Expression and clinical significance of TAp73α, p53, PCNA and apoptosis in hepatocellular carcinoma

AIM: To study the prognostic role of TAp73α, p53, proliferating cell nuclear antigen (PCNA) and apoptosis in patients with hepatocellular carcinoma (HCC) after surgical tumor ablation. METHODS: Forty-seven human resected HCC tissues and 42 adjacent non-cancerous tissues were studied with 10 normal liver tissues as control group. TAp73α, p53, and PCNA were detected with Elivision immunohistochemistry. Terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick-end labeling (TUNEL) method was used to detect the apoptosis cells. All clinical and pathological materials were analyzed by SPSS10.0 statistical package. RESULTS: TAp73α overexpressed in HCC tissues (36.2%) when compared with adjacent non-cancerous tissues (2.38%, P<0.005) and normal liver tissues (0, P<0.01). Mutant type p53 (mt-p53) overexpressed in HCC tissues (38.3%) when contracted with adjacent non-cancerous tissues (16.7%, P<0.05) and normal liver tissues (0, P<0.01). Proliferation index (PI) level in HCC tissues was significantly higher than that in adjacent non-cancerous tissues (30.34%±4.46% vs 27.88%±5.89%, t, P=0.028). Apoptosis index (AI) level in HCC tissues was higher than that in adjacent non-cancerous tissues (8.62%±2.28% vs 7.38%±2.61%, t, P=0.019). Expression of TAp73a was associated with lymph node metastasis and mt-p53, with r=0.407 and 0.265, respectively. Expression of mt-p53 was associated with Edmondson's stage and AFP, with r=0.295 and-0.357, respectively. In Kaplan-Meier univariant analysis, TAp73α, AFP, TNM stage, portal vein invasion, liver membrane invasion and HBsAg correlated with prognosis (log rank, P=0.039, 0.012, 0.002, 0.000, 0.014, 0.007, respectively). Multivariant Cox regression analysis showed that TAp73α, AFP, TNM stage, portal vein invasion, liver membrane invasion and age were independent factors of prognosis. CONCLUSION: These results suggest that TAp73α can be used as a prognostic indicator of patients with HCC undergoing surgical tumor ablation. AFP, TNM, portal vein invasion, liver membrane invasion and age also have a potency of predicting the prognosis of HCC.

Prognostic factors in 165 elderly colorectal cancer patients

AIM: To analyse the prognostic factors in 165 colorectal patients aged ≥70.METHODS: One hundred and sixty-five elderly patients with colorectal cancer diagnosed by histology were entered into the retrospective study between 1994 and 2001. Patients were given optimal operation alone, chemotherapy after operation, or chemotherapy alone according to tumor stage,histology, physical strength, and co-morbid problems.Survival rate was calculated by Kaplan-Meier method, and compared with meaningful variances by Log-rank method.Prognostic factors were analyzed by Cox regression.RESULTS: The 1,2,3,4,5 year survival rate (all-cause rnortality)was 87.76%, 65.96%, 52.05%, 42.77%, 40.51%,respectively. The mean survival time was 41.89±2.33 months (95% CI: 37.33-46.45 months), and the median survival time was 37 months. Univariate analysis showed that factors such as age, nodal metastasis, treatment method, Duke's stage, gross findings, kind of histology, and degree of differentiation had influences on the survival rate. Multivariate analysis showed that factors such as treatment method,Duke's stage, kind of histology and degree of differentiation were independent prognostic factors.CONCLUSION: This study suggests that the prognosis of elderly colorectal cancer patients is influenced by several factors. Most of elderly patients can endure surgery and/or chemotherapy, and have a long-time survival and good quality of life.

Multi-targets antidepressant mechanism of the bis-benzylisoquinoline 7-O-ethylfangchinoline:Involvement of noradrenergic,dopaminergic and AMPAergic systems

OBJECTIVE Bisbenzylisoquinoline(BBI)alkaloids have extensive pharmacological functions.The aim of this study was to investigate the mechanisms underlying the antidepressant-like action of 7-O-ethylfangchinoline(YH-200)in mice.METHODS Male ICR mice were used in the forced swimming(FST)and tail suspension tests(TST).RESULTS YH-200(60mg·kg-1,ig)decreased the immobility time in FST and TST,and prolonged the latency to immobility in FST.YH-200 revealed more potent anti-immobility activity than its BBI derivative tetrandrine.In addition,the pretreatment of mice with prazosin(1mg·kg-1,ip,anα1-adrenoceptor antagonist),propranolol(2 mg·kg-1,ip,a nonselectiveβ-adrenoceptor antagonist),SCH23390(0.05mg·kg-1,ip,a dopamine D1/D5 receptor antagonist),haloperidol(0.2mg·kg-1,ip,a dopamine D2/D3 receptor antagonist)and NBQX(10mg·kg-1,ip,an AMPA receptor antagonist)prevented the antidepressant-like effect of YH-200(60mg·kg-1,ig)in FST.Besides that,the pretreatment of mice with yohimbine(1mg·kg-1,ip,an α2 adrenoceptor antagonist)augmented the antidepressant-like effect of YH-200(30mg·kg-1,ig)in FST.After 14 dadministration,YH-200(30 and 60mg·kg-1,ig)did not develop drug resistance,but the potency was strengthened,meanwhile,it did not influence the changes in mice body weight.CONCLUSION YH-200 may possess the therapeutic potential for the treatment of depression via the multi-targets including the noradrenergic(α1,α2 and β-adrenoceptors),dopaminergic(D1/D5 and D2/D3receptors)and AMPAergic systems.