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1.
J Org Chem ; 89(1): 281-290, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38109762

RESUMEN

A visible-light-driven photoredox dialkylation of styrenes with α-carbonyl alkyl bromides and pyridin-1-ium salts for the synthesis of polysubstituted 1,4-dihydropyridines is reported. This reaction enables the formation of two new C(sp3)-C(sp3) bonds in a single reaction step and provides a strategy that employs pyridin-1-ium salts as the functionalized alkylating reagents via dearomatization to directly trap the resulting alkyl radicals from radical addition of alkenes and then terminate the alkene dialkylation.

2.
J Org Chem ; 89(5): 2885-2894, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38355424

RESUMEN

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve. Herein, nickel-catalyzed reductive cross-coupling reactions between propargyl acetates and substituted vinyl chlorosilanes for the synthesis of tetrasubstituted silylallenes are described. Therein, metallic zinc is a crucial reductant that effectively enables two electrophilic reagents to selectively construct C(sp2)-Si bonds. Additionally, a Ni-catalyzed reductive mechanism involving a radical process is proposed on the basis of deuteration-labeled experiments.

3.
Neoplasma ; 69(3): 657-669, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35293765

RESUMEN

Colorectal cancer (CRC) is a common malignant tumor with high morbidity and mortality, and significant heterogeneity among patients. In this study, we aimed to explore the role and mechanism of CLK2 in CRC, a kinase that phosphorylates SR proteins involved in splicing. Based on the analysis from The Cancer Genome Atlas (TCGA) dataset and tissue microarray, we found that CLK2 was upregulated in CRC tissues and associated with a higher tumor stage and poorer overall survival. Consistent with the bioinformatics analysis, the functional experiments validated that CLK2 acted as a tumor-promoting factor in CRC progression. CLK2 knockdown suppressed aggressive cell proliferation, migration, and invasion in vitro, as well as restrained tumor growth in vivo. In terms of mechanism, we found that the Wnt/ß-catenin signaling pathway was responsible for the CLK2-induced CRC progression, based on the results of pathway enrichment analysis and subsequent experimental validation. Thus, our study, for the first time, identified the role of CLK2 in CRC development and provided a compelling biomarker for targeted therapy in CRC treatment.


Asunto(s)
Neoplasias Colorrectales , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Vía de Señalización Wnt , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Centers for Disease Control and Prevention, U.S. , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Quinasas/genética , Estados Unidos , Vía de Señalización Wnt/genética , beta Catenina/metabolismo
4.
Org Biomol Chem ; 16(17): 3177-3180, 2018 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-29645051

RESUMEN

A convenient and efficient indium-catalyzed approach to synthesize alkenyl iodides has been developed through direct iodoalkylation of alkynes with alcohols and aqueous HI under mild conditions. This catalytic protocol offers an attractive approach for the synthesis of a diverse range of alkenyl iodides in good to excellent yields.

5.
J BUON ; 22(4): 1004-1010, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28952220

RESUMEN

PURPOSE: We conducted a network meta-analysis to evaluate the efficacy and toxicity of cetuximab and nimotuzumab in the treatment of advanced nasopharyngeal carcinoma (NPC). METHODS: A systematic literature search was performed though Pubmed, Embase, Cochran Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and Wanfang databases. Totally, 19 randomized controlled trials (RCTs) (n=1201) met the study selection criteria and were incorporated in this network meta-analysis. RESULTS: Compared with cetuximab, the results of network meta-analysis indicated that nimotuzumab may achieve higher complete remission rate (CRR) or overall remission rate (ORR) of the primary tumor, but no difference was noticed in 1- and 2-year overall survival (OS) rate and certain toxicities such as myelosuppression, radiodermatitis, mucositis and gastrointestinal reactions. Although nimotuzumab increased the 3-year OS rate, compared with cetuximab, this result needs to be interpreted cautiously because of the studies' heterogeneity. CONCLUSION: Even though we didn't find significant difference between cetuximab and nimotuzumab in terms of survival outcomes, nimotuzumab is more advantageous in short-term efficacy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Cetuximab/uso terapéutico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Cetuximab/efectos adversos , China , Humanos , Carcinoma Nasofaríngeo/mortalidad , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia
6.
Zhongguo Zhong Yao Za Zhi ; 41(9): 1596-1601, 2016 May.
Artículo en Zh | MEDLINE | ID: mdl-28891605

RESUMEN

The paper is aimed to study the distribution, population density, soil conditions and community characteristics of accompanying plants' in Enshi sub-regional different areas, with a typical habitats investigation method. The results showed that the wild Panax japonicus mainly distributed in moist places under the forests, by streams, or secondary forests of high grass, within east longitude 29°-30°, north latitude 108°-110°and about 1 000-15 00 meters above sea level. The soils were mainly tide soil and humus with yellow-brown soil, yellow soil and red soil, and the humus thickness was5-30 centimeter, pH 6.0-6.8, the moisture content of 16.8%-24.2%, soil bulk density of 1.39-2.12. Its geographical vegetation types were mainly evergreen coniferous forest, evergreen-deciduous mixture broad leaved forest and evergreen coniferous forest mixed deciduous broad-leaved forest, including three levels community structure of arbors, shrubs and herbaceous; Its accompanying plants reached 86 families, 118 genera, 134 species of seed plants, the arbors included 15 families, 21 genera, 26 species and the dominant species community mainly Pinaceae such as Pinus massoniana, P. tabuliformis, P. henryi and Taxodiaceae such as Cunninghamia lanceolata, Cryptomeria fortunei etc. The shrubs included 39 families, 54 genera, 62 species with the dominant species such as Camellia oleifera, Kalopanax septemlobus, Akebia trifoliata, Trachycarpusfortunei, Rhamnus globosa, Smilax corbularia and so on. The herbaceous included 32 families, 43 genera, 46 species, and Ferns such as the black-footed Dryopteris, Dryopteris crassirhizom, Coniogramme affinis, Polystichum tripteron, Adiantum pedatum, Lunathyrium acrostichoides, Woodsia ilvensis and Woodwardia japonica were dominant species. The cover layer covered a large number of lichens and mosses. The wild P. japonicus can be found among the P. massoniana, P. tabuliformis, P. henryi, lichens and mosses. These may indicate that the wild P. japonicusin Enshi requires higher demands on the ecological environment, its accompanying plants are mainly the tree layer-shrub layer-herb layer, and vertical structure is obvious. The study provides a basis for domestication and conservation of P. japonicus resources.


Asunto(s)
Ecosistema , Panax/crecimiento & desarrollo , China , Suelo , Árboles
7.
J BUON ; 20(6): 1510-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26854448

RESUMEN

PURPOSE: The objective of this study was to compare the efficacy of the conventional treatment (radiotherapy/RT and chemotherapy/CT) and the combination treatment with antiepidermal growth factor receptor (anti EGFR) monoclonal antibodies in patients with primary nasopharyngeal cancer (NPC) using meta-analysis of data retrieved from the literature. METHODS: Seven databases (Pubmed, Embase, Cochrane Library, CBM, CNKI, Wanfang,VIP) were searched. Of 537 identified articles, 12 satisfied our eligibility criteria and entered this meta-analysis. A total of 821 patients in 12 randomized controlled clinical trials (RCTs) were included in the study to compare the effect in the short-term and long-term treatment. RESULTS: The combination treatment improved the objective complete remission rate (CR) of primary NPC and the metastatic lymph nodes, and the 1-year distant metastasis-free survival (MFS) rate relative risk (RR=1.40, 95%CI:1.29-1.53, p=0.00; RR=1.29, 95%CI:1.18-1.42, p=0.00; RR%1.17, 95%CI:1.01-1.35, p=0.03, respectively). There was no difference in the 2- and 3-year MFS rate (RR=1.06, 95%CI:0.85-1.33, p=0.60 ; RR=0.87, 95%CI:0.63-1.22) p=0.43, respectively). CONCLUSION: The combination with anti EGFR monoclonal antibodies and conventional treatment (RT and/or CT) improved the short-term therapeutic effect, but this benefit disappeared after 1 year.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Nasofaríngeas/terapia , Quimioradioterapia , Terapia Combinada , Humanos , Metástasis Linfática , Neoplasias Nasofaríngeas/mortalidad , Sesgo de Publicación
8.
World J Gastrointest Surg ; 16(6): 1791-1802, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38983329

RESUMEN

BACKGROUND: Metastatic colorectal cancer (mCRC) is a common malignancy whose treatment has been a clinical challenge. Cancer-specific survival (CSS) plays a crucial role in assessing patient prognosis and treatment outcomes. However, there is still limited research on the factors affecting CSS in mCRC patients and their correlation. AIM: To predict CSS, we developed a new nomogram model and risk grading system to classify risk levels in patients with mCRC. METHODS: Data were extracted from the United States Surveillance, Epidemiology, and End Results database from 2018 to 2023. All eligible patients were randomly divided into a training cohort and a validation cohort. The Cox proportional hazards model was used to investigate the independent risk factors for CSS. A new nomogram model was developed to predict CSS and was evaluated through internal and external validation. RESULTS: A multivariate Cox proportional risk model was used to identify independent risk factors for CSS. Then, new CSS columns were developed based on these factors. The consistency index (C-index) of the histogram was 0.718 (95%CI: 0.712-0.725), and that of the validation cohort was 0.722 (95%CI: 0.711-0.732), indicating good discrimination ability and better performance than tumor-node-metastasis staging (C-index: 0.712-0.732). For the training set, 0.533, 95%CI: 0.525-0.540; for the verification set, 0.524, 95%CI: 0.513-0.535. The calibration map and clinical decision curve showed good agreement and good potential clinical validity. The risk grading system divided all patients into three groups, and the Kaplan-Meier curve showed good stratification and differentiation of CSS between different groups. The median CSS times in the low-risk, medium-risk, and high-risk groups were 36 months (95%CI: 34.987-37.013), 18 months (95%CI: 17.273-18.727), and 5 months (95%CI: 4.503-5.497), respectively. CONCLUSION: Our study developed a new nomogram model to predict CSS in patients with synchronous mCRC. In addition, the risk-grading system helps to accurately assess patient prognosis and guide treatment.

9.
Org Lett ; 26(16): 3401-3406, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38607850

RESUMEN

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

10.
Org Lett ; 25(39): 7263-7267, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37756013

RESUMEN

An electroreductive cross-coupling of prop-2-yn-1-yl acetates with chloro(vinyl)silanes for producing tetrasubstituted silylallenes is developed. The method enables the formation of a new C─Si bond through the cathodic reduction formation of the silyl radical, radical addition across the C≡C bond, the alkenyl anion intermediate formation, and deacetoxylation and represents a mild, practical route to the synthesis of silylallenes. Mechanistic studies reveal that CoCl2 acts as the mediator to promote the formation of the alkenyl anion intermediate via electron transfer.

11.
Water Res ; 229: 119395, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36463677

RESUMEN

Membrane fouling was still a challenge for the potential application of forward osmosis (FO) in algae dewatering. In this study, the fouling behaviors of Chlorella vulgaris and Scenedesmus obliquus were compared in the FO membrane filtration process, and the roles of their soluble-extracellular polymeric substances (sEPS) and bound-EPS (bEPS) in fouling performance were investigated. The results showed that fouling behaviors could be divided into two stages including a quickly dropped and later a stable process. The bEPS of both species presented the highest flux decline (about 40.0%) by comparison with their sEPS, cells and broth. This performance was consistent with the largest dissolved organic carbon losses in feed solutions, and the highest interfacial free energy analyzed by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory. The chemical characterizations of algal foulants further showed that the severe fouling performance was also consistent with a proper ratio of carbohydrates and proteins contents in the cake layer, as well as the higher low molecular weight (LMW) components. Compared with the bEPS, the sEPS was crucial for the membrane fouling of S. obliquus, and an evolution of the membrane fouling structure was found in both species at the later filtration stage. This work clearly revealed the fundamental mechanism of FO membrane fouling caused by real microalgal suspension, and it will improve our understanding of the evolutionary fouling performances of algal EPS.


Asunto(s)
Chlorella vulgaris , Microalgas , Purificación del Agua , Matriz Extracelular de Sustancias Poliméricas , Membranas Artificiales , Purificación del Agua/métodos , Ósmosis
12.
Org Lett ; 25(42): 7645-7649, 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37843412

RESUMEN

A palladium(0)-catalyzed ß-C(sp3)-H arylation of silyl prop-1-en-1-ol ethers with aryl halides for the synthesis of α,ß-unsaturated ketones is presented. In contrast to the reported ß-C(sp3)-H arylation of ketones, the chemoselectivity of this current method relies on the Pd(0) catalytic systems and reaction temperatures: While using the Pd(dba)2/DavePhos/KF system at 80 °C resulted in ß-C(sp3)-H monoarylation to produce ß-monoarylated α,ß-unsaturated ketones, harnessing the Pd(OAc)2/t-Bu XPhos/K2HPO4 system at 110 °C induced ß-C(sp3)-H diarylation to afford ß,ß-diarylated α,ß-unsaturated ketones. The method provides a versatile route that uses readily available ketone-derivatized α-nonsubstituted silyl prop-1-en-1-ol ethers as the alkene sources and is characterized by a good functional group compatibility, a broad substrate scope, and an excellent selectivity.

13.
Water Environ Res ; 84(11): 2060-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23356022

RESUMEN

Biomass char was prepared from mulberry branches by physical activation. An examination by Fourier transform infrared spectroscopy (FTIR) indicated that the functional groups of Si-O were mostly burnt out, significantly decreasing the ash content Analysis of data from a scanning electron microscope (SEM) and a Brunauer-Emmett-Teller (BET) test also revealed increased surface roughness and pore structure, which improved the adsorption capacity of biomass char after preparation. The optimum conditions for preparation were found to be pyrolysis at 700 degrees C for 30 minutes, and then activation at 750 degrees C for one hour, with 3.4% steam content for the activating agent. The prepared biomass char was then employed to adsorb ammonium, copper(II) actetate [Cu(II)] and hexavalent chromium [Cr(VI)] in a solution. The results indicated that the prepared biomass char had a better adsorptive performance than the raw material. Moreover, the removal of determinands increased along with the dosage, and the highest adsorption efficiency of ammonium, copper(II) acetate [Cu(II)] and hexavalent chromium [Cr(VI)] were found to be 20%, 100% and 50%, respectively. The adsorptions of ammonium and hexavalent chromium [Cr(VI)] can be simulated by a pseudo-second order model, while the adsorption of copper(II) acetate [Cu(II)] is better simulated by a pseudo-first order model. The adsorption isotherms of copper(II) acetate [Cu(II)] by biomass char were also investigated, and the Langmuir isotherm was found to best describe the adsorption process.


Asunto(s)
Biomasa , Carbón Orgánico , Morus , Purificación del Agua , Adsorción , Cinética , Compuestos Organometálicos/aislamiento & purificación , Compuestos de Amonio Cuaternario/aislamiento & purificación , Temperatura , Contaminantes Químicos del Agua/aislamiento & purificación
14.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(10): 830-3, 2012 Oct.
Artículo en Zh | MEDLINE | ID: mdl-23302669

RESUMEN

OBJECTIVE: To compare the efficacy between micro invasive occlusion procedure and extracorporeal circulation procedure for treating patients with simple ventricular septal defect. METHODS: Two hundred and twenty patients with simple ventricular septal defect (except subarterial ventricular septal defect) were randomly divided into micro invasive group (n = 116) and traditional cardiopulmonary bypass surgery group (n = 104). Clinical data were collected and compared at baseline and at 3, 30 and 180 days after surgery. RESULTS: Age, gender, body weight and ventricular septal defect type were similar between the two groups (all P > 0.05). Operation time and hospitalization duration were significantly shorter in the micro invasive group than the traditional cardiopulmonary bypass surgery group (all P < 0.05). The proportion of blood transfusion was less in micro invasive group than the traditional cardiopulmonary bypass surgery group [2.59% (3/116) vs. 72.12% (75/104), P < 0.01]. Three days after surgery, incidence of mild and above tricuspid insufficiency was less in micro invasive group than the traditional cardiopulmonary bypass surgery group [0.86% (1/116) vs. 2.88% (3/104), P < 0.05]. There was one patient developed mild pericardial effusion at 30 days post surgery in micro invasive group. There was no intracardiac infection in the two groups during follow-up. At 30 and 180 days post surgery, incidence of residual shunt was also less in micro invasive group than the traditional cardiopulmonary bypass surgery group [1.72% (2/116) vs. 7.69 (8/104) and 0(0/116) vs. 7.69(8/104), all P < 0.05]. After surgery for 3, 30 and 180 days, transthoracic echocardiography derived chamber size, left ventricular end-diastolic volume index and left ventricular ejection fraction were similar between the two groups (all P > 0.05). CONCLUSIONS: The efficacy is similar for patients with simple ventricular septal defect (except subarterial ventricular septal defect) using micro invasive occlusion therapy or extracorporeal circulation surgery. Micro invasive occlusion procedure can shorten operation and hospitalization time, and reduce the need for blood transfusion and risk of developing procedural-related tricuspid insufficiency and post-procedural residual shunt.


Asunto(s)
Cateterismo Cardíaco/métodos , Circulación Extracorporea , Defectos del Tabique Interventricular/cirugía , Niño , Preescolar , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos , Resultado del Tratamiento
15.
Zhonghua Xin Xue Guan Bing Za Zhi ; 39(11): 984-8, 2011 Nov.
Artículo en Zh | MEDLINE | ID: mdl-22336448

RESUMEN

OBJECTIVE: To evaluate the feasibility, safety and efficacy of transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) guided coated stent-graft implantation for patients with Stanford B aortic dissection. METHODS: In 5 patients with CT confirmed Stanford B aortic dissection, TEE and TTE were used to determine the parameters for pre-surgery diagnosis and selection of suitable coated stent. During surgery, TEE and TTE provided real-time and dynamic monitoring and guiding for precise implantation of the coated stent to effectively seal the tear of the aortic dissection. After surgery, efficacy of implanted coated stent was evaluated by TTE. RESULTS: In all 5 patients, the coated stents were successfully implanted in the true lumen, a small distal tear was not covered in 1 case. Displacement of stent-graft or new endoleak was not observed at follow-up examinations performed at 3 months post-surgery. There were no aortic perforation, renal failure, paraplegia or other complications. The medians of left ventricular ejection fraction (LVEF) in 2 days before surgery, 1 month post-surgery and 3 months post-surgery are 59.9%, 67.4% and 68.1% and the medians of fraction shortening (FS) are 31.4%, 33.7% and 39.1%. Compared with 2 days before surgery, significant increase of LVEF and FS was observed in 1 month post-surgery and 3 months post-surgery (all P < 0.05). CONCLUSION: Our results showed that echocardiography guided coated stent-graft implantation for patients with Stanford B aortic dissection was safe and effective with lower risk of complications.


Asunto(s)
Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Anciano , Ecocardiografía , Ecocardiografía Transesofágica , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Stents
16.
Circulation ; 120(4): 318-25, 2009 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-19597047

RESUMEN

BACKGROUND: Phosphoinositide 3-kinase (PI3K) p110alpha plays a key role in insulin action and tumorigenesis. Myocyte contraction is initiated by an inward Ca(2+) current (I(Ca,L)) through the voltage-dependent L-type Ca(2+) channel (LTCC). The aim of this study was to evaluate whether p110alpha also controls cardiac contractility by regulating the LTCC. METHODS AND RESULTS: Genetic ablation of p110alpha (also known as Pik3ca), but not p110beta (also known as Pik3cb), in cardiac myocytes of adult mice reduced I(Ca,L) and blocked insulin signaling in the heart. p110alpha-null myocytes had a reduced number of LTCCs on the cell surface and a contractile defect that decreased cardiac function in vivo. Similarly, pharmacological inhibition of p110alpha decreased I(Ca,L) and contractility in canine myocytes. Inhibition of p110beta did not reduce I(Ca,L). CONCLUSIONS: PI3K p110alpha but not p110beta regulates the LTCC in cardiac myocytes. Decreased signaling to p110alpha reduces the number of LTCCs on the cell surface and thus attenuates I(Ca,L) and contractility.


Asunto(s)
Contracción Miocárdica/genética , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Fosfatidilinositol 3-Quinasas/deficiencia , Fosfatidilinositol 3-Quinasas/genética , Animales , Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/fisiología , Fosfatidilinositol 3-Quinasa Clase I , Perros , Femenino , Masculino , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/fisiología
18.
Front Oncol ; 10: 1568, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33042801

RESUMEN

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

19.
Acta Pharmacol Sin ; 30(11): 1566-72, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19820718

RESUMEN

AIM: To quantitatively evaluate in vivo first-pass intestinal extraction of omeprazole and to investigate the possible involvement of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in this process in rabbits. METHODS: Pharmacokinetic parameters were examined after intraduodenal (id), intraportal venous (ipv), and intravenous (iv) administration of omeprazole at various doses to intestinal and vascular access-ported rabbits. Extraction ratios in the liver and intestinal tract were determined from the area under the plasma concentration-time curve (AUC). In addition, omeprazole was administered by id or iv to rabbits alone or 30 min after the id administration of CYP3A4 or P-gp inhibitors (ketoconazole or verapamil, respectively). RESULTS: Pharmacokinetic parameters of omeprazole were dose-dependent after id, ipv, and iv administration at various doses. After id administration of 3 mg/kg omeprazole, the hepatic and intestinal extraction ratio was 57.18%+/-2.73% and 54.94%+/-1.85%, while the value was 59.29%+/-3.14% and 54.20%+/-1.53% after given 6 mg/kg, respectively. Compared with the control group, the presence of ketoconazole (60 mg/kg) or verapamil (9 mg/kg) significantly increased the area under the plasma concentration time curve (AUC) and the peak concentration (C(max)) of id-administered omeprazole, while it had no significant effect on omeprazole administered by iv. CONCLUSION: Oral omeprazole undergoes marked extraction in the small intestine, and increased bioavailability of the drug after id administration of ketoconazole and verapamil suggests that this increase results from inhibition of CYP3A4 and P-gp function in the intestine rather than the liver.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Antiulcerosos/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Omeprazol/farmacocinética , Administración Oral , Animales , Antiulcerosos/administración & dosificación , Área Bajo la Curva , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Inyecciones Intravenosas , Intestino Delgado/metabolismo , Hígado/metabolismo , Masculino , Omeprazol/administración & dosificación , Conejos
20.
Microb Biotechnol ; 12(3): 528-543, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30884189

RESUMEN

Vermicomposting using black soldier fly (BSF) larvae (Hermetia illucens) has gradually become a promising biotechnology for waste management, but knowledge about the larvae gut microbiome is sparse. In this study, 16S rRNA sequencing, SourceTracker, and network analysis were leveraged to decipher the influence of larvae gut microbiome on food waste (FW) biodegradation. The microbial community structure of BSF vermicompost (BC) changed greatly after larvae inoculation, with a peak colonization traceable to gut bacteria of 66.0%. The relative abundance of 11 out of 21 metabolic function groups in BC were significantly higher than that in natural composting (NC), such as carbohydrate-active enzymes. In addition, 36.5% of the functional genes in BC were significantly higher than those in NC. The changes of metabolic functions and functional genes were significantly correlated with the microbial succession. Moreover, the bacteria that proliferated in vermicompost, including Corynebacterium, Vagococcus, and Providencia, had strong metabolic abilities. Systematic and complex interactions between the BSF gut and BC bacteria occurred over time through invasion, altered the microbial community structure, and thus evolved into a new intermediate niche favourable for FW biodegradation. The study highlights BSF gut microbiome as an engine for FW bioconversion, which is conducive to bioproducts regeneration from wastes.


Asunto(s)
Compostaje/métodos , Dípteros/metabolismo , Dípteros/microbiología , Alimentos , Microbioma Gastrointestinal , Animales , Biotransformación , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Larva/metabolismo , Larva/microbiología , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Administración de Residuos/métodos
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