scholarly journals A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, andIn VivoAntitumor Efficacy and Safety

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Wang ◽  
Ke-Chun Wu ◽  
Bing-Xiang Zhao ◽  
Xin Zhao ◽  
Xin Wang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Therapeutic Efficacy ◽  
Antitumor Efficacy ◽  
Allergic Reactions ◽  
Cremophor El ◽  
Efficacy And Safety ◽  
Tumor Bearing ◽  
Allergic Effect ◽  
Injection Product

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution,in vivoantitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P<.01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.

scholarly journals Synergistic antitumor efficacy of antibacterial helvolic acid from Cordyceps taii and cyclophosphamide in a tumor mouse model

2016 ◽  
Vol 242 (2) ◽  
pp. 214-222 ◽  
Author(s):  
Jian-Hui Xiao ◽  
Yao Zhang ◽  
Gui-You Liang ◽  
Ru-Ming Liu ◽  
Xiao-Gang Li ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Human Cancer ◽  
Antitumor Efficacy ◽  
Nuclear Antigen ◽  
Human Cancer Cells ◽  
Tumor Bearing ◽  
Organ Index ◽  
Tumor Mouse Model ◽  
Helvolic Acid

The antibacterial agent helvolic acid, which was isolated from the active antitumor fraction of Cordyceps taii, showed potent cytotoxicity against different human cancer cells. In the present study, the in vivo antitumor effect of helvolic acid was investigated in murine sarcoma S180 tumor-bearing mice. Doses of 10 and 20 mg/kg/day helvolic acid did not exert significant antitumor activity. Interestingly, co-administration of 10 mg/kg/day helvolic acid and 20 mg/kg/day cyclophosphamide (CTX) – a well-known chemotherapy drug – showed promising antitumor activity with a growth inhibitory rate of 70.90%, which was much higher than that of CTX alone (19.5%). Furthermore, the combination markedly prolonged the survival of tumor-bearing mice. In addition, helvolic acid enhanced the immune organ index. The protein expression levels of β-catenin, cyclin D1, and proliferating cell nuclear antigen were significantly suppressed in mice treated with 20 mg/kg/day helvolic acid and in those receiving combination therapy. Taken together, these results indicated that helvolic acid in combination with CTX showed potent in vivo synergistic antitumor efficacy, and its mechanism of action may involve the Wnt/ β-catenin signaling pathway.

The in vivo antitumor activity of LHRH targeted methotrexate–human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice

2012 ◽  
Vol 431 (1-2) ◽  
pp. 183-189 ◽  
Author(s):  
Azade Taheri ◽  
Rassoul Dinarvand ◽  
Fatemeh Ahadi ◽  
Mohammad Reza Khorramizadeh ◽  
Fatemeh Atyabi
Keyword(s):  
Human Serum Albumin ◽  
Antitumor Activity ◽  
Serum Albumin ◽  
Human Serum ◽  
Albumin Nanoparticles ◽  
Tumor Bearing ◽  
In Vivo Antitumor Activity

Enhanced Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV Specific Central Memory T Cells by CMV Vaccine.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3014-3014
Author(s):  
Xiuli Wang ◽  
Winnie Wong ◽  
Wen-Chung Chang ◽  
Don Diamond ◽  
Michael C. Jensen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Adoptive Transfer ◽  
Viral Antigen ◽  
Memory T Cells ◽  
Central Memory T Cells ◽  
Tumor Bearing ◽  
Nsg Mice

Abstract Abstract 3014 Development of T cell products that have engineered specificity for CD19 has broad application to adoptive transfer therapy for B-lineage lymphoma and leukemia. Clinical studies have demonstrated the safety and feasibility of cloned and bulk T cell transfer as a therapy for patients. But potency of this strategy has proven challenging, primarily due to issues relating to a lack of persistence of the adoptively transferred cells in patients. In contrast, the adoptive transfer of viral specific T cells has shown efficient efficacy for preventing progressive viral infections and exhibited long term persistence in patients, in part due to the viral specific T cells received optimal co-stimulation after engagement of their native receptors. Conceptually, engineering CMV specific T cells with CD19CAR to provide them with a second specificity for a tumor antigen may enable the transferred T cells (bi-specific T cells) to persist or numerically expand in vivo by stimulation of the endogenous TCR by virus antigen. Moreover, bi-specific T cell can be used in treatment for B cell malignancies in allo-settings without causing GVHD due to the pre-defined non-alloreactive TCR specificity. In this study, we explored the use of CMVxCD19CAR bi-specific T cells in CD19+tumor bearing NSG mice and evaluated their antitumor activity in response to CMVpp65 antigen stimulation as a consequence of CAR transduced T cell expansion. CMV specific T cells derived from central memory T cells were selectively expanded by 2 rounds of stimulation with cGMP grade pp65 protein followed a rapid expansion containing OKT3 and feeder cells. The established CMV specific Tcm, in which majority of them are CMVpp65 tetramer positive, were then transduced with cGMP grade SIN lentivirus expressing CD19R:CD28:z/EGFRt. After stimulation with CD19 positive LCL, 40% of the resultant cells co-express pp65 tetramer and CAR as detected by EGFRt/Erbitux analysis. Functionally, the bi-specific T cells exhibit specific cytolytic activity and secret IFNg, IL2 and TNFα upon engagement with pp65 or CD19 antigen, indicating that the effector function of the bi-specific T cells can be induced through endogenous TCR or the introduced CAR. To evaluate the in vivo viral antigen driven anti-tumor efficacy of the adoptively transferred bi-specific T cells, CD19+LCL expressing GFPffluc were inoculated (i.v) into huIL-15 reconstituted NSG mice. Once the tumor engraftment was confirmed by in vivo imaging, bi-specific T cells were adoptively transferred (i.v) into the tumor bearing mice. Anti- tumor activity was observed 14 days post T cell infusion. As expected, this effect is transient and tumor re-progression occurred. In order to deliver CMV antigen for vaccine, we generated T-APC by loading CMVpp65 peptide into autologous T cells and injected the CMV T-APCs (I.v) into the bi-specific T cell treated mice, Influenza specific MP1 peptide pulsed autologous T cells were used as control T-APCs. CMV T-APC induced a second wave of antitumor activity 2 weeks post vaccine and mice survived for more than 2 months post adoptive transfer of T cells, while tumor grew vigorously when MP1-T-APCs were given as stimulators. The findings demonstrated that CD19CAR modified CMV specific T cells are capable of responding to viral antigen reactivation through their endogenous TCR, which could be used to magnify the antitumor activity of CAR transduced T cells in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antitumor activity of melinjo ( Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon‐26 tumor‐bearing mouse model in vivo

2015 ◽  
Vol 4 (11) ◽  
pp. 1767-1780 ◽  
Author(s):  
Narayanan K. Narayanan ◽  
Kazuhiro Kunimasa ◽  
Yukio Yamori ◽  
Mari Mori ◽  
Hideki Mori ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Mouse Model ◽  
Seed Extract ◽  
Tumor Bearing Mouse ◽  
Colon 26 ◽  
Murine Tumor ◽  
Tumor Bearing ◽  
Gnetum Gnemon

In vivo Antitumor, Pharmacological and Toxicological Study of Pyrim-ido[4′,5′:4,5]thieno(2,3-b)quinoline with 9-hydroxy-4-(3-diethylaminopropylamino) and 8-methoxy-4-(3-diethylaminopropylamino) Substitutions

2021 ◽  
Vol 21 ◽  
Author(s):  
Hulihalli N. KiranKumar ◽  
Heggodu G. RohitKumar ◽  
Ajay S. Khandagale ◽  
Gopal M. Advirao
Keyword(s):  
Antitumor Activity ◽  
Tumor Regression ◽  
Antioxidant Property ◽  
The Body ◽  
Pharmacological Activities ◽  
In Vivo Models ◽  
Tumor Bearing ◽  
Anti Inflammatory ◽  
Analgesic Activities

Background: We previously synthesized two DNA intercalative pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (Hydroxy-DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino) pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (Methoxy-DPTQ), and reported their cytotoxicity against cancer cell lines. Objective: In the present study, we sought to analyze the antitumor activity of Hydroxy-DPTQ and Methoxy-DPTQ on Ehrlich’s ascites carcinoma in vivo models, along with other pharmacological activities and toxicity. Methods: Antitumor activity, In vivo antioxidant measurement, Anti-inflammatory activity Analgesic activity, Hematological study, Biochemical parameters, and Nephroprotective ac-tivity. Results: In this study, both the test molecules studied possess potent in vivo antitumor activity without any hematological, biochemical or nephrotoxicity. Significant tumor regression was observed after treatment with both the test molecules, which is suggested by the decrease in the body weight of tumor bearing mice. Mean survival time of mice with tumor was increased from 16 days to 25 and 29 days after 40 and 80 mg/kg Hydroxy-DPTQ treatment, respectively, with a similar result for Methoxy-DPTQ. A dose dependent increase in lifespan upto 80-85% was also displayed by both Hydroxy-DPTQ and Methoxy-DPTQ. Reduction in the tumor volume of mice, upon treatment with molecules also confirmed their antitumor ac-tivity. These molecules also exhibited pharmacological activities such as antioxidant, anti-inflammatory and analgesic activities. Administration of Hydroxy-DPTQ and Methoxy-DPTQ not only reduced the level of lipid peroxidation in tumor bearing mice, but also re-stored the superoxide dismutase, glutathione and catalase levels to normal, substantiating the antioxidant property. Also, treatment of Hydroxy-DPTQ and Methoxy-DPTQ inhibited the pain to approximately 60-80% and 19-33%, respectively. Further, the treatment with Hy-droxy-DPTQ and Methoxy-DPTQ reversed the abnormality in the RBC, WBC and haemo-globin levels, and gentamicin induced nephrotoxicity. Conclusion : Hydroxy-DPTQ and Methoxy-DPTQ are good antitumor molecules with pharmacological properties.

In Vitro and In Vivo Evaluation of Novel DTX-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes

2020 ◽  
Vol 15 (4) ◽  
pp. 341-359
Author(s):  
Moloud Kazemi ◽  
Jaber Emami ◽  
Farshid Hasanzadeh ◽  
Mohsen Minaiyan ◽  
Mina Mirian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Antitumor Activity ◽  
Cellular Uptake ◽  
Folate Receptor ◽  
Chemotherapeutic Agents ◽  
Water Soluble ◽  
Growth Monitoring ◽  
Tumor Bearing

Background: The development of biocompatible tumor-targeting delivery systems for anticancer agents is essential for efficacious cancer chemotherapy. Nanoparticles, as drug delivery cargoes for cancer therapy, are rapidly improving to overcome the limitations of conventional chemotherapeutic agents. Heparin–modified nanoparticles are currently being considered as one of the favorable carriers for the delivery of chemotherapeutics to cancer tissues. Objective: This study was aimed at evaluating the in vitro and in vivo antitumor activity of a novel targeted, pH-sensitive, heparin-based polymeric micelle loaded with the poorly water-soluble anticancer drug, docetaxel (DTX). The micelles could overcome the limited water solubility, non-specific distribution, and insufficient drug concentration in tumor tissues. Methods: DTX-loaded folate targeted micelles were prepared and evaluated for physicochemical properties, drug release, in vitro cellular uptake and cytotoxicity in folate receptor-positive and folate receptor-negative cells. Furthermore, the antitumor activity of DTX-loaded micelles was evaluated in the tumor-bearing mice. Some related patents were also studied in this research. Results: The heparin-based targeted micelles exhibited higher in vitro cellular uptake and cytotoxicity against folate receptor over-expressed cells due to the specific receptor-mediated endocytosis. DTX-loaded micelles displayed greater antitumor activity, higher anti-angiogenesis effects, and lower systemic toxicity compared with free DTX in a tumor-induced mice model as confirmed by tumor growth monitoring, immunohistochemical evaluation, and body weight shift. DTX-loaded targeting micelles demonstrated no considerable toxicity on major organs of tumor-bearing mice compared with free DTX. Conclusion: Our results indicated that DTX-loaded multifunctional heparin-based micelles with desirable antitumor activity and low toxicity possess great potential as a targeted drug delivery system in the treatment of cancer.

Compared Antitumor Activity of GA101 and Rituximab against the Human RL Follicular Lymphoma Xenografts in SCID Beige Mice.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1585-1585 ◽  
Author(s):  
Stéphane Dalle ◽  
Lina Reslan ◽  
Stéphanie Brunet Manquat ◽  
Franck Herting ◽  
Christian Klein ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Combined Therapy ◽  
Single Agent ◽  
Antitumor Efficacy ◽  
Fixed Dose ◽  
Tumor Growth Inhibition ◽  
Type I ◽  
Mice Model ◽  
Anti Cd20

Abstract GA101 is a third generation, glycoengineered type II IgG1 anti-CD20 monoclonal antibody (Mab) with enhanced ADCC and superior caspase-independent apoptosis induction in comparison to other anti-CD20 antibodies, including rituximab which is a type I antibody. We compared the antitumor efficacy of GA101 and rituximab in established RL human lymphoma xenografts in SCID beige mice. One million exponentially growing RL cells were injected SC, yielding fast growing xenografts. GA101 was given twice weekly at 3 dosages (10, 30 and 100 mg/kg), whereas Rituximab was given at fixed dose of 30 mg/kg twice weekly. Both Mabs were administered as intravenous injections, for a total of 5 injections. GA101 was dose-related active against RL xenografts in terms of tumor growth inhibition (TGI). TGI was calculated using NCI formula and showed values of 25, 75 and 85% for the 10, 30 and 100 mg/kg dosages of GA101 respectively while the 30 mg/kg dose of rituximab induced a TGI of 43% only. Both higher doses of 30 and 100 mg/kg significantly inhibited the growth of RL tumors and resulted in some complete tumor remissions (10–30 %). The antitumor activity of Rituximab against RL xenografts was inferior to equivalent dosing of GA101. Toxicity of GA101 with these regimens was excellent with no toxic deaths and no significant modification of body weight. In a separate series of experiments rituximab 30 mg/kg and GA101 30 mg/kg administered once weekly i.v. for 4 weeks were combined or not to cyclophosphamide 50 mg/kg administered once weekly intraperitoneally for 4 weeks. This study confirmed the previous observation that the new anti CD20 GA101 was more active than rituximab administered at similar doses on established RL tumors. TGI values were 79, 35% and 93% for GA101, rituximab and cyclophosphamide administered as single agents when compared to untreated controls. When groups receiving combined therapy were compared to the groups receiving the corresponding single agent Mab, cyclophosphamide increased antitumor efficacy with TGI values of 83 and 94% for rituximab and GA101, respectively. Thus using a suboptimal dose of the classical antilymphoma alkylating agent cyclophosphamide, the combination of either antibody with cyclophosphamide was more active than either agent alone, and the most active combination was GA101 with cyclophosphamide. These results show that GA101 is more active than rituximab on RL xenografts at similar doses, both administered as a single agent or in combination with cyclophosphamide. In the SCID mice model it is not expected that a major contribution to antitumor efficacy comes from the interaction of glycoengineered Mab with murine FcgRIV receptors. Complementary experiments with cobra venom factor, which is used for in vivo complement inhibition, suggest that rituximab antitumor effect was strongly dependent on complement dependent cytotoxicity while GA101 remained active when complement was depleted.

Antitumor Activity and Possible Mechanism of Crude Polysaccharides from Discorea bulbifera L. on the Mice Bearing U14 Cervical Carcinoma

2012 ◽  
Vol 560-561 ◽  
pp. 374-379 ◽  
Author(s):  
Hong Xia Cui
Keyword(s):  
Antitumor Activity ◽  
Cervical Carcinoma ◽  
T Lymphocyte ◽  
Tumor Tissue ◽  
Lymphocyte Subsets ◽  
Spleen Weight ◽  
T Lymphocyte Subsets ◽  
Tumor Bearing ◽  
Cd8 T Lymphocyte

To explore the antitumor activity of crude polysaccharides of Dioscorea bulbifera L. (DBLP) and its possible mechanism, the effects of DBLP on the tumor growth in vivo, thymus and spleen weight were examined. Apoptosis of thymus, spleen and tumor tissue in tumor-bearing mice was detected by the flow cytometry. The number of CD4+ and CD8+ T-lymphocyte subsets of peripheral blood was also determined by means of FACScan flow cytometer. Our results showed that U14 cervical carcinoma growth could be inhibited, thymus weight be increased, apoptosis of thymus and spleen be decreased, and apoptosis of tumor be increased by DBLP in tumor-bearing mice. Furthermore, DBLP had the abilities to reduce the ratio of CD4+/CD8+ T-lymphocyte according to CTX group. These results indicated that DBLP could suppress the cervical carcinoma through modulating immune response of the tumor-bearing mice and inducing apoptosis of tumor tissue.

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