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1.
Nat Prod Res ; : 1-7, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31198051

RESUMO

Three previously undescribed seco-dammarane triterpenoid glycosides O-Q (1-3) along with two known compounds (4 and 5) were isolated and characterized from the leaves of Cyclocarya paliurus. Their structures were determined by comprehensive analysis of 1 D, 2 D NMR and HRESIMS data. Compounds 1-5 were evaluated for their inhibitory effects against human pancreatic tumor (ASPC-1), human gastric carcinoma (SNU5), liver hepatocellular carcinoma (HEPG-2) and human colon tumor (HCT116) cell lines. Among them cyclocarioside P (2) showed somewhat inhibitory activity towards those tumor cells.

2.
Nat Prod Res ; : 1-7, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31109181

RESUMO

Three new biflavones, apigenin-(3',8″)-chrysin (1), (2S)-2,3-Dihydroametoflavone 5,4'-dimethyl ether (2), and (2S)-5″,7″-Dihydroxy-2″-phenoxychromonyl-(4'″,3')-naringenin (3), together with seven known biflavones (4-10) were isolated from the 75% EtOH extract of Selaginella doederleinii. The structures of new compounds were established by application of spectroscopic methods, including 1D and 2D NMR, HRMS, and CD measurements. In addition, all new compounds were evaluated for their cytotoxic potential against three human cancer cell lines A549, MCF-7, and SMMC-7721 in vitro. Compound 2 exhibited potent cytotoxic activity with IC50 values ranging from 6.35 to 10.18 µM.

3.
Cell Rep ; 26(1): 209-221.e5, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30605677

RESUMO

Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, both Dhhc4-/- and adipose-specific Dhhc5 knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.

4.
Medicine (Baltimore) ; 97(39): e12636, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30278586

RESUMO

This study was aimed to reveal the changes in survival rates and prognostic factors to survival of chondroblastic osteosarcoma (COS).Patients from the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. Kaplan-Meier survival analysis and Cox proportional hazard model were used during analysis.There were significant differences on overall survival between subtypes of osteosarcoma (P < .001*). Overall survival of COS did not change significantly during last forty years (P = .610), and cancer-specific survival increased to a plateau in 1980s and then remained stable (P = .058). Younger onset age, patients of white race, well and moderately differentiated tumors, and surgery independently predicted better overall (Hazard ratio [HR]: 1.034, P < .001*; HR: 0.538, P = .004*; HR: 0.240, P = .020* and HR: 0.350, P < .001*, respectively) and cancer-specific (HR: 1.031, P = .002*; HR: 0.592, P = .036*; HR: 0.098, P = .027* and HR: 0.253, P < .001*, respectively) survival. Metastasis at diagnosis independently predicted worse overall (HR: 3.108, P < .001*) and cancer-specific (HR: 4.26, P < .001*) survival compared to no metastasis.Younger onset age, white race, well and moderately differentiated tumors, no metastasis at diagnosis and surgical resection can independently predict better overall and cancer-specific survival of COS.


Assuntos
Neoplasias Ósseas/mortalidade , Condroblastoma/mortalidade , Osteossarcoma/mortalidade , Adulto , Idade de Início , Neoplasias Ósseas/etnologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Condroblastoma/etnologia , Condroblastoma/patologia , Condroblastoma/cirurgia , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Metástase Neoplásica , Osteossarcoma/etnologia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida
5.
J Zhejiang Univ Sci B ; 19(9): 674-688, 2018 Sept..
Artigo em Inglês | MEDLINE | ID: mdl-30178634

RESUMO

OBJECTIVE: In this study, we aimed to expand current knowledge of head and neck squamous cell carcinoma (HNSCC)-associated long noncoding RNAs (lncRNAs), and to discover potential lncRNA prognostic biomarkers for HNSCC based on next-generation RNA-seq. METHODS: RNA-seq data of 546 samples from patients with HNSCC were downloaded from The Cancer Genome Atlas (TCGA), including 43 paired samples of tumor tissue and adjacent normal tissue. An integrated analysis incorporating differential expression, weighted gene co-expression networks, functional enrichment, clinical parameters, and survival analysis was conducted to discover HNSCC-associated lncRNAs. The function of CYTOR was verified by cell-based experiments. To further identify lncRNAs with prognostic significance, a multivariate Cox proportional hazard regression analysis was performed. The identified lncRNAs were validated with an independent cohort using clinical feature relevance analysis and multivariate Cox regression analysis. RESULTS: We identified nine HNSCC-relevant lncRNAs likely to play pivotal roles in HNSCC onset and development. By functional enrichment analysis, we revealed that CYTOR might participate in the multistep pathological processes of cancer, such as ribosome biogenesis and maintenance of genomic stability. CYTOR was identified to be positively correlated with lymph node metastasis, and significantly negatively correlated with overall survival (OS) and disease free survival (DFS) of HNSCC patients. Moreover, CYTOR inhibited cell apoptosis following treatment with the chemotherapeutic drug diamminedichloroplatinum (DDP). HCG22, the most dramatically down-regulated lncRNA in tumor tissue, may function in epidermis differentiation. It was also significantly associated with several clinical features of patients with HNSCC, and positively correlated with patient survival. CYTOR and HCG22 maintained their prognostic values independent of several clinical features in multivariate Cox hazards analysis. Notably, validation either based on an independent HNSCC cohort or by laboratory experiments confirmed these findings. CONCLUSIONS: Our transcriptomic analysis suggested that dysregulation of these HNSCC-associated lncRNAs might be involved in HNSCC oncogenesis and progression. Moreover, CYTOR and HCG22 were confirmed as two independent prognostic factors for HNSCC patient survival, providing new insights into the roles of these lncRNAs in HNSCC as well as clinical applications.

6.
Fitoterapia ; 130: 184-189, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30172824

RESUMO

A pair of epimer brachyanins A (1) and B (2), along with a new phloroglucinol brachyanin C (3), were isolated from the leaves of Leptospermum brachyandrum. Brachyanins A (1) and B (2) were the first example of novel meroterpenoid with a unique skeleton that combined a synacrpic acid and a pinene units via a benzyl moiety. Their structures were elucidated through the application of extensive spectroscopic measurements and single-crystal X-ray diffraction analysis and with the absolute configurations of 1 and 2 were confirmed by the quantum chemical CD calculation. The hetero Diels-Alder as the key biotransformation was proposed to account for the biosynthesis of brachyanins A and B sheding light by the potential procursor brachyanin C.


Assuntos
Leptospermum/química , Floroglucinol/isolamento & purificação , Terpenos/isolamento & purificação , China , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Folhas de Planta/química
7.
Neurosurg Rev ; 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29732516

RESUMO

This study was aimed to analyze the survival of patients with spinal chordomas. Patients' data in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved and analyzed statistically. There were 765 patients with spinal chordomas between 1974 and 2013. The overall survival did not improve significantly over decades for patients receiving surgery and radiotherapy (SR) (P = 0.221). There were significant differences in overall survival among subgroups of patients receiving surgery (S), radiotherapy (R), and neither S nor R (NSR) (P = 0.031, 0.037, and 0.031, respectively). Cancer-specific survival did not change significantly among subgroups of patients receiving R (P = 0.411), while it increased steadily among subgroups of patients receiving S, SR, and NSR (P < 0.001, 0.001, and 0.049, respectively). In the multivariate Cox regression model, younger onset age (hazard ratio [HR] 1.052, P < 0.001), surgery (HR 0.291, P = 0.001), and tumor location of the sacrum (HR 0.401, P = 0.002) were associated with a better overall survival. Similarly, younger onset age (HR 1.036, P = 0.029), surgery (HR 0.221, P = 0.009), and tumor location of the sacrum (HR 0.287, P = 0.002) were also associated with a higher cancer-specific survival. The changes in overall and cancer-specific survival over time differ among different treatment groups. Younger onset age, surgical strategy, and tumor location of the sacrum may be correlated with a higher overall and cancer-specific survival.

8.
Medicine (Baltimore) ; 97(6): e9809, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29419679

RESUMO

BACKGROUND: Cooled radiofrequency procedure is a novel minimally invasive surgical technique and has been occasionally utilized in managing chronic sacroiliac joint (SIJ) pain. A meta-analysis was conducted to systematically assess the efficacy and safety of using cooled radiofrequency in treating patients with chronic SIJ pain in terms of pain and disability relief, patients' satisfaction degree as well as complications. METHODS: Studies of using cooled radiofrequency procedure in managing SIJ pain were retrieved from Medline and Web of Science according to inclusion and exclusion criteria. Quality evaluation was conducted using Cochrane collaboration tool for randomized controlled trials and MINORS quality assessment for noncomparative trials. Statistics were managed using Review Manager 5.3. RESULTS: Totally 7 studies with 240 eligible patients were enrolled. The overall pooled results demonstrated that pain intensity decreased significantly after cooled radiofrequency procedure compared with that measured before treatment. The mean difference (MD) was 3.81 [95% confidence intervals (95% CIs): 3.29-4.33, P < .001] and 3.78 (95% CIs: 3.31-4.25, P < .001) as measured by the Numerical Rating Scale (NRS) and Visual Analog Scale (VAS), respectively. Disability also relieved significantly after treatment compared with that measured before treatment. The MD was 18.2 (95% CIs: 12.22-24.17, P < .001) as measured by the Oswestry Disability Index (ODI). Seventy-two percent of the patients presented positive results as measured by the Global Perceived Effect (GPE). The OR was 0.01 (95% CIs: 0.00-0.05, P < .001). Only mild complications were observed in the 7 studies, including transient hip pain, soreness, and numbness. CONCLUSION: Cooled radiofrequency procedure can significantly relieve pain and disability with no severe complications, and majority of patients are satisfied with this technique. Thus, it is safe and effective to use this procedure in managing patients with chronic SIJ pain. More high-quality and large-scale randomized controlled trials (RCTs) are required to validate our findings. LIMITATIONS: The sample size of the included studies was small and various heterogeneity existed.


Assuntos
Artralgia , Ablação por Cateter/métodos , Crioterapia/métodos , Articulação Sacroilíaca/fisiopatologia , Artralgia/diagnóstico , Artralgia/fisiopatologia , Artralgia/terapia , Humanos , Cooperação do Paciente , Resultado do Tratamento
9.
Bioorg Med Chem Lett ; 26(16): 3918-22, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27423479

RESUMO

A series of novel dithiocarbamate-chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC50 values of 2.03µM and 2.46µM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase.


Assuntos
Antineoplásicos/síntese química , Chalcona/análogos & derivados , Desenho de Drogas , Tiocarbamatos/química , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chalcona/síntese química , Chalcona/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Relação Estrutura-Atividade , Tiocarbamatos/síntese química , Tiocarbamatos/toxicidade , Proteína Supressora de Tumor p53/metabolismo
10.
Molecules ; 21(5)2016 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-27213317

RESUMO

A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC50 value of 1.52 µM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma.


Assuntos
Azóis/química , Azóis/farmacologia , Linhagem Celular Tumoral , Humanos , Relação Estrutura-Atividade
11.
Contemp Oncol (Pozn) ; 19(2): 137-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26034392

RESUMO

AIM OF THE STUDY: To research the demographic and histopathological features of ESCC in southeastern China. MATERIAL AND METHODS: We retrospectively reviewed the ESCC cases in the biobank of the National Engineering Centre for Biochip in Shanghai, which cooperates with lots of hospitals and research institutions in southeastern China. The patients were pathologically confirmed as having ESCC. The demographic and histopathological features of these cases were analysed subsequently. RESULTS: A total of 1317 patients were enrolled. The overall male: female ratio was 2.88: 1. 74.34% of these cases occurred in people aged between 50-70 years. Dysphagia was the most common symptom, which accounted for 93.40% of all the patients. Stage II and III were predominant (79.73%). 72.89% of patients had a tumour length greater than 3 cm. Most of the tumours (65.83%) were located in middle third of the oesophagus. There was a significant difference among the tumour stage, length, and location in different sex groups (P < 0.05), but not between different age groups (P > 0.05). In males, ESCC is usually located in the lower parts, with a longer tumour length and higher tumour stage. 24.15% of patients had lymph nodes ratio (LNR) > 0.2. CONCLUSIONS: In our analysis, dysphagia was more common in ESCC patients, to whom more attention should be paid. Additionally, males had a higher incidence, with longer and more distant disease, which gives a poor prognosis.

12.
J Dig Dis ; 16(6): 319-26, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25858763

RESUMO

OBJECTIVE: To observe the effects of quercetin on chronic mixed reflux esophagitis (RE) in rats by inhibiting the nuclear factor-κB p65 (NF-κBp65) and interleukin-8 (IL-8) signaling pathways. METHODS: Forty-eight healthy male Sprague-Dawley rats were randomly divided into six groups, with 8 rats in each group: the normal intact group, the sham operation group, the RE control group, the RE group treated with omeprazole or 100 mg/kg and 200 mg/kg quercetin. The animals were sacrificed after 6 weeks of different interventions. The pathological characteristics of esophageal mucosa were observed according to the diagnostic criteria and the expressions of NF-κBp65 and IL-8 were assessed by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Compared with the RE control group, esophageal mucosal injury was improved and the expressions of NF-κBp65 and IL-8 were significantly decreased in the RE group treated with omeprazole or quercetin (P < 0.05). Compared with the omeprazole group, the gross and microscopic scores of esophageal mucosal injury and the expressions of NF-κBp65 and IL-8 in the 100 mg/kg and 200 mg/kg quercetin groups were not increased (P > 0.05). There was no statistically significant difference between the RE groups treated with 100 mg/kg quercetin and 200 mg/kg quercetin. CONCLUSION: Quercetin can prevent esophageal mucosal injury in RE rats by suppressing the NF-κBp65 and IL- 8 signaling pathways.


Assuntos
Antioxidantes/uso terapêutico , Esofagite Péptica/prevenção & controle , Interleucina-8/antagonistas & inibidores , Quercetina/uso terapêutico , Fator de Transcrição RelA/antagonistas & inibidores , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
13.
Psychiatry Res ; 220(3): 1138-43, 2014 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-25446465

RESUMO

Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.


Assuntos
Colo/inervação , Modelos Animais de Doenças , Gastroenteropatias/fisiopatologia , Reto/inervação , Limiar Sensorial/fisiologia , Animais , Eletromiografia , Lateralidade Funcional/fisiologia , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia
14.
Hepatobiliary Pancreat Dis Int ; 13(5): 529-38, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25308364

RESUMO

BACKGROUND: Although there are many studies on the mechanism of chemoresistance in cancers, studies on the relations between WNT5A and chemoresistance in pancreatic cancer are rare. The present study was to examine the role of WNT5A in the regulation of cell cycle progression and in chemo-resistance in pancreatic cancer tissues and cell lines. METHODS: Fresh pancreatic cancer and paracarcinoma tissues were obtained from 32 patients. The expressions of WNT5A, AKT/p-AKT and Cyclin D1 were detected by immunohistochemistry, and the correlation between WNT5A expression and clinicopathological characteristics was analyzed. The relationship between WNT5A expression and gemcitabine resistance was studied in PANC-1 and MIAPaCa2 cell lines. The effect of WNT5A on the regulation of cell cycle and gemcitabine cytotoxicity were investigated. The associations among the expressions of p-AKT, Cyclin D1 and WNT5A were also analyzed in cell lines and the effect of WNT5A on restriction-point (R-point) progression was evaluated. RESULTS: WNT5A, p-AKT and Cyclin D1 were highly expressed in pancreatic cancer tissues, and the WNT5A expression was correlated with the TNM stages. In vitro, WNT5A expression was associated with gemcitabine chemoresistance. The percentage of cells was increased in G0/G1 phase and decreased in S phase after knockdown of WNT5A in PANC-1. WNT5A promoted Cyclin D1 expression through phosphorylation of AKT which consequently enhanced G1-S transition and gemcitabine resistance. Furthermore, WNT5A enhanced the cell cycle progression toward R-point through regulation of retinoblastoma protein (pRb) and pRb-E2F complex formation. CONCLUSIONS: WNT5A induced chemoresistance by regulation of G1-S transition in pancreatic cancer cells. WNT5A might serve as a predictor of gemcitabine response and as a potential target for tumor chemotherapy.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Wnt/metabolismo , Adenocarcinoma/química , Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D/análise , Ciclina D/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , Concentração Inibidora 50 , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pâncreas/química , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/tratamento farmacológico , Fosforilação , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-akt/análise , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Proteína do Retinoblastoma/metabolismo , Proteínas Wnt/análise , Proteínas Wnt/genética , Proteína Wnt-5a
15.
Gastroenterol Res Pract ; 2013: 691026, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690762

RESUMO

Background. Specific dietary components have been associated with gastroesophageal reflux disease (GERD) in Europe and the United States. However, the relationship between dietary components and GERD in Chinese still remains unclear. Methods. A total of 268 patients who were newly diagnosed as reflux esophagitis (RE) in Outpatient Endoscopy Center of Tongji Hospital were recruited. In addition, 269 sex- and age-matched subjects were also recruited as controls. The body measurements were determined, and the dietary intake during the previous year was evaluated using food frequency questionnaire (FFQ). Stepwise multiple logistic regression analysis was performed to examine the association between nutrients and RE. Results. After adjustment for WC, WHR, total energy intake, and demographics, there were a positive dose-response relationship between RE and calcium, meat, oils, and salt and a negative dose-response relationship between RE and protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs. Conclusion. High intake of meat, oils, salt, and calcium is associated with an increased risk for RE while high intake of protein, carbohydrate, calories from protein (%), vitamin C, grains and potatoes, fruits, and eggs correlates with a reduced risk for RE.

16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 29(6): 625-30, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23225037

RESUMO

OBJECTIVE: To study SCN1A gene mutations and their inheritance in patients with Dravet syndrome(DS), and to analyze the phenotypes of their family members and genotype-phenotype correlations. METHODS: Genomic DNA was extracted from peripheral blood samples from 181 DS patients and their parents. Phenotypes of affected members were analyzed. SCN1A gene mutations were screened using PCR-DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) RESULTS: SCN1A gene mutations were identified in 128 patients (70.7%), which included 60 missense mutations (46.9%), 55 truncation mutations (43.0%), 10 splice site mutations (7.8%), and 3 cases with SCN1A gene fragment deletions or duplications(2.3%). Five patients (3.9%) had mutations inherited from one of their parents. One father has carried a somatic mutation mosaicism (C373fsx378). For the 5 parents carrying a mutation, 1 had febrile seizures, 2 had febrile seizures plus, 1 had afebrile generalized tonic-clonic seizures, whilst 1 was normal. CONCLUSION: The mutation rate of SCN1A in DS patients is about 70%. Most mutations are of missense and truncation mutations. Only a few patients have carried fragment deletions or duplications. Most SCN1A mutations are de novo, only a few were inherited from the parents. SCN1A mutations carried by the parents can be in the form of mosaicism. The phenotypes of parents with SCN1A mutations are either mild or normal.


Assuntos
Epilepsias Mioclônicas/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Sequência de Aminoácidos , Sequência de Bases , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Fenótipo , Alinhamento de Sequência
17.
Zhonghua Er Ke Za Zhi ; 50(8): 580-6, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23158734

RESUMO

OBJECTIVE: To summarize the phenotypes and identify SCN1A mutations in families with generalized epilepsy with febrile seizures plus (GEFS(+)), and analyze the genotype- phenotype correlations in GEFS(+) families. METHOD: Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS(+) families. The phenotypes of the affected members were analyzed. The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing. RESULT: In 39 GEFS(+) families, there were 196 affected members, ranging from 2 to 22 affected members in each family. Their phenotypes included febrile seizures (FS) in 92(46.9%), febrile seizures plus (FS(+)) in 62(31.6%), FS or FS(+) with partial seizures in 12(6.1%), afebrile generalized tonic-clonic seizures (AGTCS) in 11(5.6%), myoclonic atonic epilepsy in 8(4.1%), Dravet syndrome in 2(1.0%), childhood absence epilepsy in 1 (0.5%), FS(+) with myoclonic seizures in 1(0.5%), AGTCS and myoclonic seizures in 1 (0.5%), partial seizures in 1 (0.5%), unclassified seizures in 5 (2.6%). Four families were found with SCN1A mutations, including three families with missense mutation (N935H, R101Q, G1382R) and one family with truncation mutation (C373fsx378). In three families with missense mutations, the phenotypes include FS, FS(+), FS(+) with partial seizures, and AGTCS. In one family with truncation mutation, the phenotypes included FS, FS(+), and Dravet syndrome. The mother of proband in the family with missense mutation (R101Q) and the father of proband in the family with truncation mutation (C373fsx378) were both somatic mosaicism. Both of their phenotypes were FS(+). CONCLUSION: The most common phenotypes of GEFS(+) were FS and FS(+), followed by the FS/FS(+) with partial seizures and AGTCS. The most severe phenotype was Dravet syndrome. SCN1A mutation rate in GEFS(+) was about 10%. Missense mutation was common in GEFS(+) families, few with truncation mutation. Few members of GEFS(+) families had somatic mosaicism of SCN1A mutations and their phenotypes were relatively mild.


Assuntos
Epilepsia Generalizada/genética , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Convulsões Febris/genética , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA , Epilepsias Mioclônicas/genética , Feminino , Genótipo , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Linhagem , Fenótipo
18.
Zhonghua Nei Ke Za Zhi ; 51(12): 978-81, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23327962

RESUMO

OBJECTIVE: To explore influential factors of local therapeutic effect in CT guided brachytherapy of (125)I seeds for non-small-cell lung carcinoma (NSCLC). METHODS: Totally 141 primary NSCLC patients diagnosed by bronchoscope or puncture biopsy were treated with CT guided (125)I seeds implantation treatment from 2003 January to 2005 January. Among them, 26 patients were treated with seeds implantation only and remaining 115 combined with chemical therapy. Preplans were performed by using treatment planning system before the implantation. We took the implantation with the prescription dose of 80 - 110 Gy, 1 seed per 1 cm(3), under the guide of computed tomography. Six months after implantation treatment, CT graphs were taken to evaluate the therapeutic effect. RESULTS: All the patients were survival until 6 months after implantation, and 37 were complete remission, 93 were partial remissions. The effective rate was 92.2%. Among all the observed factors, pathologic type(F = 5.162, P = 0.023), dose of cover 100% tumor (D(100)) (F = 100.713, P = 0.000) and treatment methods (F = 16.205, P = 0.000) were the independent influent factors (P < 0.05). Among these, D(100) was the most important factor (P = 0.000). Single factor analysis indicated that pathologic type (χ(2) = 7.313, P = 0.007), D(100) (χ(2) = 71.6, P = 0.000) and treatment methods (χ(2) = 20.5, P = 0.000) were significant influent factors. Of all 141 cases, 24 had complications during or after implantation treatment, while no severe complications were reported. There was no significant correlation between complication and local therapeutic effect (P > 0.05). CONCLUSION: CT guided implantation of (125)I seeds for lung cancer has good clinical effects and few complications. D(100) is the most important factor to influence the local therapeutic effect. Implantation treatment combined with chemotherapy is an ideal measure for NSCLC treatment.


Assuntos
Braquiterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
Mol Biol Rep ; 39(5): 5115-23, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22160573

RESUMO

In this work, fluorescence spectroscopy in combination with circular dichroism spectroscopy and molecular modeling was employed to investigate the binding of 10-hydroxycamptothecin (HCPT) to human serum albumin (HSA) under simulative physiological conditions. The experiment results showed that the fluorescence quenching of HSA by HCPT was a result of the formation of HCPT-HSA complex. The corresponding association constants (K (a)) between HCPT and HSA at four different temperatures were determined according to the modified Stern-Volmer equation. The results of thermodynamic parameters ΔG, ΔH, and ΔS indicated that hydrogen bonds and van der Waals forces played major roles for HCPT-HSA association. Site marker competitive displacement experiment indicated that the binding of HCPT to HSA primarily took place in sub-domain IIA (site I). Molecular docking study further confirmed the binding mode and the binding site obtained by fluorescence and site marker competitive experiments. The conformational investigation showed that the presence of HCPT decreased the α-helical content of HSA and induced the slight unfolding of the polypeptides of protein, which confirmed some micro-environmental and conformational changes of HSA molecules.


Assuntos
Camptotecina/análogos & derivados , Modelos Moleculares , Albumina Sérica/metabolismo , Camptotecina/química , Camptotecina/metabolismo , Dicroísmo Circular , Humanos , Concentração de Íons de Hidrogênio , Cinética , Ligação Proteica , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , Temperatura Ambiente
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