scholarly journals Antitumor Effects of Curcumin and Glycyrrhetinic Acid-Modified Curcumin-Loaded Cationic Liposome by Intratumoral Administration

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Mingxiang Chang ◽  
Meimei Wu ◽  
Hanmin Li

Curcumin is a hydrophobic polyphenolic compound extracted from the rhizome of Curcuma longa and shows a line of active biological functions, but its application has been limited and questioned because of its low solubility, low bioavailability, and rapid metabolism. In terms of antitumor effect, these disadvantages can be overcome by intratumoral injection. In this study, we present the intratumoral injection of curcumin and glycyrrhetinic acid-modified curcumin-loaded cationic liposome (GAMCLCL) in H22 tumor-bearing mice. The experimental results demonstrated that curcumin exhibited positive antitumor activities in vitro and in vivo by intratumoral injection, but its activities were much weaker than GAMCLCL and adriamycin. Compared with free curcumin, GAMCLCL showed much better effects in improving the blood parameters (WBC, RBC, PLT, ALT, CRE, and LDH), inhibiting tumor growth, reducing tumor microvascular density, downregulating the expression of VEGF-protein and mRNA, and upregulating the expression of caspase-3 protein and mRNA in H22 tumor tissues. Under the experimental conditions of this study, the antitumor effect of high-dose GAMCLCL was similar to adriamycin. In conclusion, the experimental results demonstrated that free curcumin possessed definite antitumor efficacy, but its antitumor activities were weaker, and some strategies should be adopted to overcome its disadvantages, improve, and ensure its clinical efficacy.

2020 ◽  
Vol 8 (1) ◽  
pp. e000622
Author(s):  
Lydia Meziani ◽  
Marine Gerbé de Thoré ◽  
Pauline Hamon ◽  
Sophie Bockel ◽  
Ruy Andrade Louzada ◽  
...  

BackgroundMacrophages play pivotal roles in tumor progression and the response to anticancer therapies, including radiotherapy (RT). Dual oxidase (DUOX) 1 is a transmembrane enzyme that plays a critical role in oxidant generation.MethodsSince we found DUOX1 expression in macrophages from human lung samples exposed to ionizing radiation, we aimed to assess the involvement of DUOX1 in macrophage activation and the role of these macrophages in tumor development.ResultsUsing Duox1−/− mice, we demonstrated that the lack of DUOX1 in proinflammatory macrophages improved the antitumor effect of these cells. Furthermore, intratumoral injection of Duox1−/− proinflammatory macrophages significantly enhanced the antitumor effect of RT. Mechanistically, DUOX1 deficiency increased the production of proinflammatory cytokines (IFNγ, CXCL9, CCL3 and TNFα) by activated macrophages in vitro and the expression of major histocompatibility complex class II in the membranes of macrophages. We also demonstrated that DUOX1 was involved in the phagocytotic function of macrophages in vitro and in vivo. The antitumor effect of Duox1−/− macrophages was associated with a significant increase in IFNγ production by both lymphoid and myeloid immune cells.ConclusionsOur data indicate that DUOX1 is a new target for macrophage reprogramming and suggest that DUOX1 inhibition in macrophages combined with RT is a new therapeutic strategy for the management of cancers.


2021 ◽  
Vol 52 (1) ◽  
pp. 204-217
Author(s):  
Mohammed & Mohammed-Ridha

This study was aimed to investigate the response surface methodology (RSM) to evaluate the effects of various experimental conditions on the removal of levofloxacin (LVX) from the aqueous solution by means of electrocoagulation (EC) technique with stainless steel electrodes. The EC process was achieved successfully with the efficiency of LVX removal of 90%. The results obtained from the regression analysis, showed that the data of experiential are better fitted to the polynomial model of second-order with the predicted correlation coefficient (pred. R2) of 0.723, adjusted correlation coefficient (Adj. R2) of 0.907 and correlation coefficient values (R2) of 0.952. This shows that the predicted models and experimental values are in good agreement. The results of the kinetic study showed that the second-order kinetic model was in good agreement with the experimental results and suggested that the mechanism of chemisorption controlled the LVX adsorption. The experimental results indicated that the adsorption of LVX on iron hydroxide flocs follows Sips isotherm with the value of the correlation coefficient (R2) of 0.937. Sips isotherm shows that both homogenous and heterogeneous adsorption can occur.


2013 ◽  
Vol 790 ◽  
pp. 53-56
Author(s):  
Chen Jian ◽  
Xu Yan Ying ◽  
Wang Na

This paper presents an experimental study of fire suppression effectiveness with water mist containing FeCl2 additives.The investigation focuses on suppression effectiveness under various FeCl2 additives concentrations,working pressures and nozzle different height above the fire source . The experimental results show that: there is a significant impact on fire suppression effectiveness when adding FeCl2 to water mist. There is an optimum additive concentration of extinguishing fire, corresponding to the shortest extinguishing time, the least amount of water, the highest efficiency of extinguishing fire. The nozzle working pressures and nozzle position have effect on the performance of the water mist extinguishing: the greater the pressure is, the shorter water mist fire extinguishing time is. Under the same experimental conditions, the closer the water mist nozzles are to the oil pan, the shorter extinguishing time is.


2018 ◽  
Vol 10 (38) ◽  
pp. 32006-32016 ◽  
Author(s):  
Yanping Qian ◽  
Xiao Liang ◽  
Jingyun Yang ◽  
Chengjian Zhao ◽  
Wen Nie ◽  
...  

2021 ◽  
Vol 1033 ◽  
pp. 103-108
Author(s):  
Ying Cai ◽  
Zhan Xia Wu ◽  
Zhao Yu Zhang ◽  
Zhang Hu

To meet the requirement for high transparency of agar gel used in tissue culture, bacteriological applications, and high-quality cosmetics and food, this study on improving the transparency of agar products was carried out by using activated carbon for decolorization and perlite for aiding filtration. The results showed that the pre-coating filtration method was better than that of the mixed slurry filtration, so an orthogonal experiment optimization was conducted using the pre-coating filtration method based on the single factor experimental results. The experimental results showed that the optimal process conditions based on the transparency index were: concentration of agar of 1.30%, activated carbon dosage of 0.80%, processing temperature of 95 °C, and treatment time of 20 min. Agar products with gel transparency of 58.93% and blue-ray whiteness value of 93.82 could be obtained under these experimental conditions. The order of the factors influencing the decolorization ratio of agar was as follows: activated carbon dosage > concentration of agar > processing temperature > treatment time. The experimental results provided effective procession methods for the production enterprises based on transparency and increased economic benefits, and it was of practical significance.


MedChemComm ◽  
2019 ◽  
Vol 10 (8) ◽  
pp. 1370-1378 ◽  
Author(s):  
Chun-Mei Liu ◽  
Jia-Yan Huang ◽  
Li-Xin Sheng ◽  
Xiao-An Wen ◽  
Ke-Guang Cheng

Due to the obvious adverse effects of 5-fluorouracil and considering the diverse biological activities of pentacyclic triterpenes, twelve pentacyclic triterpene-5-fluorouracil conjugates were synthesized and their antitumor activities were evaluated.


Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2281-2286 ◽  
Author(s):  
JM Herbert ◽  
A Bernat ◽  
JP Maffrand

Abstract Venous thrombosis was induced by ligature of the inferior vena cava in rats whose blood was made hypercoagulable by intravenous (IV) administration of tissue thromboplastin. From a dose-response showing that the administration of increasing doses of tissue thromboplastin resulted in a subsequent progressive increase of thrombus weight, two concentrations of tissue thromboplastin were chosen: a high dose (550 microL/kg, IV) where thrombus formation was optimal and a concentration (7 microL/kg, IV) where tissue thromboplastin-hypercoagulability was intermediate. In both experimental conditions, leukopenia provoked by a myelotoxic drug did not influence the development of venous thrombosis. However, after thrombocytopenia induced by an antiplatelet antiserum, a dramatic decrease in thrombus formation was observed in animals that had been pre-challenged with the lower dose of tissue thromboplastin, whereas decrease in platelet count did not affect venous thrombosis under high thrombogenic challenge. When administered orally 2 hours before thrombosis induction, the ticlopidine analogue clopidogrel showed dose-dependent inhibition of thrombus formation in animals that were pre-challenged with a low dose of tissue thromboplastin (ED50 = 7.9 +/- 1.5 mg/kg, orally) but remained ineffective against high tissue thromboplastin-induced venous thrombosis. We further determined the effect of heparin and hirudin, and showed that both of these drugs exhibited a more potent antithrombotic activity after injection of the lower dose of tissue thromboplastin than after injection of a high dose of tissue thromboplastin. Therefore, using our model of stasis and hypercoagulability, platelet activation played a major role in the development of venous thrombosis when the thrombogenitic stimulus was mild.


Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 29 ◽  
Author(s):  
Daiana K. Frade Silva ◽  
Sâmia S. Duarte ◽  
Thaís M. H. Lisboa ◽  
Rafael C. Ferreira ◽  
Ana Luíza de O. Lopes ◽  
...  

Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (E)-5′-oxo-1′-((3,4,5-trimethoxybenzylidene)amino)-1′,5′-dihydro-10H-spiro[acridine-9,2′-pyrrole]-4′-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor’s total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1β, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.


2007 ◽  
Vol 81 (11) ◽  
pp. 5637-5648 ◽  
Author(s):  
Renaud Burrer ◽  
Benjamin W. Neuman ◽  
Joey P. C. Ting ◽  
David A. Stein ◽  
Hong M. Moulton ◽  
...  

ABSTRACT The recent emergence of novel pathogenic human and animal coronaviruses has highlighted the need for antiviral therapies that are effective against a spectrum of these viruses. We have used several strains of murine hepatitis virus (MHV) in cell culture and in vivo in mouse models to investigate the antiviral characteristics of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs). Ten P-PMOs directed against various target sites in the viral genome were tested in cell culture, and one of these (5TERM), which was complementary to the 5′ terminus of the genomic RNA, was effective against six strains of MHV. Further studies were carried out with various arginine-rich peptides conjugated to the 5TERM PMO sequence in order to evaluate efficacy and toxicity and thereby select candidates for in vivo testing. In uninfected mice, prolonged P-PMO treatment did not result in weight loss or detectable histopathologic changes. 5TERM P-PMO treatment reduced viral titers in target organs and protected mice against virus-induced tissue damage. Prophylactic 5TERM P-PMO treatment decreased the amount of weight loss associated with infection under most experimental conditions. Treatment also prolonged survival in two lethal challenge models. In some cases of high-dose viral inoculation followed by delayed treatment, 5TERM P-PMO treatment was not protective and increased morbidity in the treated group, suggesting that P-PMO may cause toxic effects in diseased mice that were not apparent in the uninfected animals. However, the strong antiviral effect observed suggests that with further development, P-PMO may provide an effective therapeutic approach against a broad range of coronavirus infections.


2020 ◽  
Author(s):  
Xiaobo Du ◽  
Bin Zhang ◽  
Fan Hu ◽  
Chuantao Xie ◽  
Haiyan Tian ◽  
...  

AbstractRegulating the immune system through tumor immunotherapy to defeat tumors is currently one of the most popular methods of tumor treatment. We previously found that the combinations of IL12, IL2 and GMCSF has superior antitumor activities. In this study, IL12IL2GMCSF fusion protein was produced from 293 cells transduced by expression lentiviral vector. IL12IL2GMCSF fusion protein was injected into canine tumors, and the efficacy was monitored to evaluate the potential of tumor immunotherapy. In 14 canines injected with IL12IL2GMCSF protein, 6 had a complete response (CR), 7 had a partial response (PR), and 1 had stable disease (SD). IL12IL2GMCSF fusion protein has great anti-tumor potential. Intratumoral injection of IL12IL2GMCSF can effectively treat tumors without severe adverse effects. It provides a promising immune therapeutics in canine cancers.


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