talaporfin and Astrocytoma

Talaporfin sodium (TS) is an authorized photosensitizer for photodynamic therapy (PDT) against some tumors in Japan; however, the drawbacks of the drug include its high cost and side effects. Thus, reducing the dose of TS in each round of TS-PDT against tumors is important for reducing treatment costs and improving patients' quality of life. Dichloroacetate (DCA) is approved for treating lactic acidosis and hereditary mitochondrial diseases, and it is known to enhance reactive oxygen species production and induce apoptosis in cancer cells. Therefore, DCA has the potential to enhance the effects of TS-PDT and permit the use of lower TS doses without reducing the anti-cancer effect.. U251 human astrocytoma cells were simultaneously incubated with TS and DCA using different concentrations, administration schedules, and treatment durations, followed by laser irradiation. Cell viability was determined using the CCK-8 assay.. The combinational use of DCA and TS resulted in synergistically enhanced TS-PDT effects in U251 cells. The duration of DCA treatment before TS-PDT slightly enhanced the efficacy of TS-PDT. The intensity of laser irradiation was not associated with the synergistic effect of DCA on TS-PDT. In addition, the relationship between the elapsed time after TS/DCA combination treatment and PDT ineffectiveness was identical to that of TS monotherapy.. DCA synergistically enhanced the anti-cancer effect of TS-PDT, illustrating its potential for drug repositioning in cancer therapy in combination with PDT.

Topics: Astrocytoma; Cell Line, Tumor; Humans; Japan; Photochemotherapy; Photosensitizing Agents; Porphyrins; Quality of Life

Pleomorphic xanthoastrocytoma (PXA) is categorized as grade II, other astrocytic tumors per the 2016 World Health Organization classification. Despite being a relatively benign type of tumor, PXA often has an aggressive clinical course. The more malignant form of PXA is now known as anaplastic pleomorphic xanthoastrocytoma (A-PXA) and is categorized as a grade III tumor. Clinical and genetic factors associated with malignant transformation remain unclear. In particular, typical genetic expression patterns in PXA and A-PXA remain unidentified.. We present a case of recurrent PXA in which malignant transformation followed a promoter mutation in TERT. In this case, genetic chronologic changes accompanying malignant transformation of PXA were thoroughly examined. The promoter mutation was detected in the second operative specimen after stereotactic radiosurgery (SRS) at the first tumor recurrence. Subsequently, a malignant transformation to the A-PXA occurred at the time of the second recurrence, and the tumor repeatedly recurred afterward.. TERT promotor mutations may contribute to the malignant transformation of PXA; the mechanism of this mutation is unknown, but it may have been caused by SRS. Therefore, improvident use of radiation should be avoided to prevent the malignant transformation of PXA.

Topics: Adult; Antineoplastic Agents, Alkylating; Astrocytoma; Brain Neoplasms; Cell Transformation, Neoplastic; Combined Modality Therapy; Cyclin-Dependent Kinase Inhibitor p15; Cytoreduction Surgical Procedures; DNA Mutational Analysis; DNA, Neoplasm; Female; Gene Deletion; Genes, p16; Humans; Mutation; Neoplasm Proteins; Neoplasm Recurrence, Local; Nimustine; Photochemotherapy; Porphyrins; Promoter Regions, Genetic; Proto-Oncogene Proteins B-raf; Radiosurgery; Reoperation; Telomerase; Temporal Lobe