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51.
Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis 总被引:23,自引:0,他引:23
Nam SY Lee HS Jung GA Choi J Cho SJ Kim MK Kim WH Lee BL 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(12):1105-1113
Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients. 相似文献
52.
Lee YJ Nam SW Seo DW Ahn SH Ko YK Sung DS Han JW Hong SY Lee HW 《Archives of pharmacal research》1997,20(3):239-246
In the present study, liver regeneration rate (%) was increased up to 70% 3 days after partial hepatectomy (PH). Nitric oxide
synthase (NOS) activity in liver tissue as well as serum nitrite/nitrate content had no timed response, revealing no significant
difference between shamoperated and partially hepatectomized rat liver. Contents of free methylarginines in liver tissue were
increased biphasically in a time-dependent manner after PH. However, those in serum did not exhibit the same patterns as in
liver. Taken together, the results suggest that NG-monomethyl-L-arginine (MMA) and NG, NG-dimethylarginine (DMA) play a role in inhibiting nitric oxide (NO) synthesis in regenerating rat liver because the increase
of their contents was synchronized with NOS expression. 相似文献
53.
The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethylnitrosamine
(DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using
the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased
by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr)
of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life (t1/2) in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution
at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL (8.67±4.85%) decreased
about four-folds, but in DMNA (73.00±9.85%) similar result, was observed as compared with the control. Increased free fraction
of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline
was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline
in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results
suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline. 相似文献
54.
2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s). 相似文献
55.
Yong -Hyun Kim Do -Youn Won Chang -Young Oh Nam -Tae Woo Young -Ho Park Jin -Hyun Jeong Won -Hun Ham 《Archives of pharmacal research》1999,22(3):300-301
Stereoselective synthesis of (+/-)-epibatidine analog 2, which contains the 8-azabicyclo[3.2.1]octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3. 相似文献
56.
Glutamate excitotoxicity, which is mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA receptors, directly contributes to the neuronal cell loss associated with both acute insults and chronic neurodegenerative disorders. Conjugated linoleic acid (CLA) is a group of dienoic derivatives of linoleic acid shown to have anticarcinogenic and antioxidative activities. To evaluate the effect of a mixture of CLA isomers (cis-9, trans-11 and cis-10, trans-12 octadecadienoic acids) on glutamate- and NMDA-induced excitotoxicity, primary cultures of rat cortical neurons were treated for 15 min with 300 microM glutamate or NMDA in the presence of various concentrations of CLA. After the exposure, cell cultures were maintained at 37 degrees C for 18 h in minimum essential medium supplemented with glucose. Neuronal injury was measured by a colorimetric cell proliferation assay, and a qualitative assessment was made by phase-contrast microscopy. CLA inhibited glutamate- and NMDA-induced neuronal cell death in a concentration-dependent fashion with the most effective dose for neuroprotection being 500 microM. These results demonstrate that a mixture of CLA isomers exhibits protective action against glutamate- and NMDA-induced excitotoxicity. 相似文献
57.
Gwi Eon Kim Yong Bae Kim Nam Hoon Cho Hyun-Cheol Chung Hong Ryull Pyo Jong Doo Lee Tchan Kyu Park Woong Sub Koom Mison Chun Chang Ok Suh 《Clinical cancer research》2004,10(4):1366-1374
PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix. 相似文献
58.
Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma. 总被引:1,自引:0,他引:1
Nam H Dang Fredrick B Hagemeister Barbara Pro Peter McLaughlin Jorge E Romaguera Dan Jones Barry Samuels Felipe Samaniego Anas Younes Michael Wang Andre Goy Maria A Rodriguez Pamela L Walker Yolanda Arredondo Ann T Tong Luis Fayad 《Journal of clinical oncology》2004,22(20):4095-4102
PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted. 相似文献
59.
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