Evaluation of the antitumor effect of lectin obtained from the latex of Euphorbia tirucalli against tumor cells of Ehrlich

The review examined and analyzed scientific publications on the effect of electromagnetic fields (EMF) on various systems of the human body and animals with tumors, as well as on pain in the experiment and the clinic. The theoretical foundations and practical results of the use of EMF in various modulations and modes in the goals and objectives of oncology, including how to optimize the process of anesthesia and correct the vital activity of the body's functional systems with a tumor, are consecrated. Information is given on possible physicochemical effects, features, and mechanisms of therapeutic influence at various levels of a living organism. The ability of electromagnetic waves to transfer information both within a single biosystem and at the level of a whole living organism with a tumor is shown. Studies of combined action of EMF and chemotherapy were analyzed. It has been established that there are experimental prerequisites for using this factor in order to induce changes in the permeability of the membranes of tumor cells by increasing the internalization of chemotherapeutic agents and, thus, enhance the antitumor effect. The role of EMF in the induction of apoptosis in tumor cells is shown. It has been shown that chemotherapy together with electromagnetic fields induces apoptosis and has an inhibitory effect on DNA synthesis in osteosarcoma cells, breast cancer, colon cancer, melanoma and other tumors. The role of magnetic fields in order to enhance the analgesic effect was investigated. The analgesic effect is due to the cessation or weakening of nerve impulses from the painful focus due to the elimination of hypoxia, the improvement of microcirculation, and the reduction of edema, it has been shown. Transcranial magnetic therapy is used as an analgesic tool in onconurology. The therapeutic anti-pain effect is associated with the stimulation of the antinociceptive system, an increase in the synthesis of natural analgesics — endorphins with their subsequent release into the cerebrospinal fluid and blood. As it has already been shown, with the increase in the intensity of pain and its duration, all indicators of the quality of life and the results of treatment of the patient deteriorate, so the search for ways to improve the antitumor effectiveness of specialized treatment and eliminate the causes that prevent their implementation continue to be relevant and in demand.

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4-Methylumbelliferone as a potent and selective antitumor drug on a glioblastoma model

Glycobiology ◽

10.1093/glycob/cwaa046 ◽

2020 ◽

Author(s):

Matías A Pibuel ◽

Mariángeles Díaz ◽

Yamila Molinari ◽

Daniela Poodts ◽

Lucas Silvestroff ◽

...

Keyword(s):

Tumor Cells ◽

Antitumor Effect ◽

Coumarin Derivative ◽

Brdu Incorporation ◽

Normal Brain ◽

Synthesis Inhibitor ◽

Selective Toxicity ◽

Xtt Assay ◽

Membrane Asymmetry ◽

Induced Apoptosis

Abstract Glioblastoma (GBM), the most frequent primary tumor of the central nervous system, has a median survival of 14.6 months. 4-Methylumbelliferone (4MU) is a coumarin derivative widely used as a hyaluronan synthesis inhibitor with proven antitumor activity and without toxic effects reported. We aim to evaluate the antitumor effect of 4MU alone or combined with temozolomide (TMZ) on a GBM cell line, its absence of toxicity on brain cells and its selectivity for tumor cells. The antitumor effect of 4MU alone or combined with TMZ was evaluated on GL26 cells by assessing the metabolic activity through the XTT assay, cell proliferation by BrdU incorporation assay, migration by the wound healing assay, cell death by fluorescein diacetate/propidium iodide (FDA/PI) staining, apoptosis by membrane asymmetry and DNA fragmentation and metalloproteinase activity by zymography. The levels of hyaluronan and its capacity to counteract the effects of 4MU and the expression of RHAMM and CD44 were also determined. The toxicity and selectivity of 4MU were determined by XTT assay and PI staining on normal brain primary cell culture (NBPC-GFP) and GL26/NBPC-GFP cocultures. The GL26 cells expressed RHAMM but not CD44 while synthetized hyaluronan. 4MU decreased hyaluronan synthesis, diminished proliferation and induced apoptosis while reducing cell migration and the activity of metalloproteinases, which was restored by addition of hyaluronic acid. Furthermore, 4MU sensitized GL26 cells to the TMZ effect and showed selective toxicity on tumor cells without exhibiting neurotoxic effects. We demonstrated for the first time the cytotoxic effect of 4MU on GBM cells, highlighting its potential usefulness to improve GBM treatment.

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

Molecules ◽

10.3390/molecules25010029 ◽

2019 ◽

Vol 25 (1) ◽

pp. 29 ◽

Cited By ~ 1

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.

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Tumor CT imaging using targeted nanoparticle delivery for contrast enhancement and tumor inhibition using targeted release of carboplatin nanoparticles via radiotherapy

International Journal of PIXE ◽

10.1142/s0129083514400075 ◽

2014 ◽

Vol 24 (03n04) ◽

pp. 137-149

Author(s):

S. Harada ◽

S. Ehara ◽

K. Ishii ◽

T. Sato ◽

M. Koka ◽

...

Keyword(s):

Breast Cancer ◽

Computed Tomography ◽

Hyaluronic Acid ◽

Contrast Enhancement ◽

Tumor Cells ◽

Antitumor Effect ◽

X Ray ◽

Nanoparticle Delivery ◽

Targeted Nanoparticles ◽

Targeted Release

In this paper, we used microcapsules releasing liposome-protamine-hyaluronic acid nanoparticles (LPH-NP) with/without carboplatin in response to radiation to image and treat MM48 breast cancer in C3He/N mice in two radiation sessions. The micro-particle-induced X-ray emission (PIXE) camera and quantitative PIXE were used to image and measure the release of nanoparticles from the microcapsules. In session one, iopamiron and computed tomography (CT)-detectable microcapsules containing P-selectin and LPH-NP were mixed with a solution of alginate, hyaluronate, ascorbate, and P-selectin. This solution was sprayed into an FeCl2 solution containing VEGFR-1/2 antibodies (Abs). The microcapsules obtained were injected intravenously into mice, and after 9 h, the mice were exposed to 10 or 20 Gy (140 keV) of X-ray radiation. Anti-VEGFR-1/VEGFR-2 microcapsules accumulated around tumors and released P-selectin and the iopamiron-labeled LPH-NP in response to the first radiation. The iopamiron-containing nanoparticles were detected by CT, allowing detection of MM48 tumors by CT. In the second session, the microcapsules released LPH-NH that delivered carboplatin into the tumor cells. This treatment had a significant antitumor effect [Formula: see text]. The micro-PIXE camera and quantitative PIXE successfully imaged and measured the release of contents from microcapsules. Our results indicate that targeted nanoparticles allow for accurate detection and treatment of tumors.

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Therapeutic Antimyeloma Effect of Dendritic-Tumor Cells Hybrids Transduced with Adenovirus Encoding CD40L.

Blood ◽

10.1182/blood.v112.11.1709.1709 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1709-1709

Author(s):

Eva Alvarez ◽

Esther Moga ◽

Jorge Sierra ◽

Javier Briones

Keyword(s):

T Cell ◽

Immune Responses ◽

Tumor Cells ◽

Antitumor Effect ◽

Tumor Antigens ◽

Recombinant Adenovirus ◽

Lymphoid Tissues ◽

Term Survival ◽

Mhc Ii

Abstract Dendritic cells (DCs) are the main antigen presenting cells and play a pivotal role in the stimulation of T-cell immune responses. DCs cultured in the presence of a single tumor antigen can elicit an immune response against tumor cells expressing that antigen. However, simultaneous use of several tumor antigens may be advantageous since polyclonal activation of T cells against different tumor antigens may be a better approach to eradicate tumor cells. In this sense, fusions of dendritic and tumor cells (FCs) show a broad spectrum of tumor antigens, both known and unidentified, to be presented by class I and II MHC. Although prophylactic vaccines were successful in murine models, the results in the therapeutic setting have been unsatisfactory. We hypothesised that enhancing costimulation of FCs would help to break tumor tolerance once the tumor is established. To this purpose, we transduced FCs with a recombinant adenovirus encoding CD40L (AdvCD40L or AdvGFP as control) and we studied the therapeutic antitumoral effect of the administration of FC-CD40L in a murine model of myeloma. DCs obtained from day 7-bone marrow cultures of Balb/c mice were fused with tumor cells, a syngeneic murine myeloma cell line (4TOO). FCs hybrids were generated with PEG and selected after culturing in HAT medium plus GM-CSF for 7 days. FC were quantified by determining the percentage of cells that coexpress specific DC (CD11c) and tumor markers (CD138). Mean fusion efficiency was 30% (20–40%) and FCs expressed moderate levels of CD80, CD83, CD86, CD54, CD40 and MHC II and did not express CD40L. FC-CD40L showed a significant increase of expression of costimulatory molecules (CD80, CD86, CD54, and MHC II) compared to FC-GFP (p=0.011). Moreover, in a syngeneic mixed lymphocyte reaction, FC-CD40L induced a two-fold higher T-cell proliferation than FC-GFP or FC alone. In addition, FC-CD40L had improved migration to lymphoid tissues, preferentially to spleen, in comparison with FC-GFP (2.8% versus 1.6%). The antitumor effect of FC-CD40L was analyzed in vivo. Mice (n=10 per group) were injected i.v. with 2.5×105 tumor cells and treated with irradiated FC, FC-GFP or FC-CD40L (1×106 cells each) on days 2, 6 and 10 after tumor challenge. 40% of mice treated with FC-CD40L had long-term survival (>120 days). In contrast, all of mice treated with FC or FC-GFP died between days 25 and 35 (p=0.012). In parallel, treatment with mixed cells (not fused DC+ tumor cells), mix transduced with AdvGFP, or mix transduced with AdvCD40L did not provide any significant antitumor effect. We conclude that FCs transduced with AdvCD40L better stimulate in vitro and in vivo immune responses than FC alone and may provide a new strategy for treating patients with multiple myeloma or lymphoma.

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Ublituximab (TGTX-1101), a Novel, Third-Generation Anti-CD20 Antibody Demonstrates Enhanced Antitumor Activity Compared to Rituximab in Primary CNS and Intraocular Lymphoma Murine Models.

Blood ◽

10.1182/blood.v120.21.2755.2755 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2755-2755

Author(s):

Sabrina Donnou ◽

Rym Ben Abdelwahed-Bagga ◽

Jérémie Cosette ◽

Hanane Ouakrim ◽

Lucile Crozet ◽

...

Keyword(s):

B Cell ◽

Tumor Cells ◽

Antitumor Effect ◽

Intraocular Lymphoma ◽

Third Generation ◽

Tumor Site ◽

Murine Models ◽

B Cell Lymphomas ◽

Cd20 Antibody ◽

Anti Cd20

Abstract Abstract 2755 Background: Primary Central Nervous lymphomas (PCNSL), that comprise primary cerebral lymphoma (PCL) and primary intraocular lymphoma (PIOL), are typically CD20+ diffuse large B-cell lymphomas that have no detectable disease outside the brain or eye. Rituximab (RTX), an anti-CD20 antibody, has demonstrated encouraging clinical benefit in systemic B-cell lymphomas as well as PCL and PIOL, however, the role of RTX in treatment of PCNSL/PIOL remains controversial, and these highly aggressive malignancies are often incurable with available therapies. Therefore, additional treatment options are needed. Ublituximab (UTX) is a novel, glycoengineered chimeric anti-CD20 monoclonal antibody (mAb) that has a high affinity for FcγRIIIa (CD16) receptors, and therefore greater ADCC activity than RTX (Le Garff-Tavernier et al., 2011). Herein, we assess the antitumor effects of UTX compared to RTX in murine models of PCL and PIOL. Methods: The murine lymphoma B-cell line A20.IIA-GFP-hCD20 (H-2d) was injected into the right cerebral striatum (PCL model) or the vitreous (PIOL model) of adult BALB/c mice (H-2d); 7 days later, single doses of UTX were injected either into the tumor site intracerebrally (PCL) or intravitreously (PIOL), or at distance of the tumor site (intrathecally, PCL). RTX was used as a reference compound. Survival was monitored for injected mice for up to 100 days, and flow cytometric analyses were performed to assess tumor growth and T-cell infiltration. Results: In PCL and PIOL models, single doses of UTX had a marked antitumor effect more pronounced than that obtained with an equivalent dose of RTX. In the PCL model, there was an overall survival (OS) advantage with intracerebral injections of UTX compared to RTX (50% vs. 10%, n=10 in each group, p=0.0028). The reduction in tumor cells was correlated with an increased proportion of CD8+ T cells. Moreover, intrathecal injections of UTX increased OS compared to buffer solution. In the PIOL model, the absolute number of tumor cells analyzed 8 days after treatment had decreased more significantly (p=0.027) with UTX compared to the RTX group. This finding again confirmed the superiority of UTX in this setting. Conclusions: These results confirm that the novel, third-generation mAb, UTX has a sustained and greater antitumor effect than RTX on primary cerebral and intraocular lymphomas when assessed in vivo. Additional experiments evaluating the combination of UTX + methotrexate are ongoing. Clinical trials to evaluate UTX as an innovative therapeutic approach to treat primary cerebral and intraocular B-cell lymphomas are currently being evaluated. Disclosures: Jacquet: LFB Biotechnologies: Employment. Fridman:LFB Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Sportelli:TG Therapeutics, Inc.: Employment, Equity Ownership. Urbain:LFB Biotechnologies: Employment.

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