bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4415: Differential effects of biochanin A on cell proliferation and ROS-dependent pathways in estrogen receptor positive and HER-2 positive breast cancer cells.
Authors: Dickerson Lindsy , Sehdev Vikas , Crowell Pamela L. , Lai James C.K. , Bhushan Alok 
Published: August 2014

Abstract
The naturally occurring isoflavone biochanin A has been reported to have chemo-preventative properties towards cancer. Biochanin A exhibits antioxidant properties. Because of its antioxidant properties, biochanin A may be used to target breast cancer cells with high intracellular levels of reactive oxygen species (ROS). In this study, we investigated the effects of biochanin A on two cell lines — an estrogen receptor (ER) positive and a HER-2 positive breast cancer cell line. Biochanin A is implicated to affect both hormonal receptors and receptor tyrosine kinases. Overstimulation of ER is a basis for tumor progression due to the disruption of the cell cycle and apoptosis in estrogen positive breast cancer cells. Activation of HER-2 initiates cell growth, survival and invasion promoting cell signaling events in HER-2 positive breast cancer cells. MCF-7 (estrogen positive) and SK-BR-3 (HER-2 positive) cells were treated with biochanin A (2-100 μM) for 72 hours. Then MTT (cell survival) assay was carried out to determine the effects of biochanin A on cell survival. Our results suggest that biochanin A induces a dose-related inhibition of MCF-7 and SK-BR-3 cell viability at 50 μM. MCF-7 and SK-BR-3 cells were also treated with biochanin A (50 μM) for 12 hours and subsequently treated with hydrogen peroxide (H2O2)(2 μM) for 30 minutes: then western blotting was carried out to determine their expression of ERK and transcription factor NFκB. We found that biochanin A inhibits phospho-ERK pathway in SK-BR-3 but not in MCF-7 cells. However, expression of the transcription factor NFκB was decreases in both SK-BR-3 and MCF-7 cells. Thus, biochanin A may be an effective chemotherapeutic agent for breast cancer because of its ability to affect both hormonal receptors and receptor tyrosine kinases and to decrease intracellular ROS levels. (Supported by NIH INBRE P20RR016454, URC and MSTMRI)
Citation Format: Lindsy Dickerson, Vikas Sehdev, Pamela L. Crowell, James C.K. Lai, Alok Bhushan. Differential effects of biochanin A on cell proliferation and ROS-dependent pathways in estrogen receptor positive and HER-2 positive breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4415. doi:10.1158/1538-7445.AM2013-4415
Abstract 4422: Methylcytosine topology: potential of a DNA landmark in pre-clinical epigenetic drug toxicology.
Authors: Tajbakhsh Jian 
Published: August 2014

Abstract
Cellular reprogramming through drug-based epigenetic intervention has become a novel approach in the treatment of complex diseases and in regenerative medicine towards reconstitution of normal cell, tissue and organ function. Within this context, non-specific and off-target global DNA demethylation — either directly induced by DNA demethylating drugs or indirectly caused by histone modifiers or any other agent with epigenetic consequences — could impact the cells’ DNA methylation pattern and lead to unwanted cryptic DNA methylation toxicity and carcinogenesis: by influencing chromatin conformation, genome organization, and cellular gene expression programs. The Translational Cytomics Group at the Cedars-Sinai Medical Center (Los Angeles) has developed 3D quantitative DNA Methylation Imaging (3D-qDMI), a non-disruptive image-cytometrical method that measures the differential load and spatial distribution of methylated cytosine (MeC) within individual nuclei of thousands of cells in a cell-by-cell fashion. Thus the technology has the additional capability of capturing cellular heterogeneity regarding global DNA methylation properties in response to drug exposure. Utilizing 3D-qDMI we are currently evaluating these topological parameters, which translate to differential DNA methylation phenotypes (MeC phenotypes), as potential chromatin signatures (textures) to be utilized in the characterization of cells during reprogramming, and for genotoxicity assessment of drugs.
Citation Format: Jian Tajbakhsh. Methylcytosine topology: potential of a DNA landmark in pre-clinical epigenetic drug toxicology. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4422. doi:10.1158/1538-7445.AM2013-4422
Abstract 4460: Acquisition of stem cell-like properties during acquired resistance to epidermal growth factor receptor inhibitors.
Authors: Shien Kazuhiko , Toyooka Shinichi , Yamamoto Hiromasa , Soh Junichi , Thu Kelsie L. , Hashida Shinsuke , Maki Yuho , Ichihara Eiki , Asano Hiroaki , Tsukuda Kazunori , Takigawa Nagio , Kiura Katsuyuki , Gazdar Adi F. , Lam Wan L. , Miyoshi Shinichiro 
Published: August 2014

Abstract
Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a critical issue in the treatment of lung cancer. While several mechanisms have been demonstrated to be responsible for acquired resistance, all mechanisms have not been uncovered. In this study, we investigated the molecular and cellular profiles of the acquired resistant cells to EGFR-TKI in EGFR mutant lung cancers. Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation and high-concentration exposure methods, and resistant sublines to gefitinib were established. The molecular profiles and cellular phenotypes of these resistant sublines were characterized. Although previously reported alterations including secondary EGFR T790M mutation, MET amplification, and appearance of epithelial to mesenchymal transition (EMT) features were observed, these 2 drug-exposure methods revealed different resistance mechanisms. The resistant cells with EMT features exhibited down-regulation of microRNA-200c by DNA methylation. Furthermore, the HCC827-derived subline characterized by the high-concentration exposure method exhibited not only EMT features but also stem cell-like properties, including aldehyde dehydrogenase isoform 1 (ALDH1A1) overexpression, increase of side population, and self-renewal capability. Resistant sublines with stem cell-like properties were resistance to conventional chemotherapeutic agents but equally sensitive to histone deacetylase and proteasome inhibitors, compared with their parental cells. ALDH1A1 was up-regulated in clinical samples with acquired resistance to gefitinib. In conclusion, our study indicates that the manner of EGFR-TKI exposure influences the mechanism of acquired resistance and the appearance of stem cell-like property with EGFR-TKI treatment.
Citation Format: Kazuhiko Shien, Shinichi Toyooka, Hiromasa Yamamoto, Junichi Soh, Kelsie L. Thu, Shinsuke Hashida, Yuho Maki, Eiki Ichihara, Hiroaki Asano, Kazunori Tsukuda, Nagio Takigawa, Katsuyuki Kiura, Adi F. Gazdar, Wan L. Lam, Shinichiro Miyoshi. Acquisition of stem cell-like properties during acquired resistance to epidermal growth factor receptor inhibitors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4460. doi:10.1158/1538-7445.AM2013-4460
Abstract 4486: 5-Hydroxymethyl-2’-deoxyuridine, but not temozolomide, enhances the selective synthetic lethality in BRCA1 and BRCA2-deficient cells caused by PARP inhibition.
Authors: Clement Jean , Nakamura Jun 
Published: August 2014

Abstract
Inhibition of poly(ADP-ribose) polymerase (PARP) has been determined as an attractive chemotherapeutic treatment for homologous recombination (HR)-deficient tumors. PARP is involved in repairing DNA single strand breaks (SSBs) via the base excision repair (BER) pathway; therefore, PARP inhibitor (PARPi) leads to an accumulation of DNA double strand breaks (DSBs) at the sites of SSBs during DNA replication. While the cytotoxic effect of PARPi was demonstrated to be potentiated by addition of genotoxic alkylating agent temozolomide (TMZ), it is not clear that this combined treatment further increases selectivity to cause cell death in HR-deficient cells, such as BRCA-deficient cells, over HR-proficient cells. TMZ randomly increases SSBs at scattered locations in the genome; in contrast, incorporation of 5-hydroxymethyl-2’-deoxyuridine (5-HmedU) in DNA has a potential to cause multiple SSBs within a short distance during BER. We hypothesized that a combination treatment of PARPi and 5-hmedU could increase selectivity of PARPi-mediated cytotoxicity in HR-deficient cells more so than the PARPi and TMZ combination. Here we show that in single chemical treatment experiments, the IC50 of 5-HmedU was eight times lower in BRCA1-/- and BRCA2-/- mutant cells, but in TMZ treatments the IC50 was only two times lower compared HR-proficient cells. Furthermore, the 5-HmedU and PARPi agent Olaparib combination enhanced a synergistic cell killing effect in BRCA1-/- and BRCA2-/- mutant cells with higher selectivity than the PARPi and TMZ combination. Advantages of the 5-HmedU and PARPi combination is as follows: 1] 5-HmedU causes DNA damage through vast genome incorporation in highly proliferating cells. Thus, 5-HmedU is more effective at selecting highly proliferating tumor cells; 2] 5-HmedU single treatment more selectively targeted BRCA1-/- and BRCA2-/- mutant cells than TMZ. This selectivity could be due to more efficient DSB formation by 5-HmedU through accumulation of clustered SSBs; and 3] combination treatment of 5-HmedU and PARPi produces a synergistic selectivity to kill HR-deficient BRCA1-/- and BRCA2-/- mutant cells whereas TMZ and PARPi combination does not. A possible mechanism of the selective cell killing effect by 5-HmedU and PARPi could result from an accumulation of closely located DSBs with PARP-DNA strand break complexes in HR-deficient cells.
Citation Format: Jean Clement, Jun Nakamura. 5-Hydroxymethyl-2’-deoxyuridine, but not temozolomide, enhances the selective synthetic lethality in BRCA1 and BRCA2-deficient cells caused by PARP inhibition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4486. doi:10.1158/1538-7445.AM2013-4486
Abstract 4508: Novel multifunctional nanocarriers for drug delivery, photodynamic therapy, sonodynamic therapy, MRI and PET imaging.
Authors: Lam Kit S. , Li Yuanpei , Lin Tzu-yin , Zhang Hongyong , Feng Caihong , Luo Yan , Pan Chong-Xian , Xiao Kai , Xiao Wenwu , Lee Joyce , Liu Ruiwu 
Published: August 2014

Abstract
We have previously reported the development of a versatile nanocarrier platform comprised of PEG-cholic acid cluster telodendrimers that can self-assemble together with hydrophobic cytotoxic anti-cancer agents to form stable nanoparticle drugs. We have successfully loaded these nanoparticles with a number of different cancer drugs. These include paclitaxel, doxorubicin, vincristine, vinblastine, actinomycin D, bortezomib, temsirolimus, sarofinib, and lapatinib. Using electron paramagnetic resonance spectroscopy, we have demonstrated that the micelles can be disrupted by HDL, LDL, VLDL or chylomicron causing premature drug release. Such undesirable properties can be eliminated by cross-linking the telodendrimers with disulfide bonds or boronate-catechol linkages. Very recently, we have developed a series of novel highly versatile multi-functional nancarriers that not only allow efficient delivery of hydrophobic drugs, but can also (i) deliver proteins and nucleic acids to target cells, (ii) allow efficient photodynamic therapy and sonodynamic therapy, and (iii) function as sensitive MRI and PET imaging agents for the detection of cancers. Tumor cell surface binding ligands identified through one-bead-one-compound combinatorial chemistry can be easily incorporated into these nanocarriers for effective tumor targeting. On-demand releasable mechanism can also be built into such novel nanoplatforms for more efficacious therapy.
Citation Format: Kit S. Lam, Yuanpei Li, Tzu-yin Lin, Hongyong Zhang, Caihong Feng, Yan Luo, Chong-Xian Pan, Kai Xiao, Wenwu Xiao, Joyce Lee, Ruiwu Liu. Novel multifunctional nanocarriers for drug delivery, photodynamic therapy, sonodynamic therapy, MRI and PET imaging. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4508. doi:10.1158/1538-7445.AM2013-4508
Abstract 451: Smad2 is the TGF-β receptor-regulated Smad to suppress the immunogenicity of mouse and human dendritic cells.
Authors: Yoon Jeong-Hwan , Han Jin-Soo , Park Seok Hee , Weinstein Michael , Nakae Susumu , Yamashita Tadashi , Lee In-Kyu , Sumida Takayuki , Sudo Katsuko , Kuroda Masahiko , Mamura Mizuko 
Published: August 2014

Abstract
TGF-β plays pivotal roles in the regulation of DCs. However, the molecular mechanisms by which TGF-β regulates DCs are undetermined. Here, we show that one of the TGF-β receptor-regulated Smads (R-Smads), Smad2 is the predominant intermediary for TGF-β to suppress the immunogenicity of DCs. Notably, Smad2 remained expressed, whereas Smad3 was down-regulated in mouse BM-derived DCs (BMDCs) and human monocyte-derived DCs (MoDCs) upon differentiation by GM-CSF and IL-4. Smad2 mediated the inhibitory effect of TGF-β on the expression of co-stimulatory molecules (CD80, CD86, CD40) on BMDCs. One of the TGF-β superfamily cytokines, Activin-A did not affect their expression, although it shares Smad2 and Smad3 as R-Smads. Deletion of Smad2 up-regulated the dendrite formation, co-stimulatory molecule expression, and effector cytokine production by DCs, thereby efficiently activating allogeneic T cells. Furthermore, DC-specific deletion of Smad2 by Cd11cCre-loxP system suppressed the progression of a mouse EL4 lymphoma model by enhancing anti-lymphoma cytotoxic activity. Thus, our results suggest that TGF-β signaling through Smad2 in DCs could be a therapeutic target to enhance anti-tumor immunity.
Citation Format: Jeong-Hwan Yoon, Jin-Soo Han, Seok Hee Park, Michael Weinstein, Susumu Nakae, Tadashi Yamashita, In-Kyu Lee, Takayuki Sumida, Katsuko Sudo, Masahiko Kuroda, Mizuko Mamura. Smad2 is the TGF-β receptor-regulated Smad to suppress the immunogenicity of mouse and human dendritic cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 451. doi:10.1158/1538-7445.AM2013-451
Abstract 4513: Engineering apoferritin nanocages for tumor imaging and therapy.
Authors: Xie Jin , Zhen Zipeng , Tang Wei 
Published: August 2014

Abstract
Ferritin is a major iron storage protein found in human and most living organisms. Each ferritin is comprised of 24 subunits, which self-assemble to form a cage-like nanostructure. Apoferritins (FRTs) refer to those that are without iron encapsulated. FRT is an interesting nanoplatform and holds great potential in cancer imaging and drug delivery for several reasons. 1) Biosafety. Compared to many other biomaterials, FRTs have fewer concerns in toxicity and immunogenicity. 2) Unique nanostructure. Despite the rigidness under physiological conditions, the FRT nanoarchitecture can be broken down into FRT subunits in an acidic environment (pH = 2). Interestingly, such a process is reversible. When the pH is tuned back to neutral, the FRT subunits will be reconstituted into a nanocage structure, and almost in an intact fashion. This feature can be harnessed to form hybrid nanostructures and to allow for efficient drug loading. 3) Easy surface modification. As a protein, FRT nanocages can be genetically modified to present a peptide sequence on the surface. In addition, FRTs have multiple lysine and cysteine groups on the surface that can be easily linked with functional molecules, such as a fluorescence dye or a targeting peptide. 4) High loading capacity. In addition to iron and transition metals, many small molecules are able to be encapsulated into FRT interiors efficiently. Making use of these unique characteristics, we recently developed several multifunctional FRT-based probes for tumor imaging. Very recently, we found that doxorubicin can be internalized into RGD modified FRTs (RFRTs) with high efficiency (up to 70 wt%). The Dox-loaded RFRTs kept integrin selectivity, which was confirmed by both in vitro and in vivo imaging. Therapeutic studies on U87MG subcutaneous models observed a good tumor growth inhibition rate (89.6%) and reduced cardiotoxicity.
Citation Format: Jin Xie, Zipeng Zhen, Wei Tang. Engineering apoferritin nanocages for tumor imaging and therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4513. doi:10.1158/1538-7445.AM2013-4513
Abstract 4531: Nanoscale Artificial Antigen Presenting Cells for T Cell Immunotherapy.
Authors: Perica Karlo , Bieler Joan G. , De León Medero Andrés , Chiu Yen-Ling , Durai Malarvizhi , Niemöller Michaela , Assenmacher Mario , Richter Anne , Oelke Mathias , Schneck Jonathan 
Published: August 2014

Abstract
Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for adoptive immunotherapy and in vivo T cell stimulation. Thus far, bead-based aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to beads several microns in diameter. By reducing the size of aAPC, we anticipated more efficient delivery of these stimulatory signals to tumor and lymph nodes where antigen-specific T cells reside. We thus manufactured aAPC based on two nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles, 50-100 nm in diameter, and avidin-coated quantum dot nanocrystals, less than 20 nm in diameter. Nanoscale aAPC induced antigen-specific T cell proliferation from both TCR transgenic mouse splenocytes and human, polyclonal peripheral blood T cells. In a subcutaneous mouse melanoma model, both iron-dextran particles and quantum dot nanocrystals mediated tumor rejection when injected in vivo. To our knowledge, this is the first description of a nanoscale, particle-based aAPC that induces T cell proliferation in vitro and leads to effective T cell stimulation and tumor rejection in vivo. Furthermore, nano-aAPC represent a novel platform for studying receptor-ligand interactions at the membrane-nanoparticle interface.
Citation Format: Karlo Perica, Joan G. Bieler, Andrés De León Medero, Yen-Ling Chiu, Malarvizhi Durai, Michaela Niemöller, Mario Assenmacher, Anne Richter, Mathias Oelke, Jonathan Schneck. Nanoscale Artificial Antigen Presenting Cells for T Cell Immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4531. doi:10.1158/1538-7445.AM2013-4531
Abstract 4545: Identifying neuroblastoma-specific ligands for cancer targeted therapy using a one-bead one-compound combinatorial approach.
Authors: Iskandar Andy , Duong Connie , Chen Cathy , Sanchez Eduardo , Olivos David , Lam Kit , Satake Noriko 
Published: August 2014

Abstract
Neuroblastoma is the most common extra-cranial tumor in children, with around 700 new diagnoses each year. High-risk patients have poor outcomes and only 30% survive despite the most intensive therapies available, which can also harm healthy cells. Thus, we are developing novel targeted therapies for neuroblastoma to increase treatment efficacy and limit damage to healthy cells.
We utilized the One-Bead One-Compound (OBOC) combinatorial split-mix method developed by Kit Lam (Lam et al., 1991) to identify unique ligands against neuroblastoma cells for therapeutic delivery. The OBOC libraries consist of hundreds to millions of 90 μm Tentagel beads, and each bead displays 1013 copies of a peptide on its surface. Thus, each bead has one unique compound on its exterior.
Twelve random OBOC libraries with varying peptide lengths (5 to 16 amino acids) were screened against three human neuroblastoma cell lines (SK-N-BE, SK-N-DZ, and IMR-32) to determine a library for more stringent screening of ligands. 37,500 beads from each library were screened against each cell line and the libraries averaged 2 positive candidates per 18,750 beads within 2 hours of incubation. The results also suggested preference for longer peptide libraries, but an intermediate length random decamer library was chosen for further screening due to both a good yield of positive beads and convenient sequencing.
Each neuroblastoma line was screened against 150,000 beads from the decamer library to identify potential ligands. Positive beads were selected, retested three times, and decoded using Edman degradation. Several cancer cell lines (A549 lung cancer, and Reh and Jurkat leukemia cell lines) were used as negative controls. Ten beads per cell line displaying high binding affinity were selected. Candidate beads with positive binding to all three neuroblastoma cell lines are currently being sequenced and the ligands will be synthesized. We plan to characterize the ligands for high affinity and specificity, as well as internalization capacity, and to identify their receptors.
Currently, there are very few targeted therapies for neuroblastoma. We believe our ligand discoveries can be developed for future novel targeted therapies in neuroblastoma.
Citation Format: Andy Iskandar, Connie Duong, Cathy Chen, Eduardo Sanchez, David Olivos, Kit Lam, Noriko Satake. Identifying neuroblastoma-specific ligands for cancer targeted therapy using a one-bead one-compound combinatorial approach. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4545. doi:10.1158/1538-7445.AM2013-4545