Abstract | BACKGROUND: METHODS: We have tested the antiproliferative effects of CNF1 on GL261 cells and human glioma cells obtained from surgical specimens. For the in vivo experiments, we injected GL261 cells into the adult mouse visual cortex, and five days later we administered either a single intracerebral dose of CNF1 or vehicle. To compare CNF1 with a canonical antitumoral drug, we infused temozolomide (TMZ) via minipumps for 1 week in an additional animal group. RESULTS: In culture, CNF1 was very effective in blocking proliferation of GL261 cells, leading them to multinucleation, senescence and death within 15 days. CNF1 had a similar cytotoxic effect in primary human glioma cells. CNF1 also inhibited motility of GL261 cells in a scratch- wound migration assay. Low dose (2 nM) CNF1 and continuous TMZ infusion significantly prolonged animal survival (median survival 35 days vs. 28 days in vehicle controls). Remarkably, increasing CNF1 concentration to 80 nM resulted in a dramatic enhancement of survival with no obvious toxicity. Indeed, 57% of the CNF1-treated animals survived up to 60 days following GL261 glioma cell transplant. CONCLUSIONS:
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Authors | Eleonora Vannini, Anna Panighini, Chiara Cerri, Alessia Fabbri, Simonetta Lisi, Enrico Pracucci, Nicola Benedetto, Riccardo Vannozzi, Carla Fiorentini, Matteo Caleo, Mario Costa |
Journal | BMC cancer
(BMC Cancer)
Vol. 14
Pg. 449
(Jun 18 2014)
ISSN: 1471-2407 [Electronic] England |
PMID | 24939046
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Bacterial Toxins
- Escherichia coli Proteins
- cytotoxic necrotizing factor type 1
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacology)
- Bacterial Toxins
(administration & dosage, pharmacology)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Cellular Senescence
(drug effects)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Escherichia coli Proteins
(administration & dosage, pharmacology)
- Glioma
(drug therapy, mortality, pathology)
- Humans
- Mice
- Time Factors
- Tumor Stem Cell Assay
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