bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A45: Inflammatory biomarker c-reactive protein in radiotherapy-induced skin toxicities of breast cancer patients.
Authors: Rodriguez-Gil Jorge L. , Cooley Anne , Thomas Venetta , Takita Cristiane , Wright Jean , Poitevien Martine , Allen Glenn O. , Reis Isildinha M. , Zhao Wei , Hu Jennifer J. 
Published: August 2014

Abstract
Purpose: Post-surgery adjuvant radiotherapy (RT) significantly reduces recurrence and metastasis of breast cancer. However, many patients experience early adverse skin reactions (EASRs) that impact quality of life. This study evaluated an inflammatory biomarker C-reactive protein (CRP) in RT-induced EASRs in breast cancer patients undergoing RT.
Methods: We recruited 159 breast cancer patients undergoing RT after breast conserving surgery. The pre- and post-RT plasma CRP levels were measured using a highly-sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0).
Results: RT-induced grade 2+ skin toxicities were observed in 8 (5%) and 79 (50%) patients at weeks 3 and 6, respectively. Significantly higher proportions of African Americans developed grade 3 skin toxicities (13.8% vs. 2.3% in Whites) at week 6. In multivariate analysis, there was a suggestive association between grade 2+ skin toxicities at week 3 and &gt;2 mg/L pre-RT CRP (OR=4.68, 95%CI=0.49, 44.94). However, grade 2+ skin toxicities at week 6 were significantly associated with elevated: CRP &gt; 1 mg/L (OR=3.26; 95%CI=1.35, 7.85, p=0.01), obesity (OR=2.39; 95%CI=1.19, 4.83, p=0.02), or combined both factors (OR=7.80; 95%CI=2.59, 23.49, p&lt;0.001).
Conclusion: This is the first study to suggest that CRP has value as an inflammatory biomarker in RT-induced EASRs, particularly combined with obesity. Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in breast cancer patients undergoing RT.
Citation Format: Jorge L. Rodriguez-Gil, Anne Cooley, Venetta Thomas, Cristiane Takita, Jean Wright, Martine Poitevien, Glenn O. Allen, Isildinha M. Reis, Wei Zhao, Jennifer J. Hu. Inflammatory biomarker c-reactive protein in radiotherapy-induced skin toxicities of breast cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A45.
Abstract A47: Increased levels of IL-12, IL-23 and IL-18 in skin expressing HPV16 E7 protein.
Authors: Gosmann Christina , Mattarollo Stephen R. , Blumenthal Antje , Frazer Ian H. 
Published: August 2014

Abstract
As a consequence of infection with human papillomavirus (HPV), worldwide more than 0.25 million women die of cervical cancer each year. Chronic HPV infection is thought to create an immune suppressive environment preventing successful elimination of the virus, and there is no cure for persistent virus infection and resulting lesions. In a previous study using a mouse model of HPV16 E7 protein-induced epithelial hyperplasia, we demonstrated that IFN-γ plays a crucial role in suppressing an effective immune response against E7 in the skin (Mattarollo et al., J Immunol 2010, 184(3):1242-50). In support of these findings, we now show significantly higher levels of IFN-γ in E7-expressing compared to wild type skin. To investigate the mechanisms that drive IFN-γ production in E7 transgenic skin, we assessed the presence of the inflammatory cytokines IL-12, IL-23 and IL-18, which are well known potent inducers of IFN-γ. Quantitative analysis of skin mRNA levels and of supernatants from in vitro skin explant culture revealed significantly increased expression and secretion of IL-12, IL-23 and IL-18 in E7 positive compared to wild type skin. In contrast, levels of IL-6 protein and of pro-IL-1β mRNA and protein were reduced in E7 transgenic skin. We hypothesise that in chronically HPV-infected skin, a downregulation of IL-6 and IL-1β expression aids immune evasion, while IL-12, IL-23 and IL-18 induce immune suppressive IFN-γ, thus promoting persistent virus infection and allowing for the progression to cervical cancer.
Citation Format: Christina Gosmann, Stephen R. Mattarollo, Antje Blumenthal, Ian H. Frazer. Increased levels of IL-12, IL-23 and IL-18 in skin expressing HPV16 E7 protein. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A47.
Abstract A48: Novel dual mode fluorine MRI, NIR fluorescent probe for noninvasive detection of tumor-associated inflammation.
Authors: Balducci Anthony , Wen Yi , Zhang Yang , Helfer Brooke M. , Hitchens Kevin , Meng Wilson , Janjic Jelena , Wesa Amy 
Published: August 2014

Abstract
Tumor-associated macrophage are active in both tumor progression and remission processes, affecting prognosis depending on the nature of their involvement. Imaging macrophage recruitment and persistence to gauge tumor from normal host tissue is an area of great interest. Herein we propose the use of a novel dual mode fluorine magnetic resonance imaging (MRI), near infrared (NIR) fluorescent probe for the non-invasive detection of tumor associated inflammation. The use of this technique allows for rapid optical assessment of tumor associated macrophage as well as the specificity and detailed resolution provided by pairing 19F and conventional 1H MRI. Upon administration of the 19F/NIR reagent, tumors were visible at 6h. Both the liver and spleen were also visible due to clearance through the reticuloendothelial system. Use of the dual mode reagent was also compatible with MRI visualization, where detection of inflammation was in the periphery of, and not integral to, the tumor itself, information that could not be detected by optical means. Upon resection of the tumor, liver, spleen and other regions of interest fluorescence detection within the organs/tissue correlated with fluorine content and agreed with macrophage infiltrates and regions of reagent clearance. Flow cytometric analysis of whole blood show the preferential labeling of the macrophage population and immunofluorescent analysis of labeled macrophage further confirms cellular labeling. Dual functioning contrast agents enable both quick monitoring and sensitive quantification when evaluating the tumor microenvironment and potential changes in macrophage infiltrates as a result of therapeutic intervention.
Citation Format: Anthony Balducci, Yi Wen, Yang Zhang, Brooke M. Helfer, Kevin Hitchens, Wilson Meng, Jelena Janjic, Amy Wesa. Novel dual mode fluorine MRI, NIR fluorescent probe for noninvasive detection of tumor-associated inflammation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A48.
Abstract A50: Inhibition of IL-8 production by pancreatic cancer cells with marine natural products.
Authors: Guzman Esther A. , Pitts Tara , Wright Amy E. 
Published: August 2014

Abstract
Pancreatic cancer presents one of the most negative prognoses of all cancers, as it has usually metastasized by the time a patient is diagnosed. Therefore, almost as many deaths as new cases are expected each year. Although combination therapy shows some promise, the need for new drugs to treat the disease is pressing. Harbor Branch Oceanographic Institute (HBOI) has developed a unique library of marine samples and its research program seeks to tap into the biological diversity of the oceans to find potential anti-cancer drugs. Inflammation has been connected to pancreatic cancer development and progression. A recent study has shown that IL-8 mediates the angiogenesis of tumors arising from Ras-mutations. Ras is a proto-oncogene that is mutationally activated in 90% of pancreatic adenocarcinomas. Overexpression of IL-8 in pancreatic tumors is thought to promote tumor angiogenesis and to activate survival signaling pathways. Given our interest in finding new therapies for pancreatic cancer, we set up a 96-well cell-based assay to screen our library of marine natural products for those with the ability to inhibit IL-8 production by pancreatic cancer cells. A thousand fractions were screened resulting in the identification of marine natural products with the ability to inhibit IL-8 secretion by the BxPC-3 pancreatic cancer cell line. Studies are currently underway to determine if this inhibition leads to an inhibition in angiogenesis or affects cell proliferation.
Citation Format: Esther A. Guzman, Tara Pitts, Amy E. Wright. Inhibition of IL-8 production by pancreatic cancer cells with marine natural products. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A50.
Abstract A59: Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and monkeys.
Authors: Ohgidani Masahiro , Furugaki Koichi , Kentaro Shinkai , Kunisawa Yumi , Itaka Keiji , Kataoka Kazunori , Nakano Kenji 
Published: August 2014

Abstract
A block/homo-mixed polyplex micelle, comprising of cationic homo polymer: {N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} P[Asp(DET)] and block copolymer: polyethylene glycol (PEG) -P[Asp(DET)], has been reported to exhibit the efficient transgene expression in vivo by intratracheal and systemic administration. In the present study, we investigated the potential of immunogene therapy by intraperitoneal (i.p.) administration of block/homo polyplex micelles for peritoneal dissemination. For evaluation of transgene expression in vivo, block/homo polyplex micelles showed 12-fold higher level in luciferase expression evaluated by bioluminescence imaging system at 24 h after the i.p. administration compared with block polyplex micelles in nude mice bearing peritoneal dissemination. The distribution of polyplex micelles in tumor nodules was similarly present for both polyplex micelles, where the intracellular uptake of plasmid DNA was detected for block/home polyplex micelles but little for block polyplex micelles. The i.p. administration of block/homo polyplex micelles encapsulating granulocyte macrophage colony stimulating factor (GM-CSF) gene elicited GM-CSF expression dominantly in tumors and less in normal organs (liver and spleen), inhibited the tumor growth and prolonged survival rate for the mice harboring disseminated pancreatic cancer more significantly compared with the mock. The antitumor effect of GM-CSF gene therapy was mediated via the activation of natural killer cells. For safety evaluation, block/homo polyplex micelles indicated almost no adverse events for patho-physical findings and blood examinations in mice and cynomolgus monkeys, although slight increases in serum fibrinogen were observed in the monkey model. In conclusion, block/homo polyplex micelle-based immunogene therapy via i.p. administration may be a safe and effective approach for suppressing intractable peritoneal dissemination.
Citation Format: Masahiro Ohgidani, Koichi Furugaki, Shinkai Kentaro, Yumi Kunisawa, Keiji Itaka, Kazunori Kataoka, Kenji Nakano. Block/homo polyplex micelle-based GM-CSF gene therapy via intraperitoneal administration elicits antitumor immunity against peritoneal dissemination and exhibits safety potentials in mice and monkeys. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A59.
Abstract A6: The synergy between IL-12 priming of CD8 T cells and lymphodepletion is mediated by host IL-7.
Authors: Johnson Christopher Bryce , May Bennett R. , Cloud Colleen A. , Rubinstein Mark P. , Cole David J. 
Published: August 2014

Abstract
Adoptive T-cell transfer therapy (ACT) is a promising approach for the treatment of metastatic melanoma. Using the pmel-1 transgenic mouse as a source of melanoma-reactive CD8 T-cells, our lab has shown that priming these tumor-specific cells ex vivo with IL-12 (pmelIL-12) prior to ACT results in significant anti-tumor synergy and enhanced persistence in combination with cyclophosphamide (CTX). Here we demonstrate that other currently accepted lymphodepletion approaches, total body irradiation (TBI) alone or in combination with CTX, are also capable of synergizing with ACT of pmelIL-12. Interestingly, all 3 regimens (CTX, TBI and CTX + TBI) showed a similar ability to synergize with pmelIL-12, suggesting a common underlying mechanism. To elucidate the mechanism(s) behind this observed synergy, we evaluated whether the persistence of pmelIL-12 cells transferred into a lymphopenic host required the cytokines IL-7 and IL-15, which are known to be increased in the host post lymphodepletion. We found that the early expansion of pmelIL-12 in an irradiated host was partially dependent on IL-7, but not IL-15, as both the percentage and total number of donor cells recovered from spleens of irradiated hosts 1-week after ACT were greatly diminished in mice treated with an antibody against the IL-7 receptor alpha, CD127, or with an IL-7 neutralizing antibody (clone M25). In vitro these pmelIL-12 cells were able to proliferate in response to IL-7 to a much greater extent than pmel CD8 T-cells activated without IL-12. Together, these findings demonstrate that activated CD8 T cells primed with IL-12 display enhanced responsiveness to IL-7, and that IL-7 is necessary for maximal persistence of these cells in an irradiated host. Therefore, we conclude that the observed synergy between IL-12 priming of CD8 T cells and lymphodepletion is due in part to increased availability of host IL-7 after lymphodepletion.
Citation Format: Christopher Bryce Johnson, Bennett R. May, Colleen A. Cloud, Mark P. Rubinstein, David J. Cole. The synergy between IL-12 priming of CD8 T cells and lymphodepletion is mediated by host IL-7. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A6.
Abstract A86: Inactivation of p110delta PI3K releases potent antitumor immunity.
Authors: Ali Khaled , Soond Dalya , Pinero Roberto , Pearce Wayne , Scudamore Cheryl , Friedman Lori , Turner Martin , Okkenhaug Klaus , Vanhaesebroeck Bart 
Published: August 2014

Abstract
In cancer the tumor suppressive potential of the immune system is limited by the induction of self-tolerance and chronic inflammation promoted through the activity of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs) respectively. The phosphoinositide-3-kinase (PI3K) pathway is very frequently activated in cancer cells, and clinical trials with PI3K inhibitors are ongoing. The p110delta isoform of PI3K is highly enriched in leukocytes in which it regulates various immune functions. p110delta is involved in both the adaptive and innate immune system and p110delta inhibitors may be used to treat a broad range of immune disorders including T cell mediated auto-immune disorders. An expected side effect of long-term p110delta inhibition is, immune suppression, which could pre-dispose to cancer. We now show that paradoxically, genetic or pharmacologic inactivation of p110delta protects mice against tumor growth and metastasis. Blockade of p110delta; inhibits the activation of Treg cells and the accumulation of MDSCs, thus allowing the development of an effective CD8+ T cell-dependent anti-tumor response. These data provide a rationale for the use of p110delta inhibitors as adjuvants to boost anti-tumor immune responses in cancer.
Note: This abstract was not presented at the conference.
Citation Format: Khaled Ali, Dalya Soond, Roberto Pinero, Wayne Pearce, Cheryl Scudamore, Lori Friedman, Martin Turner, Klaus Okkenhaug, Bart Vanhaesebroeck. Inactivation of p110delta PI3K releases potent antitumor immunity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A86.
Abstract B10: Potential synergistic antitumor activity between sorafenib and lenalidomide in an orthotopic murine liver cancer model.
Authors: Chang Chun-Jung , Ou Da-Liang , Lin Yi-Jang , Cheng Ann-Lii , Hsu Chiun 
Published: August 2014

Abstract
The immune modulatory drug lenalidomide has shown promising anti-tumor activity in a clinical trial of patients with advanced hepatocellular carcinoma (HCC). The present study explored whether lenalidomide can enhance the anti-tumor activity of sorafenib, the standard molecular targeted therapy for HCC. An orthotopic liver cancer model was developed by injecting the BNL liver cancer cells (from ATCC) into the liver capsule of BALB/c mice. Mice were treated by sorafenib by daily gavage or lenalidomide by daily intra-peritoneal injection, and the anti-tumor efficacy of single-agent or combination treatment was measured by change in tumor volume and animal survival. The number of IFN-γ expressing T-cell sub-populations in tumor-infiltrating lymphocytes (TILs) and the number of IFN-γ expressing tumors-specific CD8+ T cells in splenocytes derived from tumor-implanted mice were measured by flow cytometry. Depletion of relevant T cell sub-populations or cytokines was done by co-administration of relevant antibodies with study drug treatment. TUNEL assay and immunohistochemical study on tumor tissues were done to measure apoptosis and to explore potential biomarkers (Ki67, CD31). Combination of sorafenib (5 mg/kg/day) and lenalidomide (50 mg/kg/day) produced significant synergistic anti-tumor efficacy in terms of tumor growth delay and animal survival. This synergistic effect was associated with a significant increase in IFN-γ expressing CD8+ lymphocytes in TILs and splenocytes. In addition, TILs derived from mice in the combination treatment group had higher number of granzyme- or perforin- expressing CD8+ T cells, compared with vehicle- or single-agent-treatment groups. Combination treatment was associated with a significant increase in apoptotic tumor cells and decrease in microvessel density in tumor tissue. Finally, the synergistic anti-tumor effect was abolished after CD8 depletion. The combination treatment was well tolerated except that leucopenia was common. Our data indicate that lenalidomide can enhance the anti-tumor effects of sorafenib in HCC through its immune modulatory effects and CD8+ T cells play an important role in the anti-tumor synergism. (supported by grants NSC 101-2321-B-002 -014 and NSC 101-2314-B-002-162)
Citation Format: Chun-Jung Chang, Da-Liang Ou, Yi-Jang Lin, Ann-Lii Cheng, Chiun Hsu. Potential synergistic antitumor activity between sorafenib and lenalidomide in an orthotopic murine liver cancer model. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B10.
Abstract B2: T cell costimulation in cancer immunotherapy with anti-CD137 monoclonal antibodies is mediated by K63-polyubiquitin-dependent signals from endosomes.
Authors: Martinez-Forero Ivan , Azpilicueta Arantza , Bolaños-Mateo Elixabet , Nistal-Villan Estnislao , Palazon Asis , Teijeira Alvaro , Perez-Chacon Gema , Morales-Kastresana Aizea , Murillo Oihana , Jure-Kunkel Maria , Zapata Juan Manuel , Melero Ignacio 
Published: August 2014

Abstract
Agonist anti-CD137(4-1BB) mAbs enhance CD8-mediated antitumor immunity. Agonist anti-human CD137 mAbs covering four distinct epitopes on the CD137 glycoprotein co-stimulated T cell activation irrespective of the engaged epitope or its interference with CD137L binding. CD137 perturbation with all these agonist mAbs resulted in antigen and antibody internalization towards a vesicular compartment. Internalization was observed in activated T cells from humans and mice, not only in culture but also in antibody-injected living animals. These in vivo experiments were carried out upon systemic intravenous injections with anti-CD137 mAbs and showed internalization in tumor-infiltrating lymphocytes and in activated human T cells transferred to mice. CD137-internalization required K63-polyubiquitination and endocytosed CD137-containing deposits were decorated with K63-polyubiquitins. CD137 stimulation activates NF-kB through a K63-linked polyubiquitination-dependent route and CD137-associated TRAF2 becomes K63-polyubiquitinated. Consistent with a role for TRAF2 in CD137 signalling, transgenic mice functionally deficient in TRAF2 show a delayed immunotherapeutic activity of anti-CD137 mAbs
Citation Format: Ivan Martinez-Forero, Arantza Azpilicueta, Elixabet Bolaños-Mateo, Estnislao Nistal-Villan, Asis Palazon, Alvaro Teijeira, Gema Perez-Chacon, Aizea Morales-Kastresana, Oihana Murillo, Maria Jure-Kunkel, Juan Manuel Zapata, Ignacio Melero. T cell costimulation in cancer immunotherapy with anti-CD137 monoclonal antibodies is mediated by K63-polyubiquitin-dependent signals from endosomes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B2.