Upload
gwendolyn-johns
View
222
Download
3
Embed Size (px)
Citation preview
1
Post-radiotherapy plasma total glutathione is associated to outcome in patients with head and neck squamous cell carcinoma
作者: Siv Kjølsrud Bøhna, Sigbjørn Smelandb, Amrit Kaur Sakhia, Magne Thoresena et al出處: Cancer Letters 238 (2006) 240–247
報告者:中國醫藥大學 林佳璇指導營養師:吳素珍 營養師
3
The function of thiols• Thiols have essential roles in many
biochemical reactions by virtue of their ability to be reversibly oxidized
• Several low-molecular-weight-thiols are actively involved in cellular defenses against toxic exposure (Dickinson et al,2002)Homocysteine
4
Glutathione (GSH)• GSH is present in all mammalian cells
• It consists of cysteine,glutamate and glycine
• glycine
cysteine
glutamate
6
The function of glutathione• It is the most important intracellular thiol-
based redox buffer (Dickinson et al,2002)
•
• Plasma GSH may be used as a biomarker for oxidative stress (Therond et al,2002)
2GSH
GSSG
H2O2
2H2O
Glutathione peroxidase
7
Oxidative stress
• It can damage to DNA and thereby promote carcinogenesis (Seidman et al,1999)
• Many malignant cells have alterations in GSH-related mechanism or modify the concentration of GSH to cope with oxidative stress (Tatebe et al,2002)
8
Head and neck squamous cell carcinoma (HNSCC)
• Tobacco and alcohol are clearly defined as etiologic factors for these malignancies (Seidman et al,1999)
• These factors are known to increase ROS and RNS production and to induce cellular oxidative damage
• HNSCC with strongest link to oxidative damage and oxidative stress because of tobacco and alcohol
9
The purpose
• To address the role of systemic oxidative stress for survival of HNSCC patients, we have assessed low-molecular-weight-thiols in post-radiotherapy plasma of patients with HNSCC.
11
Selection of patients and controlsPatients Controls
Amount 29 HNSCC 51 healthy
gender M:22 F:7 M:31 F:20
TNM stage Ⅰ:5 :2 :7 :15Ⅱ Ⅲ Ⅳ
Tumor location Epipharynx:2 Larynx:8 Oro/hypopharynx:16 Other:3
Smoking status Smoker:19 Former smoker:2 Non smoker:4 Not known:4
Smoker:21 non smoker:30
Therapy dose 60-70Gy
12
Plasma collection
29 HNSCC patients
Post-radiotherapy After 6 weeks
Collect citrate plasma
51 healthy controls
Collect EDTA plasma
Keep at -70℃
13
Chromatographic analysis of total thiols
Collect plasma
chromatographic analyses
GSH , cysteine , homocysteine , cysteinyl-glycine
14
Statistical analysis
patients–controls →
survivors–non-survivors
two-sample t-test.
sex, smoking and BMI → ANCOVA
P < 0.05
17
Plasma thiols immediately after radiotherapy and after 6 weeks follow-up
• There were no significant changes in any of the thiols between the first plasma sample and the 6 week follow-up (P>0.33)
21
Plasma GSH level and survival rate
• There were no significant in total dose or dose-intensity of the radiotherapy given in the two group
• The patients with the lowest plasma total GSH levels had the lowest survival rate
3 out of 14 died
11 out of 15 died
22
The relation of GSH and immune function
• With Low GSH
T cellIL-2 production,IL-2 response, cytotoxic T cell activity
NK cellkilling activity• High blood NK-cell activity have a significant
longer survival time than those with low NK activity (Kinscherf,1994)
• It may be related to the study of reduced survival in patients with low plasma total GSH
23
• The patients with HIV infection disturbed GSH homeostasis in the immunopathogenesis for both plasma and intracellular GSH levels are reduced (Staal,1992)
• The therapy with N-acetylcysteine, alone or in combination with other antioxidants restores GSH levels and improves immune function in HIV-infected individuals (Mullaer,2000)
24
N-acetylcysteine
• N-acetylcysteine (NAC) is an amine protected version of cysteine that is rapidly hydrolyzed in the body to the amino acid cysteine
25
The relation of GSH and radiotherapy
• Total GSH measured of healthy adults in this study were 4.56±1.71uM
• Previous studies reported about 2-3uM (Jones,2002)
• The levels of free GSH+GSSG were reduce in plasma following radiotherapy (Jadhav,1998)
• The total GSH levels in post-radiotherapy plasma of HNSCC patients were about 20% lower than in the controls
GSH+GSSG+GSSR
GSH+GSSG
26
Conclusion
• Total GSH levels in post-radiotherapy plasma were lower in HNSCC patients than controls
• The patients with the lowest plasma total GSH levels had the lowest survival rate
• We suggest that HNSCC patients that develop excessive systemic oxidative stress, as assessed by low total GSH in plasma
27
Problem
• 為何 patients組和 controls組的血漿收集所使用的抗凝固劑不同?
• 為何之前的研究所測的血漿 total GSH 是free GSH + GSSG,而本篇作者測的是free GSH + GSSG + GSSR?
29
HNSCC
•頭頸部鱗狀細胞癌常見的有鼻咽癌 , 副鼻竇癌 , 舌癌 , 喉癌 , 下咽癌
•鼻咽癌在台灣的男性發生率為第十位 , 死亡率為第九位
•喉癌常見於男性 , 佔台灣惡性腫瘤的 4%,在台灣男性比女性的發生率為 8:1
•喜好抽煙 , 喝酒發生率較高
35
食物中 Vit B2的含量
食物 含量 (mg)
豬肝 100g 4.28
烏魚子 100g 2.39
紅蟳 100g 0.94
脫脂高鈣鮮奶 100g 0.36
低脂乳酪 100g 0.76
(行政院衛生署 )