bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 380: Magnetic nanoplatforms for tumor targeting, imaging and energy delivery
Authors: Sridhar Srinivas , Campbell Robert , Nagesha Dattatri , Gultepe Evin 
Published: June 2012

Abstract
We have developed magnetic nano-liposomes (MNL), incorporating superparamagnetic iron oxide nanoparticles (SPION), that are versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MNL are prepared with a formuation of DPPC:DOTAP:CHOL and DOPE-PEG5000. Incorporation of SPIONs results in MNL with mean diameter of 150-250 nm. MNL are easily taken up by B16-F10 melanoma, HUMVEC-D and breast cancer cell lines. They preferentially target the tumor vasculature as shown in a dorsal skin fold chamber using fluorescently labeled MNL. MNL display superparamagnetic response that is essential for magnetic targeting, MR contrast enhancement and magnetic heating.
MNL was administrated to SCID mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre-injection and post-injection MR images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by 111In labeled MNL and amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations.
We have shown that tumor signal intensities in T2 weighted images decreased an average of 20±5% and T2* values decreased and average of 14±7ms in the absence of magnetic targeting. This compares to an average signal decrease of 57±12% and a decrease in T2* relaxation times of 27±8ms with the aid of external magnet showing up to 2-fold greater accumulation by magnetic targeting.
111In radio-labeled MNL have been shown to enable multi-modal imaging in vivo using MRI and SPeCT/CT. The images show that an MNL bolus injected intra-tumorally was retained in the tumor 24 hours after injection. Application of a magnetic field enables redistribution of the MNL in the tumor.
These MNL are also responsive to ac magnetic fields applied using a Copper coil at 360 kHz and 170A driving current. Both hyperthermia (upto 45C) and thermo-ablative temperatures upto 90C were achieved in 10 – 30 minutes ex vivo in buffer. The results indicate high efficiency for magnetic heating using MNL (Specific Absorption Rate ∼ 104 W/kg) and demonstrate the capability to couple ac magnetic fields to MNL to achieve any set of temperatures needed for hyperthermia and thermal ablation.
To date there are no truly theranostic platforms that have been approved for clinical use that combine targeting, thermal heating and MRI imaging capabilities. Existing FDA approved magnetic nanoparticle formulations like ferridex and ferumoxytol, are optimized for MR imaging, and have not been shown to be usable for thermal therapy.The MNL platform is a novel nanoplatform combining multi-modal imaging capabilities, with magnetic targeting and thermal therapy.
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 380. doi:10.1158/1538-7445.AM2011-380
Abstract 4431: Antitumor activity of nanosponge-encapsulated camptotechin in human prostate tumors
Authors: Minelli Rosalba , Cavalli Roberta , Fantozzi Roberto , Dianzani Chiara , Pettazzoni Piergiorgio , Ellis Leigh , Shen Li , Pili Roberto 
Published: June 2012

Abstract
Drug delivery technologies are new and powerful approaches to enhance the pharmacological properties of drugs by improving their availability and stability and by reducing their side effects.
Camptothecin (CPT) is a potent DNA Topoisomerase I inhibitor that presents strong antitumoral efficacy in both hematological and epithelial malignancies. However, its use is limited because of its high degradability and weak solubility. Indeed, the structure of camptothecin presents a lactone ring that is subjected to hydrolysis in physiological conditions with consequent inactivation of the topoisomerase binding activity. In the present study a new formulation of CPT embedded in cyclodextrin-based nanosponges (CN-CPT) has been evaluated in vitro and in vivo on prostate cancer models. CN-CPT manifested a strong antitumoral efficacy revealed by MTT and colony forming assay on hormonal independent PC3 and DU145 cells, significantly higher as compared to the same dose of free CPT. Moreover, cell cycle analysis and annexin V/PI staining showed that CN-CPT treatments induced significant apoptotic cell death at 1 nM (61.7% apoptotic cell death; p&lt;&lt;0.001), where free CTP (4.36% apoptotic cell death) was not effective. The efficacy of CN-CPT has been tested in vivo in PC3 and DU145 xenograft experiments that have confirmed a significant improvement of antitumoral activity of CN-CPT as compared to CPT. To evaluate possible antimetastatic activity of CPT, in vitro experiments of tumor cell adhesion to HUVECs as a model of endothelium and cell motility were performed. Results showed that CN-CPT is effective at lower doses compared to CPT in inducing inhibition of adhesion and motility. In order to evaluate whether androgen receptor signaling could affect the responsiveness to either CPT or CN-CPT the AR expressing murine models of prostate cancer (MYC-AD, PTEN8 and PTEN CAP8) have been used. Results showed that expression of functional AR diminished the efficacy of both C
PT and CN-CPT. However the latter still exerted greater effects compared to CN-CPT. Taken together these results support the use of CPT and the development of nanotechnologies for drug delivery in the treatment of castrate refractory prostate 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 4431. doi:10.1158/1538-7445.AM2011-4431
Abstract 4461: MPT0B098, a novel microtubule inhibitor, displays potent anti-angiogenic activity via destabilizing hypoxia-inducible factor-1alpha mRNA
Authors: Cheng Yun-ching , Liou Jing-Ping , Lai Wen-Yang , Chang Chi-Yen , Pan Wen-Yu , Kuo Ching-Chuan , Chang Jang-Yang 
Published: June 2012

Abstract
Identification of a single agent that is able to target tumor cells, rapidly destroy tumor vasculature and inhibit angiogenesis could be an ideal approach for targeting solid tumors. We recently discover a novel sulfonamide compound, 7-aryl-indoline-1-benzene-sulfonamide (MPT0B098), as a potent microtubule inhibitor through binding to the colchicine binding site of tubulin. MPT0B098 is active against various human cancer cell growth with IC50 values ranged from 70-300 nM. Notably, HUVEC cells exhibit less susceptibility to the inhibitory effect of MPT0B098 with an IC50 of 510 nM. In addition, MPT0B098 exhibits no cross resistance with vincristine, paclitaxel, etoposide and camptothecin-resistant cell lines. Interestingly, MPT0B098 is still active toward cells (KB L30) with beta1-tubulin mutation. MPT0B098 arrests cells in G2/M phase and subsequently induces cell apoptosis through the caspase-dependent apoptotic pathway. In addition, using sub-lethal dose, MPT0B098 effectively suppressed to the tube formation and migration of HUVECs induced by VEGF. The expression levels of HIF-1alpha and VEGF were significantly inhibited in a concentration-dependent manner by MPT0B098 under hypoxic condition. Furthermore, HIF-1alpha-regulated genes, including cathepsin D, PDGF, VEGF, and VHL, were found to be down-regulated by MPT0B098 in A549 cells. Moreover, the decrease of the amount of HuR, a HIF-1alpha mRNA stability protein, translocated from nuclear to cytoplasm and suppression of AKT activity were coincided with decreased amount of HIF-1alpha mRNA by MPT0B098 treatment under hypoxia condition. MPT0B098 significantly suppressed tumor growth and microvessel density of tumor in H460 and KB-Vin10 xenografted mouse model. Taken together, our results indicate that MPT0B098 is a promising anticancer drug with potential for the treatment of human malignancies. (The study was supported by grants of DOH99-TD-C-111-004 from Department of Health and CA-099-PP-02 from National Health Research Institutes, Taiwan, R.O.C.)
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 4461. doi:10.1158/1538-7445.AM2011-4461
Abstract 4585: Targeting of CD5 on chronic lymphocytic leukemia cells with antibody mixtures
Authors: Klitgaard Josephine L. , Geisler Christian , Pedersen Mikkel W. 
Published: June 2012

Abstract
Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia found in adults in Western countries. Approximately 2 out of every 100,000 people develop CLL annually, with 90% being older than age 50. CLL arises from accumulation of CD5+ B lymphocytes. CLL cells have defective apoptotic pathways and are characterized and distinguished from other leukemic cells by expression of CD19, CD20, and CD23 along with CD5. Current targeted therapy for treatment of CLL includes monoclonal antibodies against CD20 or CD52. However, these are often either not very effective against CLL cells due to low target expression, or are associated with severe side effects due to expression of target on other immune cells. Thus, more specific and efficacious treatments of CLL are warranted.
Due to its relatively specific expression on CLL cells, CD5 is an obvious target for antibody based therapeutics. However, earlier attempts to develop antibodies against CD5 for treatment of CLL have failed to show significant therapeutic activity in patients. As in vivo studies with murine antibodies against CD5 showed no direct effect of the antibodies, activation of secondary effector functions might be important to obtain therapeutic activity with antibodies targeting CD5. Recently, it has been shown that mixtures of monoclonal antibodies against the same target increase complement-dependent cytotoxicity. Hence, it could be relevant to target CD5 with more than one monoclonal antibody to increase activation of complement-dependent cytotoxicity.
In the current work, sixty-eight chimeric IgG1 antibodies against human CD5 were cloned from CD5 immunized mice using our mSymplex™ technology. Fifteen unique clonotypes were selected for further characterization and functional analyses. The selected antibodies were epitope binned using Biacore analysis to identify antibodies with non-overlapping epitopes. Using confocal microscopy, the level of internalization of CD5 upon binding of the single antibodies and antibody mixtures to CD5 was investigated and it was shown that some combinations of two non-overlapping antibodies induce internalization of CD5, while mixtures of two other non-overlapping antibodies remain on the surface bound to CD5. Subsequently, the direct cytotoxic effect of CD5-specific antibody mixtures and the ability to mediate ADCC and CDC was investigated in vitro using CLL cells isolated from human patients. An update will be presented.
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 4585. doi:10.1158/1538-7445.AM2011-4585
Abstract 4780: c-FLIP knockdown increases apoptosis in cervical cancer cell lines
Authors: Ili Carmen , Brebi Priscilla , Garcia Patricia , LeBron Cynthia , Leal Pamela , Montenegro Sonia , Corvalan Alejandro , Guerrero-Preston Rafael , Roa Juan Carlos 
Published: June 2012

Abstract
Cervical Uterine cancer is a leading cause of cancer deaths in women worldwide. Its natural history begins gradually from low-grade and high-grades squamous intraepithelial lesions to an invasive disease. Decades of studies have confirmed a directly association between persistent high-risk Human Papillomavirus (HPV) infections and cervical cancer. However, high-risk HPV infections are not sufficient to induce cellular transformation and tumor occurrence. The cellular FLICE-like inhibitory protein (c-FLIP) has been founded overexpressed in several cancers and could be associated with cervical carcinogenesis. c-FLIP is a catalytically inactive caspase-8/-10 homologue, and when is overexpressed has the ability to inhibit the extrinsic pathway of apoptosis. Aim: To characterize c-FLIP participation in cervical carcinogenesis.Materials and Methods: Four cell lines were used in this study: ECT1 E6/E7 (squamous normal cervical epithelial), SiHa (cervical carcinoma containing an integrated HPV 16 genome), C-4I (cervical carcinoma containing an integrated HPV 18 genome) and C-33A (cervical carcinoma without HPV). c-FLIP expression in cell lines was determined by real time PCR and western blot. c-FLIP expression was transiently downregulated by siRNA directed against c-FLIP mRNA and the silencing effects on cell viability and apoptosis were analysed, by comparing with a control negative siRNA-transfected cells.Results: c-FLIP was found to be overexpressed in SiHa and C-4I cell lines and repressed in C-33A cell line. Only the long variant of c-FLIP was found in cervical cancer cell lines. Transient knockdown of c-FLIP resulted in significant reduction in cell viability (p&lt; 0.001), compared with negative control siRNA-transfected cells. Knockdown cells lines exhibited an increased apoptotic rate in comparison with controls (p&lt;0,001). Conclusions: The long variant of c-FLIP is overexpressed in cervical cancer cell lines with integrated genome of a high-risk HPV. Furthermore, the siRNA-mediated downregulation of c-FLIP expression induces apoptosis and decreases cell viability in cervical cancer cell lines. Therefore, this protein could be a potential therapeutic target in cervical 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 4780. doi:10.1158/1538-7445.AM2011-4780
Abstract 5370: PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression
Authors: Paraiso Kim H. , Rebecca Vito , Fedorenko Inna V. , Xiang Yun , Wood Elizabeth , Anderson Alexander R. , Sondak Vernon K. , Abel Ethan V. , Koomen John M. , Messina Jane L. , Smalley Keiran S.M 
Published: June 2012

Abstract
The current study has addressed the role of PTEN loss in intrinsic resistance to the BRAF inhibitor PLX4720. Immunohistochemical staining of a tissue array covering all stages of melanocytic neoplasia (n=147) revealed PTEN expression to be lost in &gt;10% of all melanoma cases. Although PTEN status did not predict for sensitivity to the growth inhibitory effects of PLX4720, it was predictive for apoptosis, with little cell death observed in melanomas lacking PTEN expression (PTEN-). Mechanistically, PLX4720 was found to stimulate AKT signaling in the PTEN- but not the PTEN+ cell lines. Liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM) was performed to identify differences in apoptosis signaling between the two cell line groups. PLX4720 treatment significantly increased BIM expression in the PTEN+ (&gt;14-fold) compared to the PTEN- cell lines (4-fold). A role for PTEN in the regulation of PLX4720-mediated BIM expression was confirmed by siRNA knockdown of PTEN and through re-introduction of PTEN into cells that were PTEN-. Further studies showed that siRNA knockdown of BIM significantly blunted the apoptotic response in PTEN+ melanoma cells. Dual treatment of PTEN- cells with PLX4720 and a PI3K inhibitor enhanced both BIM expression and the level of apoptosis. The importance of rebound PI3K/AKT signaling in BRAF inhibitor resistance was confirmed in 3D organotypic cell culture and long-term colony formation assays. In conclusion, we have shown for the first time that loss of PTEN contributes to intrinsic BRAF inhibitor resistance via the suppression of BIM-mediated apoptosis.
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 5370. doi:10.1158/1538-7445.AM2011-5370
Abstract 5455: Integrative analysis of the Cancer Cell Line Encyclopedia reveals genetic and transcriptional predictors of compound sensitivity
Authors: Barretina Jordi , Stransky Nicolas , Caponigro Giordano , Kim Sungjoon , Margolin Adam , Venkhatesan Kavitha , Kryukov Gregory , Berger Michael , Monahan John , Morais Paula , Meltzer Jodi , Mahan Scott , Sonkin Dmitriy , Raman Pichai , Jones Michael , Meyer Vic , Wilson Christopher , Thibault Joseph , Murray Lauren , Callahan Adam , Che John , Shipway Aaron , Li Nanxin , Engels Ingo , Su Andrew , Pinchback Reid , Nedzel Jared , Liefeld Ted , Niu Lili , Hatton Charles , Palescandolo Emanuele , Gupta Supriya , Onofrio Robert , Sougnez Carrie , MacConaill Laura , Winckler Wendy , Reich Michael , Mesirov Jill , Ardlie Kristin , Getz Gad , Morrissey Michael , Warmuth Markus , Meyerson Matthew , Finan Peter , Golub Todd , Weber Barbara , Harris Jennifer , Sellers William , Schlegel Robert , Garraway Levi 
Published: June 2012

Abstract
Comprehensive genomic characterization of cancer is proceeding at a rapidly accelerating pace, mainly due to the expanded use of massively parallel sequencing. Despite the promise of cancer genomics, many cancer drugs still fail in the clinic due to nonresponsive patients and this translates into a significant unmet medical need. Accurate predictions of which patients are more likely to respond to drugs in development could speed clinical trials and personalize treatments.
Here we propose the use of a compendium of experimentally tractable cancer model systems, ∼1000 human genomically-annotated cancer cell lines (at the level of gene expression, DNA copy number alterations and mutations), coupled with pharmacological profiling, to systematically link genetic and transcriptional features to drug response. This resource, the Cancer Cell Line Encyclopedia (CCLE), is available online at www.broadinstitute.org/ccle.
Through computational predictive modeling we have both rediscovered molecular features that predict response to several drugs and also uncovered a number of novel potential biomarkers of sensitivity and resistance to targeted agents and chemotherapy drugs. For instance, we have found that response to topoisomerase 1 inhibitors seem to be driven by expression of a single gene. We have also observed that tissue lineage is a key predictor for sensitivity to certain compounds, providing rationale for clinical trials of these drugs in particular cancer types.
Our cell line-based platform provides a valuable tool for the development of personalized cancer medicine, revealing critical tumor dependencies and helping to stratify patients for clinical trials.
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 5455. doi:10.1158/1538-7445.AM2011-5455
Abstract 5588: Szygium aromaticum (clove): A novel natural breast cancer inhibitor
Authors: Li Hong , Tait Larry , Raz Avraham , Nangia-Makker Pratima 
Published: June 2012

Abstract
The dried flower buds of clove (Syzygium aromaticum syn Eugenia aromaticum or caryophyllata) belonging to family Myrtaceae are used as a spice worldwide. Clove has been reported to exhibit antimicrobial, anti-viral, anesthetic, insecticidal, anti-convulsant, anti-oxidative and free radical scavenging activities. Eugenol, an active component of essential oil isolated from clove has anti-mutagenic, anti-genotoxic and anti-inflammatory properties. It also restricts DMBA induced skin carcinogenesis in mice. Aqueous extract of clove was effective in reducing the incidence of hyperplasia, dysplasia, and carcinoma in situ in benzo[a]pyrene induced lung carcinoma in mice. However, there are no reports on the effects of clove on human cancers.
In this study we have analyzed the inhibitory effects of the aqueous extract of clove (CAE) on breast cancer using in vitro studies like cell growth, cell migration, three-dimensional capillary tube formation / morphogenesis and apoptosis; and in vivo studies like breast tumor growth in nude mice. Our results indicate that CAE inhibited the growth and proliferation of breast cancer cell lines MDA-MB-231, MCF10ADCIS.com, and MCF10AEIII 8 cells in a dose dependent manner. In addition, it also reduced cell migration towards Matrigel. CAE also inhibited the enzymatic activity of the Matrix Metalloproteinase-2 (MMP-2), which was analyzed by using two substrates, namely galectin-3 and a fluorescence-quenched substrate MOCAcPLGLA2pr(Dnp)AR-NH2. Cell cycle analysis of MCF10ADCIS.com cells using flow cytometry after propidium iodide (PI) staining indicated an arrest mainly in S-phase. We also observed an inhibition of DNA synthesis in CAE-treated MCF10ADCIS.com cells by bromodeoxyuridine (BrdU) incorporation. Expressions of apoptosis-related proteins, poly(ADP-ribose)polymerase (PARP), caspase-3 and caspase-8 remained unchanged after CAE treatment, but CDK2, CDK4, cyclin A and cyclin D2 were down-regulated in treated cells indicating that CAE might affect tumor growth by inducing cell cycle arrest but not apoptosis. There was a 50% reduction in tumor volume in nude mice injected with MCF10ADCIS.com cells that received CAE extract in their drinking water compared to the control mice. The expression of proliferation, apoptosis, angiogenesis and tumor progression markers (PCNA, TUNEL, p63, CD31, smooth muscle actin, collagen IV, MMP-2 are being investigated in the xenografts. The results suggest that CAE may be explored further as a novel inhibitor of breast 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 5588. doi:10.1158/1538-7445.AM2011-5588