bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1532: Small-molecule Stat3 inhibitor sensitizes Cisplatin-resistant ovarian cancer cells to Cisplatin-induced apoptosis
Authors: Sengupta Bhaswati , Startzman A , Turkson J 
Published: June 2012

Abstract
Ovarian Cancer causes the highest number of gynecologic neoplasm related deaths in the United States. The disease and its progression to drug resistance remain poorly understood. While the aberrant activation of the Signal Transducer and Activator of Transcription (Stat) 3 protein is prevalent in ovarian cancer and is detected in chemotherapy resistance, its exact role in the development and maintenance of the drug resistance phenotype remains poorly understood. We sought to investigate the molecular mechanisms by which constitutive Stat3 activity may support Cisplatin resistance in ovarian cancer. Compared to the sensitive A2780S ovarian cancer line, which does not harbor aberrant Stat3 activity, the SKOV3 line harboring constitutively-active Stat3 was partially sensitive to Cisplatin and showed evidence of moderate apoptosis in response to Cisplatin treatment. Compared to the sensitive A2780S cells, the partly-resistant, SKOV3 cells over-express c-Myc, Survivin, and Bcl-xL, and the XIAP anti-apoptotic factor, as well as VEGF pro-angiogenic factor and the matrix metalloproteinases, MMP-2 and MMP-9. The inhibition of constitutively-active Stat3 in SKOV3 cells by the small-molecule inhibitor, S3I-201 suppressed the expression of the anti-apoptotic and the pro-angiogenic factors, and induced moderate degree of apoptosis. Significantly, treatment with S3I-201 enhanced the sensitivity of SKOV3 cells to Cisplatin. Furthermore, the combined treatment of SKOV3 cells with Cisplatin and S3I-201 strongly inhibited colony formation and cell migration in vitro. Our study together identifies potential mechanisms by which aberrant Stat3 activity might support Cisplatin resistance in ovarian cancer, raising the potential that the combination therapy with Stat3 inhibitors would be effective therapeutic and chemo-sensitizing modalities for ovarian cancer and the recurrent disease.
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 1532. doi:10.1158/1538-7445.AM2011-1532
Abstract 1538: Inhibition of adenosine-mediated stabilization of intercellular adhesions promotes hypoxia-stressed endometrial carcinoma cell metastasis
Authors: Bowser Jessica L. , Blackburn Michael R. , Shipley Gregory L. , Xie Susu , Broaddus Russell R. 
Published: June 2012

Abstract
Hypoxic microenvironments are commonly encountered in multiple epithelial malignancies. Epithelial cells classically up-regulate cellular adhesive mechanisms to counter the noxious effects of hypoxia. Inhibiting these tissue protective mechanisms is necessary for carcinoma cell invasion and metastasis. Our previous studies utilizing a transgenic model deficient for 5’nucleotidase (CD73), an enzyme responsible for adenosine biosynthesis, demonstrated that adenosine is required to circumvent hypoxia-mediated disruption of cellular adhesiveness in the normal endometrium. In endometrial carcinoma (EC), CD73 is down-regulated in poorly-differentiated, invasive, and metastatic ECs, but is expressed and functional in well-differentiated and non-metastatic disease. Based on these findings, we hypothesized that the malignant progression of EC is dependant on the loss of adenosine-mediated regulation of intercellular adhesions. Modified and unmodified Boyden chambers were used to assess migration and invasion of endometrial adenocarcinoma cells HEC-1A and HEC-1B. Hypoxia (5% or 1.5% O2) significantly reduced HEC-1A and HEC-1B migration and invasion in vitro; this effect was abrogated by CD73 RNA interference and the CD73 enzymatic inhibitor, α, β- methylenediphosphate (AoPCP). The inhibitory effect of CD73 on EC cell migration and invasion was restored by the stable, receptor-targeting adenosine analog, 5’-N-ethylcarboxamido adenosine (NECA). Quantitative RT-PCR identified two adenosine receptors, A1R and A2BR, to be expressed in HEC-1A and HEC-1B. Inhibition of the A2BR by MRS1754 significantly increased HEC-1B migration and invasion, while A1R antagonism (DPCPX) had no effect. A2BR inhibition in HEC-1A monolayers also resulted in increased paracellular permeability to FITC-labeled dextrans. Moreover, A2BR antagonism lowered cellular levels of junctional adhesion proteins claudin-1 and claudin-2, and resulted in increased accumulation of β-catenin within the cytoplasm. Intracellular pools of β-catenin re-organized to the cell membrane with NECA application. In summary, we have shown that CD73-generated adenosine is necessary to maintain normal protective epithelial barrier function in the uterus. Our results demonstrate for the first time that inhibition of adenosine-mediated stabilization of intercellular adhesions promotes cancer cell invasion and metastasis in a hypoxic microenvironment. (NIH TL1RR024147 and NIH 1P50CA098258-01)
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 1538. doi:10.1158/1538-7445.AM2011-1538
Abstract 1539: Impact of glioma cell gene expression due to semaphorin expression
Authors: Bode Julia , Kietz Silke , Lakomek Max 
Published: June 2012

Abstract
Malignant brain tumours, like the Glioblastoma multiforme, belong to the most frequent tumours encountered in childhood. Unfortunately, even with optimal therapy, consisting of surgical resection and radiotherapy, a glioblastoma multiforme is essentially incurable.
In contrast to the excellent results of well established treatment studies in pediatric patients suffering from leukaemia the cure rates of children with malignant brain tumors remained low. That is why the development of new antitumor strategies has become a major issue in experimental neurology.
Class-3 semaphorins were first identified as glycoproteins that negatively mediate neuronal guidance by binding to neuropilin. The discovery of more widespread expression of class-3 semaphorins in different tumour cell types implicates a role in tumour biology.
The overexpression of class-3 semaphorins in breast cancer cells leads to inhibition of tumour growth. We overexpressed class-3 semaphorins in the human glioma cell line U87MG and monitored a reduction of tumour growth after intracerebral implantation into mice, too. We were also able to detect changes in adhesion and migration. To determine the variation of tumour cell behaviour we analysed the gene expression profile of class-3 overexpressing cells via microarray analysis. We validated changes in transcription levels with the help of realtime-PCR. Changes in the gene expression levels of cell adhesion molecule 2 and Integrin alpha 7 confirmed the changes in adhesion and migration of class-3 semaphorin expressing glioma cells. Further investigations of changes in gene expression levels of different genes are needed to determine the effect of semaphorins on adhesion and migration and the determine the use of class-3 semaphorins as anti-tumour agent.
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 1539. doi:10.1158/1538-7445.AM2011-1539
Abstract 1544: Identification of microRNA which regulates peritoneal dissemination of ovarian cancer
Authors: Ohyagi Chifumi , Sawada Kenjiro , Morishige Ken-ichiro , Lengyel Ernst , Kimura Tadashi 
Published: June 2012

Abstract
Ovarian cancer is highly metastatic and characterized by widespred peritoneal dissemination and massive ascites, and is the leading cause of death from gynecological malignancies. We have previously identified integrin α5 as a promising target for ovarian cancer treatment by inhibiting peritoneal dissemination. Our aim is to newly identify microRNAs which regulate integrin α5 expression and analyze the therapeutic potential of targeting those microRNAs.
Based on the microRNA algorism search, we identified hsa-mira-92a as one of the candidates. Hsa-mir-92a is little expressed in ovarian cancer cells which express high level of integrin α5, whereas hsa-mir-92a is highly expressed in RMUG-S cells which hardly express integrin α5. Forced expression of mir-92a in ovarian cancer cell lines reduced integrin α5 expression in mRNA and protein level, accompanied by the inhibition of cell adhesion and invasion. On the contrary, the antagonist of mir-92a enhanced integrin α5 expression in RMUG-S cells. Luciferase assay revealed that mir-92a reduces the transcriptional activity of integrin α5 by directly binding ITGA5 3′-UTR. In vivo ovarian cancer xenografts, transducing hsa-mir-92a expressing plasmid into ovarian cancer cell lines significantly reduced peritoneal dissemination and ascites formation.
Those results suggested targeting hsa-mir-92a could be a promising therapy for a subset of ovarian cancer patients by inhibiting integirn α5 expression.
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 1544. doi:10.1158/1538-7445.AM2011-1544
Abstract 1547: Characterization of receptor-ligand interactions between head and neck circulating tumor cells and E-selectin
Authors: Marshall Jocelyn R. , Reynolds Nathan M. , Abram Courtney E. , Henson Karissa A. , Wood S. Matthew , Nimrichter Leonardo , Burdick Monica M. 
Published: June 2012

Abstract
Though the exact mechanisms of cancer metastasis are not known, it is widely believed that circulating tumor cells (CTCs) that have broken off from the primary tumor flow through the blood stream until ligands on their surface recognize receptors present on the vascular endothelium. From there, CTCs loosely attach to the endothelium surface and roll until they become firmly adherent. Cells then migrate through the blood vessel walls to establish metastatic colonies in a distant organ. Therefore, identifying the molecular structures available for adhesion on the surface of the CTCs is compulsory to fully understanding the ubiquitous and unique natures of cancer metastasis. We have previously shown that the adhesion of head and neck squamous cell carcinomas (HNSCCs) to human umbilical vascular endothelium cells (HUVECs) under flow is mediated by E-selectin present on the endothelium surface. In this study, we investigated the interaction of E-selectin with ligands present on the HNSCC surface. Protease-treated cells of the JHU-011-SCC, JHU-013-SCC, and FaDu cell lines perfused through the parallel-plate flow chamber tethered to and rolled on the HUVECs at a greater incidence rate compared to untreated control cells. These binding interactions were sialidase and fucosidase sensitive. Altogether, these results indicate that sialofucosylated glycolipids on HNSCC cells predominantly contribute to the adhesion of these cells to endothelium. This observation was further confirmed by probing western blots of SDS-PAGE resolved HNSCC lysates with HECA-452 mAb and E-selectin chimera. Neither probe was reactive with protein species. We also tested if a shielding effect of hyaluronic acid (HA) prevented glycosphingolipid engagement to E-selectin. When HNSCC cells were treated with HAse and when hyaluronic acid synthase-3 was silenced by shRNA, there was an increase in cell adhesion events. These results clearly demonstrate that proteins and HA exert shielding effects on the E-selectin glycolipid ligands, thus affecting the overall metastatic ability of the HNSCCs.
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 1547. doi:10.1158/1538-7445.AM2011-1547
Abstract 1548: The effects of synthetic triterpenoids on GSK3β and focal adhesions
Authors: To Ciric , Di Guglielmo John M. 
Published: June 2012

Abstract
Synthetic triterpenoids are a class of anti-cancer compounds that are efficacious in targeting multiple cellular functions including apoptosis, growth inhibition, anti-inflammation and cytoprotection in both cell culture and animal tumor models. However, its effects on cell migration, a precursor event to cancer metastasis, remain poorly understood. Previously, we have shown that the methyl ester derivative of 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) inhibits cell migration. The objective of our current study is to examine in further detail the mechanism by which CDDO-Me blocks cell migration. Using various proteomic approaches as well as affinity pull down assays, Glycogen Synthase Kinase 3 Beta (GSK3β) was identified and confirmed as a triterpenoid-binding protein. Since GSK3β has been shown to be an important regulator of cell adhesion, a process that is intricately connected to cell migration, we hypothesize that CDDO-Me may target GSK3β and affect cell adhesion dynamics to inhibit cell migration. Indeed, we have observed that triterpenoid treated cells have decreased GSK3β activity. We also observed that the size and shape of focal adhesions were altered in the presence of synthetic triterpenoids. The molecular link between synthetic triterpenoids, GSK3β and focal adhesions are currently being investigated to better describe how this promising anti-cancer compound may act via GSK3β to affect focal adhesions and cell migration.
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 1548. doi:10.1158/1538-7445.AM2011-1548
Abstract 1549: Regulation of inflammation and tumor growth by the novel XL313 cryptic ECM element
Authors: Ames Jacquelyn J. , Nugent Desiree P. , Contois Liangru , Caron Jennifer M. , Brooks Peter C. 
Published: June 2012

Abstract
Experimental evidence suggests that multiple cell types within the tumor microenvironment such as fibroblast, endothelial cells and inflammatory cells contribute to tumor growth. Recent evidence indicates that biomechanical alterations in the structural integrity of ECM proteins may result in exposure of cryptic regulatory elements that play roles in differentially controlling cell signaling pathways. Therefore, exposure of cryptic regulatory sites may function as biomechanical switches, allowing various cell populations to respond in distinct ways to localized structural alterations within the tumor microenvironment. Thus, identifying and characterizing biomechanical ECM switches may provide selective new therapeutic targets to regulate tumor progression. In this regard, triple helical collagen has numerous RGD containing cryptic integrin binding sites. However, it is not known whether all these cryptic RGD elements are functionally redundant or whether distinct flanking sequences may convey differential control of cellular behavior.
To examine potential functional differences between distinct RGD containing cryptic sites, we generated a series of Mabs directed to synthetic RGD containing peptides found within type-I collagen. One Mab termed XL313 selectively recognized a cryptic element containing the amino acid sequence RGDKGE, but failed to bind other RGD containing sites. Mab XL313 failed to recognize intact triple helical collagen, but did bind proteolytically cleaved collagen. Importantly, Mab XL313 significantly (P&lt;0.05) inhibited B16F10 melanoma tumor growth by greater than 50%. Given the possibility that inflammation may contribute to tumor development, we examined the impact of the XL313 epitope on growth factor induced inflammation. Our studies suggest that the XL313 cryptic site may regulate inflammation as Mab XL313 significantly (P&lt;0.05) inhibited inflammation / CAM thickening in the chick embryo model. Collectively, our studies suggest that the XL313 biomechanical ECM switch may represent an important new therapeutic target for the control of tumor growth and inflammation.
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 1549. doi:10.1158/1538-7445.AM2011-1549
Abstract 1555: Immune suppression of regulatory T cells and M2 macrophage in breast cancer patients
Authors: Imoto Shigeru , Sakemura Noriko , Ito Hiroki , Imi Kentaro , Isaka Hirotsugu , Tazaki Eri , Kanma Hiroshi , Wada Noriaki , Nakatsura Tetsuya 
Published: June 2012

Abstract
Background: Recent multi-disciplinary treatments of breast cancer (BC) could decrease the mortality rate, but successful immune therapy remains uncertain. To explore new strategy of immune therapy of BC, we are investigating about host-tumor immune response in BC patients. Materials and methods: Tumor tissue specimens and peripheral blood mononuclear cells (PBMC) were obtained from early and advanced BC patients. PBMC were also collected from healthy volunteers. Regulatory T (Treg) cells were examined by counting CD4+CD25highCD127low/-cells in PBMC with flow cytometry analysis. Immunohistochemical evaluation of tumor specimens was performed with monoclonal antibodies of HLA-ABC and DR, CD56, CD68, CD83, and CD163. The number of stained cells was analyzed using a semiquantitative ordinal scale ranging from 0 to 3 (0, +/-, ++, +++). Results: HLA type I and type II were stained negative in 44% and 82% of 50 BC cases. When host-tumor immune response were compared between 38 early BC cases and 12 advanced BC cases, numbers of CD68-positive cells significantly increased in peripheral tumor tissues of advanced BC cases than in those of early BC cases (92% versus 53%). CD163-positive tumor cells were also detected more frequently in advanced BC cases than in early BC cases (75% versus 16%). There were no significant differences of distribution of CD4, CD8, CD56, and CD83-positive cells in early and advanced BC cases. Treg cells in PBMC significantly increased in percentage of the population in 46 BC patients than in 16 healthy volunteers (3.8% versus 2.1% of CD4-positive cells at mean value). Interestingly, Treg cells decreased in percentage of the population in postoperative BC patients. Conclusions: Our results suggest that Treg cells render BC patients under immune suppression and M2 macrophage plays an important role of tumor progression. Targeted therapy against M2 macrophage traits may be a promising strategy of breast cancer. Host-tumor immune response will be reported for BC patients treated with primary chemotherapy or radiofrequency ablation therapy in comparison with those who underwent breast surgery first.
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 1555. doi:10.1158/1538-7445.AM2011-1555
Abstract 156: MicroRNA expression profiling of human esophageal metaplastic changes
Authors: Fassan Matteo , Volinia Stefano , Palatini Jeff , Pizzi Marco , Fernandez-Cymering Cecilia , Battaglia Giorgio , Balistreri Mariangela , Croce Carlo M. , Zaninotto Giovanni , Ancona Ermanno , Rugge Massimo 
Published: June 2012

Abstract
For nearly the last two decades, the diagnosis of Barrett's mucosa (BM) strictly required histologically documented intestinal metaplasia (IM). More recently, a precancerous potential has been also associated to non-goblet columnar metaplasia (i.e. gastric metaplasia, [GM]). Molecular profiling can be applied to characterize the precancerous meaning of non-intestinal versus intestinal metaplastic transformation of the native squamous esophageal mucosa. MicroRNAs (miRNAs) are a class of small non-coding RNAs controlling gene expression and they are reportedly dysregulated in Barrett's carcinogenesis.
To investigate the role of miRNAs in the natural history of esophageal metaplasia, miRNA microarray analysis (OSU-CCC version 4.0; Ohio State University) was performed in a series of 30 matched biopsy samples (10 native squamous epithelium [N], 10 GM and 10 IM) from 10 long-segment BE-patients. Microarray findings were validated by qRT-PCR using another series of 20 consecutive BE-patients.
miRNA profiling consistently disclosed different metaplasia-specific miRNA signatures for N versus GM, and N versus IM. Comparing the two signatures disclosed that they had 11 significantly dysregulated miRNAs in common, 8 of which were proportionally dysregulated in the sequence N-GM-IM (2 overexpressed [hsa-miR-192 and hsa-miR-215] and 6 underexpressed [hsa-miR-18a*; hsa-miR-20a, hsa-miR-106a, hsa-miR-203, hsa-miR-205 and hsa-miR-769-5p]).
Specific miRNAs are involved in the natural history of BE. Molecular profiling of phenotypical lesions included in Barrett's carcinogenesis supports the hypothesis that squamous epithelium is converted initially into non-goblet columnar epithelium, before goblet cell metaplasia sets in.
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 156. doi:10.1158/1538-7445.AM2011-156
Abstract 1562: The G protein-coupled receptor mFPR2 promotes antitumor host defense
Authors: Liu Ying , Chen Keqiang , Yao Xiaohong , Gong Wanghua , Yoshimura Teizo , Ford Jill , McVicar Daniel , Wang Ji Ming 
Published: June 2012

Abstract
mFPR2 is a G protein-coupled receptor interacting with chemotactic agonists produced by bacteria and the host. In vivo, mFPR2 plays a major role in innate and adaptive immune responses as shown by reduced severity of allergic airway inflammation and diminished production of Th1 and Th2 cytokines in mFPR2-deficient mice. These defects were associated with impaired trafficking of antigen presenting dendritic cells into the inflammatory sites and the draining lymph nodes. The aim of this study is to examine the role of mFPR2 in tumor progression. We found that mFPR2-deficient mice bearing subcutaneously implanted Lewis Lung Cancer cells (LLC) exhibited significantly shortened survival rate due to more rapidly growing tumors. In contrast, in mFPR2-transgenic (Tg) mice, subcutaneously implanted LLC tumors grew more slowly than those in wild type (WT) littermates. We further observed a decrease in the proportion of CD11b+ and Gr1+ myeloid cells accompanied by reduced infiltration of CD11b+Gr1low myeloid-derived suppressor cells and CD4+Foxp3+ regulatory T cells in LLC tumors in mFPR2-Tg mice. These results suggest that mFPR2 may play an important role in anti-tumor host defense by down-regulating immune suppressive cell infiltration in tumor tissues.
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 1562. doi:10.1158/1538-7445.AM2011-1562