bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5281: The effect of RF through JAG/Notch pathway in tumorigenesis, angiogenesis and migration
Authors: Kim Mi Hwa , You Ho Jin 
Published: February 2011

Abstract
RF has known as multifunctional protein with the two of domains, redox and repair domains. Although RF is highly expressed in a lot of cancer cell lines, its function has not been exactly reported. The Jagged1/Notch proteins participate in a variety of cellular processes, such as cell fates specification, proliferation, differentiation, apoptosis, adhesion, epithelial-mesenchymal transition, migration, and angiogenesis. In the present study, Jagged1 and Notch-1 are overexpressed in RF-transfected fibroblast cell(GM00637/RF) and several human cancer cell lines. Through DNA microarray, we show that JAGGED1/Notch1 expression is up-regulated by RF. In promoter study, RF regulates the expression of JAGGED1 by binding Egr-1 on JAGGED1 promoter. Also, immunofluorescence confocal microscopy shows Notch active form(Notch intracellular domain) is in the nucleus. Furthermore, down-regulation of RF or JAG by RNA interference reduces the activities of focal adhesion molecules(vinculin, pFAK) and MMP-2 which have known to be involved in cell migration and invasion in cancer. In nude mouse model, RF or JAG siRNA significantly reduces tumor size and angiogenesis. We suggest that RF may act as a potential regulator in tumorigenesis, angiogenesis and migration through JAGGED1/Notch pathway.
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 5281.
Abstract 53: Krebs cycle substrate-level phosphorylation drives metastatic cancer cells
Authors: Shelton Laura M. , Strelko Cheryl L. , Roberts Mary F. , Seyfried Thomas N. 
Published: February 2011

Abstract
Many metastatic cancers are derived from compromised respiration in tissue cells of myeloid origin (e.g., macrophages), which use glutamine as a major energy substrate. Although impaired respiration can render tumor cells dependent on glycolysis for energy in the presence of oxygen (Warburg effect), it has not been determined if glutamine alone could provide enough energy (ATP) through substrate level phosphorylation in the TCA (Krebs) cycle to maintain tumor cell viability. Using a bioluminescent-based ATP assay, we determined the viability of metastatic mouse VM-M3 tumor cells grown in serum free medium in the presence of glucose alone (25 mM), glutamine alone (4 mM), or in glucose + glutamine. The VM-M3 cells could not survive on glucose alone, but could survive in glutamine alone indicating an absolute requirement for glutamine in these metastatic tumor cells. Glucose + glutamine acted synergistically in providing growth and viability. Lactic acid production was 10-fold lower in the cells grown in glutamine alone than in glucose alone. Glutamine could also maintain viability in the absence of glucose and in the presence of the F1 ATPase inhibitor oligomycin. Glutamine could not maintain viability in the presence of the TCA cycle enzyme inhibitor, 3-Nitropropionic acid. NMR analysis indicated that glutamine metabolism via the TCA cycle was active resulting in accumulation of both succinate and aspartate. The data indicate that glutamine can provide ATP for viability in the metastatic VM-M3 cells through Krebs cycle phosphorylation in the absence of energy from either glycolysis or oxidative phosphorylation.
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 53.
Abstract 530: Evaluation of in vitro invasion of primary vs recurrent glioblastoma multiforme cells using organotypic rodent brain slice culture
Authors: Rossi Marco , Tarantino Antonio , Roncarati Renza , Salerno Massimiliano , Giordano Cinzia , Tunici Patrizia , Bakker Annette 
Published: February 2011

Abstract
Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the adult central nervous system. The highly lethal nature of this tumor partly derives from the acquisition of an invasive phenotype, which allows the tumor cells to infiltrate the surrounding brain tissues. In fact the tumor cells, leading to the recurrence of the primary neoplasm highly contribute to the lack of success in eradicating this disease.
In order to measure the migrating ability of GBM cells and the potential difference in infiltration capacity of primary versus recurrent GBM cells, we developed and validated an organotypic rodent brain slice assay and visualized the fluorescently labeled cells using confocal laser scanning microscopy. The invasion capacity has been quantified applying an innovative image analysis method using a panel of primary and recurrent glioma cell lines derived from patient biopsies and the commercially available GBM cell lines, DBTRG-05MG (recurrent) and T98G (primary).
For validation purposes, cytochalasin D, a potent inhibitor of actin polymerization and hence migration and invasion, was used. The results revealed clear differences between primary and recurrent GBM cells: They differ both in their migrating capacity on the surface of the brain slice as well as by their ability to invade into the brain slice.
A small population of recurrent GBM cells seems to acquire high infiltrative capacity allowing the invasion of brain tissue to greater distance than the primary GBM cells. Higher invasiveness may be an important characteristic of recurrent tumours, adding to our understanding of their worse clinical evolution and responsiveness to therapy.
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 530.
Abstract 5301: MUC16-Siglec-9 binding leads to adhesion between ovarian tumor cells and specific subsets of NK cells, B cells, and monocytes
Authors: Patankar Manish S. , Belisle Jennifer A. , Horibata Sachi , Felder Mildred , Gubbels Jennifer A.A. , Connor Joseph P. 
Published: February 2011

Abstract
MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian cancer cells. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates peritoneal metastasis of ovarian tumors. Both sMUC16 and csMUC16 also protect cancer cells from cytotoxic responses of natural killer (NK) cells. In a previous study, we demonstrated that sMUC16 binds to a specific subset of NK cells. Here, we demonstrate that in addition to NK cells, sMUC16 also binds to B cells and monocytes isolated from the peripheral circulation and the peritoneal fluid. The I-type lectin, Siglec-9, is identified as the sMUC16 receptor on these immune cells. The inhibitory receptor Siglec-9 is expressed on approximately 30-40% of CD16pos/CD56dim NK cells, 20-30% of B cells and &gt;95% of monocytes. sMUC16 binds to the majority of the Siglec-9pos NK cells, B cells and monocytes. sMUC16 is released from the immune cells following neuraminidase treatment. While sMUC16 binds to Siglec-9, it has no affinity for another I-type lectin Siglec-7. Experiments with Siglec-9 transfected Jurkat cells and monocytes isolated from healthy donors demonstrate that immune cells can bind to ovarian tumor cells via Siglec-9-csMUC16 interaction. Siglec-9 is an inhibitory receptor that attenuates T cell and NK cell function. Our studies indicate that sMUC16/csMUC16 may each serve as Siglec-9 ligands and mediate inhibition of anti-tumor immune responses.
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 5301.
Abstract 5307: Indomethacin reverts tumor mediated immune suppression in a murine lung adenocarcinoma
Authors: Blidner Ada G. , Salatino Mariana , Karas Romina A. , Jasnis Maria A. , Rabinovich Gabriel A. , Diament Miriam J. , Klein Slobodanka M. 
Published: February 2011

Abstract
Tumor-induced immune suppression is widespread in patients and experimental animals with malignant tumors and is likely to be a significant impediment to immunotherapy. Multiple mechanisms are thought to facilitate this suppression state, being Myeloid-Derived Suppressor Cells (MDSC) and T regulatory cells (Tregs) major contributors. Our aim was to analyze immune parameters indicative of immune suppression in BALB/C mice bearing LP07 (COX+) lung tumor (TBM) during tumor growth and the effect of a Non Steroidal Anti-inflammatory drug (NSAID), Indomethacin, which is a non-specific COX inhibitor, on these parameters. We determined 1) the effect of Indomethacin on LP07 tumor growth; 2) the content of MDSC and Treg cells in lymphoid organs (spleen, tumor-draining lymph nodes-TDLN-) and in the tumors at different times by FACS; 3) arginase activity in lung, spleen, liver and tumor measured as µg Urea/mg protein; 4) specific Delayed Type Hypersensitivity (DTH) response with formalinized LP07 cells, by the foot pad swelling assay. Results: Indomethacin treatment significantly inhibited tumor growth. The percentage of MDSC (CD11b+ Gr1+) augmented significantly in the spleen of TBM in advanced stages of tumor progression (33 days): Normal: 2,6%; TBM 10 days: 2,4%; TBM 20 days: 5,6%; TBM 33 days: 8,3%, p&lt;0,05 vs control. This rise was prevented by Indomethacin treatment (4,6%). Intratumoral and TDLN CD4+CD25+Foxp3+ Tregs frequency augmented during tumor growth, peaking at day 20. Interestingly, Indomethacin treatment decreased Treg cell and MDSC induction (p&lt;0.05) in TDLN. Arginase activity increased in all analyzed tissues of TBM compared to those of control mice. Furthermore arginase activity increase in the spleen was in line with MDSC induction. Specific DTH response decreased in late stages of tumor progression, while Indomethacin treatment reversed this inhibition (TBM: 0,06 ± 0,045 mm; Indo:0,14 ± 0,038 mm). Conclusion: In our model, the increment in MDSC and Tregs frequency during tumor progression correlates with specific immunesuppression demonstrated by DTH responses and increased arginase activity. We suggest that Indomethacin treatment prevented this immunesuppression by modulating COX activity in the tumor microenvironment, which is known to activate MDSC and differentiate Treg 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 5307.
Abstract 5310: mTOR knock-down mice exhibit altered T and B cell activation, differentiation and immune response
Authors: Zhang Shuling , Readinger Julie , Roth Laura , Pruitt Maggie , Robinson Richard , DuBois Wendy , Bliskovsky Val , Zhang Ke , Wu Julie , Tessarollo Lino , Schwartzberg Pam , Mock Beverly A. 
Published: February 2011

Abstract
Mammalian TOR (mTOR) regulates cell growth and survival by integrating nutrient and hormonal signals. Because disruption of the mouse mTOR gene leads to early postimplantation lethality, insights into in vivo function of mTOR have been limited. In this study, we generated a mouse knock-down model, which recapitulates treatment with mTOR inhibitors. Neo insertion interrupts transcription, leading to reduced mTOR expression. The homozygous knock-down mice exhibit reductions in body, organ, and cell size. T cell development in the thymus appears normal, however, T cell receptor (TCR)-induced phosphorylation of AKT was reduced in CD4+ and CD8+ T cells. Spleens are disproportionately small relative to overall body weight. The number of CD4+ and CD8+ T cells is reduced in the spleen. Cell proliferation was decreased in splenic T and B cells. Both TCR-mediated proliferation in T cells and LPS-induced proliferation in B cells were reduced. Splenic T cells show reductions in migration to TECK and SDF, and increased FoxP3 expression. Splenic B cell populations had more mature cells, with fewer transitional cells and markedly reduced marginal zone and follicular B cells. Phosphorylation of AKT was increased in B cells after LPS stimulation, similar to what has been reported in tumor cells exposed to long-term rapamycin treatment. B220+ B cells were decreased in bone marrow and alterations were seen in pre-B cell maturation. We investigated the immunologic consequences of immunization with NP-CGG, and knock-down mice show decreases in NP-specific Ig responses and defects in producing primary germinal center reactions. These data suggest that mTOR plays a role in the maturation and differentiation of immune cell lineages, as well as in the regulation of humoral immunity.
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 5310.
Abstract 5316: Inflammation-induced myeloid-derived suppressor cells have enhanced resistance to apoptosis
Authors: Chornoguz Olesya Y. , Grmail Lydia , Sinha Pratima , Artemenko Konstantin , Zubarev Roman , Ostrand-Rosenberg Suzanne 
Published: February 2011

Abstract
The purpose of this study is to deduce the influence of inflammation on apoptosis of Myeloid-Derived Suppressor cells. Myeloid-derived suppressor cells (MDSC) accumulate in patients and animals with cancer where they mediate systemic immune suppression. MDSC induced in heightened inflammatory environments with high levels of IL-1β and/or IL-6 accumulate more rapidly, are more potent suppressors of T cell activation, produce more IL-10, and have a greater ability to down-regulate macrophage production of IL-12, as compared to MDSC that develop in environments with lower levels of these cytokines. To determine how inflammation enhances MDSC levels and activity we used mass spectrometry to identify proteins produced by MDSC induced in highly inflammatory vs. less inflammatory settings. Proteomic pathway analysis identified Fas pathway and caspase network proteins, leading us to hypothesize that inflammation enhances MDSC accumulation by down-regulating Fas-mediated MDSC apoptosis. Using cytochrome C and activated caspase-3 and caspase-8 as indicators of apoptosis, confocal microscopy and flow cytometry demonstrated that inflammation-induced MDSC have enhanced resistance to Fas-mediated apoptosis. These results suggest that an inflammatory environment protects MDSC against extrinsic-induced apoptosis resulting in MDSC with a longer in vivo half-life and may explain why MDSC accumulate more rapidly and to higher levels in inflammatory settings. (supported by NIH R01CA84232 and RO1CA115880).
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 5316.
Abstract 5328: Expansion of CD11b+CD33lowCD15high immunosuppressive myeloid cell population in patients with bladder carcinoma
Authors: Kusmartsev Sergei A. , Eruslanov Evgeniy , McCullers Molly , Rosser Charles , Daurkin Irina , Vincent Charles , Willis Daniel , Vieweg Johannes 
Published: February 2011

Abstract
Recent studies highlighted the immunoregulatory role of CD11b myeloid cells in cancer-associated immune non-responsiveness. Increased presence of myeloid-derived suppressor cells (MDSC) is one of the major factors responsible for immune suppression in tumor hosts. Here we describe the expanded CD11b myeloid cell subset in peripheral blood obtained from patients with bladder cancer. Based on expression of CD33 and CD15 myeloid cells markers, the circulating CD11b-positive cells in patients with bladder cancer could be subdivided into two major subpopulations: CD33lowCD15high and CD33highCD15low. First subpopulation (CD11b+CD33lowCD15high cells) has granulocyte-type morphology, express G-CSF receptor (CD114) and secrete elevated amounts of pro-inflammatory cytokines and chemokines such as G-CSF, MCP-1 MIP-1alpha, MIP-1beta. Second major myeloid cell subset from cancer patients (CD11b+CD33high CD15lowcells) displays a monocyte-type cell morphology and co-express CD14, M-CSF receptor (CD115), CCR2 and HLA-DR. We show here that proportion of granulocytic CD33lowCD15high cells is highly elevated in cancer patients as compared to healthy individuals. Patients with bladder cancer but not healthy volunteers show weak T cell proliferative response after in vitro stimulation. We demonstrate that granulocyte-type CD33lowCD15high cell population is involved in T cell hyporesponsiveness, since specific depletion of this cell subset restored the T cell proliferation. Obtained results suggest that fraction of PBMC in patients with bladder cancer patients contains markedly elevated proportion of CD11b+CD33lowCD15high granulocyte-type myeloid cell population which contributes to cancer-associated inflammation and tumor-induced immune suppression.
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 5328.
Abstract 533: Critical role of MMP-9 dimers in cell migration: design of inhibitory peptides
Authors: Dufour Antoine , Sampson Nicole S. , Kuscu Cem , Zucker Stanley , Cao Jian 
Published: February 2011

Abstract
Non-proteolytic activities of matrix metalloproteinases (MMPs) have recently been shown to impact cell migration, but the precise mechanism remains to be understood. We previously demonstrated that the hemopexin (PEX) domain of MMP-9 is a prerequisite for enhanced cell migration. Using a biochemical approach, we now report that dimerization of MMP-9 through the PEX domain is necessary for MMP-9-enhanced cell migration. Following a series of substitution mutations within the MMP-9 PEX domain, two critical motifs in the outermost strands of the first and fourth blades of MMP-9 PEX domain were found to be involved in MMP-9 homo- and hetero- dimer formations. Peptides mimicking these motifs efficiently blocked MMP-9 dimer formations and inhibited MMP-9-mediated cell migration, but not membrane type 1- MMP (MT1-MMP)-induced cell migration. In addition, these peptides demonstrate inhibitory effects on migration of human fibrosarcoma HT1080 cells, which express high level of endogenous MMP-9. Using a shRNA approach, CD44 was found to be a critical molecule in MMP-9-mediated cell migration. Furthermore, a novel axis involving an MMP-9-CD44-EGFR signaling pathway in cell migration was identified using antibody microarray analysis and specific receptor tyrosine kinase inhibitors. In conclusion, we dissected the mechanism of proMMP-9-enhanced cell migration and developed structure-based inhibitory peptides specific targeting of MMP-9-mediated cell migration.
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 533.
Abstract 5335: The antigen target of IMGN901, CD56, is expressed at significant levels in merkel cell carcinoma (MCC)
Authors: Carrigan Christina N. , Xu Shanqin , Zhao Yiwei , O'Keefe Jessica , Qin Albert , O'Leary James , Payne Gillian , Lutz Robert 
Published: February 2011

Abstract
Background: IMGN901 consists of a CD56-binding monoclonal antibody, huN901, with a maytansinoid agent, DM1, attached via a stable disulfide linker, SPP. The CD56 antigen, also known as neural cell adhesion molecule (NCAM), is present in a number of malignancies including Merkel cell carcinoma (MCC), small cell lung carcinoma and other neuroendocrine tumors, ovarian cancers and multiple myeloma. Once bound to CD56, IMGN901 is internalized into a cancer cell and its DM1 is released to cause cell death via inhibition of tubulin polymerization. IMGN901 is currently in Phase I testing for the treatment of CD56-positive multiple myeloma and CD56-positive solid tumors. Six patients with MCC have received IMGN901, used as a single agent, in one of the Phase I trials underway. Clinical benefit was observed in 3 of these 6 patients: one complete response (CR), one partial response (PR) and one stable disease (SD).
Objective: The goal of this study was to assess the potential utility of IMGN901 as a treatment for MCC by identifying the range of CD56 antigen expression levels in MCC.
Methods: A calibrated immunohistochemical (IHC) staining method for CD56 was developed. CD56 staining conditions were established where 4 formalin fixed paraffin embedded (FFPE) MCC samples showed differential staining. FFPE cell pellet controls prepared from human tumor cell lines were next identified which showed CD56 staining in the same range as the MCC samples. The CD56 antigen level for each tumor cell line was subsequently quantified by flow cytometry. The calibrated IHC staining method was then applied to positive cell pellet controls and an extended panel of MCC tissues. For each resulting tissue section, the extent and intensity of immunostaining was evaluated and the CD56 expression level was estimated by comparing to the cell pellet controls.
Results: The majority of samples from the MCC panel exhibited heterogeneous or homogeneous staining with significant levels of CD56 expression. Tissues from primary biopsy sites and from metastases showed comparable levels of CD56 expression. To date, biopsy samples have been acquired from 3 of the 6 MCC patients who have received IMGN901 (two IMGN901 non-responders and one responder) and these all showed high and homogeneous levels of CD56 expression.
Conclusion: This IHC study indicates that the majority of MCC patient tissues express significant levels of CD56, supporting the development of the CD56-targeting compound, IMGN901, for this indication.
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 5335.