ONYX-411, a conditionally replicative oncolytic adenovirus, induces cell death in anaplastic thyroid carcinoma cell lines and suppresses the growth of xenograft tumors in nude mice.

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer variant, accounting for 1-2% of all cases, but 33% of deaths, and exhibiting an average life expectancy of 5 months. ATC is largely unresponsive to radioactive iodine, chemotherapy, external beam radiation or surgery, underscoring the need for new and effective therapies. We evaluated the therapeutic potential of an oncolytic adenovirus, ONYX-411, that replicates selectively in and kills cells with dysfunction of the retinoblastoma (RB) pathway. In the present study, we report that ONYX-411 is able to induce cell death in eight human anaplastic carcinoma cell lines in vitro. The cytopathic effect of the virus is specific to cells with RB dysfunction, which appears to be frequent in ATC. We confirmed the expression of the coxsackie adenovirus receptor, CAR, in all ATC cell lines, demonstrating the potentially universal application of this oncolytic viral therapy to ATC. In addition, the growth of xenograft tumors induced in athymic mice with the ARO and DRO cell lines was significantly reduced by ONYX-411 treatment. These results indicate that ONYX-411 can be a potential therapeutic agent for the treatment of ATC, rendering this class of conditionally replicating adenoviruses an attractive candidate for clinical trials.

Vertebra plana of the lumbar spine caused by an aneurysmal bone cyst: a case report.

The patient was a 15-year-old girl who had a lesion of the fourth lumbar vertebra. Plain radiographs suggested vertebra plana, with complete collapse of the body of the fourth lumbar vertebra and no involvement of the intervertebral disk spaces. The presumptive diagnosis was eosinophilic granuloma. Progressive neurologic symptoms required surgical excision of the lesion, decompression, and fusion. Histopathologic examination of the operative specimen confirmed the diagnosis of an aneurysmal bone cyst.

Prosthetic hip replacement for pathologic or impending pathologic fractures in myeloma.

The authors retrospectively reviewed 53 hip replacements performed in 50 patients (mean age, 65 years) for plasmacytoma (four lesions) or multiple myeloma (49 lesions) of the hip region. Perioperatively, 49 patients received chemotherapy. Twenty-four hip lesions had radiation therapy. Within a mean followup period of 32.6 months, 15 (28%) complications occurred. Late deep infection, dislocation, and aseptic loosening with medial migration of the acetabular component occurred in one patient each. Three patients died during the first postoperatively month. All of the remaining patients postoperatively regained their previous ambulatory status; hip pain relief was achieved in 98% of patients. At the time of the latest followup evaluation, 84% of the patients had died (median survival time, 18 months) and 16% were still alive (median survival time, 76 months). Patients with plasmacytoma had longer survival than did patients with multiple myeloma (median survival, 6.3 years versus 18 months, respectively). No significant association was found between patient survival and the stage of disease at diagnosis, age, gender, type or location of the myeloma lesion, or the type of implant used. Because of the relatively long survival time, prosthetic replacement is indicated for extensive hip lesions in patients with plasmacytoma or multiple myeloma.

Total joint arthroplasty in orthotopic liver transplant recipients.

Eight total hip and two total knee arthroplasties were performed from 1986 to 1991 in eight patients who had orthotopic liver transplantation. The indications for joint arthroplasty were avascular necrosis of the femoral head in five hips, pathologic femoral neck fracture caused by osteopenia in three hips, avascular necrosis of femoral and tibial condyles in one knee, and posttraumatic arthritis in one knee. Six patients (75%) had significant osteopenia. The mean interval between liver transplantation surgery and hip or knee joint arthroplasty was 2 years (8-48 months). The patients who had hip arthroplasty were followed for a mean of 4.85 years (2-8 years), and those who had a knee arthroplasty after a hip arthroplasty, for a mean of 3.5 years (2-5 years) after the knee arthroplasty. In the patients who had hip arthroplasty, the mean Harris hip score was improved from 34 to 82 points. In the two patients who had a knee arthroplasty, the mean score was improved to 100 points both for pain and function of the knee and for overall function from mean preoperative knee scores of 49 and 25 points, respectively. Radiographs did not reveal any loosening of the components. None of the patients required reoperation and there were no serious postoperative complications.