scholarly journals Synthesis and in vivo anticancer evaluation of poly(organo)phosphazene-based metallodrug conjugates

2017 ◽  
Vol 46 (36) ◽  
pp. 12114-12124 ◽  
Author(s):  
Carmen M. Hackl ◽  
Beatrix Schoenhacker-Alte ◽  
Matthias H. M. Klose ◽  
Helena Henke ◽  
Maria S. Legina ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Growth ◽  
Drug Conjugates ◽  
Polymer Conjugation ◽  
Local Side ◽  
Macromolecular Drug

Macromolecular drug conjugates: Polymer conjugation reduces local side effects and tumor growth in vivo.

Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3837-3844 ◽  
Author(s):  
Farida Djouad ◽  
Pascale Plence ◽  
Claire Bony ◽  
Philippe Tropel ◽  
Florence Apparailly ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Tumor Growth ◽  
Tumor Model ◽  
Bone Morphogenetic Protein 2 ◽  
Melanoma Tumor ◽  
Immunocompetent Mice

Abstract Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, they have gained further interest after demonstration of an immunosuppressive role. In this study, we investigated whether in vivo injection of MSCs could display side effects related to systemic immunosuppression favoring tumor growth. We first showed in vitro that the murine C3H10T1/2 (C3) MSC line and primary MSCs exhibit immunosuppressive properties in mixed lymphocyte reaction. We demonstrated that this effect is mediated by soluble factors, secreted only on “activation” of MSCs in the presence of splenocytes. Moreover, the immunosuppression is mediated by CD8+ regulatory cells responsible for the inhibition of allogeneic lymphocyte proliferation. We then demonstrated that the C3 MSCs expressing the human bone morphogenetic protein 2 (hBMP-2) differentiation factor were not rejected when implanted in various allogeneic immunocompetent mice and were still able to differentiate into bone. Importantly, using a murine melanoma tumor model, we showed that the subcutaneous injection of B16 melanoma cells led to tumor growth in allogeneic recipients only when MSCs were coinjected. Although the potential side effects of immunosuppression induced by MSCs have to be considered in further clinical studies, the usefulness of MSCs for various therapeutic applications still remains of great interest. (Blood. 2003;102:3837-3844)

A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin

2015 ◽  
Vol 146 ◽  
pp. 89-96 ◽  
Author(s):  
Jin-Quan Wang ◽  
Ping-Yu Zhang ◽  
Liang-Nian Ji ◽  
Hui Chao
Keyword(s):  
Side Effects ◽  
Tumor Growth

scholarly journals RBIO-02. COMBINING RADIOTHERAPY WITH PI3K ISOFORM-SPECIFIC INHIBITOR DECREASES RADIORESISTANCE AND SUPPRESSES TUMOR GROWTH IN GLIOBLASTOMA CELLS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii192-ii192
Author(s):  
Mi Youn Seol ◽  
Hong In Yoon
Keyword(s):  
Side Effects ◽  
Combination Therapy ◽  
Tumor Growth ◽  
Synergistic Effects ◽  
Specific Inhibitor ◽  
Akt Signaling ◽  
Growth Delay ◽  
Migration Ability ◽  
Dismal Prognosis

Abstract Glioblastoma (GBM) is the most malignant tumor that occurs within the brain and shows the dismal prognosis. The phosphoinositide 3-kinase (PI3K)-AKT signaling pathway plays a principal role in GBM. Also, Activated PI3K-AKT signaling by irradiation induces radioresistance. But, the pan-PI3K inhibitors cause side-effects in clinical trial. Different PI3K isoforms play non-redundant roles in brain tumor growth and regulating radioresistance. So it is expected that selective inhibition of PI3K isoforms decrease side effects. We demonstrated whether combining radiotherapy with the PI3K isoform inhibitor reduces radioresistance and tumor growth in GBM. Glioma261 expressed luciferase (GL261-luc) cell lines were used to investigate the synergistic effects of combining radiotherapy with the PI3K isoform inhibitors. GL261-luc were irradiated 1Gy with or without PI3K isoform inhibitors. GL261-luc irradiated by 1Gy was suppressed cell proliferation about 70% compared to control (p< 0.001). When irradiated with PI3K-isform inhibitor, each growth rate was about 18% (PI3K-pan, p< 0.00001), 25% (PI3K-alpha, p< 0.00001), 30% (PI3K-delta, p< 0.00001), 45% (PI3K-gamma/delta, p< 0.00001). Significant increase of DNA DSB and decrease of the migration ability were shown by combination radiotherapy with PI3K- isoform inhibitor. Especially, combining radiotherapy, PI3K-alpha inhibitor showed the effect similar to PI3K-pan inhibitor (In vitro). So, we analyzed combination therapy effects using PI3K-alphs inhibitor and radiotherapy in vivo. We demonstrated that combining radiotherapy with the PI3K-alpha isoform inhibitor markedly delayed tumor growth than radiotherapy only (p< 0.0001). Also, we confirmed that survival rate of intracranial GBM mouse was increased by combination therapy (p< 0.01). In addition, the expression of PD1, regulator of cancer immune system, in spleenocyte was increased by combination therapy (p< 0.001) (In vivo). Our results demonstrate that combining radiotherapy with the PI3K-alpha isoform improve radiosensitivity, which result in significant tumor growth delay and improved survival.

Abstract B114: Humanized anti-Sialyl-Tn monoclonal antibody-drug conjugates inhibit tumor growth in vitro and in vivo

2018 ◽  
Author(s):  
Daniel Dransfield ◽  
Jillian M. Prendergast ◽  
David A. Eavarone ◽  
Rawan Nazer ◽  
Linah Al-Alem ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Growth ◽  
Inhibit Tumor Growth ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
Sialyl Tn ◽  
Antibody Drug

scholarly journals DYNAMICS OF TUMOR GROWTH UNDER THE ACTION OF THE NEW NANO-FERRIMAGNETIC NANOEMBOSYL WITH TRANSARTERIAL INTRODUCTION

2020 ◽  
Vol 66 (5) ◽  
pp. 578-585
Author(s):  
Yelena Treshchalina ◽  
M. Lkunina ◽  
K. Makovetskaya ◽  
A. Stanzhevskiy
Keyword(s):  
Side Effects ◽  
Tumor Growth ◽  
Low Frequency ◽  
Arterial Embolization ◽  
Preclinical Study ◽  
Arterial Blood Flow ◽  
Low Viscosity ◽  
Arterial Blood ◽  
Long Time ◽  
Local Side

Introduction. For the treatment of primary inoperable and metastatic solid human tumors with local regional arterial blood flow, a minimally invasive embolization method is used, which causes a decrease in the growth rate and size of the malignancy (cytoreduction), local side effects of which depend on the viscosity of the embolizing agent. Nanostructured ferro- and ferrimagnetics (ferrites) allow selectively achieving not only cytoreduction, but also full effect by following the embolization of magnetic hyperthermia (MHT). Material and methods. The study of a new original embolizing nano-ferrimagnetic nanoembosil with low viscosity was performed with intra-arterial (i.a.) administration to anesthetized animals with intramuscular (i.m.) developed tumors (PC1 and VX2). This allowed us to evaluate its effectiveness using adequate criteria and the method of variation statistics (Fisher-Student’s criterion «t» in the environment of the IBM SPSS 21 package) and statistically significant differences at p≤0.05. Results and discussion. It is shown that nanoembosil in doses of 0.1 and 0.2 ml for rats and 1.5 ml for rabbits is dose-dependent, and in the case of VX2 it is statistically significant (p=0.001) for a long time in 2-6 times inhibits the rate of tumor growth without side effects with long-term stabilization and cytoreduction by 50-65%. Structural analogs of nanoembosil in the practice of medicine there. Conclusion. Thus, nanoembosil can be considered an original effective agent for selective arterial embolization and it is recommended to continue its preclinical study in therapeutic and preoperative modes. Good tolerance of i.a. administration of nanoembosil in the studied doses with no local side effects opens the possibility of studying the possibility of studying it as a thermo-sensitive nanomaterial for low-frequency MHT.

Local Treatment of Recent Arterial Thromboembolic Occlusions with Brinase

1975 ◽  
Vol 34 (02) ◽  
pp. 498-503 ◽  
Author(s):  
D Nyman ◽  
M. A da Silva ◽  
L. K Widmer ◽  
F Duckert
Keyword(s):  
Side Effects ◽  
Local Treatment ◽  
Before And After ◽  
Local Side

SummaryBrinase was administered intra-arterially in 16 patients with thrombotic or embolic arterial occlusions. Angiography could be performed before and after treatment in 13 patients. Thrombolysis was obtained in 3 of 9 patients with thrombotic and in 3 of 4 patients with embolic occlusions. In 3 patients severe local side effects occurred.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

1984 ◽  
Vol 51 (02) ◽  
pp. 248-253 ◽  
Author(s):  
R J Dupe ◽  
P D English ◽  
R A G Smith ◽  
J Green
Keyword(s):  
Pulmonary Embolism ◽  
Side Effects ◽  
Venous Thrombosis ◽  
Active Site ◽  
Acute Pulmonary Embolism ◽  
Quantitative Model ◽  
Beagle Dog ◽  
Thrombosis Model ◽  
Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

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