Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas

Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this phase 2 study, aprinocarsen was administered to patients with recurrent high-grade gliomas by continuous intravenous infusion (2.0 mg/kg/day for 21 days per month). Twenty-one patients entered this trial. Their median age was 46 years (range, 28-68 years), median Karnofsky performance status was 80 (range, 60-100), median tumor volume was 58 cm3 (range, 16-254 cm3), and histology included glioblastoma multiforme (n = 16), anaplastic oligodendroglioma (n = 4), and anaplastic astrocytoma (n = 1). The number of prior chemotherapy regimens included none (n = 3), one (n = 10), and two (n = 8). No tumor responses were observed. Patients on this therapy rapidly developed symptoms of increased intracranial pressure with increased edema, enhancement, and mass effect on neuroimaging. The median time to progression was 36 days, and median survival was 3.4 months. The observed toxicities were mild, reversible, and uncommon (grade 3 thrombocytopenia [n = 3] and grade 4 AST [n = 1]), and no coagulopathy or CNS bleeding resulted from this therapy. Plasma concentrations of aprinocarsen during the infusion exhibited significant interpatient variability (mean = 1.06 mug/ml; range, 0.34-6.08 mug/ml). This is the first study to use an antisense oligonucleotide or a specific PKC-alpha inhibitor in patients with high-grade gliomas. No clinical benefit was seen. The rapid deterioration seen in these patients could result from tumor growth or an effect of aprinocarsen on bloodbrain barrier integrity.     

Mitotic Rate as a Predictor of Sentinel Lymph NodePositivity in Patients With Thin Melanomas

Background Lymphatic mapping and sentinel lymphadenectomy (LM/SL) provide important prognostic information for patients with early-stage melanoma. Although the use of this technique in patients with thin melanomas (1.00 mm) is not routine, risk factors that may predict sentinel lymph node (SLN) positivity in this patient population are under investigation. We sought to determine whether mitotic rate (MR) is associated with SLN positivity in thin-melanoma patients and, therefore, whether it may be used to risk-stratify and select patients for LM/SL.Methods Clinical and histopathologic variables were reviewed for 181 patients with thin melanomas who underwent LM/SL from January 1996 through January 2004. Univariate and multivariate logistic regression analyses were performed to identify factors associated with SLN positivity. Risk groups were defined on the basis of the development of a classification tree.Results The overall SLN positivity rate was 5%. All patients with positive SLNs had an MR of >0. By univariate analysis, MR and thickness were significant predictors of SLN positivity. The association between MR and SLN positivity remained significant controlling for each of the other variables evaluated. On the basis of a classification tree, patients with an MR >0 and tumor thickness .76 mm were identified as a higher-risk group, with an SLN positivity rate of 12.3%.Conclusions In patients with thin melanomas, MR >0 seems to be a significant predictor of SLN positivity that may be used to risk-stratify and select patients for LM/SL. To confirm these results, the predictive value of MR for SLN positivity needs to be validated in other populations of thin-melanoma patients.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Non-invasive glycaemia blood measurements by electromagnetic sensor: study in static and dynamic blood circulation

In this paper, we present the results of non-invasive blood glycaemia measurements. The blood used in the measurements was calf blood. The measurement method uses an electromagnetic sensor based on eddy currents, which allows the detection of blood glycaemia levels through the variation of the dielectric parameters of the blood. A change in blood glucose concentration causes a variation in the dielectric parameters, in particular conductivity. Detection is only possible at a resonant frequency. The measurements were taken in a static and dynamic state (with and without circulation of blood). The blood is inside a plastic tube placed within the sensor and is surrounded by gelatine, which simulates muscular tissue. The plastic tube simulates the vein where blood circulation occurs. The in vitro results in both cases (static and dynamic) are provided. Under unfavourable conditions we can detect a change of +/- 2 g/l of glucose. We present and discuss these results.     

Hypertension with renal carcinoma. An effect of arterial embolization

A patient presented with mediastinal metastases from renal adenocarcinoma. Palliative therapy included Gelfoam and steel coil embolization of the right renal artery. Six weeks later he was found to have developed severe hypertension. Arteriogram revealed collateral vessels which supplied the tumor; the renal vein renin activity was four times higher on the right than on the left. We suspect that infarction of the kidney was not complete because of collateral arterial supply, and renin-dependent hypertension was the result. Thus, it may be hazardous to embolize large hypernephromas without subsequent nephrectomy.     

PET imaging in the assessment of normal and impaired cognitive function

PET has been used to directly quantify several processes relevant to the status of cerebral health and function, including cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism, and cerebral glucose use. Clinically, the most commonly performed PET studies of the brain are performed with fluorine-18-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic use in evaluating patients who have cognitive impairment, and in distinguishing among primary neurodegenerative dementias and other causes of cognitive decline. In certain pathologic circumstances, the normal coupling between blood flow and metabolic needs may be disturbed, and changes in oxygen extraction fraction can have significant prognostic value.     

Hyperpolarized helium-3 MR imaging of pulmonary function

Recent advances in HP MR imaging contrast agents have led to novel tests of pulmonary function. Many of these tests show promise in the clinical arena.     

FDG-PET imaging in primary bilateral adrenal lymphoma: a case report and review of the literature

Primary adrenal lymphoma is an extremely rare entity. Only 70 cases have been reported in the English literature. Most of the patients are elderly men with bilateral adrenal masses without extraadrenal involvement. The most common presenting symptoms are fever, weight loss, lumbar pain, and/or symptoms of adrenal insufficiency. Of the cases reported, CT, ultrasound, and MRI were the imaging modalities used to describe the lesions. FDG PET has been used successfully to differentiate benign and malignant adrenal masses. The authors report a 67-year-old man diagnosed as having primary bilateral adrenal lymphoma and having no evidence of extraadrenal spread who was evaluated from the time of diagnosis to complete remission with FDG PET scanning. The literature of this unusual neoplasm is reviewed in detail.