bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2386: Overexpression of 14-3-3ζ in mouse mammary gland promotes mammary tumor development and progression by enhancing multiple tumor-associated properties
Authors: Li Shau-Hsuan , Wyszomierski Shannon L. , Li Ping , Wang Qingfei , Rehman Sumaiyah K. , Xiong Yan , Yang Jun , Guo Hua , Zhang Siyuan , Fang Dexing , Medina Daniel , Muller William J. , Yu Dihua 
Published: June 2012

Abstract
The 14-3-3 proteins are a family of evolutionarily conserved proteins ubiquitously expressed in eukaryotic organisms. 14-3-3 proteins interact with and regulate many different target proteins including oncoproteins and tumor suppressors. Previously, we found that 14-3-3ζ was overexpressed in &gt;40% of human breast cancers and associated with poor clinical outcome of patients. We also showed that 14-3-3ζ contributed to the transformation of MCF10A non-transformed human mammary epithelial cells and multiple breast cancer cells in vitro. Here, to assess the oncogenic capacity of 14-3-3ζ in vivo, we generated transgenic mice with HA-tagged 114-3-3ζ overexpressed in the mammary epithelium, driven by either the whey acidic protein promoter (WAP-HA-14-3-3ζ) or the MMTV- LTR promoter (MMTV-HA-14-3-3ζ).
Multiparous WAP-HA-14-3-3ζ transgenic mice developed hyperplastic lesions and showed an increased susceptibility to the induction of mammary tumors by the carcinogen, DMBA. Remarkably, MMTV-HA-14-3-3ζ mice developed mammary tumors with a median tumor latency of 662 days without DMBA treatment. WAP-HA-14-3-3ζ and MMTV-HA-14-3-3ζ mice crossed with MMTV-neu transgenic mice (WAP-ζ.neu and and MMTV-ζ.neu) exhibited accelerated neu-mediated mammary tumorigenesis and metastasis. Compared to the mammary tumors of MMTV-neu mice, 14-3-3ζ overexpression in bitransgenic mice tumors further increased cell proliferation, reduced apoptosis and enhanced angiogenesis. These data indicate that 14-3-3ζ overexpression in the mouse mammary gland promotes the development and progression of mammary tumors and that 14-3-3ζ, in cooperation with other oncogenic events, plays a causal role in mammary tumorigenesis and metastasis.
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 2386. doi:10.1158/1538-7445.AM2011-2386
Abstract 2416: The effects of methylation-controlled DnaJD1 in hepatitis B virus X protein expressed hepatocellular carcinoma
Authors: Lai Yi-Wen , Chen Jeremy, J.W. , Chen Hsiao-Ling , Chen Chuan-Mu 
Published: June 2012

Abstract
The development of hepatocllular carcinoma (HCC) is a multistep process with accumulation of genetic and epigenetic alternations in regulatory genes, leading to activation of oncogenes and inactivation of tumor suppressor genes. In our studies, we used non-commercial MCGI (mouse CpG islands) microarray to identify many genes that were hypermethylation in the liver tumor tissues of HBx-overexpressed transgenic mice, and examined the mehtylation pattern on these selected genes by bisulfite sequencing. According to the methylation analysis results, we focused on a methylation-controlled DNAJ family (MCJ) gene, DnaJD1. It was found hypermethylation in the promoter region and followed reduced mRNA expression in Hep3B hepatoma cells, which contain HBV genome. The HBV or HBx was involved in epigenetic modification during HCC tumorgenesis still not clear. In our previous research results, we are looking forward to realize the DnaJD1 characters in HBx expressed HCC. Consequently, the over-expressed DnaJD1 in Hep3B cells were established and investigated the physiologic effects of DnaJD1 in cell proliferation, cell migration, and invasion ability in vitro. In addition, DnaJD1 shRNA fragments were also applied to realize the related roles of DnaJD1 in DnaJD1 over-expressed Hep3B cells. Data suggested that DnaJD1 re-expressed in Hep3B cells that could effect the cell physiological characterizations, and the semi-quantitative RT-PCR results showed DnaJD1 could effect the HBx gene expression. Furthermore, the tumorgenesis in xenotransplanted nude mice were also examined. In these results, we concluded that DnaJD1 could display the important role in HBx expressed HBV-related hepatocellular 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 2416. doi:10.1158/1538-7445.AM2011-2416
Abstract 2419: Glycogen synthase kinase-3 inhibitor and cisplatin synergically inhibit tumor growth of Urothelial cancer in xenograft rodent model
Authors: Naito Sei , Bilim Vladimir , Kawazoe Hisashi , Tomita Yoshihiko 
Published: June 2012

Abstract
Introduction: Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase, as a positive regulator of several cancer cell survival and proliferation. We previously showed that nuclear accumulation of GSK-3beta indicates high grade, high stage, and poor survival in bladder urothelial cancer (UC). And inhibition of GSK-3beta suppresses UC cell proliferation and induces apoptosis via NF-kappaB down-stream genes viz. BCl-2 and XIAP (Clin Cancer Res 2010). Here we were to identify the interaction between cisplatin and GSK-3 inhibitor, AR-A014418 in UC.
Experimental Procedures: We added cisplatin (0, 1, 3, 6 μg/ml) and AR-A014418 (0, 10, 20 μM) to medium in T24 and HT1376 human UC cells and assessed their viability by MTS assay. Furthermore, we intraperitoneally administrated PBS 5 time per week, 2.5 mg/kg body weight cisplatin once per week, 20 mg/kg body weight AR-A014418 5 time per week, or cisplatin and AR-A014418 into each 6 mice with subcutaneous xenografts of HT1376 for 3 weeks.
Result: Treatment of cisplatin and AR-A014418 showed synergistic effect in cell lines. Cisplatin did not change expression level of GSK-3beta, and AR-A014418 suppressed XIAP for cell lines with cisplatin. The average tumor volume of the mice treated by cisplatin was equivalent to one by PBS within treatment period. However, the tumors treated by cisplatin grew bigger than ones by PBS after withdrawal of treatment. AR-A014418 inhibited the growth of tumor compared to PBS and cisplatin. And combine use of cisplatin and AR-A014418 prevented the tumor from re-growth by cisplatin after treatment. Body weight did not vary between mice by each treatment methods.
Conclusion: Cisplatin and AR-A014418 synergistically suppressed UC cells viability. And AR-A014418 cancelled re-growth of low-dose cisplatin in xenograft model.
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 2419. doi:10.1158/1538-7445.AM2011-2419
Abstract 2425: Mechanisms of neuroblastoma metastasis to bone
Authors: Carter Larry , Varin Courtney , van Golen Cynthia M. 
Published: June 2012

Abstract
The molecular pathways leading to neuroblastoma (NBL) development and progression are understudied despite the fact this tumor is responsible for 15% of all childhood cancer deaths. Bone is one of the most common sites of metastasis in NBL, and over 90% of children with NBL bone metastasis will die. Therefore, the goal of this study is to elucidate the cell-signaling pathways responsible for the destruction of bone. Parathyroid hormone related protein (PTHrP) and Transforming Growth Factor Beta both are involved in osteoclastogenesis. PTHrP travels through the circulation to the bones, where it triggers a chain of event that encourages the dissolution of bone minerals by osteoclast. Moreover, PTHrP results in the mobilization of calcium ions, which travel back via the circulatory system allowing osteoclast differentiation to go unchecked, therefore providing further destruction to the bone microenvironment. Transforming Growth Factor Beta (TGF-β) is a protein which controls proliferation, cellular differentiation and other functions in most cells. Since TGF-β and the SMAD family of proteins modulate the activity TGF-β and its association with osteoclasts, we formulated the hypothesis that osteoclastogenesis occurs during NBL bone metastasis through PTHrP and TGF-β. NBL is a heterogeneous tumor consisting of neuronal (n) and stromal (s) cells, with metastatic cells predominantly of the n type. In our study, we focused on four NBL cell lines: IMR-32 (n), SH-SY5Y (n), SK-N-AS (s), SK-N-SH (s). Conditioned media collected from IMR32 NBL cells induces osteoclast precursors to fuse into multinucleated, TRAP positive cells, indicative of osteoclast differentiation. Whole cell lysates were collected and Western immunoblotting performed for PTHrP. We report that the more tumorigenic cells, SH-SY5Y and IMR32, express higher levels of PTHrP than the s lines SK-N-AS and SK-N-SH. These data indicate that PTHrP may be involved in NBL bone metastasis. We are currently analyzing the effects of TGF-β on NBL and the role of these proteins in NBL-induced osteoclastogenesis.
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 2425. doi:10.1158/1538-7445.AM2011-2425
Abstract 2449: Pancreatic cancer tumor initiating cells are marked by the presence of a primary cilium
Authors: Bailey Jennifer M. , Rasheed Zeshaan , Matsui William , Maitra Anirban , Hollingsworth Michael A. , Leach Steven D. 
Published: June 2012

Abstract
Primary cilia are microtubule rich projections eminating from the apical surface of epithelial cells. Primary cilia are responsible for the transduction of growth factor and morphogenetic signaling pathways, including the hedgehog, wnt and platelet-derived growth factor pathways. Initial observations in the field of pancreatic cancer have suggested the absence of primary cilia in human pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma. While absent in the majority of pancreatic cancer cells, primary cilia have been identified in differentiated acinar cells undergoing an acinar to ductal metaplasia. This metaplasia is well characterized in pancreatic injury and regeneration models and accelerates tumor formation in the presence of acinar specific KrasG12D mutations. Thus, we are addressing the hypothesis that primary cilia, while not expressed in bulk tumor populations, are maintained in pancreatic tumor-initiating cells. To address the hypothesis, we have used confocal microscopy to quantify the percentage of cells within low grade human PanIN lesions that express a primary cilium. Performing confocal microscopy on a human PanIN tissue array (n=23), we have determined that in 15% of PanIN lesions, 13-30% of the cells are expressing a primary cilium, as is evidenced by staining for acetylated alpha tubulin. We have also developed a sorting strategy using an acetylated alpha tubulin antibody to isolate ciliated cells by Fluorescence Activated Cell Sorting (FACS) analysis. Using this protocol, we have discovered that human pancreatic cancer cells bearing a primary cilium are markedly enriched in cells also positive for either CD133 or CD24/CD44, representing putative pancreatic cancer stem cell populations. We have functionally analyzed the tumor-initiating capacity of ciliated vs non-ciliated cells using tumor sphere experiments. In this assay, ciliated cells show a significant increase (100 fold) in tumor sphere-forming capacity, suggesting that the presence of a primary cilium may mark a pancreatic cancer tumor initiating population. These data are informative regarding the earliest initiating events in pancreatic 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 2449. doi:10.1158/1538-7445.AM2011-2449
Abstract 2464: Targeting liver cancer stem cells for molecular imaging and therapeutic application
Authors: Wang Lina , Liu Ze , Lu Dan , Chen Si , Li Na , Xiang Rong , Li Zongjin 
Published: June 2012

Abstract
Conventional therapies target rapidly proliferating non-tumorigenic cells and spare the relatively quiescent cancer stem cells (CSCs) and the CSCs will remain viable after therapy and re-establish the tumor. Thus developing therapeutic strategies to target CSCs to prevent tumor recurrence will be vital for cancer therapy. To date, it has been shown that CSCs in hepatocellular carcinoma (HCC) can be identified by several cell surface antigens CD133, CD90, CD44, OV6 and the epithelial cell adhesion molecule (EpCAM). Here, we developed a novel strategy which targeted CSCs by anti-CD44 antibody mediated nanoparticles delivery system loaded with a triple fusion gene containing the suicide gene-herpes simplex virus truncated thymidine kinase (TTK), renilla luciferase (RL) and RFP (TF, RL-RFP-TTK). The in situ liver cancer model was established by injection of 1.0×105 HepG2 cells, which carry a reporter system encoding the genes of firefly luciferase (FL) and GFP into the liver of NOD/SCID mice. The mice were subsequently treated with ganciclovir (GCV). Then the growth status of tumor was monitored by the optical bioluminescence imaging of firefly luciferase(FL) and the specific targeting of the nanoparticles was tracked by imaging of renilla luciferase(RL). Our results demonstrated that the anti-CD44 antibody mediated nanoparticles loaded with TTK could specifically target the CSCs of HCC, and thereafter were endocytosed by the plasma membrane to transport the triple fusion (TF, RL-RFP-TTK) into the cells, resulted in the apoptosis of the targeted cells. Taken together, our study demonstrated a novel therapeutic strategy by targeted CSCs, we also developed a useful multimodality imaging techniques to monitor HepG2 cells’ fate in vivo and assessed the targeting efficacy of the nanoparticles. This may open a new application for the treatment of the HCC by targeting CSCs.
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 2464. doi:10.1158/1538-7445.AM2011-2464
Abstract 2467: Podoplanin expressing cancer stem cells show increased resistance to DNA damage induced by ionizing radiation
Authors: Ezhilarasan Ravesanker , Love Patrice N. , Goodman Lindsey D. , Aldape Kenneth D. , Sulman Erik P. 
Published: June 2012

Abstract
The majority of patients with malignant gliomas, the most common and most lethal brain tumor, develop disease recurrence despite aggressive, multi-modality therapies. This treatment resistance has been attributed to a small population of tumor-initiating glioma cancer stem cells (GSCs). We recently described a new marker of GSCs, the transmembrane glycoprotein podoplanin (pdpn), based on analysis of gene expression profiling data and have found it to be more accurately identify the stem cell population than other described markers. Pdpn expression correlates with poor patient survival and decreased response to radiotherapy. Pdpn expressing cells form neurospheres at high rates in vitro, are more resistant to ionizing radiation, and initiate tumors in vivo. Silencing of pdpn leads to increased radiosensitivity. To identify the mechanism of radiation resistance in pdpn-expressing GSCs, we screened for putative binding partners and identified target of myb-like-1 (tom1l1), a known regulator of Src-pathway activation. We hypothesized that modulation of pdpn and/or tom1l1 expression would lead to alternations in the response of GSCs to radiation via src signaling. Mechanisms of radiation resistance in GSCs are poorly understood to date and the role of src family kinases in modulating radiosensitivity has not previously been reported in gliomas. Pdpn binding of tom1l1 was confirmed by co-immunoprecipation and src activation monitored by immunoblot. Pdpn and tom1l1 expression was downregulated by RNA interference and dsDNA damage and repair assayed by neutral comet assay and by scoring of γH2AX foci. Silencing of pdpn in primary culture, neurophere forming GSC-like cells resulted in increased DNA damage following 2 and 6 Gy ionizing radiation. We similarly examined effects of decreased tom1l1 to determine if the effects on DNA repair mediating by pdpn were acting via the src pathway. In summary, our data suggest that pdpn expression correlates with increased dsDNA repair following ionizing radiation and presents a possible mechanism by which GSCs resist treatment and regrow the tumor.
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 2467. doi:10.1158/1538-7445.AM2011-2467
Abstract 247: A novel mPGES-1/EGR1/beta-catenin signaling axis in hepatocarcinogenesis
Authors: Lu Dongdong , Han Chang , Wu Tong 
Published: June 2012

Abstract
Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that couples with cyclooxygenase-2 (COX-2) for the production of PGE2. Although COX-2-derived PGE2 is known to participate in the development and progression of several human cancers including hepatocellular carcinoma (HCC), the role of mPGES-1 in carcinogenesis remains poorly understood. This study provides novel evidence for an important role of mPGES-1 in human HCC. Forced overexpression of mPGES-1 in two HCC cell lines (Hep3B and Huh7) promoted tumor cell growth and increased clonogenic formation capacity, in vitro. Conversely, mPGES-1 knockdown inhibited tumor cell growth and prevented clonogenic formation. Overexpression of mPGES-1 in Hep3B and Huh7 cells also increased cell invasion and migration/repair capacity, whereas knockdown of mPGES-1 reduced these parameters. Flowcytometric analysis revealed that mPGES-1 knockdown caused cell cycle arrest at G1/S checkpoint. In SCID mouse tumor xenograft model, mPGES-1 overexpressed cells formed palpable tumors at earlier time points and developed larger tumor nodules when compared to the control cells (p&lt;0.01); in contrast, mPGES-1 knockdown delayed tumor development and reduced tumor growth in SCID mice (p&lt;0.01). Mechanistically, mPGES-1-induced HCC cell proliferation, invasion and migration involve activation of EGR1 and beta-catenin. mPGES-1 induced the formation of EGR1-beta-catenin complex, which interacted with TCF4 transcription factors in HCC cells. Our findings depict a novel mPGES1/EGR1/beta-catenin signaling axis that is crucial in hepatocarcinogenesis.
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 247. doi:10.1158/1538-7445.AM2011-247
Abstract 2485: The Hippo downstream effector YAP promotes survival, radiation resistance and chromosome instability in medulloblastoma
Authors: Fernandez-L Africa , Kenney Anna M. 
Published: June 2012

Abstract
Medulloblastoma, the most common solid pediatric tumor, originates in the cerebellum during postnatal development. It is postulated that cerebellar granule neuron precursors (CGNPs) are cells-of-origin for certain classes of medulloblastomas. CGNPs require the mitogen/morphogen Shh to proliferate. We identified YAP as a new Shh target that promotes CGNP proliferation. YAP is a transcriptional co-activator negatively regulated by the Hippo pathway, a signaling cascade involved in organ size regulation and cell contact inhibition. We found YAP to be highly expressed in human and mouse Shh-driven medulloblastomas. Moreover, YAP was strikingly amplified in a subset of human medulloblastomas. YAP was localized to the peri-vascular niche where cancer stem cells have recently been described to reside in brain tumors. When we irradiated medulloblastoma-bearing mice, most of the cells in the tumor underwent apoptosis 6 hours after radiation. However, cells expressing YAP were resistant to radiation-induced apoptosis. These radiation-resistant cells have been described to have the ability to re-populate the tumor. In concordance with this, mouse medulloblastoma cells over-expressing YAP and injected in P0-P4 pups grow faster than those overexpressing GFP and give rise to more aggressive tumors. In vitro, YAP-overexpressing CGNPs and medulloblastoma cells produce higher levels of IGF2, which activates Akt and promotes their survival. 24 hours after radiation, YAP-overexpressing cells contain more damaged DNA; however, they skip the G2/M checkpoint and don't arrest despite the damage in their DNA. Our results indicate that YAP promotes both chromosome instability and survival of medulloblastoma cells, thus is a new attractive potential target for medulloblastoma therapies.
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 2485. doi:10.1158/1538-7445.AM2011-2485