Strong correlation between c-erbB-2 overexpression and overall survival of patients with oral squamous cell carcinoma.

Overexpression of c-erbB-2 (also known as HER-2/neu) has been found in many human cancers, including head and neck squamous cell carcinoma (SCC). We therefore examined expression of the oncoprotein in oral SCC primary tumor samples and compared its relationship with clinical stages and survival rate. Out of 80 cases of oral SCC, high expression level (++ or +++) of c-erbB-2 was found in 41 cases. Of the 80 cases with follow-up information, 39 were further investigated for the correlation of expression level of c-erbB-2 and survival rate. Overexpression of the oncoprotein was significantly correlated with shorter overall survival, and the patients with low and no expression of c-erbB-2 had much higher survival rates. Overexpression of c-erbB-2 was also significantly correlated with nodal stage and metastasis. We found that high expression level of c-erbB-2 was frequently detected in oral cancer cell lines but not in the other head and neck SCC cell lines. Thus, we conclude that overexpression of c-erbB-2 is a frequent event in oral SCC and is correlated with poor survival and may be used as a poor prognostic factor.

Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members.

In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor (EGFR) family members (EGFR, HER-2/neu, HER-3, and HER-4). Expression of the EGFR members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis. We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3, and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/ neu, and HER-3 may help predict the outcome of patients with oral SCC.

Glucagon-like peptide-1 regulates mitochondrial biogenesis and tau phosphorylation against advanced glycation end product-induced neuronal insult: Studies in vivo and in vitro.

Our previous study has proved that glucagon-like peptide-1 (GLP-1), which is developed to treat type 2 diabetes, has a significant effect on neuroprotection against advanced glycation end product (AGE)-induced neuronal insult in vitro models of diabetes-related Alzheimer's disease (AD). However, the molecular mechanisms remain to be elucidated and it is not clear whether GLP-1 receptor mediates the down-regulation effects on AGE-induced AD-like changes in vivo. This study aims to explore the effect and mechanisms of GLP-1 receptor agonists (GLP-1RA) against the AGE-dependent signaling pathway both in vitro and in vivo. In this study, we demonstrated that GLP-1RA could inhibit oxidative stress and repair mitochondrial damage in addition to decreasing tau hyperphosphorylation in PC12 cells treated with AGEs. Importantly, we first observed AGEs in the circulatory system could induce tau hyperphosphorylation after we injected AGEs (1µg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote mitochondrial biogenesis and antioxidant system via regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway in vivo besides down-regulating the activity of glycogen synthase kinase 3ß (GSK-3ß) to reverse tau hyperphosphorylation directly. Collectively, our results suggest that GLP-1RA protects neurons against AGE-induced tau hyperphosphorylation via regulating GSK-3ß and PGC-1α two cooperative signaling pathways.

Metabolic changes in women using a long-acting monthly oral contraceptive and return of ovulation on discontinuation.

Metabolic changes were investigated in two groups of women using oral contraceptives for 5 to 16 years. Blood samples were taken during the last cycle of oral contraceptive use and three months post-treatment. One group had used a monthly oral contraceptive (MOC, 3mg quinestrol and 10mg 16-methylene chlormadinone acetate) and the second group a daily oral contraceptive (DOC, 35 micrograms ethynylestradiol and 0.625 mg norethisterone). During treatment there were increases in serum total cholesterol and triglycerides but not HDL-C, in plasma total cortisol but not in renin activity, angiotensin II or urinary free cortisol excretion, in hemoglobin and some coagulation factors but not Factor X or antithrombin III, platelet function or fibrinolysis. The area under the blood glucose concentration-time curve, but not that for serum insulin, was slightly increased and there was no change in fasting blood sugar concentrations. All metabolic parameters, except plasma cortisol, which had shown an increase on treatment, had decreased to control levels within 3 months. Ovulation returned promptly in all women, the mean time being 70 days for Group MOC and 44 days for Group DOC. Thus, in spite of the long duration of use of the oral contraceptives, metabolic changes were minor.

Determination of taxol in Taxus chinensis by HPLC method.

A method for the determination of taxol in Taxus chinensis by HPLC method using betamethasone as internal standard is described. The column employed was packed with 10 microns silica gel YWG 80 (250 x 4 mm), the eluting solvent consisted of CH2Cl2--MeOH (95:5) and the effluent was monitored at 228 nm. The coefficients of variation are less than 2%.

[Determination of ranunculin in Pulsatilla chinensis and synthetic ranunculin by reversed phase HPLC].

A method for the determination of ranunculin in Pulsatilla chinensis and synthetic ranunculin by reversed phase HPLC using betamethasone as internal standard is described. The column employed was a 10 micron LiChrosorb RP-18 (230 x 14 mm), the eluting solvent consisted of methanol-water (40:10, V/V) and the effluent was monitored at 225 nm. The advantages of this method are simple, rapid and accurate. The coefficients of variation are less than 1%.

Coulometric titration of total flavonoids in Sophora japonica L.

A method for the determination of total flavonoids in Sophora japonica L. by coulometric titration was developed. The titration was carried out in a mixture of 1 mol/L KBr--2 mol/L HCl (1:1) and bromine was generated at the anode, rutin reacted with two moles of bromine with an n value of 4. The advantages of this method are simple and rapid, it can be used to analyze small amount of sample.

[HPLC determination of six flavonoid constituents in Ginkgo biloba leaves].

Six flavonoid constituents (quercetin, isorhamnetin, kaempferol, bilobetin, ginkgetin and sciadopitysin) were isolated from Ginkgo biloba leaves and determined by reversed phase HPLC using salvianolic acid B as internal standard. The column employed was Zorbax ODS (150 mm x 4 mm ID, 5 microns). The mobile phase consisted of solvent A (methanol) and solvent B [tetrahydrofuran--water--formic acid (34:65:1)] for gradient elution. The flow rate was 1 ml.min-1 and detection was effected at 350 nm. This method is accurate, rapid and reproducible. Analytical data for various samples were given.

[Determination of bile acids in bear gall drainage by thin layer chromatographic scanning].

A method for the quantitative determination of three main bile acids, cholic acid (CA), ursodesoxycholic acid (UDCA) and chenodesoxycholic acid (CDCA), in bear gall, drainage from bear gall and bear gallstone is described. Experimental conditions: TLC Scanner CS-910, fluorescence scanning, lambda ex 470 nm and lambda em 550 nm for CA; lambda ex 380 nm and lambda em 450 nm for UDCA and CDCA. The results showed that the contents of UDCA and CDCA in bear gall drainage were higher than those in bear gall. The method is simple, rapid and sensitive. The reproducibility is good. The average recovery is 98.4%, CV is 1.4%.

[Clinicopathological analysis of 20 cases of giant cell granuloma of the jaw].

The pathological features of 20 cases of giant cell granuloma and 12 cases of giant cell tumor of the jaw were compared. Specimens of 8 cases of giant cell granuloma and 5 cases of giant cell tumor were stained with Wilder's reticular fiber stain and trichromic stain. The results showed that reticular fibers and collagenous fibers were more abundant and more focal in distribution in giant cell granulomas than in those of giant cell tumors. It is concluded that the two staining methods adopted are helpful in the differential diagnosis between these two kinds of diseases.

[Study in the combining quantity of Con A-binding sites on membrane surface of artesunate-resistance strain of Plasmodium berghei].

OBJECTIVE: To study the production mechanism of plasmodium berghei (PB) in resisting artesunate. METHODS: The combining quantity of Con A-binding sites on membrane surface of PB trophozoite labelled with fluorescein isothiocyanate (FITC) of Con A was determined by fluoromicrospectrophotometer. RESULTS: The combining quantity of PB artesunate-resistance strain (PBAR) was reduced significantly than that of PB normal strain (P < 0.01). CONCLUSIONS: The type of glucose in surface membrane of PBAR has changed and the changes of membrane fluidity could be one of the causes of the change in the combining quantity of Con A-binding sites on membrane of PBAR.

[The synergistic action of guanghuoxiang volatile oil and sodium artesunate against Plasmodium berghei and reversal of SA-resistant Plasmodium berghei].

OBJECTIVE: To study the synergistic action of a combination of guanghuoxiang volatile oil (B) and sodium artesunate (SA) against Plasmodium berghei (P. b) and the resistance-reversal activity against SA-resistant P. b (P. b SA-R). METHODS: Mice infected with P. b N or P. b R were treated with a combination of B and SA respectively by 4-day suppressive test method and linear regression to calculate the SD50 of B and SA for each drug alone and in combination (equally effective dose compatibility). RESULTS: B alone, N:SD50 = 87.64 +/- 19.58(GKD), R:SD50 = 43.24 +/- 7.71(GKD); SA alone, N:SD50 = 0.88 +/- 0.01(MGKD), R:SD50 = 27.69 +/- 0.93(MGKD). B and SA combination, N:B SD50 = 36.89 +/- 4.57(GKD), SA SD50 = 0.39 +/- 0.05 (MGKD); R:B SD50 = 7.40 +/- 1.30(GKD), SA SD50 = 4.21 +/- 0.74(MGKD). The synergistic indexes of B and SA in combination were 2.2 for N and 6.6 for R, respectivly. The multiple of resistance reversal of B vs SA was 6.6. The relative reversal rate was 87.6%. CONCLUSION: A combination of B and SA may enhance the antimalarial effect against P. b and reverse the SA-resistance of P. b and delay the occurrence of resistance to SA in N.

Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation.

We have previously demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist ameliorated neurodegenerative changes in rat models of diabetes-related Alzheimer's disease (AD), and protected neurons from glucose toxicity in vitro. Herein, we investigated the effects of GLP-1 receptor mediates on cell toxicity and tau hyperphosphorylation induced by advanced glycation end products (AGEs), which are associated with glucose toxicity, and the molecular mechanism in PC12 cells and the primary hippocampal neurons. Our study demonstrated that the similar protection effects of GLP-1 existed in PC12 cells treated with glucose-bovine serum albumin (BSA) in hyperglycemic conditions or with glycoaldehyde-BSA alone. Additionally, glucose-BSA alone did not induce significant cytotoxicity in PC12 cells, but resulted in tau hyperphosphorylation in primary hippocampal neurons in 24h. And we found that GLP-1 could reduce cell tau phosphorylation induced by high glucose or glucose-BSA. Furthermore, our data in the present study suggested that GLP-1 regulated tau phosphorylation induced by AGEs through a signaling pathway involving glycogen synthase kinase 3ß (GSK-3ß), similarly to the GSK-3ß inhibitor, lithium chloride. Our findings suggest that GLP-1 can protect neurons from diabetes-associated AGE insults in vitro, and provide new evidence for a potential therapeutic value of GLP-1 receptor agonist in the treatment of AD especially diabetes-related AD.