bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5286: Beta-arrestin2-CARMA3 signaling axis is required in lysophosphatidic acid-induced ovarian cancer migration and invasion
Authors: Sun Jiyuan , Cai Jingli , Feng Yumei , Guo Lei 
Published: February 2011

Abstract
Ovarian cancer is ranked as the 4th most common type of cancer among women in the United States. One of the biomarkers of ovarian cancer is lysophosphatidic acid (LPA). LPA is a type of G protein-coupled receptor ligand. It is strikingly elevated in 90% of ovarian cancer patients. Additionally, LPA receptors are aberrantly up-regulated in ovarian cancer patients. We have reported previously that a signaling axis consisting of beta-arrestin 2 and CARMA3 (CARD and MAGUK domain-containing protein 3) is indispensable in LPA-induced nuclear factor kappa B (NF-kappaB) activation in mouse embryonic fibroblast cells. NF-kappaB is an important transcription factor, which has been suggested to mediate LPA-induced ovarian cancer migration and invasion. However, it remains unknown whether the beta-arrestin2-CARMA3 signaling axis plays an important role in LPA-induced ovarian cancer cell migration and invasion. In the present study, using beta-arrestin 2 and CARMA3 shRNA, we knockdowned their protein expression levels in ovarian cancer cell lines. Consistent with previous reports, we found that down-regulation of beta-arrestin 2 and CARMA3 abolished LPA-induced IKK activity and NF-kappaB activation in ovarian cancer cells. In addition, in vitro transwell migration and matrigel invasion assays demonstrated that beta-arrestin 2 and CARMA3 shRNA significantly impaired LPA-induced ovarian cancer cell motility and invasiveness. Together, our results provide the evidence that beta-arrestin 2 and CARMA3 serve as critical regulators in LPA-induced, NF-kappaB-mediated ovarian cancer migration and invasion. Therefore, we speculate that beta-arrestin 2 and CARMA3 may represent attractive therapeutic targets for ovarian cancer and many other types of malignancies.
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 5286.
Abstract 5297: A novel role of cdc-family gene PFTK1 in the control of liver cancer cell motility
Authors: Leung Wilson K-C , Ching Arthur KK , Chan Anthony WH , Poon Terence CW , To Ka-Fai , Wong Alice ST , Wong Nathalie 
Published: February 2011

Abstract
Cancer metastasis remains a major cause of cancer morbidity and mortality in individuals diagnosed with hepatocellular carcinoma (HCC). We previously reported on regional chromosome 7q21-q22 gains in close association with HCC progression, and discerned a candidate proto-oncogene PFTK1 within this region by array-based CGH mapping. The PFTK1 protein, PFTAIRE protein kinase 1, is a novel member of the Cdc2-related serine/threonine protein kinases. Our earlier investigations by ectopic expression and gene knockdown of PFTK1 confirmed a functional role for the PFTAIRE protein kinase in the motile phenotype of HCC cells, yet the biological basis remained to be determined. The aims of this study are therefore to establish the clinicopathologic significance of PFTK1 in HCC, and to define the PFTK1-modulated mechanisms in the control of HCC cell motility. Recent Tissue Microarray Analysis (TMA) on 180 paired primary HCC and their adjacent non-tumoral liver suggested common up-regulated PFTK1 compared to non-malignant counterpart (76.1%; p&lt;0.0001). Correlative analysis further indicated PFTK1 over-expression in association with advanced tumor grading (P&lt;0.0001) and the presence of microvascular invasion (P=0.05). By 2D-PAGE coupled with mass spectrometry, comparative proteomic profiling for phosphorylated proteins in PFTK1-suppressed HCC cells highlighted 5 differentially down-regulated spots, which included β-actin (ACTB), transgelin2 (TAGLN2), heat shock protein 70, mitochondrial aldehyde dehydrogenase and 14-3-3 gamma protein. Western blot analysis further verified a consistent reduction on ACTB phosphorylation and the serine phosphorylation of the TAGLN2 protein in the absence of PFTK1 protein kinase. Immunofluorescence analysis for cytoskeletal organizations indicated marked reduction on the actin stress fibers in PFTK1 knockdown cells. In conclusion, our results suggested that PFTK1 can affect the actin cytoskeletal organization and thus a motile phenotype in HCC cells through phosphorylation of ACTB and TAGLN2
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 5297.
Abstract 5303: Systemic immunosuppression in glioblastoma: the interplay between lymphopenia, CD14+HLA-DRlo/neg monocytes, tumor factors, and dexamethasone
Authors: Gustafson Michael P. , Lin Yi , New Kent C. , Bulur Peggy A. , O'Neill Brian P. , Gastineau Dennis A. , Dietz Allan B. 
Published: February 2011

Abstract
Patients with glioblastoma (GBM) exhibit profound systemic immune defects that affect the success of traditional and immune-based treatments. A better understanding of the contribution of the tumor and therapy on systemic and local immune suppression is necessary to improve immune based therapies and monitor the effects of conventional and novel therapies. To identify possible sources of immunosuppression, we measured the constituents of circulating immunity in newly diagnosed and recurrent GBM patients with or without dexamethasone treatment. We identified dexamethasone dependent and independent changes in systemic immunity associated with GBM. Of note, we identified a profound lymphopenia associated with dexamethasone treatement that manifested itself in the T cell compartment with targeted effects on the CD4+ T cells. In addition, we identified tumor and dexamethasone dependent altered monocyte phenotypes. The major population of altered monocytes (CD14+HLA-DRlo/neg) inhibited T cell proliferation, was unable to fully differentiate into mature dendritic cells, was associated with dexamethasone-mediated changes in CCL2 levels, and could be re-created in vitro using tumor supernatants. Interestingly, CD14+HLA-DRlo/neg monocytes were elevated similarly in newly diagnosed and recurrent patients. These data demonstrate that both tumor and steroids contribute to systemic immunosuppression. We provide evidence that tumors express high levels of the monocyte recruitment chemokine CCL2, can contain high numbers of CD14+ cells, that tumor supernatants can transform CD14+HLA-DR+ cells into CD14+HLA-DRlo/neg immune suppressors, and that dexamethasone reduces CCL2 in vitro and is correlated with reduction of CCL2 in vivo. Consequently, we have developed a model for tumor mediated systemic immune suppression via recruitment and transformation of CD14+ cells.
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 5303.
Abstract 5306: A20 negatively regulates immunostimulatory activity of macrophage
Authors: Wang lifeng , Hong Bangxing , Jiang Xiaoxia , Jones Lindsey , Chen Siyi , Huang Xue F 
Published: February 2011

Abstract
Macrophage represents a class of professional antigen-presenting cells, but usually only exhibits low level immunostimulatory activity. Here we investigate the role of A20, a negative regulator of several key proinflammatory signaling pathways, in controlling macrophage-associated immunostimulatory ability. We find that A20-silenced macrophage has enhanced expressions of costimulatory molecules, MHC complexes, and proinflammatory cytokines. As a consequence, A20-silenced macrophage displays an elevated ability to activate CD4+ and CD8+ T cell response in vitro and in vivo, and A20-silenced macrophage immunization effectively controls onset and growth of engrafted tumors. To further search the underlying mechanism whereby A20-silenced macrophage triggers potent antitumor activity, we unexpectedly found that A20-silenced macrophage induced expression of cytotoxic molecules perforin and granzyme B not only in CD8+ T cell and NK cells, but also in CD4+ T cells, and all of these cytotoxic molecule-expressing cells display a heightened cytotoxicity against tumor cells. A20-silenced macrophage induces expression of the cytotoxic molecules likely by enhancing production and signaling of IFN-g, as depletion of IFN-g by anti-IFN antibody drastically reduced expression of these cytotoxic molecules. These results indicate that A20 negatively regulates macrophage to activate antitumor immune response, and implies silencing A20 expression would lead to generation of immunostimulatory macrophage.
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 5306.
Abstract 5312: Myeloid-derived suppressor cells express the death receptor Fas and apoptose in response to T cell-expressed FasL
Authors: Sinha Pratima , Chornoguz Olesya , Clements Virginia K. , Artemenko Konstantin , Zubarev Roman A. , Ostrand-Rosenberg Suzanne 
Published: February 2011

Abstract
Myeloid-derived suppressor cells (MDSC) accumulate to high levels in individuals with a variety of conditions including cancer, chronic inflammation, and stress, where they are potent inhibitors of adaptive and innate immunity. Some of the factors that induce their accumulation are known; however, physiological conditions that regulate their turn-over have not been identified. Mass spectrometry analysis revealed prominent expression of apoptosis pathway proteins by MDSC and led us to hypothesize that Fas/FasL-mediated apoptosis may be a key mechanism that regulates MDSC turn-over. This hypothesis was confirmed by the findings that MDSC levels significantly regress after removal of primary mammary tumors from STAT6-deficient or CD-1-deficient mice, but do not regress in mice doubly deficient for FasL and STAT6 or CD-1. Flow cytometry and confocal microscopy studies examining activated caspase 3 expression and cytochrome C localization revealed that MDSC apoptosis is triggered via the extrinsic, and not the intrinsic, pathway. Surprisingly, activated FasL+ T cells mediated MDSC apoptosis in vivo, demonstrating a retaliatory relationship between these two cell populations, and suggesting that Fas-FasL interactions could be exploited as a strategy to reduce in vivo levels of MDSC.
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 5312.
Abstract 5314: Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck
Authors: Chikamatsu Kazuaki , Takahashi Goro , Sakakura Koichi , Ferrone Soldano , Masuyama Keisuke 
Published: February 2011

Abstract
There is increasing evidence in certain malignancies that tumor cells are organized into a hierarchy originating from a small population of cancer stem cells (CSCs) that possesses extensive proliferative and self-renewal potential, and that these CSCs are responsible for maintaining the tumors. In squamous cell carcinoma of the head and neck (SCCHN), CD44+ cells with significant tumorigenic potential have been identified as CSCs; however, the immunological properties of such CSCs have not yet been elucidated. In this study, we investigated the immunological functions of CD44+ cells from a SCCHN cell line. Analysis of flow cytometry demonstrated that the expression of HLA-A2 molecules was deficient in the parental cell line, whereas the CD44+ cell population restored HLA-A2 expression, although at very low levels. Moreover, CD44+ cells exhibited weak HLA class II expression on the cell surface. Interestingly, down-regulation of TAP2 was found in CD44+ cells. The CD44+ cell population produced significantly higher levels of IL-8, G-CSF, and TGF-β than the CD44- cell population. Moreover, CD44+ cells have been shown to not only more strongly inhibit the proliferation of T cells activated with anti-CD3/CD28 mAb, but also to more efficiently induce CD4+CD25+FOXP3+ Treg cells and myeloid-derived suppressor cells as compared with CD44- cells. Additionally, CD44+ cells also suppressed Th1 responses (IFN-γ production by PBMCs) and enhanced regulatory T cell responses (IL-10 production by PBMCs). Thus, CSCs may have higher immunosuppressive ability promoting evasion from immunosurveillance; therefore, the development of novel immunotherapeutic strategies to efficiently overcome CSCs-driven immune suppression is urgently needed.
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 5314.
Abstract 5315: Human tumor antigen-specific helper and regulatory T cells share common epitope specificity but exhibit distinct T cell repertoire
Authors: Fourcade Julien , Sun Zhaojun , Kudela Pavol , Janjic Bratislav , Kirkwood John M. , El-Hafnawy Talal , Zarour Hassane 
Published: February 2011

Abstract
CD4+ regulatory T cells (Tregs) accumulate at tumor sites and play a critical role in the suppression of immune responses against tumor cells. Here, we show that two immunodominant epitopes derived from the tumor antigens (TA) NY-ESO-1 and TRAG-3 stimulate both CD4+ T-helper cells and Tregs. TA-specific Tregs inhibit the proliferation of allogenic T cells, act in a cell-to-cell contact dependent fashion and require antigen activation to suppress IL-2 secretion by T cells. TRAG-3 and NY-ESO-1-specific Tregs exhibit either a Th1-, a Th2- or a Th0-type cytokine profile and dot not produce IL-10 or TGF-β. The Foxp3 levels vary from one Treg clone to another and are significantly lower than those of CD4+CD25high Tregs. In contrast to NY-ESO-1-specific T helper cells, the NY-ESO-1-specific Treg clonotype shares a common TCR CDR3 Vβ usage with Foxp3+CD4+CD25high and CD4+CD25− T cells and was not detectable in PBLs of other NY-ESO-1+ melanoma patients and of healthy donors, suggesting that its recruitment occurs through the peripheral conversion of CD4+CD25− T cells upon chronic antigen exposure. Collectively, our findings demonstrate that the same epitopes spontaneously stimulate both T-helper cells and Tregs in patients with advanced melanoma. They also suggest that TA-specific Treg expansion may be better impaired by therapies aimed at depleting CD4+CD25high Tregs and preventing the peripheral conversion of CD4+CD25− T cells. This work was supported by NIH/NCI Grants CA90360 and CA112198 (HMZ) and Cancer Research Institute grant (HMZ).
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 5315.
Abstract 5348: Detection of herpes simplex viruses in thyroid cancer
Authors: Vasko Vasyl V. , Jensen Kirk , Patel Aneeta , Bauer Andrew 
Published: February 2011

Abstract
Introduction: There is limited information about the role of herpesviridae viruses in thyroid cancer.
Materials and Methods: Thyroid tissues from 109 patients with benign (44) and malignant (65) lesions were analyzed for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression and activation of viral-inducible signaling pathways. Expression of viral entry receptor Nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV.
Results: HSV was detected in 43/109 (39.4%) of examined samples. HSV positive tumors were characterized by interferon-beta expression, nuclear NFkB expression and Akt activation. Lymphocytes infiltration and oncocytic cellular features were common in HSV positive tumors. HSV1 was detected with same frequency in benign and malignant thyroid tumors. HSV2 was significantly associated with papillary thyroid cancer and presence of lymph nodes metastases. Nectin-1 expression was increased in thyroid tumors compared to normal thyroid tissue and further increased in papillary thyroid cancer. The level of Nectin-1 expression in cancer cell lines correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signaling did not affect the level of Nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. Thyroid cancer cell with epithelial-like morphology underwent epithelial to mesenchymal transition after chronic exposure to TNF. Induction of epithelial to mesenchymal transition was associated with increased thyroid cancer cell susceptibility to HSV.
Conclusion. HSV was detected in human thyroid tumors and HSV2 was associated with metastatic thyroid cancers. In vivo and vitro data showed that during tumor progression thyroid cells acquire increased susceptibility to HSV due to 1) increased expression of viral entry mediator Nectin-1; 2) activation of mitogenic signaling and 3) induction of EMT in metastatic cancers.
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 5348.
Abstract 5352: A high percentage of Merkel cell carcinomas is biologically associated with Merkel cell polyomavirus
Authors: Speel Ernst-Jan M. , Schmidt Andreia , Baumann M , Haesevoets Annick , Diebold J , Hofmann P , Kurrer Michael , Willi N , Offner F , Sauter Guido , Zsikla V , Cathomas Gieri 
Published: February 2011

Abstract
Merkel cell polyomavirus (MCPyV) DNA has been detected by PCR in 75-100% of Merkel cell carcinomas (MCC), an aggressive neuroendocrine skin cancer. MCPyV is a 5.4 kb DNA virus that expresses tumor (T) antigen in tumor tissues. The aim of this study was to analyze which subset of MCC is biologically associated with MCPyV using various viral detection methods.
Genomic DNA isolated from paraffin-embedded tissue of 61 MCC was analyzed by MCPyV-specific PCR. Using a 5kb MCPyV DNA probe, the physical status of MCPyV was determined by fluorescence in situ hybridization (FISH) using tyramide signal amplification and ApoTome microscopy. Expression of large T antigen was assessed by immunohistochemistry (IHC) using monoclonal antibody CM2B4 (kindly provided by Y. Chang).
A total of 44 of 61 (72%) MCC were positive for MCPyV by PCR. 34 of these 44 cases (77%) were also positive for MCPyV by FISH and 28 (64%) showed strong nuclear large T antigen expression by IHC. In contrast, none of the 17 PCR-negative tumors showed FISH signals and only 1 case showed a weak immunostaining for large T antigen. FISH analysis showed in 16 cases (47%) tumor nuclei with a single punctate signal indicating viral integration. In 8 of these tumors also areas were observed with a granular pattern with &gt;1 nuclear signals varying significantly in size and intensity, indicating the presence of episomal viral DNA and/or RNA. In the remaining 18 cases (53%) an exclusive granular FISH pattern was observed.
Our data indicate that a subset of MCC is caused by MCPyV as determined by PCR, FISH and IHC analysis (46% is positive with all 3 detection methods). FISH and IHC showed a strong positive and negative concordance. FISH signal evaluation furthermore suggests viral integration in half of the positive MCC and a non-clonal viral persistence in the remaining positive cases. Further studies have to validate these findings and elucidate the molecular mechanisms underlying MCV-positive and -negative MCC 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 5352.
Abstract 5361: Progesterone alters cell survival and cell death pathways in estrogen-induced mammary carcinogenesis
Authors: Arumugam Arunkumar , Lakshmanaswamy Rajkumar 
Published: February 2011

Abstract
Breast cancer is one of the most frequent and common malignancy in women. The incidence of breast cancer is high in postmenopausal women and majority of these cancers are estrogen receptor positive. Epidemiological data suggests that estrogen plus progesterone hormone replacement therapy increases the risk of breast cancer in postmenopausal women. Further, estrogen alone therapy did not increase the risk instead decreased the risk of breast cancer in postmenopausal women. Till date the role of progesterone in breast cancer is not well understood. Our earlier studies using ACI rats have clearly demonstrated the significant role progesterone plays in the estrogen-induced mammary carcinogenesis. We now, aim to investigate the mechanisms by which progesterone promotes estrogen-induced mammary carcinogenesis in ACI rats. We chose to use the ACI rats as it is a good model to study hormone-induced mammary carcinogenesis. In brief, seven weeks old female ACI rats were divided into the following groups: 1) untreated control, 2) rats treated with 30 mg estradiol, 3) rats treated with 30 mg progesterone, 4) rats treated with 30 mg estradiol plus 30 mg of mifepristone (a progesterone inhibitor). All hormone treatments were given for 30 days by subcutaneous implants of silastic capsules. At the end of the treatment, mammary glands were excised and used for molecular analysis. Cell survival, cell death pathways, and hormone receptor status were analyzed using different molecular techniques. Expression patterns of mRNA and proteins involved in major cell survival and apoptotic pathways were significantly altered in response to progesterone inhibition. Our data demonstrates that progesterone plays a prominent role in regulating key regulatory pathways in estrogen-induced mammary carcinogenesis.
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 5361.