scholarly journals Efficacy of Gemcitabine on Intracranial Erlich Tumor and its Determinants

Drug Research ◽  
2019 ◽  
Vol 70 (02/03) ◽  
pp. 86-90
Author(s):  
Alexander N. Stukov ◽  
Vladimir G. Bespalov ◽  
Valerij A. Alexandrov ◽  
Alexander L. Semenov ◽  
Galina S. Kireeva ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Antitumor Effect ◽  
Tumor Model ◽  
Intracranial Tumor ◽  
Therapeutic Activity ◽  
Ehrlich Tumor ◽  
Limited Ability ◽  
Wide Range ◽  
Therapeutic Doses ◽  
Sufficient Concentration

AbstractGemcitabine is quite effective in the treatment of brain tumors, although this drug has a limited ability to overcome the blood-brain barrier (BBB). Aim of study is to assess the therapeutic efficacy of gemcitabine and other drugs with different permeability of BBB in the model of intracranial tumor. The therapeutic activity of gemcitabine, carmustine, cyclophosphamide and cisplatin was studied in mice with intracranially implanted Ehrlich tumor, and also gemcitabine in various doses - with intramuscularly implanted tumor. On intracranial tumor model gemcitabine (25 mg/kg) increased the life span (ILS) by 60−89% (p<0.001), despite the fact that its permeability of the BBB is about 10%. Therapeutic activity of carmustine, cyclophosphamide and cisplatin (ILS were 44, 22 and 11%, respectively) corresponds with the BBB permeability for these drugs (90, 20 and 8%, respectively). On intramuscular tumor model, gemcitabine showed significant antitumor effect at both 25 and 2.5 mg/kg, indicating a wide range of therapeutic doses of this drug. Pronounced therapeutic effect of gemcitabine on intracranial tumor most likely is due to the small but sufficient concentration of the drug that overcomes the BBB.

Typologization of security regulation

2020 ◽  
pp. 20-27
Author(s):  
Denis Tikhomirov
Keyword(s):  
Social Relations ◽  
Scientific Literature ◽  
Legal Regulation ◽  
Procedural Understanding ◽  
Limited Ability ◽  
Methodological Basis ◽  
Wide Range ◽  
The Subject ◽  
Definition Of ◽  
Legal Understanding

The purpose of the article is to typologize terminological definitions of security, to find out the general, to identify the originality of their interpretations depending on the subject of legal regulation. The methodological basis of the study is the methods that made it possible to obtain valid conclusions, in particular, the method of comparison, through which it became possible to correlate different interpretations of the term "security"; method of hermeneutics, which allowed to elaborate texts of normative legal acts of Ukraine, method of typologization, which made it possible to create typologization groups of variants of understanding of the term "security". Scientific novelty. The article analyzes the understanding of the term "security" in various regulatory acts in force in Ukraine. Typological groups were understood to understand the term "security". Conclusions. The analysis of the legal material makes it possible to confirm that the issues of security are within the scope of both legislative regulation and various specialized by-laws. However, today there is no single conception on how to interpret security terminology. This is due both to the wide range of social relations that are the subject of legal regulation and to the relativity of the notion of security itself and the lack of coherence of views on its definition in legal acts and in the scientific literature. The multiplicity of definitions is explained by combinations of material and procedural understanding, static - dynamic, and conditioned by the peculiarities of a particular branch of legal regulation, limited ability to use methods of one or another branch, the inter-branch nature of some variations of security, etc. Separation, common and different in the definition of "security" can be used to further standardize, in fact, the regulatory legal understanding of security to more effectively implement the legal regulation of the security direction.

HCA587 protein vaccine induces specific antitumor immunity mediated by CD4+ T-cells expressing granzyme B in a mouse model of melanoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Weiming Yang ◽  
Weiheng Zhang ◽  
Xiaozhong Wang ◽  
Liming Tan ◽  
Hua Li ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antitumor Effect ◽  
Granzyme B ◽  
Cell Subset ◽  
Cell Mediated Immunity ◽  
Protein Vaccine ◽  
Tumor Tissues ◽  
Wide Range ◽  
Ifn Γ

Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy. Objective: To explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity. Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored. Results: After treatment with HCA587 protein vaccine, the vaccination generated elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. Depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated. Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.

CLINICAL AND FORENSIC ASPECTS OF PHARMACOBEZOARS

2020 ◽  
Vol 12 ◽  
Author(s):  
Francisco Basílio ◽  
Ricardo Jorge Dinis-Oliveira
Keyword(s):  
State Of The Art ◽  
Signs And Symptoms ◽  
Immediate Release ◽  
Diagnosis And Treatment ◽  
Blood Concentrations ◽  
Forensic Practice ◽  
Wide Range ◽  
Therapeutic Doses ◽  
Complete History ◽  
Lethal Blood

Background: Pharmacobezoars are specific types of bezoars formed when medicines, such as tablets, suspensions, and/or drug delivery systems, aggregate and may cause death by occluding airways with tenacious material or by eluting drugs resulting in toxic or lethal blood concentrations. Objective: This work aims to fully review the state-of-the-art regarding pathophysiology, diagnosis, treatment and other relevant clinical and forensic features of pharmacobezoars. Results: patients of a wide range of ages and in both sexes present with signs and symptoms of intoxications or more commonly gastrointestinal obstructions. The exact mechanisms of pharmacobezoar formation are unknown but is likely multifactorial. The diagnosis and treatment depend on the gastrointestinal segment affected and should be personalized to the medication and the underlying factor. A good and complete history, physical examination, image tests, upper endoscopy and surgery through laparotomy of the lower tract are useful for diagnosis and treatment. Conclusion: Pharmacobezoars are rarely seen in clinical and forensic practice. They are related to controlled or immediate-release formulations, liquid or non-digestible substances, in normal or altered digestive motility/anatomy tract, and in overdoses or therapeutic doses, and should be suspected in the presence of risk factors or patients taking drugs which may form pharmacobezoars.

scholarly journals IMMU-45. CUSTOMIZED LIPID NANOPARTICLES DELIVER NUCLEIC ACIDS TO IMMUNE CELLS IN BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii114-ii114
Author(s):  
Adam Grippin ◽  
Brandon Wummer ◽  
Hector Mendez-Gomez ◽  
Tyler Wildes ◽  
Kyle Dyson ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Nucleic Acids ◽  
Immune Cells ◽  
White Blood Cells ◽  
Lipid Nanoparticles ◽  
Intracranial Tumor ◽  
Innate Immune ◽  
Checkpoint Blockade ◽  
Normal Brain ◽  
Innate Immune Cells

Abstract BACKGROUND Brain tumors are notoriously difficult to treat in part due to their isolation behind the blood brain barrier and their power to suppress antitumor immune responses. We have previously reported cationic liposome formulations capable of delivering immune modulatory nucleic acids to immune cells in various peripheral organs, but there is currently no reliable method to deliver nucleic acids into brain tumors without direct injection into the tumor site. OBJECTIVE Here, we report the development of a customized lipid nanoparticle to deliver immune modulatory nucleic acids to immune cells in brain tumors. APPROACH Cationic liposomes composed of varying lipid combinations were evaluated for their ability to deliver functional mRNA and siRNA to innate immune cells in vitro and in intracranial tumor models. Nucleic acids were labelled with Cy3 to monitor particle distribution in vivo. RESULTS Lipids composed of DOTAP and cholesterol selectively delivered mRNA and siRNA to intracranial GL261 and KR158b tumors. Interestingly, these particles selectively delivered these nucleic acids to CD45+ white blood cells with minimal delivery to CD45- tumor cells or normal brain tissue. Encapsulation of siRNA blocking programmed death ligand 1 (PDL1) significantly reduced PDL1 expression on innate immune cells in brain tumors, with the greatest effects on tumor-associated macrophages. Co-administration of systemic checkpoint blockade with intravenous administration of these lipid nanoparticles bearing PDL1 siRNA enabled systemic and intratumoral checkpoint blockade, leading to 37% long term survivorship in an otherwise fatal intracranial tumor model. CONCLUSIONS Our customized lipid nanoparticles enable potent intratumoral immune modulation via delivery of nucleic acids to immune cells in brain tumors.

scholarly journals Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 47
Author(s):  
Jing Ding ◽  
Xiaolei Liu ◽  
Bin Tang ◽  
Xue Bai ◽  
Yang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Trichinella Spiralis ◽  
Critical Role ◽  
Tumor Model ◽  
Control Group ◽  
Tumor Inhibition ◽  
Significant Difference ◽  
Secretory Products

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

scholarly journals Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

2011 ◽  
Vol 31 (7) ◽  
pp. 1623-1636 ◽  
Author(s):  
Eugene Kim ◽  
Jiangyang Zhang ◽  
Karen Hong ◽  
Nicole E Benoit ◽  
Arvind P Pathak
Keyword(s):  
Brain Tumor ◽  
Magnetic Resonance ◽  
Brain Tumors ◽  
Three Dimensional ◽  
Region Of Interest ◽  
Tumor Model ◽  
Magnetic Resonance Microscopy ◽  
Vascular Phenotype ◽  
Brain Tumor Model ◽  
Novel Method

Abnormal vascular phenotypes have been implicated in neuropathologies ranging from Alzheimer's disease to brain tumors. The development of transgenic mouse models of such diseases has created a crucial need for characterizing the murine neurovasculature. Although histologic techniques are excellent for imaging the microvasculature at submicron resolutions, they offer only limited coverage. It is also challenging to reconstruct the three-dimensional (3D) vasculature and other structures, such as white matter tracts, after tissue sectioning. Here, we describe a novel method for 3D whole-brain mapping of the murine vasculature using magnetic resonance microscopy (μMRI), and its application to a preclinical brain tumor model. The 3D vascular architecture was characterized by six morphologic parameters: vessel length, vessel radius, microvessel density, length per unit volume, fractional blood volume, and tortuosity. Region-of-interest analysis showed significant differences in the vascular phenotype between the tumor and the contralateral brain, as well as between postinoculation day 12 and day 17 tumors. These results unequivocally show the feasibility of using μMRI to characterize the vascular phenotype of brain tumors. Finally, we show that combining these vascular data with coregistered images acquired with diffusion-weighted MRI provides a new tool for investigating the relationship between angiogenesis and concomitant changes in the brain tumor microenvironment.

Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect

2016 ◽  
Vol 27 (7) ◽  
pp. 1086-1092 ◽  
Author(s):  
Gyoung Min Kim ◽  
Man Deuk Kim ◽  
Do Young Kim ◽  
Se Hoon Kim ◽  
Jong Yun Won ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Transarterial Chemoembolization ◽  
Antitumor Effect ◽  
Tumor Model

Antitumor effect of palmitic acid‐conjugated Dsi RNA for colon cancer in a mouse subcutaneous tumor model

2019 ◽  
Vol 93 (4) ◽  
pp. 570-581 ◽  
Author(s):  
Takanori Kubo ◽  
Yoshio Nishimura ◽  
Yuta Hatori ◽  
Reiko Akagi ◽  
Keichiro Mihara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Palmitic Acid ◽  
Antitumor Effect ◽  
Tumor Model ◽  
Subcutaneous Tumor

scholarly journals Іmmunomodulаtive and antitumor effect of celandine’s preparations on brain tumors

2011 ◽  
Vol 0 (1) ◽  
pp. 23-29
Author(s):  
Nikolay Lisianyi ◽  
Lyudmila Belska ◽  
Antonina Klyuchnikova
Keyword(s):  
Brain Tumors ◽  
Antitumor Effect
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