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HIF-1α和P-gp在胰腺癌中的表达及其临床病理意义

作 者: TOURE Facinet(法西内)
导 师: 孙维佳
学 校: 中南大学
专 业: General Surgery(普外科)
关键词: HIF-1α P-gp pancreatic carcinoma Immunohistochemistry
分类号: R735.9
类 型: 硕士论文
年 份: 2011年
下 载: 14次
引 用: 0次
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内容摘要


BACKGROUND:Pancreatic cancer is a malignant neoplasm of the pancreas. The prognosis is poor, with fewer than 5%of those diagnosed may survive five years. Complete recovery is still rare. P-Glycoprotein (P-gp) is one of the xenobiotic transport proteins implicated in multidrug resistance in neoplastic tissues, it’s integral efflux protein, expressed in some normal tissues which have excretional function. Hypoxia inducible factor 1 alpha (HIF-lα) plays an important role in solid tumor formation and survival by promoting anaerobic metabolism and angiogenesis.OBJECTIVE:To investigate the expression of Hypoxia inducible factor 1 alpha and P-Glycoprotein in pancreatic carcinoma, to determine their clinicopathological significance and their correlation.METHODS:Paraffin-embedded tissue samples were collected from 34 pancreatic carcinoma,7 chronic pancreatitis and 12 normal pancreas patients, who received surgical resection. We examined the expression of HIF-1αand P-gp by immunohistochemistry (SP method). The relationship between HIF-la and P-gp protein expression and clinicopathological factors was statistically analyzed.RESULTS:The positive staining of HIF-la was shown brown-yellow in the cytoplasm or nucleus and the positive staining of P-gp was brown-yellow in the cytoplasm with some staining on the cellular membrane.1. In pancreatic cancer tissue, the positive rate of HIF-1αprotein expression was 70.50%, in chronic pancreatitis tissue was 28.57% and in normal pancreas tissue was 8.33%. HIF-la protein expression was significantly higher than that in the chronic pancreatitis tissue and normal pancreas tissues (P< 0.05).2. In pancreatic cancer tissue, the positive rate of P-gp protein expression was 58.82%, in chronic pancreatitis tissue was 14.29% and in normal pancreas tissue was 8.33%. P-gp protein expression was significantly higher than that in the chronic pancreatitis tissue and normal pancreas tissues (P<0.05). 3. HIF-la and P-gp expression in pancreatic cancer tissue were significantly related to tumor stage and lymph node metastasis (P< 0.01), while they were not shows significantly to the age, sex, tumor size, and differentiation grade of tumor (P> 0.05).4. In pancreatic cancer tissue, HIF-1αand P-gp protein expression were positively correlated(P< 0.05).CONCLUSION:1. Up-regulated expressions of HIF-1 a and P-gp exist in pancreatic carcinoma, so it can act as a fundamental guide to clinical diagnosis.2. The expression of HIF-1 a and P-gp may participate in the development, progression, invasion, metastasis and poor prognosis of pancreatic carcinoma.3. The expression of HIF-1 a and P-gp is a positive correlation between them, indicating that there may exist a crosstalk between P-gp signal pathway and HIF-la signal pathway, which may act synergistically to promote the progression of pancreatic carcinoma.

全文目录


ABSTRACT  4-6
TABLEOFCONTENTS  6-7
LIST OF ABBREVIATIONS  7-8
CHAPTER 1 INTRODUCTION  8-10
CHAPTER 2 MATERIALS AND METHODS  10-14
  2.1 Patients and specimens  10
  2.2 The main reagents and Instruments  10-11
  2.3 Slices produced  11
  2.4 Immunohistochemistry  11-13
  2.5 Scoring criteria  13
  2.6 Statistical analysis  13-14
CHAPTER 3 RESULTS  14-17
CHAPTER 4 DISCUSSION  17-20
CHAPTER 5 CONCLUSION  20-21
CHAPTER 6 REFERENCES  21-24
FIGURES  24-27
REVIEW  27-49
  REFERENCES  43-49
ACKNOWLEDGEMENTS  49

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中图分类: > 医药、卫生 > 肿瘤学 > 消化系肿瘤 > 胰腺肿瘤
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