bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-3: All-trans retinoic acid (ATRA) downregulates ALK in neuroblastoma cell lines and induces apoptotic cell death in neuroblastoma cell lines with activated ALK
Authors: Futami Hitoyasu , Sakai Ryuichi 
Published: February 2011

Abstract
Neuroblastoma is the most common extracranial solid tumors in children and high-risk patients with such tumors have a poor prognosis despite recent advances with multimodal therapies. Retinoic acids have been clinically used for some cancers including neuroblastoma although the mechanism of their antitumor effect remains to be fully elucidated. It was recently reported that gene amplification and gain-of-function mutation of ALK were found in tumors from some neuroblastoma patients; and RNAi or small molecule inhibitors of ALK induced apoptotic cell death in neuroblastoma cell lines with these genetic alterations of ALK. In this study, we found that all-trans retinoic acid (ATRA) downregulated ALK expression in neuroblastoma cell lines; and the suppression of ALK by ATRA accompanied apoptotic cell death in neuroblastoma cell lines with activated ALK.
We used four neuroblastoma cell lines: NB-39-nu cells with gene amplification of ALK, SH-SY5Y cells with gain-of-function mutation of ALK as well as TNB-1 and GOTO cells without such genetic alterations. Western blotting analysis demonstrated that the levels of ALK protein were remarkably reduced in all cell lines treated with ATRA at the concentration of 1 μM or 10 μM for 72 h. Analysis by quantitative real-time RT-PCR for mRNA expression levels in ATRA-treated NB-39-nu cells revealed that the ALK mRNA quantitative levels of the cells reduced at 24 h after such treatment. Apoptosis assays demonstrated obvious apoptosis in NB-39-nu and SH-SY5Y cells whereas it was not evident in TNB-1 and GOTO cells. Cleaved caspase-3 was also detected in NB-39-nu and SH-SY5Y cells 72 h after treatment with ATRA, but not in TNB-1 and GOTO cells. In addition, we observed cell growth inhibition that was accompanied with apoptosis in NB-39-nu and SH-SY5Y cells treated with ATRA. These results suggest that ALK downregulation by ATRA might lead to apoptotic cell death in neuroblastoma cells with activated ALK. This finding further suggests that ALK downregulation by retinoic acids could contribute to their therapeutic effect in a subset of neuroblastoma patients.
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 LB-3.
Abstract LB-30: Smac mimetic sensitizes antitumor activity of bacillus Calmette-Guerin stimulated neutrophils against bladder cancer cells
Authors: Jinesh Goodwin G. , Chunduru Srinivas K. , Kamat Ashish M. 
Published: February 2011

Abstract
Bacillus Calmette-Guerin (BCG) is the current gold standard therapy for bladder cancer. It is believed to work via recruitment of neutrophils to the tumor microenvironment and releasing cytokines, specifically TRAIL. However, BCG mediated therapy is hampered by relapse and resistance problems indicating the need for alternative or combination therapeutic options. Smac mimetics provide an alternative platform to rescue cells from TRAIL resistance by circumventing the IAP mediated inhibition of caspases. Herein we show that the KU-7 and RT4v6 bladder cancer cell lines are resistant to cell death with BCG stimulated neutrophils alone in vitro but a Smac mimetic kills bladder cancer cells in combination with BCG stimulated neutrophils. The sensitization of bladder cancer cells to Smac mimetic and BCG stimulated neutrophils is associated with the dowregulation of cIAP2 and cIAP1. TNF-α, TRAIL or Smac mimetic compound could not induce significant cell death as single agents in these cell lines, where as Smac mimetic compound in combination with TNF-α or TRAIL induced potent and massive cell death supporting our hypothesis. Our results suggest that Smac mimetics present a viable mechanism based approach to combination therapy with BCG for bladder cancer.
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 LB-30.
Abstract LB-319: A novel cancer-testis antigen, BORIS-based vaccine delivered by dendritic cells is effective against metastatic disease
Authors: Mkrtichyan Mikayel , Ghochikyan Anahit , Loukinov Dmitry , Movsesyan Nina , Davtyan Hayk , Laust Amanda K. , Lobanenkov Victor , Nelson Edward L. , Agadjanyan Michael 
Published: February 2011

Abstract
Although broad clinical benefits of anti-tumor immunotherapy have not been demonstrated, the current data suggest such strategies could be beneficial if capable of inducing strong anti-cancer cellular immune responses. We report testing for the first time, the therapeutic efficacy of a dendritic cell (DC)-based immunotherapy strategy targeting a novel cancer testis (CT) antigen, Brother of Regulator of Imprinted Sites (BORIS), which is an epigenetically acting tumor promoting transcription factor expressed in various human and mouse cancer cells.
In addition to therapeutic potency, we evaluated the cellular immune responses by assessing BORIS-specific CD4 T cell proliferation, T cell cytokine production both by intracellular cytokine staining and ELISpot analysis, and CTL responses. We evaluated the impact of this therapy on the development of metastatic disease, by analyzing the number of spontaneous clonogenic metastases after a 10-day culture of lung homogenates in presence of 6-thioguanine. The presence of CD4, CD8, Treg and myeloid derived suppressor cells (MDSCs) in the tumor and in the spleen was analyzed by flow cytometry.
DC loaded with zink-finger deleted (mutated) BORIS vaccine (DC/mBORIS) was evaluated in the non-immunogenic, very aggressive and highly metastatic mouse model of 4T1 mammary carcinoma. Vaccination of mice after 4T1 tumor implantation inhibited tumor growth (18.75% mice remained tumor-free) and dramatically lowered number of spontaneous clonogenic metastases (50% mice remained metastases-free). Higher numbers of immune-effector CD4 and CD8 T cells infiltrated the tumors of vaccinated mice compared to control animals. Therapeutic vaccination with DC/mBORIS significantly decreased the numbers of MDSC infiltrating the tumor, but not splenic MDSC, likely associated with the effect of the immunotherapy on tumor burden rather than a direct effect on MDSCs. Currently, we are testing the suppressive activity of splenocytes from tumor-bearing mice as well as MDSC isolated from these splenocytes. These data suggest that mBORIS is an attractive target for immunotherapy having substantial efficacy in this highly aggressive tumor model when incorporated into a DC-based immunotherapy, and which may be enhanced even further in combination with agents to attenuate tumor-associated immune suppression.
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 LB-319.
Abstract LB-327: Targeted microbeads for attraction and induction of specific innate immune response in the tumor microenvironment
Authors: Pitcovski Jacob , Shahar Ehud , Aizenshtein Elina , Gorodetsky Raphael 
Published: February 2011

Abstract
Anti-tumor activity of molecules and cells of the innate immune system has been reported. Here we propose a method for targeting preferred innate immune cells and magnifying their tumoricidal effect at the tumor microenvironment, by modular multiple-component complexes. As a model, micro-complexes carried monoclonal anti-HER2 antibodies, lipopolysaccharide and mannose. The complexes showed high binding capacity to HER2-positive cancer cells in vitro, high induction of interleukin-1 RNA transcription by the activated monocytes and ability to mediate monocytes’ attachment to HER2-positive cells. We thus present a new vision of targeting a desired innate immune response to the tumor microenvironment.
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 LB-327.
Abstract LB-329: Defining rgulatory T-cells as CD4+CD25hiCD127- or as CD4+CD25hiFoxP3+ in immune monitoring of cancer vaccine clinical trials
Authors: Clifton Guy T. , Patil Ritesh , Clive Kevin , Tyler Josh , Zacharia Athina , Jama Yusuf , Mursal Mohamed , Ciano Kathy , Holmes Jarrod P. , Mittendorf Elizabeth A. , Peoples George E. , Ponniah Sathibalan 
Published: February 2011

Abstract
Background: Regulatory T cells (Treg) are widely accepted to play a key role in the immune tolerance and escape of cancer cells. Originally Tregs were identified as being CD4+ T cells expressing high levels of CD25 (IL2 receptor). The identification of the transcription factor FoxP3 resulted in defining Tregs as CD4CD25hiFoxP3+ T cells by staining permeablized cells. Recently Tregs have been identified as CD4CD25hi T cells with low levels of CD127 (IL7 receptor) expressing a CD4+CD25hiCD127- cell surface phenotype. In an ongoing clinical trial with a MHC class II HER2/neu pep tide vaccine we have evaluated these various definitions of Treg phenotypes for immunological monitoring.
Methods: Tregs were quantified in disease-free, high risk BCa patients enrolled in adjuvant peptide-based breast cancer vaccine trials. Peripheral blood mononuclear cells (PBMCs) were both permeabilized and stained with CD4, CD25, and FoxP3 monoclonal antibodies and surface stained with CD4, CD25, and CD127. Samples were then analyzed by flow cytometry. The means are compared with t-test and correlation is determined with Pearson's correlation coefficient.
Results: 196 PBMC samples from 72 patients were available for Treg quantification. There was a greater mean percentage of cells identified as Treg in permeabilized than nonpermeabilized cells by staining with CD4+CD25hi (5.9±0.1% vs 4.8 ±0.1%, p&lt;0.01) and excellent correlation between the tests (r=0.78, p&lt;0.01). There was a greater mean percentage of cells identified as Tregs by CD4+CD25hi than CD4+CD25hiFoxP3+ (5.9±0.1% vs 3.6±0.1%, p&lt;0.01) with good correlation (r=0.68, p&lt;0.01). There was a greater mean percentage of Tregs by CD4+CD25+ than CD4+CD25+CD127- (4.8±0.1 vs 4.0±0.1, p&lt;0.01) with excellent correlation (r=0.89, p&lt;0.01). There was a greater mean percentage of Tregs by CD4+CD25hiCD127- than Tregs by CD4+ CD25hiFoxP3+ although levels were similar (4.0±0.1 vs 3.6±0.1, p&lt;0.01) and the two tests had good correlation (r=0.58, p&lt;0.01).
Conclusion: There was good correlation between various methods of defining Tregs with and without cell membrane permeabilization. Defining Treg cells as either CD4+CD25hiFoxP3+ or CD4+CD25+CD127- appear to be more specific than defining Tregs as CD4+CD25hi alone. Furthermore, defining Treg populations by surface staining as CD4+CD25hiCD127- yields similar levels with good correlation as CD4+CD25hiFoxP3+ and may be the preferred method for immune monitoring.
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 LB-329.
Abstract LB-338: Increased apoptosis and p53 expression in sclerotome of COX-2 transgenic embryo
Authors: Shim Minsub , Foley Julie , Anna Colleen , Mishina Yuji , Eling Thomas E. 
Published: February 2011

Abstract
Cyclooxygenases (COXs) have important functions in various physiological and pathological processes. COX-2 expression is highly induced by a variety of stimuli and is observed during certain periods of embryonic development. We examined the direct effect of COX-2 expression on embryonic development using a novel COX-2 transgenic mouse model which ubiquitously expresses human COX-2 from the early stages of embryonic development. COX-2 transgenic fetuses exhibit severe skeletal malformations and die shortly after birth. Skeletal malformations are localized along the entire vertebral column and rib cage and are linked to defective formation of cartilage anlagen. The cartilage anlagen of axial skeleton fail to properly develop in transgenic embryos because of impaired pre-cartilaginous sclerotomal condensation, which results from the reduction of cell number in the sclerotome. Despite the ubiquitous expression of COX-2, the number of apoptotic cells is highly increased in the sclerotome of transgenic embryos, but not in other tissues, suggesting that it is a tissue-specific response. Therefore, the loss of sclerotomal cells due to an increased apoptosis is likely responsible for axial skeletal malformations in transgenic fetuses. In addition, the sclerotomal accumulation of p53 protein is observed in transgenic embryos. Our result suggests that COX-2 signaling may act upstream of p53 and positively regulate the level of p53.
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 LB-338.
Abstract LB-342: Matrix metalloproteinase-9 is a novel pathogenic factor in B-cell chronic lymphocytic leukemia
Authors: Redondo-Muñoz Javier , Ugarte-Berzal Estefanía , Terol María-José , Van den Steen Philippe E. , del Cerro Mercedes Hernández , Roderfeld Martin , Roeb Elke , Opdenakker Ghislain , García-Marco José A. , García-Pardo Angeles 
Published: February 2011

Abstract
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation in peripheral blood of CD5+ B lymphocytes, which ‘ progressively infiltrate lymphoid tissues. Several molecules, including matrix metalloproteinase-9 (MMP-9), are involved in these processes and could represent therapeutic targets. We previously showed that MMP-9 plays an essential role in B-CLL cell migration through basement membranes or endothelial cells (Redondo-Muñoz et al., Blood 108: 3143, 2006). We also recently demonstrated that alpha4beta1 integrin and a 190 kDa CD44v isoform are receptors for MMP-9 in B-CLL but not in normal B cells and that the MMP-9 hemopexin domain is essential for these interactions. Binding of MMP-9 to B-CLL cells inhibited cell migration and this required MMP-9 proteolytic activity (Redondo-Muñoz et al., Blood 112: 169, 2008). To further define the role of surface-bound MMP-9 in B-CLL we have employed several techniques including western blot, zymography, immunofluorescence, immunoprecipitation, siRNA transfection, cell adhesion/soluble binding assays, apoptosis, and cell migration assays. B-CLL cells cultured on pro- or mature MMP-9, proMMP-9 hemopexin domain or proMMP-9 catalytically-inactive mutant, showed decreased spontaneous apoptosis. This was due to induction of a survival pathway involving Lyn activation, STAT3 phosphorylation and Mcl-1 upregulation and did not require catalytic activity. This pathway was induced in all B-CLL cases and was active in B-CLL lymphoid tissues. Our results highlight the role of MMP-9 in B-CLL pathogenesis and indicate that MMP-9 hemopexin domain could constitute a therapeutic target in this malignancy. Supported by grants PI060400 and SAF2009-07035 from the Ministerio de Ciencia e Innovación and by the Fundación de Investigación Médica Mutua Madrileña.
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 LB-342.
Abstract LB-345: Functional genomics reveals acute dependencies on polyadenylation for tumor cell mitotic progression
Authors: Cappell Kathryn , Sciaky Noah , Larson Brittany , Whitehurst Angelique 
Published: February 2011

Abstract
We are using genome-wide synthetic lethal paclitaxel chemosensitizer screens to understand the protein networks that support mitosis in lung tumor cells. Using this approach, we have identified several components of the polyadenylation machinery that are required for a high-fidelity mitosis in the presence of a synthetic lethal dose of paclitaxel. Here, we show depletion of multiple polyadenylation proteins in combination with low-dose paclitaxel causes a G2/M cell cycle block. We show depletion of one of these polyadenylation proteins, symplekin, has profound effects on mitotic spindle assembly resulting in over-duplicated centrosomes and impaired microtubule growth. Furthermore, we use a panel of lung lines to show symplekin is uniquely required for tumor cell mitosis as compared to normal cell mitosis. Our mechanistic studies suggest symplekin may mediate these effects on tumor cell mitosis by interacting with the centrosomally-associated protein transforming acidic coiled coil 3 protein (TACC3). Interestingly, TACC3 is typically expressed during development but becomes aberrantly upregulated in tumor cells. We propose TACC3 may become upregulated during tumorigenesis and engage symplekin to support mitosis in tumor cells. These results suggest polyadenylation components may represent an attractive therapeutic target in combination with already available anti-mitotic agents.
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 LB-345.
Abstract LB-353: From worms to humans: understanding the role of microRNAs in cancer progression
Authors: Esquela-Kerscher Aurora 
Published: February 2011

Abstract
MicroRNAs (miRNAs) regulate important developmental events and are often misexpressed in human cancers, but little is known regarding how these small RNAs contribute to tumor formation. Our laboratory uses a combination of nematode and mammalian model systems to functionally characterize miRNAs and determine the role these factors play in controlling cancer progression pathways. We have successfully used the nematode to analyze how members of the lin-4 and let-7 miRNA families functionally overlap to direct common developmental events associated with cell cycle progression and differentiation. Specifically, animals that carry a triple deletion for the lin-4 homologue, mir-237, and the let-7 homologues, mir-48 and mir-84, exhibit morphological defects and fertility problems related to abnormal mitotic and meiotic abnormalities in the germline that were not found in the single or double deletion combinations. We have also begun to determine how the let-7 miRNA family functions as tumor suppressor genes in mammals. Our experiments showing that exogenous let-7 miRNA administration in the lung using a conditionally activated KRAS lung cancer mouse model result in reduced lung tumor load in these animals highlight the therapeutic potential of miRNAs. We are also studying the role of let-7 together with other miRNA families in directing cancer progression pathways in human tissues of urothelial origin. For instance, we find that let-7 is dysregulated in human prostate cancer cell lines differing in their metastatic status and indicates a novel role for this miRNA in prostate cancer progression. Due to our access to a vast repository of human prostate specimens from the Virginia Prostate Center at Eastern Virginia Medical School, we have begun to analyze the miRNA expression profiles in FFPE specimens taken from the primary prostate tumor, normal adjacent tissue and the lymph node metastasis of individual prostate cancer patients as well as in tumors from patients presenting insignificant and organ confined cancer. We are also determining the “miRNA signatures” in blood, urine, and expressed prostatic secretions (EPS) that were obtained non-invasively from both normal and cancer patients. Our work investigating the role of miRNAs during cancer progression promises to reveal novel therapeutic approaches and diagnostic and prognostic biomarkers for human cancer.
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 LB-353.
Abstract LB-356: Characterization of microRNA expression of clear cell renal cell carcinoma by whole genome small RNA deep sequencing using human tissue cohort
Authors: Wu Huiqing , Weng Lihong , Wu Xiwei , Gao Hanlin , Mu Bing , Li Xuejun , Jin Jennifer , Wang Jin-hui , Guo Chao , Chen Zhuo , Weiss Lawrence 
Published: February 2011

Abstract
Introduction: MicroRNA (miRNA) is a group of small non-coding regulating RNA and has shown altered expression in cancer. With great advantages in test specificity and capability to detect novel (unknown) miRNA and other small RNA targets, the next-generation deep sequencing technology is replacing microarray platforms, at least in the discovery phase. Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney malignancies and one of the leading causes of death. Characterizing miRNA expression of ccRCC will enhance the understanding of its tumorigenesis and progression and will, therefore, lead to the development of cancer-specific molecular therapy. In this study, we analyzed miRNA expression using a human ccRCC cohort by whole genome small RNA deep sequencing. We characterized the miRNA expression in association with CCRCC and further validated the altered miRNA expression in a larger clinical cohort by RT-PCR. A group of tumor associated novel miRNAs have been discovered.
Design: (1) Deep sequencing of whole genome small RNA (17-52 nucleotides in size) in a 6-sample frozen CCRCC cohort (3 benign and 3 ccRCC samples) using Illumina system (Solexa) was performed. (2) The miRNA expression of benign kidney and ccRCC samples was quantitatively compared. (3) 8 miRNAs, which were randomly selected from the list of top 20 aberrantly expressed miRNAs detected by deep sequencing, were tested using ABI RT-PCR technology in a 38-sample ccRCC cohort (9 benign kidney and 29 different stage ccRCC samples) for validation. (4) Analysis of unknown small RNAs was performed to find tumor associated novel miRNAs.
Results: (1) Using a deep sequencing technology, we detected miRNAs and other small RNAs in frozen human samples of ccRCC cohort and successfully profiled miRNA expression in association with tumor. (2) We validated the altered expression of 8 selected miRNA targets in the 38-sample clinical ccRCC cohort using an RT-PCR method. (3) We discovered a group of novel miRNAs associated with ccRCC.
Conclusions: We performed whole genome small RNA deep sequencing of human ccRCC tissue with further RT-PCR validation in a clinical sample cohort. We have characterized miRNA expression and discovered a group of novel miRNAs in association with ccRCC.
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 LB-356.