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1.
Angew Chem Int Ed Engl ; 63(26): e202402568, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38650435

RESUMO

The inefficient conversion of lead iodide to perovskite has become one of the major challenges in further improving the performance of perovskite solar cells fabricated by the two-step method. Herein, the discontinuous lead iodide layer realized by introduction of a polyfluorinated organic diammonium salt, octafluoro-([1,1'-biphenyl]-4,4'-diyl)-dimethanaminium (OFPP) iodide which does not form low-dimensional perovskites, can enable the satisfactory conversion of lead iodide into perovskite, leading to meliorated crystallinity and enlarged grains in the OFPP modulated perovskite (OFPP-PVK) film. Combined with the effective defect passivation, the OFPP-PVK films show enhanced charge mobility and suppressed charge recombination. Accordingly, the OFPP-based perovskite solar cells exhibit a champion efficiency of 24.76 % with better device stability. Moreover, a superior efficiency of 21.04 % was achieved in a large-area perovskite module (100 cm2). Our work provides a unique insight into the function of organic diammonium additive in boosting photovoltaic performance.

2.
Foods ; 12(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38231861

RESUMO

Heat treatment is a widely applied technique in the preservation of fruits and vegetables, effectively addressing issues such as disease management, rot prevention, and browning. In this study, we investigated the impact of heat treatment at 35 °C for 24 h on the quality characteristics and disease resistance of two sweet potato varieties, P32/P (Ipomoea batatas (L.) Lam. cv 'Pushu13') and Xinxiang (Ipomoea batatas (L.) Lam. cv 'Xinxiang'). The growth in vitro and reproduction of Rhizopus stolonifer were significantly inhibited at 35 °C. However, it resumed when returned to suitable growth conditions. The heat treatment (at 35 °C for 24 h) was found to mitigate nutrient loss during storage while enhancing the structural characteristics and free radical scavenging capacity of sweet potato. Additionally, it led to increased enzyme activities for APX, PPO, and POD, alongside decreased activities for Cx and PG, thereby enhancing the disease resistance of sweet potato against soft rot. As a result, the heat treatment provided a theoretical basis for the prevention of sweet potato soft rot and had guiding significance for improving the resistance against sweet potato soft rot.

3.
RSC Adv ; 12(54): 35445-35451, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36540255

RESUMO

Highly efficient removal of Hg(ii) has been previously achieved through the adsorption by functionalized covalent organic frameworks (COFs). Among these COFs, thioether groups need to be deliberately introduced into the pores of COFs through either a bottom-up synthesis or post-synthesis strategy. Herein, we report a simple mercury removal strategy that used a stable alkynyl (-C[triple bond, length as m-dash]C-) based covalent organic framework (TP-EDDA COF) as an adsorbent for Hg(ii) removal. Sulfur vapor was first adsorbed by the TP-EDDA COF due to the van der Waals interaction between adsorbed sulfur and alkynyl groups. The Hg(ii) removal capability was then evaluated for the sulfur loaded TP-EDDA COF. Our results exhibited a good Hg(ii) removal performance for the sulfur loaded TP-EDDA COF. It was deduced that s⋯π interaction between sulfur atom and the alkynyl groups of the COF skeleton caused an increase in the electron density of sulfur and the electronegative sulfur atoms acted as a soft acid to accept soft-basic Hg(ii). This strategy provides a convenient platform for COFs to cope with environmental issues.

4.
Front Psychol ; 13: 1010471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312056

RESUMO

The present study investigated the influence of literacy environment on the performance of writing narratives for primary school students. Two hundred and fifty Chinese children participated in this study. There were 146 third graders (71 boys and 75 girls) and 104 fifth graders (53 boys and 51 girls). Results showed that children's writing abilities differed at the word level and sentence level between third grade and fifth grade. Formal literacy experience (parent teaching of characters) predicted the writing performance of third graders, while informal literacy experience (the visiting frequency of various places) predicted the writing performance of fifth graders. After controlling the effect of reading efficiency on the writing skills, the prediction of formal and informal literacy experiences on the writing performance remained. The results suggest the importance of formal and informal literacy experiences on the writing development of primary school students.

5.
RSC Adv ; 12(8): 4874-4882, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35425518

RESUMO

Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers that make these materials suitable for use as excellent scaffold in heterogeneous catalysis. Here we synthesize a layered two-dimensional (2D) COF (TADP-COF) through the condensation reaction between four-branched 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) and linear 2,5-dihydroxyterephthalaldehyde (Dha) and 1,4-phthalaldehyde (PA) building blocks. Porphyrin units, imine and hydroxyl groups together with imines can provide wide coordination sites for metal docking. Using a programmed synthetic procedure, Cu(ii) ions first coordinated with the imine groups in conjunction with their adjacent hydroxyl groups, and porphyrin units and subsequently added Pd(ii) ions occupied the remaining imine sites in the space between adjacent COF layers. The bimetallic Pd(ii)/Cu(ii)@TADP-COF showed high catalytic activity in a one-pot coupling/oxidation cascade reaction in water. The high surface area, one-dimensional (1D) open channel structure and predesigned catalytic active sites of this material make it ideal candidate for use as heterogeneous catalyst in a wide range of catalytic reactions.

6.
Andrologia ; 53(6): e14067, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33861880

RESUMO

Prostate cancer, the second most common cancer found in male over the world, was estimated to have 191,930 new cases and 33,330 deaths in 2020 in the United States. Prostate cancer is very common in male, about 12.1% of men will acquire this cancer in their lifetime, and a higher risk was reported in older men and African American men. Gene deregulations have been found to be extensively associated with cancer development. To gain further insight into how gene deregulation affects prostate cancer, we analysed three gene profiling datasets of prostate cancer from Gene Expression Omnibus (GEO) applying bioinformatic tools in our study. Firstly, we identified common differently expressed genes (DEGs) shared by the three gene profiling datasets, constructed protein-protein interaction network and determined top 10 hub genes. Further DEGs validation in TCGA and Human Protein Atlas Database identified AMACR as the core gene. We then analysed the role of AMACR in prostate cancer cell lines and found that AMACR-knockdown resulted in the decreased cell proliferation and increased apoptosis. These results suggest an oncogenic role of AMACR in prostate cancer, and it could be a potential biomarker for the diagnosis of prostate cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Idoso , Detecção Precoce de Câncer , Perfilação da Expressão Gênica , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/genética , Mapas de Interação de Proteínas
7.
Nat Commun ; 11(1): 3846, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737301

RESUMO

Fermi liquids (FLs) display a quadratic temperature (T) dependent resistivity. This can be caused by electron-electron (e-e) scattering in presence of inter-band or Umklapp scattering. However, dilute metallic SrTiO3 was found to display T2 resistivity in absence of either of the two mechanisms. The presence of soft phonons as possible scattering centers raised the suspicion that T2 resistivity is not due to e-e scattering. Here, we present the case of Bi2O2Se, a layered semiconductor with hard phonons, which becomes a dilute metal with a small single-component Fermi surface upon doping. It displays T2 resistivity well below the degeneracy temperature in absence of Umklapp and inter-band scattering. We observe a universal scaling between the T2 resistivity prefactor (A) and the Fermi energy (EF), an extension of the Kadowaki-Woods plot to dilute metals. Our results imply the absence of a satisfactory understanding of the ubiquity of e-e T2 resistivity in FLs.

8.
Pathol Res Pract ; 216(4): 152882, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32113795

RESUMO

AIMS: The aim of this study was to explore HER2 status and characteristics in biopsy specimens of gastric cancer (GC) in Chinese population. METHODS AND RESULTS: A total of 27,787 biopsy specimens of GC from 103 hospitals were obtained. Immunohistochemistry (IHC) staining of HER2 was performed. Overall HER2 IHC positive rate was 11.2 %. HER2 positive rate elevated with the increase of age in total patients and both genders. The rates were 7.1 %, 8.1 %, 9.0 %, 10.9 %, 11.8 %, 12.6 %, and 12.1 % when patient age was ≤30, 31-40, 41-50, 51-60, 61-70, 71-80, and >80, respectively (P < 0.001). In male, the rates were 6.5 %, 8.4 %, 9.6 %, 11.5 %, 12.4 %, 13.3 %, and 12.1 % (P < 0.001). In female, the rates were 7.4 %, 7.9 %, 8.0 %, 9.0 %, 9.6 %, 10.6 %, and 11.9 % (P = 0.128). The changes in male were more dramatic than in female (P < 0.001). Furthermore, the proportion of the intestinal type GCs increased with age in total patients and both genders (P < 0.001), and in male the changes were more dramatic (P < 0.001). While the proportion of the diffuse type showed the opposite tendency to that of the intestinal type (P < 0.001). HER2 IHC positive rate showed a positive correlation with the proportion of the intestinal type (r=0.986, P < 0.001), and a negative correlation with the proportion of the diffuse type (r=0.984, P < 0.001). CONCLUSIONS: The HER2 IHC positive rate showed age variation in biopsy specimens of GC. In male the variation was more dramatic than in female. The variation of HER2 positive rate can be attributed to the age variation of the Lauren subtypes.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/análise , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/metabolismo , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Estudos Retrospectivos , Adulto Jovem
9.
Onco Targets Ther ; 12: 5135-5142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303766

RESUMO

Background: Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a third-generation synthetic anthracycline, was accepted as a feasible alternative compared with the standard first-line chemotherapy for previously untreated ED-SCLC. While, the efficacies of these amrubicin-based regimens are unsatisfactory. Aim: Our meta-analysis was performed to assess the efficacy and toxicity of first-line therapy comparing AMR and chemotherapy in patients with ED-SCLC. Methods: Electronic databases were searched for eligible trials updated on November 2018. Randomized-controlled trials assessing the efficacy and safety of AMR in ED-SCLC were included, of which the interested results were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: A total of 6 randomized controlled trials were included in this analysis. There are no significant differences in OS (OR=1.03, 95% CI=0.66-1.60, P=0.91), PFS (OR=1.2, 95% CI=10.77-1.88, P=0.41) or ORR (OR=1.31, 95% CI=0.90-1.92, P=0.16) with AMR (OR=0.90, 95% CI=0.76-1.05, P=0.17). The most common treatment-related AEs in the AMR group are leukopenia (OR=3.13, 95% CI=1.22-7.99, P=0.02) and neutropenia (OR=3.25, 95% CI=1.38-7.65, P=0.007). Fatigue, anemia, nausea, vomiting, diarrhea the difference between the two groups had no statistical significance. Conclusion: The results of our analysis indicated that AMR therapy demonstrated non-inferiority to the standard first-line chemotherapy for previously untreated ED-SCLC. Whether it can be accepted as an alternative regimen to the standard first-line chemotherapy is still warranted.

10.
J Med Chem ; 61(20): 8947-8980, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29870668

RESUMO

DNA topoisomerase II (topo II) is an important enzyme involved in DNA replication, recombination, and repair. Despite the popular applications of topo II inhibitors in cancer therapy, there is still an urgent need to upgrade topo II inhibitors to cope with drug resistance and severe adverse effects. Accordingly, novel topo II catalytic or multitarget topo II inhibitors are gaining more attention and make it possible to ease the toxic limitations of topo II poisons. In this review, medicinal chemistry approaches are mainly discussed toward the development of potent topo II inhibitors with low toxicities.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Descoberta de Drogas/métodos , Inibidores da Topoisomerase II/farmacologia , Animais , Biocatálise , Química Farmacêutica , DNA Topoisomerases Tipo II/química , Humanos
11.
Mini Rev Med Chem ; 18(5): 392-413, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29090665

RESUMO

Among the family of nitrogen-containing heterocycles, quinoxalinone (or quinoxalin-2-one) core, characterized by pyrazin-2(1H)-one fused to benzene ring at two adjacent carbon atoms, has been frequently found in a variety of pharmacologically active compounds with biological or pharmaceutical applications. It was gratifying that a larger part of these bioactive quinoxalinone-based derivatives has entered various clinical trials, which in turn hastens the synthetic versatility and also initiates various derivatization of quinoxalinone scaffold. In this review, we highlighted the newly emerged quinoxalinone- based derivatives or analogues, with the emphasis of their biological applications and structure-activity analysis covering literatures in recent years.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Neoplasias/tratamento farmacológico , Quinoxalinas/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Bactérias/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Fungos/efeitos dos fármacos , Humanos , Estrutura Molecular , Quinoxalinas/síntese química , Quinoxalinas/química
12.
Adv Mater ; 28(46): 10211-10216, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27723115

RESUMO

Polyaniline/graphene hydrogel composites with a macroscopically phase-separated structure are prepared. The composites show high specific capacitance and excellent rate performance. Further investigation demonstrates that polyaniline inside the graphene hydrogel has low rate performance, thus a phase-separated structure, in which polyaniline is mainly outside the graphene hydrogel matrix, can enhance the rate performance of the composites.

13.
Eur J Med Chem ; 124: 311-325, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27597408

RESUMO

XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds (e.g. 13a and 13b) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert-butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA (kDNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b, 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization.


Assuntos
Desenho de Fármacos , Simulação de Acoplamento Molecular , Peptidomiméticos/síntese química , Peptidomiméticos/farmacologia , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , DNA/metabolismo , DNA Topoisomerases Tipo II/química , DNA Topoisomerases Tipo II/metabolismo , Humanos , Camundongos , Metástase Neoplásica , Peptidomiméticos/química , Peptidomiméticos/metabolismo , Conformação Proteica , Quinoxalinas/química , Quinoxalinas/metabolismo , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Bioorg Med Chem ; 24(9): 2125-36, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27039251

RESUMO

As our ongoing work on research of gelatinase inhibitors, an array of hydrazide-containing peptidomimetic derivatives bearing quinoxalinone as well as spiro-heterocyclic backbones were designed, synthesized, and assayed for their in vitro enzymatic inhibitory effects. The results demonstrated that both the quinoxalinone (series I and II) and 1,4-dithia-7-azaspiro[4,4]nonane-based hydrazide peptidomimetics (series III) displayed remarkably selectivity towards gelatinase A as compared to APN, with IC50 values in the micromole range. Structure-activity relationships were herein briefly discussed. Given evidences have validated that gelatinase inhibition may be contributable to the therapy of HIV-1 infection, all the target compounds were also submitted to the preliminary in vitro anti-HIV-1 evaluation. It resulted that gelatinase inhibition really has positive correlation with anti-HIV-1 activity, especially compounds 4m and 7h, which gave enhanced gelatinase inhibition in comparison with the positive control LY52, and also decent anti-HIV-1 potencies. The FlexX docking results provided a straightforward insight into the binding pattern between inhibitors and gelatinase, as well as the selective inhibition towards gelatinase over APN. Collectively, our research encouraged potent gelatinase inhibitors might be used in the development of anti-HIV-1 agents. And else, compounds 4m and 7h might be promising candidates to be considered for further chemical optimization.


Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Azidas/farmacologia , Gelatinases/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Peptidomiméticos , Fármacos Anti-HIV/química , Desenho de Fármacos
15.
Bioorg Med Chem ; 24(8): 1840-52, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26968648

RESUMO

Inhibition of VEGFR-2 kinase has been highlighted as one of the well-defined strategies to suppress tumor growth via blockade of angiogenesis. Guided by the principles of bioisosteric replacement and pharmacophoric fragment migration, a series of novel quinoxalinone derivates were designed, synthesized and evaluated for their VEGFR-2 inhibitory potencies. Among them, compounds 7c, 8b, 8c, 8e and 10b displayed antiangiogenic abilities via the in vitro tube formation assay (cellular level) and ex vivo rat aortic ring assay (tissue level) at a low concentration (0.1 µM). By means of in vivo zebrafish embryo model, two (Z)-3-(2-(pyridin-4-yl)vinyl)quinoxalinone derivates 8c and 8e showed significant antiangiogenesis effects, suggesting they have potentials to be developed into antiangiogenesis agents via further structural optimization. Moreover, these two compounds also demonstrated potent inhibition toward VEGFR-2 and B-raf kinases in a low concentration (1 µM). A possible interpretation of our evaluation result has been presented by a molecular docking study by docking representative compound 8c with VEGFR-2.


Assuntos
Inibidores da Angiogênese/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Neovascularização Fisiológica/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Peixe-Zebra
16.
Curr Med Chem ; 23(10): 1000-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26860998

RESUMO

Tumor angiogenesis has always been a major gap for effective cancer therapy. Interruption of aberrant angiogenesis by specific inhibitors targeting receptor tyrosine kinases (RTKs) has been of great interests to medicinal chemists. Among the factors that are involved in tumor angiogenesis, vascular endothelial growth factor receptor-2 (VEGFR-2) is validated as the most closely related factor which can drive angiogenesis through binding with its natural ligand VEGF. The well-validated VEGF-driven VEGFR-2 signaling pathway can stimulate many endothelial responses, including increasing vessel permeability and enhancing endothelial cell proliferation, migration and differentiation. Consequently, circumventing angiogenesis by VEGFR-2 inhibitors represents a promising strategy for counteracting various VEGFR-2-mediated disorders as well as drug resistance. Over the past decades, a considerable number of novel small molecular VEGFR-2 inhibitors have been exploited with diverse chemical scaffolds. Especially, recent frequently launched inhibitors have declared their research values and therapeutic potentials in oncology. Still, the antiangiogenesis based treatment remains an ongoing challenge. In this review, a comprehensive retrospective of newly emerged VEGFR-2 inhibitors have been summarized, with the emphasis on the structure-activity relationship (SAR) investigation, and also binding patterns of representative inhibitors with biotargets. On the basis of all of this information, varied strategies for developing potent VEGFR-2 inhibitors and the future prospect of the clinical application of antiangiogenic inhibitors are discussed hereby.


Assuntos
Inibidores da Angiogênese/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
ACS Appl Mater Interfaces ; 8(7): 4724-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26830192

RESUMO

Flexible solid-state supercapacitors attract more and more attention as the power supply for wearable electronics. To fabricate such devices, the flexible and economical current collectors are needed. In this paper, we report the stainless steel fabrics as the current collector for high-performance graphene-based supercapacitors. The stainless steel fabrics have superior properties compared with the widely used flexible current collectors. The flexible supercapacitors show large specific capacitance of 180.4 mF/cm(2), and capacitance retention of 96.8% after 7500 charge-discharge cycles. Furthermore, 96.4% of the capacitance is retained after 800 repeating stretching-bending cycles. The high performance is related to the excellent conductivity, good mechanical flexibility, and high electrochemical stability of the stainless steel fabrics. The achievement of such high-performance and flexible supercapacitor can open up exciting opportunities for wearable electronics and energy storage applications.

18.
Adv Mater ; 28(8): 1703-8, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26678843

RESUMO

2D ultrathin aluminum oxide (2D-Al2O3) nanosheets are prepared by duplicating graphene oxide. An amorphous precursor of the hydroxide of aluminum is first deposited onto graphene oxide sheets, which are then converted into 2D-Al2 O3 nanosheets by calcination, while the graphene oxide is removed. The 2D-Al2O3 nanosheets have a large specific surface area and a superior adsorption capacity to fluoride ions.

19.
Mol Cancer ; 13: 225, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25262009

RESUMO

BACKGROUND: Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca(2+)-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer. METHODS: The mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan-Meier method and Cox's proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro. RESULTS: 85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines. CONCLUSION: Our study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Trombospondinas/genética , Trombospondinas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Citoproteção , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos
20.
J Cancer Res Clin Oncol ; 140(12): 2143-56, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25009318

RESUMO

PURPOSE: (1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor-cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer. METHODS: We detected 26 SNPs of the genes in gastric cancer patients from the Chinese Han population by Sequenom technique and performed expression of OPN in combination with CD44 in 243 tissues samples of the cases by tissue microarray and immunohistochemistry (IHC). RESULTS: We found that the minor alleles of OPN rs4754C>T and OPN rs9138C>A remained strongly associated with decreased gastric cancer risk (P = 1.53 × 10(-4), odds ratio (OR) 0.642, 95 % confidence interval (CI) 0.511-0.808 and P = 1.59 × 10(-4), OR 0.642, 95 %CI 0.510-0.809). OPN variant rs1126772A>G and CD44 variant rs353639A>C significantly contributed to elevated risk of gastric cancer (P = 0.042, OR 1.279, 95 % CI 1.008-1.622 and P = 0.047, OR 1.334, 95 % CI 1.003-1.772). Haplotypes of OPN and CD44 variants significantly influenced risk of gastric cancer. Clinical data indicated that rs4754 and rs9138 of OPN were significantly associated with smoking (P = 0.029, OR 0.343, 95 % CI 0.127-0.926 and P = 0.029, OR 0.343, 95 %CI 0.127-0.926) and OPN rs1126772 revealed associations with tumor-node-metastasis (TNM) stage (P = 0.025, OR 1.765, 95 % CI 1.073-2.905) and tumor differentiation (P = 0.031, OR 1.722, 95 % CI 1.049-2.825). OPN expression was observed in 133 of the 243 cases (54.7 %) by IHC and was correlated with serosa invasion (P = 0.013), TNM stage (P = 0.003) and lymph node metastasis (P = 0.002). CD44 expression was found in 92 of the 243 cases (37.9 %) and was associated with tumor size (P = 0.005) and lymph node metastasis (P = 0.023), respectively. The OPN expression displayed a positive association with CD44 (P = 0.01, r s = 0.164). CONCLUSIONS: We found that the polymorphisms rs4754, rs9138 and rs1126772 of OPN gene and rs353639 of CD44 gene were significantly associated with gastric cancer. Our IHC data indicated that interaction of OPN and CD44 protein would promote progression and metastasis of gastric cancer.


Assuntos
Predisposição Genética para Doença , Receptores de Hialuronatos/genética , Osteopontina/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia
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