tbuckley/cabot-search huggingface dataset:
Abstract 4035: Extracellular secreted Ref-1 triggers triple negative breast cancer cells apoptosis
Authors: Yu Ran Lee, Ki Mo Kim, Hee Kyoung Joo, Byeong Hwa Jeon, Sunga Choi
Journal: Cancer Research (2015)

Abstract Triple-negative breast cancers (TNBCs) are most aggressive type and resistant to standard chemotherapy. There is a high demand for developing approaches to treat TNBCs. Recently, some agents inducing post-translational modification (PTM) were suggested to treat therapeutic-resistant cancer cells. We previously discovered that trichostatin A (TSA), histone deacetylase inhibitor (HDACi), - mediated acetylation induced extracellular secretion of the acetylated apurinic apyrimidinic endonuclease 1/redox factor-1 (Ac-APE1/Ref-1). This is the first report showing that the Ac-APE1/Ref-1 is not merely a secreted protein but also a signal molecule that plays a critical role in the apoptotic cell death pathway in TNBC. To study the functional significance of the secreted Ac-APE1/Ref-1, we induced PTM, hyperacetylation of intracellular proteins with co-treatment of acetylsalicylic acid (ASA) and TSA in MDA-MB-231 cells. In response to hyperacetylation, the secretion of Ac-APE1/Ref-1 in a form of exosome-like vesicles was observed in both electron microscopy and confocal image analysis. Accordingly, it was caused a statistically significant inhibition of cell viability and induction of apoptotic DNA fragmentation, leading activation of p38 mitogen-activated protein kinase and apoptotic cell death. Blockade of Ac-APE1/Ref-1 thoroughly recovered from the cell death effects. The hyperacetylation-mediated apoptotic cell death was comparably efficient in treatment of another TNBC cell lines, BT549, and MDA-MB-468. Keeping in view secreted APE1/Ref-1 following acetylation - causing apoptotic cell death we suggest that PTM qualifies as an excellent candidate to be exploited for therapeutic agents to treat TNBCs. For future clinical investigations of TNBCs, this study offers a novel paradigm, which stimulation of apoptotic pathway by action of PTM-induced auto- or paracrine signaling molecules is prior to treatment of standard chemotherapeutic resistant cancer cells. Citation Format: Yu Ran Lee, Ki Mo Kim, Hee Kyoung Joo, Byeong Hwa Jeon, Sunga Choi. Extracellular secreted Ref-1 triggers triple negative breast cancer cells apoptosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4035. doi:10.1158/1538-7445.AM2015-4035
Abstract 3687: A novel computational platform technology (VOLVOX™) for designing anticancer supramolecular therapeutics
Authors: Prithvi Raj Pandey, Shiladitya Sengupta, Sudip Roy
Journal: Cancer Research (2015)

Abstract Current chemotherapy approaches are limited by suboptimal pharmacology. For example, only a fraction of drug administered reaches the tumor. While drug delivery platforms, such as ADCs or nanoparticles, aim to address this limitation by aiming to enhance targeted tumor delivery, these too are limited by drug loading and stability. Here we describe the development of a computational platform technology, VOLVOX, for designing anticancer supramolecular therapeutics. Supramolecular therapeutics evolve as a result of supramolecular assembly of molecular building blocks, thereby altering the PK/PD profile of the building blocks, while increasing drug loading, stability and anti-tumor efficacy. Specifically, VOLVOX envisages interaction of drug candidates with lipid bilayers using molecular simulations, generating information on packing the right excipients in the lipid bilayer. This method is applicable in loading wide range of excipients or drugs having different chemical compositions governed by hydrophilicity and hydrophobicity, shape (geometry/symmetry) and size, and in varying concentrations. This method is applicable for particle based simulation technique at different length and time scale (e.g., all atomistic molecular dynamics (MD), Coarse Grained MD, or Mesoscale MD). As proof of this platform technology, we present development of a novel taxane and a PI3K targeting supramolecular therapeutic. Citation Format: Prithvi Raj Pandey, Shiladitya Sengupta, Sudip Roy. A novel computational platform technology (VOLVOX™) for designing anticancer supramolecular therapeutics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3687. doi:10.1158/1538-7445.AM2015-3687
Green Tea Component, Catechin, Induces Apoptosis of Myeloid Leukemic Cells Via Myeloperoxidase (MPO)-Dependent Highly Reactive Oxygen Species (ROS) Production.
Authors: Tomonori Nakazato, Kenji Yamato, Morihiko Sagawa, Yuriko Nishiyama, Yasuo Ikeda, Masahiro Kizaki
Journal: Blood (2005)
The validity of 5FU-Levofolinate regimen as an alternative for advanced gastric cancer with mild renal failure
Authors: Nobumichi Takeuchi, Takashi Rokuhara, Masayuki Kitahara, Akiko Uehara, Mayumi Watanabe, Chiemi Toda, Izumi Yano, Sonomi Yoshida, Kouji Koizumi
Journal: Annals of Oncology (2015)
A noninvasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA.
Authors: T. Nakamura, N. Sueoka-Aragane, K. Iwanaga, A. Sato, K. Komiya, T. Abe, N. Ureshino, S. Hayashi, E. Sueoka, S. Kimura
Journal: Journal of Clinical Oncology (2011)

e13561 Background: EGFR tyrosine kinase inhibitors (EGFR-TKIs) are widely used to treat lung adenocarcinomas with EGFR activating mutations. However, half of patients acquire resistance because of the gatekeeper T790M mutation. Non-invasive mutation detection system is desired considering the difficulty in obtaining tissue specimens during disease progression. Methods: Sixty-seven plasma DNA samples from forty-nine lung adenocarcinoma patients and thirty healthy volunteers were evaluated. T790M in plasma DNA was determined using the MBP-QP method. The method combines mutation-biased PCR (MBP) and genotyping, the latter based on analysis of the melting curve of the probe DNA binding the target mutated site using a fluorescence quenching probe (QP) system. Results: The detection limit was two copies of control plasmid and 0.2 ng of genomic DNA. The mutant plasmid could be detected when it accounted for as little as 0.3% of a mixture of plasmids carrying EGFR exon 20 with or without T790M. The T790M mutation was detected in plasma DNA from ten of nineteen patients (53%) who acquired resistance, but not in nonresponders, patients responding to treatment, or those not treated with EGFR-TKI. Other mutation detection systems, such as the nucleic acid-locked nucleic acid PCR clamp (PNA-LNA PCR clamp), the cycleave PCR technique, and allele-specific oligonucleotide PCR, detected T790M in three, four, and six patients, respectively, among ten in which T790M was detected by the MBP-QP method. Conclusions: The MBP-QP method is simple, sensitive, and—intriguingly—reflective of clinical course, compared with the other three mutation-detection systems. Thus, the MBP-QP method is an ideal non-invasive monitoring system for detecting T790M in plasma samples.
426. Oncolytic Vaccinia Virus Has Significant Activity and Induces Anti-Tumor Immunity in Bladder Cancer
Authors: Kyle Potts, Nicole Favis, Chad Irwin, Ronald Moore, David Evans, Mary Hitt
Journal: Molecular Therapy (2015)

Oncolytic viruses preferentially replicate in and lyse cancer cells while sparing normal cells. The majority of Bladder Cancers (BCa) are diagnosed as non-muscle invasive however, with a recurrence rate of up to 80%, many patients require multiple treatments that often fail, leading to disease progression. In particular, the current standard of care, Bacillus Calmette–Guérin (BCG) carries the risk of infection, including systemic, cystitis, and prostatitis and can be particularly dangerous for immunocompromised patients.
Liver Capsule: Portal Hypertension and Varices: Pathogenesis, Stages, and Management
Authors: Dennis L. Shung, Guadalupe Garcia‐Tsao
Journal: Hepatology (2016)

1Department of Internal MedicineYale University School of MedicineNew HavenCT 2Department of Internal MedicineSection of Digestive Diseases,Yale University School of MedicineNew HavenCT 3Department of MedicineSection of Digestive Diseases, VA Connecticut Healthcare SystemWest HavenCTUSA * Corresponding author: [email protected]
Apoptosis by Low-Dose Methotrexate Occurs in Fully Activated Proliferating CD4+ and CD8+ Lymphocytes and in Leukemic LGL after Mitogenic Stimulation using a FADD-Dependent Pathway.
Authors: P.K. Epling-Burnette, Jeffrey S. Painter, Fanqi Bai, Subra Mohaptra, Thomas P. Loughran
Journal: Blood (2004)
Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer Therapeutics
Authors: Kristopher A. Sarosiek, Cameron Fraser, Nathiya Muthalagu, Patrick D. Bhola, Weiting Chang, Samuel K. McBrayer, Adam Cantlon, Sudeshna Fisch, Gail Golomb-Mello, Jeremy A. Ryan, Jing Deng, Brian Jian, Chris Corbett, Marti Goldenberg, Joseph R. Madsen, Ronglih Liao, Dominic Walsh, John Sedivy, Daniel J. Murphy, Daniel Ruben Carrasco, Shenandoah Robinson, Javid Moslehi, Anthony Letai
Journal: Cancer Cell (2016)
34. Development and Validation of Identity and Homogeneity Assays for AAV Preparations
Authors: Simon Pacouret, Mathieu Mevel, Mohammed Bouzelha, Anna Maurer, Rajani Shelke, Ru Xiao, Magalie Penaud-Budloo, Heikki Turunen, Frederic Broucque, Véronique Blouin, Philippe Moullier, Eduard Ayuso, Luk H. Vandenberghe
Journal: Molecular Therapy (2016)

Adeno-associated virus (AAV) vectors have emerged as key clinical candidates for gene therapy. Yet, the efficiency and safety of these 20-25 nm biological nanoparticles remain difficult to harmonize across pre-clinical studies due to the limitations of current analytical tools. The presence of residual DNA, protein contaminants, empty particles and VP subunits resulting from incomplete capsid assembly are variables that can strongly modulate the reliability of in vivo data and that, therefore, need to be closely monitored in AAV research laboratories. In this work, 70 AAV preparations, obtained with various production (baculo/Sf9 and triple transfection system) and purification (iodixanol gradient and double cesium-chloride gradient) techniques were analyzed using a thermal shift assay based on the fluorescent dye Sypro® Orange. The fluorescence fingerprint obtained did not only allow to discriminate various AAV serotypes based on their capsid melting temperatures, but also enabled to probe the homogeneity and purity of AAV vector preparations, investigated in parallel using dynamic light scattering (DLS) and polyacrylamide gel electrophoresis. In particular, a double fluorescence transition indicated the presence of capsid-associated protein contaminants whereas a high initial fluorescence background correlated with the presence of free protein contaminants and capsid subunits, possibly resulting from capsid degradation during vector purification or storage. The variability, sensitivity and precision of this assay were further investigated in two different AAV research laboratories. This simple, fast (analysis of 94 preps in ~6 hrs) and low-cost assay emerges as a relevant tool for characterization of AAV vector preparations and will help to increase the reliability of in vivo gene transfer studies.
Abstract 4936: The interaction and effects of hypoxia, surrounding fibroblasts and p16 expression on breast cancer cell migration and invasion
Authors: Yi Lu, Jun Zhang
Journal: Cancer Research (2015)

Abstract Cell migration and invasion play essential roles in the metastatic cascade of tumor cells. Accumulated evidences suggest that intratumoral hypoxia, a characteristic of fast-growing solid tumors, promotes cancer cell motile and invasive abilities. In this study, we investigated the effects and interaction of hypoxia, surrounding fibroblasts, and p16 expression on the migration and invasion of breast cancer (BCa) cells MDA-MB-231, JygMC(A) and LM2. We found that hypoxia promoted BCa cell migration and invasion, and cocultured MEF fibroblasts stimulated invasiveness of BCa cells. Moreover, by using a Tet-on inducible system, we found that p16 is capable of inhibiting hypoxia-induced BCa cell migration and invasion (e.g., 36.0% and 85.8% inhibition on migration and invasion, respectively, in MDA-MB-231 cells), and suppressing cocultured fibroblast-stimulated invasiveness of BCa cells. These results suggest that p16, in addition to its well-known anti-tumor proliferation function, has novel anti-cancer properties capable of suppressing hypoxia-mediated cancer cell migration and invasion. This study may provide important validation for p16-mediated cancer therapy either by gene therapy or pharmacological activation of internal p16 gene that is usually inactive due to hypermethylation in the tumor cells. Note: This abstract was not presented at the meeting. Citation Format: Yi Lu, Jun Zhang. The interaction and effects of hypoxia, surrounding fibroblasts and p16 expression on breast cancer cell migration and invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4936. doi:10.1158/1538-7445.AM2015-4936
Caffeic Acid Phenetyl Ester, a Brazilian-Green-Propolis Derivative, Induces apoptosis in AML Cells, Promotes up Regulation of G-Protein Signaling and Hyper Secretion of IL-8
Authors: Priscila S Scheucher, Guilherme A dos Santos, Hamilton L Gimenes Teixeira, Carolina H Thomé, Antonio R Lucena-Araujo, Roberto P. Falcao, Eduardo M. Rego
Journal: Blood (2010)
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative Trial of AMD3100 (Plerixafor)+G-CSF vs. G-CSF+Placebo for Mobilization in Multiple Myeloma (MM) Patients for Autologous Hematopoietic Stem Cell (aHSC) Transplantation.
Authors: John DiPersio, Edward A. Stadtmauer, Auayporn P. Nademanee, Patrick Stiff, Ivana Micallef, J. Angell, G. Bridger, Gary Calandra
Journal: Blood (2007)
Abstract 5216: Potential use of saliva and hair samples to identify genetic markers for anti-VEGF therapy
Authors: Gloria R. Xue, Crystal R. Xue, Fei Shen, Bryan P. Schneider
Journal: Cancer Research (2015)

Abstract Anti-angiogenic therapy to block and disrupt tumor angiogenesis has been used in clinical treatment of various malignancies including: glioblastoma, colorectal, lung and kidney cancer. Currently, the most clinically effective anti-angiogenic agents are the humanized monoclonal antibody (bevacizumab) against vascular endothelia growth factor (VEGF) and the small molecule receptor-tyrosine-kinase inhibitors (RTKIs) of VEGF receptors. However, the therapeutic benefit varies substantially for many of these agents. Predictive biomarkers that are required for personalized treatment with these agents are currently not available. Recently the role of germline single-nucleotide polymorphisms (SNPs) has been investigated as potential biomarkers for anti-angiogenic treatments. The rationale is that these agents target the vasculature in host (vessels) rather than tumor tissue, which could mean that much of the variability is dictated by the host. Several studies reported the association of SNPs in VEGFA with differential outcomes from clinical trials with these agents. SNP genotyping assays in these studies used germline DNA extracted from blood. However, collection of peripheral blood is invasive. Saliva and hair that are known to contain genomic DNA can be used as noninvasive and convenient DNA sampling resources, but the limited quantity of DNA in the hair and the low quality of DNA in the saliva make genotyping assays non-reproducible. We have sought to improve SNP genotype assays with DNA from saliva and hair by applying SNP target pre-amplification for genotyping five SNPs (rs699947, rs833061, rs1570360, rs201093, rs3025039) in VEGFA. The concordance of genotyping calls of individual SNP using DNA from blood, saliva and hair from the same volunteer was compared. Our preliminary results demonstrated that pre-amplification substantially improved genotyping calls with saliva DNA and hair DNA samples. The average genotyping call rate with saliva and hair samples was about 45% and 10%, respectively, without pre-amplification. The pre-amplification improved the call rate with saliva and hair samples to 100% and 94%, respectively. The current report may facilitate easier clinical sample collection for genetic tests for these SNPs. Citation Format: Gloria R. Xue, Crystal R. Xue, Fei Shen, Bryan P. Schneider. Potential use of saliva and hair samples to identify genetic markers for anti-VEGF therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5216. doi:10.1158/1538-7445.AM2015-5216
The Relationship between Weekend Admissions and Outcome in Older Adults with Acute Myelogenous Leukemia (AML).
Authors: Ahmed Al-Hazzouri, Lisa Rybicki, Matt Kalaycio, Stacey Brown, Hyo Sook Han, Brad Pohlman, Anjali Advani, Barbara Tripp, Ronald Sobecks, Mikkael Sekeres
Journal: Blood (2004)
148. Screening and Optimization of Antisense Oligonucleotide for Skipping Human Dystrophin Exon 51 and 53
Authors: Bo Wu, Peijuan Lu, Sapana N. Shah, Stephanie Milazi, Lauren E. Bollinger, Qi Long Lu
Journal: Molecular Therapy (2015)

Duchenne muscular dystrophy (DMD) results from dystrophin gene mutations, causing shift of the reading frame and preventing production of a functional protein. Most DMD mutations occur in the parts of the gene that are not critical for its function, therefore restoration of the reading frame by antisense oligonucleotide-mediated exon skipping is a viable approach. The efficacy of antisense therapy has now been proven in animal models and in clinical trials. Therapeutic effect of exon skipping largely depends on the efficiency of individual antisense oligoneotide, which has to be identified by screening. This study aims specifically to search for the most effective morpholino (PMO) oligomer to target the human dystrophin exon 51 and exon 53 for the correction of the relevant DMD mutations. We established the GFP reporter myoblast cell cultures and screened more than 40 PMOs targeting each of exon 51 and exon 53. We also examined the PMOs in normal human myoblast cultures and in humanized DMD (hDMD) mice with local delivery by i.m injection to identify PMOs of maximal skipping potency. Finally we selected 5 oligomers as vivo-PMOs targeting each of the exon 51 and 53 and examined their exon skipping efficiency in the hDMD mice by systemic delivery. We were able to identify PMOs with high exon skipping efficiency in all muscles. The selected PMOs will be further validated in patient-derived fibroblasts and then be applied to clinical trials for DMD treatment.
590. Tumor-Targeted Delivery of Therapeutic siRNA by EGFR Aptamer-Conjugated Liposomes
Authors: Hwa Yeon Jeong, Seong Jae Kang, Min Woo Kim, In ho Jeong, Moon Jung Choi, Yong Serk Park
Journal: Molecular Therapy (2015)

Important considerations for effective cancer gene therapy are the targeted delivery of therapeutic genes and efficient endosomal escape of the genes in the cytoplasm. To address the first issues, target-specific aptamers and cationic lipids have been adopted for formulation of tumor-specific lipidic nanoparticles containing therapeutic genes. First of all we have developed EGF receptor (EGFR) aptamer-conjugated liposomes containing siRNA. The liposomal vehicles were optimized in terms of lipid constituents, ratio of lipid/siRNA, and aptamer conjugation process, and their biophysical characteristics were then determined by dynamic light scattering. Compared to the nonspecific cationic lipoplexes of siRNA, EGFR aptamer-conjugated liposomes encapsulating siRNA showed a relatively lower binding to EGFR-expressing cancer cells, resulting in a lower siRNA transfection. However, the EGFR aptamer-conjugated liposomes exhibited efficient transfection only to EGFR-expressing cancer cells, but not to EGFR-negative cancer cells. This research suggests that aptamer-conjugated lipidic nanoparticles can be utilized for target-specific delivery of therapeutic siRNAs.
QOL-09EFFECT OF ANTIPERSPIRANTS AND SKIN BARRIERS ON ELECTRICAL RESISTANCE DURING TTFIELDS APPLICATION
Authors: Roni Blat, Moshe Giladi, Yoram Wasserman, Tali Voloshin, Rosa S. Schneiderman, Eilon D. Kirson, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2015)

Low intensity, intermediate frequency, alternating electric fields (TTFields) are approved for the treatment of patients with glioblastoma. TTFields are applied continuously using a set of four arrays covering a skin area of about 140 cm2 each. One main TTFields-related adverse event is mild to moderate dermatitis under the arrays which may be exacerbated by local hyperhidrosis. This may occur due to a combination of factors including limited skin ventilation and the use of adhesives for array attachment. Strategies that ameliorate local skin irritation could enhance patients' quality of life and improve therapeutic compliance. Antiperspirants and skin barriers are hypothesized to alleviate factors related to TTFields-related dermatitis, however their effect on the quality of the therapy has never been tested. This study investigated the effect of applying commercially available antiperspirants and skin barriers on the electrical resistance during TTFields application using 3 different models: a metal plate phantom, a head size watermelon and a rat model. In these experiments, 200 kHz TTFields were applied using PMN-PT disks with hydrogels similar to those used with the human arrays. The results demonstrate that application of water-based antiperspirants and skin barriers on the surface below the electrodes, had no significant effect on the electrical resistance in the 3 models tested, whereas application of triglyceride and glycerin-based skin barriers and antiperspirants led to a significant increase of the electrical resistance. Increased resistance may, under certain circumstances, lead to a decrease in TTFields intensity, thus hamper treatment efficacy. These results suggest that local application of water-based antiperspirants and skin barriers could maintain the normal electrical resistance of the scalp-array interface, thereby allowing optimal delivery of TTFields to the brain. Thus, antiperspirants and skin barriers should therefore be prospectively investigated for their potential role in minimizing TTFields-related dermatitis.