Post-cardiac arrest care and targeted temperature management: A consensus of scientific statement from the Taiwan Society of Emergency & Critical Care Medicine, Taiwan Society of Critical Care Medicine and Taiwan Society of Emergency Medicine.

BACKGROUND: Post-cardiac arrest care is critically important in bringing cardiac arrest patients to functional recovery after the detrimental event. More high quality studies are published and evidence is accumulated for the post-cardiac arrest care in the recent years. It is still a challenge for the clinicians to integrate these scientific data into the real clinical practice for such a complicated intensive care involving many different disciplines. METHODS: With the cooperation of the experienced experts from all disciplines relevant to post-cardiac arrest care, the consensus of the scientific statement was generated and supported by three major scientific groups for emergency and critical care in post-cardiac arrest care. RESULTS: High quality post-cardiac arrest care, including targeted temperature management, early evaluation of possible acute coronary event and intensive care for hemodynamic and respiratory care are inevitably needed to get full recovery for cardiac arrest. Management of these critical issues were reviewed and proposed in the consensus CONCLUSION: The goal of the statement is to provide help for the clinical physician to achieve better quality and evidence-based care in post-cardiac arrest period.

Usefulness of Therapeutic Hypothermia to Improve Survival in Out-of-Hospital Cardiac Arrest.

BACKGROUND: In recent years, therapeutic hypothermia (TH) has been used to improve outcomes in patients with out-of-hospital cardiac arrest (OHCA). Despite these recommendations, many centers are still hesitant to implement such hypothermia protocols. In this study, we assessed the effects of TH for OHCA patients. METHODS: A total of 58 OHCA patients who had return of spontaneous circulation after OHCA presumed to be due to cardiac causes were enrolled. Twenty-three patients underwent TH, which was performed using a large volume of ice crystalloid fluid infusions in the emergency room and conventional cooling blankets in the ICU to maintain a body temperature of 32-34 °C for 24 hours using a tympanic thermometer. Patients in the control group received standard supportive care without TH. Hospital survival and neurologic outcomes were compared. RESULTS: There were no significant differences between the groups in patient characteristics, underlying etiologies and disease severity. In the 23 patients who received TH, 17 were alive at hospital discharge. In the 35 patients who received supportive care, only 11 were alive at hospital discharge (73.91% vs. 31.43%, p = 0.0015). Approximately 52% of the patients in the TH group had good neurologic outcomes (12 of 23) compared with the 20% (7 of 35) of the patients in the supportive group (p = 0.01). CONCLUSIONS: TH can improve the outcomes of OHCA patients. Further large-scale studies are needed to verify our results.

Curcuminoids combined with gefitinib mediated apoptosis and autophagy of human oral cancer SAS cells in vitro and reduced tumor of SAS cell xenograft mice in vivo.

Gefitinib has been used for cancer patients and curcumin (CUR), demethoxycurcumin (DMC), or bisdemethoxycurcumin (BDMC) also shown to induce cancer cell apoptosis. However, no report shows the combination of gefitinib with, CUR, DMC, or BDMC induce cell apoptosis and autophagy in human oral cancer cells. In this study, we investigated the effects of gefitinib with or without CUR, DMC, or BDMC co-treatment on the cell viability, apoptotic cell death, autophagy, mitochondria membrane potential (MMP), and caspase-3 activities by flow cytometry assay and autophagy by acridine orange (AO) staining in human oral cancer SAS cells. Results indicated that gefitinib co-treated with CUR, DMC, or BDMC decreased total viable cell number through the induction of cell apoptosis and autophagy and decreased the levels of MMP and increased caspase-3 activities in SAS cells. Western blotting indicated that gefitinib combined with CUR, DMC, or BDMC led to decrease Bcl-2 protein expression which is an antiapoptotic protein and to increase ATG5, Beclin 1, p62/SQSTM1, and LC3 expression that associated with cell autophagy in SAS cells. Gefitinib combined with CUR and DMC led to significantly reduce the tumor weights and volumes in SAS cell xenograft nude mice but did not affect the total body weights. Based on those observations, we suggest that the combination of gefitinib with CUR, DMC, and BDMC can be a potential anticancer agent for human oral cancer in future.

Benzyl isothiocyanate inhibits human brain glioblastoma multiforme GBM 8401 cell xenograft tumor in nude mice in vivo.

Benzyl isothiocyanate (BITC), a member of isothiocyanates (ITCs), has been shown to induce cell death in many human cancer cells, but there is no further report to show BITC suppresses glioblastoma multiforme cells in vivo. In the present study, we investigate the effects of BITC on the inhibition of GBM 8401/luc2 cell generated tumor on athymic nude mice. We established a luciferase expressing stable clone named as GBM 8401/luc2. Thirty male mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate xenograft tumor mice model. Group I was treated with 110 µL phosphate-buffered solution plus 10 µL dimethyl sulfoxide, Group II-III with BITC (5 or 10 µmol/100 µL/day, relatively). Mice were given oral treatment of BITC by gavage for 21 days. Results showed that BITC did not affect the body weights. After anesthetized, the photons emitted from mice tumor were detected with Xenogen IVIS imaging system 200 and higher dose of BITC have low total photon flux than that of lower dose of BITC. Results also showed that higher dose of BITC have low total tumor volumes and weights than that of low dose of BITC. Isolated tumors were investigated by immunohistochemical analysis and results showed that BITC at both dose of treatment weakly stained with anti-MCL1 and -XIAP. However, both dose of BITC treatments have strong signals of caspase-3 and Bax. Overall, these data demonstrated that BITC suppressed tumor properties in vivo. Overall, based on these observations, BITC can be used against human glioblastoma multiforme in the future.

Triptolide induced cell death through apoptosis and autophagy in murine leukemia WEHI-3 cells in vitro and promoting immune responses in WEHI-3 generated leukemia mice in vivo.

Triptolide, a traditional Chinese medicine, obtained from Tripterygium wilfordii Hook F, has anti-inflammatory, antiproliferative, and proapoptotic properties. We investigated the potential efficacy of triptolide on murine leukemia by measuring the triptolide-induced cytotoxicity in murine leukemia WEHI-3 cells in vitro. Results indicated that triptolide induced cell morphological changes and induced cytotoxic effects through G0/G1 phase arrest, induction of apoptosis. Flow cytometric assays showed that triptolide increased the production of reactive oxygen species, Ca2+ release and mitochondrial membrane potential (ΔΨm ), and activations of caspase-8, -9, and -3. Triptolide increased protein levels of Fas, Fas-L, Bax, cytochrome c, caspase-9, Endo G, Apaf-1, PARP, caspase-3 but reduced levels of AIF, ATF6α, ATF6ß, and GRP78 in WEHI-3 cells. Triptolide stimulated autophagy based on an increase in acidic vacuoles, monodansylcadaverine staining for LC-3 expression and increased protein levels of ATG 5, ATG 7, and ATG 12. The in vitro data suggest that the cytotoxic effects of triptolide may involve cross-talk between cross-interaction of apoptosis and autophagy. Normal BALB/c mice were i.p. injected with WEHI-3 cells to generate leukemia and were oral treatment with triptolide at 0, 0.02, and 0.2 mg/kg for 3 weeks then animals were weighted and blood, liver, spleen samples were collected. Results indicated that triptolide did not significantly affect the weights of animal body, spleen and liver of leukemia mice, however, triptolide significant increased the cell populations of T cells (CD3), B cells (CD19), monocytes (CD11b), and macrophage (Mac-3). Furthermore, triptolide increased the phagocytosis of macrophage from peripheral blood mononuclear cells (PBMC) but not effects from peritoneum. Triptolide promoted T and B cell proliferation at 0.02 and 0.2 mg/kg treatment when cells were pretreated with Con A and LPS stimulation, respectively; however, triptolide did not significant affect NK cell activities in vivo. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 550-568, 2017.

Clinical Outcomes of Polytetrafluoroethylene-Covered Stents for Coronary Artery Perforation in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) is associated with increased mortality. Polytetrafluoroethylene covered stents (CS) are an effective approach to treat CAP, but data regarding elderly patients requiring CS implantation for CAP are limited. The aim of this study is to report clinical data for elderly CAP patients undergoing CS implantation during PCI. METHODS: Nineteen consecutive elderly patients (≥ 65 years) undergoing CS implantation due to PCI-induced CAP in a tertiary referral center from July 2003 to April 2016 were retrospectively examined. RESULTS: There were 13 men and six women, with a mean age of 75.3 ± 5.6 years (range: 65-86 years). Perforation grade was Ellis type II in five patients (26.3%), and Ellis type III in 14 patients (73.7%). Cardiac tamponade developed in six patients (31.6%), and intra-aortic balloon pumping was needed in four patients (21.1%). The overall success rate for CS implantation rate was 94.7%. The overall in-hospital mortality rate was 15.8%; the in-hospital myocardial infarction rate was 63.2%. Among 16 survival-to-discharge cases, dual antiplatelet therapy (DAPT) was prescribed in 14 cases (87.5%) for a mean duration of 14 months. Overall, there were five angiogram- proven CS failures among 18 patients receiving successful CS implantation. The 1, 2 and 4 years of actuarial freedom from the CS failure were 78%, 65%, and 43% in the angiogram follow-up patients. CONCLUSIONS: CS implantation for CAP is feasible and effective in elderly patients, while CS failure remains a major concern that encourages regular angiographic follow-up in these case.

Alpha-phellandrene-induced apoptosis in mice leukemia WEHI-3 cells in vitro.

Although reports have shown that α-phellandrene (α-PA) is one of the monoterpenes and is often used in the food and perfume industry, our previous studies have indicated that α-PA promoted immune responses in normal mice in vivo. However, there is no available information to show that α-PA induced cell apoptosis in cancer cells, thus, we investigated the effects of α-PA on the cell morphology, viability, cell cycle distribution, and apoptosis in mice leukemia WEHI-3 cells in vitro. Results indicated that α-PA induced cell morphological changes and decreased viability, induced G0/G1 arrest and sub-G1 phase (apoptosis) in WEHI-3 cells. α-PA increased the productions of reactive oxygen species (ROS) and Ca2+ and decreased the levels of mitochondrial membrane potential (ΔΨm ) in dose- and time-dependent manners in WEHI-3 cells that were analyzed by flow cytometer. Results from confocal laser microscopic system examinations show that α-PA promoted the release of cytochrome c, AIF, and Endo G from mitochondria in WEHI-3 cells. These results are the first findings to provide new information for understanding the mechanisms by which α-PA induces cell cycle arrest and apoptosis in WEHI-3 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1640-1651, 2016.

18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways.

In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC50 value of 100 µM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨm) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways.

Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-κB and Matrix Metalloproteinase-2 and -1.

Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells' adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9) activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-κB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-κB p65 and DNA interaction is decreased. NF-κB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future.

Alpha-phellandrene-induced DNA damage and affect DNA repair protein expression in WEHI-3 murine leukemia cells in vitro.

Although there are few reports regarding α-phellandrene (α-PA), a natural compound from Schinus molle L. essential oil, there is no report to show that α-PA induced DNA damage and affected DNA repair associated protein expression. Herein, we investigated the effects of α-PA on DNA damage and repair associated protein expression in murine leukemia cells. Flow cytometric assay was used to measure the effects of α-PA on total cell viability and the results indicated that α-PA induced cell death. Comet assay and 4,6-diamidino-2-phenylindole dihydrochloride staining were used for measuring DNA damage and condensation, respectively, and the results indicated that α-PA induced DNA damage and condensation in a concentration-dependent manner. DNA gel electrophoresis was used to examine the DNA damage and the results showed that α-PA induced DNA damage in WEHI-3 cells. Western blotting assay was used to measure the changes of DNA damage and repair associated protein expression and the results indicated that α-PA increased p-p53, p-H2A.X, 14-3-3-σ, and MDC1 protein expression but inhibited the protein of p53, MGMT, DNA-PK, and BRCA-1.

Effects of diallyl trisulfide on induction of apoptotic death in murine leukemia WEHI-3 cells in vitro and alterations of the immune responses in normal and leukemic mice in vivo.

Diallyl trisulfide (DATS), a chemopreventive dietary constituent and extracted from garlic, has been shown to against cultured many types of human cancer cell liens but the fate of apoptosis in murine leukemia cells in vitro and immune responses in leukemic mice remain elusive. Herein, we clarified the actions of DATS on growth inhibition of murine leukemia WEHI-3 cells in vitro and used WEHI-3 cells to generate leukemic mice in vivo, following to investigate the effects of DATS in animal model. In in vitro study, DATS induced apoptosis of WEHI-3 cells through the G0/G1 phase arrest and induction of caspase-3 activation. In in vivo study DATS decreased the weight of spleen of leukemia mice but did not affect the spleen weight of normal mice. DATS promoted the immune responses such as promotions of the macrophage phagocytosis and NK cell activities in WEHI-3 leukemic and normal mice. However, DATS only promotes NK cell activities in normal mice. DATS increases the surface markers of CD11b and Mac-3 in leukemia mice but only promoted CD3 in normal mice. In conclusion, the present study indicates that DATS induces cell death through induction of apoptosis in mice leukemia WHEI-3 cells. DATS also promotes immune responses in leukemia and normal mice in vivo.

Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1 cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9-signaling pathways.

Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors.

Diallyl sulfide promotes cell-cycle arrest through the p53 expression and triggers induction of apoptosis via caspase- and mitochondria-dependent signaling pathways in human cervical cancer Ca Ski cells.

Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 µM decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 µM) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 µM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer.

Management of distal left main coronary artery aneurysm.

Aneurysms of the left main coronary artery are extremely rare. The cause of such aneurysms is uncertain. Although the treatment of distal left main aneurysms is very complicated, definitive treatment is necessary because the aneurysm may grow further and cause embolism or rupture. Herein, we report a case of acute myocardial infarction caused by aneurysm of the distal left main coronary artery, which was successfully treated by performing coronary artery bypass surgery, followed by implantation of a polytetrafluoroethylene-covered stent.

Late Intervention-Related Complication - A Huge Subepicardial Hematoma.

UNLABELLED: A 75-year-old man had a history of triple vessel coronary artery disease. In August 2009, he had undergone successful percutaneous coronary intervention to the left circumflex coronary artery (LCX) for management of an in-stent restenosis (ISR) lesion. However, in September 2010, he began experiencing recurrent episodes of exertional chest pain. Chest radiography showed the left cardiac border bulging upwards. Transthoracic echocardiography and chest computed tomography revealed a huge oval mass of about 10.4 cm × 7.9 cm × 8.6 cm, which showed calcification and was obliterating the LCX. Subsequent coronary angiography revealed significant instent restenosis, with extravasation of a small amount of contrast material at the stent location, suggesting that the coronary artery had ruptured. We implanted a polytetrafluoroethylene-covered stent to seal the coronary perforation and to release the occlusion. The patient was symptom-free and had an uneventful outcome until the 1-year follow up. KEY WORDS: Coronary artery perforation; Covered stent; Hematoma.

CCN3 increases BMP-4 expression and bone mineralization in osteoblasts.

The nephroblastoma overexpressed (NOV) gene, also called CCN3, regulates differentiation of skeletal mesenchymal cells. Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and bone formation, but the effects of CCN3 on BMP expression and bone formation in cultured osteoblasts are largely unknown. Here we found that CCN3 increased BMP-4 expression and bone nodule formation in cultured osteoblast. Monoclonal antibodies for α5ß1 and αvß5 integrins, and inhibitors of integrin-linked kinase (ILK), p38, and JNK, all inhibited CCN3-induced bone nodule formation and BMP-4 up-regulation of osteoblasts. CCN3 stimulation increased the kinase activity of ILK and phosphorylation of p38 and JNK. Inhibitors of activator protein-1 (AP-1) also suppressed bone nodule formation and BMP-4 expression enhanced by CCN3. Moreover, CCN3-induced c-Jun translocation into the nucleus, and the binding of c-Jun to the AP-1 element on the BMP-4 promoter were both inhibited by specific inhibitors of the ILK, p38, and JNK cascades. Taken together, our results provide evidence that CCN3 enhances BMP-4 expression and bone nodule formation in osteoblasts, and that the integrin receptor, ILK, p38, JNK, and AP-1 signaling pathways may be involved.

Prognostic significance of reciprocal ST-segment depression in patients with acute STEMI undergoing immediate invasive intervention.

PURPOSES: Reciprocal changes are frequent in patients with acute ST-segment elevation myocardial infarction (STEMI). However, their prognostic significance is not clear in patients undergoing immediate invasive intervention. BASIC PROCEDURE: We retrospectively examined 165 consecutive patients with STEMI receiving immediate invasive intervention. The first electrocardiography taken in the emergency department was analyzed. Patients were assigned to 2 groups: with a reciprocal change (group I, n = 100) and without a reciprocal change (group II, n = 65). MAIN FINDINGS: Electrocardiographs revealed that more anterolateral and inferior STEMI occurred in group I and more anterior STEMI occurred in group II. In the emergency department, group I had lower systolic and diastolic blood pressures, higher ventricular tachycardia and fibrillation rates, and higher cardiopulmonary resuscitation rates than did group II. Upon admission, peak troponin I levels were significantly higher in group I, and more group I patients required intra-aortic balloon pumping support. This unstable hemodynamic condition in group I patients was reflected by their higher in-hospital mortality rate. Multivariate analysis showed that age (odds ratio [OR], 1.103; 95% confidence interval [CI], 1.022-1.190; P = .012), Killip class (OR, 2.785; 95% CI, 1.049-7.400; P = .040), and reciprocal change (OR, 9.553; 95% CI, 1.146-79.608; P = .037) remained as independent predictors of in-hospital mortality. Actuarial freedom from all-cause mortality was worse in group I (P = .046). PRINCIPAL CONCLUSIONS: The data suggest that patients with STEMI with reciprocal electrocardiographic changes have unstable hemodynamic status and poorer outcomes. Further prospective studies using a larger patient population are needed.

Arsenic trioxide (As2O3) inhibits murine WEHI-3 leukemia in BALB/c mice in vivo.

Arsenic trioxide (As2O3) is used clinically to treat acute promyelocytic leukemia (APL) and has activity in vitro for induction of apoptosis in several solid tumor cell lines. To investigate the potential therapeutic application of As2O3 for leukemia, we analyzed the effects of As2O3 on the WEHI-3 cells-induced orthotopic leukemia animal model in vivo in this study. We established the WEHI-3 cells leukemia mice through the injection of murine WEHI-3 cells into BALB/c mice, and they were then treated with As2O3 (0.9 and 4.5 mg kg⁻¹ ; p.o.) and/or combined with all-trans-retinoic acid (ATRA), (30 mg kg⁻¹ ; i.p.). The results indicated that (1) As2O3 alone or As2O3 combined with ATRA promoted the total survival rate of leukemia mice and these effects are dose-dependent; (2) As2O3 did not affect the body weight but decreased the spleen weight; however, it did not affect liver weight; (3) As2O3 alone or As2O3 combined with ATRA increased the levels of CD3 and CD19, indicating that the differentiation of T and B cells were promoted; and (4) As2O3 alone or As2O3 combined with ATRA did not change the levels of Mac-3 and CD11b markers, indicating that the differentiation of the precursor of macrophage were not inhibited. Based on these observations, As2O3 alone or As2O3 combined with ATRA have efficacious antileukemia activity in WEHI-3 cells leukemia in vivo.

Rutin inhibits human leukemia tumor growth in a murine xenograft model in vivo.

Numerous studies have shown that rutin has anticancer effects. We have previously reported that rutin induced cell cycle arrest and apoptosis in murine leukemia WEHI-3 cells in vitro and in vivo. However, there are no data showing that rutin inhibits human leukemia HL-60 cells in vivo in a murine xenograft animal model. Human leukemia HL-60 cells were implanted into mice and treated with vehicle (1% DMSO), rutin (120 mg/kg of body weight) or vinblastine (120 µg/kg of body weight). Compounds and agents were injected once every four days intraperitoneally (i.p.) for 36 days. Treatment with 120 mg/kg of rutin or with 120 µg/kg of vinblastine resulted in a reduction of tumor weight and volume when compared with the control groups. Tumor size in xenograft mice treated with 120 mg/kg of rutin was significantly smaller than that in the untreated-control group. These novel findings indicate that rutin inhibits tumor growth in a xenograft animal model. Rutin may be useful in treating leukemia but certainly much more research is needed. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.