Gen Kondo

Suppressive effect of selective cyclooxygenase-2 inhibitor on cytokine release in human neutrophils.

To clarify whether a selective cyclooxygenase-2 (COX-2) inhibitor can affect various functions in human peripheral blood neutrophils. For this purpose, the effects of selective COX-2 inhibitors, NS-398 and nimesulide, on the expression of COX-2, PGE2 release and respiratory burst, degranulation and cytokine release in activated neutrophils were examined. Peripheral blood neutrophils were stimulated with formyl-methionyl-leucyl-phenylalanine (FMLP; 100 nM) or opsonized zymosan (OZ; 200 microg/ml). Then, the expression of COX-2 at protein and mRNA levels was detected by Western blot analysis and RT-PCR. The concentration of prostaglandin E2 (PGE2) and cytokines in the culture supernatant of neutrophils was determined using ELISA. Superoxide generation was measured by the cytochrome c reduction method. Elastase activity was measured using a chromogenic substrate assay specific for human neutrophil elastase. FMLP and OZ enhanced PGE2 release through induction of COX-2 protein and mRNA expression. FMLP- or OZ-induced PGE2 release was abolished by the addition of NS-398 or nimesulide; nevertheless, even a high concentration of COX-2 inhibitor did not change FMLP- or OZ-induced expression of COX-2 at message and protein levels. Although FMLP- or OZ-induced superoxide generation and elastase release were not affected by the addition of COX-2 inhibitor, cytokine release such as interleukin (IL)-1beta, IL-6 and IL-8 was significantly inhibited by high concentration of COX-2 inhibitor, but tumor necrosis factor-alpha (TNF-alpha) was partially attenuated. These studies showed that selective COX-2 inhibitors, NS-398 and nimesulide, suppressed PGE2 and proinflammatory cytokine release in activated neutrophils. These results suggest that selective COX-2 inhibitors may contribute to resolution of acute inflammation through the reduction of inflammatory cytokine release in activated neutrophils.

Enhanced susceptibility of oral squamous cell carcinoma cell lines to FAS-mediated apoptosis by cisplatin and 5-fluorouracil

Our study was conducted to investigate whether anticancer drugs, cisplatin (CDDP) and/or 5‐fluorouracil (5‐FU), can modulate Fas‐mediated apoptosis in oral squamous cell carcinoma (OSCC) cell lines. When OSCC cell lines, NA and HSC‐4, were treated with CDDP and/or 5‐FU, Fas and its mRNA expression on the plasma membrane were enhanced. An increase in caspase‐3 and ‐8 activities was then observed by the addition of agonistic anti‐Fas antibody, CH‐11. Apoptosis of OSCC cells treated with anticancer drugs were significantly enhanced by CH‐11, whereas untreated cells were nearly resistant to apoptosis. Moreover, the combination of CDDP and 5‐FU resulted in an increasing susceptibility to apoptosis. Caspase‐3 and ‐8 inhibitors, but not caspase‐9 inhibitor, reduced Fas‐mediated apoptosis enhanced by the anticancer drugs. Furthermore, OSCC cells treated with anticancer drugs exhibited decreased cellular FADD‐like interleukin 1‐converting enzyme‐inhibitory protein (c‐FLIP) levels, whereas neither the Fas‐associated death domain‐containing protein (FADD) nor procaspase‐8 changed the expression. Moreover, antisense oligonucleotide to c‐FLIP confirmed that down‐regulation of c‐FLIP induced sensitization to Fas‐mediated apoptosis. These results suggest that CDDP and 5‐FU may enhance the susceptibility to Fas‐mediated apoptosis through down‐regulation of c‐FLIP. From these findings, a new potential strategy may be developed to improve the efficacy of anticancer drugs.

Hybrid Desmoplastic/Follicular Ameloblastoma of the Mandible: A Case Report and Review of the Literature

Desmoplastic ameloblastoma (DA) is one of the 6 histopathological subtypes of ameloblastoma. Hybrid lesions in which histopathologically conventional ameloblastoma coexists with areas of DA are rare. A 40-year-old male was referred to our hospital complaining of a swelling in the right premolar region of the mandible. A panoramic radiograph showed an area of radiolucency with a well-defined corticated border, whereas computed tomography revealed a unilocular radiolucent lesion and buccal expansion together with cortical perforation. The lesion was treated via enucleation and curettage of the marginal bone and fenestration. A histopathological examination showed a hybrid ameloblastoma with a pronounced desmoplastic pattern and follicular changes. The patients postoperative course has been favorable up to now, and no marked changes have been observed. We presented a case of hybrid ameloblastoma and reviewed the 36 reported cases of hybrid ameloblastoma that have been reported in the English literature.