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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1344-1347, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418405

RESUMO

Abstract  Numerous studies have confirmed that abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is one of the most common induction mechanisms of T-ALL. In recent years, many literature report that multiple abnormally expressed microRNAs (miRNAs) can participate in the development of T-ALL by regulating the PI3K/AKT signaling pathway. For example, overexpression of miR-19 and miR181a can activate the PI3K/AKT signaling pathway, which leads to the development of T-ALL and induction of chemotherapy drug resistance, as well as the low expression of miR-26b and miR-29a. Apart from the inhibitors and traditional Chinese medicines that target the PI3K/AKT signaling pathway, regulation of the expression of the corresponding miRNA may also be a potential treatment protocol for T-ALL. The mechanisms of PI3K/AKT signaling pathway involved in the development of T-ALL, the role of miRNAs in the PI3K/AKT signaling pathway and the targeted therapy based on this signaling pathway are summarized briefly in this review.


Assuntos
Leucemia de Células T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais
2.
Org Lett ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31403313

RESUMO

Atom transfer radical addition and Heck-type reaction between alkenes and ethyl iododifluoroacetate by using organophosphine compounds as catalysts have been developed. The reaction proceeds under mild reaction conditions with excellent functional group tolerance and high chemo- and regioselectivities. Mechanistic study indicates that the reaction might be initiated via noncovalent interactions between an organophosphine catalyst and a carbon-iodine bond.

3.
Ying Yong Sheng Tai Xue Bao ; 30(8): 2575-2582, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418180

RESUMO

The mixed plantation of precious tree species Dalbergia odorifera and Santalum album is an important model for the development of plantations in South China. Based on an experiment with four treatments, i.e., CK (without any treatment), weeding, fertilization, weeding+fertilization, we investigated the effects of weeding and fertilization on soil net mineralization rate, net nitrification rate, net ammonification rate, and nitrogen leaching rate. Among the four treatments, the maximum net nitrogen mineralization rate in the 0-10 cm soil layer was 18.92 and 18.13 mg·kg-1·month-1 in spring and autumn, respectively; the maximum nitrification rate was 20.35 and 18.85 mg·kg-1·month-1in spring and autumn, respectively; the maximum ammonium mineralization rate was 0.22 and 0.26 mg·kg-1·month-1 in summer and winter, respectively; the maximum nitrogen leaching was 15.98 mg·kg-1·month-1 in autumn and 86.69 mg·kg-1·year-1 in the whole year. The treatments of weeding, fertilization, weeding+fertilization reduced net mineralization rate and net nitrification rate. The annual nitrogen mineralization decreased by 26.2%, 16.1% and 6.3%, respectively, and the annual nitrogen nitrification decreased by 17.1%, 16.6%, and 1.4%, respectively. Moreover, the treatments of weeding, fertilization, weeding+fertilization inhibited soil ammonium accumulation and reduced annual nitrogen leaching by 25.2%, 8.6%, and 6.1%, respectively. Compared with weeding, fertilization and weeding+fertilization, seasonal factors had more significant effects on soil nitrogen mineralization and leaching. Weeding, fertilization and weeding+fertilization decreased soil nitrogen nitrification and ammonification to a certain extent, reduced soil nitrogen mineralization and leaching loss, which contribute to the preservation of soil fertility and nitrogen accumulation.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 877-886, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204948

RESUMO

OBJECTIVE: To evaluate the coagulation function of children with Henoch-Schönlein purpura (HSP) by thromboelastography (TEG) and conventional coagulation tests (CCTs), and to explore the correlation and consistency of the 2 test methods. METHODS: A total of 468 children with HSP were selected from January 2017 to December 2017 in Beijing Children's Hospital, Capital Medical University. The TEG and CCTs data were analyzed to evaluate coagulation function of children with HSP, meanwhile, the coagulation results were analysed the superiority of the 2 test methods was compared by Pearson correlation and Kappa consistency analysis. RESULTS: There were no clinically significant abnormalities practically in HSP children by TEG and CCTs analysis, except for D-dimer level was elevated (t=9.15, P<0.001). There were no significant changes for coagulation data from, sex comparison of HSP children (P>0.05 all), but the coagulation reaction time (R), blood clot formation time (K), α-Angle, CI value, fibrinogen, D-dimer and anti-thrombin III in HSP children with different age groups showed difference (P<0.05 all), and the blood in children aged 0-2 years old tended to be hypercoagulable. The TEG indexes demonstrated no significant difference in coagulation function of children with HSP each other (P>0.05). However, CCTs data showed that the blood in children with severe kidney involvement were hypercoagulable. Comparision results of the correlation and consistency of TEG and CCTs in detecting coagulation function of HSP children showed that R was weakly correlated with prothrombin time (PT), International Normalized Ratio (INR) and activated partial thromboplastin time (APTT). There were weak correlation between K, α-Angle and Fib (0.1<|r|<0.4 all). There was no obvious consistency between them each other (kappa<0.4 all). CONCLUSION: The overall changes in coagulation function in children with HSP are not obvious, but the hyperfibrinolysis in hypercoagulable state may exists. Furthermore, younger age and severe kidney involvement may cause hypercoagulation in HSP children. The weakly correlation and consistency of TEG and CCTs in detecting coagulation function of HSP children are furtherly confirmation, and the 2 test methods may be irreplaceable.


Assuntos
Púrpura de Schoenlein-Henoch , Tromboelastografia , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos
5.
Acta Crystallogr C Struct Chem ; 75(Pt 6): 643-649, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31166915

RESUMO

Compared with the monomorphic type of ligand, combining mixed ligands in one coordination polymer offers greater tunability of the structural framework. Employment of N-heterocyclic ligands and aromatic polycarboxylates is an effective approach for the construction of metal-organic frameworks (MOFs). Two new coordination polymers incorporating both 2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole (imb) and benzenedicarboxylic acid isomers, namely, catena-poly[[[di-µ-chlorido-bis[(2-carboxybenzoato-κ2O1,O1')cadmium(II)]]-bis{µ-2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole-κ2N:N'}] dihydrate], {[Cd(C8H5O4)Cl(C11H10N4)]·H2O}n, (I), and poly[[aqua(µ2-benzene-1,3-dicarboxylato-κ3O1,O1':O3){µ2-2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole-κ2N:N'}cadmium(II)] dihydrate], {[Cd(C8H4O4)(C11H10N4)(H2O)]·2H2O}n, (II), have been prepared and structurally characterized by single-crystal X-ray diffraction. In polymer (I), imb ligands bridge CdII ions, forming a one-dimensional chain, and 2-carboxybenzoate anions coordinate to the CdII ions in a terminal fashion. Polymer (II) exhibits a two-dimensional network structure in which imb ligands and the benzene-1,3-dicarboxylate anions join CdII ions co-operatively. This indicates that changing of the aromatic dicarboxylic acids can result in polymers with different compositions and architectures. Moreover, their IR spectra, PXRD (powder X-ray diffraction) patterns, thermogravimetric analyses and fluorescence properties were also investigated.

6.
Chem Commun (Camb) ; 55(26): 3705-3708, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30775746

RESUMO

A palladium-catalyzed cross-coupling of unactivated alkylzinc reagents with 2-bromo-3,3,3-trifluoropropene (BTP) has been developed, which was used as a key step to prepare a series of trifluoromethylated and difluoromethylated amino acids that are of great interest in peptide/protein based chemical biology. The advantages of the synthesis of these fluorinated amino acids are synthetic simplicity and diversity from a simple and readily available key intermediate α-trifluoromethylalkene-containing amino acid, providing a facile route for applications in medicinal chemistry and life science.

8.
Thorac Cancer ; 10(3): 533-542, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30666800

RESUMO

BACKGROUND: Approximately 8.3-15.9% of patients with clinical stage I non-small cell lung cancer are subsequently shown to have lymph node metastasis. However, the clinical characteristics of patients with lymph node metastasis in China are not fully understood. METHODS: This is a multicenter retrospective analysis of pathological T1 non-small cell lung cancer patients who underwent surgical resection from 2 January 2014 to 27 December 2017. Clinical and pathological information was collected with the assistance of the Large-scale Data Analysis Center of Cancer Precision Medicine-LinkDoc database. The clinical and pathological factors associated with lymph node metastasis were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 10 885 participants (51.6% women; 15.3% squamous cell carcinoma) were included in the analysis. The median age was 60.0 years (range 12.9-86.6 years). A total of 1159 patients (10.6%) had metastases in mediastinal nodes (N2), and 640 patients (5.9%) had metastasis in pulmonary lymph nodes (N1). Most patients had T1b lung cancer (4766, 43.8%). Of the patients, 3260 (29.9%) were current or former smokers. The univariate and multivariate analyses showed that younger age, squamous cell carcinoma, poor differentiation, larger tumor size, carcinoembryonic antigen level ≥5 ng/mL, and vascular invasion (+) were significantly associated with higher percentages of lymph node metastases (P < 0.001 for all). CONCLUSION: This real-world study showed the significant association of lymph node metastasis with age, tumor size, histology and differentiation, carcinoembryonic antigen levels, and status of vascular invasion. Female patients with T1a adenocarcinoma in the right upper lobe barely had lymph node metastasis.

9.
J Thorac Oncol ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30521970

RESUMO

INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival (DFS) in patients with resected early-stage epidermal growth factor receptor (EGFR)-mutation positive non-small cell lung cancer (NSCLC) in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure, sites and data of first treatment failure were recorded. A post-hoc analysis of treatment failure patterns, which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat (mITT) patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the CNS in the gefitinib group (29/106 [27.4%]), extracranial metastases were most frequent in the VP group (32/87 [36.8%]). Temporal distribution analysis demonstrated lower tumor recurrence with gefitinib than with VP 0-21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9-15 months with VP and 24-30 months with gefitinib. The highest peak for CNS metastases post-surgery occurred after 12-18 months with VP and 24-36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant TKIs may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.

10.
J Am Chem Soc ; 140(45): 15149-15152, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30381942

RESUMO

The significance of identifying the fundamental mechanism of interactions between adjacent catalytic active centers has long been underestimated. Utilizing density functional theory calculations, we demonstrate controllable cooperative interaction between two nearby Fe centers embedded on nitrogenated graphene aided by CO adsorption. The interconnected adjacent Fe atoms respond cooperatively to CO molecules with communicative structural self-adaption and electronic transformation. The adsorbed CO changes not only the spin of the active site it is attached to but also that of its adjacent site. Consequently, the two adjacent Fe atoms feature unique oscillatory long-range spin coupling. Our theoretical investigation suggests cooperative communication between adjacent active sites on a single-atom catalyst is nontrivial.

11.
Chem Commun (Camb) ; 54(97): 13662-13665, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30382250

RESUMO

Fluoroalkylated enaminones, such as trifluridine and 5-trifluoromethyluracil, have widespread applications in pharmaceuticals and agrochemicals. Although these kinds of pharmaceutical agent often bear CF3 and perfluoroalkyl motifs in the core structure, access to such analogues typically requires multi-step synthesis. Here, we report a mild, metal-free and operationally simple strategy for the direct perfluoroalkylation of uracils, cytosines and pyridinones through a visible-light induced pathway from perfluoroalkyl iodides. This photochemical transformation features synthetic simplicity, mild reaction conditions without any photoredox catalyst, and high functional group tolerance, providing a facile route for applications in medicinal chemistry.

12.
Int J Mol Med ; 42(6): 3640, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30320334

RESUMO

The authors have requested that their research article entitled 'Piezo1 protein induces the apoptosis of human osteoarthritis­derived chondrocytes by activating caspase­12, the signaling marker of ER stress' published in International Journal of Molecular Medicine 40, 845­853, 2017, be retracted from the journal. Following the publication of this article, an interested reader drew to our attention that certain of the figures, or figure parts, published in this article contained data that also appeared at around the same time in a publication featuring several of the same authors in Experimental Cell Research: Li XF, Leng P, Zhang Z and Zhang HN: 'The Piezo1 protein ion channel functions in human nucleus pulposus cell apoptosis by regulating mitochondrial dysfunction and the endoplasmic reticulum stress signal pathway'. Exp Cell Res 358: 377­389, 2017. Though these studies were performed in osteoarthritic chondrocytes and nucleus pulposus cells, respectively, the authors realize that their submission to International Journal of Molecular Medicine was in breach of the requirement that a submitted paper should represent an (entirely) original study presenting novel work, and that none of the data therein had been previously submitted to or accepted by any other journal. Therefore, following the advice of the Editor, they are going to retract the paper from International Journal of Molecular Medicine. All the named authors agree to this retraction. They sincerely apologize for this mistake, thank the reader of their article who drew this matter to their attention, and regret any inconvenience this has caused. [the original article was published in International Journal of Molecular Medicine Med 40: 845-853, 2017; DOI: 10.3892/ijmm.2017.3075].

13.
Artigo em Inglês | MEDLINE | ID: mdl-30124870

RESUMO

This study aimed to report the case of a patient diagnosed with pulmonary sequestration accompanied by an intermittent haematemesis as the initial and life-threatening symptom. Emergent surgical intervention finally confirmed a rare direct fistula formation between the arterial blood supply of pulmonary sequestration and the oesophagus, which led to intermittent upper gastrointestinal haemorrhage. To our knowledge, this is the first case reported with this kind of fistula formation.

14.
Chem Asian J ; 13(21): 3239-3245, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30151862

RESUMO

Motivated by the development of transition-metal-nitrogen-carbon (TM-N-C) materials for catalysts and molecular electronics, we investigated the electronic and magnetic properties of TMN4 -graphene materials with different central atoms (TM=Ti, V, Cr, Mn, Fe, Co, Ni and Cu) and different concentrations. The first-principles results show that a widely tunable magnetic moment in the range from 0 to 4 µB can be obtained in this kind of material by varying the central TM atom, and a regular transition of the electronic property from metallic to half-metallic and to semiconducting characteristics is observed in MnN4 -graphene upon changing the concentration. We find that the peculiar relationship between the electronic characteristics of graphene and its lattice parameters plays a decisive role in determining the electronic and magnetic properties. Our findings are useful for the design of TM-N-C materials for catalysis, spintronics, and molectronics.

15.
Zhongguo Gu Shang ; 31(6): 550-555, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29945412

RESUMO

OBJECTIVE: To explore the expression characteristics of new mechanosensitive ion channel Piezo1 protein in stress models of human degenerative chondrocytes. METHODS: The stress stimulation model of human degenerative chondrocytes in vitro was constructed. Multi-channel cell stretch stress loading system FX-4000T was used to treat chondrocytes. According to the results of pre-test, the loading frequency of 0.5 Hz and the cell elongation of 20% were loaded. According to cell processing time, it was divided into 0 h, 2 h, 12 h, 24 h and 48 h mechanical stress group. The RT-PCR and Western-blot were used to test the expression of the Piezo1, also the Laser scanning confocal microscope (LSCM) was used to test the intensity of the fluorescence of the Piezo1. RESULTS: (1)The result of the RT-PCR showed that the expression of the Piezo1 in the 2 h group was higher than the 0 h group(F=13.917, q=0.037 1, P<0.05). The expression of the piezo1 in the 24 h group was the highest. While the expression of the piezo1 in the 48 h group was lower than the expression of the piezo1 in the 24 h group(F=13.917, q=0.049 5, P<0.05). (2)The result of the Western-blot showed that the 2 h group was higher than the 0 h group(F=19.341, q=0.037 1, P<0.05). The expression of the 24 h had the highest expression which was higher than the 48 h group(F=19.341, q=0.017 7, P<0.05). (3)The Piezo1 protein was extensively expressed in the cytoplasm and nucleus of the nucleus pulposus cells. And with the increase of stress processing time, the fluorescence intensity of the protein also increased. CONCLUSIONS: In human degeneration cartilage cells, the new mechanio sensitive ion channel Piezo1 protein has a trace expression. After loading periodic mechanical tensile force, the expression of Piezo1 protein increases with time dependence.

16.
Biochem Biophys Res Commun ; 501(3): 758-764, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29758195

RESUMO

Metastasis is the major cause for the death of patients with colorectal cancer (CRC). Anoikis resistance enhances the survival of cancer cells during systemic circulation, thereby facilitating secondary tumor formation in distant organs. miR-124 is a pleiotropically tumor suppressive small non-coding molecule. However, its role and mechanism in the regulation of cancer cell anoikis are still unknown. Here, we found that overexpression of miR-124 promotes anoikis of CRC cells in vitro and in vivo. In silico analysis and the experimental evidence supported that ITGA3 is a bona fide target of miR-124. Moreover, we identifies that ITGA3 plays a critical role in the regulation of anoikis sensitivity in CRC cells. Finally, our analysis in TCGA datasets demonstrates that high levels of ITGA3 are closely associated with poor prognosis in CRC patients. Collectively, we establish a functional link between miR-124 and anoikis susceptibility and provide that a miR-124/ITGA3 axis could be a potential target for the treatment of metastatic CRC.

17.
Mol Med Rep ; 17(6): 7575-7584, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29620244

RESUMO

Research has identified that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) possess large benefits for adenocarcinoma (ADC), although little benefit for squamous cell carcinoma (SCC). The aim of the present study was to investigate the percentage of patients with SCC with the EGFR mutations subset and the benefits of EGFR TKIs in SCC. In the present study, the EGFR mutations subset was detected with an amplification refractory mutation system in 1,359 clinical SCC tissues. The association of the EGFR mutations subset with clinicopathological parameters was evaluated using the Mann­Whitney U test, and Kruskal­Wallis H. Kaplan­Meier survival analysis was used to estimate the effect of the EGFR mutations subset on SCC patient survival rates. A total of 94 out of 1,359 SCC patients were identified as having EGFR mutations, an EGFR mutation rate of 6.92%. The EGFR mutations subset in the 94 cases was identified as follows: 37.2% (35/94) in exon 19; 39.4% (37/94) in L858R; 5.3% (5/94) in T790M; 4.3% (4/94) in G719X; 2.1% (2/94) in L861Q; and 11.7% (11/94) in other mutations. Kaplan­Meier survival analysis identified that the differentiation, pathological tumor, node, metastasis stage, lymph node metastasis and distant metastases were significantly associated with patients' survival (P>0.05; log­rank test), and no significant difference was observed between TKI therapy and chemotherapy in terms of patient survival rates (P>0.05). In addition, the overall discordant rate of the EGFR mutations subset in SCC patients was relatively low. Due to the non­significant difference between TKI therapy and chemotherapy in terms of patient survival and the lower discordance rate of the EGFR mutations subset in SCC patients, EGFR TKIs could be a recommended treatment for SCC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêutico
18.
Nat Prod Res ; : 1-5, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29421923

RESUMO

One new compound, colletotrichine B (1), was produced by the fungal Colletotrichum gloeosporioides GT-7. The structure of 1 was elucidated on the basis of spectroscopic analysis and X-ray crystallographic analysis. Monoamine oxidase (MAO), acetylcholinesterase (AChE) and phosphoinositide 3-kinase (PI3Kα) inhibitory activity of 1 was also evaluated. Compound 1 showed only AChE inhibiting activity with IC50 value of 38.0 ± 2.67 µg/mL.

19.
Lancet Oncol ; 19(1): 139-148, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29174310

RESUMO

BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Vimblastina/análogos & derivados , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , China , Cisplatino/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , Adulto Jovem
20.
J Asian Nat Prod Res ; 20(1): 92-100, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28675939

RESUMO

A new homoisoflavanone, (3R)-5-hydroxy-7-methoxyl-3-(2'-hydroxy-4'- methoxybenzyl)-chroman-4-one (1), together with six known analogs, were isolated from the rhizomes of Polygonatum sibiricum. Their structures were elucidated on the basis of extensive spectroscopic analysis. All compounds were tested for their estrogenic activity using the MCF-7 estrogenresponsive human breast cancer cell lines. At a dose of 0.1 µmol/L, compounds 1-7 exhibited significant proliferative effects on MCF-7 cells compared with E2. The molecular docking study results indicated that the activity of compounds 3, 5, 6, and 7 may be the binding with ERR.


Assuntos
Medicamentos de Ervas Chinesas/química , Estrogênios/isolamento & purificação , Estrogênios/farmacologia , Polygonatum/química , Rizoma/química , Estrogênios/química , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Células MCF-7 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
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