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Oncotarget ; 8(3): 5603-5618, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27901498


Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer. We show that VEGF-C triggers the activation of KRAS/MAPK signaling to increase YAP1 and downstream Slug expression, which are suppressed by an anti-VEGFR3 (VEGF receptor 3) peptide, a specific peptide targeting VEGFR3. The VEGF-C-induced migration, invasion and stemness of skin cancer cells are also abrogated by the anti-VEGFR3 peptide. Based on these data, we reveal the role of the VEGF-C/VEGFR3-mediated KRAS/MAPK-YAP1/Slug pathway in skin cancer progression and propose that the VEGF-C/VEGFR3 axis is a promising target for the anti-VEGFR3 peptide.

Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/fisiologia , Neoplasias Cutâneas/patologia , Movimento Celular/fisiologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo
Chemistry ; 21(44): 15686-91, 2015 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-26350587


Herein, potential-tunable Na2 Ni1-x Cux Fe(CN)6 nanoparticles with three-dimensional frameworks and large interstitial spaces were synthesized as alternative cathode materials for aqueous sodium-ion batteries by controlling the molar ratio of Ni(II) to Cu(II) at ambient temperature. The influence of the value of x on the crystalline structure, lattice parameters, electrochemical properties, and charge transfer of the resultant compound was explored by using powder X-ray diffractometry, density functional theory, cyclic voltammetry, galvanostatic charge-discharge techniques, and Bader charge analysis. Of the various formulations investigated, that with x=0.25 delivered the highest reversible capacity, superior rate capability, and outstanding cycling performance. These attributes are ascribed to its unique face-centered cubic structure for facile sodium-ion insertion/extraction and the strong interactions between Cu and N atoms, which promote structural stability.

Dermatol Ther ; 28(6): 351-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26088165


Inguinal lymph node dissection (ILND) for skin cancer is associated with a high incidence of wound complications. The traditional skin approaches are associated with a high risk of wound/flap necrosis of the inguinal skin, which leads to wound dehiscence and wound infection. We report a novel approach for ILND without inguinal skin incision for patients with invasive extramammary Paget disease (EMPD) to minimize the wound complications inherent in conventional ILND. We totally performed this procedure in 3 patients with invasive EMPD with inguinal nodal metastases. No patient had complications, including flap necrosis, wound dehiscence, or wound infection. Our novel surgical approach would retain the vascular supply because there was no inguinal skin incision, preventing postoperative wound complications. In addition, ILND was easily performed with satisfactory exposure of the surgical field. However, the number of patients was small and the follow-up period was short. Further evaluation of a larger case series with longer follow-up is essential to investigate the effect, safety, and indications for this novel approach.

Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Doença de Paget Extramamária/cirurgia , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Invasividade Neoplásica , Doença de Paget Extramamária/secundário , Neoplasias Cutâneas/patologia , Retalhos Cirúrgicos , Resultado do Tratamento
Arch Toxicol ; 87(1): 167-78, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22864849


Chrysin, apigenin, and luteolin are flavones that differ in their number of hydroxyl groups in the B ring. In this study, we investigated the protection by chrysin, apigenin, and luteolin against tert-butyl hydroperoxide (tBHP)-induced oxidative stress and the possible mechanisms involved in rat primary hepatocytes. Chrysin, apigenin, and luteolin dose-dependently up-regulated the protein expression of heme oxygenase 1 (HO-1) and glutamate cysteine ligase (GCL) catalytic (GCLC) and modifier subunit (GCLM) and increased the intracellular glutathione (GSH) content and the ratio of GSH to oxidized GSH. Among the flavones studied, chrysin showed the greatest induction of HO-1, GCLC, and GCLM protein expression and GSH content. Cellular reactive oxygen species production induced by tBHP was attenuated by pretreatment with chrysin, apigenin, and luteolin (P < .05), and this protection was reversed by the GCL inhibitor l-buthionine-S-sulfoximine and the HO-1 inhibitor zinc protoporphyrin. Chrysin, apigenin, and luteolin activated extracellular signal-regulated protein kinase 2 (ERK2), nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, nuclear Nrf2-antioxidant responsive element (ARE) binding activity, and ARE-dependent luciferase activity. Both ERK2 and Nrf2 siRNAs attenuated chrysin-induced HO-1, GCLC, and GCLM protein expression. Taken together, these results suggest that chrysin, apigenin, and luteolin inhibit tBHP-induced oxidative stress by up-regulating HO-1, GCLC, and GCLM gene transcription via the ERK2/Nrf2/ARE signaling pathways in rat primary hepatocytes.

Apigenina/farmacologia , Flavonoides/farmacologia , Glutamato-Cisteína Ligase/genética , Heme Oxigenase (Desciclizante)/genética , Hepatócitos/efeitos dos fármacos , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apigenina/química , Células Cultivadas , Relação Dose-Resposta a Droga , Flavonoides/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Hepatócitos/metabolismo , Luteolina/química , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Sprague-Dawley , Elementos de Resposta , Regulação para Cima/efeitos dos fármacos , terc-Butil Hidroperóxido/farmacologia
Free Radic Biol Med ; 51(11): 2073-81, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21964506


Butein and phloretin are chalcones that are members of the flavonoid family of polyphenols. Flavonoids have well-known antioxidant and anti-inflammatory activities. In rat primary hepatocytes, we examined whether butein and phloretin affect tert-butylhydroperoxide (tBHP)-induced oxidative damage and the possible mechanism(s) involved. Treatment with butein and phloretin markedly attenuated tBHP-induced peroxide formation, and this amelioration was reversed by l-buthionine-S-sulfoximine [a glutamate cysteine ligase (GCL) inhibitor] and zinc protoporphyrin [a heme oxygenase 1 (HO-1) inhibitor]. Butein and phloretin induced both HO-1 and GCL protein and mRNA expression and increased intracellular glutathione (GSH) and total GSH content. Butein treatment activated the ERK1/2 signaling pathway and increased Nrf2 nuclear translocation, Nrf2 nuclear protein-DNA binding activity, and ARE-luciferase reporter activity. The roles of the ERK signaling pathway and Nrf2 in butein-induced HO-1 and GCL catalytic subunit (GCLC) expression were determined by using RNA interference directed against ERK2 and Nrf2. Both siERK2 and siNrf2 abolished butein-induced HO-1 and GCLC protein expression. These results suggest the involvement of ERK2 and Nrf2 in the induction of HO-1 and GCLC by butein. In an animal study, phloretin was shown to increase GSH content and HO-1 expression in rat liver and decrease carbon tetrachloride-induced hepatotoxicity. In conclusion, we demonstrate that butein and phloretin up-regulate HO-1 and GCL expression through the ERK2/Nrf2 pathway and protect hepatocytes against oxidative stress.

Chalconas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glutationa/biossíntese , Heme Oxigenase (Desciclizante)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Floretina/farmacologia , Animais , Tetracloreto de Carbono/farmacologia , Células Cultivadas , Glutationa/genética , Glutationa/metabolismo , Heme Oxigenase (Desciclizante)/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , terc-Butil Hidroperóxido/farmacologia
Appl Opt ; 50(9): C368-72, 2011 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-21460966


The process of fabricating photonic crystals comprised of alternately stacked high- and low-index dielectric materials on periodic substrates to form zigzag films is called the autocloning technique. In this study, we have fabricated TiO2/SiO2 two-dimensional polarization filters by using electron beam gun evaporation with ion-beam-assisted deposition. The shape of the zigzag structure is preserved, and the total thickness is 8 µm. The symmetric structural design can be utilized as an antireflection coating applied to reduce ripples and achieve a 200 nm working wavelength range.