RESUMO
PURPOSE: Glioblastoma is the most common malignant brain tumor in central nervous system. Due to absence of the mechanism underlying glioblastoma, the clinical outcome is poor. RNF213 is a ring finger protein and mutation in RNF213 gene is detected in cancers. But the role of RNF213 in glioblastoma is unknown. METHODS: RNF213 expression was detected by qPCR, western blotting, IHC technology. RNF213 was overexpressed in plasmid pcDNA3.1. Assays including CCK-8, plate colony formation, wound healing, transwell and FITC/PI dye were used to detect cell behaviors. RESULTS: RNF213 was shown to express much lower in tumor tissues and in tumor cell lines compared to control. The patients with higher RNF213 expression displayed longer survival time. When RNF213 was overexpressed in U87MG cells, cell proliferation and colony formation were inhibited significantly. The ability of cell migration and invasion was also suppressed. FAC analysis demonstrated that cell apoptosis was increased after RNF213 overexpression. But cell cycle distribution was not affected by RNF213. Then the expression level of MEKK1, JNK, c-Jun, and cdc42 was decreased after RNF213 overexpression, but increased reversely when RNF213 was knocked down by RNAi technology. CONCLUSIONS: RNF213 suppresses carcinogenesis and affects MAPK/JNK signaling pathway in glioblastoma. This study suggests that RNF213 might be a promising target for therapy of glioblastoma.
Assuntos
Adenosina Trifosfatases/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Sistema de Sinalização das MAP Quinases , Mutação , Ubiquitina-Proteína Ligases/metabolismo , Adenosina Trifosfatases/genética , Apoptose/fisiologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Taxa de Sobrevida , Ubiquitina-Proteína Ligases/genéticaRESUMO
We examined the effects of weekly single-agent docetaxel plus three-dimensional conformal radiation therapy (3D-CRT) on apoptotic index (AI) and microvessel density (MVD) in local advanced non-small-cell lung squamous cancer patients and analyzed the correlation of MVD, AI, and 50% tumor shrinkage time (T0.5) The molecular mechanism of docetaxel radiosensitization was investigated. Sixty untreated patients with stage IIIA or IIIB lung squamous cancer were enrolled and randomly divided into two groups: observation (N = 30; 3D-CRT + docetaxel + adjuvant chemotherapy) and control (N = 30; 3D-CRT + adjuvant chemotherapy). From day 1 radiotherapy, the observation group received intravenous docetaxel (36 mg/m(2)) once weekly for 6 weeks. Post-radiotherapy, chemotherapy of docetaxel combined with cisplatin lasted 4-6 cycles in both groups. Before radiotherapy and within 24 h after radiotherapy (20 Gy), bronchoscopic biopsy was performed twice at the same site. To analyze the MVD of tumor specimens with immunohistochemical staining . The AI of lung cancer cells was assessed with TUNEL assay, T0.5 values were calculated. The observation group had significantly lower MVD than the control group (P < 0.05). AI significantly increased before and after treatment in the observation group compared with the control group (P < 0.05). The decreased MVD values negatively correlated with T0.5 values (r = -0.624, P < 0.05), whereas the increased AI values did not correlate with the T0.5 values. Docetaxel radiosensitization may occur by decrease in MVD and increase in AI values. Weekly single-agent docetaxel plus 3D-CRT can improve prognosis and quality of life in local advanced non-small-cell lung squamous cancer patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Células Escamosas/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada , Docetaxel , Feminino , Humanos , Masculino , Microvasos/efeitos dos fármacos , Microvasos/efeitos da radiação , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Neoplasias de Células Escamosas/patologia , Neoplasias de Células Escamosas/radioterapia , Prognóstico , Qualidade de Vida , Radioterapia Conformacional , Taxa de SobrevidaRESUMO
We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.
Assuntos
Animais , Masculino , Etanol/intoxicação , Isoflavonas/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Memória Espacial/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Alcoolismo/complicações , Cromatografia Líquida de Alta Pressão , Córtex Cerebral/química , Córtex Cerebral/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Ácido Glutâmico/análise , Interleucina-1beta/análise , Isoflavonas/farmacologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Vasodilatadores/farmacologia , Ácido gama-Aminobutírico/análiseRESUMO
We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1ß increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.
Assuntos
Etanol/intoxicação , Isoflavonas/uso terapêutico , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Memória Espacial/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Alcoolismo/complicações , Animais , Córtex Cerebral/química , Córtex Cerebral/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Ácido Glutâmico/análise , Interleucina-1beta/análise , Isoflavonas/farmacologia , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Vasodilatadores/farmacologia , Ácido gama-Aminobutírico/análiseRESUMO
OBJECTIVE: We investigated safety, efficacy, and acceptability of an oral regimen of medical abortion compared with surgical abortion in three developing countries. STUDY DESIGN: Women (n = 1373) with amenorrhea < or = 56 days chose either surgical abortion (as provided routinely) or 600 mg of mifepristone followed after 48 hours by 400 micrograms of misoprostol. This is the appropriate design for studying safety, efficacy, and acceptability among women selecting medical abortion over available surgical services. RESULTS: The medical regimen had more side effects, particularly bleeding, than did surgical abortion but very few serious side effects. Failure rates for medical abortion, although low, exceeded those for surgical abortion: 8.6% versus 0.4% (China), 16.0% versus 4.0% (Cuba), and 5.2% versus 0% (India). Nearly half of failures among medical clients were not true drug failures, however, but surgical interventions not medically necessary (acceptability failures or misdiagnoses). Women were satisfied with either method, but more preferred medical abortion. CONCLUSION: Medical abortion can be safe, efficacious, and acceptable in developing countries.
PIP: A multi-center comparative study of medical compared to surgical abortion confirmed that medical abortion can be safe, effective, and acceptable in developing countries. A total of 1373 women from medical centers in China, Cuba, and India with pregnancies of 56 days' gestation or less were given the choice of surgical abortion or 600 mg of mifepristone followed after 48 hours by 400 mcg of misoprostol. Since the majority selected medical abortion, researchers in China and Cuba assigned some of these women to the surgical group to equalize the size of the two groups. The surgical abortion failure rates in China, Cuba, and India were 0.4%, 4%, and 0%, respectively, while the failure rates for medical abortion were 8.6%, 16.0%, and 5.2%, respectively. In all sites, both medical failures (an adverse effect resulting in a medically indicated surgical intervention) and acceptability failures (failure to complete the entire regimen) contributed substantially to the gross failure rates for medical abortion. Medical abortion failure rates increased with gestational age. Although cramping, nausea, and vomiting were more frequent among women in the medical abortion group and bleeding was heavier, general assessments of well-being reported at exit interviews did not differ between the two treatment groups at any site. Regardless of abortion method, the majority of women were either satisfied or highly satisfied with the procedure. In all countries, a higher number of medical than surgical abortion patients indicated they would opt again for the same procedure. Neither the bleeding pattern nor the higher failure rate associated with medical abortion justify withholding this option from women in developing countries.