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Background: This study aimed to investigate the value of perioperative lymphocyte-to-monocyte ratio (LMR) changes in predicting postoperative survival among patients undergoing radical gastrectomy, and explore whether the combination of preoperative carbohydrate antigen 199 (CA199) and LMR changes would further improve the prognostic accuracy. Methods: A total of 456 patients who underwent radical gastrectomy at the Affiliated Hospital of Nantong University were included as the training set, and 210 patients from the Nantong Tumor Hospital were enrolled as the validation set. The patients' peripheral complete blood counts, including lymphocytes, monocytes, and tumor marker CA199 level, were checked regularly in all patients 1 week before and after radical gastrectomy by two technicians who were blinded to their clinical characteristics. The LMR was calculated by dividing the lymphocyte count by the monocyte count in the peripheral blood. ΔLMR could be obtained by subtracting the preoperative LMR from the postoperative LMR. The serum CA199 level was determined through a latex immunoassay (Mitsubishi Chemical Ltd., Japan). The survival curve was drawn according to the Kaplan-Meier method, and variables with P<0.05 in univariate analyses were transferred to multivariate Cox regression analysis. A nomogram was constructed using the finalized separated prognostic factors of gastric cancer (GC). The main prognostic indicator was overall survival (OS). Results: In the training and validation sets, the prognostic predictive ability of CA199 and ΔLMR (postoperative LMR minus preoperative LMR) was independently evaluated (both P<0.05). ΔLMR and CA199 were used to establish the ΔLMR-CA199 score. The results showed that the higher the ΔLMR-CA199 risk score, the worse the prognosis, especially in patients with advanced GC. Postoperative adjuvant chemotherapy improved the long-term prognosis of patients with a ΔLMR-CA199 score of 1 but had no significant effect on the survival rate of patients with 0 and 2 points. Conclusions: ΔLMR-CA199 can better predict the long-time survival of patients with GC. In addition, it can also predict the response of postoperative adjuvant chemotherapy in patients with GC.
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Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in East Asia. Surgical resection is currently the typical treatment. However, due to the highly invasive and metastatic characteristic of the disease, the mortality rate is still high. A search for potential prognostic biomarkers and therapeutic targets is very necessary. Here, we studied the expression of proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine protein kinase, in ESCC and its influence on prognosis. A total of 112 cases of ESCC and paired adjacent normal tissues (NT) were organized in tissue microarray (TMA) from the Nantong First People's Hospital. Our analysis of TMA revealed that Pyk2 levels were higher in ESCC than in paired adjacent NT by immunohistochemistry (p<0.001). Western blot and real-time quantitative PCR analysis (p=0.0359) also reached similar conclusions. To further explore the significance of Pyk2 in ESCC, another set of tissue microarrays was collected from the Affiliated Hospital of Nantong University, which includes 241 consecutive patients undergoing radical surgery for ESCC, to perform IHC scores. We demonstrated that the expression level of Pyk2 was positively correlated with N stage (node negative versus node positive, p=0.02) and clinical stage (I + II versus III + IV, p=0.042). Univariate and multivariate analyses suggested that high Pyk2 expression was an independent prognostic factor for overall survival with ESCC. Cell function studies found that Pyk2 promoted tumor proliferation and migration and reduced apoptosis. Pyk2 knockdown enhanced the sensitivity to cisplatin in ESCC cells. Western blot analysis confirmed that Pyk2 may promote tumor progression by activating the Akt signaling pathway.
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Biomarcadores de Tumor/metabolismo , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Quinasa 2 de Adhesión Focal/metabolismo , Anciano , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/enzimología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/enzimología , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Resultado del TratamientoRESUMEN
Esophageal squamous cell carcinoma (ESCC) is a common malignant tumour type of the digestive system. Long non-coding RNA (lncRNA) c-Myc upregulated (MYU), also known as VPS9 domain-containing 1 antisense 1, was recently discovered. However, the expression of lncRNA MYU in ESCC and its role in tumour progression have remained elusive. In the present study, the expression of lncRNA MYU, Ki-67 and the epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin in ESCC tissues was detected by reverse transcription-quantitative PCR. The expression of Ki-67, E-cadherin and Vimentin in ESCC tissues was also detected by immunohistochemistry. A small interfering RNA plasmid was employed to establish a TE-2 cell line with knockdown on lncRNA MYU. The results indicated that the expression of lncRNA MYU was higher in ESCC tissues than in normal adjacent tissues and that upregulation of lncRNA MYU was a potential biomarker for poor prognosis. The results also suggested that the expression levels of lncRNA MYU were correlated with the histological grade, lymph node metastasis and TNM stage (P<0.05). Silencing of lncRNA MYU expression inhibited the proliferation, migration and invasion, while the expression of lncRNA MYU increased as cell proliferation increased. In addition, the mRNA expression of Vimentin and Ki-67 was decreased in TE-2 cells after lncRNA MYU was knocked down, while E-cadherin mRNA expression was elevated. In conclusion, the present results indicated that lncRNA MYU may regulate the proliferation, migration and invasion of ESCC cells, and may serve as a prognostic biomarker for ESCC.
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BACKGROUND: 5-fluorouracil (5-FU) resistance is the leading cause of treatment failure in colon cancer. Combination therapy is an effective strategy to inhibit cancer cells and prevent drug resistance. Therefore, we studied the antitumor effect of curcumol alone or combined with 5-FU on human colon cancer drug-resistant cells. METHODS: The 5-FU resistant HCT116 cell line (HCT116/5-FU) was established by repeated exposure to gradually increasing concentrations of 5-FU; Cell viability was measured by cell counting kit-8 (CCK-8); apoptosis rate of HCT116 cells was detected using Annexin V-fluorescein isothiocyanate (FITC) assay kit; cell proliferation and invasion were detected using colony formation assays, wound healing assay and transwell invasion assays; activity of transplanted tumor in vivo in specific pathogen free (SPF) BALB/c nude mice (6 weeks old, male) was monitored by bioluminescence imaging, immunohistochemistry and western blot analysis. RESULTS: Our study showed the potent antitumor effect of curcumol by induction of apoptosis, inhibition of proliferation, invasion, migration, and improvement of the therapeutic efficacy of 5-FU toward human colon cancer HCT116 cells. From our results, curcumol could chemosensitize 5-FU-resistant HCT116 cells. The combination of curcumol and 5-FU exerted a synergistic inhibitory effect on the induction of apoptosis. Also, this combination inhibited the proliferation, invasion, and migration of both chemo-resistant and sensitive cells. Curcumol treatment decreased multidrug resistance-associated protein 2 (MRP-2), P-glycoprotein (P-gp), survivin, and ß-catenin expression, which correlated with multidrug resistance (MDR) and the target genes of Wnt/ß-catenin. It significantly increased the p-ß-catenin level and Bad/Bcl-2 ratio in HCT116/5-FU cells compared with 5-FU treatment. In vivo, curcumol significantly inhibited the growth of transplanted tumors and the expression of Ki-67, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) in colon cancer cells. CONCLUSIONS: Curcumol as a potential chemotherapeutic agent combined with 5-FU can overcome colon cancer resistance.
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BACKGROUND The purpose of our study was to determine the effects and mechanisms of honokiol on human epidermal growth factor receptor 2 (HER2)-positive gastric cancer cells by in vitro study. MATERIAL AND METHODS We measured HER2 expression in different gastric cancer cell lines by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) assay. Cell proliferation, apoptosis, and cell cycle were evaluated by cell-counting kit 8 and flow cytometry assays. The invading cell numbers and wound-healing rates were measured by transwell and wound-healing assays. Phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), P21, and matrix metalloproteinase (MMP)-9 proteins and messenger ribonucleic acid (mRNA) expression were measured by WB and RT-qPCR assay. HER2 protein expression was evaluated by cellular immunofluorescence. RESULTS Honokiol suppressed cell proliferation via increasing cell apoptosis, invasion, and migration with dose dependence. By WB and RT-qPCR assays, compared with the control group, PI3K, AKT, P21, and MMP-9 proteins and mRNA expression were significantly different (P<0.05). By cellular immunofluorescence, HER2 protein expression was significantly depressed in honokiol-treated groups compared with control groups (P<0.05). CONCLUSIONS Honokiol has suppressive effects on HER2-positive gastric cancer cell biological activities via regulation of HER2/PI3K/AKT pathways in vitro.
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Compuestos de Bifenilo/farmacología , Lignanos/farmacología , Receptor ErbB-2/antagonistas & inhibidores , Neoplasias Gástricas/metabolismo , Apoptosis/efectos de los fármacos , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , ARN Mensajero/genética , Receptor ErbB-2/genética , Neoplasias Gástricas/patología , Células Tumorales CultivadasRESUMEN
BACKGROUND: Apatinib showed promising efficacy in the treatment of advanced or metastatic gastric cancer (mGC) in previous clinical studies. However, the real-world data are limited, and this study aimed to assess the effectiveness and safety of apatinib for the treatment of advanced or mGC in this setting. METHODS: In this prospective observational study, progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were recorded and evaluated. Univariate and multivariate analyses were conducted to explore potential biomarkers which might be related to the effectiveness. RESULTS: A total of 321 mGC patients from 47 centers in China were enrolled between July 1, 2015, and March 1, 2018. Thirty-two patients achieved partial response, 155 patients achieved stable disease, and 115 patients had progressive disease, and no CR was achieved, illustrating an ORR of 10.60% and a DCR of 61.92%. The median PFS and OS were 4.0 and 8.2 months, respectively. Multivariate Cox analysis showed that the potential biomarkers associated with longer PFS were combination regimens plus taxel/docetaxel, and apatinib initial dosage ≥500mg, occurrence of AEs of leukopenia, and hand-foot syndrome. Main AEs were proteinuria (17.1%), hypertension (15.9%), and handfoot syndrome (8.7%). CONCLUSION: The present prospective observational study showed favorable effectiveness and safety of apatinib in real-world patients with advanced or metastatic GC in China. (A prospective, multi-center, non-intervention study of apatinib in the treatment of advanced gastric cancer-Trial Registry Number: ChiCTR-OPN-15006601).
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BACKGROUND: HAX-1 is involved in the regulation of cellular processes such as apoptosis, proliferation and migration and is closely related to tumorigenesis and tumor metastasis. However, expression of HAX-1 in gastric cancer and its role in tumor development and progression remain unclear. METHODS: Quantitative polymerase chain reaction was used to detect the expression of HAX-1 mRNA in gastric cancer tissues and adjacent non-tumorous tissues. Expression of HAX-1, caspase-3 and caspase-9 was detected by immunohistochemistry in gastric cancer. Small hairpin RNA (shRNA) plasmid was employed to establish SGC-7901 cell lines that expressed HAX-1 at low levels. The effect of HAX-1 expression on cell proliferation will be studied at the cell level. RESULTS: Quantitative polymerase chain reaction (qPCR) showed HAX-1 mRNA expression to be significantly upregulated in gastric cancer tissues. Based on immunohistochemical analysis, upregulation of HAX-1 protein expression correlates positively with the degree of tumor differentiation, vascular tumor thrombus, tumor-node-metastasis stage and lymph node metastatic status and negatively with expression of the apoptosis-related proteins caspase-3 and caspase-9. In addition, high HAX-1 protein expression indicates a poor prognosis. Serum starvation-release experiments revealed that HAX-1 promotes the proliferation of SGC-7901 gastric cancer cells; as cell proliferation increased, expression of HAX-1 also increased, whereas the expression levels of the apoptosis-related proteins caspase-3 and caspase-9 decreased. HAX-1 siRNA transfection experiments demonstrated that HAX-1 gene knockdown causes cell cycle arrest at the G0/G1 phase, inhibits proliferation, and downregulates HAX-1 expression while enhancing expression of apoptosis-related proteins. CONCLUSIONS: HAX-1 might exert its proliferation-promoting and anti-apoptotic effects by inhibiting expression of the apoptosis-related proteins caspase-3 and caspase-9.HAX-1 may be a potential target for the treatment of gastric cancer.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, which lacks effective biomarkers for prognosis. Therefore, it is urgent to explore new potential molecular markers to discriminate patients with poorer survival in ESCC. METHODS: Bioinformatics analysis, qRT-PCR, and western blot were applied to investigate S1PR1 expression. CCK-8 assay, colony formation assay, flow cytometry dual staining assay, and immunofluorescence were performed to examine cell proliferation ability and apoptosis rate. Mouse xenograft model of TE-13 cells was established to confirm the roles of S1PR1 in vivo. Gene set enrichment analysis (GSEA) was used to investigate the downstream signaling pathways related to S1PR1 functions. Co-IP was performed to verify the direct binding of S1PR1 and STAT3. Western blot was applied to determine the phosphorylation level of STAT3. Immunohistochemistry was conducted to identify protein expression of S1PR1 and p- STAT3 in tumor tissues. RESULTS: In the present study, we found that S1PR1 expression was higher in ESCC patients and was a potential biomarker for poor prognosis. Silencing S1PR1 expression inhibited proliferation, and increased apoptosis of ESCC cells, while overexpression of S1PR1 had opposite effects. Mechanistically, S1PR1 played the roles of promoting proliferation and attenuating apoptosis through directly activating p-STAT3. Furthermore, in vivo experiments verified this mechanism. CONCLUSION: Our findings indicated that S1PR1 enhanced proliferation and inhibited apoptosis of ESCC cells by activating STAT3 signaling pathway. S1PR1 may serve as a prognostic biomarker for clinical applications.
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Apoptosis , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Factor de Transcripción STAT3/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Animales , Biomarcadores de Tumor/genética , Movimiento Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Factor de Transcripción STAT3/genética , Transducción de Señal , Receptores de Esfingosina-1-Fosfato/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Kinesin family member 26B (KIF26B) plays a key role in the development and progression of many human cancers. However, the role and underlying mechanisms of KIF26B in breast cancer cells remain unknown. MATERIALS AND METHODS: In this study, we inhibited the expression of KIF26B in MDA-MB-231 and MCF-7 cells using lentivirus-delivered shRNA. RESULTS: Lentivirus-mediated KIF26B knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion. Furthermore, cell cycle analyses revealed that the percentage of cells in the G0/G1 phase was significantly increased in KIF26B knockdown cells. Moreover, the knockdown of KIF26B significantly promoted cell apoptosis via the upregulation of cleaved caspase-3 and Bax. CONCLUSION: Our data indicate that KIF26B plays a pivotal role in tumor growth and metastasis in breast cancer cells and may be a potential therapeutic target for treating breast cancer.
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Circulating tumor cells (CTCs) have become an important biomarker for liquid biopsy to monitor tumor progression and indicate response to therapies. Many epithelial cellular adhesion molecule (EpCAM) dependent CTC isolation methods have been developed, which have a limitation for low EpCAM expressed tumor cells. In an effort to overcome these drawbacks, we developed combined immunomagnetic beads (EpCAM, Mucin1 and epidermal growth factor receptor) to sensitively isolate CTCs for immunofluorescence analysis and genetic characterization. With this combined immunomagnetic beads, 93.35% H446 cells from spiked blood sample can be recovered. We were able to detect CTCs in 127 among 143 patients included in the study (88.8%). Some CTC clusters were captured with the combined magnetic beads system. In 17 of them, CTCs after chemotherapy significantly decreased compared to that before chemotherapy (4.42 (±â¯3.94) vs. 12 (±â¯7)/mL, Pâ¯=â¯0.002). For subsequent genetic characterization of CTCs, 2 of 6 samples, using a droplet digital PCR (ddPCR) chip, have detectable EGFR L858R mutation in the cells enriched with the combined immunomagnetic beads. In conclusion, this method integrating the combined immunomagnetic beads and the ddPCR chip for CTCs detection can be of potential application in terms of diagnosis, therapeutic evaluation and personalized medicine in lung cancer.
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Receptores ErbB/genética , Separación Inmunomagnética , Neoplasias Pulmonares/diagnóstico , Células Neoplásicas Circulantes/patología , Reacción en Cadena de la Polimerasa , Humanos , Neoplasias Pulmonares/genética , Mutación , Tamaño de la PartículaRESUMEN
OBJECTIVE: To investigate the role and prognostic importance of Dvl2 in human epithelial ovarian cancer (EOC). METHODS: A multimethod study was undertaken including patients with pathologically confirmed non-metastatic EOC who underwent surgery for maximum tumor resection at a center in China. Dvl2 expression was assessed by western blot using fresh EOC tissues and normal ovarian tissues obtained between June 2014 and January 2015. Additionally, retrospective data were obtained for patients treated between April 2004 and September 2009. Their tumor specimens were used in immunohistochemistry analysis. Kaplan-Meier survival plots were constructed to estimate the overall survival by Dvl2 expression, and a Cox proportional hazards model was used to analyze prognostic factors. Alterations in Dvl2 expression during the cell cycle were assessed by a starvation and refeeding assay. RESULTS: Dvl2 expression was higher in EOC samples than in normal tissues on western blot. Overall, 124 patients were included in immunohistochemistry analysis, and Dvl2 expression level was significantly associated with the tumor grade and Ki-67 expression. Overexpression of Dvl2 was correlated with poor prognosis. The pattern of Dvl2 expression throughout the cell cycle matched that of the cell proliferation marker cyclin D1. CONCLUSION: Dvl2 could play a part in EOC progression and might be an independent prognostic factor. Additionally, it might be a prospective therapeutic target in the treatment of EOC.
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Proteínas Dishevelled/metabolismo , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Ováricas/diagnóstico , Biomarcadores/metabolismo , Carcinoma Epitelial de Ovario , China , Proteínas Dishevelled/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
As a crucial member of the small ubiquitin-like modifier system, SUMO-specific protease 3, was identified to be essential for cell proliferation and ribosomal RNA processing. Recent studies showed that SUMO-specific protease 3 was elevated in ovarian cancer compared to normal tissue samples. However, the connection between SUMO-specific protease 3-specific expression and clinicopathological parameters of epithelial ovarian cancer, as well as the physiologically potential role of SUMO-specific protease 3 in epithelial ovarian cancer remained unclear. In this study, an analysis of 124 paraffin-embedded slices by immunohistochemistry indicated that SUMO-specific protease 3 expression was positively correlated with the International Federation of Gynecology and Obstetrics stages (p = 0.025), tumor grade (p = 0.004), and lymph node metastasis (p = 0.001) and was also a critical prognostic factor for the overall survival of epithelial ovarian cancer patients, as revealed by Kaplan-Meier curve analysis. Knockdown of SUMO-specific protease 3 weakened the proliferation, migration, and invasion capability of ovarian cancer cells, down-regulated the expression of Proliferating Cell Nuclear Antigen, Forkhead Box C2, and N-cadherin, and resulted in upregulation of p21 and E-cadherin. Consistent with our results, SUMO-specific protease 3 had been verified to promote cell proliferation, metastasis, and tumorigenesis in multiple malignant cancers, which was a redox-sensitive molecule mediating the epithelial-mesenchymal transition. Collectively, our findings for the first time specifically supported that SUMO-specific protease 3 might play an important role in the regulation of epithelial ovarian cancer progression and could serve as a potential biomarker for prognosis as well as provide a promising therapeutic target against epithelial ovarian cancer.
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Biomarcadores de Tumor/genética , Cisteína Endopeptidasas/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/genética , Adulto , Anciano , Biomarcadores de Tumor/biosíntesis , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Proliferación Celular/genética , Cisteína Endopeptidasas/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , PronósticoRESUMEN
Non-small cell lung cancer (NSCLC) is the major cause of cancer-related lethality among human cancer patients globally, and the poor prognosis of this cancer is mainly explained by metastasis, so it is essential to find out the molecule mechanisms and a novel therapeutic for NSCLC. A disintegrin and metalloprotease with thrombospondin motif 5 (ADAMTS5) belongs to the protease family. It has been reported to participate in tumor migration and invasion. In this study, we showed that the expression of ADAMTS5 was higher in lung cancer tissues by Western blot. The immunohistochemistry analysis was performed in 140 NSCLC cases, and the result indicated that ADAMTS5 was significantly associated with clinical pathologic variables. The Kaplan-Meier curve showed that the high expression of ADAMTS5 was related to poor prognosis of lung cancer patients. Wound healing assays and transwell migration assays revealed that the high expression of ADAMTS5 promoted the migration and invasion of NSCLC. In a word, our findings suggest that ADAMTS5 can regulate the migration and invasion of NSCLC and it may be a useful target of therapy in NSCLC.
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Proteína ADAMTS5/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares/patología , Apoptosis , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Estudios de Casos y Controles , Femenino , Técnica del Anticuerpo Fluorescente , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Pulmón/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Células Tumorales CultivadasRESUMEN
Homeobox C8 (HOXC8) is a transcription factor that has been reported as a potential driver oncogene in several tumors and involved in the regulation of many cancer-related proteins. In this study, we investigated the expression and role of HOXC8 in ovarian cancer. Western blot and immunohistochemistry analyses were performed to detect the expression of HOXC8. Kaplan-Meier curve showed that high expression of HOXC8 was related to poor prognosis of patients with epithelial ovarian cancer (EOC). Starvation and refeeding assay were used to assess cell cycle, suggesting that HOXC8 played a critical role in EOC cell proliferation. HOXC8 depletion by small interfering RNA inhibited cell proliferation, migration, and induced apoptosis in EOC cells. Moreover, HOXC8 knockdown increased the expression of ZAC1. Owing to the overexpression of HOXC8, our findings implied that HOXC8 is involved in the progression of EOC and could be a potential therapeutical approach of EOC.
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Proteínas de Homeodominio/metabolismo , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/metabolismo , Apoptosis , Carcinoma Epitelial de Ovario , Ciclo Celular , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , PronósticoRESUMEN
Far-upstream element (FUSE)-binding protein 2 (FBP2) was a member of single-stranded DNA-binding protein family; it played an important role in regulating transcription and post-transcription and is involved in the regulation of C-MYC gene expression in liver tumors. However, the role of FBP2 in breast cancer and its mechanism has not been studied yet. Here, we discovered that FBP2 was up-regulated in breast cancer tissues and breast cancer cell lines. Moreover, immunohistochemistry analysis demonstrated that up-regulated FBP2 was highly associated with tumor grade, Ki-67, and poor prognosis, which was an independent prognostic factor for survival of breast cancer patients. At the cellular level, we found that FBP2 was correlated with cell cycle progression by accelerating G1/S transition, and knockdown of FBP2 could weaken cell proliferation, anchorage-independent cell growth, while enhancing the sensitivity of breast cancer cells to doxorubicin. More importantly, we found that activation of PI3K/AKT pathway could phosphorylate FBP2, and then make FBP2 shuttle from cytoplasm into the nucleus, which was the main mechanism of breast cancer cell proliferation and drug resistance. Taken together, our findings supported the notion that FBP2 might via PI3K/AKT pathway influence breast cancer progression and drug resistance, which might provide a new target for the design of anti-cancer drugs for breast cancer patients.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Proteínas de Unión al ARN/metabolismo , Transactivadores/metabolismo , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Transforming growth factor-activated kinase 1 (TAK1)-binding protein 3 (TAB3) is essential for the activation of the nuclear factor kappa B (NF-κB) pathway and has important roles in cell survival. However, the contribution of TAB3 to non-small cell lung cancer (NSCLC) remains elusive. In the present study, Western blotting and immunohistochemistry assays demonstrated that TAB3 expression was frequently increased in NSCLC tissues and cells. In addition, chi-square test and Kaplan-Meier analysis revealed that upregulation of TAB3 expression correlated with a more invasive tumor phenotype and poor prognosis. In addition, a series of experiments, including serum starvation-refeeding experiment and TAB3-siRNA transfection assay, showed that TAB3 expression promoted NSCLC cell proliferation. Furthermore, the effect of TAB3 expression on the sensitivity to cis-diamminedichloroplatinum (CDDP) and possible signaling transduction pathways was investigated. When the expression of TAB3 was inhibited by siRNA transfection, the sensitivity to CDDP was enhanced. Moreover, it showed that downregulation of TAB3 enhanced CDDP-induced A549 cell apoptosis through the inhibition of the NF-κB pathway. These results suggest that TAB3 plays a critical role in NSCLC progression and chemoresistance and that TAB3 depletion may be a promising approach to lung cancer therapy.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular/fisiología , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , FN-kappa B/metabolismo , Células A549 , Proteínas Adaptadoras Transductoras de Señales , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/genética , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Interferencia de ARN , Transducción de Señal/efectos de los fármacos , Regulación hacia ArribaRESUMEN
PURPOSE: In this study, we investigated the expression and role of PSMB4 in human epithelial ovarian cancer(EOC). METHODS: Western blot was used to evaluate the expression of PSMB4 in EOC tissues, and immunohistochemical analysis was performed on 115 cases of ovarian cancers. Then, we used Fisher exact test to analyze the correlation between PSMB4 and clinicopathological parameters. Starvation and re-feeding assay was used to assess cell cycle. CCK-8 assay and plate colony formation assay showed the influence of PSMB4 on proliferation of EOC cells. RESULTS: The expression of PSMB4 in EOC tissues was higher than normal ovary tissues and was significantly associated with clinical pathologic variables. Kaplan-Meier curve showed that high expression of PSMB4 was related to poor prognosis of EOC patients. Starvation and re-feeding assay suggested that PSMB4 played a critical role in EOC cell proliferation. CCK-8 assay and plate colony formation assay showed that EOC cells treated with PSMB4-siRNA reduced cell proliferation of EOC cells. Additionally, PSMB4 knockdown decreased NF-κB activity. PSMB4 also regulated the expression of NF-κB mediated proteins, including cyclin D1, and cyclin E which involved in cell proliferation. CONCLUSIONS: Our findings implied that PSMB4 is involved in the progression of EOC and could serve as potential therapeutical target of EOC. These data suggested that PSMB4 may promote cell proliferation via the NF-κB-target gene in EOC.
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Biomarcadores de Tumor/metabolismo , Proliferación Celular/fisiología , MicroARNs/metabolismo , FN-kappa B/metabolismo , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Adulto , Biomarcadores de Tumor/genética , Carcinoma Epitelial de Ovario , Ciclina D1/genética , Ciclina D1/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , MicroARNs/genética , Persona de Mediana Edad , FN-kappa B/genética , Neoplasias Glandulares y Epiteliales/patología , Pronóstico , Complejo de la Endopetidasa Proteasomal/genética , ARN Interferente PequeñoRESUMEN
A variety of melanoma-associated antigen-A (MAGE-A) protein are commonly detected in lung cancers. Their biological function is not well characterized but may involve cell cycle progression and the regulation of apoptosis. We hypothesized that MAGE-A9 is involved in the regulation of apoptosis. To test this hypothesis, we evaluated MAGE-A9 protein expression by immunohistochemical staining and we assessed the relationship between the expression of MAGE-A9 and clinical pathological parameters. In addition, we investigated the effect of MAGE-A9 down-regulation in lung adenocarcinoma. The results showed that a high expression level of MAGE-A9 protein in lung adenocarcinoma tumor cells was related to larger tumor diameter (P = 0.013) and poor differentiation (P = 0.029). Cox regression analysis revealed that the expression of MAGE-A9 in lung adenocarcinoma tumor cells (P < 0.001) is an independent prognostic factor in five-year survival rates. NSCLC cells with silenced MAGE-A9 had decreased cell proliferation, migration and invasion in cell culture compared to corresponding control cells. The NSCLC cells showing down-regulated MAGE-A9 induced the expression of apoptosis-associated proteins. In addition, MAGE-A9 was associated with resistance to conventional chemotherapeutic agents. Our findings provide evidence that MAGE-A9 could be a potential therapeutic target in NSCLC.
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Adenocarcinoma/mortalidad , Antígenos de Neoplasias/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Proteínas de Neoplasias/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/secundario , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
This study focused on determining the role of Spy1 in human epithelial ovarian cancer (EOC). Speedy is a novel cell cycle protein capable of promoting cell proliferation. In this study, western blot and immunohistochemistrical analyses were performed to detect the expression of Spy1 in ovarian cancer. Spy1 protein levels increased with ovarian cancer grade, and Kaplan-Meier curve showed that overexpression of Spy1 was significantly correlated with reduced patient survival. In vitro, Spy1 depletion in ovarian cell lines led to reduced proliferation according to CCK8 and plate colony assays. The expression of Spy1 was positively related to pThr187-p27. Flow cytometry revealed that the reduced expression of Spy1 induced the apoptosis of the EOC cells. In summary, our findings suggested that Spy1 may be a novel independent prognostic predictor of survival for ovarian patients.
Asunto(s)
Biomarcadores de Tumor/genética , Proteínas de Ciclo Celular/genética , Proteínas de Neoplasias/genética , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Adulto , Anciano , Apoptosis/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Epitelial de Ovario , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Femenino , Expresión Génica , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Ovario/metabolismo , Ovario/patología , Pronóstico , Análisis de SupervivenciaRESUMEN
PFTK1 was a cell division cycle 2-related serine/threonine protein kinase, which was up-regulated in breast cancer tissues and breast cancer lines. And up-regulated PFTK1 was highly associated with grade, axillary lymph node status, and Ki-67. Moreover, Kaplan-Meier curve showed that up-regulated PFTK1 was related to the poor breast carcinoma patients' overall survival. Here, we first discovered and confirmed that cyclin B was a new interacting protein of PFTK1, and the complex might increase the amount of DVL2, which triggers Wnt/ß-catenin signaling pathway. Furthermore, knockdown of PFTK1 attenuated cell proliferation, anchorage-independent cell growth, and cell migration and invasion by inhibiting the transcriptional activation of ß-catenin for cyclin D1, MMP9, and HEF1, whereas exogenous expression of PFTK1 might promote MDA-MB-231 cells proliferation, migration, and invasion via promoting PFTK1-DVL2-ß-catenin axis. Our findings supported the notion that up-regulated PFTK1 might promote breast cancer progression and metastasis by activating Wnt signaling pathway through the PFTK1-DVL2-ß-catenin axis.