ABSTRACT
A systematic review of published articles based on randomized clinical trials was conducted to ascertain the efficacy or perspective of using CAR-T cell therapy for refractory multiple myeloma. The PubMed database was searched with the combination of terms "multiple myeloma", "refractory multiple myeloma", "CAR T-cell", and the PRISMA criteria were followed. Of the 78 articles found, only 5 were selected. The studies used different treatment protocols and four different types of CAR-T cells. All studies obtained interesting results in terms of increased progression-free survival and negative minimal residual disease responses. Some authors detected an expansion of CAR-T cells and noted dose-dependent relationship between treatment effectiveness and serum BCMA levels. Although the results were promising, a small number of patients still relapsed a few months after CAR-T cell infusion. Therefore, this new line of therapy should be further investigated, as it significantly increases progression-free survival and improves quality of life.
Uma revisão sistemática de artigos publicados com base em ensaios clínicos randomizados foi realizada para verificar a eficácia ou perspectiva do uso da terapia com células CAR-T para mieloma múltiplo refratário. Foi pesquisada a base de dados PubMed com a combinação dos termos "multiple myeloma", "refratory multiple myeloma", "CAR T-cell" e foram seguidos os critérios PRISMA. Dos 78 artigos encontrados, apenas 5 foram selecionados. Os estudos utilizaram diferentes protocolos de tratamento e quatro tipos diferentes de células CAR-T. Todos os estudos obtiveram resultados interessantes em termos de aumento da sobrevida livre de progressão e respostas negativas à doença residual mínima. Alguns autores detectaram uma expansão das células CAR-T e observaram uma relação dose-dependente entre a eficácia do tratamento e os níveis séricos de BCMA. Embora os resultados tenham sido promissores, um pequeno número de pacientes ainda apresentou recaída alguns meses após a infusão de células CAR-T. Portanto, esta nova linha de terapia deve ser mais investigada, pois aumenta significativamente a sobrevida livre de progressão e melhora a qualidade de vida.
Subject(s)
Multiple Myeloma , NeoplasmsABSTRACT
INTRODUCTION: Valepotriates (epoxy iridoid esters) represent an important group of constituents that contribute to pharmacological effects for the genus Valeriana. Storage and extraction of valepotriates is a demanding task, as these compounds are thermolabile and unstable: even when decomposition products are not formed, isovaleric acid liberation from the iridoid nucleus originate compounds with less complex substituents. OBJECTIVE: To study the influence of time and storage conditions on the diene valepotriates (valtrate, isovaltrate, acevaltrate, 1-ß-acevaltrate, 1-ß-aceacevaltrate) content of the Valeriana glechomifolia (native to southern Brazil), extract was obtained by supercritical fluid extraction using CO2 as the fluid (SF-CO2). METHODOLOGY: Above-ground and below-ground material of V. glechomifolia was extracted by SF-CO2 (40 °C, 90 bar). The extract was stored under nitrogen atmosphere or solubilised in methanol. Valepotriates stability was accessed during storage at -20 °C over 8 months through reverse-phase HPLC (mobile phase acetonitrile:water 50:50 (v/v); 254 nm). RESULTS: A gradual increase in valtrate levels and decrease in acevaltrate, 1-ß-acevaltrate and 1-ß-aceacevaltrate, concentration were observed from the first month of storage for the dry extract. However, for the methanol solubilised extract these changes occurred only after the third month and were accompanied by reduction in isovaltrate levels and formation of decomposition products. CONCLUSION: SF-CO2 showed high selectivity for valepotriates extraction. This is the first report on valepotriates molecular conversion, which was less accelerated when the extract was stored in methanol, but under this condition degradation products are also present, probably baldrinals, that are not observed in the dry extract.
Subject(s)
Carbon Dioxide/chemistry , Chromatography, Supercritical Fluid/methods , Iridoids/analysis , Valerian/chemistry , Drug Stability , Drug Storage , Iridoids/chemistry , Iridoids/isolation & purification , Methanol/chemistry , Molecular Structure , Plant Extracts/analysis , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Temperature , Time FactorsABSTRACT
The antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test (FST). The SCCO2 extract decreased mice immobility in the FST (0.5-20 mg/kg p.o.) and elicited a biphasic dose-response relationship in the TST (1-20 mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5 mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1 mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15 µg/kg, s.c., D1 dopamine receptor antagonist) and sulpiride (50 mg/kg, i.p., D2 dopamine receptor antagonist). However, mice pre-treatments with prazosin (1 mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4×100 mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25 mg/kg) and imipramine (10 mg/kg), desipramine (5 mg/kg) and bupropion (3 mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission.
