bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 521: 4, 4′-Dichlorodiphenyltrichloroethane (DDT) and Triclosan (TCS) decrease tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells
Authors: Hurd-Brown Tasia D. , Udoji Felicia , Martin Tamara , Whalen Margaret 
Published: August 2012

Abstract
4, 4′-Dichlorodiphenyltrichloroethane (DDT) and Triclosan (TCS) are organochlorine compounds that contaminate the environment, are found in human blood, and have been shown to decrease the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. This study examined concentrations of DDT and PCP that decrease lytic function for alteration of NK binding to tumor targets. Levels of either compound that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. CD16 is an Fc receptor and CD56 is a cognate of neural cell adhesion molecules, both of which are present on NK cells and involved in recognition and lysis of NK target. NK cells exposed to 2.5 µM DDT for 24 h (which caused a greater than 55% loss of lytic function) showed a decrease in NK binding function of about 23%, and a decrease in CD16 of 20%. NK cells exposed to 5 µM TCS for 24 h showed a decrease in ability to bind tumor cells of 44% and a decrease in expression of CD56 of about 34%. This same treatment caused a decrease in lytic function of greater than 87%These results indicated that only a portion of the loss of NK lytic function seen with exposures to these compounds could be accounted for by loss of binding function and also accompanied by loss of cell-surface protein expression. Supported by NIH grant 1U54CA163066-01 and S06 GM008092-35
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 521. doi:1538-7445.AM2012-521
Abstract 5220: Dclk1 labels quiescent pancreatic progenitor and cancer initiating cells
Authors: Westphalen Christoph Benedikt , Quante Michael , Worthley Daniel , Asfaha Samuel , Remotti Helen , Olive Kenneth P. , Wang Timothy C. 
Published: August 2012

Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the US. Despite major efforts pancreatic cancer has the highest mortality rate of all major cancers with a 5-year survival rate below 5% while the survival rate for the disease has not improved substantially in nearly 40 years. Recently, doublecortin-like kinase 1 protein (Dclk1) was proposed as a marker of putative quiescent stem cells in the gastrointestinal tract and in the pancreas although no genetic fate mapping was performed. Additionally, it was demonstrated that Dclk1 cells expand in the setting of inflammation, hyperplasia and metaplasia. While clinical relevant mouse models of PDAC exist the identity of the cell of origin for pancreatic cancer is still debated. Aim: In order to investigate the role of Dclk1 cells in pancreatic health and disease we generated a BAC transgenic mouse line (Dclk1-CreERT) that expresses tamoxifen-inducible Cre recombinase under the control of the endogenous Dclk1 gene regulation. Results: Using genetic lineage tracing, we demonstrate that Dclk1 labels rare long-lived, quiescent progenitor cells in the pancreas that can give rise to ductal and acinar tissue. Furthermore, Dclk1 cells were found to expand in the setting of pancreatic inflammation and malignancy. Importantly, the Dclk1 lineage contributed significantly to pancreatic regeneration after caerulein-induced pancreatitis. Finally, expression of mutant K-Ras (G12D) in Dclk-1 cells leads to rapid onset (2-3 months) of invasive pancreatic ductal adenocarcinoma that could be further accelerated by caerulein-induced pancreatic injury (1-2 months). Conclusion: Dclk1 labels rare quiescent progenitor cells in the pancreas. These cells take part in the regeneration of the gland after injury and are capable of giving rise to pancreatic cancer. Therefore, we propose that Dclk1 could label the cell of origin in pancreatic 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 5220. doi:1538-7445.AM2012-5220
Abstract 5228: Inhibition of myeloid cell PI3Kγ is a potential therapeutic approach to treat pancreatic cancer
Authors: Hardamon Chanae R. , Schmid Michael C. , Lowy Andrew M. , Bouvet Michael , Varner Judith A. 
Published: August 2012

Abstract
Tumor inflammation plays a significant role in initiating and perpetuating tumor growth, angiogenesis and metastasis. While normal inflammatory responses aid in wound healing, fighting infections, and destroying pathogens, tumor inflammation is self-perpetuating and plays a role in facilitating the disease, in part by inducing immunosuppression. Gr1+CD11b+ myeloid cells are the most prevalent inflammatory cells found in tumors, where they directly promote tumor angiogenesis and immunosuppression. Recent studies in our laboratories have shown that the phosphatidylinositol 3-kinase (PI3K) catalytic subunit isoform p110γ, which is expressed exclusively by Gr1+CD11b myeloid cells, directly promotes myeloid cell invasion and consequently, tumor immunosuppression. Genetic and pharmacological suppression of PI3Kγ activity substantially reduces myeloid cell trafficking to orthotopic Pdx1Cre;Kras+; p53+/- and other pancreatic ductal carcinomas, reduces expression of immunosuppressive factors, and inhibits pancreatic tumor growth and metastasis. These studies indicate that PI3Kγ inhibitors may be useful therapeutics for pancreatic ductal carcinoma.
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 5228. doi:1538-7445.AM2012-5228
Abstract 523: γα T cells are activated by protein-bound polysaccharide krestin (PSK) and contribute to the antitumor effect of PSK
Authors: Inatsuka Carol , Yang Yi , Gad Ekram , Rastetter Lauren , Disis Mary , Lu Hailing 
Published: August 2012

Abstract
Gamma delta (γδ) T cells play an important role in anti-tumor immunity, and novel methods to augment γδ T cell function are highly desired. It has recently been shown that toll-like receptor (TLR) agonists may modulate the function of γδ T cells, so we questioned whether protein-bound polysaccharide krestin (PSK), a mushroom extract with TLR2 agonist activity, can activate γδ T cell. Using splenocytes from neu-transgenic mice, we found that γδ T cells produce IFN-γ after PSK treatment and have up-regulated expression of CD25 and CD69. The expression of CD107a in γδ T cells was also enhanced by PSK. To investigate whether the effect of PSK on γδ T cells is direct or indirect via activation of dendritic cells (DC), purified γδ T cells were cultured either alone or together with bone marrow derived DC (BMDC) in a co-culture or trans-well system and then stimulated with PSK. Results showed that direct cell-to-cell contact between γδ T cells and DC is required for optimal activation of γδ T cells. In the absence of DC, PSK can co-stimulate γδ T cells with anti-γδ TCR or anti-CD3 mAb. Oral administration of PSK in neu-transgenic mice with implanted breast tumors resulted in increased percentage of γδ T cells among splenocytes and increased expression of NKG2D on γδ T cells. Depleting γδ T cells during PSK treatment decreased the anti-tumor effect of PSK. All together, these results demonstrated that γδ T cells are activated by PSK and contribute to the anti-tumor effect of PSK.
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 523. doi:1538-7445.AM2012-523
Abstract 524: Cytokine therapy by allogenic IFN-alpha-expressing murine colorectal cancer cells suppresses outgrowth of established tumors in a murine hepatocellular carcinoma model
Authors: Ishii Shigeaki , Hirosihi Kazumasa , Eguchi Junichi , Sakaki Masashi , Doi Hiroyoshi , Omori Risa , Kajiwara Atsushi , Imawari Michio 
Published: August 2012

Abstract
Although several effective therapies for hepatocellular carcinoma (HCC) have been developed, many patients with both advanced cirrhosis and HCC are not able to receive those treatments because of their poor liver function. Thus, it is needed to establish a new effective therapy that has lesser side effects for those patients. We previously reported that immunotherapy by interferon-alpha (IFNa) and dendritic cells effectively suppressed outgrowth of established tumors and showed preventive effects in the murine colorectal cancer, MC38 cell model. We also revealed that tumor-specific cytotoxic T cell responses were important for these anti-tumor effects. In this study, we investigated the antitumor effect of allogenic cytokine (IFNa and IL-4)- expressing MC38 cells in the murine hepatocellular carcinoma, BNL model. There were no differences in cell growth between BNL cells and BNL cells co-incubated with cytokine-expressing MC38 cells in vitro. Balb/c mice were injected with 5x105 of BNL cells on their flank. Once BNL tumors were established, these mice received therapeutic injection of cytokine-expressing MC38 cells (2.5x105/mouse or 5x105/mouse) and tumor size was measured twice weekly. While tumor growth of the mice injected with MC38-IL4 was not suppressed (control; 421.0±146.9mm2, MC38-IL4 (5x105); 351.3±126.1mm2, p=0.33), injection of MC38-IFNa cells significantly suppressed the tumor growth by dose-dependent manner (MC38-IFNa: 5x105 cells; 183.5±46.2mm2, p=0.02). When we injected mice with both IFNa cells and IL-4 cells, any additive anti-tumor effects were not observed (mice injected both modified MC38: 5x105 cells each; 182±44.6 mm2, p=0.01). A BNL-specific cytolysis was detected when splenocytes of mice injected with MC38-IFNa were used as effector cells in a chromium-release assay. Furthermore, immunohistocemistrical analysis revealed that CD4+ T cells, CD8+ T cells and especially Gr-1+ cells infiltrated established BNL tumors of mice injected with MC38-IFNa. Our results suggest that the immunotherapy with allogenic IFNa-expressing cells has potent antitumor effects, and that it would be applicable for treatment to advanced HCC patients.
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 524. doi:1538-7445.AM2012-524
Abstract 5251: Branching morphogenesis in the mammary gland is regulated by sprouty-2
Authors: Sigurdsson Valgardur , Ingthorsson Saevar , Hilmarsdottir Bylgja , Franzdottir Sigridur R. , Steingrimsson Eirikur , Magnusson Magnus K. , Gudjonsson Thorarinn 
Published: August 2012

Abstract
Branching morphogenesis is a conserved mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including the epidermal growth factor receptor (EGFR), and their intracellular regulators, the sprouty protein family is believed to be a critical regulator of branching morphogenesis. In this study, we show that, Sprouty-2 (Spry-2) is predominantly expressed in the luminal epithelial cells both in ducts and lobuli in the human breast gland. We have also analyzed the expression of Spry-2 and EGFR pathway in virgin, lactating and pregnant mouse mammary gland. Spry-2 is expressed at branching epithelial buds during pregnancy with increased expression during lactation. The expression of phosphorylated EGFR (Y1068) shows a similar expression pattern as Spry-2. Using D492 a breast epithelial cell line with stem cell properties, that generate branching structures in 3D laminin rich gel we show that Spry-2 expression increases during the formation of branching. Immunostaining locates expression of Spry-2 and active EGFR at the tip of lobular-like, branching ends. Interestingly, knocking down (KD) spry-2 expression using shRNA resulted in increased migration. Spry-2 knockdown also gives larger and more complex branching structures indicating loss of negative feedback control of branching morphogenesis. In co-culture with endothelial cells, D492 spry-2 KD cells generate predominantly spindle like colonies reminiscent of epithelial to mesenchymal tansition. In conclusion, these data indicate that Spry-2 is an important regulator of branching morphogenesis and dysregulation of sprouty expression can lead to aberrant development related to breast cancer, such as epithelial to mesenchymal transition in the mammary gland.
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 5251. doi:1538-7445.AM2012-5251
Abstract 526: Cancer immunoediting by the innate immune system in the absence of adaptive immunity
Authors: Bui Jack , O'Sullivan Timothy , Saddawi-Konefka Robert , Vermi William , Smyth Mark , Schreiber Robert 
Published: August 2012

Abstract
Cancer immunoediting is the process whereby the immune system protects against cancer formation and sculpts the immunogenicity of developing tumors cells. Although the full process is known to depend on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. By comparing the incidence and immunogenicity of 3′methylcholanthrene (MCA)-induced sarcomas in syngeneic wild-type, RAG2-/-, and RAG2-/- x γc-/- mice, we show that the innate immune system can edit the immunogenicity of primary tumors. Specifically, RAG2-/-x γc-/- mice displayed the highest incidence of MCA sarcomas, followed by RAG2-/- mice, and WT mice have the lowest incidence at four separate doses of MCA. Moreover, when cell lines were generated from MCA sarcomas, the cell lines derived from MCA sarcomas growing in RAG2-/-x γc-/- mice had the highest immunogenicity, followed by cell lines from RAG2-/- mice, and cell lines from WT mice had the lowest immunogenicity. These results show that the innate immune system can edit tumors in the absence of adaptive immunity. To examine the cellular basis of editing by the innate immune system, we analyzed the innate cells that infiltrate tumors formed from transplanting highly immunogenic MCA sarcoma cell lines into RAG2-/- or RAG2-/-x γc-/- mice. We found that M1 macrophages were detected at high levels in immunogenic tumors in RAG2-/- but not RAG2-/- x γc-/- mice. The accumulation of M1 macrophages required IFNγ and was associated with effective tumor editing. In the absence of γc and IFNγ, M2 macrophages were abundant, and editing was impaired. Notably, M1 macrophages can be elicited by administration of CD40 agonistic antibodies, thereby restoring cancer editing activity in RAG2-/-x γc-/- mice. Our results suggest that crosstalk between natural killer cells and M1 macrophages, through IFNγ, can be elicited in highly immunogenic tumors, leading to cancer immunoediting. Our highly immunogenic cell lines will provide a system to dissect the cellular and molecular basis of cancer immunoediting by the innate immune system.
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 526. doi:1538-7445.AM2012-526
Abstract 5329: Induction of VEGF-C expression via mGluR5 in the lymph node metastases of oral cancer by the SDF-1/CXCR4 system
Authors: Uchida Daisuke , Kuribayashi Nobuyuki , Tamatani Tetsuya , Nagai Hirokazu , Miyamoto Youji 
Published: August 2012

Abstract
Previously, we identified a metastasis-candidate gene, metabotropic glutamate receptor (mGluR)-5, which is a target gene of stromal cell-derived factor (SDF)-1/CXCR4 system in oral cancer. In this study, we examined the role of mGluR5 on the lymph node metastasis of oral cancer. We used 2 kinds of mGluR5-specific antagonists, 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP). These antagonists did not affect the growth of oral cancer cells, but did inhibit the SDF-1/CXCR4 dependent-migration of the cells. In order to confirm the drug toxicities, these antagonists were intraperitoneally injected into wild-type mice for 4 weeks. All the mice injected with MPEP (5 mg/kg) and MTEP (5 mg/kg) did not show side effects, such as hematotoxicity, allergic reaction and body weight loss. When the CXCR4 expressing-oral cancer cells were transplanted into masseter muscle of nude mice, these antagonists significantly inhibited lymph node metastases of the cells. Although SDF-1/CXCR4 dependent production of angiogenic factors, including interleukin-6, interleukin-8, and vascular endothelial growth factor (VEGF)-A were observed, mGluR5 antagonists did not influence the production of these factors. However, induction of a lymphangiogenic factor, VEGF-C was specifically inhibited by the treatment with these mGluR5 antagonists. These results suggested that SDF-1/CXCR4 system induce lymph node metastases by the production of VEGF-C via upregulation of mGluR5.
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 5329. doi:1538-7445.AM2012-5329
Abstract 5335: Identification and molecular characterization of pancreatic tumor-initiating cells
Authors: Vorvis Christina , Poultsides George A. , Norton Jeffrey A. , Iliopoulos Dimitrios 
Published: August 2012

Abstract
Pancreatic cancer has the worst prognosis of any major malignancy with complex etiology involving both environmental and genetic factors. Despite increasing knowledge in tumor biology, the treatment efficacy in pancreatic cancers has not improved significantly over the past decade. Thus, the identification of novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. The realization that tumors themselves function as complex organs birthed the concept that cancer cells with tumor-initiating properties of stem cells may be the key drivers of the complex machinery behind oncogenesis. Tumor-initiating cells (TICs) have been studied extensively in the hematopoietic system, however it is not known which subpopulation has the highest tumor-initiating potential in pancreatic cancer. We have identified that the CD133+/CD44+/ALDH1+ cell population derived from 31 pancreatic adenocarcinomas and 6 pancreatic cancer cell lines, has the highest tumorigenic potential, assessed by in vivo dilution tumor propagation assays in highly immunodeficient (NOD-SCID IL2Rγ-/-) mice. In addition, this population has the highest sphere-forming capacity and is highly resistant to gemcitabine treatment in comparison to the other subpopulations. RNA-sequencing analysis in CD133−/CD44−/ALDH1− and CD133+/CD44+/ALDH1+ subpopulations derived from BxPC3 pancreatic cells revealed the transcriptomic alterations between these cell types. Furthermore, gene network analysis revealed enrichment of inflammatory and lipid metabolism networks in pancreatic TICs, suggesting the potential role of inflammation and lipid metabolism in pancreatic TIC function. In addition, a gene network-based FDA-approved chemical library screen revealed that metformin perturbs the activated networks in pancreatic TICs leading to the suppression of their growth. Metformin suppressed pancreatic cancer growth, through suppression of pancreatic TICs, in different pancreatic cancer mouse models. Overall, we propose the identification of a novel pancreatic cancer subpopulation which harbors tumor-initiating properties and is regulated by inflammatory signals, contributing to our understanding of how inflammation is linked to pancreatic oncogenesis in the molecular level. Furthermore, by following a novel strategy, we have identified that metformin suppresses pancreatic tumor growth and relapse through inhibition of pancreatic TIC growth.
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 5335. doi:1538-7445.AM2012-5335
Abstract 5364: Correlation of immune responses and overall survival in a phase II study of belagenpumatucel-L, an allogeneic tumor cell vaccine, in non-small cell lung cancer (NSCLC)
Authors: Shawler Daniel L. , Tong Alex , Liu Lily , Carrier Ewa , Davis Charles S. , Nemunaitis John , Fakhrai Habib 
Published: August 2012

Abstract
This study examines the correlative/predictive value of cellular- and humoral-mediated immune response on the clinical responsiveness of patients who received belagenpumatucel-L, a therapeutic vaccine comprised of 4 TGF-β2 antisense gene-modified allogeneic non-small cell lung cancer (NSCLC) cell lines in a phase II clinical trial in which subjects with stage III/IV NSCLC received intradermal injections of the vaccine every 4-8 weeks. We performed assays of cellular (ELISPOT) and humoral (antibody ELISA) immunity on 36 subjects in the trial and correlated these data with the long term assessment of overall survival. All but one subject in the study showed an increase in immune reactivity in at least one of the cellular or humoral assays. Eleven subjects who demonstrated an aggregate increase in both cellular and humoral immune reactivity (positive by three of four criteria tested) had a median survival of 32.5 months (95% CI, 25.2 to 39.8). This was significantly better than the median survival of only 11.6 months (95% CI, 5.6 to 17.6) for the 25 subjects who showed an increase in one or none of the measured immune parameters (p=0.015, log-rank test). The demonstration of a statistically significant correlation between cellular and humoral immune responses and overall survival in subjects treated with belagenpumatucel-L suggest that both compartments of the immune system likely impact the clinical response and are important for the induction of clinically significant antitumor immunity by the vaccine.
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 5364. doi:1538-7445.AM2012-5364