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1.
Cell Death Differ ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097789

RESUMO

Tubulointerstitial inflammation is a common characteristic of acute and chronic kidney injury. However, the mechanism by which the initial injury of tubular epithelial cells (TECs) drives interstitial inflammation remains unclear. This paper aims to explore the role of exosomal miRNAs derived from TECs in the development of tubulointerstitial inflammation. Global microRNA(miRNA) expression profiling of renal exosomes was examined in a LPS induced acute kidney injury (AKI) mouse model and miR-19b-3p was identified as the miRNA that was most notably increased in TEC-derived exosomes compared to controls. Similar results were also found in an adriamycin (ADR) induced chronic proteinuric kidney disease model in which exosomal miR-19b-3p was markedly released. Interestingly, once released, TEC-derived exosomal miR-19b-3p was internalized by macrophages, leading to M1 phenotype polarization through targeting NF-κB/SOCS-1. A dual-luciferase reporter assay confirmed that SOCS-1 was the direct target of miR-19b-3p. Importantly, the pathogenic role of exosomal miR-19b-3p in initiating renal inflammation was revealed by the ability of adoptively transferred of purified TEC-derived exosomes to cause tubulointerstitial inflammation in mice, which was reversed by inhibition of miR-19b-3p. Clinically, high levels of miR-19b-3p were found in urinary exosomes and were correlated with the severity of tubulointerstitial inflammation in patients with diabetic nephropathy. Thus, our studies demonstrated that exosomal miR-19b-3p mediated the communication between injured TECs and macrophages, leading to M1 macrophage activation. The exosome/miR-19b-3p/SOCS1 axis played a critical pathologic role in tubulointerstitial inflammation, representing a new therapeutic target for kidney disease.

2.
FASEB J ; 33(6): 7603-7614, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30892941

RESUMO

Vascular aging has a strong relationship with cardiovascular disease. Fos-related antigen 1 (Fra-1), also referred to as Fos-like antigen 1, is a transcription factor and has been reported to be involved in many pathologic processes. Here, we demonstrate that Fra-1 plays a critical role in angiotensin II (Ang II)-induced vascular senescence. Fra-1 expression is increased significantly in Ang II-induced rat aortic endothelial cell (RAEC) senescence and the arteries from Ang II-infused mice. Interestingly, silencing Fra-1 blocks Ang II-induced senescence phenotypes in RAECs, including decreased senescence-associated ß-galactosidase staining, and mitigated proliferation suppression and senescence-associated secretory phenotype. Further, knocking down Fra-1 inhibits vascular aging phenotypes in an Ang II-infused mice model. The up-regulated Fra-1 also exists in human atherosclerotic plaques and Ang II-induced vascular smooth muscle cells as well as in replicated senescence RAECs. Mechanistic studies reveal that Fra-1 preferentially associates with c-Jun and binds to the cyclin-dependent kinase inhibitor 1a (p21) and cyclin-dependent kinase inhibitor 2a (p16) promoter region, leading to elevated gene expression, which causes senescence-related phenotypes. In conclusion, our results identify that Fra-1 plays a novel and key role in promoting vascular aging by directly binding and transcriptionally activating p21 and p16 signaling, suggesting intervention of Fra-1 is a potential strategy for preventing aging-associated cardiovascular disorders.-Yang, D., Xiao, C., Long, F., Wu, W., Huang, M., Qu, L., Liu, X., Zhu, Y. Fra-1 plays a critical role in angiotensin II-induced vascular senescence.

3.
Am J Pathol ; 188(11): 2542-2552, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30142333

RESUMO

IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glomerulopathy controls. Transmission electron microscopy and nanoparticle tracking analysis confirmed the size and morphology characteristic of urinary exosomes. Exosome markers (Alix and CD63) as well as renal cell markers [aquaporin 2 (AQP2) and nephrin] were detected, which indicate the renal origin of urinary exosomes. Exosome excretion was increased markedly in IgAN patients compared with controls and correlated with levels of proteinuria and tubular injury. More important, urinary exosome excretion correlated with greater histologic activity (mesangial hypercellularity, crescents, and endocapillary hypercellularity). Profiling of the inflammation-related mRNA revealed that exosomal chemokine (C-C motif) ligand 2 (CCL2) was up-regulated in IgAN patients. In a validation study, CCL2 was exclusively highly expressed in IgAN patients compared with healthy controls as well as minimal change disease and membrane nephropathy patients. Also, a correlation between exosomal CCL2 and estimated glomerular filtration rate levels was found in IgAN. Exosomal CCL2 was correlated with tubulointerstitial inflammation and C3 deposition. High CCL2 levels at the time of renal biopsy were associated with subsequent deterioration in renal function. Thus, urinary exosomes and exosomal CCL2 mRNA are promising biomarkers reflecting active renal histologic injury and renal function deterioration in IgAN.

4.
Cardiovasc Res ; 114(14): 1894-1906, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982434

RESUMO

Aims: Jumonji domain-containing protein 3 (JMJD3), also called lysine specific demethylase 6B (KDM6b), is an inducible histone demethylase which plays an important role in many biological processes, however, its function in vascular remodelling remains unknown. We aim to demonstrate that JMJD3 mediates vascular neointimal hyperplasia following carotid injury, and proliferation and migration in platelet-derived growth factor BB (PDGF-BB)-induced vascular smooth muscle cells (VSMCs). Methods and results: By using both genetic and pharmacological approaches, our study provides the first evidence that JMJD3 controls PDGF-BB-induced VSMCs proliferation and migration. Furthermore, our in vivo mouse and rat intimal thickening models demonstrate that JMJD3 is a novel mediator of neointima formation based on its mediatory effects on VSMCs proliferation, migration, and phenotypic switching. We further show that JMJD3 ablation by small interfering RNA or inhibitor GSK J4 can suppress the expression of NADPH oxidase 4 (Nox4), which is correlated with H3K27me3 enrichment around the gene promoters. Besides, deficiency of JMJD3 and Nox4 prohibits autophagic activation, and subsequently attenuates neointima and vascular remodelling following carotid injury. Above all, the increased expression of JMJD3 and Nox4 is further confirmed in human atherosclerotic arteries plaque specimens. Conclusions: JMJD3 is a novel factor involved in vascular remodelling. Deficiency of JMJD3 reduces neointima formation after vascular injury by a mechanism that inhibits Nox4-autophagy signalling activation, and suggesting JMJD3 may serve as a perspective target for the prevention and treatment of vascular diseases.

5.
J Fish Biol ; 93(1): 88-94, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29882375

RESUMO

A new cave-dwelling fish species Triplophysa guizhouensis is described based on specimens collected from Guizhou, China, in a subterranean system interconnected with the Hongshui River drainage. The species can be distinguished from its congeners by a combination of characters: eyes present; caudal fin with 14 branched rays; inner gill rakers of first gill arch 8-10; posterior chamber of air bladder developed; and body posterior of dorsal fin scaled. A key to species of Triplophysa in the Pearl River basin is provided.


Assuntos
Cavernas , Cipriniformes/classificação , Sacos Aéreos , Animais , Biodiversidade , China , Cipriniformes/anatomia & histologia , Olho , Brânquias , Pigmentação , Rios
6.
Cell Physiol Biochem ; 47(2): 458-474, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794432

RESUMO

BACKGROUND/AIMS: Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure. Cystathionine-γ-lyase (CSE)/ hydrogen sulfide (H2S) has potential anti-inflammatory activities in a variety of inflammatory diseases. NADPH oxidase 4 (Nox4), a member of the NADPH oxidases, is the major source of reactive oxygen species (ROS) and its expression is increased in sepsis, but its function in CSE-mediated anti-inflammatory activities remains unknown. METHODS: Macrophages were either transfected with CSE, Nox4 siRNA or transduced with lentiviral vector encoding CSE or Nox4, and then stimulated with lipopolysaccharide (LPS). The expression of inflammatory mediators and signaling pathway activation were measured by quantitative PCR (qPCR), ELISA, and immunoblotting. LPS-induced shock severity in WT, Nox4 knockdown and CSE knockout (CSE-/-) mice was assessed. RESULTS: Here we showed that CSE and Nox4 were upregulated in macrophage and mouse in response to LPS. After LPS stimulation, the inflammatory responses were significantly ameliorated by lentiviral Nox4 shRNA knockdown, but were exacerbated by lentiviral overexpressing Nox4. Furthermore, Nox4 mediated inflammation through PI3K/Akt and p-p38 mitogen-activated protein kinase signal pathway. Notably, CSE knockout served to amplify the inflammatory cascade by increasing Nox4-ROS signaling activation in septic mice and macrophage. Similarly, the enhanced production of inflammatory mediators by macrophages was reduced by CSE overexpression. CONCLUSION: Thus, we demonstrated that CSE/H2S attenuated LPS-induced sepsis against oxidative stress and inflammation damage probably largely through mediated Nox4 pathway.


Assuntos
Sulfeto de Hidrogênio/farmacologia , Lipopolissacarídeos/farmacologia , NADPH Oxidase 4/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Cistationina gama-Liase/deficiência , Cistationina gama-Liase/genética , Citocinas/análise , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 4/antagonistas & inibidores , NADPH Oxidase 4/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Cardiovasc Res ; 114(7): 1016-1028, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29529137

RESUMO

Aims: Angiotensin II (Ang II) causes vascular inflammation, leading to vascular endothelial cell dysfunction, and is associated with the development of cardiovascular diseases. Therefore, interventions in inflammation may contribute to the reduction of cardiovascular diseases. Here, we aim to demonstrate that HDAC4, one of class IIa family histone de-acetylases (HDACs) members, promotes autophagy-dependent vascular inflammation. Methods and results: By loss-of-function approaches, our study provides the first evidence that HDAC4 mediates Ang II-induced vascular inflammation in vitro and in vivo. In response to the Ang II, HDAC4 expression is up-regulated rapidly, with increased autophagic flux and inflammatory mediators in vascular endothelial cells (VECs). In turn, HDAC4 deficiency suppresses activation of autophagy, leading to reduced inflammation in Ang II-induced VECs. Consistently, using autophagy inhibitor or silencing LC3-II also alleviates vascular inflammation. Furthermore, HDAC4 regulates autophagy via facilitating transcription factor forkhead box O3a (FoxO3a) de-acetylation, thereby to increase its transcriptional activity. Loss of HDAC4 in VECs results in inhibition of FoxO3a de-acetylation to block its transcriptional activity, leading to downregulation of the downstream FoxO3a target, and hence reduces autophagy and vascular inflammation. FoxO3a silencing using siRNA approach significantly inhibits activation of autophagy. Finally, knockdown of HDAC4 in Ang II-infused mouse models ameliorates vascular inflammation, suggesting that inhibitor of HDAC4 may be potential therapeutics for vascular diseases associated with inflammation. Conclusion: These results suggest that HDAC4-mediated FoxO3a acetylation regulates Ang II-induced autophagy activation, which in turn plays an essential role in causing vascular inflammation.

8.
J Am Soc Nephrol ; 29(3): 919-935, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29295871

RESUMO

Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding. Notably, the internalization of purified TEC exosomes by cultured macrophages increased if TECs were exposed to BSA. Macrophage internalization of exosomes from BSA-treated TECs led to an enhanced inflammatory response and macrophage migration, but CCL2 silencing in TECs prevented these effects. Using a GFP-CCL2 fusion mRNA construct, we observed direct transfer of CCL2 mRNA from TEC exosomes to macrophages. Mice subjected to tail vein injection of purified BSA-treated TEC exosomes developed tubular injury with renal inflammatory cell infiltration. However, injection of exosomes from BSA-treated CCL2-deficient TECs induced less severe kidney inflammation. Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.

9.
J Cell Mol Med ; 22(2): 728-737, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29083099

RESUMO

Extracellular vesicles (EVs) are nanosized, membrane-bound vesicles released from different cells. Recent studies have revealed that EVs may participate in renal tissue damage and regeneration through mediating inter-nephron communication. Thus, the potential use of EVs as therapeutic vector has gained considerable interest. In this review, we will discuss the basic characteristics of EVs and its role in nephron cellular communication. Then, the application of EVs as therapeutic vector based on its natural content or as carriers of drug, in acute and chronic kidney injury, was discussed. Finally, perspectives and challenges of EVs in therapy of kidney disease were described.

10.
Oxid Med Cell Longev ; 2017: 7150376, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28690765

RESUMO

Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R), consistent results were obtained with decreased reactive oxygen species (ROS) production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC-) 4 which could inhibit NADPH oxidase- (NOX-) 4 and matrix metalloproteinase- (MMP-) 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO-) 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ácido Gálico/análogos & derivados , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Ácido Gálico/uso terapêutico , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Acidente Vascular Cerebral/metabolismo
11.
Phytomedicine ; 32: 15-23, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28732803

RESUMO

BACKGROUND: Endothelial inflammation is an increasingly prevalent condition in the pathogenesis of many cardiovascular diseases. (-)-7(S)-hydroxymatairesinol (7-HMR), a naturally occurring plant lignan, possesses both antioxidant and anti-cancer properties and therefore would be a good strategy to suppress tumor necrosis factor-α (TNF-α)-mediated inflammation in vascular endothelial cells (VECs). PURPOSE: The objective of this study is to evaluate for its anti-inflammatory effect on TNF-α-stimulated VECs and underling mechanisms. STUDY DESIGN/METHODS: The effect of the 7-HMR on suppression of TNF-α-induced inflammation mediators in VECs were determined by qRT-PCR and Western blot. MAPKs and phosphorylation of Akt, HO-1 and NF-κB p65 were examined using Western blot. Nuclear localisation of NF-κB was also examined using Western blot and immunofluorescence. RESULTS: Here we found that 7-HMR could suppress TNF-α-induced inflammatory mediators, such as vascularcelladhesion molecule-1, interleukin-6 and inducible nitric oxide synthase expression both in mRNA and protein levels, and concentration-dependently attenuated reactive oxidase species generation. We further identified that 7-HMR remarkably induced superoxide dismutase and heme oxygenase-1 expression associated with degradation of Kelch-like ECH-associated protein 1 (keap1) and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, 7-HMR time- and concentration-dependently attenuated TNF-α-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) and Akt, but not p38, or c-Jun N-terminal kinase 1/2. Moreover, 7-HMR significantly suppressed TNF-α-mediated nuclear factor-κB (NF-κB) activation by inhibiting phosphorylation and nuclear translocation of NF-κB p65. CONCLUSION: Our results demonstrated that 7-HMR inhibited TNF-α-stimulated endothelial inflammation, at least in part, through inhibition of NF-κB activation and upregulation of Nrf2-antioxidant response element signaling pathway, suggesting 7-HMR might be used as a promising vascular protective drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , NF-kappa B/metabolismo , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase-1/metabolismo , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Fator de Necrose Tumoral alfa/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo
12.
Neurochem Res ; 42(10): 2850-2860, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28512713

RESUMO

Chronic neuroinflammation is a pathological feature of neurodegenerative diseases. Inhibition of microglia-mediated neuroinflammation might be a potential strategy for neurodegeneration. Matairesinol, a dibenzylbutyrolactone plant lignan, presents in a wide variety of foodstuffs. It has been found to possess anti-angiogenic, anti-oxidative, anti-cancer and anti-fungal activities. In the present study, we investigated the anti-neuroinflammation effects of matairesinol on lipopolysaccharide (LPS)-induced BV2 microglia cells and the related molecular mechanisms. The results showed that matairesinol inhibited microglia activation by reducing the production of nitric oxide, the expression of inducible nitric oxide synthase and cyclooxygenase-2 in a concentration-dependent manner (6.25, 12.5, 25 µM). In the molecular signaling pathway, LPS-induced nuclear factor-kappa B (NF-κB) transcriptional activity and translocation into the nucleus were remarkably suppressed by matairesinol through the inhibition of the extracellular signal-regulated kinase (ERK)1/2 signal transduction pathways, but not p38 MAPK or c-jun N-terminal kinase (JNK). Meanwhile, matairesinol also blocked LPS-mediated microglia migration and this was associated with inhibition of LPS-induced Src phosphorylation as well as Src expression in a concentration-dependent manner. Taken together, these results suggest that matairesinol inhibited inflammatory response and migration in LPS-induced BV2 microglia, and the mechanisms may be associated with the NF-κB activation and modulation of Src pathway.


Assuntos
Furanos/farmacologia , Lignanas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteína Oncogênica pp60(v-src)/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo
13.
Redox Biol ; 10: 157-167, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27744121

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H2S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1ß-induced human rheumatoid fibroblast-like synoviocytes MH7A. In addition, SPRC blocked IL-1ß-mediated migration and invasion of MH7A cells. As expected, the protective effects of SPRC were partially abrogated by DL-propargylglycine (PAG, a H2S biosynthesis inhibitor). In vivo study also demonstrated that SPRC treatment markedly ameliorated the severity of RA in adjuvant-induced arthritis rats, and this effect was associated with the inhibition of inflammatory response. We further identified that SPRC remarkably induced heme oxygenase-1 expression associated with the degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); this effect was attributed to the sulfhydrylation of the cysteine residue of Keap1. Our data demonstrated for the first time that SPRC, an endogenous H2S modulator, exerted anti-inflammatory properties in RA by upregulating the Nrf2-antioxidant response element (ARE) signaling pathway.


Assuntos
Anti-Inflamatórios/administração & dosagem , Elementos de Resposta Antioxidante/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Cisteína/análogos & derivados , Fator 2 Relacionado a NF-E2/genética , Animais , Anti-Inflamatórios/farmacologia , Artrite Reumatoide/genética , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Cisteína/administração & dosagem , Cisteína/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
14.
J Cancer Res Clin Oncol ; 134(2): 187-92, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17611776

RESUMO

PURPOSE: To investigate the value of palliative gastrectomy and chemotherapy in a large series of patients with stage IV gastric cancer. METHODS: A total of 389 patients were identified in survival analysis. Among which, 183 cases received palliative gastrectomy (PG) and 206 cases received unresectable operation, 184 cases received palliative chemotherapy (PC) and 205 cases did not receive chemotherapy. The survival advantages of patients, based on treatments modality, were also analyzed in patients with liver metastasis, peritoneal dissemination and lymph node metastasis. RESULTS: The 1-year, 3-year, 5-year survival rate of those patients who were treated with PG + PC were 85.7% (96/112), 32.1% (36/112), and 8.9% (10/112), which were far better than those who were not. For those patients with liver metastasis, peritoneal dissemination, and/or N3 lymph node metastasis, survival advantages were also present if treated with this multimodality approach. CONCLUSION: The survival time and palliative duration were significantly longer in patients after PG than after non-resection operations. Postoperative chemotherapy prolonged the survival time of patients after palliative surgery. PG combined with adjuvant chemotherapy may improve survival in patients with stage IV gastric cancer, even with liver metastasis, peritoneal dissemination, and lymph node metastasis.


Assuntos
Gastrectomia , Cuidados Paliativos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo
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