Infrequent mutations of the PPP2R1A and PPP2R1B genes in patients with ovarian cancer.

Protein phosphatase 2, regulatory subunit A, α (PPP2R1A) and ß (PPP2R1B) are paralogous subunits of the heterotrimeric protein phosphatase 2 (PP2A) holoenzyme that catalyzes the dephosphorylation of target substrate proteins. Subtype­specific PPP2R1A mutations have been frequently observed in ovarian and endometrial cancer. Mutations in the paralogous genes were frequently observed in human malignancies. Thus, the present study aimed to analyze the mutation frequencies of the paralogous PPP2R1A and PPP2R1B genes in patients with primary and secondary ovarian cancer. A total of 251 patients with primary (n=234) and secondary (n=17) ovarian cancer were analyzed for the presence of PPP2R1A and PPP2R1B mutations by direct sequencing. For PPP2R1A, a heterozygous, somatic mutation (c.771G>T, p.W257C) was identified in 1 out of 37 patients (2.7%) with primary ovarian endometrioid carcinoma. The mutant sample was that of a 46­year­old female, who was also diagnosed with ectopic endometriosis in the benign ovary. No PPP2R1A mutations were detected in the remaining 250 patients with ovarian cancer. For PPP2R1B, no mutations were detected in our samples. The results of this study suggested that PPP2R1A mutations are less common in Chinese patients with ovarian cancer when compared with European and American patients. Furthermore, our study also supported previous observations that PPP2R1B mutations were absent in ovarian cancer, suggesting that PPP2R1B mutations are not actively involved in the pathogenesis of ovarian cancer.

Expression of UDP-glucuronosyltransferase 1A, nuclear factor erythroid-E2-related factor 2 and Kelch-like ECH-associated protein 1 in colonic mucosa, adenoma and adenocarcinoma tissue.

We investigated the expression of UDP-glucuronosyltransferase 1A (UGT1A), nuclear factor erythroid-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in normal colonic mucosa, adenoma tissue and adenocarcinoma tissue, to analyze the correlation between their expression and the clinicopathological features of adenocarcinoma and their roles in colonic carcinogenesis. Using immunohistochemical analysis, we investigated the expression of UGT1A, Nrf2 and Keap1 in normal colonic mucosa (n=24), adenoma tissue (n=30) and adenocarcinoma tissue (n=77). We found that the positive rate of UGT1A was 83.3% in normal colonic mucosa, 80.0% in adenoma tissue and significantly lower, 53.2%, in adenocarcinoma tissue (normal colonic vs. adenoma tissue, P=0.071; normal colonic vs. adenocarcinoma tissue, P=0.023; adenoma vs. adenocarcinoma tissue, P=0.019). The expression levels of Nrf2 were high in adenoma and adenocarcinoma tissues, with positive rates of 70.0 and 87.0%, respectively, but were significantly lower in normal colonic tissue, with a positive rate of 41.7% (normal colonic vs. adenoma tissue, P=0.000; normal colonic vs. adenocarcinoma tissue, P=0.000; adenoma vs. adenocarcinoma tissue, P=0.000). The positive rate of Keap1 was 54.2% in normal mucosa, 70.0% in adenoma tissue and 61.0% in adenocarcinoma tissue (normal colonic mucosa vs. adenoma tissue, P=0.200; normal colonic vs. adenocarcinoma tissue, P=0.040; adenoma vs. adenocarcinoma, P=0.002). In addition, there was no correlation between the expression of Nrf2/Keap1 in adenoma and adenocarcinoma tissues (r=0.067, P=0.723; r=0.042, P=0.715, respectively). The results suggest that decreased expression of UGT1A and the dysregulation of the Nrf2/Keap1 system may be related to colonic carcinogenesis.

[The UGT1A, Nrf2 and Keap1 protein expression and significance in colon tumor].

OBJECTIVE: To investigate the role of UDP-glucuronosyltransferase 1A (UGT1A), nuclear factor erythroid-2-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1) in the tumorigenesis of colonic carcinoma. METHODS: The expressions of UGT1A, Nrf2 and Keap1 were detected in normal colonic mucosa (24 cases), adenoma tissue (30 cases) and adenocarcinoma tissue (77 cases) by immunohistochemistry, and the relationship between their expressions and the clinical pathological characteristics was analyzed. RESULTS: The positive rates of UGT1A in normal colonic mucosa, adenoma and adenocarcinoma tissue were 83.3% (20/24), 80.0% (24/30) and 53.2% (41/77), respectively. The positive rate of UGT1A in adenocarcinoma was lower than those in colonic mucosa and adenoma (all P < 0.05).On the contrary, the positive rates of Nrf2 in adenoma [70.0% (21/30)] and adenocarcinoma tissue [87.0% (67/77)] were higher than that in normal colonic tissue [41.7% (10/24), all P = 0.000]. The positive rates of Keap1 in normal colonic mucosa, adenoma and adenocarcinoma tissue were 54.2% (13/24), 70.0% (21/30) and 61.0% (47/77), respectively (normal colonic tissue vs adenocarcinoma tissue, P = 0.040; adenoma vs adenocarcinoma, P = 0.002). There was no correlation between the expression of UGT1A, Nrf2 and the clinicopathologic features of colon carcinoma, while the differences of Keap1 positive rates in the various degrees of tumor differentiation [moderately-well differentiated vs poorly differentiated: 70.0% (35/50) vs 44.4% (12/27)] and invasion [T(1)-T(2) vs T(3)-T(4): 78.8% (26/33) vs 47.7% (21/44)] were statistically significant (all P < 0.05). CONCLUSION: The decreased expression of UGT1A and the dysregulation of Nrf2/Keap1 system may play a role in colonic tumorigenesis.

[Determination of I- by the ECL of luminol in neutral medium].

Based on the studies of electrochemiluminescence(ECL) of luminol in neutral medium, the iodide would greatly sensitize the ECL of luminol. The ECL luminous intensity responded linearly to the concentration of iodide within the range of 3.8 x 10(-7) mol x L(-1) to 2.2 x 10(-6) mol x L(-1), and the detection limit is 4.0 x 10(-8) mol x L(-1). The mechanism of enhancement effect of iodide on luminol's ECL is also discussed. The experimental results showed that it was a free radical procedure.

[Determination of total effective value of flavonoids in propolis by quenched electrochemiluminescence analysis].

Propolis is a kind of quality health foodstuff containing flavonoids, which is an important clinical effective component in many Chinese traditional medicines. The flavonoids could be used to reduce or clear free radicals, which manifests its medical functions. But there are no satisfactory methods to analyze the content of flavonoids in propolis. This paper reports a new method to determine the total effective value of flavonoids in propolis based on quenched effect for iodide-catalyzed electrochemiluminescence of luminol. It is a sensitive and simple method and might be a probable approach to examining the quality of propolis products.

[The determination of glutathione by electrochemiluminescence quenching method].

Glutathione is an important active substance in organisms. Its study and determination are very significant to human being's health and life. In neutral medium, the quenching effect of reduced glutathione on the electrochemiluminescence of luminol-iodide was studied in this paper. Therefore a novel sensitive method for the determination of reduced glutathione was developed based on it. The linear response range of this method is from 3.38 x 10(-13) mol x L(-1) to 4.72 x 10(-3) mol x L(-1). This method is the most sensitive one and its linear range is the widest among those reported in the literature.