bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 761: Comparison of different classes of CpG-ODNs to augment generation, proliferation and specific cytotoxicity of human epitope-peptide specific CTLs in vitro
Authors: Katsuda Masahiro , Iwahashi Makoto , Matsuda Kenji , Miyazawa Motoki , Nakamori Mikihito , Nakamura Masaki , Ojima Toshiyasu , Iida Takeshi , Hayata Keiji , Yamaue Hiroki 
Published: June 2012

Abstract
Three distinct classes of CpG- oligonucleotides (ODN) (CpG-A, CpG-B and CpG-C) have been identified based on differences in their structures and immune effect. So far, CpG-B is only applied for clinical treatments; however, it is still unknown which of the different CpG-ODN classes is most useful as adjuvant of human cancer vaccine therapy. In the present study, we examined the activity of these 3 types of CpG-ODNs to enhance the induction of human peptide-specific CTLs. In addition, we elucidated the effect of CpG-ODNs on tumor antigen epitope peptide-specific CTL clones to investigate the adjuvant mechanism of CpG-ODNs on peptide vaccine therapy. Our data showed that PDC activated by CpG-ODNs augmented induction of peptide specific CTLs. Importantly, CpG-A is superior to CpG-B and CpG-C in augmenting the generation, proliferation and cytotoxic activity of human peptide specific CTLs in vitro. Moreover, type-1 IFNs produced by PBMCs that were stimulated with CpG-ODNs accelerated the proliferation of peptide-specific CTL clones, and also directly augmented the peptide specific cytotoxicity of CTL clones through the up regulation of Granzyme-B. These data showed that IFN-α might play an important role for CpG-ODNs to induce the adjuvant effects in peptide vaccine therapy. In addition, because CpG-A induced high amount of type-1 IFNs, CpG-A might be the superior candidate for vaccine adjuvant than CpG-B or CpG-C.
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 761. doi:10.1158/1538-7445.AM2011-761
Abstract 763: Cranberry juice constituents as an adjuvant for protein vaccination against malignant lymphoma
Authors: Hochman Jacob , Braitbard Ori , Roniger Maayan , Bar-Sinai Allan , Weiss Ervin I. , Hochman Nira 
Published: June 2012

Abstract
Cranberry fruit and juice have been reported to exert a multitude of health-related benefits. NDM is a 12-30K molecular weight fraction, which we have derived from cranberry juice and which, as we have previously reported, impairs in vitro growth and invasion through extracellular matrix of murine lymphoma cells [N.Hochman et al. Nutrition and Cancer 60(4), 511-517,2008]. Furthermore, intraperitoneal inoculation of NDM inhibited the in vivo growth of these tumors in syngeneic hosts, demonstrating its in vivo efficacy as an anti-tumorigenic agent.
MMTV-p14 (p14 for short) is the signal peptide of the env-precursor of Mouse Mammary Tumor Virus. This peptide was found by us to localize in the nucleoli of every MMTV-containing lymphoma or mammary carcinoma tested, (as well as in some cases of human breast cancer).
Here we report that priming and boosting of mice with purified recombinant p14 +NDM results in enhanced generation of anti-p14 antibodies in the sera of inoculated mice. Furthermore, mice primed and boosted with p14+NDM are immunized against a subsequent challenge with malignant lymphoma cells that contain MMTV. Mice, primed and boosted separately with p14 or NDM were not immunized against a lymphoma challenge.
These findings demonstrate that NDM can be used as adjuvant in a protein vaccination protocol against malignant lymphoma cells that harbor the virus MMTV.
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 763. doi:10.1158/1538-7445.AM2011-763
Abstract 765: Costimulatory SA-4-1BBL and monophosphoryl lipid A as novel adjuvant system for the development of cancer vaccines with robust therapeutic efficacy
Authors: Srivastava Abhishek , Sharma Rajesh , Zhao Hong , Yolcu Esma , Shirwan Haval 
Published: June 2012

Abstract
Subunit vaccines based on tumor-associated antigens (TAAs) represent an attractive alternative to conventional treatments for cancer due to their safety profile and ability to control recurrences by establishing long-term immunological memory. However, the efficacy of TAA-based therapeutic vaccines is limited by weak immunogenic nature of these antigens and various immune evasion mechanisms employed by the progressing tumor. To overcome these limitations, we herein used SA-4-1BBL costimulatory molecule and toll-like receptor 4 agonist monophosphoryl lipid A (MPL) as two immunomodulators with distinct mechanisms of action as a novel adjuvant system for the development of HPV16 E7 and survivin TAA-based therapeutic vaccines against TC-1 cervical and 3LL pulmonary carcinoma mouse models, respectively. A single immunization with a vaccine formulation containing E7 protein plus SA-4-1BBL and MPL resulted in the eradication of established E7 expressing TC-1 tumors in 100% of mice. Similarly, a single vaccination with survivin, as a bona fide self-TAA, resulted in control and/or eradication of established 3LL pulmonary metastases and the efficacy of the vaccine was further improved by a booster injection. Combined adjuvants had better therapeutic efficacy over the individual agents while SA-4-1BBL significantly performed better than MPL. The therapeutic efficacy achieved with the combinatorial use of both adjuvants and SA-4-1BBL as monotherapy was correlated with elevated levels of IFN-γ+TNF-α+IL-2+ triple positive antigen-specific CD8+ T cells, cytotoxic response, long-term immune memory, and most importantly an increase in the intratumoral number of CD8+ T effector cells with simultaneous decrease in the number of CD4+FoxP3+ T regulatory cells, resulting in a favorable T effector/T regulatory cell ratio. In marked contrast, although MPL as monotherpay improved the effector function of CD8+ T cells, it did not increase the infiltration of these cells into the tumor. Surprisingly, MPL as monotherapy increased the number of CD4+FoxP3+ T regulatory cells infiltrating into the tumor, resulting in an unfavorable T effector/T regulatory cell ratio. Taken together, these data demonstrate the utility of using SA-4-1BBL and MPL as a novel adjuvant system for the development of therapeutic TAA-based subunit cancer vaccines with strong clinical implications.
Work is in part funded by NIH 2R44 AI071618-02, R43 AI074176, R41 CA121665, KLCP, the W.M. Keck Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund.
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 765. doi:10.1158/1538-7445.AM2011-765
Abstract 768: Lymphokine activated killer cell conditioned media induces monocytes to differentiate into a dendritic cell-like/activated monocyte phenotype with cytotoxic potential against glioblastoma
Authors: Cornforth Andrew N. , Lee Gregory , Fan Eric , Fowler Abner , Alldredge Jessica , Carbonell Denysha , Dillman Robert O. 
Published: June 2012

Abstract
Background: Despite advances in surgery and multimodal treatment regimens, Glioblastoma (GBM) continues to have poor overall survival outcomes and associated treatment morbidity. Cell-based immunotherapy is being explored as an option in the treatment of GBM. Treatment of GBM with lymphokine activated killer cells (LAK) generated by interleukin-2 (IL-2) stimulation has been associated with encouraging overall survival rates (Dillman RO et al. J Immunotherapy 2009 32:914-919). Since it has been reported that IL-2-activated lymphocytes can produce cytokines that may influence the differentiation and activation of monocytes (Kirsch M et al. J Neurooncol 1994 20:35-45), we explored the generation of activated monocytes and/or dendritic cells (DC) in LAK cell therapy products. Methods: Magnetic cell isolation of major histocompatibility complex II positive cells (HLA-DR) from LAK cell preparations revealed a small subpopulation of cells expressing CD80 and CD86 which also retained some CD14 expression. We then explored the possibility of generating activated monocytes and/or DC by incubating elutriated monocytes in the conditioned media of LAK cell preparations (LAK-CM) and examining their characteristics in comparison to standard GM-CSF/IL-4 DC or LAK cells. Results: The resulting LAK-CM incubated monocytes showed high levels of expression of CD80 (65.3%), CD86 (72.3%), HLA-DR (83.6%), comparable to the standard GM-CSF/IL-4 DC. The LAK-CM treated monocytes also retained their CD14 expression at (58.2% vs. 58.4%) and had similar levels of phagocytic ability compared to DC (14.7% vs. 12.7%) and demonstrated higher cytotoxicity levels against a model GBM cell line, U251, compared to either LAK cells themselves or the standard GM-CSF/IL-4 generated DC (85.6% vs. 55.9% vs. 60.9%, respectively). Conclusions: Combining lymphocytes and monocytes from elutriated lymphocyte fractions under LAK cell generation conditions (1000 IU/mL IL-2 in AIMV) also yielded similar dendritic cell/activated monocyte phenotypes suggesting that new combinations of cell therapy could be produced using this method with higher tumor cytotoxicity potentials as well as antigen cross presentation capabilities.
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 768. doi:10.1158/1538-7445.AM2011-768
Abstract 773: Inhibition of HIF-1 impairs TGF-β-mediated immunosuppression
Authors: Teramoto Koji , Kawaguchi You , Hori Tetsuo , Ohshio Yasuhiko , Kitamura Shoji , Hanaoka Jun , Tezuka Noriaki , Kontani Keiichi 
Published: June 2012

Abstract
Hypoxia is one of distinctive features of the tumor microenvironment. In the tumor tissues under hypoxia, a transcription factor, hypoxia-inducible factor-1 (HIF-1) plays a critical role in regulating expressions of various genes associated with tumor growth. In order to understand the immunobiology of hypoxic tumor microenvironment, it is of great interest to elucidate the anti-tumor immune responses regulated by HIF-1. From these viewpoints, we focused on a relationship between HIF-1 and transforming growth factor-beta (TGF-β). TGF-β which is derived from either tumor cells or tumor stromal cells may be regulated by HIF-1 and suppress anti-tumor immune responses in tumor-bearing hosts. In this report, we hypothesized that eliminated expression of TGF-β by inhibition of HIF-1 in tumor tissue would contribute to augmentation of anti-tumor immune responses. We examined the possibilities in tumor-bearing mice models. C57BL/6 mice bearing mouse lymphoma E.G7 were administrated HIF-1 siRNA into the tumor tissue four times at 2-day interval. Seven days after the last administration of HIF-1 siRNA, anti-tumor immune responses elicited in the mice were examined. As results, inhibition of HIF-1 in tumor tissue led to low expression of TGF-β mRNA as well as low level of TGF-β protein there. In tumor-draining lymph nodes where TGF-β derived from tumor tissue would affect anti-tumor immune responses, the numbers of CD4+CD25+Foxp3+ cells (regulatory T cells) as well as CD11b+Gr-1+ cells (myeloid-derived suppressor cells) were decreased. Meanwhile, tumor antigen-specific CD8+ as well as CD4+ cells producing IFN-γ were increased. In spleen, production of reactive oxygen species by CD11b+Gr-1+ cells was recovered to the same level as that from normal mouse. Tumor antigen-specific CD8+ as well as CD4+ cells producing IFN-γ were increased and cytotoxic activity against target E.G7 cells were enhanced in spleen. Subsequently, tumor growth was effectively suppressed by inhibition of HIF-1. Inhibition of HIF-1 in tumor tissue can reduce expression of TGF-β there. This contributes to weakening suppressor cells in tumor-draining lymph nodes, which elicits enhanced anti-tumor immune responses systemically. These results demonstrate that hypoxia and immunosuppression in tumor microenvironment are linked by HIF-1and TGF-β, respectively. Inhibition of HIF-1 can improve anti-tumor immune responses, and provides a new rationale with the cancer immunotherapy.
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 773. doi:10.1158/1538-7445.AM2011-773
Abstract 780: Immune escape in colorectal carcinoma: role of the IFN-γ pathway
Authors: Britzen-Laurent Nathalie , Naschberger Elisabeth , Rau Tilman , Schneider-Stock Regine , Hartmann Arndt , Croner Roland S. , Stürzl Michael 
Published: June 2012

Abstract
The presence of a Th1 adaptive immune response in colorectal carcinoma (CRC) has been associated with improved clinical outcome and survival of patients. The Th1 adaptive immune response is mediated by IFN-γ, a known anti-proliferative, pro-apoptotic and pro-immunogenic cytokine. We have previously identified the guanylate-binding protein 1 (GBP-1), one of the proteins the most highly induced by IFN-γ, as a sensitive marker for the detection of this immune response in CRC in vivo. In a tissue microarray study with 388 CRC tumors, 30% showed GBP-1 expression. Interestingly, in these tumors the expression of GBP-1 was only induced in the cells of the desmoplastic stroma and not observed in adjacent tumor cells. This suggested that CRC tumor cells might undergo an immune escape from the Th1 adaptive immune response, characterized by the loss of IFN-γ responsiveness. Therefore, we investigated the responsiveness to IFN-γ in sixth different CRC cell lines and in normal colon epithelial cells. After treatment with IFN-γ, three of the sixth CRC cell lines (DLD-1, SW480 and HCT116) failed to express GBP-1 as well as other IFN-induced proteins such as caspase-1 and MxA. On the contrary, a robust GBP-1 induction was present in normal colon epithelial cells, in T84, WiDr and HT29 cells.
We then investigated whether the loss of expression of IFN-γ target genes was associated with phenotypic changes in CRC cells. In fact, we found that DLD-1, HCT116 and SW480 were resistant to IFN-γ-induced apoptosis. Furthermore, the loss of IFN-γ responsiveness correlated in SW480 and HCT116 with the absence of expression of the IFN-γ receptor alpha chain (IFNγRα).
Tumor xenotransplant experiments using DLD-1 cells with reconstituted GBP-1 expression resulted in significantly reduced tumor growth as compared to xentotransplants with control vector transfected DLD-1 cells. This indicated that GBP-1 expression may mediate the anti-tumorigenic effects of the Th1 response.
Overall, these data suggested that loss of IFN-γ responsiveness may be a common event in CRC and may protect tumor cells against the anti-tumorigenic (e.g. pro-apoptotic) effects of IFN-γ. The presence of an immune escape from the Th1 adaptive immune response may have important repercussions for prognosis and patients recruitment for immune-based therapy in CRC.
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 780. doi:10.1158/1538-7445.AM2011-780
Abstract 79: Role of histone deacetylase expression in intrahepatic cholangiocarcinoma
Authors: Morine Yuji , Shimada Mitsuo , Utsunomiya Tohru , Imura Satoru , Ikemoto Tetsuya , Mori Hiroki , Hanaoka Jun , Iwahashi Syuichi , Saito Yu , Yamada Shinichiro , Asanoma Michihito , Kanamoto Mami 
Published: June 2012

Abstract
Introduction: Histone deacetylase (HDAC) plays an important role in chromatin remodeling, gene expression and in regulating cell cycle progression and differentiation. Furthermore, HDAC inhibitors have recently been found to repress the function of hypoxia inducible factors (HIF) through inducing hyperacetylation of histones. However, few studies have been conducted regarding the role of HDAC in IHCC. The aim of this study was to elucidate the role of HDAC in IHCC.
Methods: Thirty-five patients with IHCC who underwent hepatic resection were evaluated. The expressions of HDAC1 and HIF-1α were determined immunohistochemically, and the patients were divided into two groups: HDAC1 positive group (n=21); and HDAC1 negative group (n=14). Clinicopathological variables including HIF-1α expression were compared between the two groups.
Results: The HDAC1 expression correlated significantly with higher stage carcinoma, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 77.9% vs. 7.9%, p=0.001). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, p=0.0018). Furthermore, there was a significant correlation between HDAC1 expression and HIF-1α expression (p=0.007), and co-expressions of these markers in same cancer cells were proven by immunofluorescent stainings in the serial section
Conclusions: The findings suggested that a positive expression of HDAC1 is a new prognostic indicator of IHCC, and that HDAC1 might be a possible promising molecular target of IHCC, through the regulation of HIF-1α.
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 79. doi:10.1158/1538-7445.AM2011-79
Abstract 795: Patterns of T-cell distribution at the invasive margin of colorectal cancer liver metastases: Downstream recruitment of T cells and spatial heterogeneity
Authors: Halama Niels , Zoernig Inka , Spille Anna , Schirmacher Peter , Brand Karsten , Falk Christine , Grabe Niels , Jäger Dirk 
Published: June 2012

Abstract
The local immunological cancer microenvironment influences the clinical course of colorectal cancer. The interface between colorectal cancer liver metastases and adjacent normal liver represents a clear border. Typically, T cells in the vicinity of the tumor are located on the stromal compartment of the tumor and only few cells are in direct contact with the tumor epithelium. Patterns of T cell distribution at the invasive margin are heterogeneous and have not been analyzed systematically. Using high-throughput whole slide imaging technology, tissue areas of 1 mm2 size were analyzed for precise T cell density and localization, showing distinct density patterns of localization in relation to the malignant tissue across the invasive margins of samples from different patients. Unsupervised clustering revealed distinct patterns: regions with T cells in close contact to the tumor usually had significantly elevated T cell numbers further away from the tumor, whereas the other groups showed limited enrichment. Additionally, in the distance of around 20 to 40 µm from the tumor a decrease in T cells was found. The distribution of the cells in the tissues could be accounted for by cell-matrix interactions, immune cell – immune cell interactions or chemotactic fields potentially generated by tumor or other cells. Direct T cell – tumor interaction however leads to subsequent far-reaching attraction and activation of T cells.
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 795. doi:10.1158/1538-7445.AM2011-795
Abstract 802: Cytokine profiles in bone marrow supernatant and peripheral blood of patients with multiple myeloma and Waldenström's macroglobulinemia
Authors: Plyler Ryan J. , Wang Weixin , Ghobrial Irene M. , Roccaro Aldo M. , Korde Neha , Zingone Adriana , Landgren Ola , Calvo Katherine R. 
Published: June 2012

Abstract
Cytokines serve vital roles in the regulation of immune responses. In patients diagnosed with hematologic malignancies, cytokines may play a role in the tumor-host microenvironment affecting tumor survival and progression. Previous studies have quantified the variation in cytokine concentrations between malignant and normal states in patients’ serum. However the research is sparser in relation to measurement of cytokine concentrations in the bone marrow microenvironment. Multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) are two such malignancies that arise in the B-lymphoid lineage and proliferate within the bone marrow (BM) microenvironment. In this study, an ultra-sensitive IL-6 and a human TH1/TH2 multiplex ELISA system were utilized to determine protein concentrations of the following cytokines: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, IL-13, IFN-gamma, and TNF-alpha, in the BM supernatant and peripheral blood (PB) of 20 patients with WM, 16 patients with MM, and 7 controls. The BM supernatant concentration of TNF-alpha was significantly increased in MM compared to controls (10.650 pg/ml vs. 4.980 pg/ml, p=0.0158). IL-1beta was significantly decreased in the bone marrow supernatant of MM (0.038 pg/ml vs. 2.352 pg/ml, p=0.0469) and WM (0.046 pg/ml vs. 2.352 pg/ml, p=0.0435). IL-8 was also significantly decreased in the BM supernatant of patients with MM (11.520 pg/ml vs. 43.590 pg/ml, p=0.0158) and WM (7.348 pg/ml vs. 43.590 pg/ml, p=0.0036). Differences in BM supernatant concentrations of IL-6 were not significant in MM, WM, and normal controls. Analysis of PB showed IL-2, IL-5, IL-6, IL-8, IL-10, and TNF-alpha were significantly increased in both MM and WM versus controls, and IFN-gamma was significantly increased in WM. Hierarchical clustering analysis of the cytokine profiles suggested two distinct subgroups existed within both MM and WM. TNF-alpha was the only cytokine in our study that was increased in both the bone marrow and serum of MM patients. The discordant results obtained in the BM supernatant vs. PB for IL-6 and IL-8 in both MM and WM indicate that cytokine profiles vary somewhat between the PB and BM compartments. The BM supernatant and PB cytokine profiles in patients with MM and WM highlight the important role cytokines may play in the microenvironment and biology of MM and WM.
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 802. doi:10.1158/1538-7445.AM2011-802