scholarly journals In Vivo Antitumor Effect of Supercritical CO2 Extract of Mango Ginger (Curcuma amada Roxb) in U-87MG Human Glioblastoma Nude Mice Xenografts

2016 ◽  
Vol 22 (2) ◽  
pp. 260-267 ◽  
Author(s):  
Cheppail Ramachandran ◽  
Gilda M. Portalatin ◽  
Adriana M. Prado ◽  
Karl-Werner Quirin ◽  
Enrique Escalon ◽  
...  

Glioblastoma multiforme (GBM) is one the most aggressive and lethal human neoplasms with poor prognosis and very limited positive treatment options. The antitumor effect of supercritical CO2 extract of mango ginger ( Curcuma amada Roxb) (CA) with and without irinotecan (IR) was analyzed in U-87MG human glioblastoma multiforme (GBM) cells in vitro and in nude mice xenografts. CA is highly cytotoxic to GBM cells and is synergistic with IR as indicated by the combination index values of <1 in the CompuSyn analysis. CA inhibits tumor growth rate in GBM xenografts, the inhibition rate being higher than in IR treated group. GBM xenograft mice treated with IR + CA combination showed almost complete inhibition of tumor growth rate. Gene expression analysis of xenograft tumors indicated that IR + CA treatment significantly downregulated anti-apoptotic (Bcl-2 and mutant p53), inflammation-associated (COX-2) and cell division–associated (CCNB2) genes and upregulated pro-apoptotic genes (p21 and caspase-3). These results confirmed the therapeutic efficiency of IR + CA combination against GBM and the need for further clinical investigations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15011-e15011
Author(s):  
A. V. Volkova ◽  
Rostorguev Eduard Evgenievich ◽  
Anna S. Goncharova ◽  
M. V. Mindar ◽  
Ekaterina V. Zaikina ◽  
...  

e15011 Background: Poor clinical effects of standard treatment for glioblastoma determine the need for the development of new therapeutic strategies. Aberrant functioning of the proteasome system, as well as activation of the HIF-1α signaling pathway, are characteristic of glial tumor cells; they can be considered as potential therapeutic targets in the treatment of malignant brain tumors. One of the possible options for improving the results of glioblastoma treatment may involve strategies for inhibiting the HIF-1α pathway. Bortezomib, a proteasome inhibitor, can block the biological effects of HIF-1α. Bortezomib showed a pronounced antitumor effect in in vitro testing on various models of solid malignant tumors, giving grounds for further studies of its effectiveness in vivo. Patient-derived xenograft (PDX) models are characterized by a variety of cell subclones and are therefore considered the most reliable tool for predicting therapeutic responses. Methods: A PDX model of glioblastoma was created in 20 Balb/c Nude mice implanted with a subcutaneously inoculated human glioblastoma. Temozolomide (0.5 mg/kg), bortezomib (0.25 mg/kg), or a combination of temozolomide and bortezomib were administered intraperitoneally daily for 21 days. The tumor histotype was confirmed by histological analysis (staining with hematoxylin and eosin). The antitumor effect was determined by the inhibition of tumor growth (ITG%), the volume of tumor nodes, and the index of tumor growth. Results: The highest value of the inhibition of tumor growth (ITG%) was registered in the group of animals receiving a combination of temozolomide and bortezomib – 85.38%. The values in the groups receiving temozolomide or bortezomib monotherapy were 57.32% and 63.11%, respectively. Conclusions: An analysis of the antitumor efficacy of bortezomib combined with temozolomide in human subcutaneous PDX-glioblastomas demonstrated their synergistic effect.


Author(s):  
Fonghsu Kuo ◽  
Timothy Kotyla ◽  
Thomas Wilson ◽  
Lydia Kifle ◽  
Thomai Panagiotou ◽  
...  

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Fonghsu Kuo ◽  
Timothy Kotyla ◽  
Thomas Wilson ◽  
Lydia Kifle ◽  
Thomai Panagiotou ◽  
...  

2017 ◽  
Vol 22 (3) ◽  
pp. 158-163
Author(s):  
Anastasiia O. Sosnovtceva ◽  
S. Sh Karshieva ◽  
G. B Smirnova ◽  
Yu. A Borisova ◽  
O. V Lebedinskaya ◽  
...  

Oncolytic viral therapy is a promising approach to targeted therapy of malignant tumors. In this article we consider the therapeutic potential of a non-pathogenic Coxsackie A7 virus (CA7V) with neurotropic properties on a model of human neuroblastoma. Purpose to study in vitro/in vivo sensitivity of human neuroblastoma HNB (from cell line JMR-32) to Coxsackie virus A7 (CA7V). Objectives: еvaluation of cytolytic activity in vitro on NB cells verified by cytomorphology and assessment of dynamics of the growth of subcutaneous neuroblastoma xenografts in Balb/c nude male mice exposed to CA7V multiple i.v. injections. Material and methods. CA7V was produced in the cells of line-producer С-33А. Cell culture and the strain of transplanted NB (JMR-32) were obtained from the Collection of N.N. Blokhin Russian Cancer Research Center. Cytomorphologic verification of neuroblastoma and CA7V cytolytic activity were executed with the use of standard cultural methods, TCID50 and IC50 criteria. Experiments «in vivo» were performed on immunodeficient Balb/c nude male mice bred and reared in the N.N. Blokhin Russian Cancer Research Center. The experiments were made at day 6 when neuroblastoma subcutaneous xenografts developed to the Vmean = 79-82 mm3 by day 6. The treatment with CA7V at the i.v. single dose of 1×108 cells per mouse was performed 3 times with 72-hours intervals; evaluation of the efficacy was made according to standard criterion Т/С ≤ 42%; and control of the tumor growth rate (Vt/V0) in the dynamics. Statistical assessment was made with the software Excel for Windows 2007 with the use of T-test under p ≤ 0.05. Results. Cytolytic effect of CA7V on neuroblastoma cells was registered similar to basic parameters of the original line-producer С-33А: TCID50 = 0.99×10-4 pfu/cell, and IC50 = 1.11×10-4 pfu/cell; 48 and 72 hours after virus reproduction in NB cells the rate was 2.0 and 1.5-fold higher than in the line-producer cells. СA7V inhibiting effect on the growth of large subcutaneous neuroblstoma xenografts is registered after the first i.v. injection at the minimal level of T/C = 67% (criterion ≤ 42%) with the 1.5-fold decrease of the tumor growth rate and cancellation of early mice death by day 22 vs day 15 in the control group of untreated mice (n = 8). Conclusion. The obtained results allow to consider human neuroblastoma (JMR-32) to possess the low sensitivity to oncolytic effect of in vitro/in vivo. In order to obtain significant effect in vivo the treatment should be started in mice with 2-fold smaller tumors and a higher initial dose of the oncolytic agent.


2021 ◽  
Vol 22 (13) ◽  
pp. 6781
Author(s):  
Anna Kirstein ◽  
Daniela Schilling ◽  
Stephanie E. Combs ◽  
Thomas E. Schmid

Background: Treatment resistance of glioblastoma multiforme to chemo- and radiotherapy remains a challenge yet to overcome. In particular, the O6-methylguanine-DNA-methyltransferase (MGMT) promoter unmethylated patients have only little benefit from chemotherapy treatment using temozolomide since MGMT counteracts its therapeutic efficacy. Therefore, new treatment options in radiotherapy need to be developed to inhibit MGMT and increase radiotherapy response. Methods: Lomeguatrib, a highly specific MGMT inhibitor, was used to inactivate MGMT protein in vitro. Radiosensitivity of established human glioblastoma multiforme cell lines in combination with lomeguatrib was investigated using the clonogenic survival assay. Inhibition of MGMT was analyzed using Western Blot. Cell cycle distribution and apoptosis were investigated to determine the effects of lomeguatrib alone as well as in combination with ionizing radiation. Results: Lomeguatrib significantly decreased MGMT protein and reduced radiation-induced G2/M arrest. A radiosensitizing effect of lomeguatrib was observed when administered at 1 µM and increased radioresistance at 20 µM. Conclusion: Low concentrations of lomeguatrib elicit radiosensitization, while high concentrations mediate a radioprotective effect.


2010 ◽  
Vol 53 (5) ◽  
pp. 1101-1108 ◽  
Author(s):  
Fernando Guimarães ◽  
Alessandra Soares Schanoski ◽  
Tereza Cristina Samico Cavalcanti ◽  
Priscila Bianchi Juliano ◽  
Ana Neuza Viera-Matos ◽  
...  

The present study aimed at characterizing the subcutaneous development of the Walker 256 (W256) AR tumor, a regressive variant of the rat W256 A tumor. Wistar rats were injected subcutaneously with 4x10(6) W256 A or W256 AR tumor cells. The development of tumors was evaluated daily by percutaneous measurements. None of the W256 A tumors (n=20) regressed, but 62% of the W256 AR tumor-bearing rats (n=21) underwent complete tumor regression within 35 days. Continuous growth of AR tumors was characterized by an increase of the tumor growth rate from day 12, which reached values above 1.0 g/day, and were significantly higher (p<0.05) than those of the regressive AR tumors. Immunosuppression by irradiation before subcutaneous injection of AR cells completely abrogated tumor regression and was associated with severe metastatic dissemination. Daily evaluation of the tumor growth rate enabled the discrimination, in advance, between continuously growing tumors and those that regressed later on.


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