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BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.
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Apoptosis , Subtipo H3N2 del Virus de la Influenza A , Melatonina , Enfermedad Pulmonar Obstructiva Crónica , Animales , Melatonina/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/virología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Ratones , Apoptosis/efectos de los fármacos , Células RAW 264.7 , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/inmunología , Ratones Endogámicos C57BL , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Progresión de la Enfermedad , Polaridad Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologíaRESUMEN
Osteolytic bone diseases are closely linked to the over-activation of osteoclasts and enhancement of bone resorption. It has become a major health issue in orthopedic practice worldwide. Inhibition of osteoclasts is proposed to be the main treatment for osteolytic disorders. Diosmetin (DIO) is a natural flavonoid with properties of antioxidant, anti-infection, and antishock. The effect of DIO on osteoclast differentiation is poorly understood. In this study project, we found that DIO could inhibit osteoclastic formation induced by receptor activator of nuclear factor kappa-B ligand (RANKL) in a dose-dependent manner. The expression of the osteoclast differentiation marker genes, cathepsin K, nuclear factor of activated T-cells 1 (NFATc1), Acp5, Ctr, Atp6v0d2, and Mmp9 were also decreased by the treatment of DIO. In addition, DIO attenuated the formation of actin ring and the ability of bone resorption. Further, the western blotting showed that DIO inhibits the phosphorylation of the mitogen-activated protein kinases signaling pathway induced by RANKL, accompanied by the downregulation of NFATc1 and c-Fos expression. We also found that DIO could reduce the accumulation of reactive oxygen species (ROS) induced by RANKL. In vivo, the study revealed that DIO can significantly reduce LPS-induced osteolysis in mice. Collectively, our study shows that DIO can inhibit osteoclast formation and activation, and could serve as a potential therapeutic drug for osteolytic bone diseases.
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Diferenciación Celular/efectos de los fármacos , Flavonoides/farmacología , Osteoclastos/efectos de los fármacos , Osteólisis/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Osteólisis/inducido químicamente , Osteólisis/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. METHODS: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. RESULTS: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. CONCLUSIONS: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Anciano de 80 o más Años , China , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vincristina/administración & dosificaciónRESUMEN
Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
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Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapéuticos , China , Ciclofosfamida , Doxorrubicina , Estudios de Seguimiento , Linfoma Folicular , Quimioterapia , Linfoma de Células B Grandes Difuso , Quimioterapia , Estudios Prospectivos , Rituximab , Usos Terapéuticos , VincristinaRESUMEN
This study evaluated the lnc-RNAs as biomarker to predict efficacy of gemcitabine (GEM) based chemotherapy as the first-line treatment for locally advanced or advanced pancreatic cancer patients. We selected 62 patients with GEM based chemotherapy and divided two groups according to the PFS. We found that the expression of MALAT1, HOTTIP, and PVT1 in serum had a significant difference among the two groups. Furthermore, we estimated the PFS and response rate based on the expression levels of MALAT1, HOTTIP and PVT1. The response rate of two groups showed a significant difference according to the expression levels of MALAT1, HOTTIP and PVT1. Based on the expression levels of MALAT1, HOTTIP and PVT1, the response rate of high expression of PVT1 and low expression of PVT1 was respectively 14.8% and 37.1% and 18.2% (high HOTTIP group) and 37.9% (low HOTTIP group), 10.7%(high MALAT1 group) and 41.1% (low MALAT1 group). The PFS of patients with high and low expression levels PVT1 was 2.6 months and 4.0 months (p<0.001), respectively. The PFS of patients with high and low expression levels of HOTTIP was 2.7 months and 4.1 months (p<0.001), respectively, and the PFS of patients with high and low expression levels of MALAT1 was 3.0 months and 3.7 months (P=0.026), respectively. The results suggest that MALAT1, HOTTIP and PVT1 as predictors to predict the efficacy of GEM based chemotherapy in first-line treatment of pancreatic cancer patients.
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Gastric cancer is the result of multiple risk factors, including environmental factors, genetic factors and the interaction between them. The environmental factors mainly include dietary, Helicobacter pylori infection and family history of gastric cancer. Genetic factors mainly refer to the susceptible genes that cause epigenetic alterations in oncogenes, tumor suppress genes, cell cycle regulators, DNA repair genes and signaling molecules. This paper summarizes the susceptible genes of gastric cancer and explores the genetic basis of it.
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Neoplasias Gástricas/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Genes Supresores de Tumor , Genes p16 , Humanos , Oncogenes , Neoplasias Gástricas/etiologíaRESUMEN
The genus Streptomyces is a widespread genus within the phylum Actinobacteria and has been isolated from various environments worldwide. However, little is known about whether biogeography affects distributional pattern of Streptomyces in salty environments. Such information is essential for understanding the ecology of Streptomyces. Here we analyzed four house-keeping genes (16S rRNA, rpoB, recA and atpD) and salty-tolerance related genes (ectA-ectD) of 38 Streptomyces strains isolated from saline environments in Yunnan and Xinjiang Provinces of western China. The obtained Streptomyces strains were classified into three operational taxonomic units, each comprising habitat-specific geno- and ecotype STs. In combination with expressional variations of salty-tolerance related genes, the statistical analyses showed that spatial distance and environmental factors substantially influenced Streptomyces distribution in saline environments: the former had stronger influence at large spatial scales (>700 km), whereas the latter was influential at large (>700 km) and small spatial scales (<700 km). Plus, the quantitative analyses of salty-tolerence related genes (ectA-D) indicated that Streptomyces strains from salt lakes have higher expression of ectA-D genes and could accumulate larger quantities of ectoine and hydroxyectoine than strains from salt mines, which could help them resist to salinity in the hypersaline environments.
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Evolución Biológica , Filogeografía , Tolerancia a la Sal , Streptomyces/fisiología , China , Ecosistema , Genes Bacterianos , Streptomyces/genética , Streptomyces/aislamiento & purificaciónRESUMEN
PURPOSE: The aim of this study was to compare the clinical effect of graciloplasty using two different gracilis encircled loops for the treatment of fecal incontinence after anoplasty for imperforate anus. METHODS: From January 2009 to January 2012, 38 patients were treated by graciloplasty. The patients were randomly divided into two groups, one group consisting of 18 cases underwent the "γ-loop" and the other group consisting of 20 cases underwent the "υ-loop." All patients underwent postoperative defecation training and regular follow-up. All patients were evaluated via Wexner score and anal manometry (including anal resting pressure, anal maximal squeeze pressure, duration of anal squeeze, and rectal maximum tolerable volume) before and after graciloplasty. In addition, it was assessed whether the patients had difficulty defecating while squatting after surgery. RESULTS: The surgeries on the 38 patients were accomplished successfully. There were no differences in postoperative complications between the two groups (P > 0.05). The Wexner score and anal manometry parameters of the two groups were gradually improved after operation. The generalized estimating equation results of the Wexner score indicated that the difference of measurement time was statistically significant (P < 0.05) but the difference of measurement group was not statistically significant (P > 0.05). The results of anal manometry parameters using repeated measures ANOVA indicated that differences between different time points were statistically significant (all P < 0.05) but differences between different surgery groups were not statistically significant (all P > 0.05). Regarding the postoperative defecating difficulties while squatting, the probability of occurrence in the "γ-loop" group was significantly higher than that in the "υ-loop" group. The difference between the two groups was statistically significant (P < 0.05). CONCLUSIONS: Graciloplasty with different gracilis loops can improve anal function in patients. However, "υ-loop" can significantly improve difficulties in defecating while squatting.
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Canal Anal/cirugía , Ano Imperforado/cirugía , Incontinencia Fecal/cirugía , Músculo Esquelético/cirugía , Complicaciones Posoperatorias/cirugía , Adolescente , Adulto , Canal Anal/fisiología , Ano Imperforado/complicaciones , Defecación , Incontinencia Fecal/etiología , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/fisiopatología , Postura , Adulto JovenRESUMEN
The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.
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BACKGROUND: Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. METHODS: Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3-15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood-brain barrier permeability. RESULTS: We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. CONCLUSIONS: Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.
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Barrera Hematoencefálica/patología , Epilepsia Tónico-Clónica/líquido cefalorraquídeo , Epilepsia Tónico-Clónica/patología , Metaloproteinasa 9 de la Matriz/líquido cefalorraquídeo , Convulsiones/líquido cefalorraquídeo , Convulsiones/patología , Adolescente , Adulto , Anciano , Anticonvulsivantes/uso terapéutico , Recuento de Células , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Permeabilidad , Albúmina Sérica/análisis , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
The glucocerebrosidase (GBA) gene mutation is emerging as an important risk factor for Parkinson's disease. We previously reported that the GBA gene L444P mutation is an important risk factor for PD in the Chinese population. The prevalence of this mutation in other neurodegenerative diseases and movement disorders remains completely unexplored in mainland China. In the present study, we extended the screening of GBA gene L444P mutation to Chinese patients with essential tremor (ET) and multiple system atrophy (MSA). We searched for the GBA gene L444P mutation in 109 patients with ET, 54 patients with MSA, and 657 controls from mainland China. None of the 109 patients with ET or 54 patients with MSA carried the GBA gene L444P mutation. Among the 657 controls, we found one L444P heterozygote. The difference in mutation frequencies between patients with ET or MSA and the control group was not statistically significant (chi-squared test, p = 1, respectively). The results suggest that the GBA gene L444P mutation may be not responsible for ET in mainland China. Whether the GBA gene L444P mutation modifies the risk for MSA deserves further study in larger samples.
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Pueblo Asiatico/genética , Temblor Esencial/enzimología , Temblor Esencial/genética , Estudios de Asociación Genética , Glucosilceramidasa/genética , Atrofia de Múltiples Sistemas/enzimología , Atrofia de Múltiples Sistemas/genética , Mutación , Adolescente , Adulto , Anciano , Sustitución de Aminoácidos/genética , China/epidemiología , Temblor Esencial/epidemiología , Femenino , Estudios de Asociación Genética/métodos , Humanos , Masculino , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/epidemiología , Adulto JovenRESUMEN
BACKGROUND: To evaluate the efficacy and tolerability of capecitabine combined with thalidomide in patients with advanced pancreatic cancer (APC) who have previously received gemcitabine-based therapy. METHODS: A total of 31 patients were recruited prospectively in Shandong Tumor Hospital from May 2007 to April 2009. Capecitabine was offered to patients twice a day at a dose of 1250 mg/m(2) for 14-day then followed by 7-day rest. Thalidomide was administered 100 mg/day without interruption until disease progression or occurrence of unacceptable toxicity. RESULTS: Two patients presented partial response (PR), 11 patients showed stable disease (SD) and eighteen patients presented progressive disease (PD). The median progression-free survival (PFS) was 2.7 months (95% confidence interval (CI), 2.4-3.3) and the median overall survival (OS) was 6.1 months (95% CI, 5.3-6.9). In the subgroup analysis, PFS had a significant difference between the serum CA19-9 level decreasing >25% and decreasing <25%, with 3.0 months (95% CI, 2.5-3.6) and 2.5 months (95% CI, 1.8-3.2), (Log Rank = 0.02), respectively. Hematological toxicity included leukocytopenia, anemia and neutropenia. Non-hematological toxicities included diarrhea, skin rash, nausea/vomiting, hand-foot syndrome, fatigue, dizziness, drowsiness and constipation. CONCLUSION: Capecitabine combined with thalidomide is a well-tolerated second-line regimen, in patients with APC refractory to gemcitabine.
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Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Talidomida/administración & dosificación , Adulto , Anciano , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Talidomida/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyze the prognosis of rectal gastrointestinal stromal tumors (GIST). METHODS: Records of 40 patients diagnosed as rectal GIST at the Affiliated Chinese Traditional Medical Hospital of Xinjiang Medical University and the People's Hospital of Tianjin City between June 1979 and June 2010 were reviewed. Clinical features, treatment modalities and outcomes were analyzed. RESULTS: There were 23 males and 17 females with a median age of 54.5 years old (range, 28-81 years old). During the follow-up(median 52.5 months, range 1-300 months), 18 patients developed recurrence including 7 local recurrence, 6 metastasis and 5 local recurrence complicated with metastasis. The overall survival rates at 1, 3 and 5 years were 82.5%, 60.0%, and 42.5% respectively. On univariate analysis, tumor size(P<0.01), Fletcher classification(P<0.01), mitotic index(P<0.01), and post-operative distant metastasis were associated with survival. Multivariate analysis showed that tumor size(P<0.05), mitotic rate (P<0.01), and postoperative distant metastasis(P<0.01) were independent prognostic factors associated with survival. CONCLUSIONS: Surgery is the main treatment for rectal GIST. Tumor size, mitotic rate and metastasis are independent prognostic factors in patients with rectal GIST.
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Tumores del Estroma Gastrointestinal/cirugía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
<p><b>OBJECTIVE</b>To analyze the prognosis of rectal gastrointestinal stromal tumors (GIST).</p><p><b>METHODS</b>Records of 40 patients diagnosed as rectal GIST at the Affiliated Chinese Traditional Medical Hospital of Xinjiang Medical University and the People's Hospital of Tianjin City between June 1979 and June 2010 were reviewed. Clinical features, treatment modalities and outcomes were analyzed.</p><p><b>RESULTS</b>There were 23 males and 17 females with a median age of 54.5 years old (range, 28-81 years old). During the follow-up(median 52.5 months, range 1-300 months), 18 patients developed recurrence including 7 local recurrence, 6 metastasis and 5 local recurrence complicated with metastasis. The overall survival rates at 1, 3 and 5 years were 82.5%, 60.0%, and 42.5% respectively. On univariate analysis, tumor size(P<0.01), Fletcher classification(P<0.01), mitotic index(P<0.01), and post-operative distant metastasis were associated with survival. Multivariate analysis showed that tumor size(P<0.05), mitotic rate (P<0.01), and postoperative distant metastasis(P<0.01) were independent prognostic factors associated with survival.</p><p><b>CONCLUSIONS</b>Surgery is the main treatment for rectal GIST. Tumor size, mitotic rate and metastasis are independent prognostic factors in patients with rectal GIST.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Seguimiento , Tumores del Estroma Gastrointestinal , Cirugía General , Pronóstico , Neoplasias del Recto , Cirugía General , Estudios RetrospectivosRESUMEN
The Grb10-interacting GYF protein-2 gene (GIGYF2) is a PARK11 gene that reportedly has a causal role in familial Parkinson's disease (PD) among populations from Italy and France. However, no comprehensive study of the GIGYF2 gene has been conducted among PD patients from mainland China. In our previous study, the GIGYF2 gene was directly sequenced, and nine missense variants and 14 polymorphisms were identified. For these 14 polymorphisms, in the present study we performed a casecontrol analysis for 300 PD patients and 200 healthy controls from mainland China. The c.297T>C p.Ala99Ala polymorphism was associated with increased risk with respect to the pathogenesis of sporadic PD. In conclusion, within the Chinese population, the c.297T>C p.Ala99Ala polymorphism of the GIGYF2 gene may be associated with an increased risk of developing PD.
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Proteínas Portadoras/genética , Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Estudios de Seguimiento , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The ubiquitin carboxy-terminal hydrolase L1 gene (UCH-L1) has been implicated in the etiology of Parkinson's disease (PD). In several previous studies, an S18Y (C54A) polymorphism in exon 3 of the UCH-L1 gene has been found to be protective against PD. We performed polymerase chain reaction-restriction fragment length polymorphism analysis for DNA samples from 408 Chinese patients with PD and 398 Chinese healthy controls. For the S18Y variant, there was no significant difference either in the individual allele or genotype frequencies between cases and control subjects. Possession of the S18Y variant did not alter the risk of developing PD (odds ratio: 0.827; 95% confidence interval=0.596-1.147). There was no statistically significant difference in terms of age or sex distribution between the patients and controls (p>0.05). Overall, considering our present results together with those of our previous studies, we now have access to data from more than 1000 patients from different regions of China, supporting the conclusion that the S18Y polymorphism may not have a protective effect against PD in the Chinese population.
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Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Ubiquitina Tiolesterasa/genética , Adolescente , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
The aim of this study was to investigate induction of apoptosis by the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and gemcitabine in the pancreatic cancer cell line SW1990. The sensitivity of SW1990 cells to TRAIL and/or gemcitabine-induced apoptosis and the rate of apoptosis were assessed by MTT assay and flow cytometry, respectively. We used Hoechst 33342 staining to observe apoptotic morphology and expression levels of proteins were analyzed by Western blottin. Growth inhibition and apoptosis rates on treatment with the combination of TRAIL and gemcitabine were significantly higher than with each drug alone (p<0.05). Pancreatic cancer cells exhibited a typical apoptosis morphology after treatment with TRAIL or gemcitabine. The levels of cellular apoptosis-associated proteins such as Smac/DIABLO, Cyto C, and the activated fragment of caspase-3 (P17) increased, but the expression of XIAP was significantly decreased after 24 h (p<0.05). SW1990 cells responded to TRAIL and/or gemcitabine-induction of apoptosis in a time and concentration-dependent manner. The mechanism of the apoptosis-sensitization effect appeared associated with significant up-regulation of Smac/DIABLO and cytochrome C, down-regulation of XIAP, and activation of caspase-3.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Proteínas Reguladoras de la Apoptosis , Caspasa 3/metabolismo , Línea Celular Tumoral , Citocromos c/metabolismo , Desoxicitidina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Mitocondriales/metabolismo , Neoplasias Pancreáticas/patología , Regulación hacia Arriba/efectos de los fármacos , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , GemcitabinaRESUMEN
Two markers rs9652490 and rs11856808 both located in intron 3 of the LINGO1 gene have been nominated recently to be associated with essential tremor (ET). Although ET and Parkinson's disease (PD) are considered as different entities, they have many overlapping clinical and pathological features. We aimed to evaluate the role of rs9652490 and rs11856808 in the development of ET and PD. To this point, we sequenced the region involving the two markers in 109 ET cases, 425 sporadic Parkinson's disease (SPD) cases and 430 controls in Chinese population. After stratification by age, the rs9652490G allele suggested protective role in the early onset PD (EOPD, age at onset < or =50 years) group compared with age matched controls (OR=0.56, 95% CI: 0.35-0.90, p=0.015). No other significant association was found. We concluded that the two markers rs9652490 and rs11856808 were not strongly related to the development of ET or late onset SPD, but the rs9652490G allele might be a protective factor for EOPD in Chinese population.
Asunto(s)
Temblor Esencial/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Pruebas Genéticas/métodos , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
An association between mutations in the glucocerebrosidase (GBA) gene and Parkinson's disease (PD) has been reported in several populations. We searched for four common GBA mutations (L444P, F213I, R353W, and N370S) in 402 Chinese PD patients and 413 age- and sex-matched controls. In the PD cohort, 11 patients were found carrying a heterozygous GBA mutation and all of them had the L444P mutation. Heterozygous GBA mutations were detected none in controls. The GBA gene L444P mutation was detected at a significantly higher frequency among PD patients (11/402 = 2.74%), when compared with the control group (0/413): P = 0.0007. To evaluate the possible role of the GBA gene L444P mutation in PD in Ashkenazi Jewish and non-Jewish populations, we conducted a meta-analysis on the topic. In the Chinese population, the GBA gene L444P mutation was detected at a significantly higher frequency among PD patients, when compared with the control group: Z = 3.83, P = 0.0001, OR = 8.42, confidence interval = 95%, 2.83-25.06. In the non-Jewish populations, the difference was obviously significant: Z = 5.76, P < 0.00001, OR = 8.82, confidence interval = 95%, 4.21-18.48. The results suggest that the GBA gene L444P mutation appears to be a risk factor for PD in Chinese population.
Asunto(s)
Glucosilceramidasa/genética , Leucina/genética , Mutación/genética , Enfermedad de Parkinson/genética , Prolina/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Persona de Mediana EdadRESUMEN
This study was aimed to investigate the anti-leukemia activity of Tel03 in vivo. The K562 xenografted leukemia model was established and mice were divided randomly into three groups. Mice of different group were treated with PBS (control), 5 mg/kg Tel03 or 15 mg/kg Tel03 (ip, twice a week) respectively. Tumor volume, body weight and other behavior were observed regularly. Cell apoptosis was detected with TUNEL assay and the expression levels of Bcl-2 and Bax were detected by Western blot. The results indicated that Tel03 exerted anti-leukemia activity in mouse model. Tel03 significantly reduced tumor volume in Tel03-treated group compared with control. In addition, 5 mg/kg Tel03 induced cell apoptosis without exerting apparent toxicity in mice. After Tel03 treatment, the expression of Bcl-2 was inhibited, however, the expression of Bax was up-regulated. It is concluded that G-quadruplex ligand Tel03 can induce cell apoptosis in leukemia mouse model, and this agent may be a potential anticancer drug.