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19 results on '"Lokot, I"'

4. Local delivery of temozolomide via a biologically inert carrier (Temodex) prolongs survival in glioma patients, irrespectively of the methylation status of MGMT

Author

Karlsson, I, Veevnik, D., Fedulov, A., Yurkshtovich, N., Yurkshtovich, T., Pejler, Gunnar, Lokot, I, Karlsson, I, Veevnik, D., Fedulov, A., Yurkshtovich, N., Yurkshtovich, T., Pejler, Gunnar, and Lokot, I

Abstract

Glioma is the most common brain malignancy. Standard first-line therapy for glioma includes surgery, radiotherapy and systemic administration of temozolomide. However, temozolomide does not reach the brain in sufficient doses when administered orally and has poor efficiency in more than half of the patients. Strategies to improve the treatment of glial malignancies are therefore needed. We have recently developed a system (Temodex) for local administration of temozolomide by encapsulating the drug in a biologically inert matrix. Here, we assessed the effect of Temodex in combination with standard therapy in a small-scale clinical study. Since the efficacy of temozolomide therapy is known to depend on the methylation status of the O-6-methylguanine-DNA methyltransferase gene (MGMT) promoter, we also analyzed whether the effect of Temodex was influenced by the methylation status of MGMT. Our data show that the combination of standard therapy and Temodex was more efficient than standard therapy alone, promoting the overall patient survival by up to 33 weeks. Moreover, the efficacy of Temodex was not dependent on the methylation status of MGMT. Local Temodex administration in combination with standard therapy thereby emerges as a novel therapeutic option, with applicability that is independent on the methylation status of the MGMT promoter.

Published
2019
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19. Cytotoxic activity of a new paclitaxel formulation, Pacliex, in vitro and in vivo.

Author

Hassan S, Dhar S, Sandström M, Arsenau D, Budnikova M, Lokot I, Lobanov N, Karlsson MO, Larsson R, and Lindhagen E

Subjects
Chemistry, Pharmaceutical, Humans, Leukemia pathology, Micelles, Multiple Myeloma pathology, Tumor Cells, Cultured, Antineoplastic Agents, Phytogenic pharmacology, Antineoplastic Agents, Phytogenic toxicity, Paclitaxel analogs & derivatives, Paclitaxel pharmacology, Paclitaxel toxicity
Abstract

Background: The paclitaxel formulation, Taxol (Bristol-Myers Squibb), is one of the most effective anticancer agents used today. However; it is associated with serious side effects believed to be caused by the Cremophor EL used for its formulation., Aim: To evaluate the cytotoxic activity of a new paclitaxel formulation, Pacliex (developed by Oasmia Pharmaceutical, Uppsala, Sweden), a mixed micelles preparation in which an amphiphilic synthetic derivative of retinoic acid replaced Cremophor EL/ethanol vehicle., Method: In this study, three model systems were used to evaluate the cytotoxic activity of Pacliex and other paclitaxel preparations. The cytotoxic activities of Pacliex, Taxol and paclitaxel in ethanol were investigated against a panel of ten human tumor cell lines using the fluorometric microculture cytotoxicity assay (FMCA). Low- and high- proliferating in vitro hollow fiber model of two cell lines, the leukemia CCRF-CEM and the myeloma RPMI 8226/S cell lines, were used to assess the cytotoxic activity of the three formulations. The in vivo hollow fiber model of the two cell lines was used for assessment of Pacliex and Taxol activity. The [3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to analyze the in vitro and in vivo hollow fiber data., Result: Pacliex was somewhat more effective than Taxol in the more sensitive cell lines. The activity of Taxol was more pronounced in the resistant cell lines due to an additive effect of the vehicle used. The three formulations showed similar activity in both the low- and high-proliferating in vitro hollow fiber cultures. The in vivo hollow fiber cytotoxic activity of Pacliex was similar to that of Taxol. Putting all the results together, it was found that all the three formulations had similar in vitro and in vivo activity., Conclusion: The three in vitro and in vivo models confirmed the similarity of the cytotoxic activities of Pacliex and Taxol. Considering the above, Pacliex could be an interesting alternative Cremophor EL-free formulation of paclitaxel.

Published
2005
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