bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1550: Supernatant of NIH3T3/Src(Y527F) cell line induced Ana-1 macrophages to tumor-associated macrophages by IL-6.
Authors: Chen Lechuang , Hu Chenfei , Xu Qing , Ma Kai , Liu Mei , Zhu Hongxia , Xu Ningzhi 
Published: August 2014

Abstract
Macrophages (Mф) is the major components of the solid tumors. Tumor-associated macrophages (TAM) play an important role in the development of tumor inflammation. The tumor microenvironment could induce macrophages differentiation into TAM, and the TAM could regulate tumor growth and invasion.
However, the mechanisms that by which signaling pathways contribute to cell differentiation are not well deﬁned. As we known, the tumor microenvironment in vivo is complex and integrated by a variety of cells and factors. In this study, we chose NIH3T3 cell line to construct a stable Src(Y527F) expression system. We found that its supernatant could induce macrophages differentiation into TAM in vitro. When we injected the cell mixture of Ana-1 macrophages and NIH3T3/Src(Y527F) cells into nude mice, the volume of tumors increased more quickly than the control group that just injected NIH3T3/Src(Y527F) cells only. And, we also found that the tumors became more invasive than control tumors. Furthermore, 62 cytokines were tested by using Cytokine Antibody Array, the result showed that 13 of them significantly changed in the supernatant of NIH3T3/Src(Y527F) cells compared with NIH3T3. Strikingly, IL-6 was 71-fold up-regulated. When we added IL-6 in the supernatant, it could also induce Ana-1 macrophages differentiation into a TAM phenotype. Our findings indicated that IL-6 might play an important role in the differentiation of Ana-1 from macrophages to TAM by using the supernatant of NIH3T3/Src(Y527F) cell line.
Citation Format: Lechuang Chen, Chenfei Hu, Qing Xu, Kai Ma, Mei Liu, Hongxia Zhu, Ningzhi Xu. Supernatant of NIH3T3/Src(Y527F) cell line induced Ana-1 macrophages to tumor-associated macrophages by IL-6. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1550. doi:10.1158/1538-7445.AM2013-1550
Abstract 1556: Immunological naturalization of immunocompetent host mice to luciferase-GFP for consistent tracking of transplanted tumors.
Authors: Day Chi-Ping , Weaver Zoe , Carter John , Bonomi Carrie , Van Dyke Terry , Hollingshead Melinda , Merlino Glenn 
Published: August 2014

Abstract
Optical imaging of labeled cells is the most prevailing method for cell tracking in mouse models. However, the immunogenicity of xenobiotic reporter genes, such as the commonly used firefly luciferase (ffLuc) and enhanced green fluorescence protein (eGFP), results in inconsistency in cell labeling and tumor progression, preventing their use in host mice with normal immunity. To resolve this issue, we have generated a reporter gene-tolerized transgenic mouse in which an ffLuc-eGFP fusion gene was targeted to the anterior pituitary gland using a rat Growth Hormone promoter (dubbed the “glowing-head” mouse). When ffLuc-eGFP-labeled Lewis Lung Carcinoma (LLC) tissue was subcutaneously transplanted into syngeneic glowing-head mice (GH-c-brd), their non-transgenic litter-mates (WT-c-brd), and immunocompromised Nod-Scid (balb/c) mice, anti-GFP antibody was induced only in the circulation of WT-c-brd. Labeled LLC also exhibited fewer CD4+ T cells but more macrophages in GH-c-brd than in WT-c-brd, suggesting it induced adaptive immunity in the latter. Moreover, GH-c-brd exhibited faster subcutaneous tumor growth and post-resection metastatic progression, and maintained more consistent tumor labeling, as compared to WT-c-brd and even Nod-Scid mice. Interestingly, in an adjuvant chemotherapeutic setting, the immunogenicity of the labeled tumor was able to deter metastatic progression in a manner similar to that obtained by drug treatment. We conclude that the immunogenicity of xenobiotic labeling markers can significantly influence disease progression and therapeutic responses thereby compromising immunocompetent preclinical cancer models, and that the glowing-head mouse can be used to circumvent such problems and promote consistent disease monitoring.
Citation Format: Chi-Ping Day, Zoe Weaver, John Carter, Carrie Bonomi, Terry Van Dyke, Melinda Hollingshead, Glenn Merlino. Immunological naturalization of immunocompetent host mice to luciferase-GFP for consistent tracking of transplanted tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1556. doi:10.1158/1538-7445.AM2013-1556
Abstract 1567: Use of humanized NOG mice within the pre-clinical development of new human specific therapies.
Authors: Mignard Caroline , Mirjolet Jean-Francois , Kissel Holger , Bichat Francis , Duchamp Olivier 
Published: August 2014

Abstract
Immune cells within the tumor microenvironment are now well recognized as to be targets of interest for cancer treatment. However there are no available pre-clinical models that will accurately support the pre-clinical development of such therapeutic approaches. Humanized NOG (NOD/shi-scid/IL-2Rγnull) mice, bearing human immune cells with or without human target tumor cells, are relevant models to test various therapeutic strategies (e.g. antibody dependent cell cytotoxicity, Treg targeting antibodies, TLR agonists, vaccines, adoptive T cells transfer, …) in various pathologies (e.g. oncology, autoimmune disease, inflammation, transplantation, …). Humanization of NOG mice was already characterized and validated using freshly collected human PBMCs or hematopoietic stem cells (HSCs) in both newborn and adult NOG mice.
The complete characterization of the reconstituted NOG mice was done in peripheral blood as well as central lymphoid organs such as bone marrow, spleen and thymus, using FACS analysis. Moreover, the human immune reconstitution and function in NOG mice was also evidenced with human cytokine and immunoglobulin quantification in mouse plasma samples. The injection of mature human PBMC in adult NOG mice leads to the consistent development of a xenogeneic graft-versus-host disease (GvHD), which mimics human GvHD (modification of CD4/CD8 ratio, expression of T cells activation markers and cytokine production).
Growth characteristics of human tumors models on humanized mice will be presented either as subcutaneous or as disseminated intravenous model. Randomization parameters were selected regarding both tumor and immune cell sides. Required readouts to understand immune cell modulation (Cell phenotyping and functionality) and related antitumor efficacy will be described. Finally, such models, i.e. humanized NOG mice bearing or not human tumor cells in the context of evaluation of new therapies will be detailed in various pathologies.
Citation Format: Caroline Mignard, Jean-Francois Mirjolet, Holger Kissel, Francis Bichat, Olivier Duchamp. Use of humanized NOG mice within the pre-clinical development of new human specific therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1567. doi:10.1158/1538-7445.AM2013-1567
Abstract 1577: Subtype dependent carcinoma initiation by Rb tumor suppressor inactivation in multiple epithelial tissues.
Authors: Song Yurong , Yang Chunyu , Pan Wenqi , Fathalizadeh Alisan , Lu Lucy , Gilbert Debra , O'Sullivan T. Norene , Haines Diana C. , Martin Philip L. , Van Dyke Terry 
Published: August 2014

Abstract
Carcinomas arise in a complex microenvironment consisting of multiple distinct epithelial lineages surrounded by mesenchymal cells. Of major importance is to understand the relationship among cell types, initiation event, and ultimate cancer outcome. Mouse models facilitate the prospective examination of early oncogenic events, which is not feasible in humans, permitting an analysis of epithelial subtype susceptibility. Since most solid tumors harbor aberrations in the pRb network, we assessed the susceptibility of epithelial subtypes expressing cytokeratin (K) 18 or K19 to the disruption of
Rb tumor suppression (Rb-TS) in vivo. Tumorigenesis could be initiated in either K18- or
K19-expressing cells. However, the susceptibility of epithelial tissues was subtype-dependent. K19 cells were more prone to hyperplasia and neoplasia than
K18 targeted cells. Given that a single genetic event was engineered, a small percentage of animals developed carcinoma/adenocarcinoma, providing the opportunity to define progression events via engineering or spontaneous evolution. To extend our analysis to a specific tissue, we employed a prostate-specific Cre line to target either K18- or K19-expressing prostate epithelial cells. Differential responses observed in the frequency and extent of premalignant hyperplastic lesions strongly supported the notion of cell type-dependent susceptibility to Rb-TS inactivation. Our data suggest that the tumorigenic consequences of a single initiation event are dictated by cellular subtype distinctiveness, underscoring the importance of the tumor cell of origin.
Citation Format: Yurong Song, Chunyu Yang, Wenqi Pan, Alisan Fathalizadeh, Lucy Lu, Debra Gilbert, T. Norene O'Sullivan, Diana C. Haines, Philip L. Martin, Terry Van Dyke. Subtype dependent carcinoma initiation by Rb tumor suppressor inactivation in multiple epithelial tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1577. doi:10.1158/1538-7445.AM2013-1577
Abstract 1579: Establishment of transgenic medaka as a stable tumor model for in vivo screening of anticancer drugs.
Authors: Matsuzaki Yuriko , Hosokai Haru , Mizuguchi Yukiyo , Shimizu Atsushi , Saya Hideyuki 
Published: August 2014

Abstract
The development of anticancer drugs would be facilitated by the availability of an in vivo screening system based on a multicellular organism. We intended to construct an animal model which can be stable and easily detected tumors without autopsy for chemical screening and assessment. In this study, the medaka which is a small egg-laying freshwater fish native to East Asia was applied.
The medaka has proved suitable for toxicology and carcinogenesis in the past studies. Furthermore most of molecular technology is available to the medaka and the size of the medaka genome (∼800 Mb) is about half that of the zebrafish genome. To construct a tumor model using transgenic medaka fish, a promoter sequence suitable for the tissue specific tumorigenesis was selected. There are some genes having specific expression in melanocyte. Melanocyte specific expression of oncogenes may induce progression to melanoma. Therefore we selected a promoter sequence encoding Tyrosinase, one of the melanocyte specific genes.
The recombinant plasmids for microinjection are consisting of the medaka tyrosinase promoter and human oncogenes (cMyc, BRAF mutant V600E and HRAS mutant G12V). One cell stage embryos were applied for microinjection. We obtained three stable transgenic individuals derived from one cMyc and two BRAF mutant (BRAF600E) injected F0, but none from HRAS mutant (HRAS12V). The transgenic (Tg)-cMyc and the Tg-BRAF600E produced tumor in internal organs with more than 50 % of all fish, but in eyes or skins (outer detectable organs) with less than 10 %. The Tg-HRAS12V animals died before achieving adulthood. We therefore developed a conditional gene expression system in which HRAS12V is expressed in response to the induction of Cre recombinase by heat treatment, given that the Cre gene was placed under the control of a medaka heat shock promoter.
One of the stable transgenic lines developed abnormal pigment cell proliferation in the eyes and epidermis with 100% penetrance by 6 months postfertilization. Sorafenib, an inhibitor of RAS signaling, was administered to the transgenic fish and was found both to reduce the extent of melanophore proliferation and to improve survival. This Tg-HRAS12V medaka established here thus represents a promising in vivo system with which to screen potential anticancer drugs that target RAS signaling, and this system can readily be adapted for the screening of agents that target other oncogenes.
Citation Format: Yuriko Matsuzaki, Haru Hosokai, Yukiyo Mizuguchi, Atsushi Shimizu, Hideyuki Saya. Establishment of transgenic medaka as a stable tumor model for in vivo screening of anticancer drugs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1579. doi:10.1158/1538-7445.AM2013-1579
Abstract 1589: LKB1 overexpression regulates DNA repair pathway and sensitivity to radiation in LKB1 mutant non-small cell lung cancer cell lines .
Authors: Yang Chao , Giri Uma , Cortez Maria Angelica , Gudikote Jayanthi , Fan YouHong , Diao Lixia , Byers Lauren A. , Heymach John V. 
Published: August 2014

Abstract
Background: LKB1 is a serine/threonine kinase which is mutated in 20-30% of non-small cell lung cancers (NSCLC).In general, DNA repair pathway activation leads cellular resistant to DNA damaging agents. The loss of LKB1 leads NSCLC to be more invasive and resistant to DNA damage based therapies. We hypothesize that loss of LKB1 may contribute to DNA damage response. We investigated LKB1- mediated signaling pathways by stably overexpressing LKB1 in its mutated NSCLC cell lines, A549 and H460. Methods: Expression of 139 proteins was analyzed by reverse phase protein array (RPPA) in LKB1 overexpressing cell lines along with the appropriate vector control lines. Differences in protein expression at baseline in clones with LKB1 versus clones with vector control were assessed by unpaired T-test with Welch's correction. Ionizing radiation sensitivity (reproductive cell death) was assessed by clonogenic cell survival assay (CSA). Results: LKB1 overexpression in A549 and H460 showed a significant downregulation of genes involved in DNA damage and repair pathway, such as RAD50 (1.4-fold relative expression, p&lt; 0.05 and 1.5-fold relative expression p&lt;0.02 respectively), XRCC1 (1.2-fold relative expression p&lt;0.005 and 1.1-fold relative expression p&lt;0.05, respectively), and DNA-PKCS (1.2-fold relative expression p≈0.067 and 1.2-fold relative expression p&lt;0.01. Also, CSA showed that A549 with LKB1 overexpression led to enhanced sensitization of cells to radiation (DER = 2) which is in consistent with the downregulation of RAD50, XRCC1 and DNA-PKCS. Furthermore, expression of CHK2 and phosphorylation of CHK1 are downregulated, H460 with LKB1 overexpression showed a significant decreasing of CHK1 phosphorylation level (p&lt;0.05). Conclusion: Our results suggest that LKB1 overexpression modulates DNA repair capacity through downregulation of RAD50, XRCC1, DNA-PKCS, CHK1 and CHK2. LKB1 loss may lead to the resistance to DNA damaging induced cell death.
Citation Format: Chao Yang, Uma Giri, Maria Angelica Cortez, Jayanthi Gudikote, YouHong Fan, Lixia Diao, Lauren A. Byers, John V. Heymach. LKB1 overexpression regulates DNA repair pathway and sensitivity to radiation in LKB1 mutant non-small cell lung cancer cell lines . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1589. doi:10.1158/1538-7445.AM2013-1589
Abstract 160: Modulation of the serum metabolomic profiles of breast cancer patients after receiving limonene intervention.
Authors: Miller Jessica A. , Pappan Kirk , Hu Chengcheng , Want Elizabeth J. , Keun Hector , Lang Julie E. , Chow H-H Sherry 
Published: August 2014

Abstract
Background. Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. To better characterize its mechanism of action in the clinical setting, we measured the serum metabolomic profiles of breast cancer patients before and after receiving a short-term limonene intervention.
Methods. Forty women with stage 0 - II breast cancer received 2 g QD limonene daily for 2 - 6 weeks (21.5 ± 8.8 days) before surgical resection of their tumor. Pre/post intervention blood draws were taken to assess serum metabolomic profiles. Metabolomic analysis was performed on the gas chromatography mass spectrometry and liquid chromatography mass spectrometry platforms established at Metabolon, Inc.
Results. Of the 397 identified biochemicals, 71 changed significantly (p&lt;0.05) from baseline to post limonene intervention. Pathway analysis revealed several key metabolic changes. Significant increases were noted in eight bile acid conjugates following limonene intervention, including a 3-fold elevation in taurocholate, taurodeoxycholate, and glycoursodeoxycholate. There were also significant decreases in a number of steroid hormones including dehydroisoandrosterone sulfate (DHEA-S), 4-androsten-3beta, 17beta-diol disulfate, epiandrosterone sulfate, androsterone sulfate, and pregnen-diol disulfate. In addition, markers of collagen remodeling or degradation were elevated following limonene intervention. Increased circulating vitamin C, improved insulin sensitivity and glycemic control, and reduced inflammatory potential were also noted following limonene treatment. An increase in plasma levels of ten different glycerophosphocholines and four carnitines were all significantly correlated to a decrease in cyclinD1 (all p's&lt;0.01 and Rˆ2&gt;0.4) in an exploratory analysis.
Conclusions. This global metabolomic profiling study revealed several novel mechanistic insights into the potential clinical activities of limonene. Efforts are ongoing to correlate these metabolic changes to carcinogenesis, clinical characteristics, and risk markers measured in breast tissue and serum.
Citation Format: Jessica A. Miller, Kirk Pappan, Chengcheng Hu, Elizabeth J. Want, Hector Keun, Julie E. Lang, H-H Sherry Chow. Modulation of the serum metabolomic profiles of breast cancer patients after receiving limonene intervention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 160. doi:10.1158/1538-7445.AM2013-160
Abstract 1604: ABT-869 enhances radiosensitivity of head and neck squamous cell carcinoma cells.
Authors: Hsu Heng-Wei 
Published: August 2014

Abstract
Purpose: Novel targeted therapeutic strategies to overcome radio-resistance of cancer cells traditionally treated with radiation may improve patient survival with the added benefit of reduced systemic toxicity. Herein, we tested the feasibility of ABT-869 (Linifanib), a multi-receptor tyrosine kinase inhibitor of members of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families, on radio-sensitization of head and neck squamous cell carcinoma (HNSCC).
Materials and Methods: UMSCC-22A and UMSCC-22B cells were treated with ABT-869 and γ-radiation response was determined. Cell viability, cytotoxicity, apoptosis induction and cell cycle distribution were examined by MTT assay, colony formation assay and flow cytometry. In addition, expression of STAT3 and downstream signaling proteins were assessed using western immunoblotting.
Results: Treatment with ABT-869 resulted in cell growth inhibition, induction of apoptosis, G2/M cell cycle arrest, reduced phosphorylation of STAT3, which has been linked to radio-resistance, lower expression of cyclin D1, survivin and increase PARP cleavage. In addition, ABT-869 overcame the radio-resistance of the cell lines and significantly enhanced radiation-induced cytotoxicity (p &lt; 0.05).
Conclusions: These data suggest the possibility of combining targeted therapeutic such as ABT-869 with radiation to enhance inhibition of cell growth and apoptosis in HNSCC cells. Thus, it may provide a novel therapeutic strategy and improve efficacy of radiation against HNSCC in the future.
Citation Format: Heng-Wei Hsu. ABT-869 enhances radiosensitivity of head and neck squamous cell carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1604. doi:10.1158/1538-7445.AM2013-1604
Abstract 1623: PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells.
Authors: Xue Yuan , Lim Sharon , Yang Yunlong , Wang Zongwei , Jensen Lasse Dahl Ejby , Hedlund Eva–Maria , Andersson Patrik , Sasahara Masakiyo , Larsson Ola , Galter Dagmar , Cao Renhai , Hosaka Kayoko , Cao Yihai 
Published: August 2014

Abstract
PDGF signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-β+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO-specific antibody attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-β signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis.
Citation Format: Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva–Maria Hedlund, Patrik Andersson, Masakiyo Sasahara, Ola Larsson, Dagmar Galter, Renhai Cao, Kayoko Hosaka, Yihai Cao. PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1623. doi:10.1158/1538-7445.AM2013-1623