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At least 1,171 records · Page 65

Sclerotherapy of Diffuse and Infiltrative Venous Malformations of the Hand and Distal Forearm

PurposeVenous malformations (VM) involving the hand and forearm often lead to chronic pain and dysfunction, and the threshold for treatment is high due to the risk of nerve and skin damage, functional deterioration and compartment syndrome. The purpose of this study is to demonstrate that sclerotherapy of diffuse and infiltrative VM of the hand is a safe and effective therapy.Materials and MethodsA retrospective review of all patients with diffuse and infiltrative VM of the hand and forearm treated with sclerotherapy from 2001 to 2014 was conducted. All VM were diagnosed during the clinical visit by a combination of physical examination and imaging. Sclerotherapy was performed under imaging guidance using ethanol and/or sodium tetradecyl sulfate foam. Clinical notes were reviewed for signs of treatment response and complications, including skin blistering and nerve injury.ResultsSeventeen patients underwent a total of 40 sclerotherapy procedures. Patients were treated for pain (76 %), swelling (29 %) or paresthesias (6 %). Treatments utilized ethanol (70 %), sodium tetradecyl sulfate foam (22.5 %) or a combination of these (7.5 %). Twenty-four percent of patients had complete resolution of symptoms, 24 % had partial relief of symptoms without need for further intervention, and 35 % had some improvement after initial treatment but required additional treatments. Two skin complications were noted, both of which resolved. No motor or sensory loss was reported.ConclusionSclerotherapy is a safe and effective therapy for VM of the hand with over 83 % of patients experiencing relief.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Provision of Interventional Radiology Services in Europe: CIRSE Recommendations

Interventional Radiology (IR) is an essential part of modern medicine, delivering minimally invasive patient-focused care, which has been proven to be safe and effective in both elective and emergency settings. The aim of this document is to outline the core requirements and standards for the provision of Interventional Radiological services, including training, certification, manpower, and accreditation. The ultimate challenge will be the adoption of these recommendations by different countries and health economies around the world, in turn ensuring equal access to IR treatments for all patients, the appropriate distribution of resources for IR service provision as well as the continued development of safe and high-quality IR services in Europe and beyond.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multicenter Prospective Clinical Series Evaluating Radiofrequency Ablation in the Treatment of Painful Spine Metastases

BackgroundRadiofrequency ablation (RFA) of vertebral body metastases (VBM) has been reported as safe and effective in retrospective studies. This single-arm prospective multicenter clinical study evaluates RFA in the treatment of painful VBM.MethodsFifty patients with VBM were prospectively enrolled during a 13-month period at eight US centers under an IRB-approved study. Percutaneous RFA was performed under imaging guidance with cement augmentation at the discretion of the operator. Pain, disability and quality of life were evaluated at baseline, prior to discharge, days 3, 7, 30 and 90 using the Numerical Pain Rating Scale, Oswestry Disability Index (ODI), the Functional Assessment of Cancer Therapy-General 7 (FACT-G7) and Functional Assessment of Cancer Therapy Quality-of-Life Measurement in Patients with Bone Pain (FACT-BP). Adverse events were monitored throughout this time interval.ResultsTwenty-six male and 24 female patients (mean age 61.0) underwent 69 treatments (30 thoracic and 39 lumbar). Cement augmentation was performed in 96 % of reported levels. Significant improvement in mean scores for pain, disability and cancer-specific health-related quality of life from baseline to all time intervals was seen. NRPS improved from 5.9 to 2.1 (p < 0.0001). ODI improved from 52.9 to 37.0 (p < 0.08). FACT-G7 improved form 10.9 to 16.2 (p = 0.0001). FACT-BP improved from 22.6 to 38.9 (p < 0.001). No complications related to the procedure were reported.ConclusionRFA with cement augmentation safely and effectively reduces pain and disability rapidly, while increasing quality of life in patients suffering from vertebral body metastases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Transcatheter Arterial Embolization with a Mixture of Absolute Ethanol and Iodized Oil for Poorly Visualized Endophytic Renal Masses Prior to CT-Guided Percutaneous Cryoablation

PurposeTo retrospectively evaluate the feasibility of transcatheter arterial embolization (TAE) using a mixture of absolute ethanol and iodized oil to improve localization of endophytic renal masses on unenhanced computed tomography (CT) prior to CT-guided percutaneous cryoablation (PCA).Materials and MethodsOur institutional review board approved this retrospective study. From September 2011 to June 2015, 17 patients (mean age, 66.8 years) with stage T1a endophytic renal masses (mean diameter, 26.5 mm) underwent TAE using a mixture of absolute ethanol and iodized oil to improve visualization of small and endophytic renal masses on unenhanced CT prior to CT-guided PCA. TAE was considered successful that accumulated iodized oil depicted whole of the tumor edge on CT. PCA was considered successful when the iceball covered the entire tumor with over a 5 mm margin. Oncological and renal functional outcomes and complications were also evaluated.ResultsTAE was successfully performed in 16 of 17 endophytic tumors. The 16 tumors were performed under CT-guided PCA with their distinct visualization of localization and safe ablated margin. During the mean follow-up period of 15.4 ± 5.1 months, one patient developed local recurrence. Estimated glomerular filtration rate declined by 8 % with statistical significance (P = 0.01). There was no procedure-related significant complication.ConclusionTAE using a mixture of absolute ethanol and iodized oil to improve visualization of endophytic renal masses facilitated tumor localization on unenhanced CT, permitting depiction of the tumor edge as well as a safe margin for ablation during CT-guided PCA, with an acceptable decline in renal function.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

RF Ablation of Giant Hemangiomas Inducing Acute Renal Failure: A Report of Two Cases

ObjectiveIn patients that require treatment for hepatic giant cavernous hemangiomas (GCH), radiofrequency ablation (RFA) has been suggested to represent a safe and effective alternative to invasive surgery. In a recent report of bipolar RFA, using two expandable needle electrodes, was uneventfully performed in patients with large GCH (>10 cm). The objective of this report is to present two cases in which bipolar RFA of symptomatic GCH was complicated by acute kidney injury.Materials and methodsIn 2015 we treated two patients for very large symptomatic GCH (15.7 and 25.0 cm) with bipolar RFA during open laparotomy.ResultsIn both patients the urine showed a red–brown discoloration directly after the ablation. They became anuric and presented with progressive dyspnea, tachypnea, and tachycardia, requiring hemodialysis for a period of 1 month in one case. Lab results revealed hemepigment-induced acute kidney. Both patients fully recovered and both showed a complete relief of symptoms at 3 months following the procedure.ConclusionRFA for large GCHs can cause hemepigment-induced acute kidney injury due to massive intravascular hemolysis. The presented cases suggest that caution is warranted and advocate an upper limit regarding the volume of GCHs that can be safely ablated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Novel Use of a Pneumatic Compression Device for Haemostasis of Haemodialysis Fistula Access Catheterisation Sites

PurposeTransradial pneumatic compression devices can be used to achieve haemostasis following radial artery puncture. This article describes a novel technique for acquiring haemostasis of arterio-venous haemodialysis fistula access sites without the need for suture placement using one such compression device.Materials and MethodsA retrospective review of fistulograms with or without angioplasty/thrombectomy in a single institution was performed. 20 procedures performed on 12 patients who underwent percutaneous intervention of failing or thrombosed arterio-venous fistulas (AVF) had 27 puncture sites. Haemostasis was achieved using a pneumatic compression device at all access sites. Procedure details including size of access sheath, heparin administration and complications were recorded.ResultsTwo diagnostic fistulograms, 14 fistulograms and angioplasties and four thrombectomies were performed via access sheaths with an average size (±SD) of 6 Fr (±1.12). IV unfractionated heparin was administered in 11 of 20 procedures. Haemostasis was achieved in 26 of 27 access sites following 15–20 min of compression using the pneumatic compression device. One case experienced limited bleeding from an inflow access site that was successfully treated with reinflation of the device for a further 5 min. No other complication was recorded.ConclusionsHaemostasis of arterio-venous haemodialysis fistula access sites can be safely and effectively achieved using a pneumatic compression device. This is a technically simple, safe and sutureless technique for acquiring haemostasis after AVF intervention.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Routine Use of Surgical Retrograde Transtibial Endovascular Approach for Failed Attempts at Antegrade Recanalization of Chronic Peripheral Artery Total Occlusions

PurposeOur aim was to describe the technical aspects and clinical outcomes of an open surgical approach to retrograde transtibial endovascular therapy for recanalization of chronic total occlusions (CTOs) of peripheral arteries because of inability to acquire antegrade intravascular access across the occlusion.Materials and MethodsBetween January 2011 and May 2014, conventional antegrade revascularization failed in 15 limbs of 15 patients (11 males, 4 females) with complex CTOs. The mean age of the patients was 74 years (range 48–83 years). Five patients had severe claudication (Rutherford Category 3), and 10 patients had critical limb-threatening ischemia (Rutherford Categories 4–5). For each of these cases of antegrade failure, an open surgical exposure of the tibial or dorsalis pedis artery was used to allow a safe retrograde transtibial endovascular approach to recanalize the CTO.ResultsSurgical retrograde access from the tibial artery was achieved successfully in 14 of the 15 patients. In the 14 successful retrograde endovascular approaches, surgical retrograde transtibial access was achieved from the dorsalis pedis artery in 8 patients and from the posterior tibial artery in 6. The average time to obtain retrograde access was 5 min (range 2–11 min). No stenosis or occlusion occurred in the tibial or dorsalis pedis arteries used for the retrograde access sites during follow-up.ConclusionsRoutine surgical exposure can be a safe and an effective method for retrograde transtibial access to the more proximal occluded arterial segments in selected patients with CTO.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Safety of Continuing Therapeutic Anticoagulation During Inferior Vena Cava Filter Retrieval: A 6-Year Retrospective Review from a Tertiary Centre

Purpose: Assess the safety of inferior vena cava (IVC) filter retrieval in patients taking anticoagulation, compared to a non-anticoagulated cohort. Materials and Methods: Single-centre retrospective analysis of patients who underwent IVC filter retrieval between January 2012 and February 2018. Information about patient demographics, anticoagulation, tilt, major and minor complications was collected. Major complications were defined as: IVC injury from the filter retrieval, retained fragment of filter, filter fracture and filter embolisation. Minor complications were defined as: neck haematoma and puncture site infection. Results: Total of 357 patients (age 18–95, Male: 231) underwent IVC filter retrieval, comprising of Cook Celect Platinum, Cook Celect, and ALN-branded filters. Of these 182 patients were on anticoagulation and 175 patients were not on anticoagulation, based on the indication for the filter (thrombosis or prophylaxis) and at the discretion of the referring unit who were managing the anticoagulation. IVC filter retrieval was technically successful in 349 patients. Five major complications (1.4% of retrievals) were recorded and no minor complications (0% of retrievals). In the anticoagulation cohort, there were two major complications (1.1% of retrievals) both related to IVC injury. In the non-anticoagulated cohort, there were three major complications (1.7% of retrievals) relating to filter embolisation, IVC injury, and filter fracture. Conclusions: IVC filter retrieval is a safe procedure with a low complication rate. Being on anticoagulation does not increase the risk of a major complication or change the management of major complication compared with a non-anticoagulated cohort. IVC filter retrieval is safe to perform in patients currently taking prophylactic or therapeutic anticoagulation based on our cohort. Level of Evidence: Level 3, retrospective cohort study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Safety and Feasibility of Helical I-125 Seed Implants Combined with Transcatheter Arterial Chemoembolization in Hepatocellular Carcinomas with Main Portal Vein Tumor Thrombus

Purpose: To investigate the feasibility and safety of a helical iodine-125 (I-125) seed implant combined with transcatheter arterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (MPVTT). Methods: From December 2016 to February 2018, 26 cases of HCC with MPVTT patients were enrolled in this prospective study. Helical I-125 seed implants were placed into the portal vein through the percutaneous transhepatic route. Subsequently, TACE was performed. Follow-up with enhanced CT was performed every 6–8 weeks and TACE was repeated if the residual or recurrent tumor was found. Treatment response was measured with the modified response evaluation criteria in solid tumors. Complication rates and overall survival were also evaluated. Results: Implantation and TACE were successful in all patients. There were no grade ≥ 3 complications observed in the patients. The objective response rates (ORR) and disease control rates (DCR) of MPVTT at 3 months after implantation were 42.3% and 84.6%, respectively, whereas ORR and DCR of the liver lesions were 34.6% and 46.2%, respectively. The median overall survival was 10.7 months (95% CI 6.2–15.2 months). Conclusion: Helical I-125 seed implants can be safely placed into the human main portal vein. Helical I-125 seed implants combined with TACE for HCC with MPVTT are safe and feasible.

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Assessing the Need for Preprocedural Laboratory Tests and Stopping Non-steroidal Anti-inflammatory Drugs/Aspirin in Patients Undergoing Percutaneous Bone and Soft Tissue Biopsies

Purpose: Although image-guided biopsies of bone and soft tissue lesions have a low complication rate, there is limited data evaluating use of preprocedural laboratory tests. To address this issue, patients were not required to stop non-steroidal antiinflammatory drugs (NSAIDs) and aspirin or to obtain preprocedural laboratory tests [complete blood count (CBC) and international normalized ratio (INR)], except in special circumstances. The bleeding complication rate, rate of same day biopsies, and the time from when the biopsy was ordered to when it was performed were obtained. Materials and Methods: A total of 332 patients who underwent bone or soft tissue biopsies performed at our institution between 9/1/2017 and 1/9/2019 were prospectively analyzed. These data were compared to a retrospective biopsy cohort of 323 patients between 7/1/2015 and 7/1/2017. Data collected included method of image guidance and bleeding complication rate. The number of days from ordering to performing a biopsy and number of same day biopsies were recorded. Results: There were no bleeding complications in either cohort (OR 1.00, P = 1). The mean time from ordering to performing a bone biopsy was significantly decreased in the prospective group (6.6 days) compared to the retrospective group (8.1 days) (P = 0.012). There were more same day biopsies in the prospective cohort (11.4% vs. 3.4%) (P < 0.001). Conclusions: Preprocedural CBC and INR for bone and soft tissue biopsies can be safely eliminated in most patients. Biopsies performed while patients are taking NSAIDs/aspirin can safely be performed. Adopting revised preprocedural laboratory criteria can result in decreased time to completion of biopsies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

RBMK Graphite Serviceability at the Final Stage of Operation

A procedure for evaluating the technical conditions and residual service life of the RBMK-1000 graphite masonry and a program of research have been developed in order to evaluate the serviceability and the possibility of service life extension of the RBMK graphite stack at the final stage of operation. The serviceability criteria for the graphite stack, periodicity and methods of controlling them, which, in combination with predictive calculations have made it possible to validate the possibility of safe operation of the RBMK-1000 graphite stack above the assigned service life allowed to substantiate the possibility of safe operation of the graphite stack RBMK-1000 over a designated period of time, were determined.

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Biosynthesis, Microstructural Characterisations and Investigation of In-Vitro Mutagenic and Eco-Toxicological Response of a Novel Microbial Exopolysaccharide Based Biopolymer

A modified microbial polysaccharide based biopolymer has been investigated as a potential candidate towards development of sustainable biomaterials and bioplastics. An in-depth study was carried out to biosynthesize, characterize and assess any possible mutagenic potential and ecotoxicity of the microbial polysaccharide biopolymer. Microstructural investigations using confocal microscopy, Fourier transform (FT)-Raman depth profile mapping and scanning electron microscopy (SEM) of the biosynthetically modified polysaccharide revealed internal structural perturbations, as well as occlusion of granular pores by extraneous materials. The Raman 3D mapping depth profile along with time-of-flight (MALDI-TOF) mass spectrometry also indicated important structural and surface modifications, which could be correlated to the production of microbial exopolysaccharides and secondary metabolites. The study then looked into any possible genetic mutation and ecological risks associated with the biosynthetically modified polysaccharide through the investigation of genotoxicity and ecotoxicity. The genotoxicity study was carried out through bacterial reverse gene mutation (Ames) test by using two different strains (TA98 and TA100) of bacteria. The results did not indicate any mutagenic effect against either of the strains used for the biopolymer samples and was found to be genotoxically safe. Ecotoxicity tests, carried out using bioluminescent bacteria Vibrio fisheri further indicated no ecotoxicity within the given experimental conditions. The study measured the half maximal effective concentration (EC50) to cause a 50% decrease in the light output of the bacteria, a measure of ecotoxicological response of the biopolymer. Overall, results from this study indicated that the novel biopolymer was genotoxically and ecotoxically safe, which offers immense potential for future use of this biopolymer.

36 MATERIALS SCIENCE↗

Potential effects of low-dose average CT on cardiac implantable electronic devices

Background: Average CT has been shown to be more accurate than conventional helical CT in quantitation of the PET data. The risk of CT irradiation of a cardiac implantable electronic device (CIED) causing an adverse event is low and is generally outweighed by the clinical benefit of a medically indicated examination. However, irradiation of CIED over one breath cycle in cine CT scan for average CT could impose risks on a patient who is pacing dependent. The purpose of this study was to demonstrate that low-dose average CT can be safe for CIED. Methods: A Medtronic CIED of model Protecta VR was submerged in a saline bath for a series of 4-s cine CT scans on a GE CT scanner programmed to deliver a 2-cm-wide radiation at a dose rate of 0.9 to 41.2 mGy/s to the CIED. The number of over-sensings was recorded as the interference of radiation to the CIED. Results: Dose rates ≥ 1.9 mGy/s caused over-sensing. The higher the dose rate, the more over-sensings there were. The lowest dose rate of 0.9 mGy/s did not cause any over-sensing. Conclusions: Low-dose average CT at 0.9 mGy/s can be safe for a CIED patient who is pacing dependent.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Thermal characterization of the build chamber in electron beam melting

Electron beam powder bed fusion, commonly termed electron beam melting (EBM), offers great versatility in multiple-part processes and can produce high quality as-built components due to low residual stresses. The EBM process is complex and requires careful thermal management, including uniform and consistent preheating of the powder bed, in order to ensure quality and consistency of the product. However, most of the simulations in the literature focus on the selective melting stage of the process. As of today, optimal conditions for initial pre-heating temperatures are only available for specific materials. Thus, in order to extend the EBM technology to other desired build materials, a much better understanding of the pre-heating stages is required. In this work, numerical and experimental approaches are combined in order to investigate the effects and sensitivities of heat removal from the build plate during EBM pre-heating stages. For this purpose, a carefully reconstructed numerical model of the build chamber of an ARCAM Q20 + machine is developed. It includes all main parts of the chamber and all relevant heat transfer mechanisms, whereas special attention is paid to radiation heat exchange between various bodies. In order to validate the model, dedicated experiments are performed, in which a system of thermocouples is installed in the build chamber, allowing direct measurement of the local temperatures of the start-plate and heat shields. A good agreement between the simulation and experimental findings is achieved, leading to a better understanding of the thermal processes characteristic to the pre-heating stages. This basic analysis is followed by a representative pre-heating case, where a powder bed is also considered. The energy required to obtain the desired pre-heating temperatures is evaluated, and the role of the powder bed in heat transfer within the chamber is assessed. The pre-heating stage, simulated in the present work, is supposed to create proper conditions for sintering and consequent melting of the powder, which are highly dependent on the local temperatures and heat transfer features. Thus, the findings of the reported work present a step towards a better understanding of the thermal processes that characterize EBM. The reported model can be further used to provide realistic boundary condition inputs for other meso- or macro-scale models as a function of time and geometry. The model can serve also for verification of machine settings, i.e., jump-safe and melt-safe ones which actually provide desired preheat, and for development of settings for new powders.

36 MATERIALS SCIENCE↗

Metabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin

Heparosan is an unsulfated polysaccharide potentially important for its wide range of cosmetic and pharmaceutical applications, particularly as the precursor for the extensively used anticoagulant, heparin. Generally sourced from animals, commercially available heparin may encounter various immunological and contamination risks. Thus, safe and sustainable microbial platforms could serve as an alternative heparin source. Synechococcus, due to their fast photoautotrophic growth, strong sugar phosphate metabolisms and generally regarded as safe (GRAS) nature, may serve as photo-biorefineries for manufacturing heparosan. In this study, we have synthesized an integrative plasmid pUPm48 for cloning galU and PmHS2 genes in Synechococcus elongatus PCC 7942. The engineered recombinants (pgp7942) exhibited significant production of heparosan under different culture conditions, where the products were present in both supernatant and cell biomass. The maximum yield of 0.7 ± 0.2 μg/g-DCW (dry cell weight) and a titer of 2.8 ± 0.3 μg/L was achieved by pgp7942 under shake flask and continuous light conditions. Large scale plastic-bag cultures with natural diurnal light exhibited heparosan production of 0.5 μg/g-DCW with a titer of 0.44 μg/L. The analysis also found PCC 7942 encodes a promiscuous uridyltransferase for UDP-glucose synthesis and naturally produces multiple glycosaminoglycans including chondroitin sulfate (CS). This study demonstrates for the first-time cyanobacteria as a promising photoautotrophic refinery for producing a high-value polysaccharide commonly from animals.

59 BASIC BIOLOGICAL SCIENCES↗

A new algae technical standards focus group: Summarizing and guiding the algae state of the art

The value proposition of algae technical metrics was the subject of a recent, industry-led, Focus Group interactive discussion. The interactive platform allowed for real time capturing and priority ranking of the topics that are deemed critical challenges for a future successful algae-based bioeconomy. This work ultimately sets the stage for providing guidance, methods, and standard reference materials tailored to respective algae industry segments for the cultivation, processing and marketing of high-quality and safe algae-based products. The group solicits input from the broader algae community on the value proposition and presents a case here to build a consensus around algae-specific metrics. The value proposition of technical standards to the industry is that guidance obtained through these collaborations builds producers' and consumers' trust that algae and algae-derived products are safe, reliable, and may allow for expanded market access, and increased competitiveness and international trade.

59 BASIC BIOLOGICAL SCIENCES↗

Passive decay heat removal system design for the integral inherent safety light water reactor (I 2 S-LWR)

The Integral, Inherently Safe Light Water Reactor (I 2 S-LWR) is an innovative Pressurized Water Reactor (PWR) concept being developed by a multi-institutional team led by Georgia Tech and in collaboration with Westinghouse, under the Department of Energy’s Nuclear Energy University Programs Integrated Research Projects (DOE NEUP IRP). The University of Michigan leads the design of the thermalhydraulic and passive safety systems, in collaboration with Westinghouse and Bringham Young University. The I 2 S-LWR features an integral primary system configuration and is more conducive to the implementation of inherent safety features by eliminating potential accidents. In this paper, a novel passive Decay Heat Removal System (DHRS), is presented, consisting of a primary loop, an intermediate loop and a cooling tower loop. This passive system is designed to remove the I 2 S-LWR decay heat in the case of emergency heat removal transients, without the need for external power or operator action. The proposed DHR uses atmosphere as ultimate heat sink, to achieve indefinite decay heat removal. In this paper, firstly, the design of primary and secondary DHRS heat exchangers is optimized. Then the DHR heat removal characteristics are studied using the best-estimate thermal hydraulic code RELAP5. In addition, CFD simulations have been performed in order to investigate the DRHS helical coil primary heat exchanger performance with different coil pipe arrangements, and optimize its design. The performance of the proposed DHRS concept is investigated in case of a Station Black-Out (SBO) scenario. Operation of two, three and four DHRS trains is studied respectively. The findings show that three out of four DHRS trains are sufficient to indefinitely remove the core decay heat successfully during a SBO, and keep the reactor in a safe state without the need of any other auxiliary active system.

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SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.

60 APPLIED LIFE SCIENCES↗