Significance of IL28RA in diagnosis of early pancreatic cancer and its regulation to pancreatic cancer cells by JAK/STAT signaling pathway - effects of IL28RA on pancreatic cancer.

OBJECTIVE: To explore the significance of IL28RA in diagnosis of early pancreatic cancer and its regulation to pancreatic cancer cells by the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. PATIENTS AND METHODS: A total of 81 patients with early pancreatic cancer were enrolled as a pancreatic cancer group, and 81 patients with benign pancreatic diseases were enrolled as a benign disease group. Western blot was adopted to analyze the serum IL28RA expression of the two groups and its diagnostic value in early pancreatic cancer. A pancreatic cancer cell model was constructed, and the IL28RA expression in pancreatic cancer cells, PANC-1 and BXPC-3, was up-regulated to explore the biological function of pancreatic cancer cells after up-regulation of IL28RA and the effects on JAK-STAT signaling pathway. RESULTS: Lowly expressed in serum of patients with pancreatic cancer, IL28RA showed a sensitivity of 80.25%, specificity of 75.31%, and area under the curve (AUC) of 0.846 in diagnosis of early pancreatic cancer. It was found that up-regulation of IL28RA expression in pancreatic cancer cells inhibited proliferation and invasion abilities of pancreatic cancer cells, increased apoptosis rate and expression of pro-apoptotic protein bax, decreased expression of anti-apoptosis protein bcl-2, and significantly inhibited phosphorylation level of JAK2 and STAT3 proteins. CONCLUSIONS: IL28RA is lowly expressed in pancreatic cancer patients, and has certain diagnostic value for early pancreatic cancer. Its up-regulated expression can inhibit the proliferation and invasion of pancreatic cancer cells, and promote their apoptosis by inhibiting the activation of JAK-STAT signaling pathway.

Human infection with novel G3P[25] rotavirus strain in Taiwan.

Genotype P[25] rotaviruses are rare and to date have been reported to occur only in a few countries of mainland Asia. Here we report the molecular characterization of a novel human rotavirus genotype combination, G3P[25], detected in a 17-month-old child hospitalized due to severe gastroenteritis during 2009 in central Taiwan. Sequencing and phylogenetic analysis of the VP4 gene demonstrated a distinct origin from other strains bearing the P[25] VP4 gene, whereas the VP7, VP6 and NSP4 gene phylogenies identified common origins with cognate genes of other, presumed human-porcine reassortment Taiwanese strains. These results suggest that interactions between human and animal strains appear to contribute to the generation of genetic and antigenic diversity of rotavirus strains, with potential public health importance in Taiwan.

Gastroenteritis in a Taipei emergency department: aetiology and risk factors.

A matched case-control study was used to determine pathogens and risk factors associated with gastroenteritis in a Taipei Emergency Department. Viruses (40.0%) were the leading cause of gastroenteritis, with noroviruses the most prevalent (33.2%). Bacteria were found in 26.0% of all cases, mostly suspected diarrheagenic E. coli (22.2%), followed by Salmonella spp. (5.4%) and Vibrio parahaemolyticus (4.2%). Giardia lamblia was identified in 16.4% of all cases. Statistical significance was noted for seven risk factors: taking antacids before gastroenteritis (OR = 3.91; 95% CI, 2.13, 7.15), other household members with gastroenteritis (OR = 5.18; 95% CI, 2.09, 12.85), attending a banquet (OR = 1.93; 95% CI, 1.25, 2.98), eating out (OR = 2.35; 95% CI, 1.30, 4.23), drinking bottled water (OR = 1.72; 95% CI, 1.07, 2.75), eating honey peaches (OR = 3.26; 95% CI, 1.24, 8.58), and eating raw oysters (OR = 3.24; 95% CI, 1.02, 10.28). Eating out was identified as the highest risk behavior, as measured by population attributable risk fraction (PAR) (50.9%). Respective PAR values for drinking bottled water, attending a banquet and taking antacids before illness were 19.7%, 19.6% and 17.6%. Of these, additional research on bottled water appears to be the highest priority, because this is the first time it has been identified as a risk factor for gastroenteritis.

Characteristics of norovirus gastroenteritis outbreaks in a psychiatric centre.

Noroviruses are an important aetiological agent of acute gastroenteritis. They are responsible for large outbreaks of disease in the community, hospitals and long-term-care facilities. The clinical manifestations of norovirus outbreaks in psychiatric units are rarely described. The disease burden and impact highlight the importance of timely notification and investigation of these outbreaks. We analysed the characteristics of four norovirus outbreaks which occurred during a 3-year period in an in-patient psychiatric care unit. A total of 184 patients were affected which included 172 hospitalized patients, seven healthcare workers (HCWs) and five psychiatric nursing-home residents. The mean incidence rate of norovirus gastroenteritis (NVG) in hospitalized patients during these outbreaks was 12·7%. These outbreaks were characterized by higher incidence in middle-aged male patients, predominant sickness of diarrhoea, short duration of illness, peaks in late winter and early spring, and higher susceptibility in acute psychiatric patients. HCWs had longer duration of illness than psychiatric patients. More than 10% of affected patients experienced ≥ 2 infections. Infection control measures were instituted and a comprehensive, responsive standard operating procedure for NVG and outbreak management was developed. After implementation of these measures, no further outbreaks of NVG occurred during the study period.

Hospital-based surveillance and molecular epidemiology of rotavirus infection in Taiwan, 2005-2007.

To determine the distribution of rotavirus strains and facilitate vaccine policy decisions in Taiwan, active hospital-based gastroenteritis surveillance was conducted in three sentinel hospitals. From 1 January 2005 to 31 December 2007, a total of 3435 children less than 5 years old with gastroenteritis were enrolled. The presence of rotavirus was documented by enzyme immunoassay (EIA), and the G and P genotypes were determined by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing methods. Results confirmed that 856 (25%) of these gastroenteritis admissions were EIA-positive for rotavirus and 448 (52%) of the rotavirus positive admissions were less than 2 years old. The most prevalent rotavirus genotypes were G1P[8] (40%), followed by strains G3P[8] (27%), and G9P[8] (17%). These data will help inform decisions as to whether rotavirus vaccine should be considered for inclusion into Taiwan's National Immunisation Programme.

Genetic diversity of noroviruses in Taiwan between November 2004 and March 2005.

Noroviruses are a major health burden and are responsible for the majority of outbreaks of gastroenteritis in the world. Human noroviruses can be genetically divided into two main genogroups (GI and GII) and subdivided into many genotypes. In this study, stool specimens collected from 12 outbreaks of gastroenteritis in Taiwan were screened for viral agents between the 23rd of November 2004 and 9th of March 2005. Noroviruses were detected in all outbreaks. We detected six different norovirus genotypes: GI/11, GI/14, GII/3, GII/4, GII/6, and GII/18. Noroviruses belonging to GII/4 were dominant, 50 of 60 (83%) sequences, and were detected in 10 of 12 outbreaks. Furthermore, the norovirus GII/4 strains were detected throughout Taiwan, demonstrating their widespread distribution. We also found that three outbreaks had noroviruses from multiple genotypes. Our results have shown for the first time that noroviruses are an important cause of gastroenteritis in Taiwan.

Induction of antitumor immunity with combination of HER2/neu DNA vaccine and interleukin 2 gene-modified tumor vaccine.

The therapeutic effects of both cytokine-secreting tumor vaccine and DNA vaccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytokine-secreting MBT-2 cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-expression vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice at all. Tumor formation decreased significantly for the MBT-2-GM-CSF cells. MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by irradiation and tested as tumor vaccines. The irradiated MBT2-IL-2 cells could complete protect mice from the growth of the preexisting tumor cells, and the immune memory lasted for 8 months. On the other hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective. When the loading tumor mass increased, all tumor vaccines lost protective effects. DNA vaccine encoding the tumor antigen neu was additionally tested to improve the therapeutic efficacy. Coinjection of 60 microg pSV-neu DNA was effective in enhancing the antitumor effects of MBT2-IL-2; however, DNA vaccine alone cannot prevent the progression of the preexisting tumor. Immunohistochemical analysis of tumor infiltrate revealed massive increase of CD4+ lymphoid cells in the group of mice treated with both DNA vaccine and IL-2-secreted tumor vaccine. Western blotting demonstrated the presence of anti-neu antibody in the serum from immunized mice. In contrast, combination of DNA vaccine and MBT-2-GM-CSF has no additive effect. The results indicate the combination of DNA vaccine and IL-2-secreting tumor vaccine can additionally improve therapeutic efficacy, and the efficacy is correlated with the increase of CD4+ T lymphocytes and anti-neu antibody.

Source parameters for stick-slip and for earthquakes.

Source parameters of stick-slip friction events measured in the laboratory show particle and rupture propagation velocities which are similar to those observed for earthquakes and inferred from seismic source theory. This dynamic similarity strongly supports the idea that stick-slip is the mechanism for shallow earthquakes.