bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2259: Blockade of CXC chemokines/CXCR2 axis inhibits pancreatic ductal adenocarcinoma progression through anti-angiogenesis
Authors: Ijichi Hideaki , Tada Motohisa , Miyabayashi Koji , Imai Mitsuho , Mohri Dai , Asaoka Yoshinari , Ikenoue Tsuneo , Tateishi Keisuke , Omata Masao , Moses Harold L. 
Published: February 2011

Abstract
Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal neoplasms, is characterized histologically by expanded stromal components with marked fibrosis, which suggests that tumor-stromal interaction might play an important role in PDAC progression.
We have established pancreas epithelium-specific transforming growth factor-ß receptor type II (Tgfbr2) knockout mice in the context of active Kras (KrasG12D) expression (Kras+Tgfbr2KO) (Ijichi et al., Genes Dev. 2006), which developed differentiated PDAC with 100% penetrance and recapitulated histology of human PDAC described above.
In the AACR annual meeting 2009, we reported that tumor-stromal interaction in the PDAC model promoted tumor progression and blockade of CXC chemokines/CXCR2 axis inhibited tumor growth and extended survival of the mice.
We examined the underlying mechanisms of anti-tumor effects. Treating the Kras+Tgfbr2KO PDAC mice with the CXCR2 inhibitor decreased CTGF expression and macrophage infiltration in vivo, resulting in decrease of microvessel density and inhibiton of tumor size. The CXC chemokines released from the PDAC cells, CTGF, macrophage, are all considered to promote angiogesis. Taken together, treatment of the mice with the CXCR2 inhibitor achieved anti-tumor effects through anti-angiogenesis via modulating network of an array of components in the tumor microenvironment. On the other hand, treating the mice with gemcitabine, a standard chemoreagent for PDAC, also showed anti-tumor effects, but it was not through anti-angiogenesis.
PDAC is well known as a hypovascular tumor, however, angiogenesis might be important for tumor progression and could be a potent therapeutic target. Pursuing optimum combination of anti-angiogenesis and a conventional chemotherapy would provide us a more effective therapeutic strategy for PDAC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2259.
Abstract 2261: Antitumor and anti-inflammatory effect of a novel nutrient mixture on human lymphoma cell line U-937
Authors: Roomi M. Waheed , Roomi Nusrath M. , Rath Matthias , Niedzwiecki Aleksandra 
Published: February 2011

Abstract
Introduction: Phytochemicals and dietary antioxidants are known to decrease the risk of inflammation and prevent cancer development. We have developed strategies to inhibit cancer progression and its spread by natural products. A nutrient mixture (NM) containing ascorbic acid, lysine, proline and green tea extract has exhibited anticancer activity in vitro and in vivo in a number of cancer cell lines.
Objective: We investigated the effect of NM on human lymphoma cell line U-937 in vitro by measuring: cell proliferation, MMP expression, invasion, apoptosis, and Cox-2 and Cox-1 protein expression.
Materials and Methods: Human lymphoma cell line U-937 (ATCC) was cultured in RPMI medium supplemented with fetal bovine serum and antibiotics. U-937 cells were seeded on 24-well tissue culture plates with 40nM phorbol 12-myristate 13-acetate (PMA). After 24 hrs, the cells were treated with NM at 0, 50, 100, 250, 500 and 1000 mcg/ml, in triplicate at each dose. Cell proliferation was evaluated by MTT assay, MMP expression by gelatinase zymography, invasion through Matrigel, apoptosis by using live green caspase detection kit (Molecular Probe), and COX-2 and COX-1 expression by Western blot.
Results: NM was not toxic to U-937 cells at a concentration of 250 mcg/ml and exhibited an antiproliferative effect at 500 mcg/ml concentration. Zymography demonstrated only one band corresponding to MMP-9, which was inhibited by NM in a dose-dependent manner. Matrigel invasion was significantly reduced (by 95%) at 250 mcg/ml NM and completely blocked at 500 mcg/ml NM. NM induced slight apoptosis at 100 mcg/ml and moderate at 500 and 1000 mcg/ml concentration. NM inhibited Cox-2 expression in a dose-dependent fashion and had no effect on Cox-1 expression.
Conclusions: Our results suggest that NM is an excellent candidate for therapeutic use in the treatment of hematological malignancies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2261.
Abstract 2265: Expression of hyaluronan in human cancer tissue: A predictive biomarker for PEGPH20-mediated therapy
Authors: Jiang Ping , Kadhim Salam , Li Xaioming , Thompson Curtis , McMannus Craig , Osgood Ryan , Anderson Jennifer , Symons Rebecca , Fieser Gail , Bahn Jesse , Tammi Raija , Shepard Michael , Frost Gregory 
Published: February 2011

Abstract
Background: Hyaluronan (HA), a ubiquitous, high-molecular-mass polysaccharide in the precellular and extracellular matrix, is frequently elevated in malignancy, and associated with aggressive disease. Interaction of HA and tumor cells may activate receptor tyrosine kinases, enhance drug resistance, and facilitate tumor progression. A pegylated recombinant human PH20 hyaluronidase (PEGPH20) has been developed to systemically target tumors that accumulated with HA. Systemic PEGPH20 administration in mice bearing PC3 tumors induced a decrease in tumor interstitial fluid pressure (IFP), a decrease in tumor water content, and an increase in tumor vascular volume by enzymatically depleting the HA from the extracellular tumor microenvironment and resulted in significant tumor growth inhibition. PEGPH20 therefore represents an innovative potential treatment approach that may provide improved therapeutic outcomes for cancer patients.
Methods: The present study investigated the expression of HA in paraffin embedded human tissue from 9 tumor types as well as corresponding normal tissue by immunohistochemical staining of BioMax tissue arrays with biotinylated HA binding protein (HABP) as a probe. Staining intensity was quantified using Aperio Spectrum plus software. The correlation between HA expression and PEGPH20 response has also been explored using established preclinical models.
Results: Strong HA expression was found in 87% of pancreatic, 64% of breast, 50% of multiple myeloma, 46% of NSCLC, 39% of gastric, and 22% of prostate cancer tissues, when compared with corresponding normal tissue (p&lt;0.05). BxPc3 (HA high), MIA PaCa-2 (HA low) and AsPC-1 (HAlow) pancreatic tumor xenografts were evaluated for tumor growth inhibition (TGI) after systemic PEGPH20 treatment and TGI's of 25%, 9% and 15% were observed respectively. In addition, 3 prostate cancers, PC3 (HA high), MatLylu (HA high) and Du145 (HA low) were also evaluated in xenografts with significant growth inhibition shown for PC3 (72%) and MatLylu (34%). Systemic PEGPH20 treatment also induced tumor growth inhibition (60%) for 4T1 (HA high) breast cancer.
Conclusion: Accumulation of HA compared to normal tissue was commonly observed and most frequent in pancreatic adenocarcinomas (87%). Furthermore, accumulation of HA was shown to predict response to PEGPH20 therapy in xenograft models (R2=0.805, p&lt;0.01). This work provides strong rationale for exploring efficacy of PEGPH20 in clinical trials.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2265.
Abstract 2269: M402 - A novel heparan sulfate proteoglycan mimetic targeting tumor-host interactions
Authors: Zhou He , Roy Sucharita , Cochran Edward , Zouaoui Radouane , Karlgren Juliane , Dussault Nancy , Kwan Rain YQ , Duffner Jay , Zhao Ganlin , Smith Sean , Galcheva-Gargova Zoya , Moy Erick , Barnes Marishka , Honan Chris , Chu Chia Lin , Qi Yi Wei , Ganguly Tanmoy , Schultes Birgit , Venkataraman Ganesh , Kishimoto Takashi Kei 
Published: February 2011

Abstract
Heparan sulfate proteoglycans (HSPGs) play important roles in tumorigenesis by mediating tumor-stromal interactions through the presentation of growth factors, cytokines, and chemokines critical for tumor progression, survival and metastasis. M402 is a rationally engineered, non-cytotoxic HSPG mimetic, designed to disrupt tumor-host interactions. M402 binds and inhibits multiple factors including VEGF, FGF2, SDF-1α, and P-selectin. A single 20 mg/kg subcutaneous (s.c.) dose of M402 effectively reduced seeding of B16F10 murine melanoma cells to the lung in a syngeneic experimental metastasis model. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis of orthotopically implanted 4T1 murine mammary carcinoma in this model. M402 treatment also normalized circulating levels of GR1+ immature myeloid cells and platelet counts in 4T1 metastatic tumor bearing mice. Fluorescently-labeled M402 exhibited selective accumulation in the primary tumor. Immunohistological analyses of primary tumor presented a decrease in microvessel density in M402-treated animals, suggesting anti-angiogenesis may be one of the mechanisms involved in vivo. Importantly, M402, as monotherapy or in combination with chemotherapeutics, also revealed significant survival benefits in this aggressive tumor model. These data demonstrate that targeting HSPG biology may provide a useful approach to attenuate multiple pathways involved in tumor progression and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2269.
Abstract 227: Antitumor activity of glyceollins through induction of apoptosis
Authors: Kim Hyo Jung , Seo Jiyeon , Lim Ji Sun , Park Jia , Nam Dae Hwan , Garcia Annalene , Kim Jong-Sang 
Published: February 2011

Abstract
Glyceollins, which are synthesized from daidzein in soybean infected with fungi, have been shown to have anti-fungal effects and cancer preventive properties. However, the effects of glyceollins on apoptosis of cancer cell are not well known. We have investigated the antitumor effects of glyceollins on murine hepatoma cell lines. Cell viability was tested with a MTT assay. In Hepa1C1C7, glyceollins markedly reduced cell viability which was due to apoptosis. Glyceollins were observed to induce apoptosis of Hepa1C1C7 cells as evidenced by cell-morphological changes, an early redistribution of plasma membrane phosphatidylserine, increases in membrane leakage (propidium iodide) staining), Annexin-V binding, sub G1 phase in the cell cycle, and DNA laddering. Western blot analysis showed that upon treatment of tumor cells with the glyceollins, cleavage of pro-caspases-3 and significant release of mitochondrial cytochrome c into the cytosol were readily observed. This study demonstrated that glyceollins caused cell death via an apoptotic pathway, which might be exploited for prevention of tumor development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 227.
Abstract 2270: Design, synthesis, and functional characterization of new cycle-peptides inhibitors for C-X-C chemokine receptor-4 (CXCR4)
Authors: Scala Stefania , Portella Luigi , Napolitano Maria , Consales Claudia , Polimeno Maria Neve , D'Alterio Crescenzo , Palma Giuseppe , Arra Claudio , Vitale Rosamaria , Amodeo Pietro , Luca Stefania De , Monfrecola Luca , Castello Giuseppe 
Published: February 2011

Abstract
Modulation of the axis CXCR4/CXCL12 affected primary tumor growth and secondary lesions development. Moreover, CXCR4 inhibition increases hematopoietic stem cell mobility in patients undergoing autologous transplantation for myeloma and non-Hodgkin lymphoma. Although several CXCR4 inhibitors were described neither one reached satisfactory efficacy, bioavailability and acceptable toxicity. To develop new CXCR4 inhibitors through a rationale design approach, comparative studies were undertaken evaluating the N-terminal structure of the ligand CXCL12 and v-MIP II, an inhibitory chemokine like produced by the herpes virus 8-Kaposi associated. A common amino acidic motif (RFF) was identified in both structures although in inverted orientation. Having as a core this small domain, a new library (20 units) of cycle-peptide molecules was generated. 20 units of cycle-peptide molecules were synthesized that consists of 5 and 7 amino-acid residues cycled by a S-S bridge designed to interact with the receptor CXCR4. The peptides were characterized for functionally CXCR4 interaction through: 1. inhibition of CXCR4 binding; 2. inhibition of migration CXCL12-induced; 3. inhibition of calcium release CXCL12-induced; 4. Inhibition of P-Erk CXCL12-induced. Four peptides were identified as CXCR4 inhibitors. These four CXCR4 inhibitory peptides were further evaluated for the in vivo efficacy through inhibition of metastasis formation. B16 mouse melanoma cells transfected with CXCR4 were injected in the vein tail in C57 Bl mice and peptide treatment followed for 10 days. Dramatic reduction in number and size of lung metastases were registered in mice peptides-treated. Moreover, xenograft of human renal cancer cells SN12C-EGFP were subcutaneously injected and systemic peptides treatment followed for 10 days. Statistically significant decrease in tumor growth was showed in peptides treated mice. Taken together the data define four new CXCR4 inhibitory peptides, designed through innovative strategy, effective in “in vivo” systems deserving further development.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2270.
Abstract 2277: Anti-tumor effect of an apoptosis-targeting peptide-conjugated heparin derivative in breast cancer xenografts
Authors: Bae Sang Mun 
Published: February 2011

Abstract
Anti-tumor effect of an apoptosis-targeting peptide-conjugated heparin derivative in breast cancer xenografts.
Sang Mun Bae1, Jong-Ho Kim1, Kai Wang1, Sungwoo Chung2, Youngro Byun2, Byung-Heon Lee1, In-San Kim1 and Rang-Woon Park1
1Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea
2College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea
Abstract
Angiogenesis, the development of new blood vessels, is an essential process during tumor growth and metastasis. In the process of tumor angiogenesis, tumor cells secret various angiogenic growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor basic (bFGF), platelet-derived endothelial cell growth factor (PDGF), insulin-like growth factors (IGF-1 and IGF-2) and scatter factors, which are potential targets for development of angiogenesis inhibitor and depend on heparin sulfate for their biological functions. Angiogenic endothelial cells are a central challenge for therapeutic intervention since its easy accessibility. Recently, researchers have sought to develop angiogenesis inhibitor for tumor therapy since tumor cannot grow without blood-supplied oxygen and nutrients. Heparan sulfate is located in cell surface and in the extracellular matrix and plays pivotal regulatory roles in growth factor. For this reason, heparin has been highlighted as a growth factor inhibitory therapeutic agent beyond its anticoagulant indications. In a previous study, we reported new angiogenesis inhibitor, low molecular weight heparin derivative (heparin-taurocholic acid conjugate; HT), showed delay of in vivo tumor growth in MDA-MB231 human breast cancer. In this study, we sought to design a new angiogenesis inhibitor targeting tumor tissue by introducing the actively targeting moiety, tumor homing peptide, to previously developed HT. Here, we evaluate the inhibitory effect of HT-Apopep by in vivo antitumor efficacy and show the body distribution image of HT-Apopep in tumor-bearing mice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2277.
Abstract 2284: Dissecting signaling networks involved in the tumor-microenvironment crosstalk in chronic lymphocytic leukemia (CLL)
Authors: Bhattacharya Nupur , Caudron-Herger Maiwen , Busch Hauke , Rippe Karsten , Doehner Hartmut , Stilgenbauer Stephan , Mertens Daniel 
Published: February 2011

Abstract
Crosstalk between tumor cells and the microenvironment is often a prerequisite for carcinogenesis. CLL, the most common leukemia in the western world, is an excellent model system to investigate this microenvironmental crosstalk. The dependence of the CLL cells for pro-survival support from the microenvironment is apparent from the induction of rapid spontaneous apoptosis in CLL cells in vitro unless they are cultured on feeder cells or treated with microenvironmental cytokines. CLL cells are also capable of inducing other non-malignant microenvironmental cells to form a pro-survival niche.
We have used a tripartite strategy to characterize the interaction between CLL cells and their microenvironment. Firstly, we have quantified the interaction of pro-survival ligand-receptor pairs and their dose-response curves in primary CLL cells and non-malignant B cells. Of the ligand-receptor pairs tested, IL4 and CD40L were found to rescue primary CLL cells most effectively from apoptosis. The effector dependence of IL4 and CD40L displayed different saturation curves in CLL versus non-malignant B cells, pointing towards distinct differences in ligand-receptor interactions. Secondly, we have used a systems biology approach to identify central nodes in the survival network induced by the microenvironment. The model is generated from the kinetics of the transcriptome acquired from gene expression profiling CLL cells after microenvironmental stimulation. Via a procedure that involves gene-ranking, significance filtering and kinetic classification, deregulated genes have been identified. Model construction using these genes will yield central nodes which will be functionally validated on a cohort of patients. As a third approach, the pro-survival niche inducing property of CLL cells on other microenvironmental cells is studied by gene expression profiling differentiated monocytes, which arise when monocytes are cocultured with CLL cells (which support CLL survival) versus the differentiated monocytes which arise when cultured with non-malignant B cells. Analysis of the gene expression profiles revealed genes specifically deregulated due to the effect of CLL cells.
This study will give us a deep insight into the signaling networks operating between the tumor and its microenvironment. This is certainly important for the identification of drug targets which can abrogate this interaction and thereby reduce the viability of the CLL cells in vivo.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2284.
Abstract 2287: Tumors induce complex DNA damage in distant proliferative tissues in vivo
Authors: Redon Christophe E. , Dickey Jennifer S. , Nakamura Asako J. , Kareva Irina G. , Naf Dieter , Nowsheen Somaira , Kalogerinis Peter K. , Bonner William M. , Georgakilas Alexandros G. , Sedelnikova Olga A. 
Published: February 2011

Abstract
The influence of a tumor on its surrounding tissues has been extensively investigated, but whether a tumor can influence distant tissues in an organism is unknown. This question is important in understanding the relationship between cancer and overall patient health. To explore this issue we chose to investigate the DNA damage endpoint, prompted by its utility in defining the “bystander effect” which denotes the phenomenon that cells exposed to ionizing radiation (or other stresses) communicate with their neighbors resulting in the appearance of DNA damage in unstressed cells. We measured DNA damage in tissues proximal and distal to the tumor site in C57BL/6 and BALB/c mice with early-stage subcutaneous syngeneic grafts, namely, B16 melanoma, MO5076 sarcoma, and COLON26 carcinoma. When the tumors approached 100 mg, the animals were sacrificed and various organs examined. Samples of duodenum, colon, rectum, stomach, liver, kidney, lung, ovary, skin, splenic and blood lymphocytes were taken for analysis. We report that levels of two types of DNA damage, double-strand breaks (DSBs) measured by γ-H2AX focus formation and oxidatively-induced non-DSB clustered DNA lesions (OCDLs), were elevated in tissues distant from the tumor site in the tumor-bearing mice compared to their age- and sex-matched controls. The most affected tissues were crypts in the gastrointestinal tract organs and the skin, particularly the hair follicles. These tissues have high rates of proliferation, indicating that S-phase cells were the most vulnerable to influence from the distant tumor. This study is the first direct demonstration of the tumor-induced bystander effect in vivo, i.e. that the presence of a tumor impacts distant tissues, and suggests that tumors may constitutively promote complex oxidative DNA damage in highly proliferating tissues throughout an organism. These findings may have important implications for the study of genomic instability resulting from a primary tumor as well as for understanding second cancers which are a growing concern as long-term survival after a first cancer increases. This study also suggests a role for DNA damage markers as general cancer-related stress biomarkers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2287.