Pharmacists have made progress in implementing SP, which is perceived by pharmacist prescribers as beneficial for both patients and themselves. Pharmacists need more support in terms of infrastructure and integration into the healthcare team to overcome some of the barriers to implementing SP.
DNA origami is a novel self-assembly technique allowing one to form various 2Dshapes and position matter with nanometer accuracy. We use DNA origami templates to engineer Surface Enhanced Raman Scattering (SERS) substrates. Specifically, gold nanoparticles were selectively placed on the corners of rectangular origami and subsequently enlarged via solution-based metal deposition. The resulting assemblies exhibit "hot spots" of enhanced electromagnetic field between the nanoparticles. We observed a significant Raman signal enhancement from molecules covalently attached to the assemblies, as compared to control nanoparticle samples which lack inter-particle hot spots. Furthermore, Raman molecules are used to map out the hot spots' distribution, as they are burned when experiencing a threshold electric field. Our method opens up the prospects of using DNA origami to rationally engineer and assemble plasmonic structures for molecular spectroscopy.
The nonoxidizing catalytic noble metal rhodium is introduced for ultraviolet plasmonics. Planar tripods of 8 nm Rh nanoparticles, synthesized by a modified polyol reduction method, have a calculated local surface plasmon resonance near 330 nm. By attaching p-aminothiophenol, local field-enhanced Raman spectra and accelerated photodamage were observed under near-resonant ultraviolet illumination, while charge transfer simultaneously increased fluorescence for up to 13 min. The combined local field enhancement and charge transfer demonstrate essential steps toward plasmonically enhanced ultraviolet photocatalysis.
Introduction Over-expression of the anti-apoptotic protein BCL-2 in MDS has been implicated in progression and drug resistance in MDS. Venetoclax (Ven), a selective, potent, orally bioavailable BCL-2 inhibitor, was recently approved in combination with HMAs or low dose cytarabine for the frontline management of older unfit pts with AML. In this study, we sought to evaluate the safety and efficacy of Ven in pts with R/R MDS. Methods This is an ongoing phase 1b, open-label, multicenter study in R/R MDS (NCT02966782). Key eligibility criteria include age ≥18 years, failure of HMA after receiving at least 4 cycles of Aza or 4 cycles of decitabine within the previous 5 years, marrow blasts <20%, and ECOG Performance status of ≤2. Cohort 1 (C1) pts received Ven monotherapy, either 400 mg (Arm A) or 800 mg (Arm B) per cycle (28 days) and Cohort 2 (C2) pts received Aza combined with escalating doses of Ven: 100, 200 and 400 mg daily for 14 of 28-day cycles. Aza was administered at the standard dose (75 mg/m2/day) for the first 7 days of each cycle. The primary objectives were to evaluate the safety profiles and the recommended Phase 2 dose (RP2D) of Ven monotherapy and Ven+Aza. Key secondary objectives included a preliminary assessment of overall response rate (ORR, defined as complete remission [CR]+marrow complete remission [mCR]+partial response [PR]) , time to first response (TTR), progression-free survival (PFS), and overall survival (OS). We used the modified International Working Group 2006 criteria for response assessment (Cheson et. al., Blood, 2006). Results As of April 9, 2019, 46 pts [87% male, median age 76 years (range 44-91)] were enrolled. C1 (Ven monotherapy) included 22 pts, C2 (combination therapy) included 24 pts. At baseline, 37 (80%) pts received at least one prior therapy, 2 (15%) pts received 2, and 1 (2%) patient received >3 therapies prior to enrollment in the study. Baseline bone marrow blasts were: ≤5% was observed in 16 (35%) pts, >5% and ≤10% in 23 (50%), and >10% in 7 (15%) pts respectively. Cytogenetics risk was evaluated in 27/46 pts and were as follows: Good 12 (44%), Intermediate 9 (33%), and Poor 6 (22%). Overall, 9 pts discontinued study therapy (8 deaths, 1 withdrew consent). The most frequent treatment-emergent adverse events (TEAEs) included neutropenia, thrombocytopenia, nausea, and diarrhea (Table ). Infectious TEAEs included febrile neutropenia and pneumonia. Predominant Grade 3 and 4 TEAEs were hematological and included neutropenia (41%), thrombocytopenia (30%), leukopenia (24%), and anemia (15%). Serious TEAEs occurring in ≥2 pts were febrile neutropenia (n=8), pneumonia (n=6), thrombocytopenia (n=2), and epistaxis (n=2). Death on study occurred in 8 (17%) pts, of whom 6 died of progressive disease. Other causes of death were septic shock (n=1) and pneumonia (n=1). Forty of 46 pts were response evaluable. Median follow-up time was 4.7 mos (range: 3.7-6.3 mos). In C1, ORR was 7% (1/16). Stable disease was observed in 75% (12/16) pts. Median TTR was 1.6 mos (range: 1.6-1.6 mos). Median PFS was 3.4 mos (95% CI: 1.9-5.2 mos) and 6-mos estimate for OS was 57% (95% CI: 22%, 81%). In C2, ORR was 50% (12/24 pts). Of those, 13% (3/24) had CR and 38% (9/24) had mCR. Stable disease was observed in 31% (10/24) pts. Median PFS, and OS were not reached. The 6-mos estimate for PFS was 76% (95% CI: 50%, 89%) and estimated OS at 9-mos was 83% (95% CI: 55%, 95%). Finally, 4 pts came off study to receive allogeneic stem cell transplantation. Conclusion Ven monotherapy and combination Ven+Aza were well tolerated in pts with R/R MDS and most AEs were manageable. Although the study is still ongoing, the 6-mos OS estimate of 57% in monotherapy pts compares favorably to historical controls. In addition, the ORR observed with combination therapy, and the observed 9-mos OS rate of 83% also compare favorably with historical data. Updated data on safety and efficacy, including data on RP2D, will be presented at the meeting. Disclosures Zeidan: Ariad: Honoraria; Agios: Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Otsuka: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding. Pollyea:Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Diachii Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Garcia:Abbvie: Research Funding; Genentech: Research Funding. Brunner:Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Forty Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees. Roncolato:St. George Hospital: Employment. Borate:Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy. Odenike:Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; Agios: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI/Baxalta: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Incyte: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Research Funding; Oncotherapy: Research Funding. Bajel:Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria; AbbVie: Honoraria; Pfizer: Honoraria. Watson:Amgen: Other: Travel grant; Roche: Other: Travel grant. Götze:AbbVie: Membership on an entity's Board of Directors or advisory committees. Nolte:Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Tan:AbbVie Inc: Other: Investigator in AbbVie funded trial. Hong:Roche: Equity Ownership; Genentech Inc.: Employment, Equity Ownership. Dunbar:AbbVie Inc: Employment, Other: Stock/stock options. Zhou:AbbVie Inc: Employment, Other: Stock/stock options. Gressick:AbbVie Inc: Employment, Other: Stock/stock options. Ainsworth:AbbVie Inc: Employment, Other: Stock/stock options. Harb:AbbVie Inc: Employment, Other: Stock/stock options. Salem:AbbVie: Employment, Other: Stock/stock options. Hayslip:AbbVie Inc: Employment, Other: Stock/stock options. Swords:AbbVie Inc: Employment, Other: Stock/stock options. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. OffLabel Disclosure: Venetoclax is a BCL-2 inhibitor that is FDA-approved in some indications. This presentation will focus on venetoclax for treatment in myelodysplastic syndromes, which is not an approved indication.
Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.