bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4437: HSA coated iron oxide nanoparticle as a drug delivery vehicle for cancer therapy
Authors: Chen Xiaoyuan , Quan Qimeng , Xie Jin 
Published: June 2012

Abstract
An on-going effort in the field of nanomedicine is to develop nanoplatforms with both imaging and therapeutic functions, the so-called “nano-theranostics”. We have previously developed a human serum albumin (HSA) coated iron oxide nanoparticle (HINP) formula and used multiple imaging modalities to validate its tumor targeting attributes. In the current study, we sought to impart doxorubicin (Dox) onto the HINPs and to assess the potential of the conjugates as theranostic agents. In a typical preparation, we found that about 0.5 mg of Dox and 1 mg of iron oxide nanoparticles (IONPs, Fe content) could be loaded into 10 mg of HSA matrices. The resulting Dox-loaded HINPs (D-HINPs) retained a tumor targeting capability, as manifested by both in vivo MRI and ex vivo immunostaining studies. For therapeutic studies, 25 4T1 tumor mice were divided into 5 groups (5 mice/group), and were treated with 1) D-HINPs (3 mg Dox/kg); 2) free Dox (3 mg Dox/kg); 3) Doxil (3 mg Dox/kg); 4) HINPs and 5) PBS. For Group 4, HINPs were injected at the same Fe concentration as in Group 1. The drugs (including controls) were given every other day for a total of 4 doses. A dramatic increase in tumor volume was found in the PBS control group. The group injected with HINPs manifested a tumor growth pattern that was similar to the PBS group and showed no weight loss throughout the treatment, indicating that the HINPs alone had neither therapeutic nor toxic effects in the studied mice. Compared with the control group, the injection of Dox led to some tumor suppression in the first week of treatment but gradually lost efficacy. D-HINPs showed a striking tumor suppression effect that was comparable to Doxil and that greatly outperformed free Dox. Such a strategy can be readily extended to load other types of small molecules, making HINP a promising theranostic nanoplatform.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4437. doi:10.1158/1538-7445.AM2011-4437
Abstract 444: Subpopulations of circulating microvesicles have different microRNA profiles
Authors: Deng Ta , Spetzler David B. , Holterman Daniel , Pawlowski Traci , Duncan Janet E. , Smith Shannon E. , Radebach Katrina , LIttle Tanya , Kuslich Christine D. 
Published: June 2012

Abstract
The purpose of this study was to determine if circulating microvesicle (cMV) subpopulations as defined by surface protein composition also exhibit distinct microRNA (miR) expression patterns. Circulating microvesicles isolated from a prostate cancer cell line (VCaP) were sorted based on their surface protein composition and were evaluated for differential expression of miRs. Phycoerythrin-labeled antibodies targeting EpCam, CD63, or B7-H3 were used to sort the subpopulations of cMVs by fluorescence-activated cell sorting. The sorted subpopulations of cMVs were subsequently profiled by miR expression. The miR profiles for the EpCam-, CD63-, and B7-H3-positive subpopulations were compared with the profile of the total VCaP cMV population. Differential miR expression patterns were observed across the subpopulations, and all expression patterns were distinct from that observed in the total population. Patterns of both over- and under-expression were seen. Not only can subpopulations of cMVs be distinguished and separated based on surface protein markers, but they can also be differentiated based on their RNA content, in this case miRs. The ability to isolate tissue-specific cMV populations from patient plasma based on surface protein composition and then analyze them based on both surface protein composition and genetic content has considerable diagnostic, prognostic, and theranostic implications.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 444. doi:10.1158/1538-7445.AM2011-444
Abstract 4444: Targeted delivery of siRNAs to tumor cells and the tumor microenvironment
Authors: da Silva Lígia Catarina Gomes , Ramalho José , Lima Maria Conceição Pedroso , Simões Sérgio , Moreira João Nuno 
Published: June 2012

Abstract
The limited effectiveness of conventional treatment strategies has generated considerable interest on the development of new types of anticancer agents, with improved molecular target specificity. In this context, gene silencing technology constitutes such new class of anticancer agents. The identification of activated oncogenes, as fundamental genetic differences relative to normal cells has made it possible to consider such genes as targets for antitumor therapy.
A tumor is an organ, not a single cell type, which encompasses multiple cell types, each one contributing to the overall tumor aggressiveness. It is now recognized that novel therapeutic strategies should envisage the simultaneous inhibition of multiple targets or pathways, at different cell levels within a tumor, that regulate processes promoting tumor development.
The main goal of this work was to design a novel ligand-mediated targeted lipid-based nanocarrier, containing a nucleic acid (siRNA), aiming at targeting, simultaneously, human breast cancer and endothelial cells from angiogenic vessels.
We have been able to develop a novel ligand-targeted sterically stabilized lipid-based nanoparticle with adequate features for systemic administration: it is characterized by high siRNA encapsulation efficiency, efficient protection of siRNA, average size around 200 nm, and charge close to neutrality.
Our results have shown that the covalent attachment of a specific ligand at the extremity of poly(ethylene glycol) chains, brings a major advantage as it significantly improves the internalization of the lipid-based nanoparticle by both human cancer cells (MDA-MB-435 and MDA-MB-231) and endothelial cells from angiogenic blood vessels (HMEC-1). Moreover, it was not observed a significant internalization by the non-transformed cell line, BJ fibroblasts, indicating the cellular specificity of the developed targeted nanoparticle.
In order to evaluate the potential of the developed targeted nanoparticle to silence a target gene, the green fluorescent protein (GFP)-overexpressing MDA-MB-435 cells were used. A specific downregulation of GFP, both at the protein and mRNA levels, was further observed with the targeted nanoparticle when compared with the non-targeted counterpart.
As the developed nanoparticle is adequate for the encapsulation and delivery of any siRNA sequence, studies with a siRNA targeting a validated molecular target are now ongoing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4444. doi:10.1158/1538-7445.AM2011-4444
Abstract 4448: Rational design of a novel nanocarrier for doxorubicin delivery in cancer treatment
Authors: Luo Juntao , Xiao Kai , Lee Joyce S. , Li Yuanpei , Lam Kit S. 
Published: June 2012

Abstract
Doxorubicin is a very important anti-cancer drug and is currently being used in the treatment of many hematologic malignancies and solid tumors. There is a great need to develope a more effective nanoformulation of doxorubicin that can overcome cardiotoxicity of doxorubicin, as well as the problems associated with Doxil (PEGylated liposomal doxorubicin): large particle size, therefore unable to penetrate deep into the tumor, foot and hand syndrome, and myelotoxicity. We have recently developed a novel biocompatible telodendrimer (PEG block dendritic oligomer of cholic acids), which can self-assemble into stable micelles (∼50 nm) in water when mixed with a hydrophobic drug, such as paclitaxel, with high loading capacity. However, the doxorubicin delivery using this formulation suffers from lower drug loading capacity, less stability and series hemolytic properties. We have optimized the structure of the telodendrimer via introducing the specific building blocks, which has strong interactions with doxorubicin through TT- TT interaction and the hydrogen bonding. The engineered telodendrimer showed better doxorubicin drug loading capacity (4 mg/mL) and greater physical stability (18 nm, stable &gt;3 months) compared with the original formulation. Nanocarrier is nontoxic in cell culture even at &gt;1 mg/mL concentration. The doxorubicin-loaded formulation exhibited the similar potency as the free doxorubicin and Doxil in killing of cancer cells in the cell culture. This engineered formulation after loaded with doxorubicin can completely avoid the hemolysis in the in vitro red blood cell incubation. The in vivo biodistribution and the in vivo antitumor efficacy of this novel DOX-nanotherapeutics will be further studied in the animal models.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4448. doi:10.1158/1538-7445.AM2011-4448
Abstract 4450: Cisplatin intercalated zirconium phosphate nanoparticles are cytotoxic to MCF-7 breast cancer cells via apoptosis
Authors: Gonzalez Millie L. , Ortiz Mayra , Baez Adriana 
Published: June 2012

Abstract
Purpose: Nanoparticle-mediated drug delivery has great potential for anticancer therapy. The purpose of this study was to determine the effectiveness of zirconium phosphate (ZrP) nanoparticles as carrier of the cytotoxic drug cisplatin in MCF-7 breast cancer cells.
Methods: Cytotoxicity of ZrP, ZrP:cisplatin, and cisplatin were studied using the MTT Assay. Cell cycle analyses and apoptosis were analyzed using flow cytometry technology.
Results: ZrP nanoparticles were not cytotoxic to MCF-7 cells. However, cell viability was reduced to 70% when MCF-7 cells were grown with ZrP: cisplatin 100μM. Cisplatin was cytotoxic to MCF-7 cells with an IC50 of 10 μM. The cytotoxic effect of cisplatin: ZrP is mediated by induction of apoptosis. AnnexinV/PI treated MCF-7 cells showed the apoptotic events in cisplatin -induced apoptosis. ZrP nanoparticles alone did not cause apoptosis to MCF-7 cells or peripheral blood lymphocytes.
Conclusion: ZrP nanoparticles can significantly reduce side effects associated to systemic toxicity of anticancer agents and more studies are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4450. doi:10.1158/1538-7445.AM2011-4450
Abstract 446: Inhibition of peroxisome proliferator-activated receptor-gamma in myeloid lineage cells induces systemic inflammation, immunosuppression and tumorigenesis
Authors: Du Hong , Wu Lingyan , Yan Cong 
Published: June 2012

Abstract
Inflammation is a major mechanism to protect organisms from damage by responding to pathogen infection and tissue injury. However, failure to clear excessive amounts of inflammatory cells, or to control exuberant expression of pro-inflammatory molecules at the inflammatory sites can cause organ damage and cancer. Therefore, it is important to identify anti-inflammatory molecules and pathways that suppress overexpression of inflammatory molecules and eliminate excessive inflammatory cells to prevent chronic inflammation-induced cancer formation. At the cellular level, malformation and malfunction of myeloid cells contribute to inflammation and cancer formation. Peroxisome proliferator-activated receptor-γ (PPARγ) is an anti-inflammatory molecule. In order to study its biological function in myeloid cells, dominant negative PPARγ (dnPPARγ) was overexpressed in a myeloid-specific c-fms-rtTA/(TetO)7-CMV-dnPPARγ bitransgenic mouse model. In this bitransgenic system, overexpression of dnPPARγ-Flag fusion protein in myeloid lineage cells abnormally elevated frequencies and total numbers of LK, LSK, CMP and GMP progenitor populations in the bone marrow. DnPPARγ overexpression led to up-regulation of PPARγ downstream genes IL-1β, IL-6 and TNFα in the blood plasma, which are known to stimulate development and expansion of myeloid-derived suppressor cells (MDSCs). As a result, CD11b+Gr-1+ MDSCs were systemically increased in association with activation of oncogenic intracellular signaling molecules Stat3, NF-κB, Erk1/2 and p38 in doxycycline-treated bitransgenic mice. MDSCs from doxycycline-treated bitransgenic mice strongly inhibited proliferation and function of wild type CD4+ T cells in vitro. CD4+ T cells from doxycycline-treated bitransgenic mice showed much weaker activities of proliferation and lymphokine release function. As a result, both CD4+ and CD8+ T cell populations were decreased in doxycycline-treated bitransgenic mice. The bone marrow transplantation study indicated that the myeloid autonomous defect was responsible for MDSC expansion and immunosuppression. Multiple forms of carcinoma and sarcoma in the lung, liver, spleen and lymph nodes were observed in doxycycline-treated bitransgenic mice. These studies suggest that anti-inflammatory PPARγ in myeloid lineage cells plays a key role in controlling pro-inflammatory cytokine syntheses, MDSCs expansion, immunosuppression and cancer formation. Studies outlined here will have a significant impact on how to design a strategy to combat inflammation-induced cancer and pave the way for novel immunotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 446. doi:10.1158/1538-7445.AM2011-446
Abstract 4466: Characterization of the pan class I PI3K inhibitor NVP-BKM120 mechanism of action across a broad range of concentrations
Authors: Brachmann Saskia M. , Kleylein-Sohn Julia , Gaulis Swann , Stauffer Frederic , Voshol Johannes , Guthy Daniel , Wilson Christopher , Huang Alan , Wartmann Markus , Bruemmendorf Thomas , Chene Patrick , Fritsch Christine , Hackl Wolfgang , Cosaert Jan , Schnell Christian , Hofmann Francesco , Maira Michel 
Published: June 2012

Abstract
NVP-BKM120 is a pan class I PI3K inhibitor that has recently entered phase II clinical trials. The compound was shown to inhibit cell proliferation and survival of cancer models displaying PI3K pathway dependency, in a dose-dependent manner, and proportionally to the extent of pathway inhibition. To further characterize NVP-BKM120, we have investigated its mechanism of action across a broad range of relevant models and concentrations of the molecule and compared it to other PI3K inhibitors (e.g. GDC0941 and ZSTK474). The effects observed on phenotypical read-outs were similar for all compounds, when tested up to concentrations necessary to achieve near complete pathway inhibition (IC90 for Akt-S473P). More profound effects were however observed with NVP-BKM120, at higher concentrations (&gt;2 micromolar), in PI3K-independent models, suggesting that at these dose levels, NVP-BKM120 might display inhibitory activities other than PI3K.
In order to determine this potential off-target activity, a gene expression profiling study was performed in a PI3K insensitive model, comparing effects of GDC0941 and NVP-BKM120 at equipotent concentrations. Gene-Set Enrichment Analysis (GSEA) revealed that NVP-BKM120 at the highest dose only (3.6 micromolar, 2 fold above the S473-Akt IC90 of PI3K sensitive models), led to increased expression of genes involved in G2 and mitotic (M) phases. Subsequent FACS analysis showed that in contrast to the other pan-PI3K inhibitors, NVP-BKM120 was indeed able to induce a strong G2/M arrest in several PI3K non addicted cell lines when used at concentrations higher than 2 micromolar. DAPI and tubulin immuno-histochemistry studies showed that the NVP-BKM120 induced block was phenotypically similar to that of Nocodazole, suggesting effects on spindle dynamics in prometaphase. Indeed, in cellular or in in vitro purified systems, NVP-BKM120 greatly reduced microtubule polymerization.Based on analysis the antitumor activity observed in vivo in PI3K-dependent animal models, it appears that efficacy is solely due to pure PI3K inhibition, as these off-target activities are generally observed at concentrations (corrected for free fraction) that could not be achieved in animals. Based on modeling of human PK data, a similar conclusion can be reached for patients, as the exposure currently observed in plasma does predict sole coverage of PI3K inhibitory activities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4466. doi:10.1158/1538-7445.AM2011-4466
Abstract 447: A mechanism of hypoxia-induced immune escape in cancer cells
Authors: Hamilton Thomas K. , Barsoum Ivraym , Li Xin , Miles Ellen A. , Elliott Janet , Siemens D. Robert , Graham Charles H. 
Published: June 2012

Abstract
We previously showed that hypoxia induces resistance to natural killer (NK) cell-mediated lysis in tumor cells through a mechanism that involves the shedding of NK cell-activating ligands (MICA) from the cell surface. Furthermore, we were able to block this hypoxia-induced shedding of MICA, as well as resistance to NK cell-mediated lysis, by activating NO signaling in the cancer cells. The objective of the present study was to fully elucidate this mechanism of hypoxia-induced immune escape. We used siRNA knock-down to determine the role of hypoxia-inducible factor-1 (HIF-1), a transcriptional activator of hypoxia-inducible genes, and ADAM10, a metalloproteinase known to be involved in the shedding of MICA, in the hypoxia-induced immune escape in DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. Our findings revealed that in vitro exposure to hypoxia increases ADAM10 expression in a HIF-1-dependent manner, and that knock-down of ADAM10 abolishes the hypoxia-induced MICA release and resistance to NK cell-mediated lysis. Treatment of the tumor cells with low concentrations of nitroglycerin inhibited the hypoxia-induced accumulation of HIF-1α, ADAM10 up-regulation, the shedding of the NK-activating ligands, and resistance to NK cell-mediated lysis. More importantly, continuous transdermal administration of nitroglycerin (1.8 µg/h) to nude mice attenuated the growth of transplanted human DU145 prostate tumors; however, this effect of nitroglycerin was lost in mice made deficient in NK cells by treatment with anti-asialo GM1 antibody. This latter finding indicates that nitroglycerin attenuates tumor growth by sensitizing tumor cells to innate immunity. These findings are important because they indicate that nitric oxide mimetics could potentially be used as immunosensitizers in the treatment and/or prevention of cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 447. doi:10.1158/1538-7445.AM2011-447
Abstract 4473: Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model
Authors: Feng Yu-Xiong , Zhao Jiang-Sha , Li Jing-Jing , Xie Dong 
Published: June 2012

Abstract
Surgical resection is the first-line treatment for hepatocellular carcinoma (HCC) patients with well-preserved liver function. Nevertheless, postoperative recurrences occur up to 70% at 5 years, gravely jeopardizing the therapeutic outcome. Clearly, new approaches are needed for preventing relapse of this deadly disease. Taking advantage of a luciferase-labeled orthotopic xenograft model of HCC, we examined the role of Sorafenib, the first approved systemic drug for advanced HCC patients, in prevention of HCC recurrence. We found that Sorafenib suppressed the development of postsurgical intrahepatic recurrences, as well as abdominal metastasis, consequently leading to a prolonged postoperative survival of mice in this model. Furthermore, hyperactivity of ERK signaling caused by elevated levels of growth factors associated with postoperative liver regeneration enhanced the sensitivity of HCC cells to Sorafenib, providing a plausible explanation to the observation that recurrent tumors are more responsive to growth inhibition by Sorafenib. Our results strongly suggest a potential application of Sorafenib in early stage HCC patients who have received hepatectomy with curative intention, by effectively reducing postoperative recurrences.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4473. doi:10.1158/1538-7445.AM2011-4473
Abstract 4474: Cellular effects of fluorescent quinolinium drugs on normal lymphoblast and A431 carcinoma cells
Authors: Velez Christian , Molina Denisse , Rosado Carlos , Cox Osvaldo , Zayas Beatriz 
Published: June 2012

Abstract
This study aims to evaluate the cellular effects of amino benzazolo [3,2- a] quinolinium drugs on normal lymphoblast cells and compare them to effects on A431 epitheloid carcinoma cells. The drugs under study are amino containing heterocyclic compounds possessing a positive charge that could facilitate their interaction with cell organelles specially mitochondria. The fluorescent properties could also facilitate observation of their cellular binding location. These compounds have also been demonstrated to have mutagenic and DNA binding capacity on A431 cancer cells. A431 and TK6 cells in culture where exposed for 48 hours to determine the IC50 dose, mitochondrial membrane permeability, ROS generation and fluorescent microscopy analysis of intracellular binding. IC50 was determined by trypan blue exclusion and mitochondrial membrane permeability applying the Nucleo counter 3000, JC-1 assay. For ROS determination the fluorescent dye 2,7-dichlorofluorescein diacetate (DCFH-DA) was applied. Determination of intracellular binding was performed applying confocal microscopy. In the TK6 normal lymphoblast cells the observed IC50 concentrations were as follow: ABQ38=310µM, and ABQ95=270µM. On A431 IC50s were as follows: ABQ38 = 32 µM and ABQ95 = 36 µM. Overall, normal TK6 demonstrated higher tolerance to the tested ABQS than A 431. Preliminary results on ROS generation indicated a stronger ROS release on A431 than on TK6 lymphoblast. Analysis of the effects of ABQS on the mitochondrial permeability where also consistent with the cytotoxicity observed, demonstrating higher levels of membrane permeability on treated tumor cells than on normal. Microscopy images of ABQS treated cells revealed location of these fluorescent compounds in organelles such as mitochondria and DNA. DNA fragmentation analyses are being implemented. This study presents preliminary evidence of an overall higher tolerance of normal TK6 lymphoblast to the tested fluorescent drugs in comparison to treated A431.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4474. doi:10.1158/1538-7445.AM2011-4474