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31.
    
Nasopharyngeal cancer (NPC) is an Epstein‐Barr virus (EBV)‐associated head and neck cancer prevalent in Asia. Although with reasons not fully understood, the intrinsic invasiveness of NPC is believed to be EBV‐linked. Recently, EBV was found to induce STAT3 activation. Constitutive STAT3 activation correlated with advanced clinical staging in NPC. We hypothesized that STAT3 activation by EBV directly contributes to the intrinsic invasiveness of NPC cells. Phospho‐STAT3‐Tyr705 was detected in high percentage of NPC tumors (7/10 cases). Using a paired NPC cell line model, HONE‐1 and the EBV‐infected counterpart, HONE‐1‐EBV, we found that HONE‐1‐EBV expressed a higher level of phospho‐STAT3‐Tyr705 and was ~11‐fold more invasive than HONE‐1. In HONE‐1‐EBV, STAT3 siRNA targeting inhibited both spontaneous and serum‐induced invasion, as well as cell growth. Conversely, activation of STAT3 (by expressing an activated STAT3 mutant, namely STAT3C) in the parental HONE‐1, mimicking EBV‐induced STAT3 activation, significantly enhanced its invasiveness and proliferation, which was accompanied by increased expression of markers of mesenchymal status, proliferation and anti‐apoptosis. Our results demonstrated that EBV‐induced STAT3 activation is responsible for NPC cell proliferation and invasion. This was further confirmed by a small molecule inhibitor of JAK/STAT3, JSI‐124. JSI‐124 inhibited STAT3 activation in HONE‐1‐EBV, with subsequent growth inhibition, induction of PARP cleavage, abrogation of anchorage‐independent growth and invasion. We found that EBV‐independent activation of STAT3 by a growth factor, EGF, also contributed to NPC invasion. In conclusion, EBV‐induced STAT3 activation directly contributes to the intrinsic invasiveness of NPC cells and STAT3 targeting may be beneficial in treating aggressive NPC. © 2009 UICC  相似文献   
32.
    
To assess the dosimetric effect of using interpolated contours in planning intensity‐modulated radiation therapy (IMRT) for advanced T‐stage nasopharyngeal carcinoma. The present study focused on T3–T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5‐mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full‐scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.  相似文献   
33.
    
Brahma (BRM) has a key function in chromatin remodeling. Two germline BRM promoter insertion–deletion polymorphisms, BRM‐741 and BRM‐1321, have been previously associated with an increased risk of lung cancer in smokers and head and neck cancer. To further evaluate their role in cancer susceptibility particularly in early disease, we conducted a preplanned case–control study to investigate the association between the BRM promoter variants and stage I/II upper aerodigestive tract (UADT) cancers (i.e., lung, esophageal, head and neck), a group of early‐stage malignancies in which molecular and genetic etiologic factors are poorly understood. The effects of various clinical factors on this association were also studied. We analyzed 562 cases of early‐stage UADT cancers and 993 matched healthy controls. The double homozygous BRM promoter variants were associated with a significantly increased risk of early stage UADT cancers (adjusted odds ratio [aOR], 2.46; 95% confidence interval [CI], 1.7–3.8). This association was observed in lung (aOR, 2.61; 95% CI, 1.5–4.9) and head and neck (aOR, 2.75; 95% CI, 1.4–5.6) cancers, but not significantly in esophageal cancer (aOR, 1.66; 95% CI, 0.7–5.8). There was a nonsignificant trend for increased risk in the heterozygotes or single homozygotes. The relationship between the BRM polymorphisms and early‐stage UADT cancers was independent of age, sex, smoking status, histology, and clinical stage. These findings suggest that the BRM promoter double insertion homozygotes may be associated with an increased risk of early‐stage UADT cancers independent of smoking status and histology, which must be further validated in other populations.  相似文献   
34.
  总被引:2,自引:0,他引:2  
PURPOSE: Mutations of the CYP4V2 gene, a novel family member of the cytochrome P450 genes on chromosome 4q35, have recently been identified in patients with Bietti crystalline dystrophy (BCD). The aim of this study was to investigate the spectrum of mutations in this gene in BCD patients from Singapore, and to characterize their phenotype. METHODS: Nine patients with BCD from six families were recruited into the study. The 11 exons of the CYP4V2 gene were amplified from genomic DNA of patients by polymerase chain reaction and then sequenced. Detailed characterization of the patients' phenotype was performed with fundal photography, visual field testing, fundal fluorescein angiography, and electroretinography (ERG). RESULTS: Three pathogenic mutations were identified; two mutations, S482X and K386T, were novel and found in three patients. The third mutation, a previously identified 15-bp deletion that included the 3' splice site for exon 7, was found in all nine patients, with six patients carrying the deletion in the homozygous state. Haplotype analysis in patients and controls indicated a founder effect for this deletion mutation in exon 7. Clinical heterogeneity was present in the patients. Compound heterozygotes for the deletion in exon 7 seemed to have more severe disease compared to patients homozygous for the deletion. There was good correlation between clinical stage of disease and ERG changes, but age did not correlate with disease severity. CONCLUSIONS: This study identified novel mutations in the CYP4V2 gene as a cause of BCD. A high carrier frequency for the 15-bp deletion in exon 7 may exist in the Singapore population. Phenotype characterization showed clinical heterogeneity, and age did not correlate with disease severity.  相似文献   
35.
Mouse models in liver cancer research: A review of current literature   总被引:3,自引:0,他引:3  
Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver cancer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma (HCC), as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.  相似文献   
36.
  总被引:3,自引:0,他引:3  
The mortality rate of lung cancer in Asian women has increased significantly in the past few decades. Environmental factors include tobacco smoke (active and environmental), other indoor pollutions (cooking oil vapours, coal burning, fungus spores), diet, and infections. Active tobacco smoking is not the major factor. The relative risk of lung cancer among non-smoking women ever exposed to environmental smoke from their husbands was 1.20 from a meta-analysis. Cooking oil vapours associated with high temperature wok cooking and indoor coal burning for heating and cooking in unvented homes, particularly in rural areas, are risk factors for Chinese women. Chronic benign respiratory diseases due to the fungus Microsporum canis probably accounts for the high incidence of lung cancer in northern Thai women at Sarapee. Diets rich in fruits, leafy green vegetables, and vitamin A are protective, while cured meat (Chinese sausage, pressed duck and cured pork), deep-fried cooking, and chili increased the risk. Tuberculosis is associated with lung cancer. Also, a Taiwanese study showed that the odds ratio of papillomavirus (HPV) 16/18 infection in non-smoking female lung cancer patients was 10.1, strongly suggesting a causative role. Genetic factors have also been studied in Chinese women, including human leucocyte antigens, K-ras oncogene activation, p53 mutation, polymorphisms of phase I activating enzymes (cytochrome P450, N-acetyltransferase slow acetylator status), and phase II detoxifying enzymes (glutathione-S-transferases, N-acetyltransferase rapid acetylator status). New molecular screening technology would facilitate identification of molecular targets for future studies. The interaction between environmental and genetic factors should also be further elucidated.  相似文献   
37.
    
OBJECTIVE: In several large, well-designed, randomized, double-blind studies, the opiate antagonist naltrexone demonstrated efficacy in the treatment of alcohol dependence. Specifically, when combined with certain psychosocial therapies, naltrexone reduces the number of drinking days, heavy drinking, and time to relapse to alcohol use in alcohol-dependent individuals. Whether this efficacy can be generalized to individuals who have alcohol use disorders and present for treatment at front-line community treatment programs has not been well established. METHODS: A total of 145 patients who presented for treatment at a rural community substance abuse treatment center were randomized to receive naltrexone 50 mg daily plus usual program treatment (n = 54), placebo plus usual treatment (n = 43), or usual treatment alone (n = 48) for 12 week. A total of 133 participants had at least one follow-up visit. Primary outcome measures included percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days (four or more for women and six or more for men), and time to first heavy drinking day. Secondary measures included changes in serum biological markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase), craving, and psychosocial functioning. RESULTS: In the intention-to-treat analysis, there were no between-group differences for any of the primary drinking outcomes at 12 weeks. In post hoc exploratory analyses, the entire sample of participants was divided into two new groups: (1) people who drank during the 2 weeks before the start of medication (entry drinkers) and (2) people who did not drink during this interval (entry abstainers). Entry abstainers were at an advantage at study entry in that they were significantly more likely to have an inpatient hospitalization immediately before entry into outpatient treatment. Mixed-model analysis of variance revealed a main effect for entry group at the 12-week treatment endpoint on the primary outcome measures of percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days, and time to first heavy drinking day. Participants in any of the randomized groups who were entry abstainers had significantly better improvement on all of the primary outcome measures. The abstainer groups that were randomized to placebo and usual treatment had significantly better outcomes than the entry drinkers in those perspective groups. However, for the naltrexone-treated group, entry drinkers and entry abstainers had similar improvement in drinking-related outcomes. CONCLUSIONS: These data suggest that naltrexone may offer particular benefit to patients who continue to drink during the early stages of the trial as compared with those who have achieved abstinence before treatment entry.  相似文献   
38.
    
Background Heart failure (HF) is a physically and socially debilitating disease that carries the burden of hospital re-admission and mortality. As an aging society, Hong Kong urgently needs to find ways to reduce the hospital readmission of HF patients. This study evaluates the effects of a nurse-led HF clinic on the hospital readmission and mortality rates among older HF patients in Hong Kong. Methods This study is a retrospective data analysis that compares HF patient in a nurse-led HF clinic in Hong Kong compared with HF patients who did not attend the clinic. The nurses of this clinic provide education on lifestyle modification and symptom monitoring, as well as titrate the medications and measure biochemical markers by following established protocols. This analysis used the socio-demographic and clinical data of HF patients who were aged ≥ 65 years old and stayed in the clinic over a six-month period. Results The data of a total of 78 HF patients were included in this data analysis. The mean age of the patients was 77.38 ± 6.80 years. Approximately half of the HF patients were male (51.3%), almost half were smokers (46.2%), and the majority received ≤ six years of formal education. Most of the HF patients (87.2%) belonged to classes II and III of the New York Heart Association Functional Classification, with a mean ejection fraction of 47.15 ± 20.31 mL. The HF patients who attended the clinic (n = 38, 75.13 ± 5.89 yrs) were significantly younger than those who did not attend the clinic (n = 40, 79.53 ± 6.96 yrs) (P = 0.04), and had lower recorded blood pressure. No other statistically significant difference existed between the socio-demographic and clinical characteristics of the two groups. The HF patients who did not attend the nurse-led HF clinic demonstrated a significantly higher risk of hospital readmission [odd ratio (OR): 7.40; P < 0.01] than those who attended after adjusting for the effect of age and blood pressure. In addition, HF patients who attended the clinic had lower mortality (n = 4) than those who did not attend (n = 14). However, such a difference did not reach statistical significance when the effects of age and blood pressure were adjusted. A significant reduction in systolic blood pressure [F (2, 94) = 3.39, P = 0.04] and diastolic blood pressure [F (2, 94) = 8.48, P < 0.01] was observed among the HF patients who attended the clinic during the six-month period. Conclusions The finding of this study suggests the important role of nurse-led HF clinics in reducing healthcare burden and improving patient outcomes among HF patients in Hong Kong.  相似文献   
39.
From October 2013 through February 2014, human parechovirus genotype 3 infection was identified in 183 infants in New South Wales, Australia. Of those infants, 57% were male and 95% required hospitalization. Common signs and symptoms were fever >38°C (86%), irritability (80%), tachycardia (68%), and rash (62%). Compared with affected infants in the Northern Hemisphere, infants in New South Wales were slightly older, both sexes were affected more equally, and rash occurred with considerably higher frequency. The New South Wales syndromic surveillance system, which uses near real-time emergency department and ambulance data, was useful for monitoring the outbreak. An alert distributed to clinicians reduced unnecessary hospitalization for patients with suspected sepsis.  相似文献   
40.
Two cases of autoantibody formation following large volume plasmapheresis for rhesus immunisation during pregnancy are described. In each case the autoantibody was directed against the Rh complex but showed a preference for G-positive cells. It is postulated that repeated plasmapheresis in the presence of persistent antigenic stimulation has removed a feedback inhibition of the immune response. The specificity of the alloantibody has broadened resulting in cross-reactivity against self-antigens. The possible implications of these cases in relation to autoimmunity are discussed.  相似文献   
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