Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogenesis with extensive tumor necrosis.

PURPOSE: Toward improved glioblastoma multiforme treatment, we determined whether celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, could enhance glioblastoma radiosensitivity by inducing tumor necrosis and inhibiting tumor angiogenesis. METHODS AND MATERIALS: U-87MG cells treated with celecoxib, irradiation, or both were assayed for clonogenic survival and angiogenic factor protein analysis (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor [VEGF]). In vivo, survival of mice intracranially implanted with U-87MG cells and treated with celecoxib and/or irradiation was monitored. Isolated tumors were assessed for tumor necrosis and tumor microvascular density by von Williebrand's factor (vWF) immunohistochemical staining. RESULTS: Celecoxib (4 and 30 microM; 24, 48, and 72 h) enhanced U-87MG cell radiosensitivity by significantly reducing clonogenic survival of irradiated cells. Angiopoietin-1 and VEGF proteins were decreased, whereas angiopoietin-2 expression increased after 72 h of celecoxib alone and when combined with irradiation. In vivo, median survival of control mice intracranially implanted with U-87MG cells was 18 days. Celecoxib (100 mg/kg/day, 2 weeks) significantly extended median survival of irradiated mice (24 Gy total) from 34 to 41 days, with extensive tumor necrosis [24.5 +/- 8.6% of tumor region, compared with irradiation alone (2.7 +/- 1.8%)]. Tumor microvascular density was significantly reduced in combined celecoxib and irradiated tumors (52.5 +/- 2.9 microvessels per mm2 tumor region), compared with irradiated tumors alone (65.4 +/- 4.0 microvessels per mm2). CONCLUSION: Celecoxib significantly enhanced glioblastoma radiosensitivity, reduced clonogenic survival, and prolonged survival of glioblastoma-implanted mice by inhibition of tumor angiogenesis with extensive tumor necrosis.

Lacrimal gland amyloidosis.

Primary localized lacrimal gland amyloidosis is an extremely rare occurrence. The typical clinical and radiologic appearances have been suggested but not clearly established. This report describes two patients with amyloid tumor of the lacrimal gland. Both patients were middle-aged women of Asian origin, one a Chinese with unilateral lacrimal gland swelling and the other, a Malay with bilateral lacrimal gland swelling. Neither patient had associated systemic disease. They were otherwise asymptomatic except for prominence over the lacrimal gland region. Neither visual impairment nor evidence of optic nerve dysfunction was noted in either patient. CT findings mimic that of an inflammatory or lymphoproliferative disorder of the lacrimal gland. The diagnosis of amyloidosis was only proved on histology. Further investigations revealed that the disease process was truly localized and not part of a systemic process. Subsequent observation proved no recurrence.

Orbital cysts lined with both stratified squamous and columnar epithelia: a late complication of silicone implants.

Two patients presented with orbital cysts 5 and 7 years after orbital blowout fracture repair with silicone plate implants. The orbital cysts caused significant exophthalmos and restriction in ocular motility. Surgical excision revealed thick-walled cysts that were displacing the globe and encapsulating the silicone implant. On histopathologic examination, the cysts were lined with both stratified squamous and ciliated columnar (respiratory) epithelia. We propose that squamous and respiratory epithelial cells may have been deposited during surgery from the conjunctival and sinus epithelia, respectively. This case series illustrates that although an uncommon complication, epithelium-lined inclusion cysts may develop several years after orbital fracture repair with a silicone implant. A transconjunctival surgical approach is a possible risk factor.