tbuckley/cabot-search huggingface dataset:
Zero-order controlled release of BMP2-derived peptide P24 from the chitosan scaffold by chemical grafting modification technique for promotion of osteogenesis <i>in </i>vitro and enhancement of bone repair <i>in vivo</i>
Authors: Yan Chen, Xujie Liu, Rui Liu, Yong Gong, Mingbo Wang, Qianli Huang, Qingling Feng, Bo Yu
Journal: Theranostics (2017)

Combination of tissue-engineered bone scaffolds with cell-adhesive, osteoconductive, or osteoinductive biomolecules is a critical strategy to improve their properties that significantly influence cellular behaviors, such as adhesion, proliferation, and differentiation, which is beneficial for critical-sized bone defects repairing. However, the traditional surface modification techniques, such as physical adsorption, coating, and plasma treatment, et al, have great limitations for immobilization of bioactive molecules due to undesirable controlled delivery performance or overly complex multistep procedures. In this study, we functionalized the chitosan/hydroxyapatite (CS/HA) biomimetic composite scaffold for controlled delivery of BMP2-derived peptide (P24) by the chemical grafting modification technique: firstly, P24 was conjugated with a thiolated chitosan, chitosan-4-thiobutylamidine (CS-TBA); secondly, the resultant CS-P24 was then combined with HA to prepare CS-P24/HA scaffolds. The effect of CS-P24/HA scaffolds on bone regeneration was evaluated, along with the underlying biological mechanisms responsible in vitro and in vivo. In vitro, the controlled and sustained release of bioactive P24 could last up to 90 days, furthermore, the release profiles of CS-5%P24/HA and CS-10%P24/HA were linear and could be fitted according to zero-order kinetic model (R2=0.9929; R2=0.9757); P24 on the scaffold significantly promoted cell adhesion, proliferation, osteodifferentiation, and mineralization with synergistic effects. Bone marrow stromal cells (BMSCs) revealed spindle-shaped surface morphology, indicating the CS-P24/HA scaffolds supported cell adhesion and possessed a high proliferation rate that varied according to the P24 concentration levels. Furthermore, mRNA levels for OCN, Runx2, and collagen I were significantly up-regulated on CS-P24/HA scaffolds compared with cells grown on CS/HA scaffolds in vitro (p < 0.05). Similarly, the BMSCs exhibited a higher ALP expression and calcium deposition level on CS-P24/HA scaffolds compared with CS/HA scaffolds (p < 0.05). In vivo, osteoinductive studies revealed a significantly higher ectopic osteogenesis level of CS-10%P24/HA scaffolds in rat dorsal muscle pockets compared with that of CS/HA scaffolds. Finally, CS-P24/HA scaffolds showed superior performance in the reconstruction of rat calvarial bone defects. This novel CS-P24/HA scaffold is deemed a strong potential candidate for the repair of bone defects in human bone tissue engineering.
Insights into Clonal Relationships of Putative Adaptive Natural Killer Cells (NK) in Humans, Via Mapping of Somatic Piga Mutations in Patients with Paroxysmal Nocturna Hemoglobinuria (PNH)
Authors: Thomas Winkler, Marcus A.F. Corat, Delong Liu, Moonjung Jung, Danielle M. Townsley, Chuanfeng Wu, Neal S Young, Cynthia E. Dunbar
Journal: Blood (2015)
Letter to the editor: Increasing proportion of new HIV diagnoses in Ireland previously diagnosed elsewhere – potential impact on estimating incidence
Authors: Kate O'Donnell, Derval Igoe
Journal: Eurosurveillance (2017)

Preview this article: Letter to the editor: Increasing proportion of new HIV diagnoses in Ireland previously diagnosed elsewhere – potential impact on estimating incidence, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/22/9/eurosurv-22-30472-4-1.gif
Allogeneic transplant (related or unrelated donor) is the preferred treatment for adult Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL). Results from the international ALL trial (MRC UKALLXII/ECOG E2993)
Authors: A H Goldstone, H G Prentice, J Durrant, I M Franklin, G Harrison, S M Richards, H M Lazarus, P H Wiernik, M S Tallman, J M Rowe
Journal: Blood (2001)
Novel monoclonal antibody that enhances natural killer (NK) cell cytotoxicity against multiple myeloma (MM): Preclinical data and interim phase I clinical trial results
Authors: D. M. Benson, F. Romagne, P. Squiban, N. Wagtmann, S. Farag, A. Mita, C. Hofmeister, M. Smith, C. Bakan, M. Caligiuri
Journal: Journal of Clinical Oncology (2009)

3032 Background: MM is increasing in incidence and remains incurable. NK cells have modest killing activity against MM cells in part because of inhibitory signals from HLA class 1 antigens which act via the KIR receptors on NK cells. A novel anti-KIR blocking antibody (1–7F9 named IPH 2101) enhances patient NK cell cytotoxicity against autologous MM tumor cells in vitro and appears safe in an ongoing phase 1 clinical trial. Methods: NK cells from healthy controls or patients were pre-treated with IPH 2101 or IgG4 isotype control and co-cultured with MM cell lines or autologous MM tumor targets. NK cell production of interferon-gamma (IFN-γ) or granzyme B (GrB) were measured by ELISPOT. An open-label, single-agent, phase 1 dose escalation study of IPH 2101 is being conducted in patients with relapsed/refractory MM. KIR binding, pharmacokinetics, pharmacodynamics, effects on NK cell maturation, and biological effects of IPH 2101 are being monitored in all patients. Results: At an effector to target (E:T) ratio of 1:1, IPH 2101 significantly enhances NK cell IFN-γ release against MM targets (mean 33 spots/well ± 12, SEM vs. 11 ± 0.3, p = 0.005). At an E:T ratio of 10:1, IPH 2101 enhances NK cell cytotoxicity, by GrB release, of patient NK cells against autologous MM tumor cells (mean 111 spots/well ± 14, SEM vs 56 ± 10, p = 0.002). By Western blot, IPH 2101 may reduce levels of src, a kinase known to be involved in inhibitory KIR signaling. Dose escalation in the phase 1 study has been completed from 0.0003 mg/kg to 0.075 mg/kg in 14 evaluable patients. At the highest dose tested, KIR occupancy has been detected at a mean 95% ± 1.4 at 2 hours post dose, lasting up to 56% ± 18 during 2 weeks post dose. At this dose level, PK data show good correspondence with previous modeling activity. No deleterious effect on NK cell maturation has been seen. IPH 2101 has been well tolerated to date. Conclusions: IPH 2101 improves autologous NK cell killing of MM tumor cells by blocking inhibitory KIR. In the ongoing clinical trial, the antibody appears safe and well tolerated at the doses tested. This immunotherapeutic approach may hold promise as treatment for MM and further study is warranted. [Table: see text]
Abstract B19: Disruption of energy homeostasis as an approach to block the proliferation of colon carcinomatosis
Authors: Fabio Bozzi, Angela Mogavero, Luca Varinelli, Annunziata Gloghini, Valerio Leoni, Galina V. Beznoussenko, Alexandre A. Mironov, Ermanno Leo, Marco A. Pierotti, Italia Bongarzone, Manuela Gariboldi
Journal: Cancer Research (2017)

Abstract Strategies aimed at obtaining a complete cytoreduction are needed to improve long-term survival for patients with colorectal cancer peritoneal carcinomatosis (CRC-pc). We established organoid models that presented cancer stem cell characteristics from naïve CRC-pc surgical samples of two patients (C1 and C2). The organoids recapitulated their corresponding clinical samples in terms of 3D structure and immmunoistochemical profile and were enriched in LGR5 positive cancer stem cells. Proteomic analyses of organoids highlighted their strong dependence on energy producing pathways, suggesting that their targeting may be an effective therapeutic approach for the ablation of cancer cell malignancies. To test this hypothesis we treated organoids with an inhibitor of MIF/CD74 signaling axis, 4-iodo-6-phenylpyrimidine (4-IPP), and metformin, which inhibits mitochondrial oxidation. Both the drugs target metabolism acting on AMP-activated protein kinase (AMPK), the main regulator of cellular energy homeostasis. AMPK inhibits the major anabolic processes sustaining cancer cell proliferation and growth and confers cell plasticity to survive under conditions of metabolic stress, such as hypoxia and glucose deprivation, which is commonly observed in tumors with rapid growth. As a new finding we observed that treatment of organoids with 4-IPP resulted in decreased AMPK signaling activity, inducing a stress-signaling response and death of cultured organoids. Conversely, metformin treatment enhanced AMPK activation under energy stress, decreasing the activity of the anabolic factors ribosomal protein S6 and p4EBP-1 and inhibiting the mitochondrial activity, hindering cell proliferation. Furthermore, metformin treated organoids exhibited a Warburg-like metabolic profile. Our results show that organoid metabolism can be disrupted by metformin-induced AMPK activation but also through a strong reduction in AMPK functions caused by the removal of MIF/CD74 signaling axis that induces an irreversible disruption of energy homeostasis and ultimately causes cell death. Overall, we suggest that AMPK functions are crucial for energy metabolism of colorectal cancer peritoneal carcinomatosis, and regulation of AMPK activity could be a potential molecular target for the treatment of CRC-pc. Citation Format: Fabio Bozzi, Angela Mogavero, Luca Varinelli, Annunziata Gloghini, Valerio Leoni, Galina V. Beznoussenko, Alexandre A. Mironov, Ermanno Leo, Marco A. Pierotti, Italia Bongarzone, Manuela Gariboldi. Disruption of energy homeostasis as an approach to block the proliferation of colon carcinomatosis. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B19.
Third Party Cytokine-Induced Killer Cells Protect from Murine Lethal Graft-Versus-Host Disease
Authors: Rie Kuroda, Shintaro Mase, Toshihiro Fujiki, Hideaki Maeba, Raita Araki, Yasuhiro Ikawa, Masaki Fukuda, Shoichi Koizumi, Akihiro Yachie, Ryosei Nishimura
Journal: Blood (2015)
Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study
Authors: Christophe Hézode, Massimo Colombo, Marc Bourlière, Ulrich Spengler, Ziv Ben‐Ari, Simone I. Strasser, William M. Lee, Leslie Morgan, Jingjun Qiu, Peggy Hwang, Michael Robertson, Bach‐Yen Nguyen, Eliav Barr, Janice Wahl, Barbara Haber, Robert Chase, Rohit Talwani, Vito Di Marco
Journal: Hepatology (2017)

Direct‐acting antiviral agents have not been studied exclusively in patients with inherited blood disorders and hepatitis C virus (HCV) infection. The objective of the randomized, placebo‐controlled, phase III C‐EDGE IBLD study was to assess the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) in patients with inherited bleeding disorders and HCV infection. One hundred fifty‐nine adults with HCV infection and sickle cell anemia, thalassemia, or hemophilia A/B or von Willebrand disease were enrolled at 31 study sites in the United States, Europe, Australia, Canada, Israel, and Thailand. Patients were given an oral, once‐daily, fixed‐dose combination of EBR/GZR 50 mg/100 mg for 12 weeks and randomized to the immediate‐treatment group (ITG) or deferred‐treatment group (DTG; placebo followed by active treatment). The primary endpoints were the proportion of patients in the ITG with unquantifiable HCV RNA 12 weeks posttreatment (sustained virological response 12 weeks after completion of study treatment; SVR12) and the comparison of safety in the ITG and DTG. In the ITG, 100 of 107 patients (93.5%) achieved SVR12, 6 relapsed, and 1 was lost to follow‐up. SVR12 was achieved in 94.7% (18 of 19), 97.6% (40 of 41), and 89.4% (42 of 47) of patients with sickle cell disease, β‐thalassemia, and hemophilia A/B or von Willebrand disease, respectively. Serious adverse events were reported by 2.8% (n = 3) and 11.5% (n = 6) of patients in the ITG and DTG, respectively. Hemoglobin levels and international normalized ratio values were similar in patients receiving EBR/GZR and placebo; among patients with hemoglobinopathies, change in mean hemoglobin levels was similar in those receiving EBR/GZR compared to those receiving placebo. Conclusion : These results add to the expanding pool of data available for EBR/GZR, indicating a high level of efficacy and favorable tolerability in patients with HCV infection. (H epatology 2017;66:736–745)
Peripheral Blood Lymphocyte and Platelet STEM CELL Expansion in Autologous Platelet-Derived Growth Factor-RICH Plasma
Authors: Rodolfo J Salas, Dalila De Salvo, Luigi De Salvo Cardullo, Manzur Hassanhi, Luis S Paz, Dalida Salas, Alba Fuenmayor, Zulay Acurero, Ricardo Carrizo, Humberto Herrera, Iris Nunez
Journal: Blood (2012)
Prospective Evaluation of the Bone Anabolic Effect of Bortezomib in Relapsed Multiple Myeloma (MM) Patients.
Authors: Maurizio Zangari, Federica Cavallo, Larry Suva, Joshua Dilley, Guido Trico, Bart Barlogie, Michael J. Burns, Roberto Passera, Mario Boccadoro, Dixie Esseltine, Shmuel Yaccoby
Journal: Blood (2007)
Safety and antitumor activity of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (HCC): Interim analysis of dose-expansion cohorts from the phase 1/2 CheckMate-040 study.
Authors: Bruno Sangro, Ignacio Melero, Thomas Cheung Yau, Chiun Hsu, Masatoshi Kudo, Todd S. Crocenzi, Tae-You Kim, SuPin Choo, Jorg Trojan, Tim Meyer, Yoon-Koo Kang, Jeffrey Anderson, Christine Marie Dela Cruz, Lixin Lang, Jaclyn Neely, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2016)

4078 Background: HCC tumors are associated with chronic inflammation that can promote an immunosuppressive environment; anti-PD-1 therapy may counter this inhibition. Nivo, a fully human IgG4 monoclonal antibody PD-1 inhibitor, was initially evaluated in a multiple ascending-dose, phase 1/2 study in pts with advanced HCC; it was well tolerated with antitumor activity in different etiologies, across lines of therapy, justifying an expansion phase. Interim results are presented. Methods: Pts had histologically confirmed, advanced HCC and Child-Pugh class A. Dose expansion at nivo 3 mg/kg occurred in 4 cohorts: uninfected sorafenib (sor) naïve/intolerant, uninfected sor progressors, HCV-, and HBV-infected. Primary endpoint was confirmed overall response rate (ORR) by RECIST 1.1. Secondary endpoints included OS, PFS, time to progression, and biomarker assessment. Results: Dose expansion enrolled 206 pts; 75% had extrahepatic metastasis, 7% vascular invasion, and 64% prior sor. Across cohorts, pts received a median of 5–6 doses (range: 1–19). Treatment-related AEs (TRAEs) occurred in 104 pts (50%); the most frequent were fatigue (17%) and pruritus (12%). Grade 3/4 TRAEs were seen in 28 pts (14%); most common were ALT and AST increases (3% each). 68 of 174 evaluable pts (39%) had a decline in tumor burden. Preliminarily, 91 pts (55%) had ≥ 18 wks follow-up and/or PD. ORR for these pts was 9% (8/91) [14% (3/22) uninfected sor naïve/intolerant; 7% (2/27) uninfected sor progressors; 14% (3/21) HCV-infected; (0/21) HBV-infected]. 6 mos OS rate was 69% (95% CI, 0.43–0.85). Responses were observed in pts with and without quantifiable PD-L1 measured by IHC. Antiviral responses in HCV- and HBV-infected pts have been observed as measured by declines in HCV RNA and quantitative HBV surface antigen. Conclusions: AEs were consistent across nivo cohorts and similar to profiles in other tumor types. Results are preliminary and may underestimate response; data indicate activity across all etiologic subtypes and lines of therapy, supporting ongoing study of nivo in HCC. Clinical trial information: NCT01658878.
Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis
Authors: Md. Mahmudul Alam, Hwa Seung Han, Shijin Sung, Jin Hee Kang, Keum Hee Sa, Hasan Al Faruque, Jungwan Hong, Eon Jeong Nam, In San Kim, Jae Hyung Park, Young Mo Kang
Journal: Journal of Controlled Release (2017)
Ibrutinib for Bridging to Allogeneic Hematopoietic Stem Cell Transplantation (alloHCT) in Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) Is Safe and Effective: First Results of a Survey By the Chronic Malignancy and the Lymphoma Working Parties of the EBMT
Authors: Peter Dreger, Mauricette Michallet, Jennifer Hoek, Ariane Boumendil, Mohamad Sobh, Lutz Muller, Elisabeth A. Vandenberghe, Ilaria Scortechini, Niels S. Andersen, Jurgen Finke, Domenico Russo, Jakob R Passweg, Helene Schoemans, Nadira Durakovic, Helene Labussiere, Tobias Berg, Dietger Niederwieser, Wolfgang Bethge, Nicola Mordini, Michel van Gelder, Nicolaas PM Schaap, Nicolaus Kroger, Silvia Montoto, Johannes Schetelig
Journal: Blood (2016)
A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial
Authors: M.H. Kulke, P. Ruszniewski, E. Van Cutsem, C. Lombard-Bohas, J.W. Valle, W.W. De Herder, M. Pavel, E. Degtyarev, J.C. Brase, L. Bubuteishvili-Pacaud, M. Voi, R. Salazar, I. Borbath, N. Fazio, D. Smith, J. Capdevila, R.P. Riechelmann, J.C. Yao
Journal: Annals of Oncology (2017)
Allogeneic Hematopoietic Cell Transplantation From Combined Haploidentical Family Members and Unrelated Cord Blood (CB) Can Benefit High Risk Patients Lacking HLA-Identical Donors.
Authors: Elizabeth Shima Rich, Andrew Artz, Theodore Karrison, Lucy A Godley, Olatoyosi Odenike, Loren Joseph, Justin Kline, Vu H. Nguyen, Guadalupe Martinez, Paula del Cerro, Lisa Pape, Linda Schroeder, Scott Allen, Sarah Horowitz, John Cunningham, Richard A. Larson, Wendy Stock, Amittha Wickrema, Koen van Besien
Journal: Blood (2009)
Prospective cohort study of chemotherapy-induced alopecia with or without scalp cooling.
Authors: Julie Lemieux, Elizabeth Maunsell, Louise Provencher, Sophie Lauzier, Rami Younan, Belkacem Abdous
Journal: Journal of Clinical Oncology (2012)

9138 Background: Scalp cooling can prevent chemotherapy-induced alopecia. Success varies according to the type of chemotherapy. A controversy exists regarding the use of scalp cooling because of the lack of efficacy data with modern chemotherapy regimen and safety data. We present a prospective cohort study design to measure alopecia. Methods: The prospective study was conducted at the Centre des Maladies du Sein Deschênes-Fabia (CMS) in Quebec City (where scalp cooling is offered routinely and 85% of women use it) and at the Centre Hospitalier Universitaire de Montreal (CHUM), in Montreal (where scalp cooling is not available). Women were eligible if they were going to receive neoadjuvant or adjuvant chemotherapy for breast cancer. The study involved completion of questionnaires (on degree of alopecia, hair type, hair care, use of head accessories, tolerance to scalp cooling and questions related to sick leave from work) and having pictures taken at baseline, cycle 3 and at the last cycle of chemotherapy. For the last 43 patients, the EORTC QLQ-C30/BR23 and an adaptation for Hairdex were added. Results: A total of 136 patients were recruited (110 at CMS over 2 years and 26 at the CHUM over a 9-month period). Preliminary efficacy results are shown in the Table (data on quality of life have not yet been analyzed). Hair preservation was defined as a SUCCESS for hair loss (since the beginning of chemotherapy) characterized as “not at all”, “a little” or “moderate” and “FAILURE” when characterized as “a lot” or “all” or “hair shaved”. Overall, in the scalp cooling group, 34% were considered a “success” using hairdresser evaluation and 49% using patient evaluation; for the non scalp-cooling group, these rates were 9% and 4% respectively. Conclusions: Scalp cooling appears to be efficacious for preventing chemotherapy-induced alopecia in this exploratory cohort study. [Table: see text]
Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Gene Expression In Myeloma Cell Lines and Patients
Authors: Alessandra Perego, Prerna Tewari, Mark Lawler, Paul Browne, Stephen Drain, Mark Catherwood, Giuseppe Limonta, Daniele Perego, Manuela Carrera, Enrico Maria Pogliani
Journal: Blood (2010)
CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma
Authors: Bernard Escudier, Padmanee Sharma, David F. McDermott, Saby George, Hans J. Hammers, Sandhya Srinivas, Scott S. Tykodi, Jeffrey A. Sosman, Giuseppe Procopio, Elizabeth R. Plimack, Daniel Castellano, Howard Gurney, Frede Donskov, Katriina Peltola, John Wagstaff, Thomas C. Gauler, Takeshi Ueda, Huanyu Zhao, Ian M. Waxman, Robert J. Motzer
Journal: European Urology (2017)
Gene Set Enrichment Analysis of Ki-67high CLL Clones Suggests Complex Interactions of B-Cell Receptor Signaling and Normal Cell Interactions in the Disease
Authors: Xiao J. Yan, Daniel Kalenscher, Erin Boyle, Sophia Yancopoulos, Rajendra N Damle, Aarti Damle, Houman Khalili, Annette Lee, Wentian Li, Igor Dozmorov, Matthew Kaufman, Peter Gregersen, Steven L. Allen, Jonathan E. Kolitz, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2011)
Prospective Phase I Multi-Center Trial Incorporating Lenalidomide (LEN) into Dose-Adjusted EPOCH Plus Rituximab (DA-EPOCH-R) in Patients with Double Hit (DHL) or Double Expressing (DEL) Lymphomas: Final Results
Authors: Chadi Nabhan, Theodore Karrison, Justin Kline, Kenneth Cohen, Michael R. Bishop, Reem Karmali, Aaron P. Rapoport, Parameswaran Venugopal, James Wade, Paul Fishkin, Sonali M. Smith
Journal: Blood (2016)
FANCD2 Localizes to Cross-Linked Induced Nuclear Foci That Are Distinct From Those to Which αaII Spectrin and the Cross-Link Repair Protein, XPF, Co-Localize, Indicating An Involvement of These Proteins in Different Steps of the DNA Interstrand Cross-Link Repair Process.
Authors: Pan Zhang, Deepa Sridharan, Michael Acosta, Muriel Lambert
Journal: Blood (2009)