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Background: Mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinases (ERK), c-Jun NH 2 -terminal kinases (JNK) and p38 MAP kinase (p38 MAPK) are important intermediates of the signal-transduction pathway from the cell surface to the nucleus. Expression of cyclooxygenase (COX)-2, associated with proliferation, apoptosis or both of gastrointestinal cancer cells, is mediated through MAP kinase families. However, the correlation between respective MAP kinase signals and COX-2 in the proliferation of gastric and colon cancer cells has not been well elucidated. Aim: We examined the effect of selective inhibitors of MAP kinases and COX-2 on serum-induced proliferation of gastric (MKN45) and colon (HT29) cancer cells. Methods: After 24-h serum starvation, cancer cells were stimulated with 2% serum and COX-2 inhibitors (NS398 10 μmol/L, or etodolac 100 μmol/L) or 1 h after preincubation with inhibitors for ERK (PD98059 20 μmol/L) or p38 MAPK (SB203580 10 μmol/L). Phosphorylated MAP kinases and COX-2 protein were evaluated by Western blotting, and the proliferation of cancer cells was estimated by 3 H-thymidine incorporation. Transcription factors nuclear factor-KB and CREB were assayed by an electorophoretic mobility shift assay. Results: Serum increased the proliferation of MKN45 and HT29 cells by 280% and 200%, respectively, compared with the control levels (100%). In both cancer cells, phosphorylated MAP kinases were increased within 30 min after stimulation. PD98059 and SB203580 inhibited the serum-induced proliferation of MKN45 by 21% and 51% and of HT29 by 81% and 69%, respectively. NS398 and etodolac inhibited the proliferation of HT29 by 21% and 41%, respectively, but not that of MKN45. PD98059 and SB203580 also suppressed serum-induced expression of COX-2 protein in HT29 cells. In addition to the activation of MAP kinases and COX-2, activities of nuclear factor-KB and CREB were also increased during HT29 cell proliferation. Conclusions: These results suggest that the correlation of MAP kinases with COX-2 induction for cell proliferation differs between MKN45 and HT29 cells.

Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS FNAB) is a relatively new technique for obtaining specimens with excellent imaging power. The convex type of echoendoscope used with EUS FNAB provides images perpendicular to the endoscope, which differ from those of popular radial echoendoscopes and, hence, require different usage techniques. Color flow imaging is used to avoid the vessels in and around the mass during puncturing. EUS FNAB for submucosal tumors is sometimes difficult because the needle slips easily, and the gastrointestinal wall tends to be stretched when pushing the needle, which can be solved by making a dimple on the wall before puncturing. Lesions of the pancreas head, especially those at the uncus, and lymph nodes near the superior mesenteric artery are also difficult because of their distance from the endoscope and the resultant bending of the needle. Tissue sampling is more successful when the angle between the endoscope and the needle is kept at just less than 45 degrees, as this helps to transmit the hand force to the needle effectively. The complication rate of EUS FNAB is reportedly 1–2%, and so the technique is considered a safe modality, except for cystic lesions of the pancreas. Recent histological evidence is needed before applying medical therapies, such as chemoradiation and surgery, especially when imaging modalities alone cannot supply the evidence of malignancy; hence increasing importance of EUS FNAB is expected.