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1.
Cancer Sci ; 115(2): 589-599, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38146096

RESUMEN

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.


Asunto(s)
Neoplasias Encefálicas , Humanos , Bevacizumab/efectos adversos , Estudios Retrospectivos , Necrosis/etiología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patología
2.
Ann Surg ; 277(1): 1-6, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35815886

RESUMEN

OBJECTIVE: To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection. BACKGROUND: Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME. METHODS: A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned. RESULTS: Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P =0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P =0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P >0.99). CONCLUSIONS: Experienced surgeons can safely perform taTME in selected patients with rectal cancer.


Asunto(s)
Laparoscopía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Humanos , Complicaciones Posoperatorias/etiología , Cirugía Endoscópica Transanal/efectos adversos , Tempo Operativo , Neoplasias del Recto/cirugía , Laparoscopía/efectos adversos , Morbilidad , Recto/cirugía , Resultado del Tratamiento
3.
Anal Biochem ; 668: 115114, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36907310

RESUMEN

Herein, a mitochondrial targeted fluorescent nitrite peroxide probe CHP for dynamic monitoring of cellular lung injury was developed. For the practical delivery and selectivity, the structural features including pyridine head and borate recognition group were selected. CHP could respond to ONOO- with the 585 nm fluorescence signal. The detecting system indicated advantages such as wide linear range (0.0-30 µM), high sensitivity (LOD = 0.18 µM), high selectivity and steadiness under different environmental conditions including pH (3.0-10.0), time (48 h) and medium. In living A549 cells, the response of CHP towards ONOO- showed dose-dependent and time-dependent tendencies. The co-localization suggested that CHP could achieve mitochondrial targeting. Moreover, CHP could monitor the variation of endogenous ONOO- level and the cellular lung injury induced by LPS.


Asunto(s)
Lesión Pulmonar , Nitritos , Humanos , Peróxidos , Colorantes Fluorescentes/química , Ácido Peroxinitroso/química
4.
Cancer Sci ; 113(12): 4277-4288, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36056609

RESUMEN

Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard-risk patients were planned to receive 30 Gy (range 21-36) with median fractions of 3 (range 1-3) and high-risk patients 35 Gy (range 24-50) with median fractions of 5 (range 4-5) according to the spinal cord and esophagus dose constraints. The median follow-up time was 17.07 months (range 3.1-118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1-year and 2-year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1-4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk-adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.


Asunto(s)
Carcinoma , Fracturas por Compresión , Radiocirugia , Fracturas de la Columna Vertebral , Neoplasias de la Columna Vertebral , Humanos , Radiocirugia/efectos adversos , Fracturas por Compresión/complicaciones , Neoplasias de la Columna Vertebral/radioterapia , Neoplasias de la Columna Vertebral/secundario , Fracturas de la Columna Vertebral/complicaciones , Dolor/complicaciones
5.
BMC Cancer ; 20(1): 1144, 2020 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-33238967

RESUMEN

BACKGROUND: In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. METHODS: Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2-4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12-32 Gy) in the original fractions (1-3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62-68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. RESULTS: Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22-3.13% (2.62%) and 2.71-12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8-16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). CONCLUSION: One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans.


Asunto(s)
Neoplasias Encefálicas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/normas , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos
6.
Cancer Sci ; 110(11): 3553-3564, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31464032

RESUMEN

To determine the therapeutic efficacy and safety of risk-adapted stereotactic body radiation therapy (SBRT) schedules for patients with early-stage central and ultra-central inoperable non-small cell lung cancer. From 2006 to 2015, 80 inoperable T1-2N0M0 NSCLC patients were treated with two median dose levels: 60 Gy in six fractions (range, 48-60 Gy in 4-8 fractions) prescribed to the 74% isodose line (range, 58%-79%) for central lesions (ie within 2 cm of, but not abutting, the proximal bronchial tree; n = 43), and 56 Gy in seven fractions (range, 48-60 Gy in 5-10 fractions) prescribed to the 74% isodose line (range, 60%-80%) for ultra-central lesions (ie abutting the proximal bronchial tree; n = 37) on consecutive days. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), tumor local control rate (LC), and toxicity. Median OS and PFS were 64.47 and 32.10 months (respectively) for ultra-central patients, and not reached for central patients. Median time to local failure, regional failure, and any distant failures for central versus ultra-central lesions were: 27.37 versus 26.07 months, 20.90 versus 12.53 months, and 20.85 versus 15.53 months, respectively, all P < .05. Multivariate analyses showed that tumor categorization (ultra-central) and planning target volume ≥52.76 mL were poor prognostic factors of OS, PFS, and LC, respectively (all P < .05). There was one grade 5 toxicity; all other toxicities were grade 1-2. Our results showed that ultra-central tumors have a poor OS, PFS, and LC compared with central patients because of the use of risk-adapted SBRT schedules that allow for equal and favorable toxicity profiles.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Supervivencia sin Progresión , Radiocirugia/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del Tratamiento
7.
J Nat Prod ; 82(6): 1503-1509, 2019 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-31117520

RESUMEN

Six new macrolides named myrothecines D-G (1-4), 16-hydroxymytoxin B (5), and 14'-dehydrovertisporin (6), including four 10,13-cyclotrichothecane derivatives, in addition to 12 known compounds (7-18), were isolated from three endophytic Myrothecium roridum, IFB-E008, IFB-E009, and IFB-E012. The isolated compounds were characterized by MS, NMR, CD, and single-crystal X-ray crystallography. The isolated macrolides exhibited an antiproliferation effect against chronic myeloid leukemia K562 and colorectal carcinoma SW1116 cell lines. Compounds 1-6 were cytotoxic, with IC50 values ranging between 56 nM and 16 µM. Since slight structural changes led to obvious activity differences, the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were then used to explore the 3D QSAR (three-dimensional quantitative structure-activity relationship) of these macrolides. The result showed that the steric, electrostatic, hydrophobic, and H-bond acceptor factors were involved in their cytotoxicity and provided an in-depth understanding of the structure-activity relationships of these metabolites.


Asunto(s)
Antibacterianos/farmacología , Antineoplásicos/farmacología , Hypocreales/química , Macrólidos/farmacología , Hongos Mitospóricos/química , Inhibidores de la Síntesis de la Proteína/farmacología , Tricotecenos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Cristalografía por Rayos X , Macrólidos/química , Macrólidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Inhibidores de la Síntesis de la Proteína/química , Inhibidores de la Síntesis de la Proteína/aislamiento & purificación , Relación Estructura-Actividad Cuantitativa , Tricotecenos/química , Tricotecenos/aislamiento & purificación
8.
BMC Cell Biol ; 19(1): 5, 2018 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-29673312

RESUMEN

BACKGROUND: Contactin1 (CNTN1) has been shown to play an important role in the invasion and metastasis of several tumors; however, the role of CNTN1 in breast cancer has not been fully studied. The purpose of this study is to investigate the role of CNTN1 in regulating tumor growth, migration and invasion in breast cancer. RESULTS: To investigate its function, CNTN1 was expressed in Hs578T cells. CNTN1 expression was confirmed by western blot, immunohistochemistry and real-time RT-PCR. The effect of CNTN1 overexpression on proliferation, migration and invasion of Hs578T breast cancer cells was assessed in vitro and in vivo. Our results showed that CNTN1 overexpression promoted Hs578T cell proliferation, cell cycle progression, colony formation, invasion and migration. Notably, overexpression of CNTN1 in Hs578T cells enhanced the growth of mouse xenograft tumors. CONCLUSIONS: CNTN1 promotes growth, metastasis and invasion of Hs578T breast cancer cell line. Thus, therapies targeting CNTN1 may prove efficacious for breast cancer. However, further investigation is required to understand the mechanism by which CNTN1 influences proliferation, metastasis and invasion in breast cancer.


Asunto(s)
Neoplasias de la Mama/patología , Movimiento Celular , Contactina 1/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Masculino , Ratones Desnudos , Invasividad Neoplásica , Ensayos Antitumor por Modelo de Xenoinjerto
9.
Cell Physiol Biochem ; 45(4): 1663-1676, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29490291

RESUMEN

BACKGROUND/AIMS: Elevated pretreatment plasma D-dimer level has been reported as an unfavorable prognostic indicator in several malignancies. The aim of this meta-analysis was to evaluate the prognostic value of elevated D-dimer level in solid tumors. METHODS: A comprehensive search of electronic databases up to June 10, 2017 was carried out by two independent reviewers. We included studies exploring the association between pretreatment plasma D-dimer level and patients' survival outcomes in solid tumors. Overall survival (OS) was regarded as primary outcome and progression-free survival (PFS), disease-free survival (DFS) as well as cancer-specific survival (CSS) were chosen as secondary outcomes. Hazard ratio and 95% confidence interval (CI) were extracted directly or indirectly from included studies. RESULTS: 49 studies with 13001 patients were included in our meta-analysis. Elevated D-dimer was markedly associated with poor OS (pooled HR = 1.90, 95% CI = 1.63 - 2.20, P < 0.001). The effect was observed in all different tumor sites, disease stages, cut-off values and ethnicities. Meanwhile, patients with a high plasma D-dimer had a shorter PFS (HR = 1.46, 95% CI = 1.22-1.76; P < 0.001), DFS (HR = 2.02, 95% CI = 1.56-2.62) and CSS (HR = 2.04, 95% CI= 1.58 - 2.64). CONCLUSIONS: Analysis of the pretreatment plasma D-dimer might provide useful information to predict prognosis in patients with solid tumors.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/análisis , Neoplasias/patología , Biomarcadores de Tumor/sangre , Bases de Datos Factuales , Supervivencia sin Enfermedad , Humanos , Neoplasias/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia
10.
Biochem Biophys Res Commun ; 500(2): 411-417, 2018 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-29673586

RESUMEN

Spastic paraplegia 20 methylation was characterized in gastric cancer in our previous study. However, its mechanism remains unknown. Cell proliferation, colony formation, flow cytometry, wound healing, in vitro Transwell assays and in vivo xenografts were performed. A nomogram model was established to make a more accurate prognostic prediction for gastric cancer patients. Knockout of Spastic paraplegia 20 promoted gastric cancer cell proliferation, G2/M arrest in vitro and tumor growth in vivo. The EGFR/MAPK pathway was activated as a consequence of Spastic paraplegia 20 deletion. EGFR kinase or ERK1/2 inhibitors impaired Spastic paraplegia 20 knockout-induced cancer cell growth. Gastric cancer patients with poor spartin expression (72/161, 44.7%) exhibited a worse prognosis compared with the high expression group with median survival times of 16 and 54 months, respectively. The nomogram model stratified gastric cancer patients into 3 distinct prognostic groups with 3-year survival rates of 100%, 77%, and 35%. Furthermore, it had a better discrimination than the TNM staging system (C index: 0.785, AIC: 752.8708 VS. C index: 0.712; AIC: 775.1223). Methylation-induced Spastic paraplegia 20 silencing facilitates gastric cancer cell proliferation by activating the EGFR/MAPK signaling pathway. The nomogram based on spartin expression provided significantly better discrimination compared with the traditional AJCC TNM staging system and provided an individualized prediction of the survival for gastric cancer patient survival.


Asunto(s)
Receptores ErbB/metabolismo , Silenciador del Gen , Sistema de Señalización de MAP Quinasas , Proteínas/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Animales , Azacitidina/farmacología , Secuencia de Bases , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Masculino , Metilación , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Análisis Multivariante , Nomogramas , Pronóstico , Neoplasias Gástricas/enzimología , Análisis de Supervivencia , Ensayo de Tumor de Célula Madre , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Mediators Inflamm ; 2018: 3586132, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29576744

RESUMEN

The PB1-F2 protein of influenza A virus has been considered a virulence factor, but its function in inducing apoptosis may be of disadvantage to viral replication. Host mechanisms to regulate PB1-F2-induced apoptosis remain unknown. We generated a PB1-F2-deficient avian influenza virus (AIV) H9N2 and found that the mutant virus replicated less efficiently in human lung epithelial cells. The PB1-F2-deficient virus produced less apoptotic cells, indicating that PB1-F2 of the H9N2 virus promotes apoptosis, occurring at the early stage of infection, in the lung epithelial cells. To understand how host cells regulate PB1-F2-induced apoptosis, we explored to identify cellular proteins interacting with PB1-F2 and found that HCLS1-associated protein X-1 (HAX-1), located mainly in the mitochondria as an apoptotic inhibitor, interacted with PB1-F2. Increased procaspase-9 activations, induced by PB1-F2, could be suppressed by HAX-1. In HAX-1 knockdown A549 cells, the replication of AIV H9N2 was suppressed in parallel to the activation of caspase-3 activation, which increased at the early stage of infection. We hypothesize that HAX-1 promotes AIV replication by interacting with PB1-F2, resulting in the suppression of apoptosis, prolonged cell survival, and enhancement of viral replication. Our data suggest that HAX-1 may be a promoting factor for AIV H9N2 replication through desensitizing PB1-F2 from its apoptotic induction in human lung epithelial cells.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Epiteliales/virología , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Pulmón/citología , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Apoptosis/genética , Apoptosis/fisiología , Línea Celular , Perros , Células Epiteliales/citología , Células Epiteliales/metabolismo , Células HEK293 , Humanos , Virus de la Influenza A/genética , Virus de la Influenza A/patogenicidad , Replicación Viral/genética , Replicación Viral/fisiología
12.
BMC Cancer ; 17(1): 56, 2017 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-28086824

RESUMEN

BACKGROUND: Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it's stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients. METHODS: We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients. RESULTS: In three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R 2 = 0.688, p < 0.001), additionally, plasma D-dimer represent a better survival predictor than CTCs. CONCLUSIONS: Plasma D-dimer is an essential accompaniment of CTCs in GC that is easy to measure and lower in cost, and can be used in the detection of hematogenous metastasis.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Células Neoplásicas Circulantes/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Femenino , Fibrinógeno/metabolismo , Estudios de Seguimiento , Humanos , Masculino , Ratones , Persona de Mediana Edad , Metástasis de la Neoplasia/patología
13.
Tumour Biol ; 37(7): 9311-22, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26779630

RESUMEN

SET7/9 is a protein lysine methyltransferase that had been initially identified as a histone lysine methyltransferase which generates monomethylation at histone 3 lysine 4. Different functions were attributed to the protein methylation mediated by SET7/9. In this study, we found that the expression of SET7/9 declined in a majority of the human breast cancer tissues examined compared with normal tissues. Knockdown of SET7/9 promoted the proliferation, migration, and invasion of breast cancer cells. Knockdown of SET7/9 also increased the tumorigenicity of breast cancer cells in vivo. On the contrary, overexpression of SET7/9 in breast cancer cells inhibited these processes. Microarray analysis indicated that Gli-1 may play function as a downstream factor of SET7/9. Overexpression of SET7/9SET7/9 inhibits Gli-1 expression. While knockdown of SET7/9 promotes the expression of Gli-1. Gli-1 inhibited by cyclopamine blocked knockdown SET7/9-driven proliferation, migration, and invasion in breast cancer cell. Furthermore, Gli-1 expression in human breast cancer tissues is negatively correlated with SET7/9 expression. Together, these results helped to realize the antioncogene functions of SET7/9 in breast cancer cells and provided a novel direction to treat breast cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , N-Metiltransferasa de Histona-Lisina/metabolismo , Proteína con Dedos de Zinc GLI1/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Western Blotting , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína con Dedos de Zinc GLI1/genética
14.
Exp Mol Pathol ; 99(3): 617-27, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26505174

RESUMEN

Metastasis is the leading cause of death in breast cancer (BC) patients. However, until now, the mechanisms of BC metastasis remain elusive. GATA6 is a member of the GATA transcription factor family that plays critical regulatory roles in tissue development, which has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in BC remain unclear. Here we show that GATA6 is elevated in BC and its expression level is positively correlated with metastasis. In addition Kaplan-Meier survival analysis showed that high expression of GATA6 was associated with decreased overall survival of BC patients. Overexpression of GATA6 in BC cells increased epithelial-mesenchymal transition. In contrast, silencing GATA6 in aggressive BC cells inhibited this process. Mechanistically, we found GATA6 exerts its function through active slug transcription. Slug knockdown blocked the GATA6-driven EMT. Furthermore, slug expression in human BC is positively correlated with GATA6 expression. Our results, for the first time, portray a pivotal role of GATA6 in regulating metastatic behaviors of BC cells, suggesting GATA6 is a potential therapeutic target in metastatic BCs.


Asunto(s)
Neoplasias de la Mama/patología , Transición Epitelial-Mesenquimal/fisiología , Factor de Transcripción GATA6/biosíntesis , Regulación Neoplásica de la Expresión Génica/fisiología , Factores de Transcripción/biosíntesis , Animales , Western Blotting , Neoplasias de la Mama/metabolismo , Inmunoprecipitación de Cromatina , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Ratones , Microscopía Confocal , Invasividad Neoplásica/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Factores de Transcripción de la Familia Snail , Transfección , Regulación hacia Arriba
15.
Med Sci Monit ; 21: 2251-6, 2015 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-26235604

RESUMEN

BACKGROUND: Adjuvant radiation therapy is commonly administered to breast cancer patients who received breast-conserving surgery. However, lengthy treatment times of standard radiotherapy pose certain challenges. Here, we performed a prospective controlled study comparing standard radiation to hypofractionated radiotherapy in terms of efficacy and outcome. MATERIAL AND METHODS: Eighty breast cancer patients (tumor stage pT1-2N0-1M0) who had undergone breast-conservation surgery were randomly divided into 2 groups (40 patients/group). The experimental group received 43.2 Gy to the whole breast in 18 fractions for 24 days with a concomitant boost (50.4 Gy) to the tumor bed. The control group received 45 Gy to the whole breast in 25 fractions for 44 days with a boost to the tumor bed of 59 Gy. Survival, locoregional recurrence, adverse effects, and aesthetic results were all considered for analysis. RESULTS: The following criteria were included as part of study follow-up: local control, survival, adverse skin reactions, cosmetic outcome, and hematological toxicity. At a median follow-up of 27 months (follow-up rate 100%), there were no statistical differences in any of the categories between the 2 groups. The 2-year survival rate of both groups was 100% without any locoregional recurrence. Although there was some skin toxicity, these instances were not severe and they cleared on their own within 6 weeks. The most common problems encountered by patients were breast fibrosis and altered pigmentation. CONCLUSIONS: A shortened whole-breast hypofractionated irradiation schedule with a concomitant boost is as effective as standard radiation and may be a reasonable alternative following breast conservation surgery.


Asunto(s)
Neoplasias de la Mama/radioterapia , Fraccionamiento de la Dosis de Radiación , Mastectomía Segmentaria , Neoplasias de la Mama/cirugía , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
16.
World J Surg Oncol ; 13: 197, 2015 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-26055624

RESUMEN

BACKGROUND: The aim of this study is to develop a prognostic nomogram for patients with adenocarcinoma of esophagogastric junction and compare its predictive accuracy with the traditional tumor-node-metastasis (TNM) malignant staging system. METHODS: Patients from the Surveillance, Epidemiology, and End Results Program (from 1988 to 2011) and the First Affiliated Hospital of Xi'an Jiaotong University (from 2005 to 2010) were collected retrospectively. Preselected multiple potential interactions were tested irrespective of significance as nomogram parameters. And the Harrell's C-index was used to estimate the accuracy of the nomogram system. Model validation was performed using bootstrap to quantify our modeling strategy. RESULTS: In our study, six clinical associated factors (age, sex, depth of invasion, metastasized lymph nodes, examined lymph nodes, histological grade) were evaluated in the nomogram. In the training set, the nomogram exhibited superior discrimination power compared with the American Joint Committee on Cancer (AJCC) TNM classification (Harrell's C-index, 0.69 and 0.63, respectively). Calibration of the nomogram predicted survival was similar to the actual overall survival. In the validation set, the discrimination of nomogram was also better than the AJCC TNM staging system (C-index, 0.75 and 0.65, respectively), and the calibration of nomogram predicted survival was within a 10 % margin of actual overall survival. CONCLUSIONS: Based on the patients with adenocarcinoma of esophagogastric junction from a Western and an Eastern database, the nomogram provided significantly improved discrimination than the traditional AJCC TNM classification and also provided an accurate individualized prediction of the survival.


Asunto(s)
Adenocarcinoma/mortalidad , Neoplasias Esofágicas/mortalidad , Unión Esofagogástrica/patología , Nomogramas , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Pronóstico , Estudios Retrospectivos , Programa de VERF , Tasa de Supervivencia , Adulto Joven
17.
Yao Xue Xue Bao ; 50(10): 1305-8, 2015 Oct.
Artículo en Zh | MEDLINE | ID: mdl-26837178

RESUMEN

Three compounds were isolated from solid culture of endophyte Myrothecium roridum IFB-E091 in Artemisia annua. Their structures were determined as (S)-(-)-N-[2-(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (1), N-(4-hydroxyphenethyl)acetamide (2) and asperfumoid (3), in which compound 1 was a new indole derivative. In cytotoxicity assay, the compound 1 had no obvious inhibition activity in human hepatoma cell line SMMC-7721 and human cervical carcinoma cell line HeLa.


Asunto(s)
Artemisia annua/microbiología , Endófitos/química , Hypocreales/química , Indoles/química , Línea Celular Tumoral/efectos de los fármacos , Humanos , Indoles/aislamiento & purificación
18.
Zhongguo Zhong Yao Za Zhi ; 40(23): 4645-9, 2015 Dec.
Artículo en Zh | MEDLINE | ID: mdl-27141677

RESUMEN

Isolation and purification of chemical constituents from solid culture of endophyte Chaetomium globosum in Imperata cylindrical was performed through silica gel column chromatography, gel filtration over Sephadex LH-20 and preparative HPLC. Nine compounds were obtained and their structures were determined as chaetoglobosin F(1), chaetoglobosin Fex(2), chaetoglobosin E(3) cytoglobosin A(4), penochalasin C(S), isochaetoglobosin D (6), N-benzoylphenylalaninyl-N-benzoyphenylalaninate(7), uracil(8) and 5-methyluracil(9), respectively, based on HR-MS and NMR data and comparison with literatures. Compound 7 was isolated from Chaeeomium sp. for the first time. In vitro cytotoxicity of compounds was evaluated using MTT mothed and 1,3,4 and 5 showed inhibition activity to the human cervical carcinoma cell HeLa with IC50 values of 99.43, 23.77, 97.92, 86.25 micromol x L(-1), while positive cotolocisnin Ad apno1ch alse IC50 24.33 micromol x L(-1).


Asunto(s)
Factores Biológicos/química , Chaetomium/química , Endófitos/química , Poaceae/microbiología , Factores Biológicos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Humanos , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray
19.
Radiother Oncol ; 190: 110023, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37995850

RESUMEN

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.


Asunto(s)
Neuropatías del Plexo Braquial , Traumatismos por Radiación , Radiocirugia , Humanos , Radiocirugia/efectos adversos , Dosificación Radioterapéutica , Órganos en Riesgo , Neuropatías del Plexo Braquial/etiología , Planificación de la Radioterapia Asistida por Computador
20.
Arch Virol ; 158(1): 39-53, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22935945

RESUMEN

Cross-species transmission of influenza A viruses from swine to human occurs occasionally. In 2011, an influenza A H1N1 virus, A/Jiangsu/ALS1/2011 (JS/ALS1/2011), was isolated from a boy who suffered from severe pneumonia in China. The virus is closely related antigenically and genetically to avian-like swine H1N1 viruses that have recently been circulating in pigs in China and that were initially detected in European pig populations in 1979. The isolation of JS/ALS1/2011 provides additional evidence that swine influenza viruses can occasionally infect humans and emphasizes the importance of reinforcing influenza virus surveillance in both pigs and humans.


Asunto(s)
Antígenos Virales/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , Infecciones por Orthomyxoviridae/virología , Enfermedades de los Porcinos/virología , Animales , Anticuerpos Antivirales/inmunología , Antígenos Virales/genética , Preescolar , China , Variación Genética , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/inmunología , Masculino , Datos de Secuencia Molecular , Infecciones por Orthomyxoviridae/inmunología , Filogenia , Porcinos , Enfermedades de los Porcinos/inmunología
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