bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-293: Perfluorocarbon labeling of human α-type-1-polarized dendritic cells and conventional dendritic cells for in vivo trafficking by fluorine MRI
Authors: Helfer Brooke M. , Balducci Anthony , Kalinski Pawel , Wesa Amy 
Published: August 2014

Abstract
Human dendritic cells (DC) have yet to live up to their clinical promise as an immunotherapeutic intervention against cancer, in spite of their in vitro profiles of their ability to effectively prime tumor-specific T cell responses. It is still unclear which is the best route of administration for the most efficient interaction of DC with tumor-specific T cells in patients, and whether the migratory capacity and localization of DC in patients correlates with clinical responsiveness. Here we utilize a perfluorocarbon (PFC) magnetic resonance imaging (MRI) tracer agent which may enable the assessment of the migration and localization of α-type-1-polarized dendritic cells (αDC1) in the clinic. αDC1 producing high levels of interleukin-12p70 with putative strong lymph node homing capabilities, are currently being evaluated clinically for anti-cancer activity. In vivo results demonstrate the capability of 19F MRI to detect and quantify labeled cells with moderate sensitivity, detecting fewer than 1×104 cells per voxel. The lack of endogenous fluorine in the body allows highly-specific 19F MR detection of label and when paired with proton MRI provides clear and quantitative cell localization within their anatomical context.
The inertness of this tracking agent on the functional capacity of DC was examined in a panel of in vitro studies. The use of the MRI tracer with both conventional DC and αDC1 indicated similar labeling efficiencies with no observed effect on the DC's ability to stimulate T cell expansion, produce IL-12p70, process antigen or express co-stimulatory and polarizing factors. These data support the clinical translation of this tracer agent to safely track and quantify the administration and migration of human αDC1 by non-invasive 19F MRI in the treatment of cancer patients. An imminent clinical trial of PFC-labeled αDC1 will provide cell tracking data in patients, facilitating advances in greater efficacy in the next generation of DC-based cellular vaccines.
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 LB-293. doi:10.1158/1538-7445.AM2011-LB-293
Abstract LB-299: Effect of antiangiogenic therapy on tumor growth, vasculature and kinase activity in luminal and basal-like breast cancer xenografts
Authors: Lindholm Evita , Kristian Alexandr , Nalvoga Hawa , Kruger Kristi , Mælandsmo Gunhild M. , Akslen Lars A. , Engebraaten Olav 
Published: August 2014

Abstract
Angiogenesis is important for the growth and dissemination of solid tumors, and VEGF-A is one of the main stimulators of this process. Bevacizumab binds VEGF and increases the progression-free, but not overall, survival in breast cancer patients treated with chemotherapy. For determining factors of importance for treatment response and resistance, two different human breast cancer xenografts (luminal -and basal-like) were used, which respond differently to antiangiogenic mono -or combination therapy. Both doxorubicin and bevacizumab inhibited tumor growth significantly in basal-like xenografts, but with a superior effect when given in combination. In contrast, luminal-like tumors demonstrated no additional effect of combination therapy.
Vascular characterization demonstrated a total inhibition of endothelial cell proliferation (pMVD) and reduction in mean vascular density (MVD) in the basal-like tumors three days after bevacizumab treatment, not seen in the luminal-like tumors. At day 10, combination treatment reduced pMVD and MVD in both tumors, however only MVD lasted to the end of the experiment and in the basal-like tumors.
Analysis of kinase activity in the basal-like tumors after monotherapy demonstrated an early (day 3) increase in the phosphorylation of several targets, followed by a reduction at day 10. Furthermore, the most effective treatment in vivo was accompanied with increased phosphorylation of growth control -and proangiogenic kinase substrates, like PLCγ1, EGFR, PDGFRβ, VEGFR2, and MAP kinases.
Early inhibition of vascular proliferation and upregulation of specific signaling pathways, as described above, may therefore indicate important markers for response. Such markers may also be of value in patient stratification, for the prediction of treatment effect.
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 LB-299. doi:10.1158/1538-7445.AM2011-LB-299
Abstract LB-304: Bone marrow-derived endothelial cells migrate to tumor sites and contribute to functional tumor vasculature
Authors: Fontes Aparecida M. , Bonfim-Silva Ricardo , Souza Lucas Eduardo Botelho , Melo Fernanda Ursoli Ferreira , Oliveira Viviane Cassia , Magalhaes Danielle Aparecida Rosa , Cardoso Angelo A. , Rahal Paula , Covas Dimas Tadeu 
Published: August 2014

Abstract
Tumor expansion is dependent on neovascularization, a process that requires sustained new vessel formation. Although the critical role of angiogenesis by endothelial sprouting in this process, controversy still prevails on the whether vasculogenesis, involving bone marrow (BM)-derived endothelial cells, does contribute to this process. The objective of this study was to investigate the contributions of BM-derived endothelial cells to tumor vasculature, in a melanoma model using chimeric GFP mice. Methodology: First, wild-type C57BL/6 mice were was exposed to a single dose of 10 Gy X-irradition and rescued by transplantation of BM cells from C57BL/6-GFP mice. At d30 post-transplant, the animals received a subcutaneous infusion of melanoma cells stably transfected with the luciferase gene (B16/F10-Luc+). After 20 days, the tumors were harvested, and tumor stroma characterized using flow cytometry, bioluminescence-based image processing and confocal microscopy, to define the specific contribution of BM-derived cells. Results: Mice transplanted with donor GFP+ cells showed significant BM chimerism (90.9 ± 0.87%) demonstrating successful engraftment of donor BM stem/progenitor cells. Analyses of tumor specimens showed the presence of donor cells in the tumor sites (3.5±1.7%) in all animals, showing that BM-derived cells were effectively recruited to the developing melanoma. Interestingly, these cells represent endothelial cells (CD31+ cells; mean=X%) and myeloid-lineage cells (CD11b+ cells; mean=80%), but also tumor-infiltrating lymphocytes (CD8+ T cells, mean = 13.31; CD4+ T-cells, mean=2.1). Examination of the tumor endothelium by confocal microscopy clearly showed the presence of donor CD31/GFP cells in the vessel wall, namely in vessels lacking other mural components (as pericytes). Conclusions: Taken together, this study demonstrates that BM-derived cells are actively recruited to tumor sites, contributing to the tumor stroma and the formation of blood vessels in the developing tumor. We are performing studies to elucidate the molecular mechanisms involved in mobilization of of BM-derived precursor cells to the tumor microenvironment, and whether disruption of this vasculogeneic process significant impairs tumor development.
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 LB-304. doi:10.1158/1538-7445.AM2011-LB-304
Abstract LB-352: Functional significance of Zic1 and hsa-miR-23a over-expression in malignant mesothelioma
Authors: Cheng Yuen Yee , Jin Hong Chuan , Kirschner Michaela , van Zandwijk Nico , Reid Glen 
Published: August 2014

Abstract
Background: Epigenetic inactivation of tumour suppressor genes plays a crucial role in the progression of malignant mesothelioma (MM). Previous research has shown epigenetic gene silencing, through DNA methylation or through control of mRNA expression by microRNAs, to be important in MM. Our previous work indicated that Zic1 silencing in MM lines is only partially explained through DNA hypermethylation. Interestingly, miRNA microarray analysis revealed that hsa-miR-23a is over-expressed in MM cell lines, and that this miRNA has target sites in the 3′UTR of the Zic1 mRNA. The aim of the current study was to investigate the functional significance of Zic1 silencing and hsa-miR-23a over-expression in MM. Methods: We first confirmed DNA hypermethylation of Zic1 in human MM specimens using MSP, MS-HRM and COBRA. The expression level of hsa-miR-23a was also confirmed in MM using qPCR. To investigate the functional significance of Zic1 silencing, Zic1 was re-expressed in MM cell lines and effects on proliferation, migration and growth in soft agar were assessed. The relationship between hsa-miR-23a and Zic1 expression was investigated by the use of an antagonist of hsa-miR-23a. Results: Our results indicated that Zic1 is hypermethylated and ectopic expression of Zic1 inhibited cell migration and cell proliferation in MM cell lines. Hsa-miR-23a overexpression in MM is closely linked to the expression of Zic1. Our results suggest that Zic1 is a functional tumour suppressor gene that is silenced by a combination of hypermethylation and hsa-miR-23a-mediated inhibition in MM. These findings suggest that hsa-miR-23a is a potential therapeutic target for MM deserving further pre-clinical study.
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 LB-352. doi:10.1158/1538-7445.AM2011-LB-352
Abstract LB-353: Targeting pancreatic cancer stem cells by epigenetic regulation of miR-34a
Authors: Shankar Sharmila , Srivastava Rakesh 
Published: August 2014

Abstract
MicroRNA-34a (miR-34a) is a transcriptional target of p53 that is down-regulated in pancreatic cancer. This study aimed to investigate the functional significance of miR-34a on growth of pancreatic cancer stem cells through its epigenetic restoration by chromatin modulators, demethylating agent 5-Aza-2′-deoxycytidine (5-Aza dC) and HDAC inhibitor Suberoylanilide hydroxamic acid (Zolinza/vorinostat/SAHA). Re-expression of miR-34a in pancreatic cancer stem cells and pancreatic cancer cell lines on treatment with 5-Aza dC and SAHA strongly inhibited the cell proliferation, cell cycle progression, self renewal, epithelial to mesenchymal transition and invasion. miR-34a upregulation of by 5-Aza dC and SAHA in pancreatic cancer stem cells (PCSC's) also induced apoptosis by activating caspase 3/7. Modulation of miR-34a expression inhibited the protein expression of its putative target genes Bcl-2, CDK6, Cdc25, SIRT1, which was rescued by inhibiting miRNA-34a in the presence of miR-34a antagomir. miR-34a upregulation also induced acetylated p53, p21WAF1, p27, and PUMA protein levels in PCSC's. Interestingly treatment of PCSC'c with 5-Aza dC and SAHA resulted in the inhibition of epithelial -mesenchymal transition by downregulating N-Cadherin, Zeb-1, a crucial inducer of EMT, Slug and Snail expression and also by transcriptional upregulation of E-Cadherin. SAHA retards in vitro cancer stem cell migration and invasion by the inhibition of Notch signaling pathway. Inhibition of miR-34a by antogomiR abrogates the effects of SAHA and 5-Aza dC, suggesting that SAHA and 5-Aza dC regulate stem cell characteristics in PCSC's through miR-34a. The present study thus demonstrates the role of miR-34a as a critical regulator of pancreatic cancer progression. The restoration of miR-34a expression by 5-Aza dC and SAHA in human primary pancreatic cancer stem cells and cell lines will not only provide mechanistic insight and therapeutic targets for pancreatic cancer but also promising reagent to boost patient response to existing chemotherapies or as standalone cancer drug by the elimination of the cancer stem cells characteristics.
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 LB-353. doi:10.1158/1538-7445.AM2011-LB-353
Abstract LB-357: HIF-dependent over-expression of CUB domain-containing protein 1 stimulates migration in clear cell renal cell carcinoma
Authors: Razorenova Olga V. , Finger Elizabeth C. , Colavitti Renata , Chernikova Sophia B. , Boiko Alexander D. , Chan Charles KF , Krieg Adam , Bedogni Barbara , LaGory Edward , Weissman Irving L. , Broome-Powell Marianne , Giaccia Amato J. 
Published: August 2014

Abstract
Kidney cancer is the sixth leading cause of cancer death in the USA, and the primary tumor is frequently accompanied by metastasis to lungs, liver, brain and bones. Importantly a large number of kidney cancer cases are characterized by loss of von Hippel-Lindau (VHL) gene, which leads to stabilization of hypoxia-inducible factors (HIFs), which contribute to tumor progression and metastasis by multiple mechanisms. CUB-domain-containing protein 1 (CDCP1) was shown to be expressed on the cell surface of metastatic cell lines and to increase the number of nodules formed by lung adenocarcinoma cells and melanoma in lungs in tail vein injection experiments, enhance peritoneal dissemination of scirrhous adenocarcinoma, and to induce metastasis in the chicken embryo metastatic model. In the present study we investigated the role of CDCP1 protein in clear cell renal cell carcinoma (CC-RCC) and found it to be upregulated in this disease entity by a mechanism of VHL loss through HIFs. Interestingly, we found CDCP1 protein expressed not only on the membrane of kidney cancer cell lines, but also to be secreted into the media as a full length isoform. Importantly, in the knockdown experiments we found CDCP1 to promote CC-RCC cell migration in vitro, the process known to be the key during metastasis. Accordingly CDCP1 participates in the signal transduction pathway leading to PKCδ phosphorylation in CC-RCC, stimulating migration. The role of PKCδ in CDCP1-dependent migration was verified by the PKCδ knockdown experiments, which phenocopy the effect of CDCP1 knockdown; as well as migration rescue experiments, where the impairment of migration caused by CDCP1 downregulation was rescued by the overexpression of constitutively active mutant of PKCδ. Furthermore, we showed a correlation of CDCP1 cell surface expression in primary tumor with poor patient outcome. Finally, we found that suramin, a drug, which showed the clinical benefit for CC-RCC patients at premetastatic stages, causes the downregulation of CDCP1 at the protein level. Thus, the further investigation of the role of CDCP1 protein in kidney cancer metastasis is important to validate CDCP1 as a therapeutic target.
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 LB-357. doi:10.1158/1538-7445.AM2011-LB-357
Abstract LB-364: G(alpha)12 is required for thromboxane A2 to regulate tumor cell motility
Authors: Malik Babar , Zhang Xuejing , Nie Daotai 
Published: August 2014

Abstract
Introduction: Thromboxane (TX) A2 is a prostaglandin produced by metabolism of arachidonic acid through cyclooxygenase and thromboxane synthase. TXA2 is biologically active, mainly through activating its cognate, seven transmembrane, G protein coupled receptor. We previously reported that thromboxane A2 receptor (TP) was expressed in prostate cancer, and further activation of this receptor elicited cell contraction and modulated tumor cell motility through regulating small GTPase RhoA (Nie et al., Cancer Res 68: 115–121, 2008). This study aims to identify G alpha protein(s) involved in thromboxane A2 signaling in tumor cell motility.
Methods: The expression of G alpha proteins in the PC3MM cells was studied by real-time PCR. Cell contraction assay was performed by staining cells with TRITC phalliodin and evaluated under an epifluorescence microscope. Tumor cell motility and invasion were evaluated using wound healing assay and transwell Boyden Chamber assay. To determine the roles of G alpha protein in thromboxane A2 signaling, we expressed different alleles of G alpha proteins (wild type, constitutive active) in PC3MM cells and then the subsequent effects on cell contractions was determined. We also depleted G alpha protein expression by short hairpin RNA and examined subsequent changes in cell contraction and migration after activation of TP.
Results: PC3 MM cell line had the endogenous level of all the G alpha protein (G alpha 12, G alpha i1, G alpha 11, G alpha 13), but not G alpha q. Overexpressionof G alpha 12/13 increased cell contraction after activation of thromboxane A2 receptor with U46619. Expression of constitutively active G alpha 12 by itself was sufficient to cause cell contraction, regardless whether TP is activated or not. Depletion of G alpha 12 via shRNAs reduced cell contraction after TP activation. Tumor cells with G alpha 12 depleted had tumor cell motility and invasiveness.
Conclusion: The findings indicate that G alpha 12 is required for TP to induce cell contraction and to regulate tumor cell motility. The studies suggest G alpha 12 may be a promising target of intervention to reduce tumor cell motility and metastasis in prostate 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 LB-364. doi:10.1158/1538-7445.AM2011-LB-364
Abstract LB-369: A novel aniline derivative enhances radiosensitivity of lung cancer through suppression of Nrf2 activity
Authors: Ahn Jiyeon , Lee Saelooom , Lim Min-Jin , Kim Mi-Hyoung , Yu Chi-Ho , Yun Yeon-Sook , Song Jie-Young 
Published: August 2014

Abstract
The major obstacle in radiotherapy or chemotherapy is the resistance of cancer cells to the therapies. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates antioxidant enzymes. Kelch-like ECH-associated protein (Keap1) sequesters Nrf2 and leads to proteasomal degradation of Nrf2 in non-stressed condition. Keap1 is often found with biallelic mutation in non-small cell lung cancer (NSCLC) cell lines and NSCLC patients, results in constitutive activation of Nrf2 function, and contributes to resistance to anticancer drugs. Therefore, we aimed to develop small molecules that inhibit Nrf2 activity to maximize radiation-induced cell death via increasing ROS generation. A cell-based high-throughput screening using luciferase assay, we have identified an aniline derivative (IM3829) as a radiosensitizer of lung cancer in vitro and in vivo. In clonogenic assay, this compound sensitized H1299 lung cancer cells to irradiation.
IM3829 with irradiation significantly increased ROS accumulation compared with radiation alone treated cells, leading to apoptotic cell death synergistically. IM3829 inhibited Nrf2 binding activity and HO-1 expression. In H1299 xenografts mice, IM3829 with radiation significantly inhibits tumor growth by 47 % and 27 % compared with vehicle or radiation alone treated animals, respectively. Our finding suggested that IM-3829 could be a promising radiosensitizer in lung cancer patients, particularly those with a high expression of Nrf2.
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 LB-369. doi:10.1158/1538-7445.AM2011-LB-369
Abstract LB-371: Evaluating the protein SUMOylation pathway as a potential cancer therapeutic target using inducible RNA interference
Authors: He Xingyue , Bence Neil , Dick Larry , Veiby Petter , Bolen Joe 
Published: August 2014

Abstract
Protein SUMOylation is a conserved ubiquitin-like protein posttranslational modification pathway catalyzed by the SUMO enzymatic cascade. Previous studies have indicated SUMO pathway genes are highly expressed in cancer and are required for development and cell viability. We applied lentivirus based shRNA methods to efficiently knockdown SUMO pathway components in human cancer cells. shRNAs for SAE2 and UBC9 lead to reduced SUMO pathway activity as measured by cell based reporter assays. Knockdown of SUMO enzymes suppresses proliferation of human cancer cells including U2OS, HCT116 and HeLa cells. Multiple shRNAs for each gene showed a similar growth arrest phenotype suggesting that the results are not RNAi off target effects. Furthermore, SUMO pathway inhibition by RNAi sensitize U2OS cells to the DNA damage agent Camptothecin, indicating a chemo-sensitizing effect of SUMO pathway inhibition. To improve the reproducibility of our experiments and avoid an observed negative selection for the constitutively expressed shRNAs, we established a doxycycline inducible conditional shRNA (tet-on) system to achieve acute and reversible SUMO enzyme knockdown. Acute SAE2 knockdown in U2OS and HCT116 cells reduces S phase and slows cell growth in vitro. Our data demonstrate SUMO pathway is a potential therapeutic target to treat cancer and this study demonstrates that inducible shRNA systems are valuable for early stage drug discovery.
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 LB-371. doi:10.1158/1538-7445.AM2011-LB-371