Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality. Immunotherapy has emerged in clinical treatment, owing to the limitation and severe side effects of chemotherapy. In the immune system, natural killer (NK) cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex (MHC) molecule issues. Hence, treatment which could stimulate NK cells is of great interest. Here, we investigated the efficacy of the combined therapy of TT-1 (a mutant of melittin) and interferon-α (IFN-α) on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo, as well as the mechanism involved. The combination therapy significantly inhibited the growth of HepG-2/Huh7 cells in vivo, but this effect was impaired after depleting NK cells. TT-1 not only up-regulated MHC class I-related chain molecules A (MICA) expression, but also prevented the secretion of soluble MICA (sMICA). Both the mRNA and protein of a disintegrin and metallopeptidase 10 (ADAM 10) in HepG-2/Huh7 cells were decreased after TT-1 treatment. The combined therapy of TT-1 and IFN-α could suppress the growth of HepG-2/Huh7 xenografted tumor effectively via promoting the interaction of NK group 2, member D (NKG2D) and MICA, indicating that TT-1+IFN-α would be a potential approach in treating liver cancer.

1993-06-01·Cardioscience

Heterogeneity of smooth muscle in bovine coronary arteries.

Article

作者: Scatena, M ; Chiavegato, A ; Sartore, S ; Giuriato, L

The monoclonal antibodies TT-1 against troponin T and TI-1 against troponin I of cardiac muscle, together with Western blots and immunofluorescence techniques, were used to evaluate the presence of troponin-like antigens in the smooth muscle cells of bovine coronary arteries. The walls of the left coronary artery before the bifurcation, its circumflex and descending branches, the right coronary artery, and the small branches of coronary arteries and the intramural arterial vessels were found to be homogeneously stained by the TT-1 antibody. Conversely, with the TI-1 antibody, differences were observed in the distribution of the TnI-like antigen among the smooth muscle cells of extramural and intramural vessels. Heterogeneity of the smooth muscle cells of the coronary artery was also evident in the medial layer of large vessels near the branching points, where an intimal thickening was consistently observed. Double immunofluorescence assays with anti-troponin antibodies in vivo and in vitro indicated a distinct intracellular localization of troponin T and troponin I immunoreactivities in vascular smooth muscle cells. The data are compatible with the existence of distinct troponin-like antigens in smooth muscle cells of bovine coronary arteries whose distribution is in part related to the extramural or intramural localization of blood vessels.

1989-01-01·International Journal of Biochemistry

Two toxins from the venom of Trimeresurus tokarensis

Article

作者: Sugihara Hisayoshi ; Nikai Toshiaki ; Itoh Minobu ; Sekoguchi Seiichiro

1. Two toxins, Tokaratoxin-1 (TT-1) and Tokaratoxin-2 (TT-2), were isolated from the venom of Trimeresurus tokarensis using gel filtration on a Sephadex G-100 column, followed by chromatography on DEAE-Sephacel and carboxymethyl-cellulose. TT-1 possessed both hemorrhagic and proteolytic activities. However, TT-2 did not show hemorrhagic activity. 2. Homogeneity was established by the formation of a single band in acrylamide gel electrophoresis, isoelectric focusing and SDS-PAGE. 3. Molecular weights of TT-1 and TT-2 were 71,000 and 25,400, respectively. Although TT-2 is a basic protein, TT-1 is an acidic protein. 4. Biological activities of TT-1 and TT-2 were inhibited by EDTA, EGTA and o-phenanthroline, suggesting that the toxins are metalloproteins. Atomic absorption analyses indicated that TT-1 contains 2.79 mol Ca/mol protein and TT-2 contains 1.04 mol Ca/mol protein and 1.07 mol Zn/mol protein, respectively. 5. The two toxins degraded the A alpha and B beta chains of fibrinogen. 6. TT-1 induced necrosis in addition to its hemorrhagic activity while TT-2 induced necrosis only.

100 项与 TT001 相关的药物交易

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