A nanoemulsion of an anti-oxidant synergy formulation reduces tumor growth rate in neuroblastoma-bearing nude mice

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.

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Tumor growth characteristics of the Walker 256 AR tumor, a regressive variant of the rat Walker 256 A tumor

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132010000500014 ◽

2010 ◽

Vol 53 (5) ◽

pp. 1101-1108 ◽

Cited By ~ 2

Author(s):

Fernando Guimarães ◽

Alessandra Soares Schanoski ◽

Tereza Cristina Samico Cavalcanti ◽

Priscila Bianchi Juliano ◽

Ana Neuza Viera-Matos ◽

...

Keyword(s):

Growth Rate ◽

Tumor Growth ◽

Wistar Rats ◽

Tumor Regression ◽

Growth Characteristics ◽

Tumor Growth Rate ◽

Continuous Growth ◽

Tumor Bearing ◽

Walker 256 ◽

Complete Tumor

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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Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells

Neurosurgery ◽

10.1227/neu.0000000000001174 ◽

2015 ◽

Vol 79 (3) ◽

pp. 481-491 ◽

Cited By ~ 11

Author(s):

Alexander E. Ropper ◽

Xiang Zeng ◽

Hariprakash Haragopal ◽

Jamie E. Anderson ◽

Zaid Aljuboori ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Growth Rate ◽

Neural Stem Cells ◽

Tumor Growth ◽

Rat Model ◽

Weight Bearing ◽

Tumor Growth Rate ◽

Intramedullary Spinal Cord ◽

Human Neural Stem Cells

Abstract BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P <.05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG.

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