RESUMEN
PURPOSE: Colorectal cancer (CRC) is one most cancer type of high incidence and high mortality rate. Metastasis play an important role in survival rate and life quality of colorectal cancer patients. Nerve growth factor (NGF) has been shown to be involved in the metastasis and deterioration in many cancers, but the detail mechanisms in promoting the metastasis of colorectal cancer remain unknown. In this study, we aimed to explore the mechanism of NGF promoting colorectal cancer metastasis to provide new insights for developing NGF anti-colorectal cancer drugs. METHODS: We examined the expression of NGF in human colorectal cancer by immunohistochemical staining, and Western blot to evaluate the relationship between NGF and colorectal cancer metastasis. Using biochemical experiments including wound healing assay, transwell migration and invasion assay, RT-PCR, Western blot and ELISA to explore the relative mechanism of NGF promoting colorectal cancer cells metastasis in vivo. RESULTS: Our results found that the high expression of NGF was related with high incidence of metastasis. The binding of NGF to TrkA phosphorylated TrkA, which activated MAPK/Erk signaling pathway increasing the expression NGAL to enhance the activity of MMP2 and MMP9, promoted colorectal cancer metastasis. CONCLUSION: Our finding demonstrated that NGF increased NGAL expression to enhance MMPs activity to promoted colorectal cancer cell metastasis by TrkA-MAPK/Erk axis.
Asunto(s)
Neoplasias Colorrectales/patología , Lipocalina 2/fisiología , Metaloproteinasas de la Matriz/fisiología , Factor de Crecimiento Nervioso/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies and leading cancer-associated deaths worldwide. Ozone has been proposed as a promising therapeutic agent in the treatment of various disorders. PURPOSE: The purpose of this paper is to assess the potential anticancer effects of the ozone on liver cancer cells. METHOD: The liver cancer cell line of bel7402 and SMMC7721 was used in this study. Proliferation was evaluated using the CCK-8 and the colony formation assay. Wond healing assay and transwell assay without Matrigel were used to evaluate their migration ability. Flow cytometry was used for cell cycle analysis and reactive oxygen species (ROS) determination. Glutathione detection kit was used for measurement of glutathione level. Protein expression was estimated by western blot analysis. RESULTS: Ozone treatment inhibited liver cancer cell proliferation, colony formation. Ozone induced G2/M phase cell cycle arrest, which could be elucidated by the change of protein levels of p53, p21, Cyclin D1, cyclin B1, cdc2, and CDK4. We also found that ozone treatment inhibited migration ability by inhibiting EMT-relating protein. Ozone also induced ROS accumulation and decreased glutathione level decreased, which contributed to the inactivation of the PI3K/AKT/NF-κB pathway. Finally, we found that pre-treatment of liver cancer cells with N-acetylcysteine resisted ozone-induced effects. CONCLUSIONS: Ozone restrains the proliferation and migration potential and EMT process of liver cancer cells via ROS accumulation and PI3K/AKT/NF-κB suppression.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas/metabolismo , Ozono/farmacología , Especies Reactivas de Oxígeno/metabolismo , Carcinoma Hepatocelular/patología , Proteínas de Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Glutatión/metabolismo , Humanos , Neoplasias Hepáticas/patología , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayo de Tumor de Célula MadreRESUMEN
PURPOSE: The tumor immune microenvironment (TIME) is now considered as an important factor during gastric cancer (GC) development. This study identified a novel immune-related risk model for predicting prognosis and assessing the immune status of GC patients. METHODS: Transcriptomic data were obtained from the TCGA database. The differential expressed immune-related genes (IRGs) were identified through the ImmPort portal. Enrichment analysis was performed to explore the potential molecular mechanism of these IRGs. By the Cox regression analysis, we constructed the immune prognostic model. Then, the association between the model and the immune microenvironment was estimated. The model was validated in the GSE84433 dataset. RESULTS: Totally, we identified 222 differentially expressed IRGs. These IRGs were closely correlated with immune response and immune signaling pathways. Through the Cox regression analysis, we developed the immune prognostic model based on the expression of seven IRGs (CXCL3, NOX4, PROC, FAM19A4, RNASE2, IGHD2-15, CGB5). Patients were stratified into two groups according to immune-related risk scores. Survival analysis indicated that the prognosis of high-risk patients was poorer than low-risk patients. Moreover, the immune-related risk score was an independent prognostic biomarker. More importantly, we found that the infiltration level of immunosuppressive cells and the expression of inhibitory immune checkpoints were higher in high-risk patients. The immune microenvironment tended to be a suppressive status in patients with high-risk scores. CONCLUSION: This study demonstrated that our model had predictive value for prognosis and the TIME in GC. It might be a robust tool to improve personalized patient management.
Asunto(s)
Inmunidad/genética , Modelos Inmunológicos , Neoplasias Gástricas/inmunología , Microambiente Tumoral/inmunología , Quimiocinas CXC/genética , Citocinas/genética , Bases de Datos Genéticas , Progresión de la Enfermedad , Enanismo Hipofisario/genética , Neurotoxina Derivada del Eosinófilo/genética , Expresión Génica/inmunología , Humanos , Proteínas de Punto de Control Inmunitario/metabolismo , Tolerancia Inmunológica/genética , NADPH Oxidasa 4/genética , Células Madre Neoplásicas/inmunología , Pronóstico , Análisis de Regresión , Factores de Riesgo , Neoplasias Gástricas/mortalidad , Análisis de Supervivencia , Transcriptoma , Microambiente Tumoral/genéticaRESUMEN
Abstract Rhizosphere microorganisms and endophytes can help their hosts absorb nutrients and regulate the levels of plant hormones. Moreover, they can modulate the expressions of host genes, assist hosts in eliminating reactive oxygen species (ROS) and secreting volatile organic compounds. Therefore, rhizosphere microorganisms and endophytes are considered as determinant factors driving processes involved in the growth of host plants. However, the physiological and ecological functions, as well as the molecular mechanism underlying the behavior of rhizosphere microorganisms and endophytes in their role in the adaptive capacity of host plants in the karstic high-calcium environment have not been systematically studied. This review summarizes the physiological and molecular mechanisms of rhizosphere microorganisms and endophytes which help host plants to adapt to various kinds of adverse environments. The adaptive capacities of plants growing in adverse environments, partly, or totally, depends on microorganisms co-existing with the host plants.
Resumo Os microorganismos e endófitos da rizosfera podem ajudar seus hospedeiros a absorver nutrientes e regular os níveis de hormônios vegetais. Além disso, eles podem modular as expressões dos genes hospedeiros, auxiliar os hospedeiros na eliminação de espécies reativas de oxigênio (ROS) e secretar compostos orgânicos voláteis. Portanto, microorganismos e endófitos da rizosfera são considerados determinantes dos processos envolvidos no crescimento de plantas hospedeiras. No entanto, as funções fisiológicas e ecológicas, bem como o mecanismo molecular subjacente ao comportamento dos microrganismos e endofíticos da rizosfera no seu papel na capacidade adaptativa das plantas hospedeiras no ambiente cárstico de alto teor de cálcio, não foram sistematicamente estudados. Esta revisão resume os mecanismos fisiológicos e moleculares de microrganismos e endófitos da rizosfera que ajudam as plantas hospedeiras a se adaptarem a vários tipos de ambientes adversos. As capacidades adaptativas das plantas que crescem em ambientes adversos, em parte ou totalmente, dependem de microrganismos coexistentes com as plantas hospedeiras.
Asunto(s)
Simbiosis , Calcio , Plantas , Rizosfera , EndófitosRESUMEN
Rhizosphere microorganisms and endophytes can help their hosts absorb nutrients and regulate the levels of plant hormones. Moreover, they can modulate the expressions of host genes, assist hosts in eliminating reactive oxygen species (ROS) and secreting volatile organic compounds. Therefore, rhizosphere microorganisms and endophytes are considered as determinant factors driving processes involved in the growth of host plants. However, the physiological and ecological functions, as well as the molecular mechanism underlying the behavior of rhizosphere microorganisms and endophytes in their role in the adaptive capacity of host plants in the karstic high-calcium environment have not been systematically studied. This review summarizes the physiological and molecular mechanisms of rhizosphere microorganisms and endophytes which help host plants to adapt to various kinds of adverse environments. The adaptive capacities of plants growing in adverse environments, partly, or totally, depends on microorganisms co-existing with the host plants.(AU)
Os microorganismos e endófitos da rizosfera podem ajudar seus hospedeiros a absorver nutrientes e regular os níveis de hormônios vegetais. Além disso, eles podem modular as expressões dos genes hospedeiros, auxiliar os hospedeiros na eliminação de espécies reativas de oxigênio (ROS) e secretar compostos orgânicos voláteis. Portanto, microorganismos e endófitos da rizosfera são considerados determinantes dos processos envolvidos no crescimento de plantas hospedeiras. No entanto, as funções fisiológicas e ecológicas, bem como o mecanismo molecular subjacente ao comportamento dos microrganismos e endofíticos da rizosfera no seu papel na capacidade adaptativa das plantas hospedeiras no ambiente cárstico de alto teor de cálcio, não foram sistematicamente estudados. Esta revisão resume os mecanismos fisiológicos e moleculares de microrganismos e endófitos da rizosfera que ajudam as plantas hospedeiras a se adaptarem a vários tipos de ambientes adversos. As capacidades adaptativas das plantas que crescem em ambientes adversos, em parte ou totalmente, dependem de microrganismos coexistentes com as plantas hospedeiras.(AU)
Asunto(s)
Simbiosis , Calcio , Plantas , Rizosfera , EndófitosRESUMEN
Rhizosphere microorganisms and endophytes can help their hosts absorb nutrients and regulate the levels of plant hormones. Moreover, they can modulate the expressions of host genes, assist hosts in eliminating reactive oxygen species (ROS) and secreting volatile organic compounds. Therefore, rhizosphere microorganisms and endophytes are considered as determinant factors driving processes involved in the growth of host plants. However, the physiological and ecological functions, as well as the molecular mechanism underlying the behavior of rhizosphere microorganisms and endophytes in their role in the adaptive capacity of host plants in the karstic high-calcium environment have not been systematically studied. This review summarizes the physiological and molecular mechanisms of rhizosphere microorganisms and endophytes which help host plants to adapt to various kinds of adverse environments. The adaptive capacities of plants growing in adverse environments, partly, or totally, depends on microorganisms co-existing with the host plants.
Asunto(s)
Calcio , Simbiosis , Endófitos , Plantas , RizosferaRESUMEN
BACKGROUND: Surgery is becoming more practical and effective than conservative treatment in improving the poor outcomes of patients with breast cancer liver metastasis (BCLM). However, there is no generally acknowledged set of standards for identifying BCLM candidates who will benefit from surgery. METHODS: Between January 2011 and September 2018, 67 female BCLM patients who underwent partial hepatectomy were selected for analysis in the present study. Prognostic factors after hepatectomy were determined. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and intrahepatic recurrence-free survival (IHRFS). RESULTS: The 1-, 3- and 5-year OS of patients treated with surgery was 93.5%, 73.7% and 32.2%, respectively, with a median survival time of 57.59 months. The Pringle manoeuvre [hazard radio (HR) = 0.117, 95% CI0.015-0.942, p = 0.044] and an increased interval between breast surgery and BCLM diagnosis (HR0.178, 95% CI 0.037-0.869, p = 0.033) independently predicted improved overall survival for BCLM patients. The 1-, 2- and 3-year IHRFS of patients who underwent surgery was 62.8, 32.6% and 10.9%, respectively, with a median intrahepatic recurrence-free survival time of 13.47 months. Moderately differentiated tumours (HR 0.259, 95% CI 0.078-0.857, p = 0.027) and the development of liver metastasis more than 2 years after breast surgery (HR 0.270, 95% CI 0.108-0.675, p = 0.005) might be predictors of increased IHRFS. CONCLUSIONS: An interval of more than 2 years between breast cancer surgery and liver metastasis seems to be an indication of liver surgery in BCLM patients. The Pringle manoeuvre and moderately differentiated tumours are potential predictors associated with OS and IHRFS, respectively, as benefits from liver resection. Studies with increased sample sizes are warranted to validate our results.
Asunto(s)
Neoplasias de la Mama/patología , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Factores de TiempoRESUMEN
PURPOSE: To evaluate and compare the efficiency and safety of raltitrexed- or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). METHODS: We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. RESULTS: The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatment-related death occurred in either group. CONCLUSION: TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioembolización Terapéutica , Neoplasias Colorrectales/patología , Floxuridina/administración & dosificación , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Quinazolinas/administración & dosificación , Tiofenos/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Floxuridina/efectos adversos , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Pronóstico , Quinazolinas/efectos adversos , Estudios Retrospectivos , Análisis de Supervivencia , Tiofenos/efectos adversos , Resultado del TratamientoRESUMEN
Abstract Rhizosphere microorganisms and endophytes can help their hosts absorb nutrients and regulate the levels of plant hormones. Moreover, they can modulate the expressions of host genes, assist hosts in eliminating reactive oxygen species (ROS) and secreting volatile organic compounds. Therefore, rhizosphere microorganisms and endophytes are considered as determinant factors driving processes involved in the growth of host plants. However, the physiological and ecological functions, as well as the molecular mechanism underlying the behavior of rhizosphere microorganisms and endophytes in their role in the adaptive capacity of host plants in the karstic high-calcium environment have not been systematically studied. This review summarizes the physiological and molecular mechanisms of rhizosphere microorganisms and endophytes which help host plants to adapt to various kinds of adverse environments. The adaptive capacities of plants growing in adverse environments, partly, or totally, depends on microorganisms co-existing with the host plants.
Resumo Os microorganismos e endófitos da rizosfera podem ajudar seus hospedeiros a absorver nutrientes e regular os níveis de hormônios vegetais. Além disso, eles podem modular as expressões dos genes hospedeiros, auxiliar os hospedeiros na eliminação de espécies reativas de oxigênio (ROS) e secretar compostos orgânicos voláteis. Portanto, microorganismos e endófitos da rizosfera são considerados determinantes dos processos envolvidos no crescimento de plantas hospedeiras. No entanto, as funções fisiológicas e ecológicas, bem como o mecanismo molecular subjacente ao comportamento dos microrganismos e endofíticos da rizosfera no seu papel na capacidade adaptativa das plantas hospedeiras no ambiente cárstico de alto teor de cálcio, não foram sistematicamente estudados. Esta revisão resume os mecanismos fisiológicos e moleculares de microrganismos e endófitos da rizosfera que ajudam as plantas hospedeiras a se adaptarem a vários tipos de ambientes adversos. As capacidades adaptativas das plantas que crescem em ambientes adversos, em parte ou totalmente, dependem de microrganismos coexistentes com as plantas hospedeiras.
RESUMEN
Abstract Rhizosphere microorganisms and endophytes can help their hosts absorb nutrients and regulate the levels of plant hormones. Moreover, they can modulate the expressions of host genes, assist hosts in eliminating reactive oxygen species (ROS) and secreting volatile organic compounds. Therefore, rhizosphere microorganisms and endophytes are considered as determinant factors driving processes involved in the growth of host plants. However, the physiological and ecological functions, as well as the molecular mechanism underlying the behavior of rhizosphere microorganisms and endophytes in their role in the adaptive capacity of host plants in the karstic high-calcium environment have not been systematically studied. This review summarizes the physiological and molecular mechanisms of rhizosphere microorganisms and endophytes which help host plants to adapt to various kinds of adverse environments. The adaptive capacities of plants growing in adverse environments, partly, or totally, depends on microorganisms co-existing with the host plants.
Resumo Os microorganismos e endófitos da rizosfera podem ajudar seus hospedeiros a absorver nutrientes e regular os níveis de hormônios vegetais. Além disso, eles podem modular as expressões dos genes hospedeiros, auxiliar os hospedeiros na eliminação de espécies reativas de oxigênio (ROS) e secretar compostos orgânicos voláteis. Portanto, microorganismos e endófitos da rizosfera são considerados determinantes dos processos envolvidos no crescimento de plantas hospedeiras. No entanto, as funções fisiológicas e ecológicas, bem como o mecanismo molecular subjacente ao comportamento dos microrganismos e endofíticos da rizosfera no seu papel na capacidade adaptativa das plantas hospedeiras no ambiente cárstico de alto teor de cálcio, não foram sistematicamente estudados. Esta revisão resume os mecanismos fisiológicos e moleculares de microrganismos e endófitos da rizosfera que ajudam as plantas hospedeiras a se adaptarem a vários tipos de ambientes adversos. As capacidades adaptativas das plantas que crescem em ambientes adversos, em parte ou totalmente, dependem de microrganismos coexistentes com as plantas hospedeiras.
RESUMEN
The relationship between the p38-mitogen-activated protein kinase (p38-MAPK) signal pathway and high glucose-induced hepatic stellate cell (HSC) activation was investigated in this study. Sixty human HSC samples were randomly selected and used in the control (cultured normally), high-glucose (cultured in the presence of high glucose), and blocking (cultured under high-glucose conditions in the presence of the p38-MAPK inhibitor, SB203580) groups. The cells were incubated for 120 h and subsequently analyzed for morphological changes by inverted microscopy and for a-smooth muscle actin (a-SMA) expression (to determine the degree of HSC activation) by the method of streptavidin-biotin complex and western blot. Phospho-p38-MAPK protein expression was analyzed by western blotting. a-SMA and phospho-p38-MAPK expression was significantly upregulated in HSCs cultured under high-glucose conditions, compared to the HSCs cultured normally (P < 0.01). On the other hand, phospho-p38-MAPK and a-SMA protein levels were significantly lower in the blocking group compared to the high-glucose group (P < 0.01). Based on these results, we concluded that high-glucose levels induce HSC activation mediated by phospho-p38-MAPK. Therefore, blocking the p38-MAPK signal pathway could inhibit this effect.
Asunto(s)
Actinas/genética , Glucosa/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Actinas/agonistas , Actinas/antagonistas & inhibidores , Actinas/metabolismo , Células Cultivadas , Regulación de la Expresión Génica , Glucosa/metabolismo , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/metabolismo , Humanos , Imidazoles/farmacología , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Abnormal expression of the kallikrein (KLK) family of serine proteases closely correlates with onset, progression, and prognosis of endocrine gland-related malignant tumors. The aim of this study was to evaluate how downregulation of KLK12 influenced cell cycle and proliferation of the AGS gastric cancer cell line. KLK12 was detected by western blot in GES-1 normal gastric epithelial and AGS cells. AGS cells were transfected with KLK12 siRNA, a negative control siRNA, or subjected to a mock transfection, following which, we assessed mRNA and protein levels, cell proliferation, cell migration, and cell cycle progression. We found that KLK12 levels were significantly higher in AGS cells than in GES-1 cells. Transfection of AGS cells with KLK12 siRNA led to downregulation of KLK12 mRNA and protein expression, reduced cell proliferation (0.47 ± 0.03 vs 0.92 ± 0.04, P < 0.01), and lower cell counts (3.92 ± 0.25 x 105 vs 5.47 ± 0.50 x 105, P < 0.01) with respect to the negative control. We observed that KLK12 siRNA increased the number of AGS cells in G0/G1 and reduced those in S phase. Furthermore, downregulation of KLK12 in AGS cells decreased their ability to penetrate the membrane in a migration assay (P < 0.05). In conclusion, KLK12 siRNA inhibited the proliferation and migration of AGS gastric cancer cells and caused their arrest in the G0/G1 phase of the cell cycle.
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Células Epiteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Calicreínas/genética , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Células Epiteliales/patología , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Calicreínas/antagonistas & inhibidores , Calicreínas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Puntos de Control de la Fase S del Ciclo Celular/genética , Transducción de Señal , TransfecciónRESUMEN
The aim of this study was to explore the inhibition of subcutaneously implanted human pituitary tumor cells in nude mice by LRIG1 and its mechanism. For this study, athymic nude mice were injected with either normal pituitary tumor RC-4B/C cells or LRIG1-transfected RC-4B/C cells. We then calculated the volume inhibition rate of the tumors, as well as the apoptosis index of tumor cells and the expression of Ras, Raf, AKt, and ERK mRNA in tumor cells. Tumor cell morphological and structural changes were also observed under electron microscope. Our data showed that subcutaneous tumor growth was slowed or even halted in LRIG1-transfected tumors. The tumor volumes were significantly different between the two groups of mice (χ2 = 2.14, P < 0.05). The tumor apoptosis index was found to be 8.72% in the control group and 39.7% in LRIG1-transfected mice (χ2 = 7.59, P < 0.05). The levels of Ras, Raf, and AKt mRNA in LRIG1-transfected RC-4B/C cells were significantly reduced after transfection (P < 0.01). Transfected subcutaneous tumor cells appeared to be in early or late apoptosis under an electron microscope, while only a few subcutaneous tumor cells appeared to be undergoing apoptosis in the control group. In conclusion, the LRIG1 gene is able to inhibit proliferation and promote apoptosis in subcutaneously implanted human pituitary tumors in nude mice. The mechanism of LRIG1 may involve the inhibition of the PI3K/ Akt and Ras/Raf/ERK signal transduction pathways.
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Terapia Genética , Glicoproteínas de Membrana/genética , Hipófisis/citología , Neoplasias Hipofisarias/terapia , Animales , Apoptosis , Línea Celular Tumoral , Trasplante de Células , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Desnudos , Hipófisis/patología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Quinasas raf/genética , Quinasas raf/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismoRESUMEN
Target leaf spot is a sorghum leaf disease caused by Bipolaris sorghicola, a species of fungus with a global distribution. In this study, we investigated the process by which B. sorghicola invades cells of barley, onion, Arabidopsis thaliana species, and sorghum. The results showed that within 8 h of coming into contact with host cells, the hyphal ends of B. sorghicola expand and form a uniform infective penetration pegbolt-like structure; a primary infection mycelium can be formed inside host cells within 24 h after contact, which can infect closed cells after 48 h. A mycelium can grow within the gap between cells and form infective hyphae. The pathogen infection process was the same in different host cells. B. sorghicola can affect root cells through soil infection, indicating that it may also have characteristics of soil-borne pathogens.
Asunto(s)
Ascomicetos/fisiología , Interacciones Huésped-Patógeno , Raíces de Plantas/microbiología , Arabidopsis/microbiología , Hordeum/microbiología , Cebollas/microbiología , Microbiología del Suelo , Sorghum/microbiologíaRESUMEN
The long non-coding RNA MALAT-1 plays an important role in cancer prognosis. The present research aimed to elucidate its precise predictive value in various human carcinomas. A quantitative meta-analysis was performed by searching PubMed, Embase, Web of Science, and Cochrane Library (most recently, January 2015) databases, and extracting data from studies that investigated the association between MALAT-1 expression and survival outcomes in patients of various cancers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated as a measure of generalized effect. This meta-analysis included 1317 cases from 12 datasets. Our investigation revealed that poor overall survival (OS; HR = 2.14, 95% CI = 1.74-2.64) and shortened disease-free, recurrence-free, disease-specific, or progression-free survival (HR = 2.13, 95% CI = 1.22-3.72) can be predicted by high MALAT-1 expression for various cancers. Moreover, elevated MALAT-1 levels significantly correlated with decreased OS in a renal cell carcinoma (RCC) subgroup (HR = 3.43, 95% CI = 1.80-6.53). These results imply that MALAT-1 can be used to predict unfavorable prognoses for several cancers, particularly RCC.
Asunto(s)
Carcinoma/genética , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Adulto , Anciano , Biomarcadores de Tumor , Carcinoma/diagnóstico , Carcinoma/terapia , Supervivencia sin Enfermedad , Humanos , Persona de Mediana EdadRESUMEN
Lung cancer, the most common malignancy, is still the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80 % of all lung cancers. Recent studies showed Cathepsin L (CTSL) is overexpressed in various cancerous tissues; however, the association between CTSL expression and EGFR-TKI resistance remains unknown. In this study, we investigated the expression of CTSL in lung cancer specimens and matched normal tissues by quantitative real-time PCR and IHC. The functional role of CTSL in resistant PC-9/GR cell line was investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that the level of CTSL expression was higher in NSCLC tissues compared with matched normal adjacent tissue samples, and CTSL was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking-down of CTSL in PC-9/GR cells could decrease cell proliferation and potentiate apoptosis induced by gefitinib, suggesting CTSL may contribute to gefitinib resistance in NSCLC. CTSL might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Catepsina L/biosíntesis , Resistencia a Antineoplásicos/fisiología , Neoplasias Pulmonares/patología , Quinazolinas/uso terapéutico , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/análisis , Western Blotting , Catepsina L/análisis , Proliferación Celular/efectos de los fármacos , Gefitinib , Humanos , Inmunohistoquímica , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
MicroRNAs are very small endogenous RNA molecules that play a crucial role in an array of biological processes, including regulation of skin morphogenesis. The microRNA let-7b is thought to modulate animal hair growth, by binding target genes that encode growth factors. Fibroblast growth factor 5 (FGF5) has been previously reported to be involved in the initiation of the catagen phase of hair growth. In this study, we combined previous reports with bioinformatic analysis techniques to identify and validate FGF5 and, using lucerifase assay, confirmed targeted binding of let-7b to FGF5. To investigate the interaction between let-7b and FGF5, alpaca skin fibroblasts were transfected with let-7b over-expression vectors, and then mRNA and protein expression levels of FGF5 and the gene encoding its receptor, FGFR1, were evaluated. Levels of FGF5 mRNA and protein were remarkably lower in transfected groups, as compared to controls. In summary, this study confirmed that let-7b acts as a regulator of skin morphogenesis, by directly targeting FGF5 and down-regulating its expression. It provides the evidence of hair growth regulated by miRNAs in animals and may have important applications in wool production.
Asunto(s)
Camélidos del Nuevo Mundo/genética , Factor 5 de Crecimiento de Fibroblastos/genética , Regulación de la Expresión Génica , MicroARNs/genética , Lana/crecimiento & desarrollo , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular , Regulación hacia Abajo , Factor 5 de Crecimiento de Fibroblastos/metabolismo , MicroARNs/química , Transporte de Proteínas , Interferencia de ARN , ARN Mensajero/química , ARN Mensajero/genéticaRESUMEN
We evaluated the system accuracy of noninvasive prenatal diagnosis for abnormal chromosome genetic diseases using cell-free fetal DNA in maternal plasma. Previous studies were searched in the MEDLINE database using the following keywords: "prenatal" and "aneuploidy" and "noninvasive or non-invasive" and "maternal". Identified studies were filtered using a QUADAS instrument. Four studies were identified and analyzed using QUADAS. The studies included 4167 cases of Down syndrome patients determined by noninvasive prenatal diagnosis with a sensitivity of 100% and specificity of 99.3%; There were 3455 cases of Edwards syndrome patients determined by noninvasive prenatal diagnosis with a sensitivity of 97.4% and specificity of 99.95%. Therefore, noninvasive prenatal diagnosis can be used to identify abnormal chromosomes with high accuracy using free fetal DNA in the maternal plasma.
Asunto(s)
ADN/sangre , Síndrome de Down/diagnóstico , Diagnóstico Prenatal/métodos , Trisomía/diagnóstico , Adulto , Aneuploidia , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 18/metabolismo , Síndrome de Down/sangre , Síndrome de Down/genética , Femenino , Feto , Humanos , Masculino , Embarazo , Trisomía/genética , Síndrome de la Trisomía 18RESUMEN
We examined the expression of c-myc and mutations in the KRAS gene in ovarian mucinous tumors to explore the pathogenesis of these tumors and the feasibility of targeted gene therapy. Expression of c-myc protein and mutations in the KRAS gene in 24 cases of ovarian mucinous cystadenoma, 46 cases of ovarian borderline mucinous cystadenoma, and 46 cases of ovarian mucinous cystadenocarcinoma were detected using the immunohistochemistry PV-9000 2-step method and polymerase chain reaction-restriction fragment length polymorphism. The positive expression rates of c-myc in ovarian mucinous cystadenoma, borderline mucinous cystadenoma, and cystadenocarcinoma were 0, 39.1, and 65.2%, respectively (P < 0.01), while the mutation rates in KRAS were 0, 39.1 and 13.0%, respectively. The mutation rate of the borderline group was significantly higher, while rates in the other 2 groups were similar (P > 0.05). c-myc was not correlated with clinical stage, pathological grade, or age of patients with ovarian mucinous cystadenocarcinoma or borderline mucinous cystadenoma (P > 0.05), but was correlated with tumor size (P < 0.05). Mutations in KRAS were not correlated with clinical stage or tumor size in patients with borderline mucinous cystadenoma (P > 0.05), whereas it was correlated with age (P < 0.05). In borderline mucinous cystadenoma, c-myc expression and KRAS mutations were not correlated (P > 0.05). c-myc is involved in the formation of ovarian borderline mucinous cystadenoma and mucinous cystadenocarcinoma, and the KRAS gene may contribute to the formation of borderline mucinous cystadenoma.
Asunto(s)
Cistadenocarcinoma Mucinoso/genética , Cistoadenoma Mucinoso/genética , Tasa de Mutación , Neoplasias Ováricas/genética , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Factores de Edad , Anciano , Cistadenocarcinoma Mucinoso/patología , Cistoadenoma Mucinoso/patología , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Ovario/metabolismo , Ovario/patología , Polimorfismo de Longitud del Fragmento de Restricción , Carga TumoralRESUMEN
The aim of this study was to examine the relationship between genetic polymorphisms in DNA ligase 1 (LIG1) and non-small cell lung cancer (NSCLC) susceptibility and radiosensitivity in a Chinese population. This was a case-control study that included 352 NSCLC patients and 448 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was conducted to detect HaeIII polymorphisms in exon 6 of the LIG1 gene in this popula-tion. This information was used to observe the effects of radiation in pa-tients with different genotypes in order to determine the genotypes as-sociated with radiosensitivity. The CC genotype and C allele frequency were significantly higher in the NSCLC group than in the control group (P = 0.012 and P = 0.023, respectively). The relative risk of experienc-ing NSCLC was 2.55 [95% confidence interval (CI), 1.12-3.98] for CC homozygous patients and 0.87 (95%CI, 0.46-1.88) for AA homozygous patients. Analysis of LIG1 genetic polymorphisms and radiosensitiv-ity of NSCLC patients showed that AA homozygous patients were sig-nificantly more radiosensitive than the control group (AA vs AC, P = 0.014; AA vs CC, P < 0.001; AC vs CC, P = 0.023). Therefore, the LIG1 CC genotype was associated with susceptibility to NSCLC, and the AA genotype demonstrated increased radiosensitivity compared to the AC and CC genotypes.