Dissertation > Medicine, health > Oncology > Gastrointestinal Cancer > Gallbladder, bile duct cancer

P-glycoprotein in gallbladder carcinoma and its relationship with the P53 protein

Author ShenWei
Tutor ZhengShuSen
School Zhejiang University
Course Surgery (General Surgery)
Keywords Gallbladder P53 protein expression P-glycoprotein Chronic cholecystitis Abnormal expression of P53 Tumor cells Resistant MDR P53 expression Master of Medicine
CLC R735.8
Type Master's thesis
Year 2001
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Background: Clinical Oncology treatment of cancer chemotherapy is an important means. However, tumor cells become resistant to chemotherapy is an important factor in the failure of cancer chemotherapy. Mainly for MDR phenomenon, namely tumor cells Once a chemotherapy drug resistance to other structures and functions of different chemotherapeutic drugs also produce tolerance. The latest cellular and molecular biology of tumor within the groundbreaking research found that the generation of multi-drug resistance gene mdr-1 over its expression of a P-glycoprotein (P-glycoprotain, PgP) related. The abnormal expression of P53 tumor suppressor gene in tumor development plays an important role. For P53 abnormal expression of mdr-1 gene expression study of the relationship of domestic work in this area is small. In this study, immunohistochemical methods serially sectioned determination gallbladder PgP, P53 expression in order to explore their gallbladder carcinoma is associated with the biological behavior of cancer, as well as the relationship between the expression, understanding of these multidrug resistance gene in gallbladder in different roles, explore their gallbladder in predicting sensitivity to chemotherapy and prognosis in value. Zhejiang University Medical Journal three Materials and Methods: The group of 41 cases of gallbladder cancer, including 35 cases of 1995 a 2000 Jinhua City. C Hospital hepatobiliary surgical resection cases; six cases of 1995 a 2000 Jinhua People's Hospital of Hepatobiliary surgical resection cases. 17 males and 24 females; Age 40 - 83 years. All patients without preoperative chemotherapy and radiotherapy, gallbladder specimens of 10% neutral formalin-fixed, paraffin-embedded tissue blocks archiving and re-serial sections were prepared 4urn for immunohistochemical staining. Another 40 cases of chronic cholecystitis patients selected as a control group. Including 16 males and 24 females, ranging in age from 30 years old to 79 years old. Immunohistochemistry SP method (iM peroxide streptomycin avidin HRP staining), immunohistochemistry reference Verrelle judge and evaluate the results of evaluation criteria. Results: The immunohistochemical samples positive signals appear consistent with the expected signal clear background; negative control showed negative results. PgP staining mainly localized in the cytoplasm. This group of cases, PgP in gallbladder carcinoma was 56. l%, significantly higher than that of chronic cholecystitis tissues (7.5%), the difference was statistically significant (P knock knife 1). P53-positive localized in the nucleus; positive expression rate was 46.3%, significantly higher than that of chronic cholecystitis tissues, also has a significant difference. In different pathological types; differentiation; invasion and metastasis spoon cases, PgP, P53 expression was not statistically different spoon (P> 0.05). P53 expression was positive in 19 cases of cystic carcinoma of the white moon that is, P positive rate of 89.470, significantly higher than the negative expression of P53 gallbladder, gallbladder abnormal expression of mdr Diao P53 expression was significantly correlated. Discussion: chemotherapy drug phenomenon is facing the most common and the most intractable problems, the result is invalid or chemotherapy for cancer patients reduced efficacy. Multidrug resistance (MDR) tumor cells to become resistant to many commonly used chemotherapy drugs and cross-resistance capability. That is one kind of tumor cells to anticancer drug resistance occurs at the same time, on the other structure is different, the site of action of anticancer drugs also has a different resistance. Multidrug-resistant tumor cells is characterized by a distinct biochemical mdr · Diao overexpressed genes encoding PgP. PgP was first in 1976, Ling et-resistant Chinese hamster ovary (CHO) cells in the discovery of a molecular weight of the door of OM membrane glycoprotein, has confirmed that the expression levels of resistance of tumor cells positive correlation; is an energy-dependent membrane transporter, will be able to reverse the intracellular concentration of a variety of soluble mdrl related Journal of Medicine, Zhejiang University chemotherapy drugs pumped Z extracellular, intracellular drug accumulation decreased, resulting in drug resistance. Studies have shown that the degree of resistance PgP expression proportional to the degree. In this study, 41 cases of gallbladder cancer chemotherapy drugs without any tissue samples to detect the expression of PgP showed that gallbladder carcinoma that is, P positive rate compared with chronic cholecystitis with significant differences (P function knife 1). Foreign reports, originated in the liver, kidney and gastrointestinal tissues of primary tumors of MDR, derived from the above expression PgP organ malignancies have increased. This group of patients before gallbladder not accept any form of anti-cancer therapy, and PgP in tumor tissue showed increased expression; Tip PgP in the gallbladder tissue increased expression of the malignant process, which may be routine gallbladder postoperative chemotherapy failure the main reason. Studies suggest that overexpression mdr Diao, not only to the drug; biological behavior of cancer cells but also the further deterioration of indicators of primary MDR tumors occur in poorly differentiated tumors. However, this study found that, PgP expression and gallbladder histological type, degree of differentiation, invasion and metastasis no correlation (X 'test positive expression widely described PgP not reflect the degree of tumor differentiation and invasion; represent only the strength of the drug resistance , so the choice of chemotherapy should be able to avoid the application of MDR drug resistant cover. normal human hardship as a base of P53 tumor suppressor gene, encoding the nucleoprotein 50kda of wild-type P53 protein and DNA with high affinity and inhibit DNA synthesis and replication, thereby inhibiting cell proliferation of wild-type P53 protein half-life is shorter; difficult to detect; while mutant P53 protein conformational change because of ** A affinity decreases. inhibit cell proliferation diminished capacity, half-life, increased stability in the cell, can be detected by routine immunohistochemistry. P53 and P53 gene mutations in tissues is consistent. researchers found that wild-type P53 gene can inhibit gene transcription mdr Diao reduce PgP generation; The mutant gene can activate P 5 3 mdr Diao gene promoter, promoting mdrJ gene expression, we also observed that overexpression of P53 gallbladder PgP expression was positively correlated, suggesting that overexpression of P53 can enhance mdr eight base sleepy expression, gallbladder cancer cells thereby obtained MDR phenotype, promote cell resistance, but this group of negative expression of P53, there are still 12 cases of gallbladder PgP expression?

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