[Effect of endoplasmic reticulum stress induced by all-trans retinoic acid on apoptosis of FLT3-ITD mutated leukemia cells by activating autophagy in FLT3-ITD mutated protein].

Objective: Endoplasmic reticulum stress(ERS)was used as the research emphasis to further investigate the mechanisms of apoptosis of FLT3-ITD-mutated leukemia cells and decreased expression of FLT3-ITD mutated protein induced by all-trans retinoic acid(ATRA). Methods: FLT3-ITD-mutated leukemia cell lines(MV4-11 and MOLM13)were treated with ATRA. Flow cytometry was conducted to assess cell apoptosis. Real-time fluorescent quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of ERS-related and autophagy-related genes and protein, respectively. Results: A low-dose ATRA further increased FLT3-ITD cells and ERS levels. ATRA acted on the ERS-related PERK/eif2ɑ signaling pathway and continued to increase the ERS of FLT3-ITD cells, resulting in an upregulation of apoptotic gene CHOP expression. After the treatment with ATRA, FLT3-ITD protein in FLT3-ITD cells was decreased. Of the two main ERS-related protein degradation pathways, ER-associated degradation(ERAD)and ER-activated autophagy(ERAA), the expression of ERAD-related protein ATF6 in FLT3-ITD cells was not significantly changed on ATRA, whereas the expression of ERAA-related proteins Atg7 and Atg5 were significantly increased. Conclusions: ATRA further raises the ERS level of FLT3-ITD cells continuously by activating the ERS-related PERK/eif2ɑ signal pathway and induces FLT3-ITD protein autophagy degradation through ERAA pathway, which induces apoptosis of FLT3-ITD-mutated leukemia cells. These results provide preliminary evidence on the use of ATRA in the treatment of refractory leukemia with FLT3-ITD.

Prognostic role of Wnt7a expression in ovarian carcinoma patients.

Wnt7a is a secreted glycoprotein that regulates normal cellular proliferation and differentiation as well as tumorigenesis and progression. The aim of this study was to investigate the expression and prognostic significance of Wnt7a in ovarian carcinoma. Wnt7a expression was immunohistochemically examined in normal ovaries (n=15), benign tumors (n=50) and ovarian carcinomas (n=78). The correlation of Wnt7a expression with clinicopathological parameters and survival was evaluated. Wnt7a expression was higher in ovarian carcinomas compared to normal ovaries and benign tumors (p<0.001 and p=0.001, respectively). Wnt7a positive expression was significantly correlated with serous subtype (p<0.001), elder age (p=0.017), advanced stage (p<0.001), high grade (p=0.001), a high degree of ascitic fluid volume (p=0.015) and high CA125 expression (p=0.025). Wnt7a was found to be a significant prognostic factor in univariate and multivariate analysis. High Wnt7a expression in ovarian cancer may be associated with poor prognosis.

Interleukin-10 -819 promoter polymorphism associated with gastric cancer among Asians.

Studies investigating the association between interleukin-10 -819 promoter polymorphism and gastric cancer risk report conflicting results. This study aimed to summarize quantitatively the evidence for such a relationship. Two investigators independently searched the Medline (January 1966-January 2009) and Embase (January 1980-January 2009) databases for eligible studies to be included in a meta-analysis. Six case-control studies, which included 681 gastric cancer cases and 1621 control subjects were selected. Combined results for all studies showed that there was no significant difference in genotype distribution (TT, TC or CC) between gastric cancer patients and control subjects. When stratifying for race, results were similar except that Asian patients with gastric cancer had a significantly lower frequency of TT and a higher frequency of TC than Asian control subjects. When stratifying by location and Lauren's classification of gastric cancer, there was no significant difference in genotype distribution between patients with gastric cancer and control subjects. This meta-analysis suggests that the interleukin-10 -819 promoter polymorphism may be associated with gastric cancer in Asians.

Body mass index evaluating donor hepatic steatosis in living donor liver transplantation.

INTRODUCTION: Evaluation of graft hepatic steatosis is important for the safety of the donor and the recipient in living donor liver transplantation. It is necessary to establish a noninvasive evaluation method to avoid performing a liver biopsy for donor safety. The aim of this study was to identify independent factors that correlated with hepatic steatosis to create a noninvasive method to evaluate hepatic steatosis. METHODS: We retrospectively collected data from 105 living donors. No prisoners were used to obtain the grafts, all of which underwent postoperative histological evaluation for hepatic steatosis. Preoperative clinical and biochemical variables were examined with univariate analyses, and filtered variables further examined with ordinal regression analysis. RESULTS: Eighty (76.2%) donors showed no hepatic steatosis, 15 (14.3%), mild steatosis, and 10 (9.5%), moderate steatosis. In ordinal stepwise regression analysis, body mass index (BMI; P = .000) was the only independent factor that correlated with the grade of hepatic steatosis. Preoperative biochemical parameters were not significantly correlated with hepatic steatosis. A regression model based on BMI was created to evaluate hepatic steatosis grade. Furthermore, individuals with a BMI > 27.5 were most likely to show moderate steatosis, and those with BMI < 23 likely to display no or mild steatosis. CONCLUSION: BMI can help to identify the grade of hepatic steatosis among living donors. BMI is also useful to select living donors for a preoperative liver biopsy before liver transplantation.

The robotic radiosynthesis of 5-[(18)F]fluoro-2'-deoxyuridine and its biological characterization.

5-[(18)F]fluoro-2'-deoxyuridine ([(18)F]FUdR) was synthesized using a robotic system as a proliferation probe for PET. [(18)F]FUdR was prepared via radiofluorodestannylation reaction from its organotin precursor. Biodistribution study and microPET imaging of [(18)F]FUdR in NG4TL4 sarcoma-bearing FVB/n mice were performed. The tumor-to-blood and tumor-to-muscle ratio increased steadily from 15 (1.81 and 3.42) to 120min (9.10 and 11.9) post injection. The dynamic microPET imaging demonstrates remarkable radioactivity retention in the tumor, which is consistent with the results of biodistribution study.

Analysis of anthropometric growth trends and prevalence of abnormal body status in Tainan elementary-school children.

Objectives of this study were to examine the prevalence of over/underweight or obesity in Chinese children and investigate the trend of anthropometric change through the years. Cross-sectional measurements on randomly selected 6,373 Tainan elementary-school children were conducted in 1997. Anthropometric parameters such as height, weight, body mass index (BMI), triceps skinfold thickness (TSF), mid-arm circumference (MAC) and body-fat percentage (%FAT) were measured. Girls and boys had an average of 4.8 cm and 5.1 cm, or 3.7% and 3.9% increase in height, and 5.5 kg, 6.2 kg, or 19.9% and 22.2% increase in weight when compared to data of nationwide survey in 1986-88. If the height and weight were compared to the data of nationwide survey in 1993-1996, Tainan girls and boys would have similar height but have averaged 3.4% and 4.7% heavier weight. Mean BMI reached 19.4 kg/m2 for girls and 19.6 kg/m2 for boys of age 12 to 13. Mean %FAT of girls was 24.3% and of boys was 23.7%. When using weight-for-length index (WLI) larger than 1.2, mean weight exceeding 120% of age-and-sex specific mean weight, %FAT exceeding 30% to evaluate prevalence of obesity, results would be 42.1%, 17% and 22.0% respectively. In conclusion, both sexes had faster growth in weight than in height in recent 10 years. Boys had significantly higher weight, WLI, BMI, MAC than girls, while girls had significantly higher TSF and %FAT than boys. Prevalence of obesity is highly method-dependent. Appropriate index and cutoff values need to be developed.

Nutritional evaluation of Chinese working women in the city of Tainan, Taiwan.

Nutritional survey was conducted in 1994 in Tainan City, southern Taiwan. Total food duplicate samples were collected from 52 women volunteers. Clinical examinations, anthropometry, hematology and serum biochemistry were also conducted. The intakes of nutrients were estimated from the weights of food items in reference to the standard food composition tables for Taiwanese. On average, the participants took 1,973 kcal energy, 69 g protein, 73 g lipid and 269 g carbohydrate per day. Animal-based foods accounted for 49% and 36% of protein and lipid sources, respectively, but fish and shellfish contributed only 11% for protein and essentially nil for lipid. Lunch was the most substantial meal of the day. When classified by age (i.e., 22-29, 30-39 and 40-66 year-old groups), no age-related difference was detected among the three groups in all nutrients except for crude fiber. Comparison with recommended dietary allowance (RDA) for Taiwanese, the insufficiency ratios were more than 50% for minerals (i.e., Fe and Ca) and vitamins (except for vitamin C). Excess in the lipid energy ratio (> 30%) was observed in 60% of the study population. In agreement with this high lipid intake, 17% of the participants had BMI of > 25, and triglyceride levels were elevated (> 150 mg/100 ml) in 27%. There were no anemic case despite the low Fe intake (14 mg/day).

Trace elements burden in geriatric hemodialysis patients: a prospective multicenter collaborative study.

INTRODUCTION: Hemodialysis therapy and the aging process have been reported to interfere with the trace element (TE) status in the body. This multicenter collaborative study on blood levels of TE in geriatric hemodialysis (HD) patients was carried out with an aim to clarify the impact of the aging process and HD therapy on the TE status in such patients. METHODS: One hundred and fifty-one HD patients (65 male, 86 female), all aged over 60 (68.2+/-3.86 y), and 112 elderly controls (58 male, 54 female) with a mean age of 67.5+/-3.03 were enrolled. All patients underwent standard HD for at least 6 months. The artificial kidneys used were hollow-fiber dialyzers of cellulose membranes. Water used for HD was prepared by reverse osmosis. Blood was collected in the morning prior to dialysis and after fasting. Atomic absorption spectrophotometry was applied to measure blood levels of Pb, Cd and Hg as well as plasma levels of Cu, Zn and Al. Data are presented as mean +/- SEM. Student's t-test and linear regression were applied for statistics. RESULTS: Our geriatric chronic HD patients showed a marked elevation of blood Al and decreased plasma Zn concentrations. The blood levels of Cu, Cd, Pb and Hg were within normal limits. The blood concentrations of Al, Cu and Pb were significantly higher in HD patients than in the normal elderly controls, whereas Cd and Hg were similar in both groups, and Zn were lower in HD patients. Plasma Zn value decreased as dialysis duration increased, however there was a reversely linear correlation between plasma Zn and age. CONCLUSIONS: This data reported can be regarded as a starting point and may serve as an insight to further studies on TE imbalances in geriatric and chronic HD populations.

Successful management of a pregnancy with maternal phenylketonuria: report of a case.

Maternal phenylketonuria (PKU) is associated with significant complications such as mental retardation, microcephaly and congenital heart defects in nonphenylketonuric offspring. Dietary control with a low phenylalanine diet during the gestation period is effective in improving perinatal outcome in these cases. We present the case of a 27-year-old woman with classical features of PKU who had previously given birth to three babies, all of whom died of congenital heart disease. A low phenylalanine diet was started one month prior to the pregnancy and satisfactory fetal outcome was achieved.