Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.
We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspinnegative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspinnegative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.
Tumor grade differentiation is often difficult using routine neuroimaging alone. Computed tomography perfusion imaging (CTP) provides quantitative information on tumor vasculature that closely parallels the degree of tumor malignancy. This study examined whether CTP is useful for preoperatively predicting the grade of malignancy in glioma showing no enhancement on contrast-enhanced magnetic resonance imaging (MRI). Subjects comprised 17 patients with supratentorial glioma without enhancement on MRI. CTP was performed preoperatively, and absolute values and normalized ratios of parameters were calculated. Postoperatively, subjects were classified into two groups according to histological diagnosis of grade 3 (G3) glioma or grade 2 (G2) glioma. Absolute values and normalized ratios for each parameter were compared between G3 and G2. Accuracies of normalized ratios for cerebral blood flow (nCBF) and cerebral blood volume (nCBV) in predicting a diagnosis of G3 were assessed. In addition, nCBV was compared between diffuse astrocytoma, G2 oligodendroglial tumor (OT), and G3 OT. Values for nCBF and nCBV differed significantly between G3 and G2. Using nCBV of 1.6 as a cutoff, specificity and sensitivity for distinguishing G3 were 83.3% and 90.9%, respectively. No significant difference in nCBV was seen between diffuse astrocytoma and G2 OT, whereas differences were noted between G2 and G3 OTs, and between diffuse astrocytoma and G3 OT. CTP offers a useful method for differentiating between G3 and G2 in nonenhancing gliomas.
Although posterior reversible encephalopathy syndrome (PRES) is rarely associated with subarachnoid hemorrhage, to our knowledge, rupture of a concomitant cerebral aneurysm following PRES has not been reported. We describe a patient with atypical PRES involving the brainstem, thalamus, and periventricular white matter without cortical or subcortical edema of the parietooccipital lobe on magnetic resonance imaging, with rupture of a concomitant cerebral aneurysm. Preexisting extremely high blood pressure may trigger atypical PRES, and failure to lower blood pressure may lead to a concomitant aneurysm rupture. In the future treatment of hypertensive urgency with a recurrence of symptoms and mean arterial blood pressure >150 mmHg, it is advisable to immediately hospitalize the patient for aggressive blood pressure management, especially if PRES is suspected based on clinical and radiological features.
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