No abstract

Pancreatic cancer remains one of the "difficult-to-treat" cancers. Signaling of androgen receptor (AR), one of the nuclear receptors, in the pancreas may be related to carcinogenesis. Higher interleukin-6 (IL-6) levels have been observed in pancreatic cancer patients. It is also well known that IL-6 affects the AR signaling pathway and that AR is important for cell migration activities. We demonstrated that IL-6 enhances the phosphorylation of STAT3 and MAPK, which in turn enhances AR-mediated transcription in pancreatic cancer cell lines. This activity was blocked by a pharmacological inhibitor of the JAK/STAT signaling pathway, AG490, and one of the MAPK signaling pathways, U0126. IL-6 also enhances pancreatic cancer cell migration in the presence of AR. This activity is blocked by AR-siRNA. IL-6 acts as a positive regulator in AR signaling, providing further insight into the progression of pancreatic carcinogenesis.

Hepatitis A virus (HAV) infection is still an important issue worldwide. A distinct set of viruses encode proteins that enhance viral cap-independent translation initiation driven by an internal ribosome entry site (IRES) and suppress cap-dependent host translation. Unlike cytolytic picornaviruses, replication of HAV does not cause host cell shut off, and it has been questioned whether HAV proteins interfere with its own and/or host translation. HAV proteins were coexpressed in Huh-7 cells with reporter genes whose translation was initiated by either cap-dependent or cap-independent mechanisms. Among the proteins tested, HAV proteinase 3C suppressed viral IRES-dependent translation. Furthermore, 3C cleaved the polypyrimidine tract-binding protein (PTB) whose interaction with the HAV IRES had been demonstrated previously. The combined results suggest that 3C-mediated cleavage of PTB might be involved in down-regulation of viral translation to give way to subsequent viral genome replication.

SUMMARY Eighty-eight Japanese patients with rheumatoid arthritis and 104 normal Japanese persons were typed for HLA A, B, C, and DR antigens. The frequency of HLA DR4 was 70 * 5 % in patients compared with 461 % in normal controls (P<0 00 1). However, a sex difference in the frequency of HLA DR4 in patients was noted. HLA DR4 was found in 80 6% of male patients, which was highly significant compared with controls (P<0 '0005), while only a borderline increase to 60 5% was found in female patients (P<0 05). In addition, the frequency of HLA DR2 was remarkably low in male patients. These suggest the possible heterogeneity of rheumatoid arthritis in Japanese. In the study reported here Japanese patients with rheumatoid arthritis were typed for HLA DR antigens to see whether the same association was present as was the case in the Caucasian patients. Materials and methodsEighty-eight patients who were diagnosed as classical or definite rheumatoid arthritis according to the

HAV IRES derived from clinical isolates have various activities. Bicistronic reporter assay using clinical isolates may be another useful tool for testing antiviral activities like those of amantadine and the new acridines and hydrazones recently reported.