Combination of 1alpha,25-dihydroxyvitamin D(3) with dexamethasone enhances cell cycle arrest and apoptosis: role of nuclear receptor cross-talk and Erk/Akt signaling.

Previously we have shown that dexamethasone (DEX) enhances the antitumor activity and ligand binding of the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), in the murine squamous cell carcinoma model SCC VII/SF. DEX also reduces the hypercalcemia toxicity of 1,25-D(3) treatment. However, the mechanism of the enhanced antitumor activity has not been defined. Here, we demonstrate that both cell cycle arrest and apoptosis were enhanced by DEX, effects that were inhibited by RU486. We also demonstrate that vitamin D receptor (VDR) protein levels were increased by the combination of 1,25-D(3) and DEX above the level observed with 1,25-D(3) treatment alone, whereas protein levels of the heterodimeric partner of VDR, retinoid X receptor, were lower for the combination than for 1,25-D(3) alone. Glucocorticoid receptor protein levels and ligand binding were increased by 1,25-D(3) but not by the combination. Treatment with the combination of 1,25-D(3) and DEX did not result in greater activation of a vitamin D response element-reporter than 1,25-D(3) alone or of a glucocorticoid response element-reporter than DEX alone. Nevertheless, the levels of phospho-Erk1/2 and phospho-Akt, signaling molecules that are modulated in 1,25-D(3)-treated squamous cell carcinoma cells, were reduced by the combination of 1,25-D(3) and DEX more than by either agent alone. These trends were also observed in vivo. Our results suggest the involvement of the Erk and Akt signaling pathways in the antiproliferative effects of the combination of 1,25-D(3) and DEX and that phospho-Erk1/2 and phospho-Akt may be useful markers of response to this combination.

Development of a malignant peripheral nerve sheath tumor following treatment for testicular seminoma.

A novel case is reported in which an S2 nerve root malignant peripheral nerve sheath tumor was diagnosed approximately 8 years after treatment for Stage I testicular seminoma. This patient underwent right orchiectomy and subsequent irradiation therapy to the periaortic region, including the sacrum. Postoperative radiation therapy likely played a role in the development of this second malignancy.

Surgical management of nontuberculous thoracic and lumbar vertebral osteomyelitis: report of 33 cases.

BACKGROUND: Thirty-three patients with nontuberculous pyogenic thoracic and lumbar vertebral osteomyelitis were treated surgically. Indications for surgery were either progression of disease despite adequate antibiotic therapy, neurologic deficit, or both. The most common initial symptom was back pain. Seven patients had diabetes, seven patients were intravenous drug users, two patients were receiving immunosuppressive therapy, and seven patients had a debilitating disease. Eleven had infections elsewhere in their bodies. Prior to surgery organisms were grown from blood in 10 patients and at surgery in 15 patients. METHODS: Infection was evident on plain films in all patients, and either a CT scan or MRI was obtained in each. The lateral extracavitary approach was used for resection of granulation tissue and infected bone ventral to the dura. Interbody bone grafts were placed in 19 patients, usually when bone resection was extensive. Posterior instrumentation was placed in 17 patients at a second procedure 10 days-2 weeks following initial operation. Intravenous antibiotics were administered for 4-6 weeks following surgery, and solid fusion was obtained in all patients. RESULTS: Neurologic deficit was present in 28 patients prior to surgery and was functionally significant in 18 patients. Of the 11 patients with severe paraparesis, 10 achieved good functional recovery. These patients were able to walk, three with assistance and seven without, and all those who were unable to void regained this ability. CONCLUSIONS: Surgical debridement, interbody fusion, and posterior instrumentation is a safe and effective treatment for vertebral osteomyelitis and is indicated when neurologic deficit or bone destruction progress despite adequate antibiotic therapy.

Warfarin-induced spondyloarthropathy with pseudotumor-like appearance. A case report.

STUDY DESIGN: This case report illustrates an unusual complication of chronic warfarin administration. OBJECTIVES: The presurgical determination that the destructive process at L1-L2 was not infection or neoplasm involved the recognition that there was instability at this level resulting from chronic stress fractures. SUMMARY OF BACKGROUND DATA: Periosteal or osseous hemorrhagic masses (pseudotumors) have been well described in patients with hemophilia. To the authors' knowledge, this is the first reported case of this well-known phenomenon occurring in the axial skeleton as a consequence of warfarin administration. METHODS: Serial radiographic studies of the lumbar spine were available showing a progressive destructive lesion at L1-L2 and coinciding with the initiation of warfarin anticoagulation after aortic valve replacement. RESULTS: The destructive mass was demonstrated surgically to represent a large partially solidified chronic hematoma. CONCLUSIONS: Patients with stress fractures of the posterior arch and subsequent instability may be subject to development of such a spondyloarthropathy. Recognition of this unusual potential complication of warfarin therapy would prevent an incorrect diagnosis of tumor or infection. Early recognition of its occurrence could lead to early spinal stabilization.