RESUMO
BACKGROUND: The optimal sarcopenia measurement method in patients with a diagnosis of glioblastoma multiforme (GBM) is unknown. It has been found that temporal muscle thickness (TMT) may reflect sarcopenia and be associated with survival, but the relationship between temporal muscle area (TMA) and GBM prognosis has never been evaluated before. The primary outcome of the study was to evaluate the relationship between TMA/TMT and overall survival (OS) time in newly diagnosed GBM patients. METHODS: The data of patients who presented at the university hospital between January 2009 and January 2019 with a confirmed diagnosis of glioblastoma multiforme at the time of diagnosis were analyzed retrospectively. Temporal muscle thickness and TMA were measured retrospectively from preoperative MRIs of patients diagnosed with GBM. Due to the small number of patients and the failure to determine a cut-off value with acceptable sensitivity and specificity using ROC analysis, the median values were chosen as the cut-off value. The patients were basically divided into two according to their median TMT (6.6 mm) or TMA (452 mm2 ) values, and survival analysis was performed with the Kaplan-Meier analysis. RESULTS: The median TMT value was 6.6 mm, and the median TMA value was 452 mm2 . The median overall survival (OS) was calculated as 25.8 months in patients with TMT < 6.6 mm, and 15.8 months in patients with TMT ≥ 6.6 mm (p = 0.29). The median overall survival (OS) of patients with TMA < 452mm2 was 26.3 months, and the group with TMA ≥ 452mm2 was 14.6 months (p = 0.06). The median disease-free survival was 18.3 months (%95 CI: 13.2-23.4) in patients with TMT < 6.6mm, while mDFS was 10.9 (%95 CI: 8.0-13.8) months in patients with TMT ≥ 6.6mm (p = 0.21). The median disease-free survival was found to be 21.0 months (%95 CI: 15.8-26.1) in patients with TMA < 452 mm2 and 10.5 months (%95 CI: 7.8-13.2) in patients with TMA ≥ 452 mm2 (p = 0.018). DISCUSSION: No association could be demonstrated between TMT or TMA and OS of GBM patients. In addition, the median DFS was found to be longer in patients with low TMA. There is an unmet need to determine the optimal method of sarcopenia in GBM patients.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Sarcopenia , Humanos , Glioblastoma/complicações , Glioblastoma/diagnóstico por imagem , Músculo Temporal/patologia , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , PrognósticoRESUMO
SUBJECT: Nigella sativa (N. sativa) is a highly valued nutritional plant, which has long been used in traditional medicine to treat a variety of human diseases. The multifaceted pharmacological impacts of N. sativa, such as attenuating oxidative stress and inflammation, make it a suitable therapeutic candidate against cardiovascular, hepatic, and neurological disorders as well as cancer. Therefore, the current study aimed to evaluate the effect of the hydroalcoholic extract of N. sativa seeds on several pro-inflammatory cytokines in the C6 glioma cell line and to compare it with the effect of the extract on the normal fibroblast cell line. METHODS: C6 and fibroblast cell lines were treated with the extract of N. sativa seeds, and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine the half-maximal inhibitory concentration (IC50) after 72h of treatment. Real-time polymerase chain reaction (RT-PCR) was carried out to assess the expression levels of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and transforming growth factor- ß1 (TGF-ß1) at the mRNA level in both cell lines after 72h of treatment with non-toxic and IC50 concentrations obtained from C6 cell line. RESULTS: The IC50 values for the hydroalcoholic extract of N. sativa seeds were 260±20µg/mL in the C6 cell line and 398±27µg/mL in fibroblast cells. The real-time PCR results indicated that the treatment of C6 and fibroblast cells with the extract at the IC50 value of N. sativa in C6 for 72h could increase the mRNA expression levels of IL-10 and reduce the mRNA expression levels of IL-6, TNF-α, and TGF-ß1 in C6 and fibroblast cells. The N. sativa extract showed a higher anti-inflammatory effect on C6 cells in comparison with fibroblast cells. CONCLUSIONS: Regarding the anti-inflammatory effect of Nigella sativa in C6 cell line, it may be considered a promising candidate to fortify antitumor actions in combination with other therapeutic options in the treatment of patients with GBM.
Assuntos
Glioma , Nigella sativa , Humanos , Interleucina-10 , Fator de Crescimento Transformador beta1 , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Fator de Necrose Tumoral alfa , Linhagem Celular , Anti-Inflamatórios/farmacologia , Sementes , Glioma/tratamento farmacológico , RNA Mensageiro/genéticaRESUMO
Over one hundred clinical trials since 2005 have failed to significantly improve the prognosis of glioblastoma. Since 2005, the standard of care has been maximal resection followed by 60Gy irradiation over six weeks with daily temozolomide. With this, a median survival of 2 years can be expected. This short paper reviewed how the pharmacodynamic attributes of an EMA/FDA approved, cheap, generic drug to treat pain, celecoxib, intersect with pathophysiological elements driving glioblastoma growth, such that growth drive inhibition can be expected from celecoxib. The two main attributes of celecoxib are carbonic anhydrase inhibition and cyclooxygenase-2 inhibition. Both attributes individually have been in active study as adjuncts during current cancer treatment, including that of glioblastoma. That research is briefly reviewed here. This paper concludes from the collected data, that starting celecoxib, 600 to 800mg twice daily before surgery and continuing it through the chemoirradiation phase of treatment would be a low-risk intervention with sound rationale.
Assuntos
Glioblastoma , Celecoxib/uso terapêutico , Ciclo-Oxigenase 2 , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Temozolomida/uso terapêuticoRESUMO
Glioma is a type of brain tumor that is common globally, and is associated with a variety of genetic changes. It has been reported that isocitrate dehydrogenase 1 (IDH1) is overexpressed in glioma and in HeLa cells. The lncRNA IDH1-AS1 is believed to interact with IDH1, and when IDH1-AS1 is overexpressed, HeLa cell proliferation is inhibited. However, the effects of IDH1-AS1 on glioma were relatively unknown. The results from this work show that IDH1-AS1 is downregulated in the glioma tissues. We used primary glioblastoma cell lines U251 and U87-MG to study the effects of IDH1-AS1 on glioma cell growth, in vitro and in vivo. We found that when IDH1-AS1 is overexpressed cell proliferation is inhibited, cell cycle is arrested at the G1 phase, and the protein expression levels of cyclinD1, cyclinA, cyclinE, CDK2, and CDK4 are decreased. We found that cell apoptosis was increased when IDH1-AS1 was overexpressed, as evidenced by increases in the levels of cleaved caspase-9 and -3. Conversely, knockdown of IDH1-AS1 promoted cell proliferation. Moreover, we proved that overexpression of IDH1-AS1 inhibits the tumorigenesis of U251 cells, in vivo. Furthermore, IDH1-AS1 did not affect IDH1 protein expression, but altered its enzymatic activities in glioma cells. Silencing of IDH1 reversed the effects of IDH1-AS1 upregulation on cell viability. Hence, our study provides first-hand evidence for the effects of lncRNA IDH1-AS1 on gliomas. Because overexpressing IDH1-AS1 inhibited cell growth, IDH1-AS1 could also be considered as a potential target for glioma treatment.
Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Animais , Neoplasias Encefálicas/patologia , Proliferação de Células , Feminino , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , RNA Longo não Codificante/genética , Células Tumorais CultivadasRESUMO
Glioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity and the presence of a population of stem-like cells called brain tumour stem cells (BTSCs/BTICs). These cancer stem cells survive treatment and confer resistance to the current therapies - namely, radiation and the chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, and BTSCs resist this mechanism via a robust DNA damage response. Hence, recent studies aimed to sensitize BTSCs to TMZ using combination therapy, such as inhibition of DNA repair machinery. We have previously demonstrated in established GBM cell lines that eukaryotic initiation factor 5B (eIF5B) promotes the translation of pro-survival and anti-apoptotic proteins. Consequently, silencing eIF5B sensitizes these cells to TRAIL-induced apoptosis. However, established cell lines do not always recapitulate the features of human glioma. Therefore, we investigated this mechanism in patient-derived BTSCs. We show that silencing eIF5B leads to increased TMZ sensitivity in two BTSC lines: BT25 and BT48. Depletion of eIF5B decreases the levels of anti-apoptotic proteins in BT48 and sensitizes these cells to TMZ-induced activation of caspase-3, cleavage of PARP, and apoptosis. We suggest that eIF5B represents a rational target to sensitize GBM tumors to the current standard-of-care.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Fatores de Iniciação em Eucariotos/metabolismo , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Temozolomida/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Fatores de Iniciação em Eucariotos/genética , Humanos , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologiaRESUMO
Glioblastoma (GB) represents the most common malignant brain tumor, which, despite extensive research, remains of poor prognosis. The focus of recent studies of GB pathogenesis has shifted to the study of the role of noncoding RNAs (ncRNAs). In this study, we examined the expression levels of the microRNA miR-326 and the long ncRNA H19 (on which a miR-326 putative binding site was found by in-silico analysis) in brain tumor tissue from GB patients as compared to cancer-free brain tissue. Relative expression levels of miR-326 were not found to be significantly altered in GB patients. By comparison, H19 was consistently over-expressed in all GB patients (p < 0.001), and correlated with poorer overall survival (OS) and progression-free survival (PFS) (p = 0.026 and p = 0.045, respectively). At a cutoff value of 5.27, H19 up-regulation could predict OS in GB patients, with a 71.4% sensitivity and 59.6% specificity (p = 0.026). The current GB patients were clustered by the multivariate analysis into 4 groups based on miR-326 and H19 expression profiles, age at diagnosis, and PFS. Our data suggest a role for H19 in the pathogenesis of GB and could be a potential prognostic biomarker for GB.
Assuntos
Glioblastoma/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Adulto , Neoplasias Encefálicas/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Glioblastoma is the most aggressive type of brain cancer with the highest proliferation, invasion, and migration. Montelukast and zafirlukast, 2 widely used leukotriene receptor antagonists (LTRAs) for asthma treatment, inhibited invasion and migration of glioblastoma cell lines. Montelukast induces apoptosis and inhibits cell proliferation of various cancer cells. Herein, apoptotic and antiproliferative effects of montelukast and zafirlukast were investigated in 2 glioblastoma cell lines, A172 and U-87 MG. Both LTRAs induced apoptosis and inhibited cell proliferation of glioblastoma cells in a concentration-dependent manner. Montelukast was more cytotoxic and induced higher levels of apoptosis than zafirlukast in A172 cells, but not in U-87 MG cells. Both drugs decreased expression of B-cell lymphoma 2 (Bcl-2) protein without affecting Bcl-2-associated X (Bax) levels. LTRAs also reduced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, zafirlukast showed a greater antiproliferative effect than montelukast and induced G0/G1 cell cycle arrest by upregulating p53 and p21 expression. These results suggested the therapeutic potential of LTRAs in glioblastoma.
Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Antagonistas de Leucotrienos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Acetatos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclopropanos , Regulação para Baixo/genética , Fase G1/efeitos dos fármacos , Fase G1/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis , Fenilcarbamatos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quinolinas , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Fase de Repouso do Ciclo Celular/genética , Sulfetos , Sulfonamidas , Compostos de Tosil , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor, and it has been shown to improve progression-free survival in patients with recurrent glioblastome multiforme when administered as second-line therapy. However, it has been associated with serious and fatal hemorrhagic events. Here, we present a 68-year-old male who developed severe periocular bleeding while on bevacizumab for recurrent temozolamide-resistant glioblastome multiforme.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Hemorragia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Olho , Evolução Fatal , Humanos , MasculinoRESUMO
Diffuse gliomas represent the most common primary central nervous system (CNS) tumors in adults and children alike. Glioblastoma is the most frequent and malignant form of diffuse glioma with a median overall survival of 15 months despite aggressive treatments. New therapeutic approaches are needed to prolong survival in this always fatal disease. The CNS has been considered for a long time as an immune privileged organ, in part because of the existence of the blood-brain barrier. Nonetheless, immunotherapy is a novel approach in the therapeutic management of glioma patients, which has shown promising results in several clinical trials, especially in the adult population. Vaccination, with or without dendritic cells, blockade of the immune checkpoints, and adoptive T cell transfer are the most studied modalities of diffuse glioma immunotherapy. The future most likely resides in combinatorial approaches, with administration of conventional treatments (surgery, radiochemotherapy) and immunotherapy following yet to determine schedules.
Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Glioma/terapia , Imunoterapia/métodos , Adulto , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/imunologia , Vacinas Anticâncer/uso terapêutico , Criança , Terapia Combinada , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/imunologia , Terapia Genética , Glioblastoma/tratamento farmacológico , Glioblastoma/imunologia , Glioma/tratamento farmacológico , Glioma/imunologia , Humanos , Imunoterapia Adotiva , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/imunologia , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Transgênicos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Subpopulações de Linfócitos T/imunologia , Evasão TumoralRESUMO
One of the innovative principles in glioblastoma surgery consists in making the tumour fluorescent in order for it to be more easily visualised during the procedure. 5-aminolevulinic acid (5-ALA) undergoes an enzyme transformation, turning into another molecule, protoporphyrine IX (PPIX) whose property is fluorescence. It emits red light when it is stimulated by blue light.
Assuntos
Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Procedimentos Neurocirúrgicos/tendências , Neoplasias Encefálicas/enfermagem , Glioblastoma/enfermagem , Humanos , Ácidos Levulínicos/uso terapêutico , Margens de Excisão , Procedimentos Neurocirúrgicos/métodos , Procedimentos Neurocirúrgicos/enfermagem , Cirurgia Assistida por Computador/métodos , Cirurgia Assistida por Computador/enfermagem , Cirurgia Assistida por Computador/tendências , Terapias em Estudo/enfermagem , Terapias em Estudo/tendências , Ácido AminolevulínicoRESUMO
Hospitalisation forces patients with glioblastoma and their family to face a new life made up of numerous constraints and uncertainties. In this context of anxiety, nursing care is based on global support which combines technical, organisational and relational skills.
Assuntos
Neoplasias Encefálicas/enfermagem , Glioblastoma/enfermagem , Enfermagem Oncológica/métodos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/psicologia , Glioblastoma/patologia , Glioblastoma/psicologia , Humanos , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/organização & administração , Assistência Centrada no Paciente/normasRESUMO
Nurses in neurosurgical departments play a critical role as they are involved in the first stages of the care pathway of patients with glioblastoma. Indeed, surgery enables a definitive histopathological diagnosis to be established and the size of the tumour to be significantly reduced, thereby improving the prognosis.
Assuntos
Neoplasias Encefálicas/enfermagem , Glioblastoma/enfermagem , Procedimentos Neurocirúrgicos/enfermagem , Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Humanos , Neurocirurgia/enfermagem , Neurocirurgia/organização & administração , Enfermagem Oncológica/métodos , Enfermagem Oncológica/organização & administração , Padrões de Prática em EnfermagemRESUMO
Lead nurses in neuro-oncology support patients with glioblastoma and their family from the time of diagnosis. They work closely with all health professionals practising in hospitals and in the home. They coordinate patients' care pathways, from the diagnosis consultation to their death.
Assuntos
Neoplasias Encefálicas/enfermagem , Glioblastoma/enfermagem , Papel do Profissional de Enfermagem , Neoplasias Encefálicas/psicologia , Glioblastoma/psicologia , Humanos , Neurologia , Enfermagem Oncológica , Qualidade de Vida , Recursos HumanosRESUMO
A stay in a palliative care unit must not be considered as an end in itself but rather as the provision of specific support towards the end of life, whether it be in a hospital or before a return home.
Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Equipe de Assistência ao Paciente/organização & administração , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/métodos , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/organização & administração , Humanos , Comunicação Interdisciplinar , Papel do Profissional de Enfermagem , Cuidados Paliativos/métodos , Cuidados Paliativos/organização & administração , Conforto do Paciente/métodos , Conforto do Paciente/organização & administração , Assistência Terminal/métodos , Assistência Terminal/organização & administraçãoRESUMO
Glioblastomas are serious tumours of the central nervous system. Recurrence is systematic and prognosis poor. Radiotherapy and chemotherapy follow surgery, when surgery is possible, to lengthen survival, while preserving quality of life as much as possible. In this respect, symptomatic treatments and supportive care are necessary.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/enfermagem , Neoplasias Encefálicas/terapia , Terapia Combinada/enfermagem , Glioblastoma/diagnóstico , Glioblastoma/enfermagem , Glioblastoma/terapia , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , HumanosRESUMO
When a patient with glioblastoma and their families wish, a hospital at home scheme can be put in place, providing care and support for the patient in the palliative phase. The quality of life of the patient remains the priority and special attention is paid to the family.
Assuntos
Serviços de Assistência Domiciliar , Relações Enfermeiro-Paciente , Relações Profissional-Família , Procedimentos Clínicos , Família , Serviços de Assistência Domiciliar/organização & administração , Serviços de Assistência Domiciliar/normas , Humanos , Cuidados de Enfermagem/métodos , Educação de Pacientes como AssuntoRESUMO
Aberrant DNA methylation has been shown to inactivate tumor suppressor genes during carcinogenesis. MicroRNA-149 (miR-149) was recently demonstrated to function as a tumor suppressor gene in glioblastoma multiforme (GBM). However, the potential linkage of miR-149 levels and the underlying epigenetic regulatory mechanism in human GBM has not been studied. We used quantitative real-time polymerase chain reaction to investigate the levels of miR-149 in GBM tissues, their matched adjacent normal tissues, and glioblastoma U87MG cell line. Using bisulfite genomic sequencing technology, DNA methylation status of upstream region of miR-149 was evaluated in study population groups and the U87MG cell line. After treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), the DNA methylation status, gene expression, and target protein levels of miR-149 were investigated. Our studies revealed that methylation and expression levels of miR-149 were significantly increased and decreased, respectively in GBM patients relative to the adjacent normal tissues (P < 0.01). MiR-149 suppressed the expression of AKT1 and cyclin D1 and reduced the proliferative activities of the U87MG cell line. Treatment of U87MG cells with 5-aza-dC reversed the hypermethylation status of miR-149, enhanced the expression of its gene, and decreased target mRNA and proteins levels (P < 0.01). These findings suggest that the methylation mechanism is associated with decreased expression levels of miR-149, which may in turn lead to the increased levels of its oncogenic target proteins.
Assuntos
Neoplasias Encefálicas/genética , Ciclina D1/metabolismo , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Azacitidina/farmacologia , Sequência de Bases , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Metilação de DNA/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Reação em Cadeia da Polimerase em Tempo Real , Células Tumorais CultivadasRESUMO
Transcription factor 3 (TCF3) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family. Recent studies have demonstrated its potential carcinogenic properties. Here we show that TCF3 was upregulated in glioma tissues compared with normal brain tissues. This upregulation of the TCF3 gene probably has functional significance in brain-tumor progression. Our studies on glioblastoma multiforme (GBM) cell lines show that knock-down of TCF3 induced apoptosis and inhibited cell migration. Further analysis revealed that down-regulation of TCF3 gene expression inhibits Akt and Erk1/2 activation, suggesting that the carcinogenic properties of TCF3 in GBM are partially mediated by the phosphatidylinositol 3-kinase-Akt and MAPK-Erk signaling pathways. Considered together, the results of this study demonstrate that high levels of TCF3 in gliomas potentially promote glioma development through the Akt and Erk pathways.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Encefálicas/patologia , Glioma/patologia , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioma/metabolismo , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para CimaRESUMO
INTRODUCTION: The L-Valine labeled (L-[U-(13)C,(15)N] Val) is a stable isotopic tracer administered by parenteral route within the framework of a new clinical research program concerning the brain tumor metabolism. To meet regulatory requirements and have ready to use solution with an expiration date, a pharmaceutical control of active pharmaceutical ingredient followed by stability study of hospital preparation were realised. MATERIALS AND METHODS: After the pharmaceutical control of the L-[U-(13)C,(15)N] Val, the hospital preparation was prepared according to the good manufacturing preparation. Prepared bottles were stored at 5°C±3°C and 25°C±2°C for six months. The stability of the preparation was determined by physico-chemical controls (pH, osmolality, sub-visible particles, L-[U-(13)C,(15)N] Val concentration, sodium concentration, isotopic enrichment) and microbiological (bacterial endotoxin and sterility). RESULTS: Concentrations of L-[U-(13)C, (15)N] Val and sodium does not significantly decrease during the stability study. In parallel, no change in pH and osmolality were highlighted. Isotopic enrichment higher than 99.9% reflected the stability of labeling of L-valine molecule. The sub-visible particles, the bacterial endotoxin and sterility were in accordance with the European Pharmacopoeia attesting limpidity, apyrogenicity and sterility of this injectable preparation. DISCUSSION AND CONCLUSION: The stability of this hospital preparation of L-[U-(13)C, (15)N] Val has been demonstrated for six months at 5°C±3°C and 25°C±2°C, ensuring a parenteral administration as part of the clinical trial.
Assuntos
Neoplasias Encefálicas/metabolismo , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Valina/química , Valina/farmacocinética , Isótopos de Carbono , Composição de Medicamentos , Estabilidade de Medicamentos , Injeções , Marcação por Isótopo , Isótopos de Nitrogênio , Soluções Farmacêuticas , Compostos Radiofarmacêuticos/administração & dosagem , Reprodutibilidade dos Testes , Valina/administração & dosagemRESUMO
INTRODUCTION: The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined. METHODS: We compared the patterns of care and OS of all GBM patients diagnosed in 2004 (n=105) and in 2008 (n=130) in our center. RESULTS: Younger patients (aged<70 years) diagnosed in 2008 received temozolomide radiochemotherapy as the initial treatment and bevacizumab at recurrence more frequently than those diagnosed in 2004 (69% vs 26% P<10(-4) and 41% vs 3%, P<10(-4), respectively). Elderly patients (aged≥70 years) diagnosed in 2008 received an oncological treatment (radiotherapy and/or chemotherapy) more frequently than those diagnosed in 2004 (67% vs 38%, P=0.006). The patients diagnosed in 2008 had longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P=0.001). This finding was true for both younger and elderly patients (15.3 months vs 8.9 months, P=0.02 and 6.4 months vs 3.2 months, P=0.0002, respectively) and when considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P=0.004). CONCLUSION: In our center, the change in the patterns of care for GBMs between 2004 and 2008 has been associated with a significant improvement in OS.