scholarly journals Antitumor activity of Ormustine against transplanted leukemia in mice

2016 ◽  
Vol 15 (2) ◽  
pp. 24-31 ◽  
Author(s):  
N. S. Saprykina ◽  
L. M. Borisova ◽  
M. P. Kiseleva ◽  
Z. S. Smirnova ◽  
V. P. Krasnov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Effect ◽  
Evaluation Criteria ◽  
Objective Evaluation ◽  
Lymphoid Leukemia ◽  
Wide Range ◽  
Experimental Leukemia ◽  
Ascites Form

Objective: Evaluation of antitumor activity of a novel alkylnitrosoureas derivative Ormustine (an alkylnitrosocarbamoyl L-ornithine) in mouse lymphoid leukemia models. Materials and methods Antitumor activity of Ormustine has been evaluated in B6D2F1 mice with ascites form of leukemia (L1210, L1210/arenosa, L1210/citrullin and P388) and the solid (P388) form. In this study we used preparations from the alkylnitrosourea group: Ormustine, Aranoza and Lizomustine. Treatment of animals was started 24 hours after inoculation of leukemia intraperitoneally, and 48 hours after inoculation subcutaneous P388. Drugs in a wide range of doses were administrated once intravenously. The follow up period of the animals continued until their death. Criteria of antitumor effect were increasing life expectancy and cure. Evaluation criteria of antitumor effect was the increase in life of experimental mice compared to control ones. Results. Antitumor activity of a novel alkylnitrosoureas derivative, Ormustine has been studied in vivo on the growth of transplanted lymphoid leukemia, such as L1210 (ascites version) and P388 (ascites and solid tumor). Effective dose of single intravenous injection Ormustine against lymphoid leukemia L1210 and P388 was 125 mg/kg. The drug effectively inhibited growth of experimental leukemia. The significant part of the mice with limfoleukemia has been cured. We have also established the single intravenous therapeutic dose of Ormustine on L1210 and Р388 leukemia - 125mg/kg of body weight. Conclusion. The data obtained characterizes Ormustin as a promissing anticancer drug.

scholarly journals Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

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 ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Tumor Cells ◽  
Antitumor Effect ◽  
Inflammatory Responses ◽  
Lethal Dose ◽  
Ehrlich Ascites Carcinoma ◽  
Antitumor Effects ◽  
Th2 Immune Response

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.

scholarly journals In vitro and in vivo evaluation of antitumor activity of methanolic extract of Argyreia nervosa leaves on Ehrlich ascites carcinoma

2015 ◽  
Vol 10 (2) ◽  
pp. 399
Author(s):  
Bhawna Sharma ◽  
Isha Dhamija ◽  
Sandeep Kumar ◽  
Hema Chaudhary
Keyword(s):  
Antitumor Activity ◽  
Solid Tumor ◽  
Methanolic Extract ◽  
Ehrlich Ascites Carcinoma ◽  
Ehrlich Ascites ◽  
Wide Range ◽  
Antioxidant Parameters ◽  
Argyreia Nervosa

<p>The herb of importance like <em>Argyreia nervosa</em> has shown wide range of pharmacological activities. Its methanolic extract of <em>A. nervosa</em> has been explored against Ehrlich ascites carcinoma (EAC) induced liquid and solid tumor in mice. Liquid and solid tumors were induced by intraperitoneal and subcutaneous transplantation of EAC cells in Balb/C mice. Significant and dose dependant results are observed when the mice are sacrificed on 15<sup>th</sup> day for estimation of tumor proliferation, hematological, biochemical and hepatic antioxidant parameters. Mean survival time (days) was increased to 36.5 from 20.5 extract treated mice. The extract also showed a decrease (p&lt;0.001) in body weight and percentage reduction in tumor volume respectively when it was evaluated in solid tumor induced mice for a period of 30 days.  From the result it was concluded that the extract has as a potent antitumor activity and that is comparable to 5-fluorouracil.</p><p> </p>

Raspberry pulp polysaccharides inhibit tumor growth via immunopotentiation and enhance docetaxel chemotherapy against malignant melanoma in vivo

2015 ◽  
Vol 6 (9) ◽  
pp. 3022-3034 ◽  
Author(s):  
Yong-Jing Yang ◽  
Han-Mei Xu ◽  
You-Rui Suo
Keyword(s):  
Malignant Melanoma ◽  
Antitumor Activity ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Inhibit Tumor Growth ◽  
Docetaxel Chemotherapy

Raspberry pulp polysaccharides exhibit antitumor activity in vivo against malignant melanoma through immunopotentiation and enhance the antitumor effect of docetaxel.

scholarly journals The Anticancer Effects of Paeoniflorin and Its Underlying Mechanisms

2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1987640
Author(s):  
Li-Juan Deng ◽  
Yu-He Lei ◽  
Tsz-Fung Chiu ◽  
Ming Qi ◽  
Hua Gan ◽  
...  
Keyword(s):  
Recent Progress ◽  
Antitumor Effect ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Future Prospects ◽  
Anticancer Effects ◽  
Wide Range ◽  
Underlying Mechanisms

Paeoniflorin (PF) is an important pharmacological component of some Chinese traditional herbal formulas, such as Bai Shao, Chi Shao, and Dan Pi, which have been clinically used for centuries. Although many experimental studies have explored a wide range of pharmacological properties of PF, including anticancer, anti-inflammatory, antioxidant, immunoregulatory, and prevention of insulin resistance, there is no review to describe these reported effects systematically, especially the antitumor effect and the underlying mechanisms. In this review, we summarize the recent progress on the anticancer profiles both in vitro and in vivo of PF. Moreover, we highlight the integrated molecular mechanisms of PF and contemplate its future prospects as a potential anticancer drug.

scholarly journals The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma

2018 ◽  
Vol 2 (23) ◽  
pp. 3516-3525 ◽  
Author(s):  
Kyle Runckel ◽  
Matthew J. Barth ◽  
Cory Mavis ◽  
Juan J. Gu ◽  
Francisco J. Hernandez-Ilizaliturri
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Antitumor Effect ◽  
Ex Vivo ◽  
B Cell Lymphoma ◽  
Sensitive Cell ◽  
In Vivo Models ◽  
Synergistic Enhancement

Abstract Clinical observations suggest the existence of shared resistance pathways between rituximab and chemotherapy agents. To explore the mechanisms of rituximab resistance, our group created rituximab-resistant cell lines (RRCLs), which display altered expression of several inhibitor of apoptosis (IAP) family proteins. Here, we provide evidence to support pharmacologically targeting IAPs in lymphoma with LCL-161, a small molecule mimetic of the second mitochondria-derived activator of caspases (SMAC). The antitumor effect of LCL-161 was determined using luminescent adenosine triphosphate assays, flow cytometry, SCID mouse xenografts, and ex vivo patient biopsy sample studies. In vitro exposure to LCL-161 also resulted in a dose-dependent decrease in IAP levels, along with synergistic enhancement of the antitumor effect of cytotoxic chemotherapy, in rituximab-sensitive cell lines and RRCLs. In addition, LCL-161 increased the cytotoxic effect of the proteasome inhibitor carfilzomib in ex vivo lymphoma patient samples. The combination of LCL-161 with the chemotherapy regimen rituximab, gemcitabine, and vinorelbine (RGV) improved in vivo survival compared with RGV alone in severe combined immunodeficient mice implanted with RRCLs but not in animals implanted with rituximab-sensitive cell lines. In summary, LCL-161 exhibits synergistic antitumor activity in both in vitro and in vivo models of resistant lymphoma. Our data support further preclinical investigation of LCL-161 as a novel antilymphoma agent.

scholarly journals Selectively Targeting Tumor Hypoxia with the Hypoxia-Activated Prodrug CP-506

2021 ◽  
Author(s):  
Alexander M.A. van der Wiel ◽  
Victoria Jackson-Patel ◽  
Raymon Niemans ◽  
Ala Yaromina ◽  
Emily Liu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
Tumor Hypoxia ◽  
Human Tumor ◽  
Tumor Oxygenation ◽  
Antitumor Effects ◽  
Wide Range ◽  
Hypoxic Tumor

Abstract Background Hypoxia-activated prodrugs (HAPs) are a promising class of antineoplastic agents that can selectively eliminate hypoxic tumor cells. The present study evaluates the hypoxia-selectivity and antitumor activity of CP-506, a DNA alkylating HAP with favorable pharmacological properties. Methods Stoichiometry of reduction, one-electron affinity, and back-oxidation rate of CP-506 were characterized by fast-reaction radiolytic methods. In vitro, 2D monolayer and 3D spheroid and multicellular layer cultures were used to investigate the hypoxia-selectivity of CP-506. In vivo, the causal relationship between tumor oxygenation and antitumor effects of CP-506 was assessed. Mice bearing a range of human tumor xenografts were exposed to CP-506 and tumor growth was monitored. A multivariate linear regression model was used to identify factors associated with CP-506 treatment outcome. Results Net reduction, metabolism, and cytotoxicity of CP-506 were maximally inhibited at oxygen concentrations above 1 µM (0.1% O2). CP-506 demonstrated cytotoxicity selectively in hypoxic 2D and 3D cell cultures with normoxic/anoxic IC50 ratios up to 203. In vivo, the antitumor effects of CP-506 were selective for hypoxic tumor cells and causally related to tumor oxygenation. CP-506 effectively decreased the hypoxic fraction and inhibited growth of a wide range of hypoxic xenografts. Two well-oxygenated models were refractory to treatment despite intrinsic anoxic sensitivity in vitro. A multivariate regression analysis revealed baseline tumor hypoxia and in vitro sensitivity to CP-506 to significantly correlate with treatment response. Conclusions Our results demonstrate that CP-506 selectively sterilizes hypoxic tumor cells and has broad antitumor activity. Our data also indicate that tumor hypoxia and cellular sensitivity to CP-506 are strong determinants of the antitumor effects of CP-506.

scholarly journals Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

2018 ◽  
Vol 19 (9) ◽  
pp. 2594 ◽  
Author(s):  
Jephesson Santos ◽  
Monalisa Brito ◽  
Rafael Ferreira ◽  
Ana Moura ◽  
Tatyanna Sousa ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Effect ◽  
Lethal Dose ◽  
Ehrlich Ascites Carcinoma ◽  
Cytokine Profile ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Antitumor Effects

Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µg/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1β, TNF-α, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.

scholarly journals Switch receptor T3/28 improves long-term persistence and antitumor efficacy of CAR-T cells

2021 ◽  
Vol 9 (12) ◽  
pp. e003176
Author(s):  
Songbo Zhao ◽  
Chunhua Wang ◽  
Ping Lu ◽  
Yalin Lou ◽  
Huimin Liu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Lymphoid Leukemia ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cells ◽  
Car T

BackgroundChimeric antigen receptor (CAR) T cells have been successfully used in tumor immunotherapy due to their strong antitumor responses, especially in hematological malignancies such as B cell acute lymphoid leukemia. However, on-target off-tumor toxicity and poor persistence severely limit the clinical application of CAR-T cell therapy.MethodsT-cell immunoglobulin mucin domain molecule 3 (TIM-3) was used to develop a second-generation 41BB CD19 CAR linked with a T3/28 chimera, in which truncated extracellular TIM-3 was fused with the CD28 transmembrane and cytoplasmic domains. The efficacy of T3/28 CAR-T cells was evaluated in vitro and in vivo.ResultsWe demonstrated that the switch receptor T3/28 preserved the TCM phenotype, improved proliferative capacity, and reduced exhaustion of CAR-T cells, resulting in superior in vitro and in vivo antitumor activity in B lymphoma. Importantly, the switch receptor T3/28 substantially prolonged the persistence of CAR-T cells, and the interleukin-21/Stat3 axis probably contributed to the enhanced cytotoxicity of T3/28 CAR-T cells.ConclusionOverall, the T3/28 chimera significantly prolonged the persistence of CAR-T cells, and T3/28 CAR-T cells possessed potent antitumor activity in mice, shedding new light on potential improvements in adoptive T cell therapies.

scholarly journals Combination of NOS- and PDK-Inhibitory Activity: Possible Way to Enhance Antitumor Effects

2022 ◽  
Vol 23 (2) ◽  
pp. 730
Author(s):  
Marina Filimonova ◽  
Anna Shitova ◽  
Olga Soldatova ◽  
Ljudmila Shevchenko ◽  
Alina Saburova ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Antitumor Activity ◽  
Anticancer Agents ◽  
Antitumor Effect ◽  
Toxic Effects ◽  
Ehrlich Carcinoma ◽  
Inhibiting Activity ◽  
Antitumor Effects ◽  
Nos Inhibitor

We have previously demonstrated a high antitumor potential of NOS inhibitor T1023 (1-isobutanoyl-2-isopropylisothiourea hydrobromide): antitumor antiangiogenic activity in several animal tumor models and its ability to synergistically enhance the antitumor effects of bevacizumab, cyclophosphamide and γ-radiation. At the same time, rather rapid adaptation of experimental neoplasias to T1023 treatment was often observed. We attempted to enhance the antitumor activity of this NOS inhibitor by supplementing its molecular structure with a PDK-inhibiting fragment, dichloroacetate (DCA), which is capable of hypoxia-oriented toxic effects. We synthesized compound T1084 (1-isobutanoyl-2-isopropylisothiourea dichloroacetate). Its toxic properties, NOS-inhibiting and PDK-inhibiting activity in vivo, and antitumor activity on the mouse Ehrlich carcinoma model (SEC) were investigated in compare with T1023 and Na-DCA. We found that the change of the salt-forming acid from HBr to DCA does not increase the toxicity of 1-isobutanoyl-2-isopropylisothiourea salts, but significantly expands the biochemical and anti-tumor activity. New compound T1084 realizes in vivo NOS-inhibiting and PDK-inhibiting activity, quantitatively, at the level of the previous compounds, T1023 and Na-DCA. In two independent experiments on SEC model, a pronounced synergistic antitumor effect of T1084 was observed in compare with T1023 and Na-DCA at equimolar doses. There were no signs of SEC adaptation to T1084 treatment, while experimental neoplasia rapidly desensitized to the separate treatment of both T1023 and Na-DCA. The totality of the data obtained indicates that the combination of antiangiogenic and hypoxia-oriented toxic effects (in this case, within the molecular structure of the active substance) can increase the antitumor effect and suppress the development of hypoxic resistance of neoplasias. In general, the proposed approach can be used for the design of new anticancer agents.

scholarly journals LEADING NORTH AMERICAN METHODS OF RESEARCH ON CHARACTERS AS OBJECTS OF INTELLECTUAL PROPERTY (ON THE BASIS OF MATERIALS OF USA FORENSIC EXPERTS)

2018 ◽  
Vol 18 ◽  
pp. 512-518
Author(s):  
I. O. Struk ◽  
M. M. Kalinichenko
Keyword(s):  
Intellectual Property ◽  
Forensic Science ◽  
North American ◽  
Evaluation Criteria ◽  
Legal Protection ◽  
Objective Evaluation ◽  
The United States ◽  
Wide Range ◽  
History Of ◽  
Analytical Tools

Characters as a component of visual and audiovisual (as well as literary) works are among the objects of intellectual property and are subject to legal protection. The task of a forensic expert is to empirically determine the characters independence level according to objective evaluation criteria that are not presented in corresponding official methods. In the present article the history of the creation and specific features of leading scientific and methodical means and research practices of characters examination as objects of copyright which became significant spread in the modern analytical practice of North American specialists in the forensic science are briefly reviewed. Thanks to efforts of leading North American forensic science in the field of characters protection as objects of intellectual property, several professional methods have been developed and tested at the same time over past few decades and are actively used in court practice. General review of two main methodological tools that are used most often is presented in this article that purpose and task is to generalize and critically analyze the main scientific and methodological concepts of North American forensic experts which are applied in the process of studying the facts of characters use as objects of copyright. Main scientific methodological "tests" used by of the United States forensic experts ("test for a sufficient level of creative expressiveness" and "test of characters embodying essential features of the work") are considered. While general research on examined methodological materials, productive analytical tools were detailed that are worthy of being included in the arsenal of modern Ukrainian forensic science. However, their effective practical application by domestic forensic experts requires a careful critical attitude, appropriate approbation, application of a wide range of research and methodological approaches.

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