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1.
Zhonghua Yi Xue Za Zhi ; 102(19): 1445-1449, 2022 May 24.
Article in Chinese | MEDLINE | ID: mdl-35599409

ABSTRACT

Objective: To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis (MG) patients. Methods: We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020. After obtaining the patient's informed consent, the blood samples were collected. The Whole Exome Sequencing (WES) was performed on peripheral blood samples. And use biological information software and SPSS 22.0 for data processing and result analysis. Results: According to the inclusion and exclusion criteria, 54 patients with juvenile MG were included, 28 males and 26 females. And the average age of onset was (3.79±0.89) years. Among the enrolled patients, there were 52 (96.3%) patients with ocular MG, the MG-ADL scores of 54 patients were (3.44±0.44) points, and the titer of AChR antibody was (5.88±2.45) nmol/L. Two patients had thymic hyperplasia, and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients, of which TTN gene variants had the largest number, with a total of 17 variants (31.5%). In the TTN gene variant group, 7(41.2%) patients had eye fixation symptoms, and 4 (10.8%) patients in the non-mutation group had eye fixation symptoms. And The difference between the two groups was statistically significant (P=0.016). In addition, the synaptic nucleus envelope protein-1 (SYNE1) and the ryanodine receptor-1 (RYR1) gene variations were also found in 7 cases (13.2%), and no clear relationship between these gene variations and clinical manifestations of MG was found. Conclusions: The incidence of juvenile MG was preschoolers with no gender difference, and ocular MG was more common. The proportion of TTN gene variation in adolescent MG was higher, suggesting that this gene may be a potential therapeutic target for juvenile MG patients.


Subject(s)
Myasthenia Gravis , Thymus Hyperplasia , Adolescent , Antibodies , Child, Preschool , Female , Genetic Variation , Humans , Male , Myasthenia Gravis/diagnosis , Myasthenia Gravis/genetics , Receptors, Cholinergic/genetics , Retrospective Studies
2.
Zhonghua Yi Xue Za Zhi ; 102(13): 942-947, 2022 Apr 05.
Article in Chinese | MEDLINE | ID: mdl-35385966

ABSTRACT

Objective: To investigate the clinical manifestations, treatment characteristics and outcomes of myasthenia gravis (MG) dually positive for anti-acetylcholine receptor antibody (AChR-Ab) and anti-muscle-specific tyrosine kinase antibody (MuSK-Ab). Method: MG patients hospitalized in the First Affiliated Hospital of Sun Yat-sen University from August 2017 to November 2020 were retrospectively collected. Thirty-four MuSK-Ab positive MG (MuSK-MG) patients, 11 double-antibodies positive MG (DP-MG) patients, and 80 AChR-Ab positive MG (AChR-MG) patients were included and allocated to three different groups. The clinical data of patients in the three groups were collected, and the differences of demographic characteristics, clinical manifestations and treatment outcomes between DP-MG patients and AChR-MG and MuSK-MG patients were analyzed. Result: The proportion of female and male patients in DP-MG group was 7/11 and 4/11 respectively, and the onset age of DP-MG was (41±27) years.The difference in gender distribution between DP-MG and AChR-MG groups was statistically significant (P<0.05). The proportion of extraocular muscle involvement in the DP-MG and MuSK-MG groups (8/11 and 52.9%) was lower than that in the AChR-MG group (83.8%), and the difference was statistically significant (P<0.05). The incidence of myasthenia crisis in DP-MG and MuSK-MG groups (54.5% and 61.8%) were higher than that in AChR-MG group (20.0%), with astatistically significant difference(P<0.05). The positive rate of neostigmine test in DP-MG and MuSK-MG groups(8/11 and 74.2%) were lower than that of AChR-MG group (96.8%), and the positive rate of low frequency repetitive nerve stimulation (RNS) in DP-MG group (5/10) was lower than that in AChR-MG group (85.1%), with statistically significant differences (all P<0.05). MuSK-Ab titer was positively correlated with the course of disease (r=0.466, P<0.05), and antibody titer decreased after symptom improvement (P<0.05). The response of patients in DP-MG and MuSK-MG groups to cholinesterase inhibitors (2/11 and 9.1%) was worse than that in the AChR-MG group (66.3%), and the incidence of side effects in the two groups (5/11 and 39.4%) was higher than that in the AChR-MG group (15.0%), with statistically significant differences (all P<0.05). There were 4 DP-MG patients underwent thymectomy, and the pathological results detected two cases of thymoma and two cases of thymic hyperplasia. Subsequent follow-up showed that 5 (5/11) DP-MG patients achieved minimal manifestation status or better status. Conclusion: The gender distribution, age of onset, pharmacological characteristics and electrophysiological examination of DP-MG patients were similar to those of MuSK-MG patients, but the severity of DP-MG patients was between that of AChR-MG and MuSK-MG patients.


Subject(s)
Myasthenia Gravis , Thymus Neoplasms , Adolescent , Adult , Aged , Autoantibodies , Female , Humans , Male , Middle Aged , Muscles/pathology , Myasthenia Gravis/diagnosis , Receptor Protein-Tyrosine Kinases , Receptors, Cholinergic , Retrospective Studies , Tyrosine , Young Adult
3.
Zhonghua Yi Xue Za Zhi ; 99(32): 2522-2526, 2019 Aug 27.
Article in Chinese | MEDLINE | ID: mdl-31484280

ABSTRACT

Objective: To retrospectively analyze the characteristics of the electromyography (EMG) study in generalized myasthenia gravis (gMG) patients. Methods: A total of 111 gMG patients were enrolled. Patients were divided into two groups: 36 severe patients discontinuing pyridostigmine bromide (PB) for 8 hours were included in 8 h group, and 75 g MG patients discontinuing PB for at least 18 hours were included in>18 h group. The clinical information and EMG study data were collected and analyzed. Results: There were statistically significant differences in the initial location of the myasthenia muscle (P=0.027), the affected muscle detected by the EMG (P=0.015) and quantitative myasthenia gravis (QMG) score (P<0.01) between the two groups. Comparisons in each group revealed that the highest positive rate of low-frequency repetitive nerve stimulation (RNS) of facial in 8 h group and>18 h group was 94.4% and 60.0%, respectively. Comparisons between the two groups showed that the positive rate of low-frequency RNS in 8 h group was significantly higher than that in>18 h group (94.4% vs 70.7%, χ(2)=8.115, P=0.004). In particular, the positive rate of RNS in facial nerves and the extent of the amplitude decrease under different electrical stimulations (1 Hz, 3 Hz, and 5 Hz) were dramatically higher in the 8 h group (P<0.01). Conclusions: For gMG patients, the facial and accessory nerve detection can improve the positive rate of RNS. Different muscles had various sensitivity to PB, and orbicularis oculi muscle seemed the least sensitive muscle to PB. For suspect MG patients in severe condition, only discontinuing PB medication for 8 h before low-frequency RNS testing can avoid the deterioration and also obtain similar positive rate.


Subject(s)
Myasthenia Gravis , Electric Stimulation , Electromyography , Facial Muscles , Humans , Retrospective Studies
4.
Zhonghua Yi Xue Za Zhi ; 97(37): 2884-2889, 2017 Oct 10.
Article in Chinese | MEDLINE | ID: mdl-29050155

ABSTRACT

Objective: To investigate the clinical features of the Pre-Crisis State and analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis. Methods: We included 93 patients with myasthenia gravis (MG) who experienced 127 times Pre-Crisis State between October 2007 and July 2016. Those patients were hospitalized in the MG specialize center, Department of Neurological Science, first Affiliated Hospital of Sun Yat-sen University. The information of the general situation, the clinical manifestations and the blood gas analysis in those patients were collected using our innovated clinical research form. Statistic methods were applied including descriptive analysis, univariate logistic analysis, multivariate correlation logistic analysis, etc. Results: (1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100% not requiring intubation or non-invasive ventilation), bulbar-muscle weakness (121 times, 95.28%), the increased blood partial pressure of carbon dioxide (PCO(2)) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The occurrence of dyspnea in combination with bulbar-muscle weakness (P=0.002) or the increased blood PCO(2) (P=0.042) often indicated the tendency of crisis. (2) The MG symptoms which were proportion to the occurrence of crisis includes: bulbar-muscle weakness (P=0.028), fever (P=0.028), malnutrition (P=0.066), complications (P=0.071), excess oropharyngeal secretions (P=0.005) and the increased blood PCO(2) (P=0.007). The perioperative period of thymectomy would not increase the risk of crisis. Conclusions: Dyspnea indicates the occurrence of the Pre-Crisis State of MG. In order to significantly reduce the morbidity of myasthenia crisis, the bulbar-muscle weakness, the increased blood PCO(2), expectoration weakness, sleep disorders, infection & fever and excess oropharyngeal secretions should be treated timely.


Subject(s)
Myasthenia Gravis , Humans , Multivariate Analysis , Postoperative Complications , Risk Factors , Thymectomy
5.
Aliment Pharmacol Ther ; 46(8): 722-730, 2017 10.
Article in English | MEDLINE | ID: mdl-28815645

ABSTRACT

BACKGROUND: Lenalidomide has immunomodulatory and anti-angiogenic effects and showed moderate anti-tumour efficacy in patients with. advanced hepatocellular carcinoma (HCC) AIM: To explore potential biomarkers of lenalidomide efficacy as second-line therapy for HCC. METHODS: Eligible patients were diagnosed with advanced HCC, documented progression on sorafenib, and Child-Pugh class A liver function. Patients received 25 mg/day lenalidomide orally on days 1-21 every 4 weeks. The primary endpoint was 6 month progression-free survival rate. Early α-fetoprotein response was defined as a > 20% decline of α-fetoprotein levels from baseline within the first 4 weeks of treatment. Vascular response, evaluated using dynamic contrast-enhanced magnetic resonance imaging, was defined as a > 40% decline in Ktrans after 2 weeks of treatment. The percentage of peripheral blood lymphocyte subsets were also analysed. RESULTS: Fifty-five patients were enrolled. The response rate was 13%, and the disease-control rate was 53%. The 6 month progression-free survival rate was 9.1%. The median progression-free and overall survival was 1.8 months and 8.9 months respectively. Early α-fetoprotein response was significantly associated with higher disease-control rate (76% vs 22%, P = .001) and longer progression-free survival (P = .020). Vascular response was not associated with any treatment outcomes. Patients with a high pre-treatment B cell percentage were more likely to have disease control (70% vs 36%, P = .010) and exhibited longer progression-free survival (P < .001) and overall survival (P = .042). CONCLUSIONS: Lenalidomide exhibited moderate activity as second-line therapy for advanced HCC. Its immunomodulatory effects should be further explored (www.clinicaltrials.gov NCT01545804).


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Thalidomide/analogs & derivatives , Adult , Aged , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/adverse effects , Biomarkers, Tumor/metabolism , Disease Progression , Disease-Free Survival , Female , Humans , Lenalidomide , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/analogs & derivatives , Phenylurea Compounds/administration & dosage , Sorafenib , Thalidomide/administration & dosage , Treatment Outcome , alpha-Fetoproteins/metabolism
6.
Zhonghua Yi Xue Za Zhi ; 97(19): 1463-1468, 2017 May 23.
Article in Chinese | MEDLINE | ID: mdl-28535636

ABSTRACT

Objective: To investigate the characteristics of the distribution and amount of different subtypes of dendritic cell (DC) in myasthenia gravis(MG). Methods: We collected the thymic specimens from 32 patients who received thymoctomy because of cardiac surgery from January 2016 to December 2016 and selected 14 of them as normal control. Meantime, 61 MG patients who combined with thymic hyperplasia and received extended thymectomy were collected and selected 8 of them as experiment group.Immunohistochemical methods were used to label the two subtype DCs: plasmacytoid dendritic cell (pDC) and classical/conventional dendritic cell (cDC), to observe the distribution of these two DC subtypes in thymus and also quantify them in different thymus structures by image analysis software.Comparing with normal thymus of the same age, we intended to demonstrate the characteristics of distribution and density of DC subtypes in patients who had MG and hyperplastic thymus. Results: (1) We labeled pDC and cDC by staining with CD123 and CD11c.The two DC subtypes distributed in both cortex and medulla, and the majority gathered in medulla, the density of pDC in thymus cortex was (34±6)/mm(2)(n=14), the density of pDC in thymus medulla was (247±35)/mm(2)(n=14), the density of cDC in thymus cortex was (21±4)/mm(2)(n=14), the density of cDC in thymus medulla was (123±16)/mm(2) (n=14). (2) The density of pDC in thymus cortex and medulla of patients with MG was lower when compared with the normal group (the density of pDC in thymus cortex, [(39±10)/mm(2) vs (29±5)/mm(2)], the density of pDC in thymus medulla, [(279±48)/mm(2) vs (236±49)/mm(2)], but with no significant difference.There was no significant difference between the density of cDC in thymus cortex of patients with MG patients and normal people, however, the amount of cDC increases in medulla and the difference was statistically significant (P<0.05). (3) The density of cDC in thymus medulla (except for germinal center) was higher than normal people (110±18) /mm(2) vs (187±29/mm(2)), though the difference was not statistically significant (P=0.059 9). The density of cDC in the ectopic germinal center (GC) of MG patients increased obviously compared with that in thymus medulla [(203±44) /mm(2) vs (439±69)/mm(2)] and the difference was statistically significant (P<0.05). Conclusions: The density of cDC increases significantly in thymus medulla of MG patients, especially gathering around or in the ectopic GC. It indicates that cDC may play an important role in the formation of ectopic GC in the hyperplasia thymus, thus involves in the disease process.


Subject(s)
Dendritic Cells , Myasthenia Gravis/pathology , Thymus Hyperplasia/surgery , Humans , Myasthenia Gravis/therapy , Thymectomy , Thymus Gland
7.
J Perinatol ; 35(9): 678-82, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26087317

ABSTRACT

OBJECTIVE: To evaluate the effects of gestational subclinical hypothyroidism (SCH) on early neurodevelopment of offspring. STUDY DESIGN: A prospective study included 106 infants born to mothers with gestational SCH and 106 infants born to mothers who were euthyroid during pregnancy. The neurodevelopment of 12 to 24-month-old infants was assessed and compared using the Gesell developmental test (revised version). RESULTS: Infants born to mothers with gestational SCH and those born to euthyroid mothers had similar scores on the Gesell development test. No correlations were observed between maternal TSH concentration and Gesell developmental test scores of offspring. Infants born to mothers who had gestational SCH during the first trimester specifically and those born to euthyroid mothers had similar scores on the Gesell development test. No significant correlations were detected between maternal TSH concentration during the first trimester and offspring neurodevelopment. CONCLUSIONS: No detectable neurodevelopment deficit was observed in offspring up to 24 months old from mothers who had gestational SCH.


Subject(s)
Hypothyroidism , Nervous System/growth & development , Pregnancy Complications , Prenatal Exposure Delayed Effects , Adult , Behavior Rating Scale , China/epidemiology , Female , Humans , Hypothyroidism/blood , Hypothyroidism/complications , Hypothyroidism/diagnosis , Hypothyroidism/epidemiology , Infant , Infant, Newborn , Intelligence Tests , Longitudinal Studies , Male , Neuropsychological Tests , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/diagnosis , Pregnancy Complications/epidemiology , Pregnancy Trimester, First/blood , Prenatal Exposure Delayed Effects/diagnosis , Prenatal Exposure Delayed Effects/epidemiology , Prenatal Exposure Delayed Effects/etiology , Prospective Studies , Statistics as Topic , Thyroxine/blood
8.
Br J Cancer ; 107(10): 1672-7, 2012 Nov 06.
Article in English | MEDLINE | ID: mdl-23059748

ABSTRACT

BACKGROUND: Patients enrolled in clinical trials of advanced hepatocellular carcinoma (HCC) are usually required to have good liver reserve and organ function. However, their outcomes are still highly variable. We aimed to examine whether current staging systems can predict the survival of these highly selected patients. METHODS: Patients from clinical trials involving first-line anti-angiogenic therapy were assigned to different stage groups using the American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), China integrated score, Cancer of the Liver Italian Program (CLIP) score, Chinese University Prognostic Index (CUPI), Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH), Japan Integrated Staging (JIS) score, Okuda, Tokyo score, and a new staging system recently proposed. Survival prediction by the 10 systems was then compared by both univariate and multivariate analyses. RESULTS: A total of 157 patients were selected for this study. In univariate analysis, all staging systems can predict patient survival except AJCC, BCLC, and JIS score. Concordance indexes for CLIP score, CUPI, and GETCH (0.752, 0.775, and 0.791, respectively) were significantly higher than those obtained for other staging systems. In multivariate analysis, the CLIP score and CUPI (P<0.001 and 0.009, respectively) predicted survival more accurately than did the other tested staging systems. Hepatitis B infection and poor performance status were also associated with poor survival. CONCLUSION: Several HCC staging systems, especially the CLIP score and CUPI, can predict prognosis of patients who are enrolled in clinical trials of advanced HCC.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Staging/methods , Adult , Aged , Aged, 80 and over , Clinical Trials as Topic/methods , Female , Humans , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prognosis , Young Adult
9.
Eur J Neurol ; 19(9): 1245-50, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22524995

ABSTRACT

BACKGROUND AND PURPOSE: Owing to its low morbidity but high mortality, no accurate scoring system focuses on primary pontine hemorrhage (PPH) has been established. We aim to compare the performances of the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Simplified Acute Physiology Score (SAPS) II with the ICH score in predicting the 30-day mortality in patients with PPH. METHODS: We conducted a retrospective analysis of patients admitted with a diagnosis of PPH to a university-affiliated hospital in southern China from May 2000 to June 2011. Data related to patient demographics and that necessary to calculate APACHE II, SAPS II, and ICH score were recorded. Performances of these scoring systems were presented as calibration and discrimination, which were measured by the Hosmer-Lemeshow goodness-of-fit test and the area under the receiver operating characteristic (ROC) curve, respectively. RESULTS: Among 75 patients with PPH finally included, 31 (41.3%) died within 30 days. SAPS II (χ(2) = 6.57, P = 0.682) had the best calibration, followed by APACHE II (χ(2) = 8.06, P = 0.428) and ICH score (χ(2) = 4.94, P = 0.176). Furthermore, in terms of area under the ROC curve, APACHE II (0.919) was more discriminative than SAPS II (0.890) and ICH score (0.844). CONCLUSIONS: In predicting 30-day mortality in patients with PPH, SAPS II has the best calibration, while APACHE II has the highest discrimination. The ICH score, which is easier and simpler to calculate, should be modified for PPH.


Subject(s)
Intracranial Hemorrhages/mortality , Pons/pathology , APACHE , Adult , Aged , Female , Humans , Intracranial Hemorrhages/classification , Intracranial Hemorrhages/diagnosis , Male , Middle Aged , ROC Curve , Retrospective Studies , Severity of Illness Index
10.
Br J Cancer ; 102(6): 981-6, 2010 Mar 16.
Article in English | MEDLINE | ID: mdl-20160718

ABSTRACT

BACKGROUND: Molecularly targeted agents with anti-angiogenic activity, including bevacizumab, have demonstrated clinical activity in patients with advanced/metastatic hepatocellular carcinoma (HCC). This multicentre phase II study involving patients from several Asian countries sought to evaluate the safety and efficacy of bevacizumab plus capecitabine in this population. METHODS: Histologically proven/clinically diagnosed advanced HCC patients received bevacizumab 7.5 mg kg(-1) on day 1 and capecitabine 800 mg m(-2) twice daily on days 1-14 every 3 weeks as first-line therapy. RESULTS: A total of 45 patients were enrolled; 44 (96%) had extrahepatic metastasis and/or major vessel invasion and 30 (67%) had hepatitis B. No grade 3/4 haematological toxicity occurred. Treatment-related grade 3/4 non-haematological toxicities included diarrhoea (n=2, 4%), nausea/vomiting (n=1, 2%), gastrointestinal bleeding (n=4, 9%) and hand-foot syndrome (n=4, 9%). The overall response rate (RECIST) was 9% and the disease control rate was 52%. Overall, median progression-free survival (PFS) and overall survival (OS) were 2.7 and 5.9 months, respectively. Median PFS and OS were 3.6 and 8.2 months, respectively, for Cancer of the Liver Italian Programme (CLIP) score < or =3 patients, and 1.4 and 3.3 months, respectively, for CLIP score 4 patients. CONCLUSION: The bevacizumab-capecitabine combination shows good tolerability and modest anti-tumour activity in patients with advanced HCC.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Liver Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Capecitabine , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease Progression , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Survival Analysis , Treatment Outcome , Young Adult
11.
Braz J Med Biol Res ; 39(5): 677-85, 2006 May.
Article in English | MEDLINE | ID: mdl-16648906

ABSTRACT

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 microM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 +/- 3.9% in HNE1-LMP1 cells vs 37.89 +/- 4.9% in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 +/- 3.5 vs 65.87 +/- 5.9%), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 +/- 3.7 and 27.91 +/- 2.1%), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 +/- 3.9 vs 29.19 +/- 6.27%) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.


Subject(s)
Antineoplastic Agents/pharmacology , Arsenicals/pharmacology , Matrix Metalloproteinase 9/drug effects , Nasopharyngeal Neoplasms/drug therapy , Oxides/pharmacology , Viral Matrix Proteins/drug effects , Arsenic Trioxide , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic , Humans , Matrix Metalloproteinase 9/genetics , Microscopy, Confocal , Nasopharyngeal Neoplasms/pathology , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/pathology , RNA, Messenger/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Viral Matrix Proteins/genetics
12.
Braz. j. med. biol. res ; 39(5): 677-685, May 2006. ilus, graf
Article in English | LILACS | ID: lil-425788

ABSTRACT

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 æM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9 percent in HNE1-LMP1 cells vs 37.89 ± 4.9 percent in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9 percent), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1 percent), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27 percent) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.


Subject(s)
Humans , Antineoplastic Agents/pharmacology , Arsenicals/pharmacology , Matrix Metalloproteinase 9/drug effects , Nasopharyngeal Neoplasms/drug therapy , Oxides/pharmacology , Viral Matrix Proteins/drug effects , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic , Microscopy, Confocal , Matrix Metalloproteinase 9/genetics , Nasopharyngeal Neoplasms/pathology , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/pathology , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger/drug effects , Viral Matrix Proteins/genetics
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