Curcumin for the Prevention of Epithelial-Mesenchymal Transition in Endoxifen-Treated MCF-7 Breast Cancer Cells

Background: Curcumin was shown to reduce epithelial-mesenchymal transition (EMT) markers in previous shortterm studies. This study was aimed to investigate the potential of curcumin in the prevention of EMT activation inMCF-7 cells induced by endoxifen. Methods: MCF-7 breast cancer cells were treated with Endoxifen 1000 nM+betaestradiol1 nM with or without curcumin (8.5μM or 17 μM). Cells treated with dimethyl sulfoxide (DMSO) 0.001%were used as negative control. After 8 weeks of continuous treatment, the cells were counted, analyzed for mRNAE-cadherin, vimentin, TGF-β expression, total reactive oxygen species (ROS) and observed for morphological changesusing confocal microscope and transmission electron microscope. Result: MCF-7 cell viability was increased inendoxifen + β-estradiol group. Cell viability was significantly decreased in curcumin 17 μM, but not in curcumin8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNAexpressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. Theresults showed that administration of curcumin in all the dose administered were incapable improving the expressionsof vimentin, TGF-β1 and E-cadherin. There was a decrease in ROS concentration in curcumin treated cells (8.5 μM)while in curcumin 17 μM, ROS concentration was increased. Morphological observation using confocal microscopeand TEM showed the presence of mesenchymal cells and adherens junction. Conclusion: endoxifen treatments foreight weeks resulted in upregulation of EMT markers and changes in morphology of MCF-7 breast cancer cells. Theaddition of curcumin did not prevent the activation of EMT.     

Outcomes following treatment for patients with cranial nerve involvement from nasopharyngeal cancer

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).     

Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P- postlabeling and electrochemical detection

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.      

朝藿甙A的结构

从朝鲜淫羊藿(Epimedium koreanum Nakai)地上部分分离得到一个新黄酮醇甙类成分:朝藿甙A(ChaohuosideA,I),经光谱分析证明,其结构为7-O-β-D-吡喃葡萄糖-脱水淫羊藿素-3-O-β-D-(3,6-O-二乙酰基)-吡喃葡萄糖-(1→3)-α-L-(4-O-乙酰基)-吡喃鼠李糖甙。     

Overview on SARS in Asia and the World

Severe Acute Respiratory Syndrome (SARS) is the first major novel infectious disease to hit the international community in the 21st century. It originated in southern China in November 2002, reached Hong Kong in February 2003 and spread rapidly thereafter to 29 countries/regions on five continents. At the end of the epidemic, the global cumulative total was 8098 with 774 deaths. Seven Asian countries/regions were among the top ten on the list. Mainland China and Hong Kong, SAR, accounted for 87% of all cases and 84% of all deaths. Severe acute respiratory syndrome is caused by a novel coronavirus. It has alarmed the world with its infectivity and significant morbidity and mortality, its lack of a rapid, reliable diagnostic test and lack of effective specific treatment and vaccination. The adverse impact on travel and business around the world, particularly in Asia, has been enormous.
Some lessons learnt from this epidemic included: (1) any outbreak of infectious disease can rapidly spread around the world by air travel; (2) early reporting of the outbreak to neighbouring countries/regions and the World Health Organization is essential to prevent international spread; and (3) infection control, tracing and quarantine of contacts are essential to control the epidemic. Many questions remain unanswered, including the origin and pathogenesis of the novel coronavirus, the natural history and the best specific treatment of the disease. The SARS-CoV has probably jumped from an animal host to humans. There is an urgent need to evaluate the human–animal habitat in southern China and to remove animal reservoirs if found.     

心房扑动患者的下腔静脉-三尖瓣环峡部和房间隔缓慢传导的电生理意义

目的　用电 解剖标测方法标测右心房 ,然后比较心房扑动 (AFL)和房室结折返性心动过速(AVNRT)患者在下腔静脉 三尖瓣环峡部 (CTI)和心房间隔部 (AS)的电冲动传导速度 ,以便确定AFL患者除了解剖结构上的异常外 ,是否伴有心房电生理方面的异常变化。方法　 1 0例AFL患者 ,男性 7例 ,女性 3例 ,平均 (53± 1 0 )岁 ;1 3例AVNRT患者 ,男性 5例 ,女性 8例 ,平均 (51± 1 1 )岁。对这两组患者进行了详细的电 解剖标测、电生理检查和射频消融术。分别以周长为 60 0、40 0、和 30 0ms在冠状静脉窦 (CS)起搏的情况下测量AFL和AVNRT患者的CTI和AS的冲动传导速度 ,并将两组患者在CTI和AS的冲动传导速度进行比较。结果　与AVNRT患者相比 ,AFL患者在各个起搏周长 (PCL)时CTI和AS的冲动传导速度都明显减慢 (P <0 0 5)。另外 ,在AFL组 ,AS的冲动传导速度在起搏周长 60 0、40 0ms时低于CTI,但在 30 0ms时差异无显著性 (P >0 0 5)。因为在AFL组 ,PCL为 30 0ms时的冲动传导速度明显低于 60 0和 40 0ms时的冲动传导速度 ,致使PCL为 30 0ms时CTI和AS的冲动传导速度差异无显著性。结论　与CTI相比 ,AS的冲动传导速度在所有患者都较慢 ,而AFL患者在CTI和AS的冲动传导速度减低更明显 ,并且在CTI的冲动传导速度减慢具有频率依     

Hepatogastric fistula after chemoembolization of liver metastasis: a case report

Liver metastases of colorectal cancer are a challenge in current oncology. Less than 5% of untreated patients are alive after 5 years of diagnosis. The only curative treatment is surgical resection, but there are other options for palliative or neoadjuvant treatment such as transarterial chemoembolization. Serious complications after liver chemoembolization are very rare, and one of the possible complications is a liver abscess. We report a case of hepatogastric fistula caused by a liver abscess ten days after the chemoembolization of a liver metastasis. It was treated surgically with left hepatectomy and parcial gastrectomy, with good outcome. There are only a few reported cases of hepatogastric fistula after liver transarterial chemoembolization.     

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection

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.