RESUMO
OBJECTIVE: To conduct a meta-analysis to determine whether progesterone, compared with placebo or no treatment, influences mortality and neurologic outcome in traumatic brain injury (TBI). METHODS: To identify eligible studies, systematic searches for randomized controlled trials of progesterone treatment in TBI were conducted in PubMed, Web of Science, EMBASE, Cochrane Library, and ClinicalTrials.gov databases. The search yielded 8 studies that were included in the meta-analysis. Included data were study characteristics, patient demographics, baseline characteristics, progesterone treatment protocol, main outcome of mortality, and secondary neurologic outcome evaluated using the Glasgow Outcome Scale. RESULTS: The 8 studies comprised 2585 patients. The meta-analysis indicated that there was no evidence that progesterone treatment decreased the risk of mortality in patients with TBI; the overall risk ratio was 0.852 (95% confidence interval, 0.632-1.144; P = 0.284). In the secondary outcome analysis, progesterone had no neuroprotective role in improving neurologic outcome; the overall risk ratio was 1.151 (95% confidence interval, 0.0991-1.338; P = 0.06). Subgroup analysis according to the degree of injury assessed by the Glasgow Coma Scale demonstrated similar results. CONCLUSIONS: This study is the largest meta-analysis conducted to date to determine whether progesterone is effective in the treatment of TBI. The findings indicate that progesterone treatment does not decrease mortality or improve neurologic outcome in patients with TBI.
Assuntos
Encefalopatias/mortalidade , Encefalopatias/prevenção & controle , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/mortalidade , Progesterona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causalidade , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Prevalência , Fatores de Risco , Distribuição por Sexo , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To investigate the effect of Ad-ING4 on proliferation and migration of glioma cells and explore its probable mechanism. METHODS: U251 were infected with Ad-ING4. ING4 gene expression was evaluated by RT-PCR. MTT assay was adopted to evaluate the effect of ING4 on proliferation of U251; Boyden chamber assay was used to check the effect of ING4 on the migration of U251. In ING4 transfected U251, Western blot was used for detecting NGF and TrkA expression; Pull-down assay was used for detecting active RhoA expression. RESULTS: ING4 was overexpressed in Ad-ING4 transfected U251 cells. ING4 inhibited proliferation and migration of U251 significantly. Moreover, overexpression of ING4 result in depression of NGF, TrkA and active RhoA. CONCLUSION: ING4 mediated inhibition of the proliferation and migration of human glioma cells by down regulating NGF, TrkA and active RhoA expression.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Glioma/metabolismo , Glioma/patologia , Proteínas de Homeodomínio/metabolismo , Receptor trkA/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Proteínas de Ciclo Celular/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Proteínas de Homeodomínio/farmacologia , Humanos , Fator de Crescimento Neural/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Receptor trkA/efeitos dos fármacos , Transfecção , Proteínas Supressoras de Tumor/farmacologia , Proteína rhoA de Ligação ao GTP/efeitos dos fármacosRESUMO
BACKGROUND: Recent studies have discovered that nuclear translocation of nerve growth factor (NGF) and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological significance. METHODS: Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical (IHC) and hemotoxylin & eosin (HE) staining. Preoperative cerebrospinal fluid (CSF) specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as control. RESULTS: NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury (TBI) tissue. NGF nuclear-positive rate (NPR) of grades III - IV astrocytomas (70.0%) was higher than that of grades I - II astrocytoma (28.6%, P < 0.05). NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid (CSF) (r = 0.755, P < 0.01). Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade I - II patients and 42 months in NGF nuclear negative (NGF-NN) astrocytoma grade I - II patients (P < 0.05). In astrocytoma III - IV patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients (P < 0.01). Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy increased. CONCLUSIONS: NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma patients. Because of the easy access of CSF, it may be developed as an index for early diagnosis and surveillance of astrocytoma.
