bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5514: Targeted liposomes in cancer therapy
Authors: Mulamalla Hari Chandana R. , Lambros Maria P. , Huang Ying 
Published: February 2011

Abstract
The purpose of this project was to design a liposomal formulation which targets the SLC transporter. Daunorubicin, an anticancer drug, used as a model was encapsulated in the targeted liposomal formulation and the cellular uptake and cytotoxicity of targeted liposomal daunorubicin (TLD) as well as the mechanisms of cellular uptake were evaluated using the A549 lung cancer cell line. A quantity of 3×105/2ml cells of A549 were cultured in each well of 6 well plates in RPMI medium. The cells were treated with TLD, non targeted liposomal (NTL) daunorubicin and free, non-encapsulated daunorubicin containing 10µM and 5µM drug. They were incubated for 5-6 hours at 37oC and analyzed using flow cytometry and fluorescence imaging. The cytotoxicity of the formulations was determined using MTS assay. The IC50 was determined from the growth inhibition curves of cell viability. Furthermore, the mechanism of internalization of the TLD formulation was studied using inhibitors specific to each pathway of internalization. The results show that the cellular uptake TLD showed a significant increase of 2- fold compared to that of NTL and free drug for both concentrations (10µM and 5µM). These results were also consistent with the cytotoxicity study showing higher cytotoxicity of TLD compared to NTL and free drug, The IC50 of TDL showed a 2.3-fold and 3.4-fold decrease compared to NTL and free drug, respectively. Also the data showed decrease in the cellular uptake of TLD when the macropinocytosis pathway was inhibited. Depletion of cholesterol in the cellular wall also reduced the cellular uptake of the TLD formulation. The results indicate that our novel targeted liposomal formulation shows enhanced cellular uptake and cytotoxicity likely due to macropinocytosis.
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 5514.
Abstract 5515: Design and synthesis of releasable folate-drug conjugates possessing optimized carbohydrate-based spacer units
Authors: Vlahov Iontcho R. , Santhapuram Hari Krishna R. , Wang Yu , You Fei , Kleindl Paul J. , Fan Mingjin , Vaughn Jeremy F. , Han Spencer J. , Leamon Christopher P. 
Published: February 2011

Abstract
The spacer region of releasable folate-drug conjugates may play an important role in “tailoring” the properties of the molecules for targeted therapies by: 1) modulating the affinity toward the folate receptor, 2) providing desirable hydrophilicity, and 3) changing dramatically the biological properties. Herein we describe the design and synthesis of a variety of novel carbohydrate-based spacers mimicking a peptidic backbone. After carefully optimizing the chemical structure of the carbohydrate units, we incorporated such spacers in a folate-containing molecular systems using standard solid phase synthesis (SPS). The synthetic utility of this elegant and innovative approach was exemplified by creating novel releasable folate conjugates of single cytotoxic agents, e.g. Tubulysin-Folate conjugate (currently in preclinical development) and Vinblastine-Folate conjugate, (already in clinical development). Furthermore, using the same powerful method, we synthesized several constructs containing a rational combination of two drugs (e.g. Vinblastine and Doxorubicin) attached to a single folate-targeting ligand via a dual-headed releasable Spacer-Linker system.
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 5515.
Abstract 5526: Development of dithiocarbamate/metal complexes in Pluronic® micelles for the treatment of malignancies
Authors: Rudrapatna Venkatesh K. , Kosak Ken M. , Terrazas Moises C. , Kennedy Thomas P. , Shami Paul J. 
Published: February 2011

Abstract
Dithiocarbamate/metal complexes are potently cytotoxic towards malignant cells of different tissues of origin. We synthesized DETC/Cu, a chelate of diethylthiocarbamate (DETC) and copper (Cu2+). We formulated DETC/Cu in P123 Pluronic® micelles and studied its in vitro anti-cancer activity against the following human cancer cell lines: HL-60 (acute myeloid leukemia), PPC-1 (prostate cancer), HEP-3B (hepatocellular carcinoma) and DLD-1 (colon cancer). Controls were treated with empty P123 Pluronic® micelles. Cells were cultured with varying concentrations of the drug for 24 hrs, 48 hrs and 72 hrs upon which cell growth was measured using an MTS cell proliferation assay. DETC/Cu inhibited growth in vitro at submicromolar concentrations. The 50% growth inhibitory concentration (IC50) was 0.015 μM, 0.023 μM, 0.10 μM and 0.19 μM for HL-60, PPC-1, HEP-3B and DLD-1 cells, respectively. We also performed caspase activity assays at various time points and concentrations using the DETC/Cu. At concentrations of 0.25 μM, 0.5 μM and 1 μM DETC/Cu increased caspase 3 activity after three hours by 162, 265 and 318 percent over baseline, respectively. At the same concentrations and time point, DETC/Cu increased caspase 8 activation by 97, 97 and 82 percent over baseline, respectively. At the same concentrations and time point, DETC/Cu increased caspase 9 activity by 128,164, and 178 percent over baseline, respectively. These results demonstrate that DETC/Cu activates both the intrinsic and the extrinsic apoptosis pathways.
In another experiment, the effect of DETC/Cu chelates on leukemia cell growth in vivo was studied. NOD/SCID IL2Rγnull mice were implanted bilaterally in the flanks with HL-60 cells. When tumors became palpable, treatment was started with DETC/Cu formulated in P123 Pluronic® micelles and administered intravenously every other day at a dose of 2 μmol/kg. There were 4 mice in each treatment group (Pluronic® P123 micelle control and DETC/Cu in P123 micelles). The experiment was terminated at day 15. At that point 3 out of 4 control animals had died and the one remaining alive had tumor volumes that had exceeded 10% of initial body weight. Tumor volumes were decreased by 22 and 33% in DETC/Cu-treated animals as opposed to vehicle controls on days 12 and 15, respectively. At the time of termination of the experiment, none of the animals treated with DETC/Cu had died.
These results demonstrate that dithiocarbamate/metal complexes hold great promise for medicinal development as anti-cancer 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 5526.
Abstract 5549: p53-independent radiosensitization of lung cancer cells by inhibition of mTOR pathway
Authors: Nagata Yoko , Tojo Takashi , Ota Ichiro , Ohnishi Ken , Takahashi Akihisa , Ohnishi Takeo , Taniguchi Shigeki 
Published: February 2011

Abstract
A high extent of activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and mutations in the p53 gene are involved in lung cancer therapeutic resistance. The mammalian target of rapamycin (mTOR) acts as a downstream effector for Akt and activation of the Akt/mTOR signal is a contributing factor to decreased radiation sensitivity. The aim of this study was to examine whether the effect of rapamycin on radiation sensitivity is affected by cellular p53 gene status in two human non-small cell lung cancer (NSCLC) cell lines with the same genetic background except for their p53 gene status (H1299/wtp53 and H1299/mp53). Cellular radiation sensitivity was evaluated with colony formation assays and apoptosis assays, using Hoechst33342 staining. Rapamycin synergistically enhanced the cytotoxicity of radiation regardless of p53 gene status, and promoted the induction of apoptosis. Moreover, the combined treatment augmented the cytostatic effects of radiation independently of cellular p53 gene status. In agreement with this result, cell cycle analysis by flow cytometry showed increased G1 arrest and suppression of progression to S phase in both cell lines. Western blotting revealed a prominent p53-independent down-regulation of the mTOR signal and pro-survival molecule, cyclin D1 after the combined treatment, suggesting that rapamycin can enhance the effect of radiation through the repression of pro-survival signals and the reduction in the apoptotic threshold. This study indicates that inhibition of the mTOR signal may be a promising strategy for radiosensitization with no relevance to p53 gene status from two aspects of cell lethality and cell growth depression.
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 5549.
Abstract 5554: The proteome analysis of human lung adenocarcinoma
Authors: Tei Keikou , Kakehashi Anna , Yamano Shotaro , Wei Min , Nishiyama Noritoshi , Wanibuchi Hideki 
Published: February 2011

Abstract
Lung cancer is the leading cause of cancer death in the worldwide. Despite advances in early diagnostic methods and treatment modarities, lung cancer is often diagnosed at an advanced stage and has a poor prognosis. There is a need for the development of new biomarkers for early detection, defining cancer risk, prognosis, and therapy targets. The purpose of this study was to investigate the molecular background of lung carcinogenesis and to search useful biomarkers for clinical treatment including early detection and prognosis prediction of lung cancer by performing proteome analysis of human lung adenocarcinoma. Subjects were cases with primary lung adenocarcinoma on which surgical resection was performed. Tumor and adjacent non-tumor tissue sample were collected and proteome analysis was carried out. All through the examined cases, 52 proteins were found overexpressed and 13 proteins localized in extracellular space were detected and these proteins were thought as potential biomarkers associated with lung adenocarcinoma. We noticed one protein of them and performed immunohistochemical staining, 94% of cases were expressed. We assessed the statistical significance of the associations between expression level of this protein and clinicopathologic variables, it was showed that this protein had possibility to be a novel prognosis prediction biomarker of lung adenocarcinoma. This study enables the indentification of biomarker candidates for novel tumor markers and therapetic targets that will eventually lead to early detection, prevention and treatment of 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 5554.
Abstract 5566: Phosphoproteomic profiling of Met / K-Ras signaling in colorectal cancer by label-free LTQ-Orbitrap mass spectrometry
Authors: Organ Shawna L. , Tong Jiefei , Taylor Paul , Navab Roya , St. Germain Jonathan , Moran Michael F. , Tsao Ming-Sound 
Published: February 2011

Abstract
Background: Colorectal cancer (CRC) is the second leading cause of death from cancer overall. Mutations in the K-ras oncogene are the most frequently observed mutations in CRC. Activation of receptor tyrosine kinases, including Met, is also common in CRC. Co-activation of both Met and K-Ras could result in preferential over-activation of specific downstream cascade(s). To address the potential importance of Met and K-Ras tandem activation, we use the DLD1 CRC cell line model. DLD1 cells contain one mutated K-ras allele, resulting in a constitutively active protein. These cells express a relatively low level of Met. A derivative of this cell line, DKO4, has its mutant K-ras allele inactivated by somatic recombination. Our lab has previously shown that overexpression of Met in DLD1 cells (DLD1-Met) enhances the tumorigenicity and metastatic potential of these cells. This did not occur in DKO4-Met cells, suggesting that activated K-Ras is necessary for these Met-mediated processes. We hypothesize that Met and K-Ras co-operate to activate novel tumourigenic and metastatic signaling pathways.
Methods: We undertook a label-free mass spectrometry (MS)-based proteomics examination of protein-phosphotyrosine (pY) in the DLD1 CRC model. DLD1-Met and DKO4-Met cells were enriched for pY-containing peptides and then analyzed by LC-MS/MS using an LTQ-Orbitrap mass spectrometer. Peptide quantification was achieved by using both peptide ion spectral counting and normalized extracted ion current methods. To determine ligand-dependent vs. -independent differences in Met signaling, the parental DLD1 and DKO4 cells were stimulated with an HGF time course. Previous results in the lab show that DLD1 cells with activated K-Ras have prolonged MAPK signaling in response to HGF compared to DKO4 cells.
Results: 9 proteins were found to be differentially regulated in these DLD1-Met vs. DKO4-Met. Validation by Western blotting in the empty vector and Met-overexpressing lines confirmed MS findings, as well as uncovered some pY changes mediated by both Met and K-Ras. Results from temporal analyses of pY in response to HGF stimulation will be presented to address this occurrence and suggest mechanisms of Met and K-Ras dependent tumourigenesis.
Conclusions: We have identified a phosphoproteomic network associated with Met/K-Ras signaling. It may include novel therapeutic targets or prognostic markers for CRC.
Supported by the CIHR MOP-64345 and the CIHR Banting and Best Doctoral Research Graduate Scholarship to SO
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 5566.
Abstract 5569: N-glycosylation in cultured cells and hepatocellular carcinoma
Authors: Brnakova Zuzana , Chandler Kevin B. , Bekesova Slavka , Lenco Juraj , Bebu Ionut , Kosti Ourania , Shetty Kirti , Korba Brent E. , Ressom Habtom W. , Varghese Rency S. , Novotny Milos V. , Goldman Radoslav 
Published: February 2011

Abstract
Purpose: Incidence of hepatocellular cancer (HCC) continues to increase primarily due to hepatitis C viral (HCV) infection. Prognosis and survival of patients is highly affected by the disease stage at the time of diagnosis. Our mass spectrometric study evaluated N-glycans during the progression of HCV infection to cancer. Glycosylation of immunoglobulins and other serum proteins was examined in cultured cells and in serum of patients with hepatocellular carcinoma. Methods and Results: Protein associated N-glycans were released with PNGaseF and analyzed by MALDI-TOF/TOF analysis following solid phase permethylation. Analysis of less than 0.04 ml of serum led to relative quantification of 70 N-glycan structures. Immunoaffinity isolation of immunoglobulins and other serum proteins allowed us to study protein-specific glycosylation. Progression of HCV infection to HCC was strongly associated with changes in the glycosylation of immunoglobulins. In a pilot case-control study (25 HCC cases and 35 controls), N-glycosylation of eight glycans was significantly different in HCC compared to chronic liver disease controls. The glycosylation of serum proteins was further compared to the proteins secreted by the Huh-7.5 cell line. Conclusion: This study demonstrates mass spectrometric analysis of 70 N-glycans in serum, cultured cells, and isolated proteins. Our results show that the analysis of permethylated N-glycans helps to define changes associated with the progression of HCV infection to HCC. Evaluation of glycan abundance suggests the potential to use glycans for the detection of liver disease.
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 5569.
Abstract 557: Galectin-3 binding protein produced by neuroblastoma cells stimulates the expression of interleukin-6 in bone marrow mesenchymal cells
Authors: Silverman Ayaka M. , Fukaya Yasushi , Shimada Hiroyuki , Groshen Susan G. , DeClerck Yves A. 
Published: February 2011

Abstract
There is recent evidence that bone marrow-derived mesenchymal cells (BMMC) play an important role in bone metastasis in several cancers, including myeloma and neuroblastoma. We previously reported that in neuroblastoma these cells are a source of interleukin-6 (IL-6) that promotes the growth and survival of neuroblastoma cells and bone degradation. We have recently isolated and identified Galectin-3 binding protein (Gal-3BP) as a soluble factor produced by a neuroblastoma cell line as a factor upregulating the production of IL-6 by BMMC. Here we document the production of Gal-3BP in several neuroblastoma cell lines, in particular those without MYCN amplification that correlates with their ability to induce the production of IL-6 in BMMC. The stimulation of IL-6 by Gal-3BP is mediated by Gal-3, a multifunctional glycoprotein that binds Gal-3BP and is present in BMMC. It is also dependent on the activation of the Ras/Raf/MEK/ERK1/2 pathway by Gal-3BP/Gal-3 and is blocked by the ERK1/2 inhibitor PD980559. Transcriptional activation of IL-6 by Gal-3BP/Gal-3 requires a 115 bp region (−97 to −212) in the IL-6 promoter that contains recognition motifs for a cAMP responsive element binding protein (CREB) and a CCAAT/enhancer binding protein (C/EBP). The expression of Gal-3BP was also examined by immunohistochemistry in 38 primary neuroblastoma tumors with (n=9) and without (n=29) MYCN amplification. This analysis revealed that Gal-3BP is paradoxically more abundant in MYCN non-amplified tumors. This unanticipated observation suggests a significant difference in the Gal-3BP/Gal-3/IL-6 pathway between subgroups of neuroblastoma tumors.
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 557.
Abstract 5572: Analysis of changes in RTK phosphorylation using microplate-based antibody arrays
Authors: Finkel David J. , Johnson Wade M. , Johnson Wade M. , Buehl Christopher J. , Coleman Rebecca A. , Campos Maria T. , Luhowskyj Stefan M. , Boldin Kristina M. , Stoesz Steven P. , Campos-Gonzalez Roberto , Krzyzek Richard A. , Brumbaugh Kathryn M. 
Published: February 2011

Abstract
Receptor-tyrosine kinases (RTKs) are transmembrane proteins that have been implicated in various cancers and are considered therapeutic targets. The phosphorylation of RTKs on tyrosine residues leads to their activation. Therefore, methods to identify the effect of RTK inhibitors or modifying antibodies on RTK phosphorylation are effective tools for drug screening. The Proteome Profiler 96 Human Phospho-RTK Antibody Array is a unique and powerful, plate-based multiplex immunoassay that utilizes ELISA techniques to measure changes in the phosphorylation of multiple RTKs simultaneously. In this assay, antibody/antigen reactions take place on the surface of a microplate that has been pre-spotted with antibodies against each RTK. Each spot corresponds to a unique analyte. A horseradish peroxidase-conjugated anti-Phospho-Tyrosine detection antibody is subsequently added to each well. A chemiluminescent substrate mix and a camera imaging system are used to determine the relative amount of analyte bound in individual spots. Experiments were performed by incubating the MDA-MB-453 breast cancer cell line with specific kinase inhibitors or with antibodies to ErbB receptors prior to NRG1-
β1/HRG1-
β1 treatment. Cells were lysed directly in 96-well plates and transferred to the Proteome Profiler 96 Human Phospho-RTK Array for analysis. NRG1-
β1/HRG1-
β1-dependent tyrosine phosphorylation of all four ErbB receptors was monitored simultaneously and the effects of different kinase inhibitors or modifying antibodies were determined. Proteome Profiler 96 Antibody Arrays offer the advantages of small sample and volume size requirements with as little as 5
μg of total cellular protein in a total volume of 100
μL being required, while still offering the specificity and sensitivity of sandwich immunoassays.
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 5572.
Abstract 5575: Mass spectrometry analysis of the posttranslational modifications of alpha-enolase from pancreatic ductal adenocarcinoma cells
Authors: Zhou Weidong , Capello Michela , Fredolini Claudia , Novelli Francesco , Liotta Lance A. , Petricoin Emanuel F. 
Published: February 2011

Abstract
Enolase is one of the most abundantly expressed cytosolic proteins in many organisms, and it is a key glycolytic enzyme that catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate. Recently, accumulating evidence revealed that, in addition to its innate glycolytic function, the well characterized old enzyme enolase is a multifunctional protein and plays an important role in several biological and pathophysiological processes: 1) by using an alternative start codon, the α-enolase mRNA can be translated into a 37 kDa protein which lacks the first 96 amino acid residues. This protein is localized in the nucleus and can bind to the c-myc P2 promoter and negatively regulate transcription of the proto-oncogene; 2) α-enolase has been detected on the surface of hematopoietic cells such as monocytes, T cells and B cells, neuronal cells and endothelial cells as a strong plasminogen-binding receptor, modulating the pericellular and intravascular fibrinolytic system. The expression of α-enolase on the surface of a variety of eukaryotic cells has been found to be dependent on the pathophysiological conditions of these cells, however, how α-enolase is displayed on the cell surface remains unknown; 3) increased expression of enolase has been reported to correlated with progression of tumors, such as neuroendocrine tumors, neuroblastoma and lung cancers, and enolase has been considered to be a diagnostic marker for many tumors. Our previous studies demonstrated that α-enolase is up-regulated at both the mRNA and protein levels in pancreatic ductal adenocarcinoma (PDAC). PDAC is the fourth leading cause of cancer-related deaths in Western countries. The mean life expectancy is 15-18 months for patients with local and regional disease, and only 3-6 months for those with metastatic disease. In this present work, we further characterized the α-enolase from PDAC by reversed-phase liquid chromatography nanospray tandem mass spectrometry (LC-MS/MS) analysis and an LTQ-Orbitrap instrument, and identified multiple posttranslational modifications of α-enolase, such as phosphorylation, acetylation, and methylation. The mass spectrometer LTQ-Orbitrap provides high accuracy mass measurement that is essential for the validation of modified peptide identifications and the reduction of false positive identifications.
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 5575.