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2.
World J Surg Oncol ; 14(1): 169, 2016 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-27349965

RESUMO

BACKGROUND: Numerous epidemiological studies have evaluated the association between the CDH1 -160C/A polymorphism and the risk of breast cancers. However, these studies have yielded conflicting results. To derive a more precise estimation of this association, this meta-analysis was conducted. METHODS: A comprehensive search using the keywords "CDH1," "E-Cadherin," "polymorphism," "SNP," and "variant" combined with "breast," "cancer," "tumor," or "carcinomas" was conducted. Pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were appropriately calculated using a fixed effect or random effect model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 checklist was used for this meta-analysis. RESULTS: Four publications including five studies were identified. It was found that the CDH1 -160C/A polymorphism was significantly associated with breast cancer risk in the dominant model (CA + AA vs. CC: OR = 1.207, 95 % CI = 1.031-1.412, P = 0.019). CONCLUSIONS: Our meta-analysis demonstrated that the -160C/A polymorphism in the CDH1 gene might contribute to breast cancer susceptibility. Further investigations using a much larger sample including different ethnicities are still needed to verify this association.


Assuntos
Neoplasias da Mama/genética , Caderinas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Antígenos CD , Feminino , Humanos , Fatores de Risco
3.
COPD ; 12(4): 444-52, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25415045

RESUMO

In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. Type II alveolar epithelial cells (AECII) play a vital role in maintaining alveolar homeostasis and lung tissue repair. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance. The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo. During the induction of emphysema in rats, administration of SRT1720 improved lung function including airway resistance and pulmonary dynamic compliance. SRT1720 treatment up-regulated the levels of surfactant protein (SP)A, SPC, SIRT1 and forkhead box O 3, increased SIRT1 activity, down-regulated the level of p53 and inhibited AECII apoptosis. Lung injury caused by emphysema was alleviated after SRT1720 treatment. SRT1720 could protect against AECII apoptosis in rats with emphysema and thus could be used in COPD treatment.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ativadores de Enzimas/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Lesão Pulmonar/prevenção & controle , Enfisema Pulmonar/tratamento farmacológico , Células Epiteliais Alveolares/fisiologia , Animais , Biomarcadores/metabolismo , Western Blotting , Ativadores de Enzimas/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Masculino , Enfisema Pulmonar/complicações , Enfisema Pulmonar/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Resultado do Tratamento
4.
Cancer Sci ; 105(11): 1402-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25230369

RESUMO

Increased expression of galectin-1 (Gal-1) in carcinoma-associated fibroblasts (CAFs) has been reported to correlate with progression and prognosis in many cancers. However, rarely have reports sought to determine whether high Gal-1 expression in CAFs in gastric cancer is involved in the tumor process, and the specific mechanism by which it promotes the evolution of gastric cancer is still unknown. In this study, we cultured gastric cancer CAFs, which showed strong expression of Gal-1, and established a co-culture system of CAFs with gastric cancer cells. Specific siRNA and in vitro migration and invasion assays were used to explore the effects of the interaction between Gal-1 expression of CAFs and gastric cancer cells on cell migration and invasion. We found that the overexpression of Gal-1 in CAFs enhanced gastric cancer cell migration and invasion, and these stimulatory effects could be blocked by specific siRNA which reduced the Gal-1 expression level. A set of cancer invasion-associated genes were then chosen to identify the possible mechanism of Gal-1-induced cell invasion. Among these genes, integrin ß1 expression in cancer cells was considered to be associated with Gal-1 expression. Pre-blocking of the integrin ß1 expression in gastric cancer cells with siRNA could interrupt the invasion-promoting effect of CAFs with high Gal-1 expression. Furthermore, immunohistochemical assay confirmed a positive correlation between Gal-1 and integrin ß1 expression. Our results showed that high expression of Gal-1 in CAFs might facilitate gastric cancer cell migration and invasion by upregulating integrin ß1 expression in gastric cancer.


Assuntos
Fibroblastos/metabolismo , Galectina 1/genética , Integrina beta1/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Feminino , Fibroblastos/patologia , Galectina 1/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Integrina beta1/metabolismo , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Gástricas/mortalidade , Carga Tumoral , Regulação para Cima
5.
BMC Cancer ; 14: 218, 2014 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-24655788

RESUMO

BACKGROUND: Recent studies have shown that miR-199a-5p plays opposite roles in cancer initiation and progression of different cancer types, acting as oncogene for some cancer types but as tumor suppressor gene for others. However, the role and molecular mechanism of miR-199a-5p in gastric cancer are largely unknown. METHODS: In this study, miR-199a-5p expression level in gastric cancer was first analyzed by qPCRand then validated in 103 gastric cancer patients by in situ hybridization (ISH). Gastric cancer cell lines were transfected with miR-199a-5p inhibitor and mimic, and underwent in vitro transwell assays. Target genes (klotho) were identified using Luciferase reporter assay. Immunohistochemical staining was also used to investigate on how miR-199a-5p regulates the tumour-suppressive effects of klotho in gastric cancer. RESULTS: In our present study, we found that miR-199a-5p level was significantly increased in gastric cancer tissues compared to paired normal tissues. We observed that miR-199a-5p could promote migration and invasion of gastric cancer cells. In situ hybridization of miR-199a-5p also confirmed that higher miR-199a-5p expression level was associated with increased likelihood of lymph node metastasis and later TNM stage. Luciferase reporter assay and immunohistochemistry revealed that klotho might be the downstream target of miR-199a-5p. CONCLUSIONS: Our present study suggests that miR-199a-5p acts as an oncogene in gastric cancer and functions by targeting klotho.


Assuntos
Glucuronidase/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Glucuronidase/genética , Humanos , Proteínas Klotho , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Reprodutibilidade dos Testes , Neoplasias Gástricas/patologia
6.
J Surg Oncol ; 108(3): 197-202, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23832550

RESUMO

BACKGROUND AND OBJECTIVES: miR-301a is significantly overexpressed in many cancers. However, its expression and biological role in gastric cancer remain poorly understood. We investigated microRNA-301a (miR-301a) expression in gastric cancer and determined its effects on cancer cell behavior and its clinical significance in the development and progression of gastric cancer. METHODS: We determined miR-301a expression in gastric tumors and gastric cancer cell lines by reverse transcription-polymerase chain reaction. The effects of miR-301a on cell clone formation, migration, and invasion of HGC-27 and SGC-7901 cells were detected following transfection of an miR-301a inhibitor. miR-301a expression in a 304-tissue gastric cancer microarray was determined by in situ hybridization and its role in progression and prognosis was analyzed. RESULTS: miR-301a was upregulated in gastric tumor tissues and cell lines. Down-regulation of miR-301a significantly inhibited cell clone formation, migration, and invasion of HGC-27and SGC-7901 cells. Overexpression of miR-301a in primary gastric cancer tissues was associated with tumor size, invasion depth, lymph node metastasis, and TNM stage. CONCLUSIONS: miR-301a overexpression correlated with TNM stage and prognosis, suggesting that miR-301a is involved in cellular clone formation, migration, and invasion in vitro and may play an important role in the clinical progression and prognosis of gastric cancer.


Assuntos
MicroRNAs/fisiologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Análise Serial de Tecidos , Regulação para Cima
7.
World J Surg Oncol ; 11: 132, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23742050

RESUMO

BACKGROUND: Golgi protein 73 (GP73) is a type II Golgi transmembrane protein. It is over-expressed in several cancers, including hepatocellular carcinomas, bile duct carcinomas, lung cancer and prostate cancer. However, there are few reports of GP73 in gastric cancer. This study is aimed at investigating the expression of GP73 and its relationship with clinical pathological characters in gastric cancer. METHODS: GP73 mRNA level was determined by quantitative real-time RT-PCR in 41 pairs of matched gastric tumorous tissues and adjacent non-tumorous mucosal tissues. Western blotting was also performed to detect the GP73 protein level. GP73 protein expression was analyzed by immunohistochemistry in 52 clinically characterized gastric cancer patients and 10 non-tumorous gastric mucosal tissue controls. RESULTS: The mRNA and protein level of GP73 were significantly down-regulated in gastric tumorous tissues compared with the non-tumorous mucosal tissues. In non-tumorous mucosa, strong diffuse cytoplasmic staining can be seen in cells located at the surface of the glandular and foveolar compartment; while in tumorous tissues, the staining was much weaker or even absent, and mainly in a semi-granular dot-like staining pattern. The expression level of GP73 protein was associated with patients' gender and tumor differentiation. CONCLUSIONS: GP73 was normally expressed in non-tumorous gastric mucosa and down-regulated in gastric cancer. Its expression in gastric cancer was correlated with tumor differentiation.


Assuntos
Biomarcadores Tumorais/metabolismo , Diferenciação Celular , Mucosa Gástrica/patologia , Proteínas de Membrana/metabolismo , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/genética , Western Blotting , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Seguimentos , Mucosa Gástrica/metabolismo , Humanos , Metástase Linfática , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
8.
Zhonghua Yi Xue Za Zhi ; 93(46): 3691-3, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24534352

RESUMO

OBJECTIVE: To explore the indications, timing and approaches of surgical interventions for severe acute pancreatitis (SAP). METHODS: A retrospective study was performed for 115 hospitalized SAP patients from 2007 to 2013. RESULTS: Among them, 62 underwent surgery and another 53 were treated conservatively. The curative and mortality rates of surgical intervention and non-operation groups were 87.1%vs 84.9% (P > 0.05) and 9.68% vs 9.43% (P > 0.05) respectively. Twenty-five patients received early surgical intervention (<2 week) and another 37 delayed surgical intervention. The interval from diagnosis to surgical intervention of two groups were 7.5 ± 3.3 and 23.9 ± 8.5 days respectively. The mortality rates of early and delayed surgical groups were 16.0% and 5.4% respectively (P > 0.05). CONCLUSIONS: Individualized comprehensive therapy should be offered in the treatment of SAP. Timing of surgery for those with pancreatic necrosis and infection should be delayed to 3-4 weeks later until their general conditions permit.


Assuntos
Pancreatectomia , Pancreatite Necrosante Aguda/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo
9.
Cancer Sci ; 103(4): 620-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22168593

RESUMO

Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumor-suppressor genes. Microribonucleic acids (miR) are a recently-described class of genes encoding small non-coding RNA molecules, which primarily act by downregulating the translation of target mRNA. It has become apparent that miR are also key factors in cancer, playing both oncogenic and tumor-suppressing roles in gastric cancer. Recent studies have shown that a substantial number of miR show differential expression in gastric cancer tissues, and they are turning out to be just like any other regulatory gene. In this connection, miR dysregulation are reported to be associated with incidence, early diagnosis and prognosis of gastric cancer. Therefore, investigation of the biological aspects of miR dysregulation might help us better understand the pathogenesis of gastric cancer and promote the development of miR-directed therapeutics against this deadly disease. The aim of the present review was to describe the mechanisms of several known miR, summarize recent studies on oncogenic miR (e.g. miR-21, miR-106a and miR-17), tumor suppressor miR (e.g. miR-101, miR-181, miR-449, miR-486, let-7a) and controversial roles of miR (e.g. miR-107, miR-126) for gastric cancer. In addition, their potential clinical applications and prospects in gastric cancer, such as biomarkers and clinical therapy tools, are also briefly discussed.


Assuntos
MicroRNAs/genética , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Oncogenes , Prognóstico , Pequeno RNA não Traduzido , Neoplasias Gástricas/patologia
10.
Cancer Sci ; 103(12): 2082-91, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22957785

RESUMO

Recent studies have shown that overexpression of regenerating gene family member 4 (REG4) is associated with the initiation and progression of pancreatic cancer. In our study, we explored the role of REG4 in the invasion of pancreatic cancer. Real-time PCR and Western blot analysis were used to determine REG4 expression in pancreatic cancer cell lines. An MTT assay was carried out to test the effect of REG4 on the growth of pancreatic cancer cells. The involvement of REG4 in cancer cell invasion was examined by Transwell invasion assay. Two MMPs, MMP-7 and MMP-9, were identified from a pool of candidate genes as being related to REG4-induced cell invasion by PCR and Western blotting. Immunohistochemistry was used to confirm the correlation between REG4 and the two MMPs. High expression of REG4 was found in BXPC-3 cells and its culture media. But in PANC-1 and ASPC-1 cell lines, REG4 expression levels were very low, and no detectable protein was found in the culture medium. The MTT and Transwell invasion assays showed that recombinant REG4 protein and BXPC-3 conditioned media significantly promoted the proliferation and invasiveness of pancreatic cancer cells. It was also shown that MMP-7 and MMP-9 are upregulated by REG4 induction using real-time PCR and Western blotting analysis. Immunohistochemical study further verified this result. In conclusion, REG4 promotes not only growth but also in vitro invasiveness of pancreatic cancer cells by upregulating MMP-7 and MMP-9.


Assuntos
Lectinas Tipo C/genética , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Neoplasias Pancreáticas/genética , Regulação para Cima , Proliferação de Células , Humanos , Imuno-Histoquímica , Lectinas Tipo C/metabolismo , Masculino , Metaloproteinase 7 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Neoplasias Pancreáticas/patologia , Proteínas Associadas a Pancreatite , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
11.
Front Cell Dev Biol ; 10: 1051612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619871

RESUMO

Digestive system malignancies, the most common types of cancer and a major cause of death in the worldwide, are generally characterized by high morbidity, insidious symptoms and poor prognosis. NLRP3 inflammasome, the most studied inflammasome member, is considered to be crucial in tumorigenesis. In this paper, we reviewed its pro-tumorigenic and anti-tumorigenic properties in different types of digestive system malignancy depending on the types of cells, tissues and organs involved, which would provide promising avenue for exploring new anti-cancer therapies.

12.
World J Gastrointest Oncol ; 14(8): 1528-1539, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36160735

RESUMO

BACKGROUND: Approximately half of all new cases of gastric cancer (GC) and related deaths occur in China. More than 80% of patients with GC are diagnosed at an advanced stage, which results in poor prognosis. Although HER2-directed therapy and immune checkpoint inhibitors have been somewhat successful, new drugs are still needed for the treatment of GC. Notably, several gene fusion-targeted drugs have been approved by the United States Food and Drug Administration for solid tumors, including GC, such as larotrectinib for NTRK fusion-positive cancers and zenocutuzumab for NRG1 fusion-positive cancers. However, gene fusions involving targetable genes have not been well characterized in Chinese patients with GC. AIM: To identify the profile of fusions involving targetable genes in Chinese patients with GC using clinical specimens and determine the distribution of patients with gene fusion variants among the molecular subtypes of GC. METHODS: We retrospectively analyzed gene fusion events in tumor tissue samples from 954 Chinese patients with GC. Clinicopathological characteristics were obtained from their medical records. Genetic alterations, such as single nucleotide variants, indels, amplifications, and gene fusions, were identified using a targeted sequencing panel containing 825 genes. Fusions were validated by fluorescence in situ hybridization (FISH) using break-apart probes. The microsatellite instability (MSI) status was evaluated using MSIsensor from the targeted sequencing panel data. Tumor mutational burden (TMB) was calculated using the total number of nonsynonymous mutations divided by the total genomic targeted region. Chi-square analysis was used to determine the enrichment of gene fusions associated with the molecular subtypes of GC. RESULTS: We found that 1.68% (16/954) of patients harbored 20 fusion events involving targetable genes. RARA fusions (n = 5) were the most common, followed by FGFR2, BRAF, MET, FGFR3, RET, ALK, EGFR, NTRK2, and NRG1 fusions. Two of the RARA fusions, EML4-ALK (E6:E20) and EGFR-SEPTIN14 (E7:E10), have been identified in other tumors but not in GC. Surprisingly, 18 gene fusion events were previously not reported in any cancer types. Twelve of the eighteen novel gene fusions included complete exons encoding functional domains of targetable genes, such as the tyrosine kinase domain of receptor tyrosine kinases and the DNA- and ligand-binding domains of RARA. Consistent with the results of detection using the targeted sequencing fusion panel, the results of FISH (fluorescence in situ hybridization) confirmed the rearrangement of FGFR2 and BRAF in tumors from patients 04 and 09, respectively. Genetic analysis indicated that the fusion genes were significantly enriched in patients with ERBB2 amplification (P = 0.02); however, there were no significant differences between fusion-positive and fusion-negative patients in age, sex, MSI status, and TMB. CONCLUSION: We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68% of patients with GC harbor potential targetable gene fusions, which were enriched in patients with ERBB2 amplification. Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.

13.
Cancer Sci ; 102(2): 336-42, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21134074

RESUMO

Abundant macrophage infiltration and increased expression of coagulation factors have been observed in cancer patients. The aim of the present study was to determine how the interaction between activated coagulation factors and monocytes/macrophages contributes to gastric cancer (GC) cell migration and invasion. We assessed cytokine/chemokine production of coagulation-factor-treated macrophages by ELISA. The effects of the interaction between coagulation factors and tumor-associated macrophages (TAM) on GC cell migration and invasion were determined by in vitro migration and invasion assay. In addition, we used an in vitro co-culture system of GC cells/TAM treated by coagulation factors to evaluate the effect of coagulation factor/TAM interaction on the human umbilical vein endothelial cell line (HUVEC). We found that the M2-like phenotype of interleukin (IL)-4(high), IL-10(high), transforming growth factor (TGF)-ß(high), tumor necrosis factor (TNF)-α(high) was exhibited when the human monocytic cell line THP-1 was stimulated by coagulation factors III (TF), VIIa (FVIIa) and XIIa (FXIIa). For the migration assay, the GC cells (BGC-823 or SGC-7901) that were co-cultured with activated coagulation factor/TAM both showed increased migration. For the invasion assay, both BGC-823 and SGC-7901 cells co-cultured with TF/TAM showed increased invasion. We also found that TAM activated by coagulation factors could induce vascular endothelial growth factor/MMP-9 expression, which could promote invasion of GC cells. The HUVEC co-cultured with TAM (PMA-treated THP-1 macrophages co-cultured with GC cells) expressed high levels of FXIIa. In conclusion, coagulation factors might facilitate GC cell migration and invasion by transforming macrophages toward TAM-like cells. Interaction of coagulation factors and TAM mediates migration and invasion of GC.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Macrófagos/metabolismo , Invasividade Neoplásica/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Separação Celular , Técnicas de Cocultura , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos
14.
J Surg Oncol ; 103(2): 116-23, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21259244

RESUMO

BACKGROUND: The metalloproteinase domain-containing protein 10 (ADAM 10) has been implicated in the development and progression of gastric cancer. METHODS: Expression of ADAM 10 and C-erbB-2 were examined immunochemically in 436 clinicopathologically characterized gastric cancer cases. RESULTS: Protein levels of ADAM 10 and C-erbB-2 were up-regulated in gastric cancer lesions compared with adjacent non-cancerous tissues. Positive expression of ADAM 10 correlated with age, size of tumor, location of tumor, depth of invasion, vessel invasion, lymph node, and distant metastasis and TNM stage, and also with expression of C-erbB-2. In stages I, II, and III, the 5-year survival rate of patients with high ADAM 10 expression was significantly lower than in patients with low expression. However, in stage IV, ADAM 10 expression did not correlate with the 5-year survival rate. Further multivariate analysis suggests that up-regulation of ADAM 10 and C-erbB-2 were independent prognostic indicators for the disease, along with depth of invasion, lymph node and distant metastasis and TNM stage. CONCLUSION: Expression of ADAM 10 in gastric cancer is significantly associated with lymph node and distant metastasis, high C-erbB-2 expression, and poor prognosis. ADAM 10 and C-erbB-2 proteins could be useful markers to predict tumor progression and prognosis.


Assuntos
Proteínas ADAM/análise , Adenocarcinoma/química , Adenocarcinoma/secundário , Secretases da Proteína Precursora do Amiloide/análise , Biomarcadores Tumorais/análise , Carcinoma de Células em Anel de Sinete/química , Proteínas de Membrana/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Proteína ADAM10 , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/secundário , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/mortalidade
15.
Zhonghua Yi Xue Za Zhi ; 91(39): 2765-8, 2011 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-22322056

RESUMO

OBJECTIVE: To explore the clinical significance of sphingosine kinase 1 (SPHK1) in the invasion, metastasis and prognosis of gastric cancer. METHODS: Immunohistochemistry was employed to analyze the expression of SPHK1 in 206 clinicopathologically characterized gastric cancer cases from January 2001 to December 2005 at Zhejiang Provincial People's Hospital. RESULTS: SPHK1 protein was detected in 3 (7.5%) of 40 human non-tumor mucosa. All samples expressed the protein at a low level. SPHK1 protein was detected in 181 (87.9%) of 206 human gastric cancer cases. An elevated expression of SPHK1 protein was detected in 126 (61.2%) tumors. And SPHK1 protein was up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues (P = 0.001). The expression of SPHK1 was correlated with the depth of invasion, lymph node metastasis, distant metastasis and TNM stage (P = 0.039, 0.003, 0.020, 0.003). In stages I-II and III, the 5-year survival rate of the patients with a high expression of SPHK1 was significantly lower than those with a low expression (53.6% (15/28) vs 68.6% (24/35), 7.8% (6/77) vs 30.8% (12/39), P = 0.009, 0.006). In stage IV, the expression of SPHK1 was not correlated with the 5-year survival rate (P > 0.05). Further multivariate analysis suggested that lymph node metastasis, distant metastasis, TNM stage and the up-regulation of SPHK1 were independent prognostic indicators for gastric cancer. CONCLUSION: The expression of SPHK1 in gastric cancer is significantly associated with lymph node metastasis, distant metastasis and a poor prognosis. SPHK1 may become a useful marker of predicting tumor progression and prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico
16.
Ann Surg Oncol ; 17(1): 89-97, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19820999

RESUMO

BACKGROUND: The present study investigated the clinical significance of S100 calcium binding protein A4 in the development, progression, and metastasis of gastric cancer. METHODS: Tumor tissue, adjacent normal tissue, and lymph node and peritoneal metastases were obtained from patients with gastric cancer, and their gene expression profiles were analyzed by Affymetrix GeneChip HG-U133A2.0 array. The expression of S100A4 was detected by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) in gastric tumor tissue and lymph node and peritoneum metastasis. Immunohistochemistry was employed to analyze S100A4 expression in 436 clinicopathologically characterized gastric cancer cases and in corresponding distant metastases from 61 patients. RESULTS: A total of 434 genes and 169 expressed sequence tags were upregulated by at least twofold in the tumor tissue. The expression of S100A4 in lymph node and peritoneal metastases was significantly higher than that in gastric tumor tissue. The expression of S100A4 messenger RNA (mRNA) or protein differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph node and peritoneal metastases. Further multivariate analysis suggested that depth of invasion, lymph node and distant metastases, tumor-node-metastasis (TNM) stage, and upregulation of S100A4 were independent prognostic indicators for the disease. CONCLUSION: Gene expression profiles are a useful way to perform simultaneously large-scale analysis of the expression level of thousands of genes. Expression of S100A4 in gastric cancer is associated significantly with lymph node and distant metastases, and poor prognosis. S100A4 may be a useful marker to predict development, progression, and metastasis of gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Mucosa Gástrica/metabolismo , Proteínas S100/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/secundário , Adenocarcinoma Papilar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/secundário , Carcinoma de Células em Anel de Sinete/cirurgia , Feminino , Seguimentos , Gastrectomia , Mucosa Gástrica/patologia , Perfilação da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína A4 de Ligação a Cálcio da Família S100 , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
17.
Zhonghua Yi Xue Za Zhi ; 90(17): 1184-6, 2010 May 04.
Artigo em Chinês | MEDLINE | ID: mdl-20646565

RESUMO

OBJECTIVE: To determine the value of reoperation in the treatment of recurrent gastric cancer. METHODS: Clinical and survival data of 85 patients undergoing reoperation for recurrent gastric cancer from January 1986 to December 2003 were studied retrospectively. RESULTS: Among 85 cases, there were 46 cases with recurrence within the stump stomach and 58 cases recurred within 2 years post-operation. Resection was performed in 45 patients including 34 cases treated by radical resection and 11 cases by palliative residual stomach resection. The 1, 3, 5-year survival rate of 34 cases after radical resection was 86%, 57% and 21% respectively. The mean survival time of palliative and comprehensive treatment cases was 16 months (range: 6 - 26) while all patients undergoing reoperation without resection died within 6 months post-operation. CONCLUSION: An early diagnosis of recurrent gastric cancer depends on frequent re-examinations. Most postoperative recurrent gastric cancers, within the residual stomach, may be treated by re-operation.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação
18.
J Pharm Pharmacol ; 72(2): 209-217, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31736093

RESUMO

OBJECTIVES: This study is designed to investigate the effects and mechanisms of sinomenine (Sin) in stress load-induced heart failure in mice. METHODS: We used aortic constriction (AB) to cause pressure overload as our heart failure model. Sin was received in mice as the treatment group. Cardiac function and structural changes were detected using echocardiography. Heart-lung mass ratios were measured. The serum levels of IL-10 and IL-17 proteins were detected by using ELISA, cardiac hypertrophy markers atrial natriuretic peptide (ANP), myocardial I and III collagen mRNA levels were detected by RT-PCR. Myocardial type I and III collagen protein levels were detected by Western blotting. KEY FINDINGS: Sin significantly improved stress load-induced heart failure (P < 0.05), reduced the heart-lung mass ratio, ANP, collagen-I and -III mRNA and protein levels (P < 0.05); Sin can enhance the ratio of IL-10/IL-17. CONCLUSION: Sin may be a promising drug target to improve heart failure. Its role is related to reduce serum ANP levels, inhibit the mRNA and protein level of type I and III collagen and enhance the ratio of IL-10/IL-17.


Assuntos
Cardiotônicos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Morfinanos/farmacologia , Animais , Fator Natriurético Atrial/sangue , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Interleucina-10/sangue , Interleucina-17/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
Cancer Immunol Immunother ; 58(9): 1387-96, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19169879

RESUMO

BACKGROUND: The aim of this study was to screen and identify novel B cell epitopes within the human heparanase protein and to investigate the impact of self-developed anti-heparanase polypeptide antibodies on growth and invasion of HCCLM6 human hepatocellular carcinoma cells in vitro. METHODS: The flexible regions of secondary structure and the B cell epitopes of the human heparanase amino acid sequence were predicted by DNAStar and Bcepred software.The multiple antigenic peptides (MAP) of the epitopes were synthesized in eight-branched form. Rabbits were immunized with the eight-branched MAPs mixed with the universal T-helper epitope human IL-1beta peptide (VQGEESNDK, amino acid 163-171). The immunogenicity of the synthesized peptides was evaluated by ELISA, western blot and immunohistochemistry. The impact of the self-developed rabbit anti-heparanase polyclonal antibodies on growth and invasion ability of HCCMLM6 cells were analyzed in a cell culture model. The cells were first treated with one of the three antibodies, respectively, and then measured by using MTT, flow cytometry, plate clone formation, invasion assay and heparan sulfate degrading enzyme assay. RESULTS: The three amino acid sequences 1-15 (MAP1), 279-293 (MAP2), and 175-189 (MAP3) in the large subunit of the human heparanase protein were predicted as its most potential epitopes. ELISA, western blot and immunohistochemistry analysis showed that all three MAPs were capable to induce high titer of serum antibodies. Antibodies induced by MAP1 and MAP2 were high specific. Furthermore, anti-MAP2 antibodies showed the strongest avidity towards liver cancer tissues. Under the treatment with the three anti-heparanase antibodies, respectively, the growth, cell cycle and clone formation of the cells remained unchanged when compared with a treatment with normal rabbit IgG. However, an inhibition of cell invasiveness and heparanase activity could be detected under the treatment with anti-MAP1- or anti-MAP2-antibody (with a terminal concentration of 100 mug/ml). The cell invasiveness was decreased by 54 and 38%, respectively, the heparanase activity by 43 and 39%, respectively. CONCLUSION: The multiple antigenic peptides MAP1 (AC 1-15) and MAP2 (AC 279-293) may be the dominant B cell epitopes in the human heparanase protein. The induced polypeptide antibodies can effectively inhibit the heparanase activity of HCCLM6 liver cancer cells and therefore influence their invasion ability, which provides a theoretic basis for the development of anti-heparanase antibodies and their clinical use as vaccine.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Movimento Celular , Epitopos de Linfócito B/imunologia , Glucuronidase/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Animais , Western Blotting , Carcinoma Hepatocelular/metabolismo , Adesão Celular , Ciclo Celular/imunologia , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Glucuronidase/metabolismo , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/metabolismo , Masculino , Fragmentos de Peptídeos/imunologia , Coelhos
20.
Zhonghua Zhong Liu Za Zhi ; 31(1): 10-4, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19538861

RESUMO

OBJECTIVE: To investigate the effects of the self-developed anti-heparanase polypeptide antibodies on growth and invasion of human hepatocellular carcinoma HCCLM6 cells. METHODS: Using MTT, flow cytometry, plate clone formation, transwell invasion and heparan degrading enzyme assay, the growth and invasion changes of human hepatocellular carcinoma HCCLM6 cells by co-culture with each of three self-developed rabbit anti-heparanase polyclonal antibodies were detected. RESULTS: Compared with normal rabbit IgG, in the presence of each anti-heparanase polypeptide antibody, the growth, cell cycle and clone formation remained unchanged, and under the P1 or P2 anti-heparanase polypeptide antibody (with final concentration 100 microg/ml), the cell invasiveness was inhibited by 52.5% and 36.6%, respectively, and the heparanase activity was inhibited by 42.9% and 39.1%, respectively. CONCLUSION: The P1 and P2 anti-heparanase polypeptide antibodies can effectively inhibit the invasion ability and heparanase activity of liver cancer HCCLM6 cells. However, All the three antibodies have no effects on its growth, cell cycle and clone formation.


Assuntos
Carcinoma Hepatocelular/patologia , Diferenciação Celular , Glucuronidase/imunologia , Neoplasias Hepáticas/patologia , Anticorpos/farmacologia , Carcinoma Hepatocelular/enzimologia , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Técnicas de Cocultura , Ativação Enzimática , Glucuronidase/metabolismo , Humanos , Neoplasias Hepáticas/enzimologia , Invasividade Neoplásica
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