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1.
Dig Endosc ; 36(2): 141-151, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37059698

RESUMO

OBJECTIVES: Subepithelial lesions (SELs) are associated with various endoscopic resection (ER) outcomes and diagnostic challenges. We aimed to establish a tool for predicting ER-related outcomes and diagnosing SELs and to investigate the predictive value of endoscopic ultrasound (EUS). METHODS: Phase 1 (system development) was performed in a retrospective cohort (n = 837) who underwent EUS before ER for SELs at eight hospitals. Prediction models for five key outcomes were developed using logistic regression. Models with satisfactory internal validation performance were included in a mobile application system, SEL endoscopic resection predictor (SELERP). In Phase 2, the models were externally validated in a prospective cohort of 200 patients. RESULTS: An SELERP was developed using EUS characteristics, which included 10 models for five key outcomes: post-ER ulcer management, short procedure time, long hospital stay, high medication costs, and diagnosis of SELs. In Phase 1, 10 models were derived and validated (C-statistics, 0.67-0.99; calibration-in-the-large, -0.14-0.10; calibration slopes, 0.92-1.08). In Phase 2, the derived risk prediction models showed convincing discrimination (C-statistics, 0.64-0.73) and calibration (calibration-in-the-large, -0.02-0.05; calibration slopes, 1.01-1.09) in the prospective cohort. The sensitivities and specificities of the five diagnostic models were 68.3-95.7% and 64.1-83.3%, respectively. CONCLUSION: We developed and prospectively validated an application system for the prediction of ER outcomes and diagnosis of SELs, which could aid clinical decision-making and facilitate patient-physician consultation. EUS features significantly contributed to the prediction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, http://www.chictr.org.cn (ChiCTR2000040118).


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Endossonografia/métodos , Sensibilidade e Especificidade
2.
Biochem Biophys Res Commun ; 533(4): 1240-1246, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33069359

RESUMO

PURPOSE: In the present study, we attempted to explore the role of chloride channel 3 (CLC-3) in colorectal cancer (CRC) and its related mechanism. METHODS: First, the expression level of CLC-3 in CRC tumor tissues and cell lines were measured by RT-qPCR, immunohistochemistry or western blot analysis. CLC-3 expression knockdown in CRC cells was achieved by siRNA transfection. The effect of CLC-3 silence on cell viability, cell cycle, invasion and migration of CRC was estimated by CCK8, flow cytometry based cell cycle assay, and transwell assay, respectively. In order to investigate whether Wnt/ß-catenin signaling was perturbed by CLC-3 knockdown, CLC-3 knockdown cells were treated with pathway activator LiCl, followed by the measurement of the expressions of pathway related genes, cell viability, cell cycle, metastasis ability. RESULTS: The expression of CLC-3 was gradually increased from normal adjacent tissues to CRC tumor tissues, and the increase in tumor tissues was related to TNM stages. CLC-3 was overexpressed in four CRC cell lines (HCT116, SW480, LoVo and SW620), compared with NCM460 cells. CLC-3 knockdown significantly reduced cell proliferation, invasion and migration ability, reflected by declined cell viability, arrested G0/G1 cell cycle, decreased invasion and migration ability. In contrast, the declined cell proliferation, invasion and migration of LoVo and SW620 cells induced by CLC-3 knockdown were reversed by the addition of Wnt/ß-catenin activator LiCl. CONCLUSION: CLC-3 contributed to the CRC development and metastasis through Wnt/ß-catenin signaling pathway. CLC-3 could be proposed as the candidate target for CRC treatment.


Assuntos
Canais de Cloreto/fisiologia , Neoplasias Colorretais/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Canais de Cloreto/antagonistas & inibidores , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Técnicas de Silenciamento de Genes , Humanos , Metástase Neoplásica , beta Catenina/metabolismo
3.
World J Gastroenterol ; 24(5): 593-601, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29434448

RESUMO

AIM: To study the role of semaphorin 4D (Sema4D) expression promoted by tumor-associated macrophages (TAMs) in gastric carcinoma cells and its clinical significance in the invasion and metastasis of gastric carcinoma. METHODS: CD68 and Sema4D expression was analyzed in gastric carcinoma and adjacent normal tissues from 290 patients using the immunohistochemical streptavidin-peroxidase method, and their relationships with clinicopathological features were evaluated. Human M2 macrophages were induced in vitro and co-cultured in non-contact with gastric carcinoma SGC-7901 cells. Changes in the secretory Sema4D level in the SGC-7901 cell supernatant were measured using an enzyme-linked immunosorbent assay. The effects of TAMs on SGC-7901 cell invasion and migration were assessed with invasion and migration assays, respectively. RESULTS: CD68 and Sema4D protein expression was significantly higher in gastric carcinoma tissues than in adjacent normal tissues (71.7% vs 33.8% and 74.5% vs 42.8%, respectively; P < 0.01). CD68 and Sema4D protein expression was significantly associated with histological differentiation, TNM stage, and lymph node metastasis (P < 0.05), and their expression levels were positively correlated with one another (r = 0.467, P < 0.01). In the in vitro experiment, secretory Sema4D protein expression was significantly increased in the supernatant of SGC-7901 cells co-cultured with TAMs compared with the blank control (1224.13 ± 29.43 vs 637.15 ± 33.84, P < 0.01). Cell invasion and metastasis were enhanced in the Transwell invasion and migration assays (P < 0.01). CONCLUSION: TAMs promote the invasion and metastasis of gastric carcinoma cells possibly through upregulated secretory Sema4D protein expression. Combined detection of TAM markers, CD68 and Sema4D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma/patologia , Macrófagos/imunologia , Semaforinas/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular/imunologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Neoplasias Gástricas/imunologia , Regulação para Cima
4.
Mol Med Rep ; 12(2): 2636-42, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25936980

RESUMO

Tumor necrosis factor α-induced protein 8 (TNFAIP8) has been associated with the tumorigenicity of various types of cancer, however, the expression of TNFAIP8 and its function in gastric cancer remain to be fully elucidated. Therefore, the present study examined the expression and biological function of TNFAIP8 in gastric cancer. The expression levels of TNFAIP8 were determined in 86 gastric cancer tissue samples and adjacent normal tissues using immunohistochemistry, and in four gastric cancer cell lines and GES-1 cells using reverse transcription-quantitative polymerase chain reaction. The expression of TNFAIP8 and its association with the tumor, node, metastasis (TNM) status and lymphatic metastasis of gastric cancer was evaluated. Furthermore, the functions of decreased expression levels of TNFAIP8 were analyzed in human gastric cancer cell lines. The expression of TNFAIP8 was significantly upregulated in the gastric cancer tissues and in the gastric cancer cell lines, and its expression levels were associated with the TNM staging and lymphatic metastasis. Furthermore, decreased expression of TNFAIP8 inhibited the growth, invasion and migration of gastric cancer cells. These data provided an innovative insight suggesting the downregulation of TNFAIP8 as a meaningful approach for treating human gastric cancer and other types of cancer. In addition, the expression levels of TNFAIP8 may be considered as a biomarker of gastric cancer progression.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/genética , Adulto , Idoso , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
5.
World J Gastroenterol ; 21(7): 2191-8, 2015 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-25717256

RESUMO

AIM: To investigate semaphorin 4D (Sema4D) and hypoxia-inducible factor-1α (HIF-1α) expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance. METHODS: Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery, and none of them received preoperative radiochemotherapy. Normal proximal adjacent bowel tissue, which served as an internal control, was obtained from 52 randomly selected patients. Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesis-related protein HIF-1α in normal colorectal tissues and colorectal carcinoma tissues. The relationships between the expression and clinical characters and prognosis were analyzed. RESULTS: HIF-1α and Sema4D were positively expressed in 58% and 60% of colorectal carcinoma tissues, respectively. Significantly lower expression levels were observed in normal mucosa (8% and 12%, respectively). HIF-1α and Sema4D expression was closely correlated with histological tumor type, tumor-node-metastasis (TNM) stage, and lymphatic metastasis (P<0.05), but not with age or tumor size (P>0.05). HIF-1α and Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma, as determined by Spearman rank correlation analysis (r=0.567; P<0.01). Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis (P<0.05). CONCLUSION: These findings suggest that HIF-1α and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.


Assuntos
Antígenos CD/análise , Biomarcadores Tumorais/análise , Carcinoma/química , Neoplasias Colorretais/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Semaforinas/análise , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma/secundário , Carcinoma/cirurgia , Distribuição de Qui-Quadrado , Colectomia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Resultado do Tratamento , Regulação para Cima
6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 17(4): 388-92, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-24760652

RESUMO

OBJECTIVE: To compare the expressions of hypoxia-inducible factor 1 alpha(HIF-1α) and Semaphorin 4D(Sema4D) in colorectal carcinoma and normal colorectal tissues, and to investigate their correlation and clinical significance. METHODS: The expressions of HIF-1α and Sema4D were examined in 86 cases of colorectal carcinoma and 52 normal colorectal tissues by SP immunohistochemical staining. Correlation between these two expressions and association of the expressions with clinicopathological characters and prognosis were analyzed. RESULTS: The positive rates of HIF-1α and Sema4D protein in colorectal carcinoma tissues were significantly higher than those in normal colorectal tissues(58.1% vs. 7.7%, χ(2)=34.624, P<0.01; 60.5% vs. 11.5%, χ(2)=31.839, P<0.01). HIF-1α and Sema4D protein expressions were closely associated with colorectal carcinoma histological types(P=0.003, P=0.010), TNM staging (P=0.003, P=0.017) and lymphatic metastasis (P=0.003, P=0.020), and a significant correlation was observed between the expressions of HIF-1α and Sema4D protein (r=0.567, P<0.01). The 5-year overall survival rate was 37%. Univariate analysis showed that 5-year survival rates of patients with positive and negative HIF-1α protein expression were 24% and 56%(P=0.003), and those with positive and negative Sema4D protein expression were 23% and 59%(P=0.001). Multivariate Cox analysis showed that expression of Sema4D was an independent prognostic factor of colorectal cancer patients(P=0.026), while expression of HIF-1α was not(P=0.501). CONCLUSION: Combined detection of HIF-1α and Sema4D has the potential to predict the development trend of colorectal carcinoma and prognosis of patients.


Assuntos
Antígenos CD/metabolismo , Neoplasias Colorretais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Semaforinas/metabolismo , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
7.
Chin Med J (Engl) ; 127(20): 3568-75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25316231

RESUMO

BACKGROUND: Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha (HIF-1α) plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D (Sema4D) also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages (TAMs) can increase the expression of HIF-1α and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-1α and the impact of biologic behavior in colon cancer cells. METHODS: Immunohistochemistry was used to analyze HIF-1α and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software (SPSS Inc., USA). Differences between two groups were analyzed with Student's t test. RESULTS: HIF-1α (58%) and Sema4D (60%) were expressed at a significantly higher level in tumors than in normal tissues (P < 0.01, for both). Furthermore, HIF-1α and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages (P < 0.05), but not with age and tumor size (P > 0.05). Sema4D expression was correlated with that of HIF-1α (r = 0.567, P < 0.01). TAMs markedly induced HIF-1α and Sema4D expression in colon cancer cells and subsequently increased their migration and invasion. CONCLUSIONS: HIF-1α and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-1α and Sema4D.


Assuntos
Antígenos CD/metabolismo , Neoplasias do Colo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Metástase Neoplásica/patologia , Semaforinas/metabolismo , Adulto , Idoso , Antígenos CD/genética , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Semaforinas/genética
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