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Depsipeptide (FK228) is a novel histone deacetylase inhibitor currently in clinical trials and the first to demonstrate clinical activity in patients. Responses have been observed in patients with T-cell lymphomas, despite prior treatment with multiple chemotherapeutic agents. To better understand the effects of histone deacetylase inhibitors on T-cell lymphoma, the human T-cell lymphoma cell line HUT78 was tested for sensitivity and molecular response to depsipeptide. Treatment with depsipeptide, as well as other histone deacetylase inhibitors, caused induction of histone acetylation, induction of p21 expression, and substantial apoptosis without significant cell cycle arrest. Treatment with the caspase inhibitor z-VADfmk significantly inhibited depsipeptideinduced apoptosis, enabling detection of cell cycle arrest. Treatment with depsipeptide increased expression of the interleukin-2 (IL-2) receptor, and combination with the IL-2 toxin conjugate denileukin diftitox resulted in more than additive toxicity. Cells selected for resistance to depsipeptide overexpressed the multidrug resistance pump, P-glycoprotein (Pgp).However, cells selected for resistance to depsipeptide in the presence of a Pgp inhibitor had a Pgp-independent mechanism of resistance. These studies confirm the activity of depsipeptide in a T-cell lymphoma model and suggest a general sensitivity of T-cell lymphoma to histone deacetylase inhibitors, an emerging new class of anticancer agents. IntroductionThe histone deacetylase inhibitors (HDIs) are a new class of antineoplastic agents currently being evaluated in clinical trials. HDIs induce growth arrest usually associated with cellular differentiation or apoptosis. Alterations in the enzymes controlling histone acetylation and deacetylation have been shown to be a direct mechanism of transformation in some malignancies. 1 The consequence of a decrease in histone acetylation is a decreased expression of cell cycle inhibitors and other genes involved in regulating a differentiated phenotype. 2 Depsipeptide (FK228) is an HDI that has in vitro and in vivo cytotoxic activity. 3 Several families of HDIs have been characterized. These include the short-chain fatty acids, such as sodium butyrate and valproic acid; the organic hydroxamic acids, such as trichostatin A (TSA) and suberanilohydroxamic acid (SAHA); the benzamides, such as CI-994 and MS-27-275; the cyclic tetrapeptides, such as trapoxin A; and the bicyclic depsipeptides, such as depsipeptide. Similar to other HDIs, depsipeptide has been shown to induce cell cycle arrest, cellular differentiation, and apoptosis. Depsipeptide induces a p53-independent/ p21-dependent G1 arrest and a p21-independent G2/M arrest. In addition, depsipeptide causes alterations in gene expression, including increased expression of p21 and cyclin E and decreased expression of cyclin D1 and c-myc. [4][5][6] T-cell lymphomas are composed of a spectrum of clinical phenotypes ranging from low-grade, cutaneous T-cell lymphomas (CTCLs) to highly aggressive peripheral T-cell...

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Isotropic SPACE T2-weighted imaging provides high-quality imaging of lumbar spondylosis, with multiplanar reformatting capability. Our SPACE-based rapid protocol had sensitivities and specificities for herniations and neural compromise comparable to those of the protocol without SPACE. This protocol fits within a 15-minute slot, potentially reducing costs and discomfort for a large subgroup of patients.

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Mobile schwannomas of the spine have been sparsely documented in the literature. In cases referred to in existing literature, the migratory schwannoma was documented to occur in the lumbar spine. We added another case to the small available literature. In our case report, the patient had a previously known lumbar schwannoma that was being managed conservatively. Due to an acute change in clinical symptoms, repeat imaging was performed. A magnetic resonance imaging (MRI) of his spine revealed migration of the schwannoma two levels rostral to his recent imaging from six weeks earlier. The patient underwent surgical resection of his lesion. During the operation, the ultrasound was utilized to confirm the lesion prior to dural opening. In this report, we attempt to provide further evidence of the utility of an intraoperative ultrasound for intradural lesions and intend to add to the published literature of mobile schwannomas of the spine

Bow hunter's syndrome is a diagnosis typically made using dynamic digital subtraction angiography. The authors present the case of a 68-year-old woman who presented with symptoms consistent with bow hunter's syndrome that was accurately diagnosed utilizing noninvasive dynamic MR angiography. The dynamic MR angiogram clearly illustrated unilateral vertebral artery compression upon turning of the head. A subsequent CT of the cervical spine showed a ventral C-1 osteophyte within the foramen. The patient underwent posterior surgical decompression of the left vertebral artery. Sufficient decompression was confirmed using intraoperative fluorescent angiography with the patient's head turned. This case report is the first to illustrate that dynamic MR angiography can be a reliable and less invasive diagnostic tool. It can also be used to confirm sufficient postoperative decompression and monitor for recurrence. Intraoperative fluorescent angiography has been previously used in the evaluation of intracranial and extracranial vascular patency. This report is the first to show that fluorescent angiography can offer rapid and reliable intraoperative evaluation of vertebral artery decompression in bow hunter's syndrome.