Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen
The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA...
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| Format: | Article |
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MDPI AG
2018-11-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/8/12/203 |
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| author | Richard E. Kast Nicolas Skuli Iacopo Sardi Felix Capanni Martin Hessling Guido Frosina Anton P. Kast Georg Karpel-Massler Marc-Eric Halatsch |
| author_facet | Richard E. Kast Nicolas Skuli Iacopo Sardi Felix Capanni Martin Hessling Guido Frosina Anton P. Kast Georg Karpel-Massler Marc-Eric Halatsch |
| author_sort | Richard E. Kast |
| collection | DOAJ |
| description | The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its preferential conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently-marketed drugs—the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat—that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial. |
| first_indexed | 2024-04-12T19:56:59Z |
| format | Article |
| id | doaj.art-c5c4fcd90cbc48afa9dd842d36b4d774 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-04-12T19:56:59Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-c5c4fcd90cbc48afa9dd842d36b4d7742022-12-22T03:18:37ZengMDPI AGBrain Sciences2076-34252018-11-0181220310.3390/brainsci8120203brainsci8120203Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA RegimenRichard E. Kast0Nicolas Skuli1Iacopo Sardi2Felix Capanni3Martin Hessling4Guido Frosina5Anton P. Kast6Georg Karpel-Massler7Marc-Eric Halatsch8IIAIGC Study Center, 22 Church Street, Burlington, VT 05401, USAAbramson Family Cancer Research Institute, University of Pennsylvania, Cancer Center, 438 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USANeuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, viale Pieraccini, 24, 50139 Florence, ItalyRer. Hum. Biol, Department of Mechatronics and Medical Engineering, Ulm University of Applied Sciences, Albert-Einstein-Allee 55, D-89081 Ulm, GermanyDepartment of Mechatronics and Medical Engineering, Ulm University of Applied Sciences, Albert-Einstein-Allee 55, D-89081 Ulm, GermanyMutagenesis & Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, ItalyIIAIGC Study Center, 22 Church Street, Burlington, VT 05401, USADepartment of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, GermanyDepartment of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, GermanyThe CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its preferential conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently-marketed drugs—the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat—that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.https://www.mdpi.com/2076-3425/8/12/2035-aminolevulinic acidciprofloxacindeferipronefluorescence5-fluorouracilfebuxostatglioblastomaphotodynamic treatmenttemozolomide, |
| spellingShingle | Richard E. Kast Nicolas Skuli Iacopo Sardi Felix Capanni Martin Hessling Guido Frosina Anton P. Kast Georg Karpel-Massler Marc-Eric Halatsch Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen Brain Sciences 5-aminolevulinic acid ciprofloxacin deferiprone fluorescence 5-fluorouracil febuxostat glioblastoma photodynamic treatment temozolomide, |
| title | Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen |
| title_full | Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen |
| title_fullStr | Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen |
| title_full_unstemmed | Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen |
| title_short | Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen |
| title_sort | augmentation of 5 aminolevulinic acid treatment of glioblastoma by adding ciprofloxacin deferiprone 5 fluorouracil and febuxostat the caala regimen |
| topic | 5-aminolevulinic acid ciprofloxacin deferiprone fluorescence 5-fluorouracil febuxostat glioblastoma photodynamic treatment temozolomide, |
| url | https://www.mdpi.com/2076-3425/8/12/203 |
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