Safety and tolerability of anti-diabetic drugs should be among the most concern when it comes to management of Type 2 Diabetes.With the understanding of functions of incretin and degrading enzyme dipeptidepeptidase (DPP-4),several DPP-4 inhibitors with different chemical structures are now available.They are welltolerated with few weight gain,hypoglycemia or adverse effects.Therefore,DPP-4 inhibitors are considered to be among the ideal anti-hyperglycemic agents.

Caveolae is a specified micro-domain of plasma membrane, which consists of caveolin and many lipid molecules and membrane proteins. Caveolae plays important roles in internalization of extra-membrane molecules, transmembrane signal transdution and transport of cholesterin. Recent studies indicated that caveolae and its components were up-regulated in multidrug resistant tumor cells and might participate the development of multidrug resistance of tumor cells. This paper concentrated on the role of caveolae in tumor multidrug resistance.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant inherited disease,and may be related to the mutation of CDH1 or CTNNA1 genes.Microscopically,signet-ring cell carcinoma is suggested frequently in endoscopic biopsy or gastrectomy specimens.Some patients may have concomitant extra-stomach tumor (frequently breast cancer in females).Detection of CDH1 gene mutation should be performed in high-risk individuals,and diagnosis and treatment should be carried out by a multidisciplinary team.Prophylactic gastrectomy is recommended for those with pathogenic CDH1 mutation.Endoscopic surveillance is an option for those with CDH1 mutation of undetermined significance and those without germline CDH1 mutation.This review discussed the concept,genetic characteristics,clinicopathological features and genetic screening of HDGC for providing a reference for clinicians.

The prevalence of prediabetes is increasing rapidly in China, and with higher prevalence in coronary heart disease and hypertension patients. Diabetes can be controlled and prevented, previous studies have confirmed that lifestyle interventions and drug interventions can delay the progression of prediabetes to diabetes, and acarbose can be used for the primary prevention of cardiovascular events in impaired glucose tolerance(IGT) and diabetic patients, but benefits of drug intervention for secondary prevention of cardiovascular disease in IGT population are uncertain. The Acarbose Cardiovascular Evaluation(ACE) Study is a multicentre, randomized, placebo-controlled, double-blind study, with the aim of assessing the use of acarbose to reduce the risk of cardiovascular events and the onset of diabetes in IGT patients with cardiovascular disease in China , the results will be very meaningful and valuable for the prevention and treatment of diabetes. We will predict the results of ACE Study based on previous evidences.

By molecular cloning technique, the expressing plasmids pDOR-SV40-Bcl-2 cDNA were successfully constructed. The reconstructed plasmids with lipofectamine were transduced into gastric cancer cell line SGC7901 and then the positive clones which contained the reconstructed plasmids were choosed by G418. Circa 150 positive clones were choosed from 2 x 10_5 gene transduced cells, which suggested that the transducing efficiency was more than 1%o; 2 positive clones were expanded and passage, then 1 drug-resistance cell strain (SGC7901 anBcl-2 cells) was obtained. The bloting results suggested, Bcl-2 cDNA were expressed in both gene transduced and not transduced cell strains, but the expressing level of mRNA and protein in gene transduced cell strain was very low than that in gene not transduced cell strain were positive by the means of Southern blot, Northern blot and Western blot. This results showed that normally in gastric cancer cells the expressing level of Bcl-2 gene was very high, and the cDNA fragment of antisense Bcl-2 were successfully transduced into gastric cancer cells, and in gene transduced cell strains the expressing of Bcl-2 gene was effi-cientlv blocked.

Objective To study the expression of 9 delayed rectifier potassium channel subunits in human gastric cancer cell line AGS, as well as the effect of down-regulation of the expression of Kv1.5 on AGS cells proliferation. Methods RT-PCR technique was employed to detect the mRNA expression of Kv1.1, Kv1.2, Kv1.3, Kv1.5, Kv1.6, Kv2.1, Kv2.2, Kv3.1 and Kv3.2 in AGS cells. Once the expression of Kv1.5 protein was confirmed by immunofluorescence, small interference RNA (siRNA) was applied to down-regulate the Kv1.5 protein expression, then MTT assay and flow cytometry were used to observe the cell proliferation and the cell cycle distribution. Results Totally 7 delayed rectifier potassium channel subunits were detected in AGS cells, among them the mRNA levels of Kv1.3, Kv1.5 and Kv2.1 were much higher than that of the others. It was confirmed by immunofluorescence that the Kv1.5 protein was expressed mainly in AGS cytomembrane. After the endogenous Kv1.5 expression in AGS cells was down regulated by siRNA, the cell proliferation obviously slowed down and the cell growth stopped in G1 period. Conclusion Multiform expression of delayed rectifier potassium channel subunits existed in AGS cells, and Kv1.5 may be involved in the regulation of gastric carcinoma cell proliferation by modulating the cell cycle.

Objective To study the effects of activation and inhibition agents of protein kinase C on the function and expression of P glycoprotein in drug resistant gastric cancer cells. Methods Immunohistochemical staining and FACS were used to determine the expression of P glycoprotein on drug resistant gastric cancer cells SGC7901/VCR and its parent cells SGC7901, which were treated or not treated by activation or inhibition agents of protein kinase C(PMA or H 7). Double labeled immunoflurescent and laser scan confocal microscopy were used to detect the coexpression of protein kinase C ? and P glycoprotein on drug resistant gastric cancer cells. Rohdamin 123 was used as fluorescent probe to observe the effects of PMA and H 7 on the function of P glycoprotein and drug accumulation in SGC7901/VCR. Results P glycoprotein had positive staining on SGC7901 cells and much stronger staining on SGC7901/VCR cells. Protein kinase C ? and P glycoprotein exhibited coexpression on SGC7901 cells and much higher coexpression level on SGC7901/VCR cells. When treated by PMA, SGC7901/VCR cells showed time dependent decreasing of drug accumulation, enhancing function and decreasing expression of P glycoprotein. When treated by H 7, SGC7901/VCR cells showed time dependent increasing of drug accumulation, weakening function and increasing expression of P glycoprotein.Conclusion Protein kinase C may play a role in multidrug resistance of gastric cancer cells via modulating the expression and function of P glycoprotein.

Objective To study the effect of ribosomal protein S13(RPS13) encoding genes on the development of mutidrug resistance (MDR) in human gastric cancer cell line. Methods RPS13 cDNA was amplified by RT-PCR. The sense and antisense eukaryotic expression vectors were constructed by DNA recombination. Gastric cancer cell line SGC7901 and Vincristine-resistant SGC7901/VCR cells were transfected with the sense and antisense recombinant vectors respectively using liposome-mediated method. RNA dot blotting assay was used to verify the changes of mRNA level in stable clones. To investigate effects of the sense, antisense vector transfection on the chemotherapeutic drug sensitivity, thiazolyl blue (MTT) cytotoxicity assay was used. Cell cycle was detected by flow cytometry (FCM). Results Whole length of RPS13 cDNA gene was amplified by RT-PCR. The sense, antisense eukaryotic expression vectors were constructed by the directed cloning of the target genes into eukaryotic expression vector pcDNA 3.1(+). RNA dot blotting assay suggested that mRNA level of the RPS13 was up-regulated in the sense recombinant vector transfected cells, and down-regulated in the antisense recombinant vector transfected cells. By MTT cytotoxicity assay, the enhanced resistance to adriamycin, 5-fluorouracil and vincristine was found in the RPS13 sense recombinant vector transfected SGC7901 cells. RPS13 antisense recombinant vector rendered SGC7901/VCR cells partially sensitive to mitomycin and vincristine. Cell cycle analysis suggested that the proportion of G1, S, and G2 cells was 47.0%, 33.2% and 19.8% respectively in up-regulated RPS13 cells; the proportion of G1, S and G2 cells was 62.9%, 1.0% and 36.1% respectively in down-regulated RPS13 cells. Conclusions RPS13 may take part in the mediation of MDR in gastric cancer cells.

The specific binding capacity of androgen receptor (AR)and estrogen receptor (ER)in the peripheral lymphocytes was estimated by radioligand binding assay in 130 diabetic patients (type Ⅰ 18 cases and type Ⅱ 112 cases). Results were as follows:1)plasma estradiol (E2) of diabetic patients was significantly lower than that of the controls (P

To explore the expression and function of MG 7 Ag on gastric cancer cell line SGC7901 and its drug resistant subline,SGC7901/VCR, with different resistance index (0 3, 0 7, 1 0) The expression of MG 7 Ag on SGC7901 and SGC7901/VCR cells was determined by immunohistochemical method and flow cytometry (FCM) MTT assay was used to explore the effects of monoclonal antibody MG 7 on drug sensitivity of gastric cancer cells FCM was used to explore the effects of MG 7 on adriamicine accumulation of SGC7901/VCR cells SGC7901/VCR cells exhibit increasing positive staining of MG 7 than SGC7901, according to the increasing resistance index Sensitivity of vincristine of both SGC7901 and SGC7901/VCR cells was reduced after being treated with MG 7 And SGC7901/VCR cells showed decreased adriamicine accumulation when they were incubated with MG 7 Therefore, the conclusion is that MG 7 Ag may be a novel molecule associated with multidrug resistance of gastric cancer, and play an important role in maintaining the drug resistant phenotype of SGC7901/VCR cells.