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Expression Of HIF-1α In Cervical Carcinoma And The Effect Of Neutron Radiation Treatment On It

Posted on:2006-08-10Degree:MasterType:Thesis
Country:ChinaCandidate:S LinFull Text:PDF
GTID:2144360155473893Subject:Obstetrics and gynecology
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Cervical carcinoma is the most common tumor in women. The rise of early period diagnosis and treatment technic has made the death rate of cervical carcinoma patients decreased. But there are still many patients suffered from cervical carcinoma died of relapse or metastasis of cervical carcinoma because of the dificiency invesitigation of the biological characteristics of cervical carcinoma. So the investigation of the biological characteristics of cervical carcinoma is the hot spot of numerous researchers.HIF-1 α (hypoxia inducible factor-1 α ) is the active functional subunit of hypoxia inducible factor. Under the condition of hypoxia, the hydroxy inhibition of HIF-1 α is relieved. The conjugation with the hypoxia response component enhancer is reinforced. The transcription and expression of hypoxia response related genes are activated. According to some investigation, HIF-1 α can influence the energy metabolism and angiogenesis of cervical carcinoma through adjustment the effection of vascular endothelial growth factor (VEGF) and epoetin(Epo). All these investigation hint that HIF-1 α is an important role in the occurrence, development and hypoxia adaptation of malignant tumor.E-cadherin is an important intercellular adhesion molecule. Changes of E-cadherin induced by any agent will lead to the functional influence of itself, leading to incursion and metastasis of tumor. Accorrding to some investigation, under the condition of hypoxia or tissue necrosis, the disintegration of E-cadherin complex may occur because of the release of epidermal growth factor (EGF) and TNF-α Tumor necrosis factor of tumor cells, leading to the increasing of incursions of tumor cells. And the regulatory element SNAIL of E-cadherin just is the hypoxia response component of HIF-1 α . So HIF-1 α has correlation with the invasiveness of tumor.At present, we do not know any more about the expression and invasiveness of HIF-1 α in cervical carcinoma. So the relatioship of the expression of HIF-1 α with cervicalcarcinoma of different staging and pathological grade need to be investigated.Neutron radiation treatment is a new type treatment of cervical carcinoma. According to some investigation. 252Cf neutron radiation treatment has many virtues. The relative biological effect is very high. This treatment has effect on cells in different proliferation period. It has effect on malignant tumor. But the changes of HIF-1 a expression under low dosage neutron ray need to be reseached.In this reseach, the clinical date of patients suffered from cervical carcinoma was ananlysised. Immunohistochemistry staining echnique was used to detect the expression of HIF-1 a of cervical carcinoma. The relationship of the expression with clinical character and significance was ananlysised too. Besides, RT-PCR technique was used to investigate the level of HIF-1 a mRNA and E-cadherin mRNA of Hela cells under different content of oxygen. The correlation of expression of HIF-1 a to invasiveness of Hela cells were investigated too. At last, the expression of HIF-1 a of cervical carcinoma of patient treated with neutron radiation treatment were detected. The chang law of HIF-1 a was analysised to provide date for the treatment with neutron radiation.The results were as follows:1. In 0 period of cervical carcinoma, the expression rate of HIF-1 a was 14.8% ± 4.8%. In I period, II periodJIIperiod and IVperiod, the expression rate of HIF-1 a were 28.6%±7.2%, 45.3%±9.7%, 56.7%±11.4% and 74.3%±13.6%. The expression rate of HIF-1 a gradually increased with the clinical staging of cervical carcinoma.2. The expression rate of HIF-1 a in low,middle and high differentiation carcinoma were 60.4% ±14.8%, 46.6%±15.1%JfP 37.2% ±12.2%. The expression rate of HIF-1 a gradually decreased with the pathlogical grade of cervical carcinoma.The expression rate of HIF-1 a of squamous carcinoma, adenocarcinoma and adeno-squamous carcinoma had not any significant difference.3. Under the condition of norml oxygen 5%O2,3%O2and 1%O2, the optical density ratio ofHIF-1 a mRNA/ & -actin were 0.423 ±0.116, 0.764+0.111,1.068 ±0.126and 0.215 ±0.099, showing that the level of HIF-1 a mRNA had a tendency of first deceasing and then increasing with the decreasing oxygen content.4. Under the condition of norml oxygen, 5%O2,3%O2and 1%O2, the optical density ratio of cadherin/P -actin were 1.045±0.171,0.719±0.114,0.386±0.105 and 0.157 +0.063, showing a decreasing tendency with the the deresing of oxygen content.5. Under the condition of norml oxygen, 5%C>2,3%O2and 1%O2, the invasiveness of Hela cells were 112.5 ±20.7, 254.3 ±27.5, 333.7+45.2 and 124.5 + 24.6, showing that the invasiveness of Hela cells had a tendency of first deceasing and then increasing with the deresing oxygen content.6. The positive ratio of HIF-1 a before treatment was 57.4% +15.4%. The positive ratio of HIF-1 a after the first treatment and the 4th were 39.6%+ 16.4%, 8.6% + 4.8%,which had significant difference with that of before treatment.Conclusion can be obtained:1. The positive rate of HIF-1 a of cervical carcinoma increases significantly with the clinical staging, decreases with the descending of pathogical grade. The expression of HIF-1 a has close relationship with the progress and malignancy of cervical carcinoma.2. In vitro, the expression of HIF-1 a of Hela cells has a tendency of first deceasing and then increasing with the decreasing oxygen content and had relationship with the adhesiveness and invasiveness of tumor cells.3. The expression of HIF-1 a decreased after cervical carcinoma treated with neutron radiation treatment.
Keywords/Search Tags:HIF-1 α, neutron radiation, cervical carcinoma
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