Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

Inorganic nanoparticles for photothermal treatment of cancer.

In recent years, inorganic nanoparticles (NPs) have attracted increasing attention as potential theranostic agents in the field of oncology. Photothermal therapy (PTT) is a minimally invasive technique that uses nanoparticles to produce heat from light to kill cancer cells. PTT requires two essential elements: a photothermal agent (PTA) and near-infrared (NIR) radiation. The role of PTAs is to absorb NIR, which subsequently triggers hyperthermia within cancer cells. By raising the temperature in the tumor microenvironment (TME), PTT causes damage to the cancer cells. Nanoparticles (NPs) are instrumental in PTT given that they facilitate the passive and active targeting of the PTA to the TME, making them crucial for the effectiveness of the treatment. In addition, specific targeting can be achieved through their enhanced permeation and retention effect. Thus, owing to their significant advantages, such as altering the morphology and surface characteristics of nanocarriers comprised of PTA, NPs have been exploited to facilitate tumor regression significantly. This review highlights the properties of PTAs, the mechanism of PTT, and the results obtained from the improved curative efficacy of PTT by utilizing NPs platforms.

Gold nanoparticles decorated on MOF derived Cu5Zn8 hollow porous carbon nanocubes for magnetic resonance imaging guided tumor microenvironment-mediated synergistic chemodynamic and photothermal therapy.

Combining chemodynamic therapy (CDT) with photothermal therapy (PTT) has developed as a promising approach for cancer treatment, as it enhances therapeutic efficiency through redox reactions and external laser induction. In this study, we designed metal organic framework (MOF) -derived Cu5Zn8/HPCNC through a carbonization process and decorated them with gold nanoparticles (Au@Cu5Zn8/HPCNC). The resulting nanoparticles were employed as a photothermal agent and Fenton catalyst. The Fenton reaction facilitated the conversation of Cu2+ to Cu+ through reaction with local H2O2, generating reactive hydroxyl radicals (·OH) with potent cytotoxic effects. To enhance the Fenton-like reaction and achieve combined therapy, laser irradiation of the Au@Cu5Zn8/HPCNC induced efficient photothermal therapy by generating localized heat. With a significantly increased absorption of Au@Cu5Zn8/HPCNC at 808 nm, the photothermal efficiency was determined to be 57.45 %. Additionally, Au@Cu5Zn8/HPCNC demonstrated potential as a contrast agent for magnetic resonance imaging (MRI) of cancers. Furthermore, the synergistic combination of PTT and CDT significantly inhibited tumor growth. This integrated approach of PTT and CDT holds great promise for cancer therapy, offering enhanced CDT and modulation of the tumor microenvironment (TME), and opening new avenues in the fight against cancer.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.

Synergistic effect of photothermal and magnetic hyperthermia for in situ activation of Fenton reaction in tumor microenvironment for chemodynamic therapy.

Traditional cancer treatments are ineffective and cause severe adverse effects. Thus, the development of chemodynamic therapy (CDT) has the potential for in situ catalysis of endogenous molecules into highly toxic species, which would then effectively destroy cancer cells. However, the shortage of high-performance nanomaterials hinders the broad clinical application of this approach. In present study, an effective therapeutic platform was developed using a simple hydrothermal method for the in-situ activation of the Fenton reaction within the tumor microenvironment (TME) to generate substantial quantities of •OH and ultimately destroy cancer cells, which could be further synergistically increased by photothermal therapy (PHT) and magnetic hyperthermia (MHT) aided by FeMoO4 nanorods (NRs). The produced FeMoO4 NRs were used as MHT/PHT and Fenton catalysts. The photothermal conversion efficiency of the FeMoO4 NRs was 31.75 %. In vitro and \ experiments demonstrated that the synergistic combination of MHT/PHT/CDT notably improved anticancer efficacy. This work reveals the significant efficacy of CDT aided by both photothermal and magnetic hyperthermia and offers a feasible strategy for the use of iron-based nanoparticles in the field of biomedical applications.

Association of Aortic Arch Calcification with Acute Ischemic Stroke Subtypes and Endovascular Thrombectomy Outcomes.

PURPOSE: To analyze the aortic arch calcification (AAC) on computed tomography (CT) scans, with the goal of predicting the subtypes of patients with ischemic stroke and endovascular thrombectomy (EVT) outcomes. MATERIALS AND METHODS: Automated analysis was used to quantify AAC on CT scans. From January 2020 to March 2021, 119 patients diagnosed with ischemic stroke were analyzed, and the feasibility of EVT was assessed; 43 underwent the procedure. RESULTS: AAC was present in 117 (98.3%) of 119 patients. There was a significant difference (P <.001) in AAC severity among all patients with ischemic stroke according to the Trial of ORG 10172 in Acute Stroke Treatment classification. In patients who underwent EVT, AAC severity was significantly related to the thrombolysis in cerebral infarction grade, thrombectomy procedure time, and modified Rankin scale at discharge (P =.002, P =.035 and P =.015, respectively). Multivariate logistic regression analysis also showed that severe AAC (volume, ≥1,000 mm3) (adjusted odds ratio [OR], 12.1; adjusted 95% confidence interval [CI]), 2.1-36.4; P =.001) and intracranial atherosclerotic disease (adjusted OR, 9.5; adjusted 95% CI, 2.3-33.7; P =.001) were both independently associated with poor thrombolysis reperfusion rate. CONCLUSIONS: A high proportion of patients with ischemic stroke have AAC, the severity of which is a potential imaging marker of ischemic stroke subtypes and the outcome of EVT.

Diazotrifluoroethyl Radical: A CF3-Containing Building Block in [3 + 2] Cycloaddition.

We present herein a visible-light-induced [3 + 2] cycloaddition of a hypervalent iodine(III) reagent with α-ketoacids for the construction of 5-CF3-1,3,4-oxadiazoles that are of importance in medicinal chemistry. The reaction proceeds smoothly without a photocatalyst, metal, or additive under mild conditions. Different from the well-established trifluorodiazoethane (CF3CHN2), the diazotrifluoroethyl radical [CF3C(·)N2], a trifluoroethylcarbyne (CF3CC:) equivalent and an unusual CF3-containing building block, is involved in the present reaction system.

Polyelectrolyte multilayer composite coating on 316 L stainless steel for controlled release of dual growth factors accelerating restoration of bone defects.

A composite coating of polyelectrolyte multilayers (PEMs) consisting of collagen, a chitosan barrier, and poly-γ-glutamic acid was fabricated using a spin coating technique to investigate and overcome the limited osseointegration capacity of 316 L stainless steel (316 L SS). To further enhance the biocompatibility, bone morphogenetic protein 2 (BMP-2) and basic fibroblast growth factor-2 (FGF-2) were loaded separately as dual growth factors, allowing for progressive drug release following the natural process of bone regeneration. The first burst release of FGF-2 triggered the proliferation of surrounding cells, and the subsequent release of BMP-2 stimulated their differentiation. The microstructure, surface potential, hardness, reduced Young's modulus, and wettability were assessed using scanning electron microscopy, nanoindentation, and water contact angle. The formation of apatite layers after immersion in simulated body fluid confirmed the bioactivity of this PEM. PEMs loaded with BMP-2 and FGF-2 showed a long sustained release of growth factors for up to 48 days. The biological properties were studied in vitro with rat bone mesenchymal stem cells (rBMSCs) and in vivo using a rat critical-sized calvarial defect model. PEMs loaded with growth factors further stimulated the proliferation and osteogenic differentiation of rBMSCs and the histology results indicated that new bone tissues could directly grow onto the PEMs. These findings suggest that PEM composite coating possesses significant potential for surface modification and long-term drug release of metallic implants to assist with bone restoration.

Study on proanthocyanidins crosslinked collagen membrane for guided bone tissue regeneration.

The goal of this study is to understand the ability of a newly developed barrier membrane to enhance bone tissue regeneration. Here in this study we present the in vitro characterization of the barrier membrane made from type I collagen and crosslinked by oligomeric proanthocyanidins (OPCs). The effects of the membrane (P-C film) on cell cycle, proliferation, alkaline phosphatase activity, and mineralization were evaluated using the human osteoblast cell line MG-63, while the barrier ability was examined using MG-63 cells, as well as the human skin fibroblast cell line WS-1. The pore size is one of the factors that plays a key role in tissue regeneration, therefore, we evaluated the pore size of the membrane using a capillary flow porometer. Our results showed that the mean pore size of the P-C film was approximately 7-9 µm, the size known to inhibit cell migration across the membrane. The P-C film also demonstrated excellent cell viability and good biocompatibility, since the cell number increased with time, with MG-63 cells proliferating faster on the P-C film than in the cell culture flask. Furthermore, the P-C film promoted osteoblast differentiation, resulting in higher alkaline phosphatase activity and mineralization. Therefore, our results suggest that this P-C film has a great potential to be used in guided bone regeneration during periodontal regeneration and bone tissue engineering.

The psychological symptoms of patients with mild symptoms of coronavirus disease (2019) in China: A cross-sectional study.

AIMS: To determine psychological symptoms of patients with mild symptoms of coronavirus disease 2019 in China and to explore the influencing factors. DESIGN: A cross-sectional study. METHODS: A convenience sample of 296 mild coronavirus disease 2019 patients were recruited from a Fangcang hospital in Wuhan, Hubei Province, from 3-5 March, 2020. Participants were assessed using a sociodemographic and clinical characteristics questionnaire, and Symptom Check List 90. The binary logistic regression was utilized to explore the influencing factors of psychological symptoms of patients with mild symptoms of coronavirus disease 2019. RESULTS: In total, 296 of 299 patients with mild symptoms of coronavirus disease 2019 participated in the study (response rate: 99.0%). The findings revealed that 12.8% patients with mild symptoms have mental health problems; the most common psychological symptoms are phobic anxiety (58.4%), paranoid ideation (50.7%) and psychoticism (40.2%). Female patients [OR = 3.587, 95% CI (1.694-7.598)] and those having physical symptoms currently [OR = 2.813, 95% CI (1.210-6.539)] are at higher risk, while those in the middle duration of hospitalization [OR = 0.278, 95% CI (0.121-0.639)] protect against mental-health problems. CONCLUSIONS: The minority of patients with mild symptoms of coronavirus disease 2019 were still suffering from psychological symptoms. Healthcare providers are recommended to pay particular attention to screening these high-risk groups (women, those in the initial stages of hospitalization and those with physical symptoms currently) and implement targeted psychological care as required. IMPACT: This study found that most patients of coronavirus disease 2019 in Fangcang hospital exhibited normal mental health at par with the general Chinese norm and the minority of them were suffering from psychological symptoms. The findings can provide a reference for healthcare providers to screen high-risk psychological symptoms groups and implement targeted psychological intervention for patients with coronavirus disease 2019.

Study on strontium doped tricalcium silicate synthesized through sol-gel process.

We successfully synthesized a strontium-doped tricalcium silicate (SrxCa3-xSiO5, Sr = 0 to 2 mol%) bone cement using the sol-gel process. The material properties including crystallinity, setting time, mechanical strength, and hydration products were characterized. Release of ions and pH values of simulated body fluid soaked with the bone cement were measured. In vitro biocompatibility of different concentrations of the material was evaluated by the viability of L929 cells. The setting times of as-prepared slurries were all <70 min. Doping with 0.5 mol% Sr reduced the final setting time by 20 min. After 14 days curing, 0.25 mol% Sr-doped SrxCa3-xSiO5 possessed the highest compressive strength of 45 MPa among all the Sr-doped groups with no statistical difference to Ca3SiO5. The bioactivity of the materials was confirmed with the formation of an apatite layer on the surface of the materials after immersion in simulated body fluid. In addition, the proliferation of L929 cells exposed to 1 mol% Sr was significantly promoted as compared to no Sr doping. SrxCa3-xSiO5 is a novel and advanced material that has the potential to serve as a bone cement in bone restoration with appropriate mechanical strength and favorable biocompatibility.

Effects of transtheoretical model-based intervention on the self-management of patients with an ostomy: A randomised controlled trial.

AIMS AND OBJECTIVES: To determine the effect of a transtheoretical model (TTM)-based intervention on patients with an ostomy and provide patient-centred, accessible assistance and dynamic education to improve patient self-management. BACKGROUND: Proper self-management may promote the rehabilitation of patients with an ostomy. TTM-based interventions have resulted in positive health behavioural changes. DESIGN: Randomised controlled trial performed according to the CONSORT guidelines. SUBJECT AND SETTING: The sample comprised 55 men and 37 women (24-77 years old, mean ± SD = 52.8 ± 11.13 years). The study settings included three tertiary hospitals in Changsha, Hunan, China. METHODS: The 92 patients, recruited from August 2012 to March 2013, were randomised into a control group and an intervention group. Randomisation was done by using a block randomisation list with a block size of 4. Self-management behaviours were assessed at the baseline, 2 days before discharge and after 1, 3 and 6 months of follow-up. The chi-squared test, independent sample t test and repeated measures analysis of variance were used to analyse the data. RESULTS: Patients in the intervention group were more likely to be at the action and maintenance stages compared with those in the control group. We also observed significant improvements in the self-management ability in the process of change, the decisional balance and self-efficacy in the intervention group compared with those in the control group after four intervention sessions and up to 6 months of follow-up. No serious intervention-related adverse events were observed. CONCLUSIONS: The TTM-based intervention had positive effects on self-management behaviours of patients with an ostomy. RELEVANCE TO CLINICAL PRACTICE: The TTM-based intervention had positive effects on self-management behaviours of patients with an ostomy and may provide a reference for health providers to develop behaviour promotion programmes to improve the self-management of patients with an ostomy.

Psychometric properties and performance of existing self-efficacy instruments in cancer populations: a systematic review.

BACKGROUND: This study aims to provide a systematic compilation of existing measures of self-efficacy developed specifically for use in cancer patients and provide descriptions and comparative evaluations of the characteristics, psychometric properties and performance parameters. METHOD: A systematic electronic database search was conducted in PubMed, Ovid (PsyINFO), EBSCO, Elsevier, Scopus to identify self-efficacy assessment tools for cancer patients, between January 1977 to February 2018. The characteristics of target population, instrument, development process and psychometric properties were summarized. All included instruments were subsequently appraised using a psychometric quality assessment tool based on previous publications. Validity of the quality assessment was reviewed and confirmed by five experts. RESULTS: Fifteen cancer-related self-efficacy instruments were identified. Among them, (40.0%) 6/15 were task-specific, focusing on cancer-related health issues such as fatigue, communication, rehabilitation, exercise, and narcotic pain killer usage. Six instruments were disease-specific for breast cancer, lung cancer, or advanced cancer. Weaknesses of the development processes included the singularity of instrument construction methods, and non-transparent selection of the final items. The main limitation seen in the validation processes was that some important properties of instruments (e.g. test-retest reliability, criterion validity, responsiveness, interpretability, feasibility, and acceptability) were not evaluated. CONCLUSIONS: This review summarizes the limitations and strengths of current self-efficacy instruments for cancer patient. The information reported here can assist clinicians and researchers in the selection of the appropriate instrument. Finally, it points out the need for reporting validation statistics to facilitate the use of these instruments.

Non-Enzymatic Glucose Sensor Composed of Carbon-Coated Nano-Zinc Oxide.

Nowadays glucose detection is of great importance in the fields of biological, environmental, and clinical analyzes. In this research, we report a zinc oxide (ZnO) nanorod powder surface-coated with carbon material for non-enzymatic glucose sensor applications through a hydrothermal process and chemical vapor deposition method. A series of tests, including crystallinity analysis, microstructure observation, and electrochemical property investigations were carried out. For the cyclic voltammetric (CV) glucose detection, the low detection limit of 1 mM with a linear range from 0.1 mM to 10 mM was attained. The sensitivity was 2.97 µA/cm²mM, which is the most optimized ever reported. With such good analytical performance from a simple process, it is believed that the nanocomposites composed of ZnO nanorod powder surface-coated with carbon material are promising for the development of cost-effective non-enzymatic electrochemical glucose biosensors with high sensitivity.

An Enzymatic Glucose Sensor Composed of Carbon-Coated Nano Tin Sulfide.

In this study, a biosensor, based on a glucose oxidase (GOx) immobilized, carbon-coated tin sulfide (SnS) assembled on a glass carbon electrode (GCE) was developed, and its direct electrochemistry was investigated. The carbon coated SnS (C-SnS) nanoparticle was prepared through a simple two-step process, using hydrothermal and chemical vapor deposition methods. The large reactive surface area and unique electrical potential of C-SnS could offer a favorable microenvironment for facilitating electron transfer between enzymes and the electrode surface. The structure and sensor ability of the proposed GOx/C-SnS electrode were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and cyclic voltammetry study (CV).

Latent classes of resilience and psychological response among only-child loss parents in China.

Only-child loss parents in China recently gained extensive attention as a newly defined social group. Resilience could be a probable solution out of the psychological dilemma. Using a sample of 185 only-child loss people, this study employed latent class analysis (a) to explore whether different classes of resilience could be identified, (b) to determine socio-demographic characteristics of each class, and (c) to compare the depression and the subjective well-being of each class. The results supported a three-class solution, defined as 'high tenacity-strength but moderate optimism class', 'moderate resilience but low self-efficacy class' and 'low tenacity but moderate adaption-dependence class'. Parents with low income and medical insurance of low reimbursement type and without endowment insurance occupied more proportions in the latter two classes. The latter two classes also had a significant higher depression scores and lower subjective well-being scores than high tenacity-strength but moderate optimism class. Future work should care those socio-economically vulnerable bereaved parents, and an elastic economic assistance policy was needed. To develop targeted resilience interventions, the emphasis of high tenacity-strength but moderate optimism class should be the optimism. Moderate resilience but low self-efficacy class should be self-efficacy, and low tenacity but moderate adaption-dependence class should be tenacity.

The resilience status of empty-nest elderly in a community: A latent class analysis.

OBJECTIVE: The aim of this study was to examine the status and characteristics of resilience among empty-nest elderly in a community in China using exploratory latent class analysis (LCA). METHODS: This study enrolled 250 empty-nest elderly as the study respondents. General information regarding the resilience of empty-nest elderly was investigated using the General Information Questionnaire and Connor-Davidson Resilience Scale, Chinese version, and we then used LCA and multivariate logistic regression to discuss the characteristics of resilience among empty-nest elderly individuals. RESULTS: Through the analysis, we found that the resilience of empty-nest elderly had obvious group characteristics and that statistical indicators can support the three categories of potential model. On the basis of the conditional probability on the various items of the questionnaire in each category, they were named "high resilience group," "low pressure resilience group," and "low resilience group," and the proportion was 26.6%, 40.4%, and 32.9%, respectively. Further study showed that age, marital status, education level, relationship with children, and physical exercise had a significant effect on the high resilience group compared to the low resilience group. Gender, education level, relationship with children, and physical exercise had a significant effect on the low pressure resilience group compared to the low resilience group. CONCLUSIONS: The resilience status of empty-nest elderly in communities can be divided into three categories. Each category had different characteristics of demographic information.

Latent Profiles of Posttraumatic Growth and Their Relation to Differences in Resilience among Only-Child-Lost People in China.

AIMS: Since the early 1980s, the one-child policy has been implemented nationwide in China. A special group called the "only-child-lost family" (OCL family) has emerged and has become a social phenomenon that cannot be ignored. We report latent profiles of posttraumatic growth and their relation to differences in resilience among OCL people in China. METHODS: A total of 222 OCL people were investigated using the Posttraumatic Growth Inventory and the Connor-Davidson Resilience Scale. Latent profile analysis was applied to explore PTG latent profiles. Multinomial logistic regression was used to analyze the socio-demographic variables in each latent profile and the association between profile membership and resilience. RESULTS: Three latent profiles were identified and labeled the "high appreciation-power group" (30.6%), the "general moderate growth group" (47.7%) and the "low growth and extreme possibility group" (21.7%). Compared to those in the high appreciation-power group, individuals with monthly income >2000 ($312) were less likely to be in the general moderate growth group (OR = 0.13, P<0.01), whereas individuals with a spouse were less likely to be in the low growth and extreme possibility group (OR = 0.43, P<0.01). Individuals in the "general moderate growth group"(OR = 0.92, P<0.01, 95%CI:0.89-0.94) and the "low growth and extreme possibility" groups (OR = 0.83, P<0.01, 95%CI:0.79-0.87) demonstrated significantly lower levels of resilience compared to the high appreciation-power group. CONCLUSION: The PTG patterns in only-child-lost parents were varied. Promoting resilience may be a way to foster these parents' PTG. Targeted intervention should be developed based on the characteristics of each latent class, and timely attention must be paid to the mental health of OCL parents who are without a spouse and have low income.

Cabozantinib is selectively cytotoxic in acute myeloid leukemia cells with FLT3-internal tandem duplication (FLT3-ITD).

Cabozantinib is an oral multikinase inhibitor that exhibits anti-tumor activity in several cancers. We found that cabozantinib was significantly cytotoxic to MV4-11 and Molm-13 cells that harbored FLT3-ITD, resulting in IC50 values of 2.4 nM and 2.0 nM, respectively. However, K562, OCI-AML3 and THP-1 (leukemia cell lines lacking FLT3-ITD) were resistant to cabozantinib, showing IC50 values in the micromolar range. Cabozantinib arrested MV4-11 cell growth at the G0/G1 phase within 24 h, which was associated with decreased phosphorylation of FLT3, STAT5, AKT and ERK. Additionally, cabozantinib induced MV4-11 cell apoptosis in a dose-dependent manner (as indicated by annexin V staining and high levels of cleaved caspase 3 and PARP-1), down-regulated the anti-apoptotic protein survivin and up-regulated the pro-apoptotic protein Bak. Thus, cabozantinib is selectively cytotoxic to leukemia cells with FLT3-ITD, causing cell-cycle arrest and apoptosis. In mouse xenograft model, cabozantinib significantly inhibited MV4-11 and Molm-13 tumor growth at a dosage of 10 mg/kg and showed longer survival rate. Clinical trials evaluating the efficacy of cabozantinib in acute myeloid leukemia (AML) with FLT3-ITD are warranted.