bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4342: Inhibition of radiation-enhanced cell adhesion in breast cancer cells by ROS scanvenger
Authors: Cheng Huiwen , Lee Shinhee , Wu Shiyong 
Published: August 2012

Abstract
Ionizing radiation (IR) therapy is one of the main therapies to treat breast cancer, but accumulating evidence suggests that IR is potentially associated with increased invasion and metastasis. A great increase in breast cancer cell adhesion to fibronectin after high dose α-radiation was observed in our group, and it accompanied with ROS boost. However it is not known whether ROS increase related to the cell adhesion increase after α-radiation. In this report, we showed that the increased cell adhesion to fibronectin was reduced by ROS scavenger L-NAC by 21.8% after α-radiation, but was not affected by H2O2 scavenger, catalase or by cNOS inhibitor, L-NAME with 24 h treatment. We then determined that the cell adhesion inhibition after α-radiation involve reduced ROS, and reduced vinculin expression and integrin activation after treating with L-NAC for 24 h. However, a short-term, 1 h pre-IR followed by 2 h post-IR, treatment of L-NAC promotes ROS production and has no effect on cell adhesion at 24 h post-IR. These results suggest that L-NAC long-term treatment could potentially have an impact on breast cancer metastasis by inhibiting the ROS and cell adhesion. These results suggest that to inhibit IR-induced breast cancer adhesion, an uninterrupted treatment of L-NAC may be required.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4342. doi:1538-7445.AM2012-4342
Abstract 4346: Influence of ionizing radiation on transcription of human endogenous retrovirus-K (HERV-K) in breast cancer cell lines
Authors: Agoni Lorenzo , Lenz Jack , Guha Chandan 
Published: August 2012

Abstract
Ionizing Radiation (IR) has been reported to increase the transcriptional activity of many viruses, including retroviruses. We hypothesized that IR could reactivate subsets of Human Endogenous Retroviruses (HERVs), which are retroviruses integrated into the human genome, remnants of ancient retroviral infections, and that HERV-derived peptides, the final product of HERVs transcription, will increase the diversity of the antigen repertoire presented by irradiated cancer cells, thereby inducing anti-tumor immune responses. IR has been shown to increase the immunogenicity of cancer cells by modulating various cellular processes, including antigen presentation by MHC. HERVs are known to be transcribed in numerous diseases including cancer, HIV infection, and autoimmune disorders. HERV-K is the most recently integrated and thus intact HERV family, with approximately 350 loci in the human genome, 98 to 99% identical. Previous experiments in our laboratory have shown IR-dependent increases in HERV-K transcription, plus increased HERV-K-derived peptides in irradiated prostate carcinoma cell lines upon proteomic LC-MS/MS analysis of peptides eluted from MHC-I complexes. HERV-K activation has been reported in breast cancer. To test the influence of IR on HERV-K transcription, three breast cancer cell lines (MDA-MB-468, MDA-MB-231 and MCF7) were analyzed by RT-PCR and qRT-PCR at specific time-points, from 1 to 72 hours, after different doses of α-irradiation (0, 2.5, 5, 10 and 20 Gy). HERV-K transcription was detected in all cell lines studied. After IR, each cell line showed distinct dose-response curves of HERV-K transcription during the time-frame of observation. Overall, the peak of HERV-K transcription in irradiated samples, when compared to non-irradiated samples, was increased by an average of 2- to 5-fold. Multiple, active, individual HERV-K loci were detected. Cloning and sequencing are ongoing to identify specific active loci for each cell line. These findings show that HERV-K is actively transcribed in breast carcinoma cell lines. The IR-dependent increase in HERV-K transcription may enhance antigen repertoire diversity, contribute to the immunomodulatory properties of IR, and offers attractive targets for the development of novel IR-enhanced immunotherapies for cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4346. doi:1538-7445.AM2012-4346
Abstract 4353: Tristetraprolin (TTP) mediates radiation-induced TNF-α production in lung macrophages
Authors: Ray Dipankar , Helman Abigail , Shukla Shirish , Ramanand Susmita Gurjar , Tran Linda , Bassetti Michael , Nyati Mukesh K. , Zhang Ming , Lawrence Theodore S. 
Published: August 2012

Abstract
The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by lung macrophages. Tristetraprolin (TTP), an adenosine-uridine (AU) rich element (ARE) associated RNA binding protein, is known to destabilize TNF-α mRNA during lipopolysaccharide-induced inflammatory response and now we have identified that radiation causes TTP inactivation via inhibitory (Ser178) phosphorylation and induction of proteasome-mediated degradation, leading to increased TNF-α mRNA stability and secretion. Our preliminary studies indicate possible involvements of PI3K and p38 signaling in radiation-induced inactivating phosphorylation of TTP and we further identify an ubiquitin ligase [Skp-Cullin-F-box (SCFα-TrCP)] responsible for controlling radiation-induced TTP protein stability. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4353. doi:1538-7445.AM2012-4353
Abstract 4355: Use of MnSOD tet on transgenic mice as a model for evaluating irradiation protection and mitigation
Authors: Epperly Michael W. , Chaillet J. Richard , Cao Shaonan , Zhang Xichen , Greenberger Joel S. 
Published: August 2012

Abstract
Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme responsible for the dismutation or reduction of superoxide produced by cellular respiration. Absence of MnSOD is lethal two to three days after birth. Following irradiation there is an increase in superoxide production which combined with nitric oxide can result in the formation of the highly reactive radical peroxynitrite. Increased expression of MnSOD in a cell increases survival by the reduction of superoxide produced following irradiation. Decreased MnSOD production has resulted in decreased survival following irradiation. To better understand the role of MnSOD in cellular respiration as well as protecting the cell from irradiation damage, we have developed a MnSOD tet on mouse which has no MnSOD activity. In the absence of doxycycline the homozygous MnSOD tet on mouse does not survive past 2 or 3 days after birth. If doxycycline (2 µg/ml) is added to the water of heterozygous mothers, the MnSOD tet on mice develop normally and are fertile as long as they remain on the doxycycline treated water. Long term bone marrow cultures (LTBMCs) were established from homozygous MnSOD tet on mice, heterozygous tet on mice and control C57BL/6J mice. The cultures from the control mice had more hematopoietic cell activity than the MnSOD tet on cultures. To determine when the MnSOD gene is turned on after addition of doxocycline, bone marrow stromal cell lines were developed from the LTBMCs were incubated in 1 µg doxocycline/ml media for time points up to 24 hr, RNA was extracted and RT-PCR for the MnSOD transgene was performed. By 12 hours there was an increase in MnSOD RNA expression in the MnSOD tet on cells. Removal of the doxycycline resulted in a decrease in MnSOD RNA by 1 hr in the MnSOD tet on cells as well as the heteroxyzous cells. This mouse model will be useful for testing new compounds for radiation protection and mitigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4355. doi:1538-7445.AM2012-4355
Abstract 4360: CD87 is essential for mediating growth-factor induced angiogenesis via distribution of integrin beta-1
Authors: Unseld Matthias , Poettler Marina , Novotny Rene , Zielinski Christoph , Prager Gerald W. 
Published: August 2012

Abstract
CD87 (urokinase-type plasminogen activator receptor, uPAR) expression has been correlated with tumor progression most likely via its functional ole as a central receptor for extracellular proteolysis, but also via its role in initiating intracellular signal transduction. The role of CD87 in angiogenesis has recently been elucidated. Thus, we observed that in VEGF-stimulated ndothelial cells CD87 is essential for endothelial cell survival as well as for n efficient growth factor- induced endothelial cell migration. Thereby, the PI-anchored protein CD87 formed a complex with its ligand urokinase uPA) as well as the inhibitor plasminogen activator inhibitor-1 (PAI-1), which became redistributed to the leading edge via low density lipoprotein receptor- (LDLR-) like proteins. In this study, we analyzed the functional role of CD87 in integrin redistribution during growth factor-induced endothelial cell migration. CD87, thereby, directly interacted with integrin adhesion receptors (a5b1) as well as with LDLR- proteins. Either by interfering with CD87/integrin nteraction or by interfering with CD87/LDLR-protein interaction by using specific interfering peptides, we observed disruption of integrin redistribution to the leading edge in migrating cells. As a consequence diminished focal adhesion formations were observed and endothelial cell migration was diminished. In CD87-deficient HEK 293 cells as well as in endothelial cells derived from CD87 -/- mice, expression of CD87 mutants (mutL3/uPAR), which lacked the binding motif for LDLR, led to an impaired cell spreading as well as a diminished migratory response towards VEGF, while full length CD87 (wt/CD87) reconstituted this phenotype. That CD87 plays a central role in growth factor induced endothelial cell invasion and capillary-like tube formation in vivo was demonstrated by a directed in vivo angiogenesis assay (DIVAA), which was performed either in CD87 deficient or wild type animals in the presence or absence of interfering peptides. Our data give novel insights into the central role of CD87 in pro- angiogenic endothelial cell behavior as well as in its role in angiogenesis. Thus, CD87 might lead to a novel therapeutic strategies in tumor- angiogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4360. doi:1538-7445.AM2012-4360
Abstract 4363: Tumor regulation of myeloid-derived suppressor cell proliferation, circulation and apoptosis.
Authors: Talmadge James E. , Dafferner Alicia J. , Britton Holly C. , Younos Ibrahim H. 
Published: August 2012

Abstract
In response to stress, myeloid progenitor cells (MPCs) mobilize and establish sites of extramedullary hematopoiesis (EMH) within lymphoid and parenchymal organs. We report that the spleens of 4T1 mammary tumor-bearing (TB) mice are the primary site of MPC proliferation resulting in extensive EMH in association with decreased apoptosis, increased myeloid cell survival, and increased hematopoietic growth factor (GF) transcription by the tumor cells. MPC trafficking and survival differs between TB and naïve mice with leukocyte arrest in the lungs of naïve mice and accumulation in the splenic red pulp of TB mice with little marrow or tumor arrest or proliferation. Indeed, despite the high levels of GF transcription by tumor cells MDSC apoptosis in tumors is very high perhaps due to the high levels of NOS2 in the tumor microenvironment. Further myeloid proliferation directly correlates with the decrease in T-cell frequency, which is associated with extrathymic, but not thymic T-cell proliferation. In summary, tumor cytokines regulate a dynamic relationship between MPCs and T-cells regulating their proliferation, trafficking, accumulation, apoptosis, and survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4363. doi:1538-7445.AM2012-4363
Abstract 4365: A cellular model for investigation of circulating tumor cells and identification of therapeutic target and regimen
Authors: Chang Yao-Wen , Chong Kowit-Yu , Lin Pei-Yun , Hsieh Pei-Wen , Liao Chang-Hui , Tseng Ching-Ping 
Published: August 2012

Abstract
Tumor cells disseminating into circulatory system is crucial for cancer metastasis during cancer progression and surgical operation in removing tumor mass. Due to technical hurdles, it is not yet available to culture and propagate circulating tumor cells derived from cancer patients. Not yet any model system has been established to investigate the cellular and molecular changes associate with the entry of primary tumor cells into bloodstream. In this study, genetically modified C6 glioma cells (C6-LG) that elicit high procoagulant activity and express luciferase/GFP reporter gene were used for xenograft injection into nude mice to establish a metastatic model. Two C6-derived sublines, C6-lung and C6-blood, were isolated and established from the cells that colonized at lung tissue and from blood circulation, respectively. Cellular analyses revealed that C6-lung and C6-blood had differential cell cycle distribution, cell growth rate, migration and metastatic potential. Microarray analyses also revealed differential gene expression signatures between these two sublines. Nevertheless, podoplanin was up-regulated in both cell lines when compared to the parental C6-LG. Consistent with these observations, C6-lung and C6-blood activated platelet and induced platelet aggregation that is closely associated with their in vivo metastatic potential as revealed by gene knockdown analysis. Using these C6-sublines as the cellular screening platform, we have identified a novel compound designated as CGU-07 that elicited inhibitory activity in cancer cell-induced platelet aggregation. In conclusion, circulating and primary tumor cells have both common and distinguished cellular and molecular profiles. Targeting on the common molecular signature such as podoplanin raises the hope to further application of its therapeutic use in the prevention and treatment of tumor metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4365. doi:1538-7445.AM2012-4365
Abstract 4428: Diethylnitrosamine-induced hepatocarcinogenesis is suppressed in mice lacking hepatic retinoid storage
Authors: Shirakami Yohei , Blaner William S. , Shimizu Masahito , Moriwaki Hisataka 
Published: August 2012

Abstract
Retinoids are known to possess anti-cancer effects and a clinical trial of a synthetic retinoid for hepatocellular carcinoma (HCC) is ongoing recently in Japan. Loss of retinoid-containing lipid droplets upon hepatic stellate cell (HSC) activation is one of the first events in the development of liver disease leading to hepatocellular carcinoma (HCC). Although retinoid stores are progressively lost from HSCs during the development of hepatic disease, how this affects hepatocarcinogenesis is unclear. To investigate this, we used diethylnitrosamine (DEN) to induce hepatic tumorigenesis in matched wild-type (WT) and lecithin:retinol acyltransferase (LRAT) knockout (KO) mice, which lack stored retinoid and HSC lipid droplets. Male 15 day-old WT or Lrat KO mice were given intraperitoneal injections of DEN (25 mg/kg body weight). Eight months later Lrat KO mice showed significantly less liver tumor development compared to WT mice, characterized by less liver tumor incidence and smaller tumor size. Two days after DEN injection, lower serum levels of alanine aminotransferase and decreased hepatic levels of cyclin D1 were observed in Lrat KO mice. Lrat KO mice also exhibited increased levels of retinoic acid-responsive genes, including p21, lower levels of cytochrome P450 enzymes required for DEN-bioactivation, and higher levels of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), both before and after DEN treatment. Our results indicate that Lrat KO mice are less susceptible to DEN-induced hepatocarcinogenesis due to increased retinoid signaling and higher expression of p21, which is accompanied by altered hepatic levels of DEN-activating enzymes and MGMT in Lrat KO mice also contribute to decreased cancer initiation and suppressed liver tumor development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4428. doi:1538-7445.AM2012-4428
Abstract 443: Expression of the RECK tumor and metastasis suppressor gene in human breast cancer: a poor prognosis marker
Authors: Gomes Luciana R. , Fujita Andre , Soares Fernando A. , Labriola Leticia , Sogayar Mari C. 
Published: August 2012

Abstract
Metastasis is the main cause of mortality in breast cancer human patients. The organized breakdown of the extracellular matrix (ECM) compounds by matrix metalloproteinases (MMPs) is the key event in this metastatic process. Consistent with their role in tumor progression, high levels of several MMP family members have been shown to be correlated with poor prognosis. The MMP activities are tightly regulated by their inhibitors, namely: the metalloproteinases tissue inhibitors (TIMPs) and the membrane-associated inhibitor (RECK - Reversion-inducing Cysteine-rich protein with Kazal motifs). Due to RECK's ability to down modulate MMPs (MMP-2, 9 and 14), it is described as an important inhibitor of invasion and metastasis in several types of cancer. In order to investigate possible correlations between the RECK expression profile and clinical-pathological data in a breast cancer model, we evaluated the RECK protein in 1,040 tissue samples from invasive breast tumors using Tissue Microarray Assays (TMA). Associations between RECK expression and different clinical-pathological parameters and other biomarkers were evaluated using the Chi-square test. RECK immunoreactivity was significantly associated with higher SBR grade (p&lt;0.05) and TNM stage (p=0.002). Moreover, higher RECK expression levels were correlated with p53 (p&lt;0.001), her-2 (p=0.011), CK5,6 (p&lt;0.001) and egfr (p&lt;0.001) positivity. We also analyzed the relationship between RECK expression and the patient outcome, using Kaplan-Meier curves, demonstrating that patients with RECK positive tumors display significantly shorter disease free survival time (p=0.031) than those with RECK negative tumors. Furthermore, RECK expression was positively correlated with short disease free survival in five-years in patients diagnosed with tumors: low SBR grade (p=0.03), her-2 negative (p&lt;0.05) and luminal markers (CK8/CK18) positive (p=0.02 and p=0.003, respectively). In addition, RECK was a predictor of poor prognosis for post-menopause (p=0.011) and patients older than 50 years (p=0.05). All together, our results indicate that higher RECK expression is associated with poor prognosis variables, being a predictor of shorter disease-free survival in five years. Moreover, we verified that RECK is a biomarker of poor prognosis mainly for patients diagnosed with less aggressive breast tumor. Therefore, in contrast to other tumor types, our results indicate that RECK is related to a more aggressive phenotype. Support: FAPESP, CNPq, FINEP, CAPES, BNDES
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 443. doi:1538-7445.AM2012-443
Abstract 4432: Pancreatic normal duct epithelial and cancer cells express an autocrine catecholamine loop that is activated by the α3, 5 and 7 nicotinic acetylcholine receptors
Authors: Al-Wadei Mohammed H. , Al-Wadei Hussein A. , Schuller Hildegard M. 
Published: August 2012

Abstract
Pancreatic cancer is the fourth leading cause of cancer deaths in developed countries. Smoking is an established risk factor for this malignancy but the underlying mechanisms are poorly understood. Previous reports have provided evidence that nicotinic acetylcholine receptors (nAChRs) and beta-adrenergic receptors (α-ARs) stimulate the growth and migration of pancreatic cancer cells. But a potential cooperation of these two receptor families in the regulation of pancreatic cancer has not been studied to date. Using two pancreatic cancer cell lines and immortalized pancreatic duct epithelia in vitro, our current data show, that all three cell lines synthesized and released the catecholamine neurotransmitters noradrenaline and adrenaline upon exposure to nicotine and that this activity was regulated by the α3, 5 & 7-nAChRs. In accord with the established function of these catecholamines as α-AR agonists, nicotine-induced cell proliferation was blocked by the α-AR antagonist propranolol. Nicotine-induced proliferation was also abolished by the α7-nAChR antagonist α-bungarotoxin and catecholamine production in response to nicotine was blocked by α3, 5 or 7-nAChR gene knockdown. Moreover, our results show that the nicotinic agonists acetylcholine, nicotine, and its nitrosated carcinogenic derivative NNK induced the phosphorylation of CREB, ERK, Src and AKT and that those responses were inhibited by the beta-blocker, propranolol. Our findings identify this hitherto unknown autocrine catecholamine loop as an important regulatory cascade in pancreatic cancer that may prove a promising new target for cancer intervention. Supported by R01CA042829 and R01CA130888 with the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4432. doi:1538-7445.AM2012-4432