This study demonstrates that CDDP specifically induces apoptosis via activation of caspases and the other anticancer drugs induce death of HOS cells via different signaling pathways. It also demonstrates that caspase-8 is a key molecule in the earliest stage of the signaling pathway of CDDP-induced apoptosis of HOS cells, and caspase-3 works downstream of caspase-8.

No abstract

Human promyelocytic leukemia HL-60 cells are well known to differentiate into granulocytes or monocytes in the presence of some agents such as DMSO or PMA, respectively. Differentiated HL-60 cells become resistant to some apoptotic stimuli including anticancer drugs or irradiation though undifferentiated cells significantly respond to these stimuli. TRAIL (TNF-related apoptosis-inducing ligand) which is also known as Apo2 ligand (Apo2L), a new member of TNF family, can induce apoptosis in some tumor cells but not in many normal cells. We show here that apoptosis is well induced in HL-60 cells by TRAIL, but susceptibility to TRAIL is reduced during granulocytic differentiation by DMSO. We also suggest some possible mechanisms by which granulocytic differentiated cells become resistant to TRAIL-induced apoptosis. First, in granulocytic differentiated cells, expression of antagonistic decoy receptors for TRAIL (TRAIL-R3/TRID/ DcR1/LIT and TRAIL-R4/TRUNDD/DcR2) were enhanced. In addition, expression of Toso, a cell surface apoptosis regulator, seemed to block activation of caspase-8 by TRAIL via enhanced expression of FLIP L in granulocytic differentiated cells. These findings suggest that differentiated cells are resistant using plural mechanisms against various apoptosis-inducing stimuli rather than undifferentiated cells. Cell Death and Differentiation (2000) 7, 939 ± 946.

The malignant tumor patient tends to develop various neuropathy by direct invasion, metastasis, secondary infectious disease of tumor, metabolic disorders, vascular damage and adverse drug reactions with a treatment, and, however, it rarely appear by mechanism of autoimmunization. Tumor tissue with paraneoplastic neurological syndrome (PNS) produces an antigen attacking nerve tissue by it's cross reaction, and many studies indicates that there are a few kinds of antineuritic antibodies occurred by the charactor of malignant diseases or the patterns of progression. There is no relationship between the symptoms and the progression of disease. We report a case of malignant testicular tumor presented the paraneoplastic limbic encephalitis which is one of paraneoplastic neurological syndrome.