RESUMO
Colorectal cancer (CRC) remains a major public health concern, associated with a high rate of morbidity and mortality. Several factors have been implicated in its occurrence and development, which includes histone chaperones. The role of spty2d1 (spt2)-a novel histone chaperone protein-has rarely been investigated in CRC. Therefore, we demonstrated in this study that spt2 undergoes different genetic alterations in colorectal adenocarcinoma datasets and that it was associated with the proliferation of colon carcinoma. Spt2 silencing can reduce the ability of proliferation and increase the rate of apoptosis of LoVo cells. Regarding the overall survival associated with spt2, only the quartile disease-free survival of colon adenocarcinoma (COAD) was found to be statistically significant, while that of rectum adenocarcinoma (READ) was not. The positive (+++) expression of spt2 was correlated with a deeper invasion depth in colorectal adenocarcinoma, and this effect was more pronounced in COAD. These data collectively suggest that spt2 can influence the progression and prognosis in some subtypes of colorectal adenocarcinoma. Therefore, we propose spt2 as a potential target for application in enhancing the overall therapeutic efficacy in some specific subtypes of colorectal adenocarcinoma.
Assuntos
Adenocarcinoma , Neoplasias Colorretais , Chaperonas de Histonas , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Apoptose/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Chaperonas de Histonas/genética , Chaperonas de Histonas/metabolismo , HumanosRESUMO
OBJECTIVES: The aim of this study was to assess the diagnostic usefulness of vascular endothelial growth factor (VEGF) and endostatin mRNA in cervical specimens of patients with cervical dysplasia and carcinoma. STUDY DESIGN: Transcription levels of VEGF and endostatin were detected by RT-PCR in cervical liquid-based preparation specimens and compared with cytological assessments. RESULTS: VEGF as well as endostatin mRNA expression was significantly associated with either cytological or histological diagnosis (p < 0.05). VEGF mRNA and endostatin mRNA were significantly more likely to be expressed in squamous cell carcinomas (SCC) than in cervical intraepithelial neoplasia (CIN) III (p < 0.01 and p < 0.05), and obviously also more likely to be expressed in CINII than in CINI and in CINIII than in CINII (p < 0.05). Eleven inflammation lesions gave positive results by cytology but negative results by RT-PCR for VEGF and endostatin mRNA. Twenty-four SCC lesions gave false-negative or precancerous lesion results by cytology but positive results by RT-PCR for VEGF and/or endostatin mRNA expression. CONCLUSION: Transcription levels of VEGF and endostatin by RT-PCR may be an adjunct to cytology screening for early detection of cervical carcinomas and may determine the progressive potentiality of individual lesions, especially in high-risk patients.
Assuntos
Citodiagnóstico , Endostatinas/isolamento & purificação , RNA Mensageiro/biossíntese , Displasia do Colo do Útero/diagnóstico , Fator A de Crescimento do Endotélio Vascular/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Transcrição Gênica , Displasia do Colo do Útero/patologiaRESUMO
The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration (Cmax) of repaglinide (P=0.003) in SLCO1B1*1b homozygotes (P=0.015) and SLCO1B1*15 carriers (P=0.031). Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity (AUC0â∞) of repaglinide (P=0.091). There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the Cmax of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported.
Assuntos
Carbamatos/farmacocinética , Transportadores de Ânions Orgânicos/genética , Piperidinas/farmacocinética , Quinolinas/farmacologia , Área Sob a Curva , Povo Asiático , Glicemia/efeitos dos fármacos , Glicemia/genética , Carbamatos/sangue , Estudos Cross-Over , Interações Medicamentosas , Genótipo , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipoglicemiantes/sangue , Hipoglicemiantes/farmacologia , Transportador 1 de Ânion Orgânico Específico do Fígado , Masculino , Transportadores de Ânions Orgânicos/metabolismo , Piperidinas/sangue , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The aim of this study was to analyze the amplification of the human telomerase gene (TERC) in cervical specimens by fluorescence in situ hybridization (FISH), and FISH findings were compared with cytologic and histologic diagnoses. Slides prepared from 123 liquid-based preparations from cervical specimens with cytologic diagnoses of negative for squamous intraepithelial lesion or malignancy (n=20), atypical squamous cells of undetermined significance (n=22), low-grade squamous intraepithelial lesion (n=55), high-grade squamous intraepithelial lesion (n=21), or invasive cervical carcinomas (n=5) were analyzed for the amplification of TERC using a 2-color FISH probe. The results of the cytologic analysis and those of concurrent or subsequent biopsies were compared with the FISH findings. Results showed that amplification of TERC was significantly associated with both cytologic and histologic diagnoses (P<0.05). Patients with high-grade squamous intraepithelial lesion or squamous cell carcinoma cytology diagnoses had significantly higher percentages of cells with the amplification of TERC than did patients with low-grade squamous intraepithelial lesion, ASC-US, and negative for squamous intraepithelial lesion or malignancy (P<0.005). FISH can be performed on cervical liquid-based preparations to detect the amplification of TERC. This test may be an adjunct to cytology screening, early detection of cervix neoplasm, and may determine the progressive potential of individual lesions, especially in high-risk patients.
Assuntos
Telomerase/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Feminino , Amplificação de Genes , Histocitoquímica , Humanos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Telomerase/metabolismo , Displasia do Colo do Útero/enzimologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: The liquid-based cytological test (LCT) is successfully and widely used to assess cervical cytology. This study aimed to compare the cytological findings and diagnostic sensitivity of LCT with those of the pick-and-smear (PS) method for diagnosing lung cancer. METHODS: Sputum specimens from 101 patients diagnosed with lung cancer were studied. RESULTS: LCT slides showed decreased areas of cell monolayers, a clearer background and distinct, stereoscopic cytological features. The LCT had a significantly higher diagnostic sensitivity for lung cancer (80.2%) than the PS method (63.4%, P < 0.05), particularly for small cell lung carcinoma (P < 0.05). Combination of the LCT with the conventional PS method showed significantly higher diagnostic sensitivity for the detection of adenocarcinoma (80.6%) compared with the PS method alone (55.6%, P < 0.05). CONCLUSIONS: LCT is a useful and easily performed technique that can be widely applied, and is suitable for mass screening for the early diagnosis of lung cancer.
Assuntos
Citodiagnóstico/métodos , Neoplasias Pulmonares/prevenção & controle , Programas de Rastreamento/métodos , Manejo de Espécimes/métodos , Escarro/citologia , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Diagnóstico Precoce , Humanos , Neoplasias Pulmonares/patologia , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/patologia , Coloração e Rotulagem/métodosRESUMO
BACKGROUND: Osteosarcoma is one of the most common primary malignant tumors of bone with poor prognosis. TNF-related apoptosis inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) cytokine family. TRAIL induces apoptosis in various tumor cell lines but is not found to be cytotoxic to many normal cell types in vitro. We investigated the cytotoxic activity of TRAIL and chemotherapeutic agents, including methotrexate (MTX), doxorubicin (DOX) and cisplatin (CDDP), on established osteosarcoma cell line--S-732. METHODS: OS-732 cells were incubated with chemotherapeutic agents MTX, DOX and CDDP at various peak plasma concentrations (PPC), 0.1PPC, 1PPC and 10PPC, alone or with 100 ng/ml of TRAIL for 24 hours or 48 hours. MTT was used to evaluate the cytotoxic activity of different agents on OS-732. The apoptosis proportion was assayed by flow cytometry. Cellular morphologic changes were observed by phase contrast microscope, scan electron microscope, and transmission electron microscope. RESULTS: The inhibitory rate was (24.438 +/- 3.414)% with TRAIL of 100 ng/ml for 24 hours. The cells were responsive to DOX and CDDP with a dose-effect relationship (P < 0.05). In OS-732 cells, DOX and CDDP cooperated synergistically with TRAIL when incubated the cells with them for 24 hours (the combined inhibitory rate is (58.360 +/- 2.146)% and (54.101 +/- 2.721)%, respectively). TRAIL alone or drugs alone induced the apoptosis rate was less than 25% (P < 0.05). However, the combination of TRAIL and MTX did not present synergistic effects on OS-732 cells (P > 0.05, compared with TRAIL alone). CONCLUSIONS: Osteosarcoma OS-732 cells were not responsive to TRAIL-induced apoptosis. DOX and CDDP sensitize osteosarcoma OS-732 cells to TRAIL-induced apoptosis. The combination of TRAIL and MTX presented no synergistic effects on killing OS-732 cells.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/ultraestrutura , Linhagem Celular Tumoral , Sinergismo Farmacológico , Citometria de Fluxo , Humanos , Microscopia de Contraste de Fase , Osteossarcoma/patologia , Osteossarcoma/ultraestruturaRESUMO
Atmospheric ultrafine particles (UFPs) were measured with fast mobility particle sizer(FMPS) in Hangzhou, during March 2011 to February 2012. The number concentration and size distribution of UFPs associated with meteorology were studied. The results showed that the number concentration of UFPs was logarithmic bi-modal distribution, and the seasonal levels presented winter > summer > spring> autumn. The highest monthly average concentration was 3.56 x 10(4) cm-3 in December and the lowest was 2.51 x 10(4) cm-3 in October. The seasonal values of count medium diameter(CMD) were spring > winter > autumn > summer. The highest monthly average CMD was 53. 51 nm in April and the lowest was 16.68 nm in June. Meteorological factors had effects on concentration of UFPs.
Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Atmosfera , China , Cidades , Monitoramento Ambiental , Tamanho da PartículaRESUMO
To investigate the removal efficiency of synthetic wastewater and characteristics of simultaneous nitrification and denitrification (SND) performances, a new type of moving bed membrane bioreactor (MBMBR) had been developed by using carriers instead of activated sludge in membrane bioreactor (MBR). Results showed that good organics removal and SND performances was achieved during the 67 d experimental period. COD, ammonium and total nitrogen removal efficiencies of MBMBR remained 88.3%-99.2%, 72.1%-99.8% and 62.0%-96.3% respectively as influent COD were 573.5-997.7 mg/L and ammonium nitrogen were 45.5-99.2 mg/L. Moreover, batch experiments results showed the optimum DO for nitrogen removal was 1 mg/L, ammonium and total nitrogen removal efficiencies were 100% and 60.0%, respectively. Aerobic denitrification may occur in biofilm system. When DO concentration was 3 mg/L and the organic carbon source was abundant, 99.0% total nitrogen removal efficiency and 99.8% SND efficiency was achieved in batch experiment. The microstructure of biofilm was examined using SEM. Results showed that some cavities were present, which would be favorable to enhance substrate and oxygen to transfer from the bulk to the interior of biofilm.
Assuntos
Biofilmes , Reatores Biológicos , Nitratos/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Aerobiose , Membranas Artificiais , Nitratos/metabolismo , Nitrogênio/isolamento & purificação , Nitrogênio/metabolismoRESUMO
The performances of A/O-MBR/RO system for the removal of nitrogen and COD were investigated. Result indicated that most organic was removed in the A/O-MBR and the average removal efficiency was 95.6%. The water quality of RO effluent which in terms of TOC < 0.9 mg x L(-1), TN < 12.65 mg x L(-1), total rigidity < 0.038 mol x L(-1), total alkalinity < 14.6 mg x L(-1) could meet the water quality requirements for the town wastewater reuse. The average removal efficiency of organic was almost unaffected by COD/N, but the process of TN removal was affected by COD/N. TN removal was primarily based on simultaneous nitrification and denitrification (SND) process occurred in the aerobic zone and the average removal efficiency of TN was 89.4% with average COD/N of 10.2. Both aerobic SND and conventional biological nitrification/denitrification contributed to nitrogen removal, the average removal efficiency of TN was 72%, 74% with average COD/N of 7.1 and 5.6. The fouling cake layer formed on the RO membrane surface was observed by scanning electric microscopy. The membrane fouling was characterized by Fourier transform infrared spectroscopy technique which showed that the major components of the foulants were soluble microbe products.
Assuntos
Reatores Biológicos/microbiologia , Carbono/isolamento & purificação , Nitrogênio/isolamento & purificação , Compostos Orgânicos/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Membranas ArtificiaisRESUMO
A membrane bioreactor (MBR) was developed successfully to carry out partial nitrification process. Temperature, and dissolved oxygen (DO) were investigated as the factors which may affect the results. It has been proved that the optimal operational parameters were at 35 degrees C, ammonia loading 0.45 kg x (m3 x d)(-1) and < 0.5 mg/L, respectively, with the effluent NO3(-) -N concentration below 20 mg x L(-1) and rho(NO2(-) -N)/rho(NH4(+) -N) ratio being close to 1.0. It is not observed severe membrane fouling during all the experiment. Fluorescence in situ hybridization analysis indicated that aerobic ammonium oxidizers were the dominant population, and nitrite-oxidizing bacteria were inhibited. The microbiological community analysis further provided the necessary biological information for the realization of partial nitrification.