1. Nuclear magnetic resonance metabolic fingerprint of bevacizumab in mutant IDH1 glioma cellsTanja Mesti, Nadia Bouchemal, Claire Banissi, Mohamed N. Triba, Carole Marbeuf-Gueye, Maja Čemažar, Laurence Le Moyec, Antoine F. Carpentier, Philippe Savarin, Janja Ocvirk, 2018, original scientific article Abstract: Malignant gliomas are rapidly growing tumours that extensively invade the brain and have bad prognosis. Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation, associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of vascular endothelial growth factor (VEGF). However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Materials and methods The immunoassay and MTT assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using high resolution magic angle spinning spectroscopy (HRMAS). Results mIDH1-U87 cells secreted VEGF (13 ng/mL). Regardless, bevacizumab had no cytotoxic effect, even after a 72h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (polyunsaturated fatty acids [PUFA], glycerophosphocholine, and phosphocholine). Conclusions In mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle that runs in reductive manner, as a probable mechanism of action of bevacizumab in IDH1 mutated gliomas and propose a new target pathway for effective treatment of malignant gliomas.
Keywords: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer, idh1 mutation, malignant glioma, bevacizumab, metabolic fingerprint
Published in DiRROS: 11.06.2024; Views: 48; Downloads: 17
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2. Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapyMartina Vrankar, Mojca Unk, 2018, review article Abstract: Uncommon responses during immunotherapy is a new challenging issue in oncology practice. Recently, new criteria for evaluation of response to immunotherapy immune response evaluation criteria solid tumors (iRECIST) were accepted. According to iRECIST, worsening of performance status (PS) accompanied to pseudoprogression reflects most probably the true progression of the malignant disease. Methods. A systematic review of the literature was made by using several electronic database with the following search criteria: symptomatic pseudoprogression, atypical response, immunotherapy and lung cancer. Results. In the literature, we identified five reports of seven patients treated with immunotherapy that met the inclusion criteria. We also report our experience of patient with pseudoprogression and almost complete response after one dose of immunotherapy. Conclusions. As seen from our review, iRECIST criteria might be insufficient in distinguishing true progression from pseudoprogression in some patients with advanced NSCLC treated with immunotherapy. More precise assessment methods are urgently needed.
Keywords: symptomatic pseudoprogression, atypical response, immunotherapy, lung cancer
Published in DiRROS: 11.06.2024; Views: 41; Downloads: 11
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