Single nucleotide polymorphisms on SHIP2 is associated with Type 2 diabetes mellitus in Chinese Han population.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance in the target tissue of insulin with insufficient insulin secretion in pancreatic ß-cells. Src homology 2-containing 5'-inositol phosphatase 2 (SHIP2) is a lipid phosphatase that hydrolyzes PI3-kinase product PI(3,4,5)P3 to PI(3,4)P2, which contributes to the negative regulation of insulin signaling both in vitro and in vivo. Some polymorphisms of SHIP2 have been reported to be associated with the metabolic syndrome including T2DM and hypertension in British, French and Japanese T2DM population. PATIENTS AND METHODS: In our present study, we investigated the relation between single nucleotide polymorphisms (SNPs) on SHIP2 gene and the pathogenesis of T2DM in Chinese Han population. RESULTS AND CONCLUSIONS: Our results indicated that the genotype and allele frequency of SHIP2 (+1893CC/AA) locus in T2DM patients showed significantly different from between the healthy control population. In addition, the G allele of SHIP2 (+2945A/G) seemed to increase the susceptibility to hypertension for T2DM patients.

Correlative study on the expression of p53 and DNA ploidy in acute nonlymphocytic leukemia.

We used the flow cytometric immunoassay to study the correlation between the rumor-suppressor gene product p53- and the DNA ploidy in 30 de novo cases of acute nonlymphocytic leukemia (ANLL). The results showed that 15 cases were positive expression for p53. As compared with p53 negative (p53) cases, the patients with positive p53 (p53+) had higher percentage of bone marrow blasts and lower peripheral leukocyte and platelet counts, which had no influence on the complete remission rate. Before treatment, DNA diploidy was seen in 18 cases including 12 p53- cases, and DNA aneuploidy in 12 cases including 9 p53+. After therapy, aneuploidy could be transformed into diploidy. Patients with P53+ or having aneuploidy in complete remission were at risk for early relapse. We believe that p53 may be involved in the process of leukemogenesis and progression of ANLL.

[Quantitative study of P53 gene protein expression in the benign disease and cancer of breast].

P53 gene protein expression in breast benign disease and cancer was studied quantitatively using flow cytometry and cellular immunofluorescence staining technique. The results showed that P53 positive expression rate and content were lower in the benign disease of breast than that of the breast cancer. The content of P53 protein expression was also associated with the DNA ploidy in breast cancer. The content of P53 protein expression was higher in tumors with aneuploid cells than those with the diploid ones. The five year survival rate were also lower in P53 protein expression positive cases than the P53 negative one's.

Smooth muscle tumors of the gastrointestinal tract. Expression of ras P21 oncogene product and the association with clinicopathology.

Quantitative analysis of ras oncogene product P21 was performed on paraffin blocks from 55 smooth muscle tumors of the gastrointestinal tract by immunofluorescence and flow cytometry. No positive evidence for P21 was found in 5 cases of normal smooth muscle tissues. Eight of 14 leiomyomas were P21 positive (57%) but all of them were lower expressed with fluorescence index (FI) < 1.25, whereas a total of 29 leiomyosarcomas and 12 potential malignant smooth muscle tumors were found to be P21 positive (100%), and the majority were overexpressed with FI > 1.25 (P < 0.005). ras P21 was overexpressed significantly in the tumors with mitotic counts of more than 1/10 high power field (P < 0.005). It was also overexpressed significantly as soon as the mild cytologic atypia of the tumor was found (P < 0.005). Five-year survival rate was significantly higher in the patients with lower-expression of ras P21 than those with overexpression (P < 0.005). It was suggested that the expression of ras oncogene product P21 could be used as an objective parameter in distinguishing malignants from benigns and predicting the prognosis of the patients with smooth muscle tumors of the gastrointestinal tract.

[Quantitative study of oncogene p21ras expression in premalignant lesion and carcinoma of the stomach].

The oncogene P21ras expression in premalignant lesions and carcinomas of the stomach was quantitatively studied by flow cytometry and immunofluorescence methods and the relation of P21ras to DNA ploidy and cellular proliferation was analysed. The results showed that P21ras expression was higher in carcinomas than premalignant lesions of the stomach. The fluorescence index in P21ras expression increased with the rise in histological grade. DNA ploidy correlated with the amount of P21ras expression.

[Analysis of DNA ploidy in 3,050 cases of malignant tumors].

DNA ploidy in paraffin-embedded sections collected from 3,050 cases of malignant tumors was analysed by flow cytometry. The result showed that DNA index distribution was ranged from 0.6 to 2.6, mostly at 1.10 to 1.85. DNA ploidy distribution showed that 536 cases (17.6%) were DNA diploid tumors; 2,227 cases (73.0%) were tumors with DNA aneuploid; 126 cases (4.1%) accompanied with tetraploid; and 161 cases (5.3%) with multiploid. Additionally, relationship between the histologic type as well as the grading and DNA ploid were also analysed in 1,117 cases of malignant tumors. The results indicated that DNA index was not correlated with the histologic typing, but correlated with the histologic grading (grade I DI = 1.24, grade II DI = 1.38, grade III DI = 1.51). It's considered that flow cytometry DNA grade index may be an objective and precise quantitative marker in judging the degree, grade and differentiation of tumor malignancy.

Studies on pathological morphology, clinical features and nuclear DNA contents by flow cytometry in adrenal neoplasms.

Pathological morphology, clinical features and nuclear DNA contents determined by flow cytometry (FCM) were studied in 11 cases of normal adrenals and 41 cases of adrenal neoplasms. It was found that despite differences in clinical manifestations and in degrees of cellular atypia of the adenomas their DNA contents were the same as in normal adrenals. On the other hand, the pheochromocytomas were benign in nature, but most of them (16/19) showed DNA aneuploidy and the DNA indices were correlated with their clinical and morphological features.

[Effect of sodium artesunate on Plasmodium yoelii analysed by flow cytometry].

The effect of sodium artesunate on Plasmodium yoelii-infected mouse erythrocytes was analysed by flow cytometry. The results showed that malarial DNA content in experimental group was obviously decreased 2-5 hours after the drug was administered, fluorescence distribution of malarial DNA almost disappeared within 24 hours after the administration. Thus we deem that sodium artesunate can inhibit the DNA synthesis in P. yoelii.

[DNA ploidy in gastric precancerous lesions].

A study on DNA ploidy by flow cytometry was carried out on human gastric tissues with normal mucosa, chronic atrophic gastritis, varying grades of gastric dysplasia or early carcinoma. The results showed that no DNA aneuploidy was found in all 8 cases with normal mucosa, 13 cases with chronic atrophic gastritis, and 18 cases with grade I gastric dysplasia. DNA aneuploidy was found in 2 among 19 cases with grade II gastric dysplasia, in 8 among 14 cases with grade III gastric dysplasia, and in all 12 cases with early gastric cancer. There was significant differences in DNA index and S% phase cells from cases with gastric dysplasia of varying grades. The findings indicate that DNA aneuploidy might be a marker of malignant change of gastric precancerous lesions.

[Flow cytometric DNA content analysis in thyroid carcinoma].

DNA content and proportion of Phase S cells in 69 paraffin embedded thyroid tumors (15 adenomas and 64 adenocarcinomas) were analysed by flow cytometry. The results showed that 14/15 adenomas were diploid; DNA content was abnormal in 1 papillary adenoma (DNA index 1.14). In the 64 cases of adenocarcinomas, 53 were aneuploid and 11 near diploid. The DNA content and proportion of Phase S cells were closely related to degree of malignancy and prognosis.

[Flow cytometry in exfoliative cytology of malignant tumor].

Exfoliative cells from 170 cases of malignant tumor and 70 cases of normal tissue were studied by flow cytometry. The results showed that 155/170 (91.2%) cases were positive and 15/170 (8.8%) were false-negative; 4/70 (6.0%) cases were false-positive. The authors consider that flow cytometry has achieved a diagnostic accuracy comparable to the conventional cytology. Flow cytometry is a useful supplementary method in the diagnosis of tumors.

Flow cytometric DNA-ploidy as a prognostic indicator in oral squamous cell carcinoma.

In an attempt to evaluate the significance of DNA-ploidy as an objective prognostic indicator of oral squamous cell carcinoma, a retrospective analysis of 70 paraffin-embedded specimens using flow cytometry was performed. Forty-one patients (58.6%) had aneuploid tumors and 29 patients (41.4%) had diploid DNA distribution patterns. There was a significant difference in 5-year disease-free survival rates between patients with aneuploid and diploid tumors. The difference in cervical metastatic rates between aneuploid and diploid group approximated statistical significance. No obvious correlation was observed between DNA indices and histologic grade, clinical stage or tumor size. It is concluded that patients with aneuploidy primary tumors have a significantly poorer prognosis and higher risk for regional metastases than those with diploid tumors.

[Flow cytometry in analysis of precancerous lesions of the esophagus].

DNA content of the severe dysplasia cells in the esophageal epithelium was quantitatively analysed using flow cytometry and compared with those of the normal, mild dysplasia and cancer cells. The results showed that DNA index of the severe dysplasia cells was 1.27 +/- 0.11 and there was a significant difference between its value and those of the normal (1.0 +/- 0.02), mild dysplasia (1.01 +/- 0.03) and cancer cells (1.73 +/- 0.35). The DNA content of severe dysplasia cells lies between the normal and cancer cells. The hyperplasia degree of the severe dysplasia cells parallels their DNA contents. This study indicates that flow cytometry is a useful supplementary tool for diagnosis of the tumor.