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Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of p-glycoprotein and p53 protein in advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第6期12卷 868-873页

作者： MasahideAkimoto MasaharuYoshikawa MasaakiEbara TsunenobuSato HiroyukiFukuda HiromitsuSaisho Fukuo Kondo Department of Medicine and Clinical Oncology Chiba UniversitySchool of Medicine1-8-1 InohanaChuo-kuChiba CityChiba 260-0856 Japan Department of Molecular pathology Chiba UniversitySchool of MedicineChiba Japan

AIM： To investigate the relationship between the chemotherapeutic drug efficacy and the expression of p-glycoprotein （pGp） and p53 protein in advanced hepatocellular carcinoma （HCC）. METHODS： The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect pGp and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug （epirubicin hydrochloride; anthracycline group）, and the remaining 21 were treated with a non-anthracycline drug （mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group）. The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS： Before the start of the treatment, pGppositive rate was 90.2% （strongly-positive, 36.6%） and p53 protein-positive rate was 34.1% （strongly-positive, 19.5%）. In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive pGp expression （p= 0.005）, and their prognoses were poor （p= 0.001）. in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the pGp or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients （p= 0.012）, irrespective of the survival outcome. CONCLUSION： The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical a

关键词： Arterial infusion chemotherapy Hepatocellularcarcinoma p-glycoprotein p53 protein

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Correlation and Expression of COX-2 and p53 protein in Basal Cell Carcinoma of Eyelid

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第3期29卷 383-386页

作者：陈志雄杨炯黄琼 Department of Geriatrics Renmin Hospital of Wuhan University Department of Ophthalmology Renmin Hospital of Wuhan University

The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma （BCC） of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases （aged 28-68 y） at the Department of pathology, Renmin Hospital of Wuhan University, and Department of pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance （A） and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was sig- nificantly higher than that in paracancerous tissues （p〈0.01）. Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 （r=0.113, p=0.421）. It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.

关键词： eyelid basal cell carcinoma COX-2 p53 protein

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Effects of nanometer particles and water decoction of the Chinese medicine mixture of pinellia ternate and scorpion on p53 protein contents and apoptosis in the cerebral cortex and hippocampus of epileptic rats

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Neural Regeneration Research 2008年第7期3卷 701-704页

作者： Shuxiang Wang Lei Liu Yuming Kang Shuqiu Wang Dixiang Sun Xiaoru Ma Yanfeng Liang Fangfang Wang Department of Function College of Basic Medicine Jiamusi University Jiamusi 154007 Heilongjiang Province China Department of pharmacology College of Basic Medicine Jiamusi University Jiamusi 154007 Heilongjiang Province China Department of physiology College of Basic Medicine Shanxi Medical University Taiyuan 030001 Shanxi Province China Department of pathology and physiology College of Basic Medicine Jiamusi University Jiamusi 154007 Heilongjiang Province China

BACKGROUND： Water decoction of the Chinese traditional medicine mixture of pinellia ternate and scorpion is an effective treatment for epilepsy. OBJECTIVE： To compare nanometer particles and effects of water decoction of Chinese traditional medicine mixture on p53 protein levels and apoptosis in the cerebral cortex and hippocampus of epileptic rats. DESIGN, TIME AND SETTING： This randomized, controlled molecular biology study was performed at the Key Laboratory of Child Neural Rehabilitation of Jiamusi University from October to December 2007. MATERIALS： Forty healthy male Wistar rats were used in this study. Convulsion rat models were established by intraperitoneal infusion of 35 mg/kg pentylenetetrazol, once a day, for 28 successive days. The Chinese traditional medicine mixture, comprising pinellia ternate, scorpion, centipede, bupleurum, peach pit and glycyrrhiza, was purchased from Beijing Tongrentang, China. The mixture was made into nanometer particles and water decoction. The apoptosis determination kit and p53 immunohistochemistry kit were bought from Boster, China. METHODS： Forty Wistar rats were randomly divided into four groups of ten rats per group, control, nanometer particle, water decoction and epileptic model groups. Rats in the nanometer particle and water decoction groups were respectively treated with 300 mg/kg Chinese herb nanometer particle suspension and water decoction by gavage, once a day, for 28 days. Rats in the epileptic model group were fed an equal volume of saline by gavage. Rats in the control group were only administered with the same volume of saline by gavage. MAIN OUTCOME MEASURES： Terminal deoxynucleotidyl Transferase Biotin-dUTp Nick End Labeling （TUNEL） and immunohistochemistry were used to respectively detect neuronal apoptosis and p53 protein expression in the rat brain cortex and hippocampus at 28 days following administration. RESULTS： The number of apoptotic neurons was lower in the nanometer particle and wate

关键词： epilepsy pentylenetetrazol p53 protein apoptosis

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EXpRESSION OF p53 protein AND pROLIFERATING CELL NUCLEAR ANTIGEN IN HUMAN GESTATION TROpHOBLASTIC DISEASE

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Chinese Journal of Cancer Research 2004年第2期16卷 147-149页

作者：黄铁军王志忠方光光刘志恒 The Second Hospital of Shenzhen Shenzhen 518035 Department of Nuclear Medicine The Nongkens Hospital of Hainan Province Haikou 570311

To study the relationship between p53 protein, proliferating cell nuclear antigen (pCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and pCNA. Results: The frequency of p53 and pCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor pCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both p53 and pCNA are valuable in diagnosis of human gestational trophoblastic disease.

关键词： p53 protein proliferating cell nuclear antigen (pCNA) Gestational trophoblastic disease(GTD)

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DNA　pLOIDY，EXpRESSION　OF　p53　protein　AND　METASTATIC　BEHAVIOUR　OF　GASTRIC　CARCINOMA

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Chinese Medical Sciences Journal 1996年第3期11卷 147-151页

作者：辛彦赵凤凯吴东瑛王艳萍徐蕾 BurnneCurran MaryLeader KristinHenry CancerInstituteofChinaMedicalUniversity Shenyang110001 Departmentofpathology RoyalCollegeofSurgeonsinIreland DepartmentofHistopathology CharingCrossandWestminsterMedicalSchoolUniversityofLondon

DNA ploidy of 57 gastric carcinomas with metastases(12 liver,1 adrenal,4 ovary and 48 lymph node) were measured by flow *** anueploidy was significantly related to liver metastases:9 out of 12 gastric carcinomas with liver metastases were anueploid(75%) as compared to 13 out of 45(28.8%) of cases without liver metastases(pploidy was not related to ovarian or lymph node *** interesting finding was that all of 3 gastric carcinomas with liver metastases which showed a diploid DNA pattern,expressed p53 protein, while all of 3 carcinomas with liver metastases but no p53 protein expression were *** expression of p53 protein was not related to ovarian *** results suggested that an anueploid DNA pattern and the expression of p53 protein are both objective markers valuable in predicting high risk potential of metastases to the liver,and that the combined detection of these markers can be a most useful method in the follow-up of patients with gastric carcinoma in detecting those at high risk of developing metastases following surgical *** the poorer prognosis of patients with gastric carcinoma showing an anueploid DNA pattern may be related to the development of distant organ metastases through the blood vascular ***,the clone of gastric carcinoma cells which accumulate p53protein or show an anueploid DNA pattern may have a causative role in the development of liver(&.adrenal) metastases.

关键词： DNA ploidy p53 protein gastric carcinoma

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THE QUANTITATIVE MEASUREMENT OF BCL-2, p53 protein AND pCNA EXpRESSION IN BREAST CARCINOMA AND THEIR CORRELATION WITH pROGNOSIS

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Journal of pharmaceutical Analysis 1998年第2期12卷 120-124,132页

作者：张学斌王鸿雁 Department of pathology First Affiliated Hospital Xi'an 710061 China

To study quantitative index of bci-2, p53, Nroliferating cell nuclear antigen (pCNA),ER and pR in breast carcinoma and their correiation and their relatiousbip with prognosis, the ex expression of bcl-2, p53 and pCNA were studied by immunohistochemical technique. The measurementof ER and pR used enzyme linked affinuity histochemical methods. The quantitative index was analyzed by image technique. All analyses were hased on 60 breast carcinomas. The results were as follows:the more bcl-2 protein, the lower histological graded the longer survival term and the highersurvival rate (pp53 and pCNA expression were ofvalue in evaluating the degree of differentiation and prognosis in breast carcinoma. The quantitativeand qualitative measurement or p53 protein expression showed a Ⅰwerful evidence in evaluatingprognosis of bcl-2 were more significant in evaluating poor prognosis of breast carcinoma. A relationship between bcl-2 and ER, pR showed a better value for response to endocrine therapy in breastcarcinoma patients.

关键词： breast carcinoma p53 protein bcl-2 protein pCNA image analysis technique

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Association between HpV16/18 Infection and Expression of p53 protein in Laryngeal papillomas

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第4期19卷 275-276页

作者：褚汉启 Department of Otorhiolaryngology Tongji Hospital Tongji Medical University Wuhan ORL Grenoble University Hospital La Tronche France

To understand the relationship between expression of p53 protein and HpV16/18 infection in laryngeal papillomas, pCR and immunohistochemical tech-niques were used to examine the paraffin-embedded tissue samples of laryngeal pa-pillomas from 35 subjects. HpV 16/18-DNA was found in 24 cases of laryngeal papillomas (68. 8 %). Overexpression of p53 protein was detected in 19 cases (54. 3 % ). Both HpV16/18-DNA and overexpression of p53 protein were demon-strated in 12 cases of laryngeal papillomas (34. 3 % ). Our results suggest that HpV16/l8 infection and p53 gene mutation are associated with pathogenesis of la-ryngeal papillomas. The relation between HpV infection and p53 mutation in tis-sues of laryngeal papillomas remains to be clarified.

关键词： human papillomavirus laryngeal papillomas p53 protein

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p53 protein expression and cell viability in irradiated peripheral blood mononuclear cells as bioindicators of radiosensitivity

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Journal of Biophysical Chemistry 2011年第2期2卷 63-67页

作者： Mariana Brayner Cavalcanti Ana paula Galvao da Silva Rafael de Freitas e Silva Ademir Amaral Grupo de Estudos em Radioprotecao e Radioecologia(GERAR) Laboratorio de Modelagem e Biodosimetria Aplicada(LAMBDA)Departamento de Energia NuclearUniversidade Federal de PernambucoCidade UniversitariaPernambucoBrazil Anaptysbio Incorporation Cell BiologySan DiegoUSA

Cellular radiosensitivity is directly correlated with the mechanism of DNA repair, in which p53 protein plays a major role. In this context, this study correlated cell death with p53 expression in lymphocytes irradiated in vitro with different doses of gammaradiation. For this, peripheral blood samples were collected from 10 healthy subjects. Each sample was divided in aliquots and, separately, irradiated with doses of 0,5;2 and 4 Gy. After this, peripheral blood mononuclear cells (pBMCs) were isolated and cultivated during 72 hours in 5% CO2 at 37oC without mitogen stimulation. The expression of p53 protein was evaluated by flow cytometry. In parallel, cell viability was determined by trypan blue staining. Statistical analysis was performed us-ing analysis of variance (ANOVA), differences were considered as statistically significant when p p53 expression with the absorbed dose, which was proportional to cell death, suggesting that p53 can be used as bioindicator of individual radiosensitivity.

关键词： p53 protein Radiosensitivity Lymphocytes Flow Cytometry Cell Viability

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Expression and significance of p53 protein and MDM-2 protein in human gliomas

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Chinese Medical Journal 2011年第16期124卷 2530-2533页

作者： WANG An-liu LIU Zhao-xia LI Guang ZHANG Li-wei Department of pathology Beijing TiantanHospital Capital Medical University Beijing 100050 China Department of Neurosurgery Beijing TiantanHospital Capital Medical University Beijing 100050 China

Background p53 is one of the most studied tumor suppressors in the cancer research, and over 50% of human tumors carry p53 mutations. MDM-2 is amplified and/or overexpressed in a variety of human tumors of diverse tissue origin. The aim of this study was to examine the expression of p53 protein and MDM-2 protein in gtiomas, and to investigate the relationship between the expression of the two proteins and the histopathological grades of glioma. The relationship between MDM-2 protein expression and p53 protein expression was also analyzed. Methods The expression of p53 protein and MDM-2 protein was immunohistochemically detected using monoclonal antibodies in 242 paraffin embedded tissues, including 30 normal brain tissues from patients with craniocerebral injury and 212 tissues from patients with primary glioma （grade Ⅰ-Ⅱ group： 5 cases of grade Ⅰ, 119 cases of grade Ⅱ; and grade Ⅲ-Ⅳ group： 53 cases of grade Ⅲ, and 35 cases of grade Ⅳ）. Results The p53 positive rate was significantly higher in the glioma groups than in the control group （p 〈0.0001）. The p53 positive rate was significantly higher in glioma tissues of grade Ⅲ-Ⅳ than in glioma tissues of grade Ⅰ-Ⅱ group （p=-0.001）. The MDM-2 positive rate was significantly higher in glioma groups than in the control group （p 〈0.0001）. There was no significant difference in the MDM-2 positive rate between the two glioma groups （p=0.936）. The expression of p53 protein was not related to expression of MDM-2 protein （p=-0.069） Conclusions Overexpression of p53 protein might be related to the occurrence and progression of glioma. Overexpression of MDM-2 protein may play an important role in glioma tumorigenesis, but may not be involved in glioma progression. The overexpression of MDM-2 protein was an early event in malignant transformation of glioma. MDM-2 may be a key player in glioma in its own right.

关键词： p53 protein MDM-2 protein glioma

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Insulin Resistance in Alzheimer＇s Disease and the Role of p53 protein

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Journal of pharmacy and pharmacology 2014年第6期2卷 327-335页

作者： Kazimierz Gasiorowski Barbara Brokos Elzbieta Trypka Jerzy Leszek Department of Basic Medical Sciences University of Wroclaw Wroctaw 50-556 Poland Department of psychiatry University of Wroclaw Wroctaw 50-367 Poland

Recent evidence reveals significant metabolic changes in AD （Alzheimer＇s disease）, in which brain glucose utilization and energy production are impaired. The complex picture of metabolic disturbances in AD brains could be explained by increase of p53 protein stabilization and activation in neurons exposed to diverse metabolic stress conditions. Activated p53 helps cells to adapt to various types of metabolic stresses. Chronic stress and long lasting p53 increase lead to inhibition of glucose uptake, downregulation of glycolysis, enhancement of lipid catabolism and fatty acid β-oxidation, also promote function of tricarboxylic acid cycle and force an oxidative phosphorylation. These effects are opposite to those of insulin, thus p53 activation leads to insulin resistance of cells. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic rnetabolites （e.g., cerarnide, products of advanced glycation） and ROS （reactive oxygen species）---modified cellular components, together with activation of proapoptotic genes, could finally move a suicide death program of autophagy/apoptosis in neurons. The important role of p53 in driving insulin resistance in AD brains validates attempts to inhibit p53 activity in neurons since it could promise an improvement of the disease therapy.

关键词： Insulin resistance p53 protein Alzheimer's disease.

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