Introduction: Since the era of Marshall, H. pylori has been to be implicated in many upper digestive tract diseases, such as gastritis, peptic ulcer disease, mucosa- associated lymphoid tissue lymphoma, and even gastric adenocarcinoma. In 1994, WHO recognized H. pylori as a definite carcinogen for gastric cancer. Many study had shown that microbial pathogens may induce oxidative stress in infected host cell. And this may also represent an important mechanism leading to epithelial injury in H. pyloric infection. Oxidative stress plays a role in altering epithelial cell turnover, accelerating apoptosis and increasing oxidative DNA damage. One of the evidences for this phenomenon is increasing level of reactive oxygen species (ROS) measured in the mucosa of infected stomach. ROS may activate HIF-11£\ transcription. HIF-1£\ overexpression had been
detected in several human cancers. Furthermore its overexpression
correlates significantly with highly aggressive disease, lymph node
metastasis, clinicopathological status and poor prognosis in some cancer
types. It may up regulate hypoxia-induced gene, such as the vascular
endothelial growth factor (VEGF) transcription and angiogenesis.
Therefore we propose Sp1-pVHL-HIF-1£\ pathway may play a role the
carcinogenesis in Hp -associated gastric cancer.
Material and methods: We took Paraffin-embedded specimens from 89patients, who had undergone UGI endoscopy and gastric mucosa biopsy.
We assessed the Sp1, pVHL, HIF-1£\ in all cases by immunohistochemistry
and then evaluated their correlation with the H pylori infection. Chi-square
and Fisher¡¦s exact test was performed to determine the significance of the
difference between Sp1, pVHL, HIF-1£\.
Results: There are not significant difference in nuclear Sp1 expression and
H. pylori different (p=0.59). Sp1 expression was not significant, (p=0.91,
0.93, 0.36, 0.42, 0.51) with sex, age, location, TNM stage and cell
differentiation. pVHL protein was mainly expressed in the cytoplasm.
There are no significant difference with H. pylori infection (p=0.14). The
relationship pVHL protein expression between with sex, age, lesion site,
TNM stage and cell differentiation were not significant (p=0.39, 0.70, 0.69,
0.83, 0.70). HIF-1£\ protein was mainly expressed in the nuclei. There are
not significant association with H. pylori infection (p=0.49). There were
no significant differences between HIF-1£\ protein expression with sex,
age, location, TNM stage and cell differentiation (p=0.94, 0.32, 0.75, 0.35,
0.60).
Furthermore, In normal tissue the expression of HIF-1£\ had significant
association with pVHL(p=0.0002), and the expression also had no a
mariginally significant association with Sp1(p=0.096). Expression of Sp1
had significant association with pVHL(p=0.0016)in tumor tissue, Therewas a significant association between normal and tumor tissue expression
of the pVHL and Sp1(p=0.038, 0.019), but the expression of HIF-1£\ had
no significant(p=0.23).
Conclusion: In this study, we attempt to determine the association
between Sp1-pVHL -HIF-1£\ pathway and a role in the carcinogenesis in
H. pylori infection. Although we didn¡¦t confirm the hypothesis Sp1-pVHL
-HIF-1£\ pathway playing an critical role in the mechanism of gastric
cancer. We concluded that there is no significance between the expression
of Sp1, pVHL and HIF-1£\ and gastric cancer, but the role of this pathway
in the Hp infection associated carcinogenesis is still to be clarified.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0901108-160552 |
| Date | 01 September 2008 |
| Creators | Lee, Yi-Chern |
| Contributors | Hurng-Wern Huang, Deng-Chyang Wu, Chee-Yin Chai, Angela Chen |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0901108-160552 |
| Rights | off_campus_withheld, Copyright information available at source archive |
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