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1.
Funct Plant Biol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34637699

RESUMO

In vascular plants, bryophytes and algae, the photosynthetic light reaction takes place in the thylakoid membrane where two transmembrane supercomplexes PSII and PSI work together with cytochrome b6f and ATP synthase to harvest the light energy and produce ATP and NADPH. Vascular plant PSI is a 600-kDa protein-pigment supercomplex, the core complex of which is partly surrounded by peripheral light-harvesting complex I (LHCI) that captures sunlight and transfers the excitation energy to the core to be used for charge separation. PSI is unique mainly in absorption of longer-wavelengths than PSII, fast excitation energy transfer including uphill energy transfer, and an extremely high quantum efficiency. From the early 1980s, a lot of effort has been dedicated to structural and functional studies of PSI-LHCI, leading to the current understanding of how more than 200 cofactors are kept at the correct distance and geometry to facilitate fast energy transfer in this supercomplex at an atomic level. In this review, we review the history of studies on vascular plant PSI-LHCI, summarise the present research progress on its structure, and present some new and further questions to be answered in future studies.

2.
Exp Biol Med (Maywood) ; : 15353702211038511, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514884

RESUMO

In breast cancer, tumor-associated macrophages with activated phenotypes promote tumor invasion and metastasis. The more aggressive mesenchymal-like breast cancer cells have a selective advantage, skewing macrophages toward the more immunosuppressive subtype. However, the mechanism underlying this shift is poorly understood. Cyclin D1b is a highly oncogenic variant of cyclin D1. Our previous study showed that non-metastatic epithelial-like breast cancer cells were highly metastatic in vivo when cyclin D1b was overexpressed. The present study determined whether cyclin D1b contributed to the interaction between breast cancer cells and macrophages. The results showed that cyclin D1b promoted the invasion of breast cancer cells in vitro. Specifically, through overexpression of cyclin D1b, breast cancer cells regulated the differentiation of macrophages into a more immunosuppressive M2 phenotype. Notably, tumor cells overexpressing cyclin D1b activated macrophages and induced migration of breast cancer cells. Further investigations indicated that SDF-1 mediated macrophage activation through breast cancer cells overexpressing cyclin D1b. These results revealed a previously unknown link between aggressive breast cancer cells and Tumor-associated macrophages, and highlighted the importance of cyclin D1b activity in the breast cancer microenvironment.

3.
Oral Dis ; 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174132

RESUMO

Adiponectin (APN) is a kind of endogenous anti-tumor adipocytokine, which exerts its function by binding to its receptors (AdipoR1 and AdipoR2). However, hyperadiponectinemia is found in some pathophysiological processes without significant protective effect, which indicates the existence of APN resistance. Here, we aimed to investigate the locoregional expression of APN in tongue squamous cell carcinoma (TSCC) tissues, and to explore the potential regulatory mechanism of APN resistance under hypoxia. Consequently, we found that the protein expression of APN and AdipoR1, but not AdipoR2, was upregulated in the early stage of TSCC and after hypoxic treatment ex vivo and in vitro. Knockdown of HIF-1α decreased the level of APN and AdipoR1, and simultaneously, HIF-1α was identified as transcriptor of the APN. Intriguingly, a regenerative feedback of HIF-1α was unexpectedly detected after application of recombinant globular APN (gAPN), which most likely contributed to the APN resistance. Furthermore, HIF-1α blockade combined with gAPN has a prominent synergistic antitumor effect, which suggested an effective amelioration in APN resistance. In all, our study revealed the possible mechanism of APN resistance under hypoxia and provides a promising strategy of bi-target treatment with APN and HIF-1α for TSCC therapy.

4.
Int J Food Microbiol ; 343: 109090, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33631606

RESUMO

Plasma-activated water (PAW) has good liquidity and uniformity and may be a promising candidate to inactivate Penicillium italicum and maintain the quality attributes of kumquat. In this study, the effect of plasma-activated water (PAW) on the viability of Penicillium italicum on kumquat and quality attributes of PAW-treated kumquats were then systematically investigated to elucidate the correlation between PAW and kumquat quality attributes. The effects of PAW on fruit decay, microbial loads, and firmness of postharvest kumquats during the 6-week storage were also investigated. The results showed that the viability of Penicillium italicum was notably inhibited by PAW on kumquats. Moreover, PAW did not significantly change the surface color of kumquats. No significant reductions in ascorbic acid, total flavonoid, and carotenoids were observed in kumquats after the PAW treatment. Results from nitrate and nitrite residue analyses showed that PAW did not leave serious nitrate and nitrite residues after treatment. The decay analysis results demonstrated that PAW has the potential to control kumquat decay and fungal contamination as well as maintain the firmness of postharvest kumquats throughout 6-week storage. Transmit electron microscope observation confirmed that PAW could cause the surface sculpturing in the skin cell wall of kumquat. The information obtained from this research may provide insight into the utilization of PAW to fight against fungal infection during the storage of citrus fruit.


Assuntos
Desinfetantes/farmacologia , Penicillium/efeitos dos fármacos , Gases em Plasma/farmacologia , Rutaceae/microbiologia , Água/farmacologia , Parede Celular/efeitos dos fármacos , Microbiologia de Alimentos , Armazenamento de Alimentos , Frutas/microbiologia , Viabilidade Microbiana/efeitos dos fármacos , Água/química
5.
Artigo em Inglês | MEDLINE | ID: mdl-32190078

RESUMO

Natural plants are considered as a huge treasure for anticancer. Amomum tsaoko, a plant of Zingiberaceae, is used widely as a food and traditional medicine in East Asia. In previous studies, Amomum tsaoko has antitumor effect on liver cancer cells, but the mechanism is not clear. Here, we demonstrated that ethanol extract from Amomum tsaoko (At-EE) could inhibit ovarian cancer and decrease angiogenesis in vivo. At-EE did not influence vascular endothelial cells directly, but decreased IL-6 and VEGF secreted by ovarian cancer cells to inhibit angiogenesis through inhibition of p-STAT3 and NF-kB activation. In addition, we demonstrated that p-STAT3 and NF-kB could adjust each other and IL-6 and VEGF also mediate p-STAT3 and NF-kB too, which created a loop. In addition, At-EE interrupted p-STAT3/NF-kB/IL-6 and VEGF loop through induced ER stress. These results reveal that p-STAT3/NF-kB/IL-6 and VEGF is a cascade amplification loop in ovarian cancer for angiogenesis, and induced ER stress can interrupt it. Taken together, this work explored the anticancer activities of Amomum tsaoko, which could be a potential therapeutic candidate in the treatment of ovarian cancer.

6.
J Sci Food Agric ; 100(8): 3297-3307, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086813

RESUMO

BACKGROUND: The content of protein components of glutinous rice significantly affects the quality of Chinese rice wine. Therefore, the effects of protein components on the quality of Chinese rice wine were investigated by adding the exogenous proteins glutelin and albumin individually or in combination RESULTS: Compared with the control, the samples with increased glutelin components exhibited improved formation of numerous alcohol esters with alcoholic and fruity representatives. The promotion rates of glutelin to total alcohols and total esters were 18% and 99%, respectively. The amount of 4-vinylguaiacol characterized by a spicy, smoky odor was reduced to 40%. Correlation analysis between chemical composition and sensory characteristics showed a significant positive correlation between umami and amino nitrogen (r = 0.935) and total amino acid content (r = 0.729). The bitterness of Chinese rice wine was related to the change of alcohol content (r = 0.689) and total soluble solid (r = 0.904). Sensory analysis revealed that the increase of the glutelin component of Chinese rice wine increased its alcoholic, fruity, and honey-like features, as well as its umami, acidity and bitterness. The increase also reduced the caramel-like, herb-like, and smoky sensory characteristics of Chinese rice wine and its Qu aroma and sweetness CONCLUSION: The protein content of glutinous rice significantly affects the quality of rice wine. The Glutelin has a significant relationship with fruity, honey, and umami flavors; the albumin has a significant relationship with medicinal, bitter, and astringent flavors. Therefore, reasonable adjustment of the glutelin content of glutinous rice can effectively improve the sensory quality of rice wine. © 2020 Society of Chemical Industry.


Assuntos
Aromatizantes/química , Glutens/química , Oryza/química , Compostos Orgânicos Voláteis/química , Vinho/análise , Aminoácidos/análise , Aminoácidos/metabolismo , China , Fermentação , Aromatizantes/metabolismo , Glutens/metabolismo , Humanos , Odorantes/análise , Oryza/metabolismo , Paladar , Compostos Orgânicos Voláteis/metabolismo
8.
Curr Med Sci ; 38(3): 467-472, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30074214

RESUMO

Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis, and is relevant to the inflammatory microenvironment. Lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to induce EMT of cancer cells through TLR4 signal. We previously reported that LPS promoted metastasis of mesenchymallike breast cancer cells with high expression of cyclin D1b. However, the role of cyclin D1b in LPS-induced EMT has not been fully elucidated. In the present study, we described that cyclin D1b augmented EMT induced by LPS in MCF-7 breast cancer cells. Cyclin D1b markedly amplified integrin αvß3 expression, which was further up-regulated under LPS stimulation. Our results showed ectopic expression of cyclin D1b promoted invasiveness of epithelial-like MCF-7 cells under LPS stimulation. Additionally, LPS-induced metastasis and EMT in MCF-7-D1b cells might depend on αvß3 expression. Further exploration indicated that cyclin D1b cooperated with HoxD3, a transcription factor promoting αvß3 expression, to promote LPSinduced EMT. Knockout of HoxD3 repressed LPS-induced EMT and αvß3 over-expression in MCF-7 cells with high expression of cyclin D1b. Specifically, all these effects were in a cyclin Dla independent manner. Taken all together, LPS up-regulated integrin αvß3 expression in MCF-7 cells with high expression of cyclin D1b and induced EMT in breast cancer cells, which highlights that cyclin D1b may act as an endogenous pathway participating in exogenous signal inducing EMT in breast cancer cells.


Assuntos
Processamento Alternativo/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclina D1/genética , Transição Epitelial-Mesenquimal/genética , Integrina alfaVbeta3/metabolismo , Lipopolissacarídeos/farmacologia , Processamento Alternativo/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Fibrinogênio/farmacologia , Proteínas de Homeodomínio/metabolismo , Humanos , Células MCF-7 , Invasividade Neoplásica , Metástase Neoplásica , Fatores de Transcrição , Transfecção , Regulação para Cima/efeitos dos fármacos
9.
Oncotarget ; 8(45): 78466-78479, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108242

RESUMO

The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo. Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo. Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro. Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.

10.
Oncol Rep ; 36(4): 2177-83, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27499367

RESUMO

An essential step in the peritoneal spread of ovarian cancer is the adhesion and implantation of tumor cells to the mesothelium layer. Integrin α5 and ß1 have been reported to mediate the initial adhesion process and to correlate with disease survival in ovarian cancer. However, the molecular mechanism of integrin α5ß1 dysregulation in tumorigenesis and metastasis remained enigmatic. In the present study, using the US NCI60 database, we identified miR-17 as a candidate regulator targeting both integrin α5 and ß1. The level of miR-17 was evidently inversely correlated with that of α5 and ß1 in ovarian cancer cell lines. Specifically, miR-17 bound directly to the 3' untranslated region (3'UTR) of α5 and ß1 and suppressed their expression. Forced expression of miR-17 led to markedly diminished adhesion and invasion of ovarian cancer cells in vitro, and notably reduced metastatic nodules inside the peritoneal cavity in in vivo SKOV3 xenografts model. Moreover, ectopic expression of miR-17 in ovarian cancer cells resulted in repressed ILK phosphorylation as well as decreased production of active matrix metalloproteinase-2 (MMP-2). Our results indicated that miR-17 hampered ovarian cancer peritoneal propagation by targeting integrin α5 and ß1. These findings supported the utility of miR-17/α5ß1 to be considered as valuable marker for metastatic potential of ovarian cancer cells, or a therapeutic target in ovarian cancer treatment.


Assuntos
Integrina alfaV/biossíntese , Integrina beta1/biossíntese , Metaloproteinase 2 da Matriz/biossíntese , MicroRNAs/genética , Neoplasias Ovarianas/genética , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfaV/genética , Integrina beta1/genética , Metaloproteinase 2 da Matriz/genética , Camundongos , MicroRNAs/biossíntese , Invasividade Neoplásica/genética , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Onco Targets Ther ; 9: 1969-79, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27103823

RESUMO

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue neoplasms that are extremely rare and are frequently associated with neurofibromatosis type 1 patients. MPNSTs are typically fatal, and there is no effective treatment so far. In our previous study, we showed that flaccidoside II, one of the triterpenoid saponins isolated from Anemone flaccida Fr. Schmidt, has antitumor potential by inducing apoptosis. In the present study, we found that flaccidoside II inhibits proliferation and facilitates apoptosis in MPNST cell lines ST88-14 and S462. Furthermore, this study provides a mechanism by which the downregulation of heme oxygenase-1 via extracellular signal-regulated kinase-1/2 and p38 mitogen-activated protein kinase pathways is involved in the apoptotic role of flaccidoside II. This study suggested the potential of flaccidoside II as a novel pharmacotherapeutic approach for MPNSTs.

12.
Cancer Lett ; 355(1): 159-67, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25193465

RESUMO

Cyclin D1b, a splice variant of the cell cycle regulator cyclin D1, holds oncogenic functions in human cancer. However, the mechanisms underlying cyclin D1b function remain poorly understood. Here we introduced wild-type cyclin D1a or cyclin D1b variant into non-metastatic MCF-7 cells. Our results show that ectopic expression of cyclin D1b promotes invasiveness of the cancer cells in a cyclin D1a independent manner. Specifically, cyclin D1b is found to modulate the expression of αvß3, which characterizes the metastatic phenotype, and enhance tumor cell invasive potential in cooperating with HoxD3. Notably, cyclin D1b promotes αvß3-mediated adhesion and invasive migration, which are associated with invasive potential of breast cancer cells. Further exploration indicates that cyclin D1b makes breast cancer cells more sensitive to toll-like receptor 4 ligand released from damaged tumor cells. These findings reveal a role of cyclin D1b as a possible mediator of αvß3 transcription to promote tumor metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Adesão Celular , Ciclina D1/metabolismo , Integrina alfaVbeta3/metabolismo , Integrina beta3/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular , Ciclina D1/genética , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Integrina alfaVbeta3/genética , Integrina beta3/genética , Ligantes , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metástase Linfática , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Fenótipo , Isoformas de Proteínas , Fatores de Tempo , Receptor 4 Toll-Like/metabolismo , Fatores de Transcrição , Transfecção
13.
Cancer Lett ; 317(2): 157-64, 2012 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-22115967

RESUMO

Intracellular HSP70 has been implicated as a cytoprotective protein, whereas the effect of extracellular HSP70 on tumor cells has not been fully understood to date. Here we report that extracellular HSPA1A, a stress-inducible member of HSP70 family, could promote tumor growth. HSPA1A promoted the proliferation of H22 hepatocarcinoma cells through TLR2 and TLR4 signaling. The effect of HSPA1A was abolished by inhibiting NF-κB. HSPA1A also augmented the apoptosis-resistance of H22 cells by activating NF-κB, thus to promote the proliferation of H22 cells in presence of mitomycin C. Furthermore, the promoting effect of HSPA1A on tumor cell proliferation was existent after the removal of HSPA1A, which might involve HSPA1A-promoted upregulation of TLR4 expression in tumor cells and release of HMGB1 from tumor cells. These findings suggest that extracellular HSPA1A functions as endogenous ligand for TLR2 and TLR4 to facilitate tumor growth.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/farmacologia , Neoplasias Hepáticas Experimentais/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Transplante Heterólogo , Carga Tumoral/efeitos dos fármacos
14.
Breast Cancer Res Treat ; 133(3): 853-63, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22042369

RESUMO

Triggering of Toll-like receptor 4 (TLR4) on tumor cells has been found to promote tumor progression by promoting tumor cell proliferation and survival. So far, however, the effect of TLR4 signaling on tumor metastasis has not been well elucidated. Here, we report that triggering of TLR4 on metastatic breast cancer cells could reciprocally regulate the expression of αvß3 and the expressions of TPM1 and maspin, and promote αvß3-mediated adhesion and invasive migration of the cells. In metastatic breast cancer cells, TLR4 signaling increased the expression of integrin αvß3 by activating NF-κB, resulting in the increased adhesion capacity of tumor cells to the ligand for αvß3, and the increased polymerization of actin and production of MMP-9 in tumor cells in response to ECM. HoxD3 was required for the up-regulation of αv and ß3 expressions by NF-κB. Moreover, TLR4 signaling increased the expression of miR-21 in breast cancer cells by activating NF-κB. Accordingly, the expressions of TPM1 and maspin were decreased at protein level, whereas the transcription activity of these genes was not influenced. Consistent with the promoting effect on αvß3-mediated adhesion and invasive migration, TLR4 signaling promoted the arrest of metastatic breast cancer cells in circulation and following invasion. The effect of TLR4 signaling could be abrogated by inhibiting NF-κB. These findings suggest that metastatic breast cancer cells could acquire higher metastatic potential due to triggering of TLR4 and activation of NF-κB in the cells, and that both TLR4 and NF-κB could be therapeutic targets for preventing metastasis of breast cancer cells.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Integrina alfaVbeta3/genética , Receptor 4 Toll-Like/genética , Animais , Neoplasias da Mama/metabolismo , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Camundongos , Camundongos Nus , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Metástase Neoplásica , Ligação Proteica , Inibidores de Proteínas Quinases/farmacologia , Serpinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fatores de Transcrição , Tropomiosina/metabolismo
15.
Food Chem ; 127(3): 1237-42, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25214120

RESUMO

Cucumber fruit were pre-treated with 25µll(-1) nitric oxide (NO) for 12h at 20°C, and then stored at 2±1°C and 95% relative humidity for 15days. Chilling injury index, membrane permeability, lipid peroxidation, superoxide anion (O2(-)) production rate, H2O2 content, activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), and DPPH-radical scavenging activity were measured. The results showed that the application of NO at 25µll(-1) was most effective in reducing CI in cucumber fruit. The treatment reduced the increases in membrane permeability and lipid peroxidation, delayed the increases in both O2(-) production rate and H2O2 content. The NO-treated fruit exhibited significantly higher activities of SOD, CAT, APX and POD and higher DPPH-radical scavenging activity than control fruit during the storage. The overall results suggest that NO enhanced chilling tolerance in cucumber fruit by improving the antioxidative defence system.

16.
Oncol Rep ; 24(3): 693-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20664975

RESUMO

T cell immunoglobulin and mucin domain-3 (Tim-3) is originally recognized as a receptor of Th1 cells. We found that Tim-3 could be expressed in endothelial cells after stimulation with tumor cell-released TLR4 ligand. Tim-3 expressed by endothelial cells does not function as the receptor of galectin-9, but mediates the interaction of endothelial cells with tumor cells. The engagement of endothelial cell-expressed Tim-3 with a non-galectin 9 putative receptor on B16 melanoma cells could trigger the NF-kappaB signaling pathway in B16 cells. The activated NF-kappaB not only promoted the proliferation of B16 cells, but also enhanced apoptosis resistance of B16 cells by up-regulating Bcl-2 and Bcl-xL and down-regulating Bax. Consistently, Tim-3 facilitated the survival of B16 cells in the blood stream, arrested in the lung and following invasion, resulted in more metastatic nodules in the lung. These findings suggest that endothelial cell-expressed Tim-3 increases tumor cell metastatic potential by facilitating tumor cell intravasation, survival in blood stream and extravasation. Thus, anti-inflammation or blockade of Tim-3 may contribute to the prevention of metastasis.


Assuntos
Células Endoteliais/metabolismo , Neoplasias Pulmonares/metabolismo , Melanoma Experimental/metabolismo , NF-kappa B/metabolismo , Receptores Virais/metabolismo , Animais , Apoptose , Células CHO , Proliferação de Células , Sobrevivência Celular , Cricetinae , Cricetulus , Proteína HMGB1/metabolismo , Receptor Celular 2 do Vírus da Hepatite A , Ligantes , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Comunicação Parácrina , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Virais/genética , Fatores de Tempo , Receptor 4 Toll-Like , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
17.
Chem Asian J ; 5(2): 309-14, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20041457

RESUMO

An efficient domino cyclization method for the construction of aza-podophyllotoxin/aza-conidendrin derivatives has been established. Reactions of different dienes with aryl halides in the presence of a palladium catalytic system produced different kinds of podophyllotoxin derivatives through a highly regioselective C-H functionalization. Treatment of dienes with aryl halides that have electron-withdrawing substituents on the phenyl ring created aza-podophyllotoxin derivatives by means of the functionalization of the C-H bonds ortho to the C-halide bonds of the incoming aryl halides. The reaction of dienes with 1-iodobenzene or aryl halides that incorporate electron-donating groups produced aza-conidendrin derivatives by means of the functionalization of both sp(3) C-H and sp(2) C-H bonds. The regioselective C-H functionalization for the formation of different pseudo-podophyllotoxin/-conidendrin derivatives is proven by analyses of the (1)H NMR spectra of the products and selective X-ray analyses of the structures of the products. Thus, the palladium-catalyzed domino cyclization of 1,6-dienes for the preparation of aza-podophyllotoxin/aza-conidendrin derivatives can be controlled by selectively controlling the C-H functionalization.


Assuntos
Compostos Aza/química , Compostos Aza/síntese química , Lignanas/química , Podofilotoxina/química , Tetra-Hidronaftalenos/química , Cristalografia por Raios X , Ciclização , Modelos Moleculares , Conformação Molecular
18.
Chemistry ; 14(10): 3110-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18257004

RESUMO

Tri- and tetracyclic heterocycle systems were constructed by a palladium-catalyzed domino reaction of linear 1,6-dienes that contain acryl groups with aryl halides through C-C coupling and aromatic C-H functionalization. Three different acrylamides have been shown to be very active for the reaction. The substituents on the aryl halides could be ethoxycarbonyl, ketyl, chloro, sulfonyl, cyano, etc. Thus, the ready accessibility of the starting materials, the wide range of compatibility of substrates including both dienes and aryl halides, and the generality of this process make the reaction highly valuable in view of the synthetic and medicinal importance of these kinds of heterocycles.


Assuntos
Alcadienos/química , Compostos Heterocíclicos/síntese química , Catálise , Cristalografia por Raios X , Ciclização , Compostos Heterocíclicos/química , Modelos Moleculares , Estrutura Molecular , Paládio/química , Estereoisomerismo
19.
Biochem Biophys Res Commun ; 367(1): 144-9, 2008 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-18162175

RESUMO

The interaction of integrin alphavbeta3 and its ligands are crucial for tumor metastasis. Recombinant CBD-HepII polypeptide of fibronectin, designated as CH50, suppressed the binding of tumor cells to ECM molecules, and abolished the promoting effect of soluble fibronectin and fibrinogen on tumor cell adhesion to ECM molecules. The underlying mechanisms involve the blockade and downregulation of alphavbeta3 and its co-receptor syndecan 1 by CH50. The activation of FAK, upregulation of cdc2, the production and activation of MMP-2 and MMP-9 by ECM molecules-stimulated tumor cells were inhibited by CH50. CH50 reduced the tumor cell arrest during blood flow, and also inhibited the invasive ability of tumor cells. The in vivo expressed CH50 suppressed the lung metastasis of circulating tumor cells, and prolonged the survival of mice after tumor cell inoculation. These findings suggest a prospective utility of CH50 in the gene therapy for prevention of tumor metastasis.


Assuntos
Fibronectinas/uso terapêutico , Terapia Genética , Integrina alfaVbeta3/antagonistas & inibidores , Metástase Neoplásica/tratamento farmacológico , Proteínas Recombinantes/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Proteína Quinase CDC2/metabolismo , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Matriz Extracelular/metabolismo , Fibrinogênio/química , Fibrinogênio/metabolismo , Fibronectinas/farmacologia , Quinase 1 de Adesão Focal/metabolismo , Integrina alfaVbeta3/genética , Integrina alfaVbeta3/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica/patologia , Proteínas Recombinantes/farmacologia , Transdução de Sinais/fisiologia , Taxa de Sobrevida
20.
Int J Cancer ; 121(1): 184-92, 2007 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-17330234

RESUMO

Unlike the intact fibronectin (FN) molecule, some proteolytic or recombinant fragments of FN possess inhibitory activities on tumor, providing potential strategies in tumor therapeutics. Using the hydrodynamics-based gene delivery technique, we demonstrated that the treatment by in vivo expression of a recombinant CBD-HepII polypeptide of FN, designated as CH50, strongly inhibited the tumor growth, tumor invasion and angiogenesis. Such inhibitory effects of CH50 on tumor were partly ascribed to its influence on the activities of MMP-9 and alphavbeta3 integrin. The in vivo expressed CH50 decreased both the production and the activity of MMP-9 in tumor tissues. CH50 also down-regulated alphavbeta3 expression in tumor cells and endothelial cells in vitro. The decreased activity of alphavbeta3 integrin was proved by its reduced binding ability to fibrinogen and the down-regulation of cdc2 expression. The gene therapy with CH50 not only prolonged the survival of mice bearing hepatocarcinoma in the liver, but also suppressed the growth and invasive ability of tumor in spleen and its metastasis to liver. Taken together, these findings suggest a prospective utility of CH50 in the gene therapy of liver cancer.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Fibronectinas/metabolismo , Terapia Genética , Heparina/metabolismo , Peptídeos/metabolismo , Proteínas Recombinantes/metabolismo , Motivos de Aminoácidos , Animais , Sítios de Ligação , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Fibronectinas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfaVbeta3/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Neovascularização Patológica/patologia , Peptídeos/genética , Proteínas Recombinantes/genética , Taxa de Sobrevida
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