bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2281: Host CXCR2 expression regulates mammary tumor growth, angiogenesis and progression
Authors: Nannuru Kalyan C. , Varney Michelle L. , Singh Rakesh K. 
Published: February 2011

Abstract
Breast cancer is a devastating clinical condition affecting more than 100,000 women in a year and is responsible for more than 40,000 deaths every year. Chemokines and their receptors have been shown to regulate various aspects of tumor development and progression. Constitutive expression of pro-inflammatory chemokines, a hallmark of many human cancers, helps establish a supportive tumor stroma, and, in some cases, directly stimulates tumor proliferation and invasion via receptors on tumor cells. Evidence suggests that CXCR2 regulate multiple functions in leukocytes, endothelial cells (ECs), and/or tumor cells and their precursors and thus play important role in tumor angiogenesis, growth and metastasis. In this study, we investigated the role of host CXCR2 expression in mammary tumor growth, neovascularization and tumor induced osteolysis using a syngenic mouse mammary tumor model. Eight week old BALB/c mice either expressing CXCR2 (mCXCR2 WT) or genomic knock down of CXCR2 (mCXCR2 −/−) were used to study the functional role of host CXCR2 in mammary tumor growth and progression. Orthotopical implantation of mammary tumors in mouse mammary fat pad reveals a significant decrease in tumor growth in mCXCR2 −/− compared to wild type mice. Knock-down of host CXCR2 has significantly reduced tumor-induced neovascularization in orthotopical tumors. Bone is the most common site of metastasis in breast cancer. To access the role of host CXCR2 in tumor-induced osteolysis and tumor growth in bone microenvironment, mammary tumor cells were implanted on calvaria. Tumor-induced osteolysis and osteoclast homing at the tumor-bone interface was significantly reduced in CXCR2 knockout mice compared to wild type mice. These results suggest that host CXCR2 may play a critical role in tumor development and angiogenesis as well as tumor-induced osteolysis. These data demonstrate direct evidence of host CXCR2 in breast cancer progression and metastasis, and will allow development of CXCR2 targeting as a novel approach to breast cancer treatment.
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 2281.
Abstract 229: Omega-3 fatty acids strongly induce apoptosis in human breast cancer cells in vitro and in vivo via formation of reactive oxygen species and caspase 8 activation
Authors: Wang Pan , Kang Ki-Sung , Yamabe Noriko , Fukui Masayuki , Jay Taylor , Zhu B T. 
Published: February 2011

Abstract
[Hypothesis] The present study sought to investigate the in vitro and in vivo anticancer effect of two representative omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with a focus on assessing the role of fatty acid-induced oxidative stress and apoptosis as mechanisms for their anticancer actions.
[Methods] We used in vitro cell culture of MCF-7 human breast cancer cells and in vivo athymic nude mice model to study the effect of omega-3 fatty acids on cancer cell proliferation and the mechanism of the cell death.
[Results] In vitro studies showed that DHA and EPA each strongly reduced the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and they also promoted cell death via apoptosis. Mechanistically, accumulation of reactive oxygen species and activation of caspase 8 contributed critically to the induction of apoptotic cell death. Co-presence of antioxidants or a selective inhibition or knockdown of caspase 8 each effectively abrogated the cytotoxic effect of DHA. Using athymic nude mice as an in vivo model, we found that feeding animals with 5% fish oil-containing diet for 6 weeks significantly reduced the growth of MCF-7 human breast cancer cells through inhibition of cancer cell proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that fish oil diet significantly increased oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and tissues showed that feeding animals a 5% fish oil diet significantly increased DHA and EPA levels in both normal and tumorous mammary tissues by 329 and 300%, respectively.
[Conclusion] The results of this investigation clearly showed that omega-3 fatty acids strongly inhibited human breast cancer proliferation both in vitro and in vivo via formation of reactive oxygen species and induction of apoptosis by caspase 8 activation. This study calls for further studies in human subjects to assess the effectiveness of fish oil as a dietary supplement in the treatment of certain types of cancers.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 229.
Abstract 2290: A novel function in metastasis for YY1 overexpression in the initiation of the EMT phenotype
Authors: Baritaki Stavroula , Huerta-Yepez Sara , Yeung Kam , Neonakis Ioannis , Bonavida Benjamin 
Published: February 2011

Abstract
Metastasis is the main cause of death in cancer patients. The underlying molecular mechanisms of the metastatic process and their regulation in different malignancies are unknown. Survival pathways, such as the constitutively activated NF-κB pathway, contribute to the initiation of metastasis, a process known as epithelial to mesenchymal transition (EMT). The EMT phenotype is characterized by several gene modifications such as inhibition of epithelial gene products (e.g. E-cadherin, cytokeratin 18) and upregulation of mesenchymal gene products (e.g. vimentin and fibronectin). In addition, the cells exhibit invasive properties. The metastasis-inducer transcription factor, Snail, is intimately involved in EMT and is transcriptionally regulated, in part, by NF-κB. A recent report demonstrated that Snail is transcriptionally regulated, in part, by the transcription factor Yin Yang 1 (YY1) and YY1 is downstream of NF-κB. We have reported that YY1 expression is a prognostic marker in prostate cancer and YY1 also regulates tumor cell resistance to apoptosis by cytotoxic therapeutics. Based on these findings, we hypothesized that the expression levels of YY1 in cancer may also regulate EMT directly and/or indirectly through its regulation of Snail transcription. This hypothesis was tested using the human metastatic prostate carcinoma cell lines, PC-3 and DU-145, that exhibit the EMT phenotype as models. The relationship between inhibition of YY1 and inhibition of EMT was established by several lines of evidence. Treatment of the tumor cells with the proteasome inhibitors, NPI-0052 or Bortezomib, inhibited NF-κB, Snail and YY1 activities and correlated with inhibition of EMT. The direct role of YY1 expression and activity in the regulation of EMT was shown by treating cells with YY1 siRNA and resulting in the inhibition of the EMT phenotype. In turn, inhibition of Snail resulted in upregulation of the expression of the metastasis-suppressor/immune surveillance cancer gene product, Raf-1 kinase inhibitor protein (RKIP). The upregulation of RKIP by YY1 siRNA was due to the inhibition of the RKIP transcription repressor Snail. These findings establish a novel role for YY1 in the regulation of EMT. The findings also establish the dysregulation of the circuitry NF-κB/Snail/YY1/RKIP in cancer and metastasis resulting in the initiation of EMT. Further, this dysregulation has also been recently reported by us to regulate tumor cell resistance to apoptotic-inducing stimuli. Therefore, this dysregulated circuitry and downstream regulated gene products may be considered as novel targets for the regulation of both metastasis and resistance.
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 2290.
Abstract 2313: Role of ferritin dysregulation in human breast cancer cells
Authors: Shpyleva Svitlana I. , Tryndyak Volodymyr P. , Kovalchuk Olga , Starlard-Davenport Athena , Chekhun Vasyl’ F. , Beland Frederick A. , Pogribny Igor P. 
Published: February 2011

Abstract
Breast cancer is the most common malignancy in women. Successful treatment of breast cancer relies on a better understanding of the molecular mechanisms involved in breast cancer initiation and progression. Recent studies have suggested a crucial role of perturbations in ferritin levels and tightly associated with this, the deregulation of intracellular iron homeostasis; however, the underlying molecular mechanisms for the cancer-linked ferritin alterations remain largely unknown and often with conflicting conclusions. Therefore, the present study was undertaken to define the role of ferritin in breast cancer. We determined that human breast cancer cells with an epithelial phenotype, such as MCF-7, MDA-MB-361, and T-47D cells, expressed low levels of ferritin light chain (FTL), ferritin heavy chain (FTH1), transferrin (Tf), iron regulatory protein 1 (IRP1), and IRP-2. In contrast, expression of these proteins was substantially elevated in breast cancer cells with an aggressive mesenchymal phenotype, such as Hs-578T, BT-549, and especially MDA-MB-231 cells. The up-regulation of FTH1 and FTL in MDA-MB-231 cells was accompanied by alterations in the subcellular distribution of these proteins as characterized by an increased level of nuclear ferritin and a lower level of the cellular labile iron pool as compared to MCF-7 cells. We established that FTH1 is a target of miR-200b, suggesting that FTH1 up-regulation in MDA-MB-231 cells may be triggered by the low expression of miR-200b. Ectopic up-regulation of miR-200b by transfection of MDA-MB-231 cells with miR-200b substantially decreased the level of FTH1. More importantly, miR-200b-induced down-regulation of ferritin was associated with an increased sensitivity of the MDA-MB-231 cells to the chemotherapeutic agent doxorubicin. These results suggest that perturbations in ferritin levels are associated with the evolution of breast cancer toward a more advanced malignant phenotype.
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 2313.
Abstract 2358: MUC13 mucin augments pancreatic tumorigenesis
Authors: Chauhan Subhash C. , Ebeling Mara C. , Maher Diane M. , Koch Michael D. , Friez Matthew H. , Watanabe Akira , Aburatani Hiroyuki , Lio Yuhlong , Pandey Krishan K. , Jaggi Meena 
Published: February 2011

Abstract
Pancreatic cancer is one of the most lethal malignancies with extremely poor prognosis. The high death rate of pancreatic cancer is attributed to a lack of reliable methods of early diagnosis and underlying molecular mechanisms associated with aggressive pathogenesis. MUC13, a newly identified transmembrane mucin, is known to be aberrantly expressed in ovarian, gastric and colon cancer. However, the expression and functions of MUC13 in pancreatic cancer are unknown. Herein, we have investigated the expression and functions of MUC13 mucin, in pancreatic cancer to determine its potential for early cancer diagnosis and its role in pancreatic cancer pathogenesis. The expression profile of MUC13 in pancreatic cancer was investigated using a recently generated monoclonal antibody (MAb, clone PPZ0020) and pancreatic tissue microarrays. The expression of MUC13 was significantly (p&lt;0.005) higher in cancer samples compared to the normal/non-neoplastic pancreatic tissues. For the functional analyses, a full length MUC13 gene cloned in pcDNA3.1 was expressed in MUC13 null pancreatic cancer cell lines, MiaPaca and Panc1. The exogenous MUC13 expression induced morphological changes, including scattering of cells. These changes were abrogated through c-jun NH2-terminal kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (p&lt;0.05) increases in cell motility, invasion, proliferation, clonogenicity and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with the up-regulation of HER2, p21-activated kinase1 (PAK1), extracellular signal-regulated kinase (ERK) and S100A4 (metastasin) and suppression of p53. Inhibition of MUC13 expression by MUC13 siRNA or shRNA resulted in suppression of tumorigenic characteristics in HPAFII pancreatic cancer cells. These results, for the first time, suggest that MUC13 expression augments pancreatic cancer progression and has potential as a diagnostic and/or therapeutic target.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 2358.
Abstract 236: Sleeping Beauty transposon integration within the Dlk1-Dio3 imprinted domain is associated with hepatocellular carcinoma development
Authors: Riordan Jesse D. , Keng Vincent W. , Ryan Barbara J. , Podetz-Pedersen Kelly M. , Copeland Neal G. , Jenkins Nancy A. , Largaespada David A. , Dupuy Adam J. 
Published: February 2011

Abstract
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed and deadliest cancers worldwide. In the United States, age-adjusted incidence has tripled over the last three decades. While traditional cancer treatments, such as radiation and chemotherapy, are ineffective in treating HCC, therapeutic approaches targeted at the underlying molecular causes are proving to be more efficacious. However, compared to other common cancers, relatively little is known about the molecular pathogenesis of HCC. We have used a Sleeping Beauty transposon-based insertional mutagenesis screen to identify novel oncogenes and tumor suppressors involved in HCC development and progression. This forward genetics approach identified a link between disruption of gene expression within the Dlk1-Dio3 imprinted domain and development of HCC in mice; over half of the induced HCCs contained transposon integrations within a ten kilobase region of this domain. Analysis of gene expression within the domain identified two consistent and significant events associated with transposon integration: activation of Delta-like 1 homolog (Dlk1) and inhibition of microRNA-370 (miR-370). These results led us to hypothesize that Dlk1 and miR-370 possess oncogenic and tumor suppressive functions, respectively, in HCC pathogenesis.
The Dlk1 gene encodes a Notch receptor ligand. Overexpression has been documented in a subset of human HCC cases, and the effects of modulating expression level in cultured hepatocytes are consistent with a tumor-promoting role. To test Dlk1's oncogenic potential in vivo, we drove overexpression in adult mouse livers using a hydrodynamic gene delivery technique. Hepatic nodule formation was observed in ∼50% of mice, supporting our hypothesis that Dlk1 functions as an oncogene in HCC.
miR-370 is a relatively uncharacterized microRNA, although it has been demonstrated to suppress proliferation of cultured cholangiocytes. Similarly, manipulation of miR-370 activity in cultured hepatocytes has proliferative consequences consistent with a tumor suppressor role. Efforts to examine the effect of modulating miR-370 activity in vivo are currently underway.
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 236.
Abstract 2364: Overexpression of SATB1 (Special AT-Rich Sequence-Binding Protein 1) in prostate cancer potentiates metastatic phenotype
Authors: Shukla Sanjeev , MacLennan Gregory T. , Fu Pingfu , Gupta Sanjay 
Published: February 2011

Abstract
One of the reasons for the most prostate cancer-related deaths is the growth of secondary tumors due to metastases and not the primary organ-confined carcinoma. Metastasis in cancer cells results in acquiring abilities of increased motility and invasiveness, to home in other parts of the body. The key regulator involved in the control of metastasis genes in prostate cancer is presently unknown. Special AT-rich sequence-binding protein 1 (SATB1) is a transcription factor and functions as genome organizer. SATB1 being a transcription factor tend to bind with AT rich base unpaired sequences of the target gene. SATB1 acquires a “3 D chickenwire” network by forming anchor loops around chromatin, recruits chromatin remodeling complexes on the anchorage sites, and regulates histone modifications by rendering DNA sequences accessible or inaccessible for transcription. Earlier studies suggested the role of SATB1 in breast cancer progression. We aimed to observe the role of SATB1 in prostate cancer progression. We used different grades of human prostate cancer specimens, non tumorigenic and aggressive prostate cancer cells. Immunohistochemical evaluation of SATB1 in prostate cancer specimens of various Gleason grades exhibited significantly increased expression with increase in Gleason grade. A progressive increase in nuclear SATB1 expression was observed as tumor grade increased along with its presence in the cytoplasm. Further, SATB1 protein levels were higher in human prostate cancer cell lines viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M compared to non-tumorigenic prostate epithelial cells PZ-HPV-7. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells. Introduction of SATB1 through transient infections into non-tumorigenic PZ-HPV-7 cells increased its invasiveness and migration capabilities, whereas these properties were inhibited by silencing SATB1 through shRNA techniques. Furthermore, knock down of SATB1 caused increased E-cadherin expression and simultaneous reduction in matrix metalloproteinase-9 expression, providing further evidence that SATB1 significantly influences the metastasis process. Taken together, our results suggest that SATB1 is a master regulator of the metastasis process in prostate cancer and, therefore, could be considered as an independent prognostic factor and a potential therapeutic target for prostate cancer.
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 2364.
Abstract 2393: Pathological angiogenesis in vascular tumors is driven by endothelial Akt1 and inhibited by rapamycin
Authors: Phung Thuy L. , Xue Qi , Antonello Zeus , Gerald Damien , Perruzzi Carole , Rojano Rafael , Cunningham Michael , Hochman Marcelo , Benjamin Laura E. 
Published: February 2011

Abstract
Vascular tumors are abnormal angiogenic proliferations of neoplastic endothelial cells with a wide spectrum of clinical diseases ranging from common hemangioma in children to malignant angiosarcoma in adults. To date, the mechanisms leading to vascular tumor formation are poorly understood and under-investigated. We found reduction in PTEN levels and increased Akt activation in benign and malignant human vascular tumors. Akt1 promoted the proliferation and migration of vascular tumor cells. Expression of constitutively active Akt1 in vascular endothelial cells was sufficient to induce hemangioma formation in vivo, and sustained endothelial Akt1 activation was necessary to maintain tumor growth. Inhibition of mTOR activity downstream of Akt1 with rapamycin blocked VEGF-induced angiogenesis in vascular tumor cells and tumor growth in animals. In vascular tumors, rapamycin inhibited the activities of both TORC1 (which phosphorylates p70 S6-Kinase downstream of mTOR) and TORC2 (which phosphorylates Akt) and may provide a mechanism for the high efficacy of rapamycin in these tumors. As a topical agent, rapamycin was effective in inhibiting cutaneous vascular tumors with minimal systemic blood levels of the drug. In summary, these studies showed that endothelial Akt1 plays a key role in vascular tumor formation, and topical rapamycin holds promising clinical utility in the treatment of cutaneous vascular tumors.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
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 2393.
Abstract 2394: Spontaneous immune responses against XAGE-1b in patients with non-small cell lung cancer (NSCLC)
Authors: Ohue Yoshihiro , Eikawa Shingo , Mizote Yu , Okazaki Nami , Isobe Midori , Uenaka Akiko , Fukuda Minoru , Nakayama Eiichi , Oka Mikio 
Published: February 2011

Abstract
BACKGROUND: Cancer/testis (CT) antigen is expressed only in the testis in normal adult tissues and in various types of cancers. There is no expression of MHC antigen in the testis. Therefore, CT antigen is thought to be a promising target for cancer immunotherapy. The XAGE-1 gene has been identified as a CT-like antigen and consists of several isoforms. We recently reported that XAGE-1b was predominantly expressed in lung adenocarcinoma by immunohistochemistry using XAGE-1b mAb (clone USO 9-13). In this study, we investigated humoral and cellular immune responses against XAGE-1b in patients with non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS: Sera and PBMCs were obtained from NSCLC patients who visited Kawasaki Medical School Hospital between 2005 and 2009. Antibody response to XAGE-1b was analyzed by ELISA using synthesized XAGE-1b protein. CD4 and CD8 T-cell responses against XAGE-1b were examined by IFN-γ ELISA and/or secretion assay using 17 16- or 17-mer XAGE-1b-overlapping peptides (OLPs) spanning the entire XAGE-1b protein in antibody-positive patients. Epitope peptides recognized by antibody and T-cells were determined by ELISA using XAGE-1b OLPs.
RESULTS: Antibody positive frequencies of total 200 NSCLC patients and 69 stage IIIB/IV lung adenocarcinoma patients were 10.0% (20/200) and 18.8% (13/69), respectively. The peptide regions frequently recognized by the antibody were XAGE1b peptides 25-40, 29-44 and 33-48. CD4 and CD8 T-cell responses against XAGE-1b were observed in 14 (87.5%) of 16 patients and 6 (66.7%) of 9 patients, respectively, in the antibody-positive patients. No response was observed in 5 antibody-negative patients and 5 healthy donors. The XAGE-1b peptide regions dominantly recognized by CD4 and CD8 T-cells were XAGE-1b peptides 13-28 and 33-48 for CD4 and XAGE-1b peptide 29-44 for CD8. Furthermore, the minimal epitope peptides bound to HLA-DR4.1 and DP5 recognized by CD4 T-cell clones and those bound to HLA-A2 and Cw1 recognized by CD8 T-cell clones were determined.
CONCLUSION: Our findings indicate that CT antigen XAGE-1b is highly immunogenic in NSCLC patients inducing antibody, and CD4 and CD8 T-cell responses. Thus, XAGE-1b is a promising target antigen for immunotherapy against lung adenocarcinoma.
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 2394.