ABSTRACT
Malignant fibrous histiocytoma (MFH) is one of the highest-grade sarcomas arising in bone and soft tissue. Its prognosis is poor because of chemoresistance and high metastatic potential to various organs. Few cases arising of MFH of the mandible or oral cavity have been documented. We established a tumor line in nude mice (MFH-N), which was derived from human MFH of the mandible and examined the characteristics of this tumor line. Histologically, MFH-N was identical to the original tumor and showed a storiform-pleomorphic pattern, but had low metastatic potential. Immunohistochemically, both the original and xenografted tumors expressed vimentin, S-100, alpha-SMA, and histiocytic marker CD68. Lysozyme was expressed by the original tumor, but only sporadically by the xenografted tumor. RT-PCR analysis demonstrated human beta-actin in this tumor line, indicating the human origin. In a parallel experiment, we established a new MFH cell line (MFH-NC) from MFH-N. Tumor cells inoculated into the flanks and submandibular region of nude mice developed into tumors histologically similar to MFH-N and the original tumor; multiple lung metastases were detected approximately 5 months after inoculation. The expression levels of various metastasis-related molecules differed between MFH-N and MFH-NC on Western blotting. In MFH-NC, the expressions of MMP7, MMP9, MT1-MMP, CXCR4, COX-2 and integrin alpha4 were up-regulated, while those of MMP2 and TIMP1 were down-regulated. Expression of TIMP2, integrinalphaL and sialyl lewis X were not detected in either line. Our findings suggest that the MFH-N tumor line transplantable in nude mice is a useful model for studying the biological behavior of MFH.
Subject(s)
Histiocytoma, Malignant Fibrous/secondary , Lung Neoplasms/secondary , Lung/pathology , Mandibular Neoplasms/pathology , Aged , Animals , Cell Line, Tumor , Disease Models, Animal , Female , Histiocytoma, Malignant Fibrous/pathology , Humans , Lung Neoplasms/pathology , Male , Mice , Mice, Nude , Neoplasm Metastasis , Neoplasm TransplantationABSTRACT
A 21-year-old man with no history of contact allergy developed eczema over his entire body 2 days after he had had intermaxillary fixation (IMF) of a mandibular fracture. Patch testing showed a strong reaction to nickel so the arch bars and wires that had been used for fixation were removed and replaced with resin brackets, elastic bands, and a chin cap. The eczema disappeared 2 days later.
Subject(s)
Eczema/chemically induced , Jaw Fixation Techniques/adverse effects , Nickel/adverse effects , Adult , Fracture Fixation/adverse effects , Humans , Hypersensitivity, Delayed/etiology , Jaw Fixation Techniques/instrumentation , Male , Mandibular Fractures/surgeryABSTRACT
Colorectal carcinomas are well known to highly express COX-2 and their growth is markedly inhibited by COX-2 inhibitors, but little is known about head and neck carcinomas. In this study, we investigated the effect of a selective COX-2 inhibitor, celecoxib, on growth and apoptosis induction of four human head and neck carcinoma cell lines, SCC25, KB, HSG and HSY, in comparison with frequently used COX inhibitor sulindac. Also, we examined whether celecoxib augments the sensitivity of these cell lines to anticancer drugs such as doxorubicin (DOX), vincristine (VCR), cisplatin (CDDP), bleomycin (BLM) and 5-fluorouracil (5-FU). The growth of all cultured cell lines particularly SCC25 and HSG was inhibited by celecoxib and sulindac in a dose-dependent manner. The IC50 of celecoxib was ten times lower than that of sulindac. SCC25 produced ample PGE2 whereas KB, HSG and HSY produced a small amount of PGE2. The PGE2 production and COX-2 expression were inhibited more efficiently by celecoxib than by sulindac. Exogenous addition of PGE2 resulted in an increased cell growth of SCC25 even under the celecoxib-treated condition, but not of HSG. These results suggested that PGE2 is involved in the growth of SCC25 but not of HSG. The ability of celecoxib to induce apoptosis is greater than that of sulindac. Treatment of SCC25 and HSG with non-cytotoxic 1 micro M or less cytotoxic 5 micro M of celecoxib enhanced the sensitivity of both cell lines to anticancer drugs, particularly in DOX, VCR and BLM two to ten times as demonstrated by lowering of IC50s. The enhanced rate was almost parallel to the degree of apoptosis induction. These findings indicated that a selective COX-2 inhibitor celecoxib inhibits cell proliferation, induces apoptosis and augments sensitivity to anticancer drugs in human head and neck carcinoma cells. Therefore, celecoxib would be useful as biological modulator in treatment of head and neck cancer.
