PURPOSE: 5-fluorouracil is one of the widely used chemotherapeutic agent whose metabolic product forms tight covalent binding complex with thymidylate synthase (TS) and thereby blocks the DNA synthesis process. Expression of TS has been studied as a mechanism of drug resistance and as a prognostic factor for various cancers. METHODS: The relation between TS expression in surgically resected specimens and clinicopathologic features was examined in 62 patients with gastric cancer. Immuno histochemical demonstration of the protein was achieved using an anti-TS monoclonal antibody. RESULTS: In Lauren's classification, TS expressions of the intestinal type and the diffuse type were 21.93% and 14.96% respectively (P=0.02). And TS expression in a group with lymphatic invasion was higher (26.15%) than that in a group without lymphatic invasion (16.15%)(P=0.0001). There were no significant differences between the TS expressions associated with other clinicopathologic features (P>0.05). CONCLUSION: For the purpose of assessing the applicability of TS expression as a prognostic factor and as a mechanism for drug resistance, assessment of TS expression must be standardized. Although direct correlations between TS expression and other clinicopathologic features were found only in Lauren's classification and lymphatic invasion, further investigations of the relation between TS expression and drug resistance of 5-FU must be continued to provide data for choosing chemotherapuetic agents for use in patients with gastric cancer.
Classification ; DNA ; Drug Resistance ; Fluorouracil ; Humans ; Stomach Neoplasms* ; Thymidylate Synthase*

These study was designed to observe the appearance and the characteristics of apoptotic cells during the development of knee joint in rat. The fetus were collected on the 16th, 17th, 18th, 19th, and 20th day of pregnancy. In this study, TUNEL staining, electron microscopic investigation and immunocytochemical gold labeling techniques were used. In the immuno-cytochemical gold labeling techniques, primary antibodies were used, which were to be polyclonal rabbit anti-mouse/ rat Bax, polyclonal rabbit anti-tissue transglutaminase C, and polyclonal goat anti-cpp32p20. The samples were observed under JEOL 1200 EX-II transmission electron microscope. The results were as follows. 1. In a 16-day-old fetus, between femur and tibia cartilages, mesenchymal cells were observed. Mesenchymal cells had marginated heterochromatin and dilated rough endoplasmic reticulum. 2. In a 17-day-old fetus, the knee joint clefts were first formed. In the primordial cruciate ligaments between the cartilages, capillaries were scattered. The apoptotic cells, which had fragmented and condensed nucleus, showed in the synovium. And necrotic cells, which had nuclear chromatin margination, perinuclear cisternae, and dilated rough endoplasmic reticulum, also were observed in the joint cleft surface. 3. From the 18-day-old fetus, phagocytic synovial cells and secretory synovial cells could be confirmed. The apoptotic cells were not seen. 4. In a 17-day-old fetus, a few cells were positive for TUNEL reaction in the joint cleft region. 5. In a 17-day-old fetus, Bax were marked on the mitochondria, endoplasmic reticulum of apoptotic cells. Also, it was marked at the phagocytosed apoptotic bodies in the neighboring cells. 6. In a 17-day-old fetus, the tissue Transglutaminase C were marked in the perinuclear region, vacuoles, cell membrane and extracellular matrix of the apoptotic cells. Also, it was marked at the phagocytosed apoptotic bodies in the neighboring cells. 7. In a 17-days-old fetus, CPP32 labeling were marked in the cytoplasm of the apoptotic cells. Practically, it was distributed between the phagocytosed apoptotic bodies and the neighboring cells. On the basis of above findings, it is obvious that the joint cleft are first formed in a 17-day-old fetus, a few cells are to be TUNEL positive signals, and the apoptotic cells contain Bax, tissue Transglutaminase C, and CPP32. Therefore the apoptotic cells and the necrotic cells are appeared in the 17-day-old fetus, and these cells are concerned with joint cleft formation.
Animals ; Antibodies ; Apoptosis ; Capillaries ; Cartilage ; Cell Membrane ; Chromatin ; Cytoplasm ; Endoplasmic Reticulum ; Endoplasmic Reticulum, Rough ; Extracellular Matrix ; Femur ; Fetus ; Goats ; Heterochromatin ; In Situ Nick-End Labeling ; Joints ; Knee Joint* ; Knee* ; Ligaments ; Mitochondria ; Pregnancy ; Rats* ; Synovial Membrane ; Tibia ; Vacuoles