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Mei Ling Yap Bok Ai Choo Yiong Huak Chan Jay Jiade Lu Khai Mun Lee Ivan WK Tham 《Journal of Medical Imaging and Radiation Oncology》2012,56(5):548-553
Introduction: Patients with locally advanced nasopharyngeal carcinoma (NPC) commonly present with cranial nerve (CN) involvement, which can cause significant morbidity. We aimed to characterise the pattern of involvement and outcomes of these patients, as well as determine if these differed according to the mode of diagnosis. Methods: Patients were included if they had non‐distant metastatic NPC, presented with CN involvement and completed radiotherapy treatment between 2002 and 2008. The clinical response was categorised as complete response, partial response, stable or progressive disease. The radiological response was assessed using the Response Evaluation Criteria in Solid Tumors criteria. The loco‐regional control and disease‐free survival rates were estimated with the Kaplan–Meier method. Results: Forty‐seven patients fulfilled the inclusion criteria. CN lesions were diagnosed on clinical examination in 15% of patients, radiologically in 40% and both clinically and radiologically in 45% of patients. A complete or partial response of the CN lesions was seen clinically in 82% and radiologically in 95% of patients. The 3‐year local relapse free survival was 64.3%, distant metastasis‐free survival was 46.1% and overall survival was 82.8%. There were no differences in outcomes between patients with clinically versus radiologically detected CN lesions. Conclusion: Most of these patients are likely to undergo clinical and/or radiological resolution of the nerve lesions following chemoradiotherapy, but the outcome was not determined by the mode of diagnosis (radiological or clinical). 相似文献
45.
Shawn A Ritchie Pearson WK Ahiahonu Dushmanthi Jayasinghe Doug Heath Jun Liu Yingshen Lu Wei Jin Amir Kavianpour Yasuyo Yamazaki Amin M Khan Mohammad Hossain Khine Khine Su-Myat Paul L Wood Kevin Krenitsky Ichiro Takemasa Masakazu Miyake Mitsugu Sekimoto Morito Monden Hisahiro Matsubara Fumio Nomura Dayan B Goodenowe 《BMC medicine》2010,8(1):1-20
Background
There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.Methods
Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total n = 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total n = 220).Results
Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 ± 0.04).Conclusions
A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC. 相似文献46.
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Schuler D; Otteneder M; Sagelsdorff P; Eder E; Gupta RC; Lutz WK 《Carcinogenesis》1997,18(12):2367-2371
8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for
oxidative DNA damage. Reported basal levels determined by 32P- postlabeling
(PPL) method were 10-fold or more higher than those obtained with
HPLC/electrochemical detection (ECD). This discrepancy was investigated. In
commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per
10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and
PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen
phosphodiesterase and nuclease P1 (as used in the standard PPL method),
followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA
spiked with chemically synthesized 8-oxo-dGp to give an increment of 9
8-oxo-dG/10(6) dN, the added standard produced a significant increase with
HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the
added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of
65%. In order to investigate the role of ionizing radiation from 32P for
the higher 8-oxo-dG levels in PPL, incubation times and amounts of
radioactivity in the phosphorylation reaction with commercial dGp were
increased, and external irradiation of commercial dG with 32P was
investigated. All modifications resulted in higher values of 8-oxo-dG
measured, but the effect was not large enough to fully explain the
discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of
[gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even
higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during
the PPL workup is attributed to the presence and oxidation of unmodified
dGp in the reaction mixture. For a determination of true basal levels, the
PPL method will have to be modified, including the removal of dGp prior to
the phosphorylation reaction.
相似文献
48.
A series of promoting and non-promoting barbiturates and hydantoins were
examined for their ability to sustain the growth of a phenobarbital
(PB)-dependent hepatocyte line in cell culture. The effective liver tumor
promoters, pentobarbital, allobarbital and 5- ethyl-5-phenylhydantoin,
replaced PB and supported 6/27C1 hepatocyte colony formation in vitro at
52-87% of the level induced by PB. The weak promoters secobarbital and
amobarbital supported colony formation at only 11-19% of the PB control. A
significant correlation was observed for in vivo and in vitro promotion
activities of barbiturates and hydantoins, indicating that clonal expansion
by 6/27C1 hepatocytes was promoter-dependent. Cell density also appeared to
influence hepatocyte growth in vitro. Hepatocyte colonies acquired the
ability to grow in the absence of PB, such that after 10 days incubation
with PB, approximately 50% of colonies continued to grow in the absence of
promoter. This phenomenon of clone-size-dependent hepatocyte growth
suggested the operation of an autocrine growth factor pathway. Addition of
the hepatocyte mitogen and autocrine growth factor, transforming growth
factor-alpha (TGF-alpha), to culture medium lacking PB induced a
dose-dependent increase in 6/27C1 hepatocyte colony formation. At the
optimal concentration of 3 ng/ml, TGF-alpha sustained hepatocyte clonal
expansion at 84% of the level induced by 2 mM PB. Individual 6/27C1
colonies that grew from single cells in the presence of TGF-alpha were
tested for promoter-dependent colony formation. Either PB or TGF-alpha
supported colony formation by these cells at similar levels and when
combined at optimal concentrations, the response appeared to be saturated.
When these factors were tested in combination at suboptimal concentrations,
the two compounds were additive for supporting colony formation by the
parental 6/27C1 line. The ability of TGF-alpha to replace PB and sustain
hepatocyte clonal expansion was confirmed with the tumorigenic 6/15
hepatocyte line. These results suggest that TGF- alpha and PB may promote
hepatocarcinogenesis by stimulating a common signal transduction pathway.
相似文献
49.
OBJECTIVE: Epidemiologic studies in Caucasian populations suggested that symptomatic obstructive sleep apnea (OSA) occurred at a prevalence of 1-10%. The condition has been increasingly recognised among the Chinese in Hong Kong. We therefore, summarize our experience with OSA at the Department of Medicine, The University of Hong Kong at Queen Mary Hospital from 1985-1996. METHODS: All clinic records concerning demographic data, anthropometric data, clinical features, polysomnographic findings and treatment were reviewed. RESULTS: One hundred and twenty-two patients were diagnosed to have OSA. Demographic and clinical features were similar to Caucasian data with a male predominance of 84%, a mean age of about 50 years, and obesity as a risk factor at a mean body mass index of 30.4, which was higher than that of the average local population, although lower than that of OSA patients in Caucasian series. About 27% of the patients have a body mass index (BMI) similar to or below the population average. Nearly all were habitual snorers, and the majority had excessive daytime sleepiness. On polysomnography, the mean apnea-hypopnea index was 38. Common associated medical conditions were hypertension (34%), diabetes mellitus (10%), ischemic heart disease (9%), hyperlipidemia (6%). Most patients were managed successfully with nasal continuous positive airway pressure. Treatment with oral appliances for milder cases is being explored. CONCLUSIONS: OSA has been increasingly recognised among Chinese adults in Hong Kong in the past decade. Demographic features were similar to Caucasian data. The majority of patients were overweight, although 27% were not, and further investigation on the contribution of faciomaxillary morphology to OSA in this group is warranted. 相似文献
50.
WK Jacyk A La Cock 《Journal of the European Academy of Dermatology and Venereology》2006,20(3):311-313
Congenital hemidysplasia with ichthyosiform naevus and limb defects (CHILD) syndrome is a rare X-linked dominant disorder. The first case of squamous cell carcinoma arising within the affected ichthyosiform skin in a 33-year-old woman is reported. 相似文献