Synergistic Anticancer Effects of Cisplatin Combined with Combretastatin A4 Phosphate on Human Osteosarcoma-Xenografted Mice

2021 ◽  
pp. 1-8
Author(s):  
Guo Dai ◽  
Di Zheng ◽  
Gaiwei Liu ◽  
Qi Song
Keyword(s):  
Vehicle Control ◽  
Toxic Effects ◽  
Combination Group ◽  
Control Group ◽  
Histopathological Analysis ◽  
Therapeutic Effects ◽  
Osteosarcoma Cells ◽  
Transplanted Tumors ◽  
Human Osteosarcoma ◽  
Combretastatin A4

This study aimed to investigate the effectiveness of anticancer therapy combining a cytotoxic chemotherapeutic agent, cisplatin (DDP), and a vascular disruptive drug, combretastatin A4 phosphate (CA4P), in osteosarcoma. First, a human osteosarcoma-xenografted mice model was established. Second, the transplanted tumor models were treated with DDP and CA4P in combination or as monotherapy. Third, the therapeutic effects and the mechanism of the drug combination in the inhibition of transplanted tumors was studied. Finally, the toxic effects of the drugs were observed and recorded. The results showed that DDP combined with CA4P significantly inhibited the growth and lung metastasis of transplanted tumors compared with the monotherapy drug group and vehicle control group. Histopathological analysis revealed that apoptotic and necrotic cell death significantly increased in the combination group, and combined treatment significantly inhibited the proliferation of osteosarcoma cells compared with either agent alone or the vehicle control. Additionally, no obvious toxic effects were observed in the combination group. These results indicate that the combined effects of DDP and CA4P on the progression of human osteosarcoma in vivo were superior to that of either agent alone. DDP combined with CA4P exerted synergistic effects at lower concentrations and promoted apoptosis and necrosis, as well as inhibited proliferation of osteosarcoma cells, but it did not increase the systemic toxic effects of chemotherapy. Our findings highlight CA4P as an effective anticancer agent candidate for combination with DDP in clinical applications to treat osteosarcoma.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

Concurrent administration of acetaminophen and ethanol: impact on mouse liver and testis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Jonah Sydney Aprioku ◽  
Precious Gospel
Keyword(s):  
Sperm Count ◽  
Serum Levels ◽  
Combination Group ◽  
Control Group ◽  
Histopathological Analysis ◽  
Epididymal Sperm ◽  
Concurrent Administration ◽  
Simultaneous Treatment ◽  
The Individual ◽  
Biochemical Indices

AbstractObjectivesAcetaminophen (paracetamol) and alcohol are widely consumed as analgesic/antipyretic and recreational agent, respectively. High doses of both agents induce liver and male reproductive toxicities. This study investigated the toxicological outcome of concurrent administration of paracetamol and ethanol in the liver and testis in mice.MethodsAnimals were gavaged paracetamol (250 mg/kg), ethanol (3 g/kg) or paracetamol + ethanol for 2 d. Some groups were sacrificed 12 h after the last dose, while others were sacrificed 21 d posttreatment for reversibility study. Control group received carboxymethylcellulose sodium (0.2%). Serum levels of liver biochemical indices and epididymal sperm were analysed. Histopathological analysis of the liver and testis were also performed.ResultsAlkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin in serum were elevated (p<0.001); whereas albumin and total protein were reduced (p<0.001) in paracetamol or ethanol groups compared to control. In the combination group, only mild elevation of ALT (p<0.05) was observed. Additionally, hepatocyte necrosis occurred in the livers of paracetamol and ethanol groups, while only mild inflammatory changes were seen in the combination group. All liver indices were normal in reversibility study animals. Furthermore, sperm count, motility, viability and morphology did not change in all treated animals, except that sperm count was decreased (p<0.05) in paracetamol group. Testis histology of all animal groups were normal.ConclusionsThe results demonstrated that simultaneous treatment with acute paracetamol and ethanol doses will possibly minimize hepatotoxicity and reduction of epididymal sperm reserve by the individual agents, and the toxicities are reversible.

scholarly journals Effects of Cabozantinib on Human G292 Osteosarcoma Cells

2021 ◽  
Vol 9 (9) ◽  
Author(s):  
Longjie Chen ◽  
Dinh Nguyen ◽  
Ryan Kaminsky ◽  
Jennifer Helfer ◽  
Rosemary Dziak
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Complex Nature ◽  
Therapeutic Effects ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Igf I

Cabozantinib (CBZ) N-(4-((6,7-dimethoxyquinolin-4-yl) oxy) phenyl)-N-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide) (XL184), an inhibitor of MET and vascular endothelial growth factor receptor (VEGFR-2), is an agent approved for the treatment of several types of carcinoma such as medullary thyroid and renal. Recent studies are encouraging for the effectiveness of CBZ in the treatment of osteosarcoma. Because of the complex nature of the microenvironment of osteosarcoma cell sites, in order to better understand the direct effects of CBZ on osteosarcoma cells, in vitro studies were conducted with the human osteosarcoma cell line, G292. Experiments were focused on the effects of CBZ on cell metabolic activity, differentiation, and apoptosis as well as the modulation of responses to growth factors such as platelet-derived growth factor (PDGF) and insulin like growth factor (IGF-I). The results indicate that CBZ can increase the activity of caspase 3/7 as an indicator of apoptosis as well as decrease cellular activity, measured by MTT assay and differentiation assessed by alkaline phosphatase activity. The drug partially downregulated the effects of PDGF on MTT activity and had significant inhibitory effects on the G292 cells response to IGF-I and production of VEGF. This study presents original information on responses of G292 human osteosarcoma cells to the chemotherapy agent, CBZ, and provides in vitro data consistent with the potential therapeutic effects of this agent for osteosarcoma.

scholarly journals Effect of Cyclophosphamide and Its Combination with Metformin on the Survival Rate in Mice

2019 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Alhowail ◽  
Sultan Sajid ◽  
Yasser Almogbel ◽  
S. I. Rabbani ◽  
Mansour Alsharidah
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Survival Rate ◽  
The Body ◽  
Toxic Effects ◽  
Combination Group ◽  
Control Group ◽  
First Line Therapy ◽  
Body Weights ◽  
Daily Dose

Background: Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, is widely used to treat several types of cancer. Its toxic effects are well-established and include hepatotoxicity, nephrotoxicity, and bone marrow suppression. Metformin (MET) is an anti-diabetic medication that is considered a first-line therapy for type 2 diabetes mellitus. In this study, we aimed to investigate the effect of co-administration of MET on CYP-induced toxicity by recording the survival rate in mice. Methods: Fifty mice (body weight 30–35 gm) were divided into four groups as control and treatments and comprised of 12-13 animals of either sex. The animals in the control group received 4 doses of saline by injection. The animals in the CYP group received 4 doses of CYP (100 mg/kg) (intraperitoneal). The animals in the MET group received lower daily dose (30 mg/kg) in drinking water (3 mg/ml), starting 3 days prior to CYP injection and lasting until the final injection of CYP. The animals in the combination group (CYP and MET) received 4 doses of CYP (100 mg/kg) and a daily dose of MET in drinking water (3 mg/ml). The animals were observed daily to record the mortality and their body weights were recorded every alternate day. The data obtained from the study was statistically analyzed by one-way ANOVA, and p<0.05 was considered significant. Results: The data obtained from the study indicated that CYP administration increased the rate of mortality significantly (p < 0.01) when compared to the control animals, while MET reduced the rate. When the combination of CYP and MET was tested, the mortality rate was found to be increased. Both CYP and MET significantly reduced the body weight compared to the control animals. Conclusion: The results indicated that the combination of CYP and MET reduced the survival rate of animals, suggesting that although MET possesses anti-proliferative action, it has the potential to increase the toxic effects of CYP when combined with CYP.

Abstract 14321: Administration of Laminin511 Combined With Prostacyclin Agonist Enhances Endogenous Stem Cell Recruitment in Acute Myocardial Infarction Model Rat

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nagako Sougawa ◽  
Shigeru Miyagawa ◽  
Akima Harada ◽  
Noriko Oda-Mochizuki ◽  
Ryoko Sato-Nishiuchi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cell ◽  
Infarct Size ◽  
The Other ◽  
Combination Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Cell Recruitment ◽  
Endogenous Stem Cell

Backgroud: Although treatment by endogenous stem cell recruitment is one of the promising therapeutic options for the damaged tissues, the therapeutic efficacy is not enough to repair the severely damaged heart. How to enhance migration of stem cells to injured site and confine them there may be key point to improve the therapeutic effects. In this study, we hypothesized that combined strategy of prostacyclin agonist (ONO1301), which is enhancer in stem cell recruitment, and laminin (LM) 511 as stem cell bed may enhance regeneration processes in failed heart. Methods and Results: To examine the therapeutic effect of ONO1301 and LM511, we administrated ONO1301 and LM511 immersed collagen sheet (Combination group), only LM511 immersed collagen sheet (LM group), only ONO1301 immersed collagen sheet (ONO group), and PBS immersed collagen sheet (control) to rat acute infarction model. Four weeks later, qPCR analysis and histological analysis revealed that the expression of cytokines related to cell migration or angiogenesis were significantly higher in the combination group as compared to the other groups. The number of mesenchymal stem cell (PDGFRα and CD90 double positive cells) tended to be higher in the combination group compared to the other groups (combination: 388 ± 7 cells/mm 2 , LM: 292 ± 34 cells/mm 2 , ONO: 216 ± 30 cells/mm 2 , control: 160 ± 34 cells/mm 2 ). In addition, the number of matured arterioles which have both endothelial cells and smooth muscle cells was markedly higher in the combination group compared to the control group (combination: 616 ± 44 cells/mm 2 , control: 226 ± 60cells/mm 2 ; p < 0.05). In addition, infarct size was remarkably reduced in the combination group than the other groups (combination: 11.5 ± 0.1%, LM: 14.8 ± 0.8%, ONO: 23.6 ± 2.9%, control: 29.2 ± 2.0%). Ultrasonographically, ejection fraction significantly improved in the combination group compared to the other groups (combination: 55.0 ± 0.9%, LM: 51.6 ± 1.4%, ONO: 46.9 ± 1.4%, control: 43.5 ± 2.9%). Conclusion: The combined administration of LM511 and ONO1301 promotes arteriogenesis by enhanced endogenous repair with declined infarct size and improved cardiac function in rat acute myocardial infarction model, proposing new therapeutic strategy for ischemic cardiomyopathy.

The Quantitative Ultrastructure of the Heart Muscle of Japanese Quail by Hypergravitation, Hypodynamy and Combination

1990 ◽  
Vol 48 (3) ◽  
pp. 188-189
Author(s):  
Anton Bózner ◽  
Mikuláš Gažo ◽  
Jozef Dostál
Keyword(s):  
Japanese Quail ◽  
Heart Muscle ◽  
Relative Size ◽  
Combination Group ◽  
Control Group ◽  
Group V ◽  
Group Iii ◽  
Space Flights ◽  
Group I ◽  
Quantitative Ultrastructure

It is anticipated that Japanese quail /Coturnix coturnix japonica/ will provide animal proteins in long term space flights. Consequently this species of birds is of research interest of international space program INTERCOSMOS. In the year 1987 we reported on an experiment /2/ in which the effect of chronic acceleration of 2 G hypergravitation, the hypodynamy and the simultaneous effect of chronic acceleration and the location in the centre of the turntable of the centrifuge on the protein fractions in skeletal muscles was studied. The ultrastructure of the heart muscle was now in this experiments examined as well.Japanese quail cockerels, aged 48 days were exposed to 2 G hypergravitation /group IV/ in a 6,4 m diameter centrifuge, to hypodynamy /group III/ and their combination /group V/, respectively for 6 days / Fig.1/. The hypodynamy in group III was achieved by suspending the birds in jackets without contact the floor. The group II was located in the centre ofthe turntable of the centrifuge. The control group I. was kept under normal conditions. The quantitative ultrastructure of myocard was evaluated by the methods of Weibel/3/ - this enables to determine the number, relative size and volume of mitochondria volume of single mitochondria, defficiency of mitochondrial cristae and volume of myofibrils.

Antiproliferative properties of oleuropein in human osteosarcoma cells

2016 ◽  
Author(s):  
Jose M Moran ◽  
Olga Leal-Hernandez ◽  
Maria L Canal-Macias ◽  
Jesus M Lavado-Garcia ◽  
Raul Roncero-Martin ◽  
...  
Keyword(s):  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

PRECLINICAL STUDY OF THE VETERINARY DRUGS TOXICITY

1970 ◽  
pp. 61-64
Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov
Keyword(s):  
Lethal Dose ◽  
Clinical Manifestations ◽  
Preclinical Study ◽  
Veterinary Drugs ◽  
Toxic Effects ◽  
Laboratory Animals ◽  
Therapeutic Effects ◽  
Significant Information ◽  
Important Indicator ◽  
Organ Systems

Preclinical study of the drugs toxicity was analysed it allows predicting the safety of veterinary drugs in laboratory animals. The fundamental normative instruments in the field of preclinical study of drugs for veterinary medicine and animal husbandry are Order of the Ministry of Agriculture of the Russian Federation dated 06.03.2018 N 101 and GOST 33044-2014 Principles of Good Laboratory Practice. An important indicator of the preclinical study of the veterinary drugs is the determination (calculation) of median lethal dose value (lethal dose for half of the animals tested) or concentration (LD50 or LC50). Existing methods for determining this indicator make it possible at the initial study stage to determine the degree and class the drug of toxicity. Studying the symptoms of intoxication in the analysis of pharmacological substances one obtains significant information about the nature of the action of the future drug. The clinical manifestations of intoxication with damage to various organ systems are presented. As criteria for assessing the toxic effects of veterinary drugs it is recommended to determine LD50, cumulation coefficient, latitude index of therapeutic effects, dose level of toxic effects in the experiment which allows predicting the nature and degree of toxic effects of the drug even at the stage of preclinical veterinary drugs study.

Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats

2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Brain Aging ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Histopathological Analysis ◽  
Hippocampal Damage ◽  
Common Belief ◽  
Mao B ◽  
Positive Effects ◽  
The Brain

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

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