibroblasts on the vimentin expression of gastric cancer cells.
Materials & Methods: A gastric cancer cell line, OCUM-2MD3, and 3 gastric fibroblasts, CaF1, CaF32, and CaF33 those are derived from gastric tumor, were used in this study. Serum-free conditioned medium (SF-CM) from gastric fibroblasts was collected and stored at −20°C. As a control, DMEM was used instead of SF-CM. Following the addition of SF-CM into OCUM-2MD3 cells for 3 days, vimentin expression of OCUM-2MD3 was analyzed by reverse transcription-PCR. Correlation between vimentin expression of cancer cells and α-smooth muscle actin expression of fibroblasts was analayzed by Pearson's correlation coefficient test.
Results: Vimentin expression of gastric cancer cells was 2.3 fold, 1.1 fold, and 1.3 fold increased by addition of SF-CM from CaF1, CaF32, and CaF33, respectively. α-Smooth muscle actin expression of each fibroblasts from CaF1, CaF32, and CaF33 was 7.7 fold, 1.3 fold, and 2.1 fold higher compared to the normal fibroblasts, respectively. Gastric cancer cells showed EMT by SF-CM. A significant correlation (p=0.017) was found between the α-smooth muscle actin expression level of fibloblast and the vimentin expression level of cancer cells.
Conclusions: Tumor-stromal myofibroblast may stimulate malignant phenotype of gastric cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1003.
Abstract 1013: Hepatic stellate cells promote progression of cholangiocarcinoma in vitro and in vivo
Authors: Okabe Hirohisa , Beppu Toru , Hayashi Hiromitsu , Ishiko Takatoshi , Masuda Toshiro , Otao Ryu , Watanabe Masayuki , Takamori Hiroshi , Baba Hideo 
Published: February 2011

Abstract
Background: Although tumor-stroma interaction has been discussed, the role of hepatic stellate (HS) cells against cancer, especially cholangiocarcinoma, has not been clarified. Although hepatic stellate cells have been known to have a pivotal role in fibrogenesis in liver, the influence of them on liver cancer has been poorly investigated. We previously reported hepatic stellate cells may exist in cancer stroma of intrahepatic cholangiocarcinoma and interact with cancer cells in vitro. The aim of this study was to investigate the effect of HS cells on cholangiocarcinoma cells progression in vitro and in vivo and to identify key proteins which regulate their interaction.
Methods: The effects of cholangiocarcinoma cells’ conditioned medium (CC-CM) on activation and proliferation of HS cells (LI90 and LX-2), the influences of HS cells conditioned medium (HS-CM) on in vitro proliferation and invasion of cholangiocarcinoma cells (HuCCT-1 and RBE), and the effects of their interaction on human umbilical venous endothelial cells (HUVECs) tube formation were assessed using each of conditioned medium. The effect of HS cells on tumor growth was examined in vivo by subcutaneous co-injection of them. To clarify the factors inducing their interaction, cytokine array was performed to assess the secreted proteins induced by co-culture of cholangiocarcinoma and HS cells.
Results: CC-CM activated HS cells and increased their proliferation. HS-CM dose-dependently increased cholangiocarcinoma cell proliferation and invasion. Chemotherapy to cholangiocarcinoma cells was less effective treated with HS-CM. HS-CM activated the mitogen-activated protein kinase (MAPK) and Akt pathways in tumor cells. The indirect interaction of cholangiocarcinoma and HS cells promote the tube formation of HUVECs. Subcutaneous co-injection of tumor cells with HS cells in nude mouse resulted in increased tumor size and weight. There found to be several proteins including interleukin-1β (IL1β) that remarkably increased by co-culture of them in culture medium and they were thought to be key proteins which regulated tumor-stromal interaction.
Conclusions: This study indicated that HS cells have an important role in accelerating cholangiocarcinoma progression. Several proteins including IL1β induced by co-culture model may be therapeutic targets which focus tumor-stromal interaction in cholangiocarcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1013.
Abstract 1028: Regulation of glucocorticoid-evoked apoptosis in human leukemic CEM cells by the C. elegans ces2 ortholog E4BP4
Authors: Jessica Beach A. , Medh Rheem D. 
Published: February 2011

Abstract
Identification of regulatory gene pathways is crucial for fully understanding apoptosis in human cells. In C. elegans, motorneuron apoptosis is regulated via the ces2→ces1→egl1 pathway. We propose that an analogous pathway exists in humans. It has been confirmed that the ces2 ortholog E4BP4 and the egl1 orthologs bim/puma are regulators in glucocorticoid (GC)-evoked apoptosis in human lymphoid leukemic CEM cells. We aim to determine whether E4BP4 regulates bim/puma in a manner similar to ces2's regulation of apoptosis via the down regulation of the ces1 ortholog slug/snail. In this study, E4BP4-dependence of slug/snail and bim/puma regulation by GCs was evaluated in CEM sister cell lines. Cells were treated with ethanol (control) or 1 μM Dexamethasone (a synthetic GC) for 24 h for evaluation of transcript and protein levels, and for 96 h for trypan blue exclusion-based viability assays. Relative mRNA expression and protein abundance of bim/puma and slug/snail were evaluated by qRT-PCR and Western analysis, respectively. Both bim/puma and slug/snail promoters were analyzed using promoter scanning software (Transcriptional Regulatory Element Database) to locate potential E4BP4 response elements. GC-evoked apoptosis in sensitive CEM-C7-14 cells correlated with E4BP4 upregulation, and GC-resistance in CEM-C1-15 cells could be overcome by stable ectopic expression of mouse E4BP4 (cell line CEM-C1-15-mE#3). Flow cytometric analysis of DNA content following propidium iodide labeling has confirmed the expected G1 arrest and accumulation of sub-G1 populations in C7-14 and C1-15-mE#3 cells. qRT-PCR and Western blotting results have confirmed differential bim expression; with C7-14 cells showing a significant two-fold increase in comparison to C1-15 cells. qRT-PCR results for puma, slug, and snail did not show significant differences in expression levels between C7-14, C1-15 and C1-15-mE#3 cells. Furthermore, the expected down regulation of slug/snail in the GC-sensitive C7-14 cells was not observed. Our data suggest that in CEM cell apoptosis, E4BP4-dependent downregulation of slug/snail is not an intermediate for bim upregulation. Unlike the ces2→ces1→egl1 pathway in C. elegans, E4BP4 may use alternative pathways (c-myc, c-jun, cyclin D3, etc.) or directly upregulate bim to evoke apoptosis in CEM cells.
JAB is a recipient of a CSUN Graduate Equity Fellowship & a Graduate Fellowship for Outstanding Research Promise in Science & Mathematics from the CSUN College of S&M. Project funding by NIH grant (SC3 GM 081099-01) awarded to RDM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1028.
Abstract 1030: Arsenic trioxide plus ethacrynic acid-butyl ester is synergistic to induce apoptosis in myeloid leukemia cells through upregulation of NOXA
Authors: Wang Rui , Liu Changda , Waxman Samuel , Jing Yongkui 
Published: February 2011

Abstract
Arsenic trioxide (As2O3) induces complete remission in acute promyelocytic leukemia (APL) patients. However, other types of myeloid leukemia patients are less responsive to As2O3 treatment. APL t(15;17) NB4 cells are more sensitive to As2O3 apoptosis induction than other types of myeloid leukemia cells such as HL-60 and K562 cells. Previously we reported that As2O3 induces apoptosis in NB4 cells through a reactive oxygen species (ROS)-mediated pathway which is attenuated by the expression of glutathione-s-transferase π (GSTπ). NB4 cells contain lower levels of GSTπ than other types of myeloid leukemia cells. Therefore, inhibition of GSTπ should enhance As2O3 induction of apoptosis in other types of myeloid leukemia cells. We investigated the combined effect of As2O3 with ethacrynic acid (EA) and a more potent non-diuretic EA analogue ethacrynic acid-butyl ester (EABE), known GSTπ inhibitors, to induce apoptosis in HL-60 and K562 cells. As2O3 at clinical achievable concentrations (1-2 µM) did not induce apoptosis in HL-60 cells nor in K562 cells. EA at a concentration lower than 60 μM did not induce apoptosis in both cell lines either. As2O3 at 2 μM plus EA at 60 μM are synergistic to induce apoptosis in both HL-60 and K562 cells as measured by Annexin V staining, PARP cleavage and caspase activation. More intriguing, EABE at 1 μM (60 fold lower than EA), which inhibits GSTπ activity, exhibited synergistic induction with As2O3 in K562 cells. Combined index of As2O3 with EABE to induce apoptosis in K562 cells calculated by CompuSyn software was less than 1.0 which indicated synergism. Apoptosis induction by the combination treatment of As2O3 with EABE correlated with the upregulation of the Bcl-2 homology 3 (BH3)-only pro-apoptotic protein NOXA. Knock-down of NOXA using siRNA blocked apoptosis induction of As2O3 plus EABE, while, knock-down of Mcl-1 enhanced the apoptosis induction of As2O3 plus EABE. Immunoprecipiation with Mcl-1 antibody revealed that NOXA bond to Mcl-1 in the K562 cells treated with As2O3 plus EABE. Inhibition of ROS production did not inhibit the upregulation of NOXA nor the apoptosis induction of As2O3 plus EABE treatment. Our data suggest that As2O3 plus EABE induce apoptosis through a novel mechanism which induces NOXA and sequesters Mcl-1 leading to the activation the intrinsic apoptotic pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1030.
Abstract 1040: Most putative BH3 mimetics preferentially antagonize the anti-apoptotic protein MCL-1 rather than BCL-2
Authors: Albershardt Tina C. , Pletnev Alexandre A. , Eastman Alan 
Published: February 2011

Abstract
The anti-apoptotic proteins of the BCL-2 family (BCL-2, BCL-X and MCL-1) have been variously implicated in the resistance of tumors to anti-cancer therapies. Numerous small molecules have been developed to mimic the binding of BH3-only proteins to the BH3 pocket of anti-apoptotic proteins. These “BH3 mimetics” thereby disrupt the ability of anti-apoptotic proteins to bind and inhibit pro-apoptotic proteins. ABT-737 is a BH3 mimetic that inhibits BCL-2 and BCL-X but not MCL-1 and kills cells in a BAX/BAK-dependent manner. The ability of other BH3 mimetics to inhibit anti-apoptotic proteins has been questioned because they kill cells in a BAX/BAK-independent manner. It has thus been assumed that the actions of these BH3 mimetics must be mediated by off-target effects. In the NB4 leukemia cell line, we show for the first time that most BH3 mimetics preferentially inhibit MCL-1. Six putative BH3 mimetics investigated (GX015-070, gossypol, apogossypol, methoxy-antimycin A, HA14-1 and S1) led to an increase in both NOXA and MCL-1. NOXA binds to MCL-1 and targets the NOXA/MCL-1 complex for degradation. Hence, their accumulation is consistent with these BH3 mimetics disrupting the formation of the complex and preventing its degradation. The rapid increase in NOXA observed within 6 h is associated with the induction of apoptosis within 24 h. Considering a recent report that NOXA can induce cell death through a calcium-dependent pathway, our findings suggest that the BAX/BAK-independent cell death induced by BH3 mimetics may in fact be the result of their on-target mechanism of action. ABT-737 did not increase the levels of NOXA or MCL1, which is consistent with its inability to inhibit the binding of MCL-1 to NOXA. Furthermore, ABT-737 was the only BH3 mimetic that disrupted the binding of BCL-2 to BAD, suggesting that the other BH3 mimetics did not inhibit BCL-2. Lastly, gossypol, S1, and HA14-1 at a concentration that increased NOXA but not apoptosis, sensitized NB4 cells to ABT-737, inducing apoptosis within 6 h. We thus conclude that most BH3 mimetics inhibit MCL-1 but not BCL-2 or BCL-X, while combinations can be used to inhibit all these anti-apoptotic proteins and rapidly induce apoptosis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1040.
Abstract 1054: Identification of progesterone receptor membrane component-1 as the putative sigma-2 receptor
Authors: Xu Jinbin , Zeng Chenbo , Chu Wenhua , Pan Fenghui , Mach Robert H. 
Published: February 2011

Abstract
Sigma binding sites represent a unique class of receptors and are highly expressed in tumor cells. Two sigma binding site subtypes, known as sigma-1 and sigma-2 receptors, were distinguished based on differences in their pharmacological profiles and molecular weights. The sigma-1 receptor gene has been cloned and well characterized in the CNS and cancer biology. However, the sigma-2 receptor has not yet been cloned. The purpose of the current study is to identify and clone sigma-2 receptor. We have synthesized an irreversible sigma-2 receptor selective photoaffinity probe, WC-II-21, containing a fluorescein isothiocyanate (FITC) group. This ligand has high binding affinity for sigma-2 receptor (Ki = 13 nM) and relatively low binding affinity for sigma-1 receptor (Ki &gt; 1,000 nM). This ligand irreversibly labeled sigma-2 receptors in the rat liver membrane fractions after UV irradiation. The ligand-labeled proteins were solubilized, enriched and then separated through sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The position of a predominant band of the ligand-labeled protein in the gel was determined by western blot analysis using FITC antibody. MALDI-mass spectrometry analysis for the ligand-labeled proteins indentified the protein progesterone receptor membrane component-1 (PGRMC-1) with a convincingly high score of 81. Based on the similarities of the reported biological characteristics and functions between PGRMC1 and sigma-2 receptor, PGRMC1 was investigated in the current study. Immunocytochemistry revealed that PGRMC1 colocalized with molecular markers of endoplasmic reticulum and mitochondria in human melanoma cell line MDA-MB435. The subcellular localization of sigma-2 receptor also colocalized with fluorescent markers of endoplasmic reticulum and mitochondria as reported previously from our group (Cancer Res 2007; 67, 6708-6716). Thus, PGRMC1 and sigma-2 receptor appear to localize in the same subcellular organelles in the cell. PGRMC1 was knocked down with PGRMC1 siRNA in MDA-MB435 cells. Sigma-2 radioligand binding activity was significantly reduced in the PGRMC1 knocked down cells relative to the nontargeting siRNA transfected cells. These data suggest that PGRMC1 is the putative sigma-2 receptor. Further validation of PGRMC1 as the sigma-2 receptor is ongoing in our group. (Supported by CA 102869).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1054.
Abstract 1060: Regulation of SDF-1 (CXCL12) production by mesenchymal stromal cells in the tumor microenvironment
Authors: Amiri Sohrab , Lin Siang-Yo , Picinich Sonia , DeRenzo Christopher , Li Jiadong , Banerjee Debabrata , Glod John W. 
Published: February 2011

Abstract
The tumor microenvironment is made up of a number of cell types including fibroblasts, pericytes, endothelial cells, macrophages, and neoplastic cells. The interaction between cellular components of the microenvironment is critical for processes such as tumor growth, angiogenesis, and metastasis. Mesenchymal stromal cells (MSCs) are an important component of the tumor microenvironment with roles in key aspects of tumor progression such as cell growth and metastasis. Stromal-derived factor −1 (SDF-1) has been identified as a key signaling molecule in the interaction between MSCs and neoplastic cells. SDF-1 acting through its cognate receptors CXCR4 and CXCR7 is known to mediate diverse processes such as chemotaxis, angiogenesis, hematopoiesis, metastasis, and tumor growth. In this study we investigated the regulation of SDF-1 production by MSCs.
We show that the tumor suppressor p53 is one of the major regulators of SDF-1 signaling in MSCs within the tumor stroma. We also illustrate that a decrease in p53 function leads to increased SDF-1 production by MSCs which results in increased migration of MSCs. Decreased p53 expression by MSCs leads to increased SDF-1 production with and increased recruitment to the tumor microenvironment. An improved understanding of the molecular mechanisms controlling SDF-1 production by MSCs may identify novel ways of therapeutically targeting tumor - stromal interactions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1060.
Abstract 1083: Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53 mutated human epidermoid carcinoma A431 cells, and p53 wild-type human melanoma UACC-62 cells
Authors: Zhang Xiaoying , Chen Wei , Guillermo Ruth , Chandrasekher Gudiseva , Kaushik Radhey S. , Fahmy Hesham , Dwivedi Chandradhar 
Published: February 2011

Abstract
α-Santalol, an active component of sandalwood oil, has shown chemopreventive effects on skin cancer development in murine models by either chemical- or UVB-induced skin carcinogenesis. α-Santalol has shown induction of apoptosis in both murine models and epidermoid carcinoma A431 cells. However, to the best of our knowledge, effects of α-santalol on cell cycle have not been studied. Thus, the objective of this study was to investigate the effects of α-santalol on cell cycle progression and protein components involved in the regulation of cell cycle in both p53 mutated human epidermoid carcinoma A431 cells and p53 wide-type human melanoma UACC-62 cells to elucidate the mechanism(s) of action.
MTT assay was used to determine cell viability in A431 cells, UACC-62 cells and monkey kidney CV-1 cells; fluorescence-activated cell sorting (FACS) analysis of propidium iodide staining was used for determining cell cycle distribution in A431 cells and UACC-62 cells, and Western immunoblotting was used for determining the expression of various proteins involved in the cell cycle progression.
Results showed that α-santalol at concentration of 25 to 75 μM resulted in a concentration-and time-dependent decrease in cell viability from 24 h treatment in both A431 and UACC-62 cells. Cell cycle analysis by flow cytometry showed that α-santalol at 50 μM and 75 μM induced G2/M phase cell cycle arrest starting from 6 hour treatment in both UACC-62 and A431 cells. Furthermore, Western immunoblotting data showed that α-santalol altered the expressions of cell cycle proteins such as cyclin A, cyclin B1, cell division cycle 2 (cdc2), cdc25c and cyclin-dependent kinase 2 (Cdk2) in A431 cells which are required for G2/M transition. α-Santalol treatment upregulated the expression of p21CIP1/WAF1 and suppressed the expression of mutated p53 in A431 cells; whereas, α-santalol treatment increased the expressions of wide-type p53 in UACC-62 cells.
Taken together, this study for the first time identifies the effects of α-santalol in G2/M phase arrest and describes the detailed mechanisms of G2/M phase arrest by this agent in both p53 mutated A431 cells and p53 wide-type UACC-62 cells, which might be contributing to its overall cancer preventive efficacy in various mouse skin cancer models in addition to induction of apoptosis by α-santalol. (Supported by 2010 Research Initiative Grant from the State of South Dakota funded as Translational Cancer Research Center).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1083.