tbuckley/cabot-search huggingface dataset:
Abstract 4396: Nanocarrier for monoclonal antibody delivery
Authors: Andrew Gdowski, Amalendu Ranjan, Anindita Mukerjee, Jamboor Vishwanatha
Journal: Cancer Research (2015)

Abstract Antibodies represent a large class of drugs that have a number of different therapeutic uses. The use of monoclonal antibodies against potential intracellular protein-protein interactions in cancer cells has remained largely unexplored. This lack of consideration is due largely to a number of factors that include poor intracellular uptake and rapid lysosomal degradation of monoclonal antibodies within cells. Encapsulating monoclonal antibodies within biodegradable nanoparticles is one strategy that can improve antibody cellular uptake and protect from lysosomal degradation so that the antibody can be released inside the cell and remain functional against the therapeutic target. Purpose: The purpose of this study is to characterize a human monoclonal antibody encapsulated within poly(lactic-co-glycolytic) acid (PLGA) nanoparticles. We hypothesized that encapsulation of an antibody within PLGA nanoparticles is feasible and will release in a favorable manner. Method: Anti-AnnexinA2 (AnxA2) monoclonal antibody was encapsulated within PLGA nanoparticles utilizing a water/oil/water double emulsion solvent evaporation method. Nanoparticles and released antibodies were characterized through a number of different modalities. Results: Our results show encapsulation efficiency ranging from 16-22% with a mean of 18.725% (SEM 1.289) depending on initial concentration of antibody used in the nanoparticle formulation. Nanoparticles were formed in a favorable mono disperse manner as evidenced through dynamic light scattering. All of the formulations created maintained a hydrodynamic size below 250nm. Release kinetics revealed that at day 12 the cumulative release of the antibody is approximately 35%. In addition after release the antibody maintained functionality as evidenced through Western Blot analysis and immunocytochemistry. Conclusions: Encapsulation of a monoclonal antibody within polymeric PLGA nanoparticles is feasible, exhibits sustained release kinetics, and maintains functionality upon release. This encapsulation technique may be used as a method to load antibodies in targeted nanoparticles and release the antibodies inside cancer cells to interfere with aberrantly expressed proteins. Future experiments will focus on utilizing this monoclonal antibody encapsulation approach to screen intracellular protein-protein interactions as potential new therapeutic cancer targets. Note: This abstract was not presented at the meeting. Citation Format: Andrew Gdowski, Amalendu Ranjan, Anindita Mukerjee, Jamboor Vishwanatha. Nanocarrier for monoclonal antibody delivery. [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 4396. doi:10.1158/1538-7445.AM2015-4396
Can a reduced-intensity conditioning regimen cure blastic plasmacytoid dendritic cell neoplasm?
Authors: Mathieu Leclerc, Régis Peffault de Latour, Mauricette Michallet, Didier Blaise, Patrice Chevallier, Pierre-Simon Rohrlich, Pascal Turlure, Stéphanie Nguyen, Fabrice Jardin, Ibrahim Yakoub-Agha, Sébastien Maury
Journal: Blood (2016)
478. An Essential and Ubiquitous Protein Receptor for AAV; Glycans as Attachment Receptors
Authors: Nancy L. Meyer, Sirika Pillay, Qing Xie, Omar Davulcu, Andreas Puschnik, Jonathan Diep, Yoshi Ishikawa, Lucas Jae, Jonathan Wosen, Claude Nagamine, Alex Noble, Scott Stagg, Jan E. Carette, Michael S. Chapman
Journal: Molecular Therapy (2016)

Motivated by unsuccessful attempts to observe physical binding between AAV-2 and heterologously expressed domains of previously reported co-receptors, we set out to identify novel protein receptor(s) for AAV2 through an unbiased genome-wide knockout screen in human cells. Using an mCherry AAV vector, resistant cells were iteratively selected by FACS for gene trap screening in a library of mutagenized haploid cells. Upon deep sequencing, refractory cells had significantly high frequencies of mutation in genes encoding glycan synthesis and retrograde transport, but most significantly in a hitherto poorly characterized transmembrane protein, now termed AAVR. Genetic confirmation of AAVR's role in the entry of multiple AAV serotypes has come through CRISPR-Cas9 knockouts in multiple cell lines then restoration of susceptibility through complementation; infection of poorly permissive cells following AAVR transduction; and creation of a mouse knockout with greatly diminished susceptibility. Various AAVR ectodomain constructs have been heterologously expressed and purified as fusion proteins, and these have been shown to inhibit in vitro viral transduction at concentrations consistent with effective nM binding constants (between AAV & AAVR) measured by surface plasmon resonance (SPR). Pre-incubation with antibodies to AAVR also inhibits infection or transduction. AAVR is transiently expressed on the plasma membrane. Expression of chimeric constructs suggests that AAV takes advantage of its trafficking to the perinuclear trans Golgi network as the dominant, but non-exclusive, entry pathway. Identification of AAVR and its apparently ubiquitous use has interesting implications for AAV's cell specificity. Progress towards structure of complexes will be reported. AAVR exhibits the classic characteristics of a viral receptor, casting the roles ascribed to glycan "primary" receptors in new light. Electron microscopy has been used to visualize AAV-DJ in complex with various heparin analogs at increasingly high resolution. A structure at 2.8 Å resolution, as a pentasaccharide complex, shows some disorder in the glycan, but the side chains of viral amino acids are clearly resolved and in different conformations from those seen in a sucrose octasulfate complex. With little change to the backbone, the binding site accommodates diverse glycan sequences through adjustments to side chains, consistent with SPR binding assays of AAV-2 to a library of heparanoids. This, together with comparisons of heparan and AAVR cell knock-outs, indicates a more accessory role for glycans than is implied by the term "primary". As for several other viruses, in AAV-2 at least, the glycan is an attachment receptor that likely elevates the AAV concentration proximal to the membrane, improving the efficiency with which the virus then binds to AAVR.
ATP11C Encodes a Major Flippase in Human Erythrocyte and Its Genetic Defect Causes Congenital Non-Spherocytic Hemolytic Anemia
Authors: Nobuto Arashiki, Yuichi Takakuwa, Hiromi Ogura, Taiju Utsugisawa, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Shouichi Ohga, Narla Mohandas, Hitoshi Kanno
Journal: Blood (2015)
Abstract 3610: DMH4, A VEGFR2 inhibitor effectively suppresses proliferation and migration of lung cancer cells
Authors: Hao Li, Chay Bae, Nicky Gazy, Jijun Hao, Li Zhong
Journal: Cancer Research (2015)

Abstract Background Currently there is a major unmet medical need for effective therapy of the non-small cell lung cancer (NSCLC). It is well known that vascular endothelial growth factor (VEGF) signaling plays a critical role in regulating tumor angiogenesis, and bevacizumab is the only approved antiangiogenic agent for the treatment of NSCLC to date. Due to individual differences in drug response, developing novel angiogenic inhibitors is essential for NSCLC treatment. We have recently developed DMH4, a small molecule which specifically inhibits VEGF signaling by targeting VEGF receptor 2 (VEGFR2) (Hao, et al 2010). Here, we show that DMH4 can effectively suppress proliferation and migration of NSCLC cells. Method Briefly, NSCLC cell line H460, A549 and a lung fibroblast cell line MRC5 was treated by DMH4 at concentrations of 0.25 ug/ml, 0.5 ug/ml,1 ug/ml, 2 ug/ml, 4 ug/ml, 8 ug/ml and 16 ug/ml. MTT assay was taken out for testing cell viability at 24 hr, 48 hr and 72 hr. Meanwhile, FITC Annexin V/PI double staining was taken out to distinguish apoptosis and necrosis. Scratch assay was taken out to evaluate cell migration. Cell lysate was collected at the same time. Phospho-VEGF Receptor 2 level and Phospho-Akt level were tested through Western Blot. 43 apoptosis related protein levels were measured using human apoptosis antibody array assay. Result The data from MTT assay showed that DMH4 treatment decreased cell viability in a dose-depend manner. At the concentrations of 1 ug/ml, DMH4 effectively decreased viabilities of both H460 (82.1%, P&amp;lt;0.01) and A549 (78.5%, P&amp;lt;0.01) NSCLC cells, but had no effect on the normal lung MRC5 cells (103.6%). In addition, our study demonstrated that DMH4 promoted apoptosis in NSCLC cells, but did not show significantly effects in normal lung cells. Our further study indicated that DMH4 also suppressed NSCLC migration. Through Western Blot, phospho-VEGFR2 and phosphor-Akt levels were both detected lower in H460 and A549 than in MRC5. Conclusion As it can effectively suppress cell proliferation and migration in NSCLC cells but not in normal lung cells, DMH4 may be a good drug lead as a new VEGFR2 inhibitor for NSCLC treatment in the future. Note: This abstract was not presented at the meeting. Citation Format: Hao Li, Chay Bae, Nicky Gazy, Jijun Hao, Li Zhong. DMH4, A VEGFR2 inhibitor effectively suppresses proliferation and migration of lung cancer cells. [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 3610. doi:10.1158/1538-7445.AM2015-3610
Remission Induction in a Phase 1 Study of a Bispecific Single Chain Immunotoxin Targeting CD22 and CD19 (DT2219) for Refractory B-Cell Malignancies
Authors: Veronika Bachanova, Arthur Frankel, Qing Cao, Dixie Lewis, Michael Verneris, Aleksandr Lazaryan, Linda J. Burns, Daniel Vallera
Journal: Blood (2014)
Elevated Serum Ferritin Predicts the Delay of Engraftment and High Incidence of Blood Stream Infection within 100 Days After Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Heiwa Kanamori, Takayoshi Tachibana, Hirotaka Takasaki, Masatsugu Tanaka, Yoshiaki Ishigatsubo, Atsuo Maruta
Journal: Blood (2009)
Immunohystochemical analysis of SOCS3 in prostatic adenocarcinoma biopsies.
Authors: F. Pierconti, T. Cenci, C. Pozzo, F. Pinto, A. Totaro, P. F. Bassi, L. M. Larocca
Journal: Journal of Clinical Oncology (2011)

e15132 Background: Chronic inflammation and the subsequent tissutal alterations may play a key role in prostate carcinogenesis. Molecular alterations of the suppressor of cytokine signaling (SOCS)3, can contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of cancer. In a recent study, we demonstrated that methylation of SOCS3 may be involved in the pathogenesis of prostate cancer and could identify in a subset of tumor with an aggressive behavior. Methods: We analyzed the protein expression of SOCS3 by immunohistochemistry in 50 prostate cancer biopsies: 30 prostatic carcinoma with Gleason score 7, 10 with Gleason score <7 and 10 with Gleason score >7. Slides were incubated with monoclonal antibody SOCS3 (1E4) (1.5 mg/ml; Abnova, Taiwan). The SOCS3 staining intensity were evaluated by two pathologist (FP and LML) in three different way: positive; negative; weak intensity staining with negative neoplastic glands. Colonic mucosa were used as positive control. Results: SOCS3 positive were found in all cases of adenocarcinoma Gleason score < 7 and in 10 cases with Gleason score 7, negative staining were found in all cases of adenocarcinoma Gleason score > 7 and in 8 cases with Gleason score 7. Weak SOCS3 staining with presence of negative neoplastic glands were found in 12 cases of adenocarcinoma Gleason score 7. The group of tumor SOCS3 negative were significantly more aggressive than group SOCS3 positive in terms of TNM stage,positivity of surgical margin. Cases with weak SOCS3 staining and negative neoplastic glands displayed more aggressive clinical behavior than cases SOCS3 positive (increase number of T3a and positive surgical margins), on the other hand unlike SOCS3 negative no stage T3b and lymphnode metastasis were found. Conclusions: Immunohystochemical analysis of SOCS3 protein unlike methylathion study identify three different groups of tumors: positive, negative and with weak SOCS3 staining with the presence of negative neoplastic glands. In this last group the reduction of expression protein and the presence of negative neoplastic glands could indicate an intermediate stage of tumor turning towards shutdown of SOCS3 and thus object of strict follow-up and suitable to demethylating agents therapy.
Effect of heat treatment on mechanical and biodegradable properties of an extruded ZK60 alloy
Authors: Junxiu Chen, Lili Tan, Ke Yang
Journal: Bioactive Materials (2016)

ZK60 magnesium alloy possess good mechanical properties and is a potential biodegradable material. But its high degradation rate is not desirable. In this study the effect of heat treatment on the biodegradable property of ZK60 alloy was investigated. T5 treated, T6 treated, as-cast and as-extruded ZK60 alloys were studied. Microstructure characterization, electrochemical measurement and immersion test were carried out. The results showed that both the mechanical properties and degradation behavior were improved after T5 treatment due to the formation of small and uniformly distributed MgZn phases. The as-cast alloys also exhibited good corrosion resistance. However, the as-extruded and T6 treated samples were severely corroded due to the formation of large amounts of second phases accelerating the corrosion rate owing to the galvanic corrosion. The corrosion resistance of ZK60 alloy was as following: T5 treated > as-cast > T6 treated > as-extruded.
Abstract 3970: Development of novel form of mimic microRNA for lung cancer therapy
Authors: Shinichiro Ohno, Karen Itano, Yuichirou Harada, Koutaro Asada, Keiki Oikawa, Mikie Kashiwazako, Masakatsu Takanashi, Katsuko Sudo, Norihiko Ikeda, Masahiko Kuroda
Journal: Cancer Research (2015)

Abstract Exogenously supplied tumor suppressor miR-34a induces apoptosis and cell cycle arrest in lung cancer cell lines. It is suggested that miRNA replacement therapy of miR-34a is a promising approach for the treatment of lung cancer. On the one hand, the immunological response to nucleic acid via Toll like receptors (TLRs) and RIG-I like receptors (RLRs) that restrict the practical use of nucleic acid drugs in the clinical setting. It is known that the immunological response to the nucleic acid is strongly depends the length of nucleic acid. Therefore, we have tried to develop a shorter nucleic acid drugs that can escape immune surveillance. The deletion of nucleotide with maintenance of the secondary structure of short miR-34a keeps the activity and the target specificity of miR-34a. Finally, miR-34a can be shortened from 44 to 30 nucleobase. The shortened 30 nucleotides miR-34a was named “Guide hairpin RNA (ghR) -34a” and analyzed in detail. The inhibitory activity against miR-34a targets genes such as AXL, MET and CDK6 were comparable between ghR-34a and physiological form of miR-34a at both the mRNA and protein levels. Similarly, there is no difference in the antiproliferative activity against lung cancer cell line between ghR-34a and miR-34a. On the other hand, the ghR-34a does not induce inflammatory response and unwanted gene inhibition by passenger strand. These data indicated that ghR-34a can inhibits lung cancer with low side effects. Furthermore, the shortening methods can be broadly applied to the other miRNAs. Thus, the shortening methods of miRNA developed in the study may be provide a novel, safe and effective nucleic acid drug platform and promote the clinical usefulness of nucleic acid therapy. Note: This abstract was not presented at the meeting. Citation Format: Shinichiro Ohno, Karen Itano, Yuichirou Harada, Koutaro Asada, Keiki Oikawa, Mikie Kashiwazako, Masakatsu Takanashi, Katsuko Sudo, Norihiko Ikeda, Masahiko Kuroda. Development of novel form of mimic microRNA for lung cancer 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 3970. doi:10.1158/1538-7445.AM2015-3970
Training partners to look for melanoma signs does not increase embarrassment, study shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Training the partners of melanoma patients can help them effectively check for new skin cancers without increasing their embarrassment or discomfort, a research letter in JAMA Dermatology shows.1

Researchers from Northwestern University Feinberg School of Medicine in Chicago, USA, evaluated a skin self examination education training programme given to 395 patients and their partners. …
Recommendations for Clinical Trial Development in Follicular Lymphoma
Authors: Kami Maddocks, Paul M Barr, Bruce D Cheson, Richard F Little, Lawrence Baizer, Brad S Kahl, John P Leonard, Nathan Fowler, Leo I Gordon, Brian K Link, Jonathan W Friedberg, Stephen M Ansell
Journal: JNCI Journal of the National Cancer Institute (2016)

Follicular lymphoma (FL) is the second most common lymphoid malignancy, representing 20% to 25% of all cases of non-Hodgkin's lymphoma (NHL), and the most common of the indolent NHLs. FL is considered incurable in the majority of patients with the current standard therapeutic approaches, although outcomes have improved in the last few decades with our current therapies, with a median overall survival that now exceeds 18 years. While the majority of patients with FL have improved outcomes with our current therapeutic approaches, there are patients with high-risk disease features that have inferior outcomes to these therapies. There is an urgent need to integrate novel therapeutic agents into the treatment regimens for these patients to improve outcomes with continued evaluation of biomarkers indicative of prognosis and effects of these regimens on quality of life.
Core Binding Factor Acute Myeloid Leukemia of the Elderly Treated with Conventional Chemotherapy: A Collaborative Study of the French CBF AML Intergroup
Authors: Thomas Prebet, Nicolas Boissel, Christian Recher, Xavier Thomas, Jacques Delaunay, Jean-Yves Cahn, Arnaud Pigneux, Bruno Quesnel, Francis Witz, Sylvain Thépot, Valérie Ugo, Christine Terre, Emmanuelle Tavernier, Sylvie Castaigne, Francois Guilhot, Hervé Dombret, Norbert Vey
Journal: Blood (2008)
Tyro3, Axl Ve Mer (TAM) Receptors On Surfaces of Mononuclear Cells in Patients with B-Cell Chronic Lymphocytic Leukemia
Authors: Dilvin Guney, Aysin Tulunay, Funda Pepedil, Isik Kaygusuz, Cafer Adiguzel, Tülin Tuglular, Muzaffer Demir, Emel Eksioglu-Demiralp, Fikriye Uras
Journal: Blood (2012)
Percutaneous cryoablation for hepatocellular carcinoma
Authors: Kyoung Doo Song
Journal: Clinical and Molecular Hepatology (2016)

Local ablation therapy is considered as a conventional treatment option for patients with early stage hepatocellular carcinoma (HCC). Although radiofrequency (RF) ablation is widely used for HCC, the use of cryoablation has been increasing as newer and safer cryoablation systems have developed. The thermodynamic mechanism of freezing and thawing used in cryoablation is the Joule-Thomson effect. Cryoablation destroys tissue via direct tissue destruction and vascular-related injury. A few recent comparative studies have shown that percutaneous cryoablation for HCCs is comparable to percutaneous RF ablation in terms of long term therapeutic outcomes and complications. Cryoablation has several advantages over RF ablation such as well visualization of iceball, no causation of severe pain, and lack of severe damage to great vessels and gallbladder. It is important to know the advantages and disadvantages of cryoablation compared with RF ablation for improvement of therapeutic efficacy and safety. Keywords: Cryoablation; Hepatocellular carcinoma; Radiofrequency ablation
Modern implant dentistry based on osseointegration: 50 years of progress, current trends and open questions
Authors: Daniel Buser, Lars Sennerby, Hugo De Bruyn
Journal: Periodontology 2000 (2016)

In the 1960s and 1970s, implant-supported prostheses based on subperiosteal or blade implants had a poor reputation because of questionable clinical outcomes and lack of scientific documentation. The change to a scientifically sound discipline was initiated by the two scientific pioneers of modern implant dentistry, Professor P. I. Brånemark from the University of Gothenburg in Sweden and Professor André Schroeder from the University of Bern in Switzerland. Together with their teams, and independently of each other, they laid the foundation for the most significant development and paradigm shift in dental medicine. The present volume of Periodontology 2000 celebrates 50 years of osseointegration. It reviews the progress of implant therapy over the past 50 years, including the basics of implant surgery required to achieve osseointegration on a predictable basis and evolving innovations. The development of bone-augmentation techniques, such as guided bone regeneration and sinus floor elevation, to correct local bone defects at potential implant sites has increased the indications for implant therapy. The paradigm shift to moderately rough implant surfaces resulted in faster and enhanced bone integration and led to improvements in various treatment protocols, such as immediate and early implant placement in postextraction sites, and made various loading protocols possible, including immediate and early implant loading. In the past 15 years, preoperative analysis and presurgical planning improved as a result of the introduction of three-dimensional imaging techniques. Hereby, cone-beam computed tomography offers better image quality with reduced radiation exposure, when compared with dental computed tomography. This opened the door for digital planning and surgical modifications. Over the last 50 years this evolution has facilitated tremendous progress in esthetic outcomes with implant-supported prostheses and improved patient-centered outcomes. This volume of Periodontology 2000 also discusses the current trends and open questions of implant dentistry, such as the potential of digital implant dentistry in the surgical and prosthetic field, the trend for an increasing average age of implant patients and the related adaptations of treatment protocols, and the second attempt to establish ceramic implants using, this time, zirconia as the implant material. Finally, some of the hottest controversies are discussed, such as recent suggestions on bone integration being a potential foreign-body reaction and the evidence-based appraisal of the peri-implantitis debate.
Artificial Antigen Presenting Cells Expand NY-ESO-1 Antigen-Specific CD8+ T Cells From Patients with Melanoma
Authors: Marcela V. Maus, Isabelle Riviere, Oriana Borquez-Ojeda, Xiuyan Wang, Jianda Yuan, Taha Merghoub, Jason Plotkin, Richard J. O’Reilly, Jedd D Wolchok, Michel Sadelain
Journal: Blood (2011)