1.Repeated oral treatment with polysaccharide sulfate reduces insulin resistance and dyslipidemia in diabetic dyslipidemic rat model.
Mei-Mi ZHAO ; Zhi LI ; Zan TENG ; Jin-Sheng ZHAO ; Xiu-Hua YU ; Yasuo WATANABE ; Li-Mei ZHAO
Acta Pharmaceutica Sinica 2007;42(5):488-491
Polysaccharide sulfate (PSS) is a new type of antiatherosclerotic medicine for its effects of anticoagulation, anti-thrombosis and modulation of dyslipidemia. However, it is still uncertain whether PSS could modulate the diabetic dyslipidemia or not. Here, the rat model of diabetic dyslipidemia was developed and the effects of PSS on glucose and lipid levels were investigated in this animal model. Wistar rats were iv injected with streptozotocin 20 mg x kg(-1) after feeding with high fat diet for one and a half month. Then, rats received orally PSS (30, 90, and 180 mg x kg(-1)) for 1 month. After oral treatment with PSS (90 and 180 mg x kg(-1)) for 1 month, the levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) were significantly reduced and the level of high density lipoprotein-cholesterol (HDL-C) increased, compared with diabetic control rats. Moreover, PSS (30, 90, and 180 mg x kg(-1)) had a tendency to reduce glucose and insulin levels, and significantly increased insulin sensitivity index. Our results suggest that PSS could improve insulin sensitivity and relieve dyslipidemia in diabetic dyslipidemic rats.
Administration, Oral
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Animals
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Blood Glucose
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metabolism
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Cholesterol, HDL
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blood
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Cholesterol, LDL
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blood
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Diabetes Mellitus, Experimental
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blood
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chemically induced
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complications
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Dyslipidemias
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blood
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etiology
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Hypolipidemic Agents
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administration & dosage
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pharmacology
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Insulin
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blood
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Insulin Resistance
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Male
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Polysaccharides
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administration & dosage
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pharmacology
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Random Allocation
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Rats
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Rats, Wistar
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Streptozocin
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Sulfates
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administration & dosage
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pharmacology
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Triglycerides
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blood
2.Blockade of Autophagy Aggravates Endoplasmic Reticulum Stress and Improves Paclitaxel Cytotoxicity in Human Cervical Cancer Cells.
Li XU ; Jing Hua LIU ; Jing ZHANG ; Na ZHANG ; Zan Hong WANG
Cancer Research and Treatment 2015;47(2):313-321
PURPOSE: Autophagy is one of the ways to degrade unfolded proteins after endoplasmic reticulum (ER) stress. The purpose of this study is to determine whether a blockade of autophagy leads to aggravated endoplasmic reticulum stress, which then induces cells apoptosis in HeLa cells treated with paclitaxel. MATERIALS AND METHODS: Autophagy activation and the proapoptotic effects were characterized using monodansylcadaverine labeling and Hoechest staining, respectively. A Western blot analysis was used to detect the expression of apoptotic and autophagy-related genes. A flow cytometry was used to assess the cell apoptosis ratio. RESULTS: Paclitaxel exposure induced the aggregation of autophagosomes in the cytoplasms of cervical cancer HeLa cells. The expression of Beclin 1 and LC3 II were upregulated, but p62 was downregulated, which suggests that autophagy was promoted by paclitaxel. On the other hand, the expression of GRP78 obviously increased, suggesting that ER stress was induced after paclitaxel treatment. The cell proliferation assay indicated that a knockdown of Beclin 1 sensitized HeLa cells to paclitaxel. Furthermore, paclitaxel-mediated apoptotic cell death was further potentiated by the pretreatment with autophagy inhibitor chloroquine or small interfering RNA against Beclin 1. These results suggest that an induction of autophagy by paclitaxel may induce cell survival rather than cell death in HeLa cells; moreover, inhibition of autophagy led to an aggravated ER stress and an induction of downstream apoptosis. CONCLUSION: Our results reveal autophagy induced by paclitaxel conferred protection of tumor cells against apoptosis, and blockade of autophagy subsequently aggravated ER stress, enhancing the apoptosis associated with paclitaxel treatment in HeLa cells.
Apoptosis
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Autophagy*
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Blotting, Western
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Cell Death
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Cell Proliferation
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Cell Survival
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Chloroquine
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Cytoplasm
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Endoplasmic Reticulum
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Endoplasmic Reticulum Stress*
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Flow Cytometry
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Hand
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HeLa Cells
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Humans
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Paclitaxel*
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RNA, Small Interfering
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Uterine Cervical Neoplasms*
3.Target therapy of gefitinib in advanced adenocarcinoma of the lung.
Hua ZHENG ; Jingping WANG ; Qiyi MENG ; Zan LIU ; Baolan LI ; Yunzhong ZHU
Chinese Journal of Lung Cancer 2007;10(3):229-233
BACKGROUNDGefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which is used to treat advanced non-small cell lung cancer, especially adenocarcinoma. The aim of this study is to evaluate the efficacy, side effects and prognostic factors of gefitinib in adenocarcinoma of the lung.
METHODSA total of 26 patients with advanced adenocarcinoma of the lung were enrolled in the study. Gefitinib was orally administered 250mg once daily until disease progression or the occurrence of intolerable toxicity. They were evaluated regularly and their survival was analyzed.
RESULTSIn 26 patients, there was 1 with complete regression (3.8%), 11 with partial response (42.3%), 9 with stable disease (34.6%) and 5 with progression of disease (19.2%). The objective response rate was 46.2% and the disease control rate was 80.8%. The median progression-free survival time was 8.2 months and the median overall survival time was 10.4 months. The 1-year survival rate was 31.6%. Age ( < 70 years old), skin rash and CEA decrease were significantly related to longer survival, however, times of prior chemotherapy and gefitinib treatment stage did not influence the survival. Mean PS (ECOG) was 3.0 before treatment, and 1.8 after treatment. Mean symptom relief time was 5.2 days.
CONCLUSIONSGefitinib is an effective target drug with slight side effect. It can significantly improve quality of life of patients with adenocarcinoma. It can be used as first-line therapy to patients who are not suitable for chemotherapy.
4.Early and long-term results of combined cardiac surgery and neoplastic resection in patients with concomitant severe heart disease and neoplasms.
Qiang FU ; Quan-zheng LI ; De-gang LIANG ; Xin-hua RUAN ; Zan-xin WANG ; Min-xin WEI
Chinese Medical Journal 2011;124(13):1939-1942
BACKGROUNDIt is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms.
METHODSWe reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2 ± 12.5) years and the mean left ventricular ejection fraction was (57.4 ± 11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1 ± 11.2) months).
RESULTSFifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n = 7), aortic valve replacement (n = 3), mitral valve replacement (n = 3), mitral valve replacement with coronary artery bypass grafting (n = 1) and left atrial myxoma resection (n = 1). Neoplastic resection consisted of lung cancer resection (n = 5), colonic cancer resection (n = 3), gallbladder resection (n = 1), colonic cancer resection with gallbladder resection (n = 1), hysterectomy (n = 2), hysterectomy with bilateral salpingo-oophorectomy (n = 2) and left ovariectomy (n = 1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method).
CONCLUSIONSSimultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not appear to adversely affect survival in patients with malignant disease. The long-term survival was determined by tumor stage.
Adult ; Aged ; Colonic Neoplasms ; surgery ; Female ; Heart Diseases ; surgery ; Humans ; Hysterectomy ; adverse effects ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Ovariectomy ; adverse effects ; Thoracic Surgery ; statistics & numerical data ; Treatment Outcome
5.Studies on effect of microemulsion in enhancing solubility of baicalin and puerarin.
Hua YANG ; Hong YI ; Man-Ling LI ; Zan-Ye CAO ; Wei-Hong FENG
China Journal of Chinese Materia Medica 2007;32(19):1996-1999
OBJECTIVETo study the effect of O/W Microemulsion in enhancing solubility of baicalin and puerarin.
METHODThe Pseudo-ternary phase diagram was employed to selected the formulations of O/W microemulsion. The partical size of microemulsion, and solubility of baicalin and puerarin in water, oil phase, surfactant, microemulsion and alcohol were determined, respectively.
RESULT11 types of microemulsion formulations have the effect in enhancing the solubility of baicalin and puerarin; the solubility of Baicalin in microemulsion is higher as 5-15 times than it in water, the solubility of Puerarin in microemulsion is higher as 3 - 4 times than it in water.
CONCLUSIONMicroemulsion is good in enhancing solubility of effective compounds extracted from Chinese medical herbs.
Drug Compounding ; methods ; Emulsions ; Flavonoids ; analysis ; chemistry ; Isoflavones ; analysis ; chemistry ; Oils ; chemistry ; Particle Size ; Solubility ; Surface-Active Agents ; chemistry ; Water ; chemistry
6.A multi-center, randomized control trial on clinical research education to diabetes patients.
Zan-hua LI ; Su-qin YANG ; Jian-ping LIU
Chinese Journal of Integrated Traditional and Western Medicine 2011;31(10):1359-1363
OBJECTIVETo assess the effect of implementing education about clinical research in changing the awareness and attitudes of diabetic patients.
METHODSA randomized control trial was implemented in 258 patients with diabetes from 6 hospitals. The participants were assigned to the intervention group (129 cases, who received education about the clinical research) and the control group (129 cases, who received no intervention). The outcome indicators were the variables on knowledge, attitude for the clinical research between before and after intervention in the same group and between the two groups.
RESULTSThere was no withdrawal or lost in the two groups. Comparing the contents between inter-groups and intra-group for 19 assignment questions, it showed statistical significance (P<0.05). After the patients received education, their knowledge about and attitude towards clinical research, informed consent, placebo, follow-up, random allocation, and ethics, etc. were markedly improved. Their attitudes for the participants to join in scientific research, opinion, confidence were obviously changed, and it also showed that the method was feasible. The patients' education level was positively correlated with the clinical research educated outputs.
CONCLUSIONThis study proved the necessity for patients participating in future clinical trials to receive education, as well as its feasibility and effectiveness.
Adult ; Aged ; Aged, 80 and over ; Biomedical Research ; education ; Diabetes Mellitus ; prevention & control ; Female ; Humans ; Male ; Middle Aged ; Patient Education as Topic
7.Management of thyroid goiters invading mediastinum and thoracic cavity
Jie CHEN ; Jian-Jun YU ; Wei WEI ; Zan LI ; Wen-Xiao HUANG ; Rong-Hua BAO ; Li XIE ; Jin-Yun LI ; Hai-Lin ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2011;46(8):654-657
Objective To investigate the diagnosis and treatments of thyroid goiters invading mediastinum and thoracic cavity. Methods Seventy-eight cases of thyroid goiters invading mediastinum and thoracic cavity and undergoing surgery from 1995 to 2005 were reviewed. There were 22 males and 56 females and their age ranged from 45 years to 78 years with a median age of 59 years. According to the classification of intrathoracic thyroid goiters, there were 50 cases in Class Ⅰ , 20 cases in Class Ⅱ and 8 cases in Class Ⅲ. In these patients,38 cases suffered from dyspnea at degree [ and 20 cases at degree Ⅱ.Of the patients, 71 underwent thyroidectomy through neck approach and 7 underwent thyroidectomy by a combined approach of neck incision plus stemotomy or lateral thoracotomy. Tracheal defects in 4 cases and esophageal defects in 3 cases were repaired. Postoperative residual diseases were found in tracheoesophageal wall(5 cases) and mediastinum (6 cases). Eleven patients received postoperative radiotherapy and 18 underwent 131 Ⅰ treatment. No case died of operation and no case with wound infection. Results The time of follow-up was 60 - 180 months with a median of 110 months. Three patients lost follow-up. Dyspnea in 58 cases were improved after operation. Three of 49 patients with nodular goiters died from cardiocerebrovascular diseases. Of 29 patients with thyroid papillary carcinoma, 2 died from lung metastasis and 3 died from neck relapse. Five-year survival rate was 75.0% in the patients with thyroid cancer.Conclusions Most of thyroid goiters invading mediastinum and thoracic cavity can be completely resected via neck approach, but a combined approach of neck incision plus stemotomy or lateral thoracotomy may be used in some cases with malignant goiters to dissect the diseases completely. Postoperative external beam radiotherapy are required for the residual diseases. 131Ⅰ may be considered in high-risk differentiated thyroid carcinoma cases.
8.Surgical managements for residual or recurrent diseases in the neck after radiotherapy in nasopharyngeal carcinoma
Jie CHEN ; Wen-Xiao HUANG ; Wei WEI ; Xiao ZHOU ; Jian-Jun YU ; Zan LI ; Li XIE ; Rong-Hua BAO ; Jin-Yun LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2012;47(3):180-184
Objective To investigate the surgical managements for residual or recurrent diseases in the neck after radiotherapy in nasopharyngeal carcinoma. Methods Seventy-eight cases of neck masses (39 cases for unilateral residual diseases,9 for bilateral residual diseases and 30 for reccurent diseases)after radiotherapy in nasopharyngeal carcinoma who were treated surgically between January 1990 and December 2005 were retrospectively analyzed.There were 56 males and 22 females.Their ages ranged from 28 to 65 years( median 41 years).There were 27 patients with skin involvement. After preoperative imaging assessment,17 patients whose common carotid arteries or internal carotid arteries were difficult to separate routinely attained the carotid balloon occlusion test which confirmed that 15 cases of cerebral arterial circle open to compensation,however,two cases of poor compensation.Surgical procedures included expanded neck mass resection (21 cases),unilateral radical neck dissection (49 cases)and bilateral radical neck dissection(8 cases).Of them 5 patients were with unilateral internal carotid artery resection.Neck defects were repaired with pectoralis major muscle flaps (15 cases),free anterolateral femoral skin flaps (9 cases)and trapezius muscle flaps(3 cases).Of the 78 patients,13 with microscopic positive diseases and 2 with residual diseases in internal carotid artery walls underwent postoperative radiotherapy,with the doses of 45 to 50 Gy.Results All patients were closely followed-up more than 5 years.Three- and five-year survival rates were 46.2% and 28.3% respectively.Neck defects were successfully repaired with skin flaps immediately after resecting diseases in 27 cases,only one patient with delayed healing.Of 51 patients without skin flap repair,neck wounds healed successfully in 45 patients and with delayed healing in 6 patients.Pathological positive rates of lymph nodes located in the level Ⅰ,Ⅰ,Ⅲ,Ⅳ and Ⅴ were 10.5%,61.4%,10.5%,1.8% and 28.1% respectively.Conclusions Preoperative balloon occlusion test is required to assess the function of Willis'ring before determining ligation or resection of internal carotid artery.Residual or recurrent diseases commonly exist in level Ⅱ,Ⅴ A and Ⅲ,which should be included in neck dissection.Pectoralis major muscle flap and free anterolateral femoral skin flap are recommended for the repair of neck defect.
9.Comparison of the effect of local administration of endothelial progenitor cells and VEGF on improving neovascularization in flap prefabrication.
Tao ZAN ; Ji-ying DONG ; Hua LI ; Rui WENG ; Mei YANG ; Yun XIE ; Qing-feng LI
Chinese Journal of Plastic Surgery 2009;25(6):451-455
OBJECTIVETo compare the effect of local administration of endothelial progenitor cells (EPCs) and VECF on improving neovascularization and augmenting the survival areas in a rat model of prefabricated flap.
METHODSPrefabricated flaps were created by ligating the right femoral vascular pedicle and implanting it underneath the abdominal flap. The in vitro cultured EPCs (Group I , n=15) and VEGF protein (Group II , n=15) were injected subcutaneously around the implanted pedicle in experimental groups. PBS was injected in control group (Group Ill , n=15). 4 weeks later, the abdominal island flap based solely on the implanted vessels was elevated and sutured back. Then flap viability and numbers of capillary were evaluated on day 7.
RESULTSThere was more statistically significant augmentation of flap survival [(87.26 +/- 10.13) % versus (66.13 +/- 9.9)% and (55.59 +/- 13.06)%, P < 0.001], a higher capillary density (38.67 +/- 9.52 versus 25.83 +/- 6.33 and 26.5 +/- 5.61 capillary/mm2 , P < 0.05) in EPCs group than in the other two groups.
CONCLUSIONSEPCs are superior to VEGF in improving neovascularization during flap prefabrication. Local transplantation of bone marrow-derived EPCs may be a useful strategy for augmentation of the survival areas of prefabricated flaps.
Animals ; Cells, Cultured ; Endothelium, Vascular ; cytology ; Graft Survival ; Male ; Neovascularization, Physiologic ; Rats ; Rats, Wistar ; Stem Cell Transplantation ; Surgical Flaps ; blood supply ; Vascular Endothelial Growth Factor A ; pharmacology
10.The relationship between p120ctn translocation and malignant features of hepatocellular carcinoma.
Hua-yi HUANG ; Chao-zan NONG ; Wei-sheng HE ; Ling-xiao GUO ; Shao-yun NONG ; Li-li PAN ; Xi-liang ZHA
Chinese Journal of Oncology 2004;26(7):398-402
OBJECTIVETo investigate the effect of catenin p120 (p120ctn) translocation on the malignant features of hepatocellular carcinoma and its interrelation with beta-catenin in E-cadherin-mediated cell signaling.
METHODSExpression and translocation of p120ctn, tyrosine phosphorylation, and its binding capacity to E-cadherin were detected by DNA transfection, immunoblotting and immunoprecipitation. Cellular localization of p120ctn and beta-catenin was detected by immunofluorescent microscopy. Cell adhesion, cell migration and cell proliferation were also studied.
RESULTSExpression of p120ctn increased after cells transfected with p120ctn isoform 3A, and it was located mainly at cell-cell contact region. Its binding to E-cadherin was enhanced. After EGF stimulation, tyrosine phosphorylation of p120ctn was increased, membrane expression of p120ctn and beta-catenin was decreased while cytosol expression was increased. It was translocated into the nucleus, cell adhesiveness was increased but mobility decreased. With over-expression of p120ctn, beta-catenin was recruited by nucleus export. Cell proliferation was reduced but it was increased after EGF treatment.
CONCLUSIONp120tn plays an important role in cell adhesion, migration and proliferation of hepatocellular carcinoma, and its tyrosine phosphorylation might contribute to this mechanism. There might be a competitive relationship between p120ctn and beta-catenin.
Cadherins ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Catenins ; Cell Adhesion ; Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Cell Membrane ; metabolism ; Cell Movement ; Cell Nucleus ; metabolism ; Cell Proliferation ; Cytoskeletal Proteins ; metabolism ; Cytosol ; metabolism ; Epidermal Growth Factor ; pharmacology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Phosphoproteins ; metabolism ; Phosphorylation ; Protein Transport ; Trans-Activators ; metabolism ; Tyrosine ; metabolism ; beta Catenin