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1.
Invest New Drugs ; 39(4): 949-960, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33534026

RESUMO

As a potential cancer therapy, we developed a recombinant adenovirus named Ad-VT, which was designed to express the apoptosis-inducing gene (apoptin) and selectively replicate in cancer cells via E1a manipulation. However, how it performs in bladder cancer remains unclear. We examined the antitumor efficacy of Ad-VT in bladder cancers using CCK-8 assays and xenograft models. Autophagy levels were evaluated by western blotting, MDC staining, and RFP-GFP-LC3 aggregates' analyses. Here, we report the selective replication and antitumor efficacy (viability inhibition and apoptosis induction) of Ad-VT in bladder cancer cells. Using xenograft tumor models, we demonstrate that its effects are tumor specific resulting in the inhibition of tumor growth and improvement of the survival of mice models. Most Importantly, Ad-VT induced a complete autophagy flux leading to autophagic cancer cell death through a signaling pathway involving AMPK, raptor and mTOR. Finally, we suggest that treatment combination of Ad-VT and rapamycin results in a synergistic improvement of tumor control and survival compared to monotherapy. This study suggests that Ad-VT can induce selective autophagic antitumor activities in bladder cancer through the AMPK-Raptor-mTOR pathway, which can be further improved by rapamycin.


Assuntos
Adenoviridae/genética , Autofagia/genética , Terapia Viral Oncolítica/métodos , Neoplasias da Bexiga Urinária/terapia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteínas do Capsídeo/genética , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Regulatória Associada a mTOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Bexiga Urinária/genética , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Huan Jing Ke Xue ; 42(1): 38-44, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372455

RESUMO

To reveal the pollution characteristics and the health risks of the trace heavy metals in the atmospheric particles in Baoding, Hebei province, PM2.5 samples were collected using a middle volume sampler, and the mass concentrations of V, Cr, Mn, Co, Ni, Cu, Zn, As, Cd, and Pb in the samples were determined by microwave digestion-inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that the PM2.5 concentration in Baoding ranged from 16.84-476.2 µg·m-3. During sampling, 65 samples were above the second-level standard of the Ambient Air Quality Standards (GB 3095-2012) by 54.2%. The most heavy metal elements showed higher levels in nighttime than during the daytime, except for except for Ni, Mn, and Co. Obvious seasonal variation was found with the trend of winter > autumn > spring > summer. The enrichment factors for Cu, Zn, Pb, and Cd were more than 1.5, indicating that those metals mainly came from anthropogenic emissions, such as traffic sources. Health risk assessment results indicated that the non-carcinogenic risk of heavy metals in PM2.5 in Baoding was small, and the carcinogenic risk resulting form As, Cr, Cd, and Co was greater for adults than for children.


Assuntos
Poluição do Ar , Metais Pesados , Adulto , Poluição do Ar/análise , Criança , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Material Particulado/análise , Medição de Risco
3.
Huan Jing Ke Xue ; 37(4): 1230-9, 2016 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-27548941

RESUMO

Accurate measurement of organic carbon (OC) and elemental carbon (EC) in atmospheric fine particulate is an important scientific basis for studying the formation and source apportionment of carbonaceous aerosol. The selection of different analysis programs will lead to difference in the OC and EC concentrations, and further result in the misjudgment of the results. The OC and EC concentrations observed using three temperature protocols including RT-Quartz ( R) , NIOSH 5040 (N) and Fast-TC (F) were compared and analyzed in combination with the degree of air pollution in Beijing. The results showed that there was no significant difference in the TC (TC = OC + EC), OC and EC concentrations observed using R, N and F protocols and certain deviation was found among the TC (TC = OC + EC) , OC and EC concentrations. For TC, the results observed using R protocol were 5% lower than those using N protocol; hut 1% higher than those using F protocol. For OC, the results obtained using R were 9% lower than those using N protocol and 1% higher than those using F protocol. For EC, the results obtained using R were 20% higher than those using N protocol and 11% lower than those using F protocol. The variation coefficients for TC, OC and EC obtained based on R protocol were less than the other two temperature protocols under different air quality degrees. The slopes of regression curves of TC, OC and EC between on-line analysis using R protocol and off-line analysis were 1.21,1. 14 and 1.35, respectively. The correlation coefficients of TC, OC and EC were 0.99, 0.99 and 0.98, respectively. In contrast with the Black carbon ( BC) concentrations monitored by multi-angle absorption spectrophotometer (MAAP), the EC concentrations measured by on-line OC/EC analyzer using R protocol were obviously lower. When the BC concentrations were less than or equal to 8 gg*m3, the EC/BC ratio was 0.39. While the EC/BC ratio was 0.88, when the BC concentrations were greater than 8 ggm3. The variation trends of EC and BC concentrations were similar, while systematic error existed between the results obtained using those two instruments.


Assuntos
Poluentes Atmosféricos/análise , Carbono/análise , Monitoramento Ambiental , Aerossóis/análise , Atmosfera/análise , Pequim , Fuligem/análise , Temperatura
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