RESUMEN
PURPOSE: The combined therapy of inhibiting T cell immunoglobulin domain and mucin domain 3 (TIM3) and programmed cell death 1/programmed death-ligand 1 (PD1/PDL1) has shown encouraging therapeutic effects in some solid tumors. However, the expression of PD1/PDL1 and TIM3 in fibroblastic tumors is ill defined, which has limited the application of these immune checkpoint inhibitors in such tumors. METHODS: Immunostaining of 68 tissue microarray cores of fibroblastic tumors, including intermediate dermatofibrosarcoma protuberans and malignant myxofibrosarcoma and adult-type fibrosarcoma, was used to determine the expression of PD1, PDL1 and TIM3, as well as their relationship with the accumulation of tumor-infiltrating T lymphocytes (TILs). RESULTS: Both PD1 and PDL1 expression was only observed in a small proportion of fibroblastic tumors, whereas TIM3 was expressed in almost all tumors. However, only the positive expression of PDL1 was related to tumors with high grade and staging. A considerable number of TILs, including CD4- and CD8A-positive T cells and a small group of FoxP3-positive T cells, was also observed in most tumors. The density of TIM3 was positively correlated with that of TILs. Furthermore, higher densities of TIM3, CD4, CD8A and FoxP3 were observed in PD1 and PDL1 double-positive fibroblastic tumors. CONCLUSIONS: This study indicates that TILs with high expression of TIM3 may contribute to immunosuppression in the tumor microenvironment of fibroblastic tumors. Patients with fibroblastic tumors with high expression of PD1/PDL1 and TIM3 may therefore benefit from combination therapy with PD1/PDL1 and TIM3 inhibitors.
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Antígeno B7-H1/biosíntesis , Fibrosarcoma/inmunología , Fibrosarcoma/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/biosíntesis , Linfocitos Infiltrantes de Tumor/inmunología , Receptor de Muerte Celular Programada 1/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
One lung ventilation (OLV) often results in trauma to the unventilated contralateral lung. This study aims to evaluate the effects of different OLV regimens on the injury of the unventilated contralateral lung to identify the best conditions for OLV. Forty rabbits were divided into five groups: a sham group, OLV group I (fraction of inspired oxygen (FIO2) 1.0, tidal volume (VT) 8mL/kg, respiratory rate (R) 40 breaths/min and inspiratory/expiratory ratio (I:E) 1:2), OLV group II (FIO2=1.0, VT 8mL/kg, R 40 breaths/min, I:E 1:2, and positive end-expiratory pressure (PEEP) 5 cm H2O), OLV group III (FIO2 1.0, VT 6mL/kg, R 40 breaths/min, I:E 1:2 and PEEP 5 cm H2O) and OLV group IV (FIO2 0.8, VT 6mL/kg, R 40 breaths/min, I:E 1:2 and PEEP 5 cm H2O). Animals from all OLV groups received two-lung ventilation (TLV) to establish a baseline, followed by one of the indicated OLV regimens. The rabbits in the sham group were intubated through trachea and ventilated with fresh air. Arterial blood gas samples were collected, lung injury parameters were evaluated, and the concentrations of TNF-α and IL-8 in bronchoalveolar lavage fluid (BALF) and pulmonary surfactant protein A (SPA) in the unventilated lung were also measured. In OLV group I, the unventilated left lung had higher TNF-α, IL-8 and lung injury score but lower SPA than the ventilated right lung. In OLV groups I to III, the concentrations of TNF-α, IL-8 and lung injury score in the left lung decreased but SPA increased. No differences in these parameters between OLV groups III and IV were observed. Strategic ventilation designed for OLV groups III and IV reduced OLV-induced injury of the non-ventilated contralateral lung in rabbits.(AU)
Ventilação pulmonar unilateral (OLV) frequentemente resulta em trauma no pulmão contralateral não ventilado. Este estudo visa avaliar os efeitos de diferentes regimes de OLV sobre a lesão do pulmão contralateral não ventilado para identificar as melhores condições para OLV. Quarenta coelhos foram divididos em cinco grupos: um grupo falso, OLV grupo I (fração de oxigênio inspirado (FIO2) 1.0, volume corrente (VT) 8mL/kg, frequência respiratória (R) 40 respirações/min e relação inspiração/expiração (I:E) 1:2), OLV grupo II (FIO2=1.0, VT 8mL/kg, R 40 respirações/min, I:E 1:2, e pressão positiva expiratória final (PEEP) 5 cm H2O), OLV grupo III (FIO2 1.0, VT 6mL/kg, R 40 respirações/min, I:E 1:2 e PEEP 5 cm H2O) e OLV grupo IV (FIO2 0.8, VT 6mL/kg, R 40 respirações/min, I:E 1:2 e PEEP 5 cm H2O). Os animais de todos os grupos OLV receberam ventilação nos dois pulmões (TLV) para estabelecer uma linha de base, seguida por um dos regimes OLV indicados. Os coelhos do grupo falso foram intubados através da traqueia e ventilados com ar fresco. Amostras de gases no sangue arterial foram coletadas, parâmetros de lesão pulmonar foram avaliados e as concentrações de TNF-α e IL-8 no fluido de lavagem bronco alveolar (BALF) e proteína A do surfactante pulmonar (SPA) no pulmão não ventilado também foram medidas. No grupo OLV I, o pulmão esquerdo não ventilado tinha maior índice de TNF-α, IL-8 e lesão pulmonar, mas menor SPA do que o pulmão direito ventilado. Nos grupos OLV I a III, as concentrações de TNF-α, IL-8 e a pontuação de lesão pulmonar no pulmão esquerdo diminuíram, mas o SPA aumentou. Não foram observadas diferenças nestes parâmetros entre os grupos OLV III e IV. A ventilação estratégica projetada para os grupos OLV III e IV reduziu a lesão induzida por OLV do pulmão contralateral não ventilado em coelhos.(AU)
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Animales , Conejos , Ventilación Pulmonar , Lesión Pulmonar Aguda/complicaciones , Ventilación Unipulmonar/veterinariaRESUMEN
PURPOSE: This study set out to probe into the effect and mechanism of miR-144-3p on radiosensitivity of gastric cancer (GC) cells. METHODS: Cancer tissue and paracancerous tissue of GC patients admitted to our hospital were collected, their miR-144-3p expression was tested, GC cells were transfected, and survival and biological behavior of those cells under radiation were detected. RESULTS: After detection, miR-144-3p expression was down-regulated in GC tissue, while ZEB1 was up-regulated. There was no remarkable difference in the survival fraction of cells in each group before receiving radiation, but that of tumor cells decreased obviously (p < 0.05) after radiation exposure. Survival fraction of cells overexpressing miR-144-3p or silencing ZEB1 decreased more obviously, while the inhibition of miR-144-3p or overexpressing ZEB1 was weaker. Biological behavior of cells under 6 Gy radiation was detected. It was found that miR-144-3p overexpression or silencing ZEB1 dramatically inhibited the proliferation activity of GC cells under 6 Gy radiation, increased the levels of pro-apoptotic Bax and caspase-3 proteins (p < 0.05) and decreased the anti-apoptotic protein Bcl-2 level (p < 0.05), resulting in an increase in the apoptosis rate of cells. miR-144-3p was confirmed to be ZEB1 targeting site by dual luciferase report. Moreover, rescue experiments prove that it can increase the radiosensitivity of GC cells by regulating ZEB1 expression. CONCLUSION: miR-144-3p expression was down-regulated in GC, and it can increase the radiosensitivity of those cells by inhibiting ZEB1 expression.
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MicroARNs/metabolismo , Tolerancia a Radiación , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/radioterapia , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Supervivencia Celular , Regulación hacia Abajo , Femenino , Mucosa Gástrica/metabolismo , Silenciador del Gen , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Dosis de Radiación , Transfección/métodos , Regulación hacia Arriba , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To explore the role of ADMA in gastric cancer. METHODS: The specimens of 115 gastric cancer patients were analyzed by ELISA and survival analysis. Functional assays were used to assess the effects of ADMA on gastric cancer cells. Experiments were conducted to detect the signaling pathway induced by ADMA in GC. RESULTS: Gastric cancer patients with high ADMA levels had poor prognosis and low survival rate. Furthermore, high level of ADMA did not affect the proliferation while promoted the migration and invasion of gastric cancer cell. Moreover, ADMA enhanced the epithelial-mesenchymal transition (EMT). Importantly, ADMA positively regulated ß-catenin expression in GC and promoted GC migration and invasion via Wnt/ß-catenin pathway. CONCLUSIONS: ADMA regulates gastric cancer cell migration and invasion via Wnt/ß-catenin signaling pathway and which may be applied to clinical practice as a diagnostic and prognostic biomarker.
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Adenocarcinoma/sangre , Adenocarcinoma/patología , Arginina/análogos & derivados , Transición Epitelial-Mesenquimal , Neoplasias Gástricas/sangre , Neoplasias Gástricas/patología , Vía de Señalización Wnt , Adenocarcinoma/mortalidad , Arginina/sangre , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/fisiopatología , Pronóstico , Neoplasias Gástricas/mortalidad , Cicatrización de Heridas/fisiologíaRESUMEN
Utilizando um anticorpo monoclonal contra a aflatoxina B1 (AFB1) como ligante, foi identificado um mimotopo específico de aflatoxina B1 após se realizarem quatro ciclos de seleção biológica de 7-peptídeos aleatórios em biblioteca de fago exibida. O mimotopo é denominado P10, e sua sequência de aminoácidos é YRRHEKD. O soro imunológico de ratos Balb/c imunizados com P10 foi especificamente ligado à aflatoxina B1-albumina, indicando que o anticorpo era específico ao AFB1. Esses resultados sugerem que é possível desenvolver a vacina baseada em mimotopo associado à toxina.(AU)
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Animales , Ratas , Vacunas Fúngicas/análisis , Aflatoxina B1 , Aptámeros de Péptidos/inmunología , Inmunogenicidad Vacunal , Ratones Endogámicos BALB C/inmunologíaRESUMEN
Utilizando um anticorpo monoclonal contra a aflatoxina B1 (AFB1) como ligante, foi identificado um mimotopo específico de aflatoxina B1 após se realizarem quatro ciclos de seleção biológica de 7-peptídeos aleatórios em biblioteca de fago exibida. O mimotopo é denominado P10, e sua sequência de aminoácidos é YRRHEKD. O soro imunológico de ratos Balb/c imunizados com P10 foi especificamente ligado à aflatoxina B1-albumina, indicando que o anticorpo era específico ao AFB1. Esses resultados sugerem que é possível desenvolver a vacina baseada em mimotopo associado à toxina.(AU)
Asunto(s)
Animales , Ratas , Vacunas Fúngicas/análisis , Aflatoxina B1 , Aptámeros de Péptidos/inmunología , Inmunogenicidad Vacunal , Ratones Endogámicos BALB C/inmunologíaRESUMEN
OBJECTIVE: To observe the effects of different doses of propofol on the growth of transplanted liver tumor in BALB/C mice and check the expression of PCNA, CD34 and pAKT proteins to clarify the mechanism on molecule level. METHOD: Human primary liver cancer cells SMMC-7721 were subcutaneously cultured in BALB/C mice, and the transplanted tumor model of BALB/C mice was constructed. Forty mice successfully modeled were randomly divided into 5 groups (n = 8): the blank control group (group C), low-fat milk group (group I), low-dose (50 mg/kg) propofol group (P1), middle-dose (100 mg/kg) propofol group (P2) and high dose (150 mg/kg) propofol group (P3). Tumor volume changes were observed at 3, 6, 9, 12, 15 and 18 days (T1, T2, T3, T4, T5, T6 and T7) before and after administration of the drug, and tumor growth curves were plotted. After 19 days of administration, all mice were killed for tumor collection, tumor weight was measured, and the tumor inhibition rate of propofol was calculated. The protein expression of cluster of differentiation 34 (CD34) in transplanted tumor was detected by immunohistochemistry, and the protein expression of proliferating cell nuclear antigen (PCNA) and phospho-Akt (pAKT) was detected by immunofluorescence. RESULTS: Compared with group C, there was no significant difference in tumor volume in group I. At T2 ~ 7, the tumor volume of group P1, P2 and P3 decreased successively (P < 0.05). There was no significant difference in the inhibitory rate of tumor in group I, and the inhibitory rate of tumor in group P1, P2 and P3 increased successively (P < 0.05). There was no significant difference in PCNA, CD34, and pAKT protein expression in group I, while PCNA, CD34, and pAKT protein content in P1, P2, P3 groups were successively decreased (P < 0.05). CONCLUSION: Propofol had a dose-dependent effect on the growth of liver cancer xenografts in mice, inhibiting the expression of PCNA, CD34 and pAKT proteins, and the effect was most obvious in the 150 mg/kg propofol group.
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Antígenos CD34/análisis , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Antígeno Nuclear de Célula en Proliferación/análisis , Propofol/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/análisis , Animales , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Propofol/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ovarian cancer is the most common malignant tumors of the female reproductive system, and its standard treatments are cytoreductive surgery and platinum-based adjuvant chemotherapy. Great advances have been achieved in novel treatment strategies, including targeted therapy and immunotherapy. However, ovarian cancer has the highest mortality rate among gynecological tumors due to therapeutic resistance and the gap between preclinical data and actual clinical efficacy. Organoids are a 3D culture model that markedly affects gene analysis, drug screening, and drug sensitivity determination of tumors, especially when used in targeted therapy and immunotherapy. In addition, organoid can lead to advances in the preclinical research of ovarian cancer due to its convenient cultivation, good genetic stability, and high homology with primary tumors.
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Inmunoterapia/métodos , Terapia Molecular Dirigida/métodos , Organoides , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales/métodos , Femenino , Genómica , Xenoinjertos , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia Adoptiva/métodos , Organoides/crecimiento & desarrollo , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Esferoides Celulares , Microambiente TumoralRESUMEN
PURPOSE: This study aimed at investigating the efficacy of percutaneous transhepatic biliary stenting (PTBS) combined with 125I seeds intracavitary irradiation in the treatment of extrahepatic cholangiocarcinoma (EHC) and to preliminarily explore the prognostic values of inflammation-based scores in these patients. METHODS: A total of 113 clinically/pathologically diagnosed cases of EHC who received PTBS combined with 125I seeds implantation were retrospectively analyzed. The postoperative changes of clinical symptoms and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TBIL), direct bilirubin (DBIL), and albumin (ALB) were observed. Preoperative clinical data were extracted to calculate inflammation-based scores, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR). Kaplan-Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of inflammation-based scores. RESULTS: After operation, clinical symptoms such as jaundice and fever significantly improved in all patients. At 1 month and 3 months postoperatively, serum levels of ALT, AST, ALP, TBIL, and DBIL significantly reduced, and ALB significantly increased, compared with preoperative values. The median survival time of the patients was 12 months and the 1-year survival rate was 56.8%. Univariate analysis revealed that factors related to overall survival were CA19-9, TBIL, ALB, SII, and NLR. Multivariate analysis further identified SII and NLR as independent prognostic models. CONCLUSION: The combination of PTBS and 125I seeds intracavitary irradiation is an effective palliative treatment for advanced EHC. Elevated SII and NLR can be used to predict poor survival.
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Neoplasias de los Conductos Biliares/mortalidad , Procedimientos Quirúrgicos del Sistema Biliar/mortalidad , Colangiocarcinoma/mortalidad , Mediadores de Inflamación/metabolismo , Inflamación/diagnóstico , Radioisótopos de Yodo/uso terapéutico , Stents , Anciano , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Masculino , Siembra Neoplásica , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. The present study investigated the possible difference on a molecular level between two duck breeds. The digital gene expression profiling (DGE) technology was used to enrich the differentially expressed genes (DEGs) in BF between the Jianchang and Nonghua-P strains of ducks. DGE data identified 195 DEGs in the bursa. Gene Ontology (GO) analysis suggested that DEGs were mainly enriched in the metabolic pathways and ribosome components. Pathways analysis identified the spliceosome, RNA transport, RNA degradation process, Jak-STAT signaling pathway, TNF signaling pathway and B cell receptor signaling pathway. The results indicated that the main difference in the BF between the two duck strains was in the capabilities of protein formation and B cell development. These data have revealed the main divergence in the BF on a molecular level between genetically different duck breeds and may help to perform molecular breeding programs in poultry in the future.
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Animales , Ontología de Genes , Patos/genéticaRESUMEN
The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. The present study investigated the possible difference on a molecular level between two duck breeds. The digital gene expression profiling (DGE) technology was used to enrich the differentially expressed genes (DEGs) in BF between the Jianchang and Nonghua-P strains of ducks. DGE data identified 195 DEGs in the bursa. Gene Ontology (GO) analysis suggested that DEGs were mainly enriched in the metabolic pathways and ribosome components. Pathways analysis identified the spliceosome, RNA transport, RNA degradation process, Jak-STAT signaling pathway, TNF signaling pathway and B cell receptor signaling pathway. The results indicated that the main difference in the BF between the two duck strains was in the capabilities of protein formation and B cell development. These data have revealed the main divergence in the BF on a molecular level between genetically different duck breeds and may help to perform molecular breeding programs in poultry in the future.(AU)
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Animales , Ontología de Genes , Patos/genéticaRESUMEN
BACKGROUND: The subgroup of young patients with non-small-cell lung cancer (NSCLC) is poorly understood. We retrospectively studied the clinical characteristics, gene mutations, and outcomes of patients with NSCLC (aged ≤ 40 years). RESULTS: Of the 7494 patients with lung cancer diagnosed from February 2001 to October 2016, 252 aged ≤ 40 years showed NSCLC. We divided their cases into non-squamous cell carcinoma and squamous cell carcinoma groups according to their histology results. Of the 252 young NSCLC patients, 173 (69%) patients had stage IIIB or IV, and 196 (78%) had never smoked. The four most common metastases were intrapulmonary lesions, pleura, bone, and brain. Among patients with adenocarcinoma, 29 (40%, n = 73) harbored epidermal growth factor receptor (EGFR) mutations, 25 (34%, n = 74) harbored anaplastic lymphoma kinase (ALK) translations, and 1 (14%, n = 7) harbored ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) translations. The median progression-free survival (PFS) and overall survival (OS) were 3.3 and 27.6 months for patients receiving chemotherapy (n = 65), and 12.1 and 33.6 months for patients receiving EGFR tyrosine kinase inhibitors (TKIs) (n = 13), respectively. Patients receiving crizotinib had a median PFS time of 21.9 months (n = 8). CONCLUSIONS: Young patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación , Adulto , Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Pronóstico , Proto-Oncogenes Mas , Proteínas Tirosina Quinasas Receptoras/genética , Estudios RetrospectivosRESUMEN
PURPOSE: The expression of miR-489 is linked to tumor development and progression; nevertheless, its role in tumor growth and invasion of colorectal cancer (CRC) and the underlying mechanism has not been clarified. EXPERIMENTAL DESIGN: We used quantitative RT-PCR to measure the expression of mature miR-489 in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were predicted with TargetScan and substantiated by dual-luciferase reporter assay. Furthermore, we did in vitro and in vivo analysis with expression vectors and small interfering RNAs, to elucidate the precise role of miR-489 and its target gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion. RESULTS: Compared to the corresponding non-tumor tissues, miR-489 was frequently downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC recurrence free survival years in the group with elevated miR-489 expression than those with lower miR-489 expression. In addition, we examined that miR-489 obviously inhibited the migratory and invasive capability in CRC. In further study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and downregulates its expression, and HDAC7 expression promoted tumor cell proliferation and invasion. We demonstrated that miR-489 suppresses tumor invasion and metastasis in CRC by targeting HDAC7. CONCLUSIONS: We identified that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial light on how miR-489 functions in CRC pathogenesis.
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Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias Colorrectales/patología , Histona Desacetilasas/metabolismo , Neoplasias Hepáticas/secundario , MicroARNs/genética , Recurrencia Local de Neoplasia/patología , Animales , Apoptosis , Biomarcadores de Tumor/genética , Movimiento Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasas/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The mRNA expression of cell adhesion molecule 1 (CADM1) and its clinicopathological significance in esophageal squamous cell carcinoma (ESCC) tissues were investigated. CADM1 mRNA and protein expression were detected in tissue samples from 50 patients with ESCC by reverse transcription-polymerase chain reaction (RT-PCR) and streptavidin-peroxidase (SP) immunohistochemistry; adjacent tissues served as controls. The average CADM1 mRNA expression was significantly downregulated in the cancer tissues (0.522 ± 0.247) than in the controls (0.871 ± 0.192), (t = 7.882, P < 0.05). CADM1 mRNA expression was significantly downregulated in ESCC patients with positive lymph node metastasis than in those with negative lymph node metastasis (t = 3.207, P < 0.05). There was a correlation between CADM1 mRNA expression and tumor-node-metastasis (TNM) stage (t = 2.673, P < 0.050), but not with age, gender, and histological grade (P > 0.05). The positive expression rate of CADM1 protein in the 50 cases of ESCC was significantly lower than that of the control group (χ2 = 29.87, P < 0.01). Out of 28 patients with non-lymph node metastasis, 20 (71.43%) positively expressed CADM1; out of 22 patients with lymph node metastasis, only 7 (31.82%) positively expressed CADM1. There was a significant difference in the positive protein expression rates of CADM1 between the two groups (χ2 = 7.782, P < 0.01). CADM1 mRNA expression was highly upregulated in normal tissues compared to ESCC tissues, indicating that the loss of CADM1 expression influenced the pathogenesis, invasion, and metastasis of ESCC, and allowing for the prognosis of the disease in patients with ESCC after treatment.
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Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Moléculas de Adhesión Celular/genética , Neoplasias Esofágicas/genética , Inmunoglobulinas/genética , ARN Mensajero/genética , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Molécula 1 de Adhesión Celular , Moléculas de Adhesión Celular/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunoglobulinas/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , ARN Mensajero/metabolismo , Regulación hacia ArribaRESUMEN
The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300-320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.
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Proteína GAP-43/metabolismo , Expresión Génica/efectos de los fármacos , Infarto de la Arteria Cerebral Media/prevención & control , Fármacos Neuroprotectores/farmacología , Tretinoina/farmacología , Regulación hacia Arriba/efectos de los fármacos , Animales , Isquemia Encefálica/prevención & control , Proteína GAP-43/genética , Inmunohistoquímica , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Masculino , Distribución Aleatoria , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy worldwide with surgery as the only curative treatment. Long-term overall survival (OS) of ovarian cancer is far from satisfactory, even though significant improvement has been made in post-operative chemotherapy. One of the most important death cause is the chemoresistance due to consecutive chemotherapy. Therefore, understanding the molecular mechanisms involved in ovarian cancer development and identification of novel therapeutic targets are urgently required. METHODS: Immunohistochemical (IHC) staining was used to explore the expression pattern of mitogen-activated protein kinase (MAPK)-interacting kinase 1 (MNK1) in tumor tissues from 138 epithelial ovarian cancer (EOC) patients. Clinicopathological data were subjected to Kaplan-Meier survival and Cox multivariate analyses to evaluate the prognostic value of MNK1 in EOC. Overexpression and silencing procedures were performed on OVCAR-5 cells to investigate the mechanisms of MNK1 in regulating EOC development. The anti-tumor effects of CGP57380, a specific MNK inhibitor, were examined by cell viability assay. RESULTS: Higher MNK1 expression showed significant relationship with advanced FIGO stage and positive lymph node metastasis of EOC. Univariate and multivariate analyses revealed that MNK1 was an independent prognostic factor for OS of EOC patients. In vitro study demonstrated that MNK1 can promote cell proliferation through regulating the phosphorylation level of eukaryotic initiation factor 4E. In addition, inhibition of MNK1 by CGP57380 significantly down-regulated the OVCAR-5 cell viability. CONCLUSION: High MNK1 expression in EOC tissues indicates poor clinical outcomes, and MNK1 can act as a potential target for novel chemotherapy development towards EOC.
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Biomarcadores de Tumor/análisis , Péptidos y Proteínas de Señalización Intracelular/biosíntesis , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Proteínas Serina-Treonina Quinasas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/análisis , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Ováricas/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Serina-Treonina Quinasas/análisisRESUMEN
We evaluated serum total bilirubin levels as a predictor for metabolic syndrome (MetS) and investigated the relationship between serum total bilirubin levels and MetS prevalence. This cross-sectional study included 1728 participants over 65 years of age from Eastern China. Anthropometric data, lifestyle information, and previous medical history were collected. We then measured serum levels of fasting blood-glucose, total cholesterol, triglycerides, and total bilirubin, as well as alanine aminotransferase activity. The prevalence of MetS and each of its individual component were calculated per quartile of total bilirubin level. Logistic regression was used to assess the correlation between serum total bilirubin levels and MetS. Total bilirubin level in the women who did not have MetS was significantly higher than in those who had MetS (P<0.001). Serum total bilirubin quartiles were linearly and negatively correlated with MetS prevalence and hypertriglyceridemia (HTG) in females (P<0.005). Logistic regression showed that serum total bilirubin was an independent predictor of MetS for females (OR: 0.910, 95%CI: 0.863-0.960; P=0.001). The present study suggests that physiological levels of serum total bilirubin might be an independent risk factor for aged Chinese women, and the prevalence of MetS and HTG are negatively correlated to serum total bilirubin levels.
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Bilirrubina/sangre , Síndrome Metabólico/sangre , Anciano , Biomarcadores/sangre , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Síndrome Metabólico/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
Monema flavescens Walker (Lepidoptera: Limacodidae) is a serious polyphagous defoliator. Using scanning electron microscopy, the external morphology of the antennal sensilla of this pest was examined for a better understanding of the mechanisms of insect-insect and insect-plant chemical communications. The antennae of M. flavescens were filiform in shape, and 11 morphological types of sensilla were found in both sexes. Six types of likely chemosensory sensilla were identified: uniporous sensilla chaetica, multiporous sensilla trichodea, and four types of multiporous sensilla basiconica. The sensilla identified as likely mechanoreceptors included two subtypes of aporous sensilla chaetica, aporous sensilla coeloconica, aporous sensilla styloconica, and Böhm's bristles, whereas the position of the antennae was monitored by Böhm's bristles.
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Lepidópteros/citología , Sensilos/citología , Animales , Antenas de Artrópodos , Femenino , Masculino , Microscopía Electrónica de RastreoRESUMEN
PURPOSE: CD44v6 plays a controversial role in tumor progression and patient outcome in colorectal cancer by plenty of conflicting reports. The purpose of this study was to profile the intratumoral heterogeneity of CD44v6 in rectal cancer and investigate its role in lymph node metastasis. METHODS: Sixty patients were included in this study. Immunohistochemistry for CD44v6 was performed in normal mucosa, primary tumor, and lymph node metastasis with whole tissue sections. The staining intensity in tumor center and invasive front was separately measured. Sampling bias was evaluated by quantitative real-time PCR with 15 pairs of frozen tissues from different sites of the primary tumor. RESULTS: CD44v6 expression increased from normal mucosa to primary tumor to lymph node metastasis. Multiple intratumoral staining patterns was observed in primary tumor, and CD44v6 expression in invasive front was significantly higher than that in tumor center. In addition, mRNA expression levels differed across different geographical regions of the tumor. No association between CD44v6 expression and lymph node metastasis was revealed. CONCLUSIONS: Substantial intratumoral heterogeneity of CD44v6 exists in rectal cancer that impacts the outcome of individual studies. CD44v6 expression should be assessed in a more precise way with a specified staining pattern and in a designated location.
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Adenocarcinoma/secundario , Biomarcadores de Tumor/metabolismo , Receptores de Hialuranos/metabolismo , Membrana Mucosa/metabolismo , Neoplasias del Recto/patología , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/genética , Femenino , Estudios de Seguimiento , Humanos , Receptores de Hialuranos/genética , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Clasificación del Tumor , Invasividad Neoplásica , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias del Recto/genética , Neoplasias del Recto/metabolismo , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300–320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.