bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 568: Biomarkers of phenethyl isothiocyanate-mediated mammary cancer prevention in MMTV-neu mouse model
Authors: Singh Shivendra V. , Kim Su-Hyeong , Sehrawat Anuradha , Arlotti Julie A. , Sakao Kozue , Lee Joomin , Chandra-Kuntal Kumar , Hahm Eun-Ryeong 
Published: August 2012

Abstract
Biomarker(s) predictive of efficacy is necessary for clinical development of promising cancer chemopreventive agents because cancer incidence is too rigorous of an end point for malignancies with long latency such as breast cancer. The present study was undertaken to identify biomarker(s) associated with phenethyl isothiocyanate (PEITC)-mediated mammary cancer prevention in MMTV-neu transgenic mouse model. The PEITC is a promising cancer chemopreventive constituent of cruciferous vegetables (e.g., watercress). Two-dimensional gel electrophoresis-mass spectrometry of tumor specimens from control and PEITC-fed mice (n= 3) revealed alterations in expression of several proteins, including hexokinase-1, isoform CRA_f (1.36-fold increase by PEITC administration), L-lactate dehydrogenase A chain isoform 1 (1.57-fold increase by PEITC administration), pyruvate kinase isozymes M1/M2 (1.33-fold decrease by PEITC administration), and mitochondrial ATP synthase, H+ transporting F1 complex beta subunit (1.38-fold decrease by PEITC administration). Interestingly, the PEITC-induced apoptotic cell death in cultured cancer cells is associated with inhibition of oxidative phosphorylation leading to production of reactive oxygen species. Down-regulation of mitochondrial ATP synthase protein in tumors of PEITC-fed mice was confirmed by immunohistochemistry. Expression of mitochondrial ATP synthase was reduced by about 66% in the tumors from PEITC-fed mice in comparison with control (P= 0.05 by two-sided Student's t-test, n= 6-7). In addition, plasma level of transthyretin was significantly higher in the PEITC treatment group compared with control (P= 0.04 by two-sided Student's t-test, n= 5). In conclusion, the present study not only underscores the power of proteomics in cancer chemoprevention research but also suggests that mitochondrial ATP synthase, and possibly hexokinase-1, pyruvate kinase isozymes M1/M2, and/or L-lactate dehydrogenase A chain isoform 1, may be useful biomarkers to assess the biological activity of PEITC in future clinical trials. This study was supported in part by the US PHS grants CA101753 and CA129347, awarded by the National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 568. doi:1538-7445.AM2012-568
Abstract 5681: A high throughput soft agar assay on a panel of 60 tumor cell lines to study compounds for potential anti-oncogenic properties
Authors: Weber Holger , Mueller Melanie , Ehlert Jan E. 
Published: August 2012

Abstract
In the course of drug development, analysis of cellular efficacy represents a critical stage before drugs proceed into in vivo studies. For anti-cancer drugs, one method of choice is to assess the drug's impact on tumor cell proliferation. Usually proliferation is analysed in 2D format, analysing cell growth on a flat surface. However, accumulating data suggest that cells behave in a more physiological manner when growing in a 3D matrix. In fact, the gold standard for analysing the transformed status of cells is growth in soft agar, a semi-solid medium in which epithelial cells grow in 3D due to their transformation-related anchorage-independent status. In order to allow a more physiological cellular drug screening for proliferation as well as for transformation, we have now established soft agar assays in 96 well format for 60 tumor cell lines derived from solid tumors. Our data show the multitude of outcomes that may be expected from such a comprehensive study, e.g. we present IC50 analyses indicating that the same compound can have seemingly contradictory, i.e. stimulatory as well as inhibitory activity on soft agar growth, depending on concentration and tested cell line. We propose screening of compounds for impact on cellular soft agar growth as a mandatory prerequisite before testing a drug in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5681. doi:1538-7445.AM2012-5681
Abstract 5683: Design and characterization of novel targeted nanoparticle delivery systems for cancer chemotherapy
Authors: Yin Juanjuan , Sneed Kevin Bernard , Zhou Shufeng 
Published: August 2012

Abstract
The success of cancer chemotherapy was considerably hindered by tumor resistance and drug toxicity. A possibly efficient approach to overcoming drug resistance and serious toxicities is the application of targeted nanoparticles linked to or encapsulating cytotoxic drugs. In this study, novel self-assembly targeting supramolecular nanodrug complex was synthesized using αv-intergrin targeting peptidyl cyclodextrins (CyDs) and classic chemotherapeutic drugs used in the therapy of tumor. The targeting supramolecular drug complex were obtained through host-guest interaction between the tripeptide RGD with sequence Arg-Gly-Asp or cyclotripeptide cRGDyk with sequence c (Arg-Gly-Asp-DTyr-Lys) grafting β-cyclodextrin (or γ-cyclodextrin) and a cytotoxic prodrug; the supramolecular drug inclusion are in specific and efficient binding to integrin-expressing tumor cells and would release the chemotherapeutics in a prolonged period. The guest molecule was generated by the reaction of adamantyl chloride and doxorubicin hydrochloride in which the adamantly group acts as a perfect candidate for the host-guest interaction with CyDs. The host moiety was gained through the reaction of mono-6-deoxy-6-(p-tolylsulfonyl)-β-cyclodextrin and the N-terminal of the oligopeptides through nuclephilic reaction. The promising nanodrug complex is expected to offer attractive pharmacokinetic and pharmacodynamic properties for cancer treatment and is undergoing preclinical evaluation using cancer cell lines and nude mouse models.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5683. doi:1538-7445.AM2012-5683
Abstract 5686: Engineering multifunctional nanoparticles to selectively target multiple myeloma cells and overcome cell adhesion-mediated drug resistance
Authors: Kiziltepe Tanyel , Ashley Jonathan D. , Stefanick Jared F. , Alves Nathan J. , Handlogten Micheal W. , Qi Yu Meng , Suckow Mark , Navari Rudolph , Bilgicer Basar 
Published: August 2012

Abstract
In the continuing search for effective treatments for cancer, here we report the rational engineering of a novel multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-cellular-adhesion functionalities to selectively target multiple myeloma (MM) cells and overcome cell adhesion-mediated drug resistance (CAM-DR). Anti-cellular-adhesion evolves as a promising target in oncology. VLA-4-mediated adhesion to the bone marrow extracellular matrix and stromal cells confers MM cells with CAM-DR. In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin conjugates simultaneously to selectively target MM cells and to overcome CAM-DR. Doxorubicin was conjugated to the nanoparticles through an pH-sensitive hydrazone bond to prevent premature release and thus non-specific toxicity. Peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities per nanoparticle. The nanoparticles, which exhibited a size of ∼20nm, were efficiently internalized by MM cells with an optimal peptide valency of 20 per micelle, and induced cytotoxicity to MM cells. Mechanistic studies revealed that nanoparticles induced DNA double strand breaks as evidenced by H2AX phosphorylation, and triggered apoptosis, which was associated with PARP and caspase-8 cleavage. Importantly, multifunctional nanoparticles were more efficacious than doxorubicin in the presence of fibronectin (IC50=0.15±0.04 μM and 0.42±0.09 μM, respectively), and overcame CAM-DR induced by adherence of MM cells to fibronectin. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors, with a ∼10 fold more drug accumulation when compared to doxorubicin, and demonstrated dramatic tumor growth inhibition with much reduced overall systemic toxicity. Taken together, we demonstrate the disease-driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5686. doi:1538-7445.AM2012-5686
Abstract 5690: Validating sigma-2 receptor ligand as a novel tumor-targeted drug delivery agent for treating ovarian cancer
Authors: Zeng Chenbo , Vangveravong Suwanna , Rothfuss Justin M. , Xu Jinbin , Mach Robert H. 
Published: August 2012

Abstract
The sigma-2 receptor is overexpressed in various human tumors. Sigma-2 receptor selective radiotracers have been shown to target various solid tumors in rodents and in human patients using positron emission tomography. Sigma-2 receptor ligands can be internalized into tumor cells by the endocytotic pathway. Therefore, sigma-2 receptor ligands are excellent candidates as tumor-targeted delivery agents when covalently attached to drugs. Smac is a protein released from mitochondria into the cytosol in response to apoptotic stimuli. Small-molecule Smac mimetic compounds (SMC) have been developed by several laboratories as anticancer drugs. In this study we validate sigma-2 ligand as a tumor-targeting drug delivery agent for treating ovarian cancer. We have synthesized sigma-2 ligand-conjugated SMC (SSMC), SW III-123. Our data show that SW III-123 has adequate sigma-2 receptor binding affinities (Kiα2 =190 nM and Kiα1 =2046 nM). SW III-123 exhibits potent antitumor activities with EC50 values at 4.0 μM, 2.3 μM and 2.4 μM in human ovarian cancer cell lines SKOV-3, CaOV-3, and BG-1, respectively. In contrast, unconjugated SMC, SW IV-52s, shows little cytotoxicity in these cell lines (EC50 &gt; 200 μM). These results suggest that the sigma-2 ligand has successfully delivered SMC into ovarian cancer cells. Western blot results show that SW III-123 degrades inhibitor of apoptosis proteins (IAPs), XIAP and cIAP-1, in SKOV-3 cells, possibly by interacting with the baculovirus IAP repeat (BIR) domains of IAPs. SW III-123 cleaves caspase-3, 8, and 9 dose-dependently in SKOV-3 cells, indicating that SW III-123 kills ovarian cancer cells by activating both intrinsic and extrinsic apoptotic pathways. In conclusion, sigma-2 ligand is a promising tumor-targeting drug delivery agent. SSMC will likely offer a novel class of therapeutic drugs for treating ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5690. doi:1538-7445.AM2012-5690
Abstract 5698: Concurrent delivery of paclitaxel and 17-AAG via micellar nanocarriers
Authors: Katragadda Usha , Fan Wei , Tan Chalet 
Published: August 2012

Abstract
Combination therapy of paclitaxel and 17-allylamino-17-demethoxygeldanamycin (17-AAG) had previously been tested in patients with advanced solid malignancies. Owing to the very low aqueous solubility of both drugs, large volumes of organic solvents were employed in the intravenous formulations, which contributed to serious toxicities in cancer patients and consequently restricted the optimal use of these drugs in the clinical setting. The aim of the present study was to develop micellar nanocarriers for concomitant delivery of paclitaxel and 17-AAG without the inclusion of any organic solvent. At clinically relevant concentrations, paclitaxel and 17-AAG were simultaneously loaded into polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) micelles by a dry film method. The physicochemical and biological characteristics of the dual drug-loaded micelles were evaluated in vitro and in vivo. The simultaneous incorporation of paclitaxel and 17-AAG into PEG-DSPE micelles was confirmed by 1H NMR analysis. The drug-loaded micelles had an average diameter of 11 nm with a surface charge at −22 mV. In the presence of 90% serum, the release half-lives of paclitaxel and 17-AAG from PEG-DSPE micelles were 7.1 h and 4.8 h, respectively. Paclitaxel/17-AAG-loaded micelles were as effective in blocking the proliferation of human ovarian cancer SKOV-3 cells as the combined free drugs. When administered intravenously to nude mice bearing SKOV-3 tumor xenografts, paclitaxel/17-AAG-loaded PEG-DSPE micelles resulted in significantly elevated drug concentrations in the blood circulation and tumor tissues, compared to the free drug counterparts. These results suggest that paclitaxel/17-AAG-loaded micelles preferentially accumulate in the tumor tissue via the enhanced permeability and retention (EPR) effect. PEG-DSPE micellar nanocarriers may provide a novel and advantageous delivery approach for paclitaxel/17-AAG combination therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5698. doi:1538-7445.AM2012-5698
Abstract 57: Adipocyte oxidative stress promotes epithelial-mesenchymal transition (EMT) related gene expression and estrogen receptor (ER) negative phenotype in breast cancer cells
Authors: Yao-Borengasser Aiwei , Monzavi-Karbassi Behjatolah , Hedges Rebecca A. , Kieber-Emmons Thomas , Kadlubar Susan A. 
Published: August 2012

Abstract
Epidemiological studies have linked obesity with basal-like breast cancer risk in both premenopausal and postmenopausal women, suggesting that obesity may affect tumor phenotype by skewing the microenvironment toward support of more aggressive tumor cell phenotypes (typically ER/PR−, HER-2−). In order to study the interactions between adipocytes and breast tumor cells, we developed an adipocyte-breast cancer cell co-culture system. The adipocytes SGBS (Simpson-Golabi-Behmel Syndrome) and human ER positive breast cancer MCF7 cells were co-cultured for 24 hours. Following co-culture, the cells from the inserts (MCF7 cells) and wells (SGBS cells) were collected separately and total RNA was then isolated. The mRNA levels of the NADPH oxidase subunit NOX4 and hypoxia-inducible factor 1α (HIF1α) were determined by RT-PCR and normalized to 18S RNA levels. When SGBS cells were co-cultured with MCF7 cells, SGBS NOX4 and HIF1α mRNA levels increased more than 10 fold and 3 fold, respectively, while there were no changes in NOX4 and HIF1α expression detected in co-cultured MCF7 cells. We also compared several epithelial-mesenchymal transition (EMT) process-related gene expression levels. Expression in MCF7 cells of the EMT-inducing transcription factors FOXC2 and Twist1 were increased more than 8 fold and 5 fold respectively, after co-culture with SGBS. E-cadherin mRNA level was decreased 2 fold, while N-cadherin mRNA level was increased more than 6 fold in co-cultured MCF7. We also found that mRNA levels of ER-α were significantly (p&lt;0.05) repressed in MCF7 cells co-cultured with SGBS cells. To explore the mechanism of the effect of adipocyte co-culture on ER expression in breast cancer cells, SGBS cells were transfected with 30nM of siHIF1α for 48 hours before co-culture with MCF7 cells. ER gene expression level did not change in MCF7 cells co-cultured with SGBS cells that had been transfected with siHIF1α. In summary, we have shown that adipocytes and breast tumor cells interact with each other: MCF7 cells increased hypoxia and oxidative stress in SGBS cells, while SGBS increased the expression of EMT-inducing factor genes in MCF7 cells, as well as repressing ER expression. This repression was controlled, at least in part, by HIF1α. These results suggest that hypoxia and oxidative stress from adipocytes can modify ER gene expression and promote EMT processes in breast cancer cells, supporting an important role of obesity in aggressive breast cancer development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 57. doi:1538-7445.AM2012-57
Abstract 5707: The EPR effects of Elastin-like polypeptide of differnt molecular sizes in animal tumor models
Authors: Ryu Jung Su , Raucher Drazen 
Published: August 2012

Abstract
Elastin-like polypeptide (ELP) biopolymers are thermally responsive macromolecular carriers that are soluble in aqueous solution at physiological temperature (37° C), but aggregate when the temperature is raised above its transition temperature (Tt, 42° C). We have developed this carrier system for the delivery of anticancer therapeutic peptides and small molecule drugs, which has the potential to be targeted to the tumor site by applying local hyperthermia. Molecular size is one of the key determinants of trans-vascular transport of therapeutic agents in tumors as it affects not only the retention in the tumor but also the transition temperature of the macromolecule. As an effort to develop the optimal ELP carrier system, three Bac-ELP macromolecular drug carriers with a clinically relevant range of molecular weights (35, 60 and 120kD) were designed. The three sizes of ELP were initially synthesized and modified by the addition of the cell-penetrating peptide Bac on the N-terminus. In order to measure enhanced permeability and retention (EPR) effects of the three sizes of conjugates, we compared the distribution of conjugates in tumors of animals and their pharmacokinetics in the three fluorescently-labeled Bac-ELP constructs. First, we confirmed that the transition temperature of all 3 constructs fall between the ideal concentration ranges of 10 - 40 μM. In distribution studies with tumor-bearing mice, three peptides showed increased uptake in tumors during the initial 8 hours after local hyperthermia was applied, but the elimination patterns from the tumors differed according to size over a 3 day period. Local hyperthermia was found to produce a more prolonged retention of ELP conjugates in tumors except in the 35 kD Bac-ELP (Bac-E80), which was the smallest construct tested. In addition, the pharmacokinetic analysis showed that the two larger polypeptides have long half-lives and increased AUC in comparison with Bac-E80. From all these results, we suggest that the larger ELP conjugates (60 and 120kD) have advantages over 35kD of Bac-E80 in terms of enhanced permeability and retention effects when combined with local hyperthermia.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5707. doi:1538-7445.AM2012-5707
Abstract 5711: Applying new light to the detection and treatment of brain cancers using targeted photodynamic therapy
Authors: Meyers Joseph D. , Broome Ann-Marie , Cheng Yu , Agnes Richard S. , Wang Xinning , Kenney Malcolm E. , Burda Clemens , Basilion James P. 
Published: August 2012

Abstract
Currently, an estimated 11.4 million people in the US have been affected by cancer and this number is expected to double by 2020 as indicated by the NIH NCI in 2006. Each year approximately 20% of these people are expected to die of cancer, with brain cancers among the most deadly. Brain cancer patients have a median life expectancy of only 6-10 months after diagnosis, and those with recurring brain cancer survive less than 20 weeks after any therapeutic regime. Consequently, there is a critical need to develop and improve the detection, diagnosis, and treatment of brain cancers, including gliomas. Theranostic drugs have the potential to do all of these and are becoming lifesaving alternatives. However, the current standard of care suffers from lack of specificity and systemic toxicity, often requiring invasive surgical procedures. These are significant obstacles when dealing with minimizing offsite damage to the healthy brain while maximizing treatment efficacy in the tumor. Our study presents a novel drug delivery platform using targeted-gold nanoparticles (Au NP) to deliver a therapeutic photodynamic therapy (PDT) drug, phthalocyanine 4 (Pc 4), across the blood-brain tumor barrier (BBTB), which allows both detection and treatment of gliomas within mere hours. Targeting Pc 4 to cancer-specific biomarkers concentrates the drug specifically at the brain tumor, significantly reducing collateral damage to healthy brain tissue. Once Pc 4 is delivered, it offers selectivity based on its defined light activation. Our targeted delivery vehicle possesses several advantages over systemic drug delivery: greater control over bioavailability of the drug, controlled release of Pc 4 directly to the site, lower concentration of drug required for PDT effect, and avoidance of systemic drug exposure. The drug delivery mechanism of targeted-Au NP Pc 4 was investigated utilizing in vivo and in vitro fluorescence imaging, immunohistochemistry, elemental analysis, biodistribution studies, and therapeutic efficacy. We are able to target cancer biomarkers specifically, deliver hydrophobic drugs across the BBTB, increase drug accumulation into the tumor, alter drug localization, and enhance PDT killing affect. As a result, this study presents a unique application of PDT to the treatment of brain tumors using photosensitizing drugs like Pc 4.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5711. doi:1538-7445.AM2012-5711