bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2654: 5-Fluorouracil increases and decreases proteins involved in oncogenic pathways
Authors: Wu Sherry Y. , Mori Noriko , Krishnamachary Balaji , Mironchik Yelena , Bhujwalla Zaver M. 
Published: June 2012

Abstract
Cancer cells are remarkably adaptive to treatments. 5-Fluorouracil, 5-FU, is a pyrimidine analogue, that is widely used for treatment of solid tumors1. It interferes with nucleoside metabolism and is incorporated into RNA and DNA, leading to cell death1. Its use, however, has been associated with increased cyclooxygenase-2 (COX-2) levels in breast, ovarian, esophageal, and colon cancers2 that could lead to the emergence of a more aggressive phenotype3. Here we have determined the effect of 5-FU in the expression of oncogenic molecules that are involved in phospholipid metabolism (choline kinase (Chk) and phospholipase D1 (PLD1)), inflammation (cyclooxygenase (COX)-2), and hypoxia response (hypoxia inducible factor (HIF)-1α) in order to facilitate a rational therapeutic design. Two triple negative breast cancer cell lines, MDA-MB-231 and SUM-149, were investigated. Cells were treated with 5-FU at various concentrations (1-25 μg/mL) and protein levels were examined at 24 and 48 hrs post treatment. Both HIF-1α and PLD1 levels decreased in a dose dependent manner following 5-FU treatment. In contrast, COX-2 level increased in response to 5-FU treatment together with an increase in Chk. Increased expressions of HIF-1α, PLD1, COX-2, and Chk have been associated with increased invasion and metastasis3-6. Our data suggest that in addition to its ability to interfere with DNA/RNA synthesis, 5-FU inhibits HIF-1α and PLD1 but increases the expression of two enzymes associated with invasive metastatic cancers. Importantly, while the mechanism by which 5-FU elevates COX-2 and Chk levels in these cancer cells remains to be investigated, these results provide a molecular basis for the combinational treatment of 5-FU with COX-2 and/or Chk inhibitors in cancer therapy.
References
(1) Arias J. Molecules, 2008.
(2) Mercer S.J., et al. Anticancer Drugs, 2005.
(3) Stasinopoulos I, et al. Neoplasia, 2008.
(4) Pai J.K., et al. Anticancer Drug Des, 1994.
(5) Shah T., et al. NMR Biomed, 2010.
(6) Lu X and Kang Y. Clin Cancer Res, 2010
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2654. doi:10.1158/1538-7445.AM2011-2654
Abstract 2655: Visualization of G1 arrest of cell cycle induced by inhibition of PI-3 kinase in cancer cells: in vitro evaluations
Authors: Mukai Yumiko , Dan Shingo , Okamura Mutsumi , Inoue Yasumichi , Hanyu Aki , Sakaue-Sawano Asako , Imamura Takeshi , Miyawaki Atsushi , Yamori Takao 
Published: June 2012

Abstract
The phosphoinositide 3-kinase (PI3K) pathway is frequently activated in cancer, and is considered as a promising therapeutic target of cancer therapy. Since PI3K pathway mediates growth- and anti-apoptotic signals, inhibition of PI3K is expected to induce apoptosis and/or growth arrest in cancer cells. We previously developed Fluorescent Ubiquitination-based Cell Cycle Indicator (Fucci) system to enable real-time visualization of cell cycle progression in live cells. Taking advantage of Fucci system, we examined cell cycle progression after treatment of various PI3K inhibitors by using a time-lapse fluorescent microscope. As a result, we could visualize the induction of G1 arrest of cell cycle in breast cancer MCF-7 cells within 24 h after treatment with ZSTK474, and the G1 arrest lasted at least 48 h. Similar results were obtained after treatment with other PI3K inhibitors such as NVP-BEZ235 and GDC-0941. These results clearly indicate that PI3K inhibitors exert antitumor activity via a cytostatic mechanism by inducing G1 arrest of cell cycle.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2655. doi:10.1158/1538-7445.AM2011-2655
Abstract 2660: Downregulation of Bora gene expression in human tumor cells results in radioresistance by promoting repair of double strand breaks
Authors: Hou Junmei , Qin Bo , Lou Zhenkun , Wang Liewei 
Published: June 2012

Abstract
DNA double-strand breaks (DSBs) are highly cytotoxic lesions caused by genotoxin such as ionizing radiation (IR). Following DSB, cells activate the DNA-damage response pathway by activating protein kinases such as ATM, ATR and DNA-PK, which then trigger histone H2AX phosphorylation and the accumulation of proteins such as Mediator of DNA damage checkpoint protein 1 (MDC1), 53BP1, and BRCA1 into IR-induced foci. This process initiates the repair of DSB. Previously we have identified a novel biomarker for radiation response, Bora, by using a genome-wide association approach using data generated with 300 human lymphoblastoid cell liens. Bora is known as a cofactor of Aurora-A, which is involved in mitosis regulation. During G2, Aurora-A, in complex with Bora, phosphorylates Plk1 at Thr-210. Activated Plk1 phosphorylates Cdc25C and Wee1, which induces activation of cyclin B-cdk1 complexes and promotes mitotic entry. In this study, we want to determine the underlying mechanisms by which Bora regulates response to IR. We found that knockdown of Bora in human cancer cell lines including HupT3, MIAPaCa-2 and Hela (siBora) exhibit increased clonogenic survival rate in response to IR, an observation that is opposite from the effect of Plk1 knockdown, suggesting a different mechanism involved. Knockdown of Bora also desensitize cancer cells to chemotherapeutic agents including gemcitabine and oxiplatin. This enhanced resistance to genotoxin is primarily due to increased DNA DSB repair. More than 90% of DSBs were repaired in siBora cells compared with 60% in control cells 8 hours after cell exposure to 2 Gy IR. Upon IR, more cells with Bora knockdown retained in G2-M phase compared with control. Furthermore, Bora directly interacts with BRCT domain of MDC1 via its C terminus, and over expression of Bora can abolish MDC1 foci formation induced by IR. All of these observations suggested a role of Bora in DNA damage response pathway and in turn, in chemo-radio resistance. Indeed, overexpression of the full length or C-terminus of Bora sensitized cancer cells to IR treatment, while the N-terminal Bora did not have significant effect on IR response. In summary, we have identified a novel function of Bora involved in DNA damage and repair pathway, which indicates a broad role of Bora in both tumorgenesis and chemo-radio resistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2660. doi:10.1158/1538-7445.AM2011-2660
Abstract 2678: Effect of amentoflavone on radiation response in neuronal cells
Authors: Wang Yi , Kong Xiangjuan , Tang Xiaobing , Zheng Xiaoke , Zhu Yanhui , Wang Shengqi , Wang Shengqi , Wang Huichen 
Published: June 2012

Abstract
Ionizing radiation induces DNA damage and oxidative stress, leading cell death during cancer therapy or genomic instability and carcinogenesis amentoflavone is a purified component extracted from medicine plants that are used to treat various diseases. Here we investigated the role of amentoflavone in radiation response in hippocampal neurons (HT22) and glioblastoma cells (U87 MG) following exposure to high linear transfer (LET) radiation and low LET radiation We found that Amentoflavone protects hippocampal neurons from radiation and enhances radiosensitivity of glioblastoma cells.Treatment of amentoflavone increased survival fractions in hippocampal neuronal cells following exposure to X-Ray radiation and 56Fe particles, though amentoflavone enhanced radiosensitivity of glioblastoma cells. Amentoflavone attenuated reactive oxygen species (ROS) and regulated DNA damage repair in irradiated hippocampal neurons through superoxide dismutase 1 (SOD1) and Foxkhead box O3 a (FOXO3a) pathways. Pretreament of amentoflavone also increased the survival rate of mice from whole body gamma irradiation. This suggests that amentoflavone may have a potential function on cancer chemo- radiotherapy and radiation protection from cancer risks. The mechanism needs to be further studied.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2678. doi:10.1158/1538-7445.AM2011-2678
Abstract 2681: Identification of potential immunologic targets found in mice and man that are expressed in colon adenomas and colorectal cancer
Authors: Broussard Elizabeth K. , Pritchard David K. , Lubet Ronald A. , Disis Mary L. 
Published: June 2012

Abstract
Multiple recent studies have demonstrated that colorectal cancer (CRC) is immunogenic and that host adaptive immunity may play a role in inhibiting disease relapse. We have shown that overexpressed tumor associated proteins, those abundant in the cancer state but expressed at basal levels normal cells, can be immunogenic. The purpose of this study was to identify genes overexpressed in colorectal adenoma that maintain upregulation in CRC using publicly available microarray datasets in the Gene Expression Omnibus. Such genes may encode proteins that could be suitable as immunologic targets for a colon cancer vaccine. We identified 7 high-quality datasets (GSE 867, 4183, 1095, 5206, 15960) where human adenomatous or CRC tissue was directly compared to normal colon. Inclusion criteria for the datasets included: commercial platforms, primary tissue, normal colon expression included, data generated after 2005, and access to microarray data. We reanalyzed these datasets and identified 100 genes that were ≥ 2-fold up-regulated in both adenomas and CRC, relative to normal colon. We further characterized these genes using a scoring system using the following criteria: 1) strong expression in CRC as compared to normal colon (RNA and protein), 2) evidence that the gene is biologically important in CRC initiation or progression, 3) limited expression of the gene in normal tissues, and 4) proven immunogenicity of the encoded protein. We hypothesized that genes that were highly conserved across species would potentially have greater biologic relevance, so we identified relevant microarray studies in mouse CRC models. We identified 2 studies (GSE 422, 784) which were limited in their data set and performed a similar analysis. We identified 93 murine genes that were conserved from adenoma to carcinoma. Comparison of the human and rodent data set revealed an overlap of 11 genes. We conclude that there are a limited number of genes up-regulated in adenoma and carcinoma and conserved across disease in mouse and man. If these proteins are immunogenic, they may serve as novel immunologic targets to prevent the progression from normal colonic epithelium to adenoma or carcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2681. doi:10.1158/1538-7445.AM2011-2681
Abstract 2687: Immunopotentiator, protein-bound polysaccharide K, is efficient for advanced gastric cancer with negative expression of MHC Class I
Authors: Gentaro Ito , Hiroaki Tanaka , Mami Yoshi , Takehiro Iwauchi , Kazuya Muguruma , Naoshi Kubo, , Hisashi Nagahara , Kenjiro Kimura , Ryosuke Amano , Eiji Noda , Nobuya Yamada , Masakazu Yashiro , Naoyoshi Onoda , Kiyoshi Maeda , Bunzo Nakata , Masaichi Ohira , Tetsuro Ishikawa , Kosei Hirakawa 
Published: June 2012

Abstract
It has been reported that down-regulation of MHC class I in cancer cells was associated with poor prognosis of gastrointestinal cancer, because of immunological escape from the attack of antigen specific cytotoxic T lymphocytes. Protein-bound polysaccharide K (PSK), nonspecific immunopotentiator, is approved for adjuvant chemotherapy against Stage II/III gastric cancer in Japan. Several randomized studies have demonstrated the efficacy of immunochemotherapy using PSK for colon and gastric cancer. The aim of this study was to investigate whether expression of MHC class I was associated with prognosis of the patients who received PSK as postoperative adjuvant therapy. We retrospectively analyzed total of 349 gastric cancer patients who underwent curative gastric cancer surgery in Department of Surgical Oncology, Osaka City University from 1995 to 2008. We investigated the expression of MHC class I antigen in primary lesions using immunohistchemistry to compare the relapse-free survival (RFS) between the patients receiving only oral fluoropyrimidine agents (the control group) and plus PSK (the PSK group). 124 patients were assigned to the PSK group and 225 patients to the control group. There were no differences between two groups in background factors. In analysis of MHC class I expression, 193 patients were classified as MHC class I positive, and 156 patients as MHC class I negative. RFS was significantly better in MHC class I positive group. Combination of anti cancer agents with PSK did not improve the RFS among total patients. However, in patients with multiple lymph node metastasis and negative expression of MHC class I, the 5-year RFS of the PSK group was significantly better than the control group. These results suggested that the expression of MHC Class I in primary lesion could be one of the prognostic markers related to the efficiency of adjuvant immunochemotherapy for patients with gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2687. doi:10.1158/1538-7445.AM2011-2687
Abstract 269: DACH1 (Dachshund homolog 1) attenuates forkhead signaling through recruiting transcription elongation regulator 1 (TCERG1)
Authors: Wang Chenguang , Zhou Jie , Wu Kongming , Tozeren Aydin , Zhao Keji , Pestell Richard G. 
Published: June 2012

Abstract
The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant, ellipse, encodes a key component of the Retinal Determination Gene Network (RDGN) that governs cell fate. DACH1 (Dachshund homolog 1) regulates gene expression either indirectly as a co-integrator or through direct DNA binding. CAST identified a DACH1 DNA-binding sequence which resembles the FOX (Forkhead Box containing protein) binding site. Genome-wide in-silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP-Seq mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the CAST-defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contact-independent growth. Further studies were conducted to understand, at a higher level of resolution, the mechanisms governing DACH1-mediated transcriptional repression via DNA-sequence specific binding. DACH1 repressed, while FOX proteins enhanced, both DRE and FOXA responsive element-driven gene expression. Reduced DACH1 expression using a shRNA approach enhanced FOX protein activity. As DACH1 antagonized FOX target gene expression and attenuated FOX signaling, we sought to identify limiting co-integrator proteins governing DACH1 signaling. Proteomic analysis identified transcription elongation regulator 1 (TCERG1) as the transcriptional co-regulator of DACH1 activity. The FF2 domain of TCERG1 was required for DACH1 binding, and the deletion of FF2 abolished DACH1 trans-repression function. The carboxyl terminus of DACH1 was necessary and sufficient for TCERG1 binding. Thus, DACH1 represses gene transcription through direct DNA binding to the promoter region of target genes by recruiting the transcriptional co-regulator, TCERG1. Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 269. doi:10.1158/1538-7445.AM2011-269
Abstract 2695: Lactobacillus plantarum induces TRAIL production and facilitates natural killer activity against cancer cells
Authors: Horinaka Mano , Yoshida Tatsushi , Kishi Atsuko , Akatani Kaoru , Yasuda Takashi , Kouhara Junji , Wakada Miki , Sakai Toshiyuki 
Published: June 2012

Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-tumor agent due to its induction of apoptosis in various types of malignant tumor cells with little or no toxicity in normal cells. TRAIL is an endogeneous cytokine, and thus, it may be possible to develop agents that can induce endogeneous TRAIL production as an anti-tumor strategy. Here, we show for the first time that lactobacilli induce TRAIL production in normal human peripheral blood mononuclear cells (PBMC). Treatment with heat-killed Lactobacillus (L.) plantarum, a type of lactobacilli, induced TRAIL expression on the surface of PBMC. L. plantarum also enhanced the release of soluble TRAIL into the culture medium. Moreover, L. plantarum increased the level of TRAIL mRNA as well as TRAIL protein, indicating that L. plantarum up-regulates TRAIL gene expression. L. plantarum also increased the secretion of interferon-γ (IFN-γ) from PBMC. The release of soluble TRAIL from PBMC was partially blocked by IFN-γ neutralization antibody, indicating that the TRAIL production induced by L. plantarum at least partially depends on IFN-γ. To examine whether TRAIL production by L. plantarum leads to cytotoxicity in cancer cells, we co-cultured prostate cancer cells with L. plantarum-treated PBMC and measured natural killer (NK) activity. L. plantarum facilitated NK activity, and the dominant negative form of TRAIL receptor and TRAIL neutralization antibody efficiently prevented NK activity. Our results indicate that L. plantarum facilitates TRAIL-dependent NK activity through TRAIL production, and raise the possibility of a new strategy for TRAIL-based prevention or therapy against malignant tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2695. doi:10.1158/1538-7445.AM2011-2695
Abstract 2705: Glycoprotein 90K's antitumor effects through activation of the dendritic cells
Authors: Lee Ji Hee , Park Myong Suk , Park Mi Ra , Bae Woo Kyun , Hwang Jun Eul , Lee Jae Hyuk , Chung Ik Joo 
Published: June 2012

Abstract
The secreted glycoprotein, 90K is also known as Mac-2 binding protein belonging to the scavenger receptor cysteine-rich domain superfamily that is implicated in immune defense and immune regulation. We examined the relation between over-expressed 90K in tumor cells and immune activation.
Here, we investigated whether over-expressed 90K enable the activation of signal transduction pathways and subsequent modulation of DC-maturation status. In vitro cell functional assay, transduction of 90K to dendritic cells was achieved by adenoviral system. Also, we tried to make a mouse model with cancer overexpressing 90K and cancer knockdowned 90K. Then, we analyzed the infiltrated immune cell into tumor region and splenocytes of tumor bearing mice. Dendritic cells transfected with 90K showed IL12p70 and IFN-gamma incensement in DC-cytokine profile and induction of Th1 responses. Tumor infiltrating cells (TIL) into splenocytes were increased in tumor bearing mice knockdowned 90K. Our data indicate that 90K can induce robust maturation of dendritic cells and tumor regression through recruiting TIL. We suggest that 90K may play role in a new target for the treatment of cancer by immune modulation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2705. doi:10.1158/1538-7445.AM2011-2705
Abstract 271: Rapid regulation of ion channel KCNK5 by ERα in breast cancer cell lines MCF-7 and T47D promotes cell proliferation
Authors: Alvarez-Baron Claudia P. , Jonsson Philip , Dryer Stuart , Williams Cecilia 
Published: June 2012

Abstract
Many human breast tumors rely on the proliferative effect of estrogen to propagate. Estrogenic compounds, such as the endogenous ligand 17β-estradiol, signals in various manners, most prominently through the estrogen receptors (ERs). The ERs – alpha and beta, respectively – are transcription factors belonging to the superfamily of nuclear receptors. They act by genomical and non-genomical mechanisms in a ligand-dependent as well as -independent manner, exerting ligand-, promoter- and tissue-specific transcriptional programs. Due to the proliferative effect of ERα in breast it is an important factor in tumor progression. ERα is used clinically as a biomarker and is therapeutically targeted by treatment with antagonistic compounds, for instance tamoxifen. Although extensively studied, the mechanism by which ERα promotes proliferation remains to be fully established. Here we present the finding that ERα rapidly upregulates the potassium ion channel KCNK5 (TASK-2, K2P5.1) in human breast cancer cell lines MCF-7 and T47D. ERα binds at the enhancer of the KCNK5 gene upon estrogen stimulation, subsequently inducing increases in transcript and protein levels of KCNK5. The observed upregulation was strikingly quick, with a sharp peak within one to two hours, before leveling off. Protein levels, however, did not increase until after 12 hours. Treatment with compounds antagonizing ERα transactivation efficiently suppressed this upregulation, further supporting the notion of direct ERα regulation, as compared to non-genomic signaling. Estrogen treatment also increased KCNK5 currents in both cell lines. Various roles for potassium channels in cancer cells have previously been suggested, as for example proliferative, metastatic and anti-apoptotic factors. Knockdown of KCNK5 by siRNA in MCF-7 and T47D cells decreased their proliferation. Additionally, in T47D cells, the estrogen-induced proliferation was repressed when KCNK5 was silenced. This prompts further studies to understand the role of KCNK5 in the proliferation of breast cancer cells and clinical relevance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 271. doi:10.1158/1538-7445.AM2011-271