bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1082: IL27 promotes papilloma formation via inducing a pro-inflammatory milieu in the skin
Authors: Dibra Denada , Xia Xueqing , Newman Melissa , Keenan Camille , Li Shulin 
Published: May 2015

Abstract
Ras activation plays an important role in Squamous Cell Carcinomas (SCC) development. Additionally, there is large evidence confirming the role of inflammation during cancer initiation. However, the interaction between inflammation and oncogene activation is poorly understood in tumorigenesis. We found that IL27 promotes papilloma formation in a 2 step skin carcinogenesis (DMBA followed by benzoyl peroxide) model where DMBA causes Ras mutation. Because K15-positive follicular stem cells contribute to papillomas in the two-step skin carcinogenesis model, we used an inducible oncogenic K-RasG12D under the K15 promoter, which marks follicular stem cells. Indeed, treating mice with IL27 increased papilloma incidence earlier in these K15-K-RASG12D mice. Mechanistically, we see that ETAR+ macrophages are significantly increased in IL27-treated K15-K-RasG12D mice. Additionally, the ETAR ligand ET1, and the downstream factor of ETAR, COX2, are upregulated in these K15-KRasG12D mice by IL27, suggesting that ET1/ETAR pathway is involved in IL27 mediated papilloma formation. Indeed, IL27-mediated papilloma formation was reversed by using the ETAR inhibitor ZD4054. Therefore, the data shown here suggest that IL27 drives accumulation of ETAR+ macrophages, ET1, and Cox-2 in the skin and ultimately causes faster papilloma formation in K-Ras mutated follicular stem cells. These findings propose an unrecognized role of IL27 during initiation of skin carcinogenesis.
Citation Format: Denada Dibra, Xueqing Xia, Melissa Newman, Camille Keenan, Shulin Li. IL27 promotes papilloma formation via inducing a pro-inflammatory milieu in the skin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1082. doi:10.1158/1538-7445.AM2014-1082
Abstract 1083: Host-tumor immune response for early breast cancer patients treated with radiofrequency ablation therapy
Authors: Imoto Shigeru , Nakatsugawa Noriko , Ueno Takayuki , Ito Hiroki , Imi Kentaro , Miyamoto Kaisuke , Kitamura Manami , Isaka Hirotsugu , Nakatsura Tetsuya 
Published: May 2015

Abstract
[Background] We demonstrated immune suppression of regulatory T (Treg) cells in preoperative breast cancer (BC) patients at AACR 2011. Last year we also reported at this meeting that Th17 cells might have some potential to control tumor progression in the same cohort. Modern treatment of operable BC consists of breast surgery, drug therapy and radiation therapy. [Aim] To explore new strategy of BC treatment, we conducted a phase II study on radiofrequency ablation (RFA) in early BC between 2009 and 2013. Twenty patients were enrolled. To examine host-tumor immune response under thermal ablation therapy, Treg cells in peripheral blood mononuclear cells (PBMC) and plasma IL-17A were measured. [Patients and methods] Blood samples were collected from 13 patients before RFA and at the time of 1 month after RFA. Treg cells were examined by counting CD4+CD25highCD127low/-cells in PBMC. Plasma IL-17A was measured using cytometric beads array system. Statistical significance was analyzed using Mann-Whitney U-test. [Results] As of November 2013, all patients were free of recurrence. The percentages of Treg cells had no significant change in 13 patients before and after RFA (2.8% versus 2.7% of CD4-positive cells at mean value). In addition, there was no statistical difference in levels of plasma IL-17A before and after RFA (76 pg/ml versus 116 pg/ml at mean level). [Discussion] Unexpectedly, RFA had no favorable immune response in BC patients, because we observed significant decrease in percentages of Treg cells after breast surgery. The reason is that most patients had T1 tumor and Luminal A-like BC. They had lower percentages of Treg cells in comparison to those of tumor-bearing patients reported previously (2.8% versus 4.2%). [Conclusion] RFA is a promising alternative to breast surgery. However, it may make little effect on host-tumor immune response in favorable subtype of early BC.
Citation Format: Shigeru Imoto, Noriko Nakatsugawa, Takayuki Ueno, Hiroki Ito, Kentaro Imi, Kaisuke Miyamoto, Manami Kitamura, Hirotsugu Isaka, Tetsuya Nakatsura. Host-tumor immune response for early breast cancer patients treated with radiofrequency ablation therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1083. doi:10.1158/1538-7445.AM2014-1083
Abstract 1085: Glioma-infiltrating myeloid derived suppressor cells inhibit anti-tumor T cell responses
Authors: Kamran Neha , Assi Hikmat , Candolfi Marianela , Moreno Mariela , Li Youping , Lowenstein Pedro R. , Castro Maria G. 
Published: May 2015

Abstract
Efficacy of immunotherapeutic approaches against glioma is limited by the immunosuppressive tumor microenvironment. Tumor derived TGF-β, IL-10 and Prostaglandin E2 along with the presence of regulatory T cells (Tregs) and tumor associated macrophages (TAMs) promote the immune escape in gliomas. Also, tumor derived factors induce the expansion of myeloid derived suppressor cells (MDSCs). MDSCs represent a heterogeneous population of myeloid cells at various stages of differentiation that have the potential to inhibit anti-tumor T cell responses. Herein we demonstrate the accumulation of MDSCs in GL26 brain tumor bearing mice. Absolute numbers of Ly-6G+ (Gr-1high) MDSCs showed a 200 fold increase within the tumor mass 28 days post-tumor implantation. In contrast, the numbers of Ly-6C+ (Gr-1low) MDSCs did not significantly change within the tumor microenvironment. While this massive influx of MDSCs was noted within intracranial tumors, the levels of Ly-6G+ or Ly-6C+ MDSCs did not increase in the tumor draining lymph nodes (dLNs), spleen, bone marrow or blood of intracranial tumor bearing mice. Mice bearing GL26 or B16-F0 tumors in the flank showed a ∼3 fold increased influx of Ly-6G+ MDSCs within the tumor mass, the spleen and circulating MDSCs. Ly-6G+ MDSCs isolated from the brain tumors and spleens of GL26 intracranial tumor bearing mice inhibited tumor antigen-specific CD8+ T cell proliferation and T cell proliferation mediated by CD3 ligation . On the other hand, Ly-6C+ MDSCs did not did not elicit inhibition of T cell proliferation. Preliminary experiments using tumor cells' conditioned media indicate that CXCR2 signaling mediates the migration of MDSCs in a transwell assay and suggest the possibility that it could mediate MDSCs' migration into the tumor microenvironment in vivo. Overall, our data shows that MDSCs accumulate within the glioma mass and inhibit tumor-specific T cell responses. Strategies that inhibit MDSC recruitment to the tumor microenvironment and/or block their activity may therefore enhance the T cell mediated tumor clearance and suppress glioma progression.
Supported by National Institutes of Health/ National Institute of Neurological Disorders & Stroke (NIH/NINDS) Grants RO1-NS074387 and RO1-NS054193
Citation Format: Neha Kamran, Hikmat Assi, Marianela Candolfi, Mariela Moreno, Youping Li, Pedro R. Lowenstein, Maria G. Castro. Glioma-infiltrating myeloid derived suppressor cells inhibit anti-tumor T cell responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1085. doi:10.1158/1538-7445.AM2014-1085
Abstract 1089: Matrix stiffening and β1 integrin promote fibroblast accumulation in lung squamous cell carcinomas but not in adenocarcinomas
Authors: Alcaraz Jordi , Puig Marta , Lugo Roberto , Giménez Alícia , Velásquez Adriana , Galgoczy Roland , Ramírez Josep , Gómez-Caro Abel , Gascón Pere , Reguart Noemi 
Published: May 2015

Abstract
The mechanisms underlying the abundance of tumor associated fibrobasts (TAFs) in non-small cell lung cancer (NSCLC) remain poorly understood. To address this gap of knowedge, we examined the relative contribution of mechanical (i.e. matrix rigidity) and soluble biochemical (i.e. serum) cues in the accumulation of primary TAFs from either adenocarcinoma (ADC) or squamous cell carcinoma (SQC) NSCLC patients. For this purpose, fibroblasts were cultured on collagen-I coated gels engineered to exhibit either normal- or tumor-like stiffnesses at different serum concentrations. In fibroblasts from non-malignant tissue, matrix stiffening alone was sufficient to increase fibroblast accumulation by 20%. In addition, matrix stiffening-induced accumulation was dominant or comparable to that due to soluble growth factors up to moderate serum concentrations. These mechanical stimulatory effects were β1 integrin-dependent, and were associated with both increased integrin mechanosensing through FAKpY397and a post-transcriptionally-driven rise in β1 integrin expression. The latter mechanoregulatory circuit could be extended to TAFs in a subtype-dependent fashion, since SQC-TAFs exhibited higher FAKpY397 and β1 expression than ADC-TAFs. Remarkably, SQC-TAF density was enhanced &gt; 50% in response to matrix stiffening, whereas they were largely desensitized to serum. Conversely, substantial accumulation of ADC-TAFs required large serum concentration, whereas it was poorly induced by either matrix stiffening or low serum concentration. These results reveal that a therapeutic strategy aiming to inhibit soluble growth factors may be effective against ADC-TAFs, whereas a strategy aiming to rescue normal lung elasticity may be more efficient against SQC-TAFs.
Citation Format: Jordi Alcaraz, Marta Puig, Roberto Lugo, Alícia Giménez, Adriana Velásquez, Roland Galgoczy, Josep Ramírez, Abel Gómez-Caro, Pere Gascón, Noemi Reguart. Matrix stiffening and β1 integrin promote fibroblast accumulation in lung squamous cell carcinomas but not in adenocarcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1089. doi:10.1158/1538-7445.AM2014-1089
Abstract 109: PET imaging of 89Zr-labeled Pertuzumab in HER2-positive breast cancer xenografts
Authors: Marquez Bernadette V. , Ikotun Oluwatayo F. , Wright Brian , Zheleznyak Alexander , Richard Pierce , Lapi Suzanne E. 
Published: May 2015

Abstract
The sensitivity and quantitative properties of Positron Emission Tomography (PET) imaging combined with the selectivity and high affinity of radiolabeled monoclonal antibodies (mAbs) make a powerful tool in molecular imaging of diseases including breast cancer. Radiolabeling mAbs with the positron-emitting 89Zr has recently been useful in clinical trials due to its relatively long half-life (t1/2 = 3.3 days), which matches the pharmacokinetic properties of mAbs. Pertuzumab (Perjeta™) is an FDA-approved mAb for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, in combination with Trastuzumab (Herceptin™) and chemotherapy. Herein, we evaluated 89Zr-labeled Pertuzumab as a PET imaging agent in transgenic mice-bearing human breast cancer. The 89Zr chelator, p-isothiocyanatobenzyl-desferrioxamine, was conjugated to Pertuzumab and subsequently radiolabeled with 89Zr. The immunoreactivity and specificity of 89Zr-Pertuzumab for HER2-expressing cells were determined in vitro and showed retention of 89Zr-Pertuzumab immunoreactivity and specific binding to HER2-expressing cells. Human breast cancer cells were inoculated subcutaneously in severely immunocompromised NOG mice, a model which allows for the growth of HER2-positive tumors without exogenous stimuli. 89Zr-Pertuzumab was injected via tail vein and imaged and 5 and 7 days post-injection (p.i.) followed by biodistribution studies. Optimal contrast was achieved at 5 days p.i., with higher tumor uptake in the HER2-positive xenograft than the HER2-negative model. Immunohistochemical analysis of these tumors is in agreement with PET imaging analysis. These results illustrate that 89Zr-Pertuzumab may be beneficial for the noninvasive assessment of HER2 expression.
Citation Format: Bernadette V. Marquez, Oluwatayo F. Ikotun, Brian Wright, Alexander Zheleznyak, Pierce Richard, Suzanne E. Lapi. PET imaging of 89Zr-labeled Pertuzumab in HER2-positive breast cancer xenografts. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 109. doi:10.1158/1538-7445.AM2014-109
Abstract 1094: Dynamics of Gemcitabine induced interleukin-8 (IL-8) expression in pancreatic tumor microenvironment
Authors: Gomez Sobeyda , Fujii Takahiko , Huang Haojie , Hwang Rosa , Ramachandran Viji , Logsdon Craig , Arumugam Thiru 
Published: May 2015

Abstract
Background: The clinical standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) is treatment with Gemcitabine (Gem) despite Gem's limited benefits. To date, no surrogate marker has been identified to indicate whether Gem treatment directly affects PDAC tumor cells. In order to identify such a marker, we analyzed Gem treated cell lines and clinical samples. Methods: 12 PDAC cell lines were treated with 5μM Gem for three hours and then allowed to grow in the absence of Gem for 24hrs before mRNA expression analysis (Illumina Gene Expression Array). IHC and WB were used to quantify IL-8 expression. ShRNA mediated silencing was utilized to study the therapeutic value of IL-8. Results: mRNA expression and WB confirmed the induction of IL-8 after Gem treatment. Gem induced IL-8 expression was transcriptionally controlled by NFκB and C/EBP. PDAC cells (MPanc96 and BxPc-3-CXCR1), HPSC (Human Pancreatic Stellate Cells-CXCR1) and HUVEC (Human Umbilical Vein Endothelial cells-CXCR1 & 2) expressed the receptor of IL-8. Conditioned media from Gem treated cells and rIL-8 treated cells, stimulated cell growth (PDAC, HPSC and HUVEC), polygon formation in HUVEC and α-SMA expression in HPSC. Stable silencing of IL-8 in Capan2 cells, which develop an abundant stroma, led to a significant reduction in tumor volume. Histologically, IL-8 silenced tumors showed reduced micro-vessel density (CD37), as well as highly reduced desmoplasia (Trichrome stain & α-SMA) associated with necrosis. Further, IHC revealed strong IL-8 expression in neo-adjuvant Gem-treated human PDAC tissues (strong expression 42.1%, weak expression 57.9%, negative 0%) in comparison to tissue from patients that underwent surgery alone (strong expression 0%, weak expression 77.8%, negative 22.2%).Conclusion: Gem induced IL-8 functions as a growth factor for cancer cells and its microenvironment. Thus, IL-8 can serve as a surrogate marker to indicate Gem effects in PDAC.
Citation Format: Sobeyda Gomez, Takahiko Fujii, Haojie Huang, Rosa Hwang, Viji Ramachandran, Craig Logsdon, Thiru Arumugam. Dynamics of Gemcitabine induced interleukin-8 (IL-8) expression in pancreatic tumor microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1094. doi:10.1158/1538-7445.AM2014-1094
Abstract 1095: microRNA-26a expression may suppress tumor growth by modulating macrophage infiltration in tumor through down-regulation of M-CSF in hepatocellular carcinoma
Authors: Chai Zong-Tao , Zhu Xiao-Dong , Ao Jian-Yang , Kong Ling-Qun , Zhang Yuan-Yuan , Sun Hui-Chuan 
Published: May 2015

Abstract
Purpose
To Study molecular changes specific to tumor-derived endothelial cells.
Materials and methods
Tumor tissue and adjacent nontumor tissue were obtained from 27 hepatocellular carcinoma (HCC) patients. Primary cultured CD31+ and CD105+ tumor endothelial cells (TECs) and nontumor endothelial cells (NECs) were isolated by magnetic-activated cell sorting. Affymetrix GeneChip Human Gene ST Arrays were used to determine gene expression profiles of HCC cells and matched TECs and NECs. A capillary tube formation assay was used to evaluate tube formation by the endothelial cells. The tumorigenicity of isolated TECs was monitored in nonobese diabetic/severe combined immunodeficient mice.
Results
The isolated CD31+ and CD105+ TECs and NECs displayed features of endothelial cells. Both cultured HCC cells and TECs induced capillary tube formation in vitro and were incorporated into tumor vasculature in vivo. The TEC isolates had a gene signature resembling that of HCC cells, and TEC-specific genes were associated with poorer HCC survival.
Conclusions
A subset of TECs may originate from tumor cells, and they express a unique set of genes linked to HCC prognosis.
Note: This abstract was not presented at the meeting.
Citation Format: Zong-Tao Chai, Xiao-Dong Zhu, Jian-Yang Ao, Ling-Qun Kong, Yuan-Yuan Zhang, Hui-Chuan Sun. microRNA-26a expression may suppress tumor growth by modulating macrophage infiltration in tumor through down-regulation of M-CSF in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1095. doi:10.1158/1538-7445.AM2014-1095
Abstract 1097: Potentiating antitumor CD4+ T cell responses with chemotherapeutic agents
Authors: Zhou Gang , Lu Xiaoyun 
Published: May 2015

Abstract
Chemotherapy is a major treatment modality for many types of cancers. Even though chemotherapeutic drugs are chosen for their cytotoxicity toward cancerous cells, increasing numbers of anticancer drugs have been found to exert immune enhancing effects through a variety of mechanisms. These findings have led to a growing recognition that elicitation of endogenous host immunity may intrinsically contribute to the efficacy of some antineoplastic agents. Although standard chemotherapy can reduce the symptoms of cancer, chemotherapy alone is rarely curative. Tumor relapses often occur in patients after the initial treatment, suggesting that the endogenous antitumor immunity elicited by chemotherapy is not sufficient or durable enough to support long-term therapeutic efficacy. There is accumulating evidence that integration of chemotherapy and immunological maneuvers, such as adoptive T-cell therapy (ACT) and therapeutic vaccines, can effectively treat established tumors. In a mouse model of B-cell lymphoma, we previously reported that polyfunctional CD4+ effector cells arising from ACT play a critical role in sustaining an effective antitumor immunity in the post-chemotherapy setting. In the current study, we have screened a panel of widely used chemotherapeutic agents and identified those that can exert immunostimulatory effects on tumor-specific CD4+ T cells. We also examined the impact of these drugs on lymphoid and myeloid cell homeostasis, and cytokine/chemokine milieu. These data provide insight into the mechanisms by which certain anticancer drugs potentiate antitumor CD4+ T cell responses.
Citation Format: Gang Zhou, Xiaoyun Lu. Potentiating antitumor CD4+ T cell responses with chemotherapeutic agents. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1097. doi:10.1158/1538-7445.AM2014-1097
Abstract 1107: Tumor microenvironment based modulation of thyroid cancer phenotype
Authors: Tuli Neha Y. , Cabin Jonathan , Suriano Robert , Bednarczyk Robert , Hanly Elyse , Geliebter Jan , Shin Edward , Tiwari Raj K. 
Published: May 2015

Abstract
Inflammation plays a pivotal role in the progression of solid malignant tumor with studies showing that the presence of specific inflammatory-immune cells, such as macrophages, at the tumor site leads to poor prognosis. M1 polarized macrophages secrete pro-inflammatory chemokines and cytokines which induce an epithelial to mesenchymal transition (EMT) in tumor cells; a process where epithelial cells acquire mesenchymal traits, thus facilitating tissue infiltration and consequent metastasis. EMT as a marker of cancer progression is understudied in thyroid cancer. In our present study, we evaluated the crosstalk between the macrophages and the epithelial cells in the thyroid tumor microenvironment with the use of an in vitro model system consisting of an immortalized thyroid cell line (Nthy-ori 3-1), three papillary cancer cell lines (BCPAP, 8505C and TPC-1) and one follicular cancer cell line (CGTHW-1). We observed the halt in proliferation of the thyroid cancer cells as the epithelial cells differentiate into mesenchymal cells under the influence of activated macrophage conditioned media. We also observed a statistically significant (p&lt;0.05) upregulation of migration and invasion of thyroid tumor cells in presence of macrophage conditioned media. Using nuclear and cytoplasmic extracts from the thyroid cancer cell lines, we observed that EMT markers including E-cadherin, β-catenin, vimentin, NFk-B, snail, slug and twist are modulated in response to activated macrophage conditioned media. Downregulation of E-cadherin, required for maintenance of stable junction and β-catenin essential for cell-cell adhesion was noticed in response to macrophage conditioned media. Transcription factors like NFk-B, snail and slug were translocated to the nucleus, which is indicative of the initiation of EMT. Our data provides evidence that macrophage secreted proteins play a crucial role in epithelial-mesenchymal transition in thyroid tumor advancement and metastasis. We have successfully identified some significant markers including transcription factors such as NFk-B, slug, twist and snail that play a critical role in the induction of epithelial to mesenchymal transition in thyroid cancer. These findings will allow for the possible development of targeted therapy designed at inhibiting EMT and subsequent suppression of thyroid cancer metastasis and dissemination.
Citation Format: Neha Y. Tuli, Jonathan Cabin, Robert Suriano, Robert Bednarczyk, Elyse Hanly, Jan Geliebter, Edward Shin, Raj K. Tiwari. Tumor microenvironment based modulation of thyroid cancer phenotype. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1107. doi:10.1158/1538-7445.AM2014-1107