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.

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The expression of thrombospondin-1 (TSP-1) and its role in gliomas have not been well examined. In the present study TSP-1 expression in a panel of malignant glioma cell lines and the expression of TSP-1 and transforming growth factor (TGF-beta) proteins in low-grade and malignant glioma tissues were investigated. Reverse transcription-polymerase chain reaction analysis showed that nine of nine malignant glioma cell lines expressed TSP-1 mRNA, and seven of nine glioma lines expressed TSP-2 mRNA. Production and secretion of TSP-1 were examined in the T98G glioblastoma cell line by western blot analysis. Total TSP-1 protein content in the supernatant was 10 times higher than that in the cell lysate. Secretion of TSP-1 was examined in these glioma cell lines by western blot analysis. All glioma lines secreted significant levels of TSP-1. Bioassay showed that all tumor lines had the capacity to activate latent TGF-beta. Localization of TSP-1, TGF-beta1, -beta2, and -beta3 was examined immunohistochemically in surgically resected glioma tissues, including 11 glioblastomas, six anaplastic astrocytomas, and eight astrocytomas. Most glioblastomas expressed high levels of both TSP-1 and TGF-beta. Anaplastic astrocytomas expressed moderate levels of TSP-1 and TGF-beta. Most malignant gliomas expressed various levels of TGF-beta1, -beta2, and -beta3. The expression of both proteins, however, was weak in low-grade gliomas. Normal brain tissues around the tumors were negatively or very weakly positively stained for TSP-1 and TGF-beta. These results indicate that most malignant glioma cells express TSP-1 in vitro and in vivo, and the expression of TSP-1 and TGF-beta in vivo correlates with the histologic malignancy of glioma. Overexpression of both TSP-1 and TGF-beta may increase the biologic malignancy of malignant gliomas, through generating the active form of TGF-beta in tumor tissues.

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Most tumour cells are sensitive to TRAIL-induced apoptosis, but not normal cells; thus, cancer therapy using TRAIL is expected clinically. Several tumour cells are resistant to TRAIL-induced apoptosis, and various mechanisms of such resistance were reported in individual cases. In this study, we established a TRAIL-resistant glioma cell line, which completely lacked TRAIL receptors. In addition, this tumour cell line had wild-type p53 tumour-suppressive gene, suggesting new mechanisms for tumour cells to expand and escape from immune surveillance. The present study further explored the mechanisms that determine the sensitivity to TRAIL. We show that genotoxic agents such as cisplatin, doxorubicin and camptothecin, in addition to UV radiation, can induce TRAIL-R2 on the cell surface of TRAIL receptor-negative tumour cells. Newly synthesised TRAIL-R2 is functional, so apoptosis is effectively induced by TRAIL, but it is significantly inhibited by constitutive expression of dominant-negative p53. In addition, apoptosis induced by pretreatment of genotoxic agents and additional stimulation of TRAIL is efficiently inhibited by either antagonistic anti-TRAIL-R2 antibody or pan-caspase inhibitor z-VAD-FMK. Taken together, these findings suggest that resistance to TRAIL by lack of TRAIL receptors on glioma is restored by genotoxic agents, which support the new strategies for tumour killing by TRAIL-bearing cytotoxic cells in combination with genotoxic treatment.

Systemic pathological alterations were studied in thirty‐seven autopsied patients with Kawasaki disease. Systemic vasculitis was the most characteristic pathological finding and was present in all the patients. In addition to the vasculitis, there was a high incidence of inflammatory lesions in various organs and tissues: in the heart, endocarditis, myocarditis, and pericarditis; in the digestive system, stomatitis, sialoduct‐adenitis, catarrhal enteritis, hepatitis, cholangitis, pancreatitis, and pancreas ductitis; in the respiratory system, bronchitis and segmental interstitial pneumonia; in the urinary system, focal interstitial nephritis, cystitis, and prostatitis; in the nervous system, aseptic leptomeningitis, choriomeningitis, ganglionitis, and neuritis; in the hematopoietic system, lymphadenitis, splenitis, and thymitis. Dermatitis, panniculitis or myositis were also observed in some patients. Therefore, Kawasaki disease is a systemic inflammatory disease which mainly affects the cardiovascular system. These systemic inflammatory lesions are considered to correspond to the variegated clinical manifestaitions. The relationship between Kawasaki disease and infantile polyarteritis nodosa (IPN) were discussed, based on the clinicopathological characteristics.