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Regulatable Transgene Expression for Preventionof Chemotherapy-Induced Peripheral Neuropathy
Get PDFChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.博士（医学）旭川医科大
大血管手術後における神経学的予後予測因子としての血清神経特異的エノラ－ゼ値
Get PDFBACKGROUND:
This study aimed to evaluate the significance of serum neuron-specific enolase (NSE) level as a predictor of neurologic injury in thoracic aortic surgery.
METHODS:
We neurologically assessed 60 consecutive patients who underwent thoracic aortic surgery for thoracic aortic aneurysm (n = 26) and aortic dissection (n = 34). Using moderate hypothermic circulatory arrest with antegrade cerebral perfusion, total arch replacement and hemiarch replacement were performed in 37 and 23 patients, respectively. Serum NSE levels in venous blood samples drawn before surgery and at 1 day after surgery were measured. Severity of neurologic injury was categorized as either uncomplicated (n = 48), temporary neurologic dysfunction (TND, n = 5), or permanent neurologic dysfunction (PND, n = 7). The extent of stroke was estimated on computed tomography or magnetic resonance imaging.
RESULTS:
The NSE level significantly differed among the three groups (PND > TND > uncomplicated) on the first postoperative day. Receiver-operating characteristic curve analysis showed that the cutoff value of NSE level was 34.14 ng/mL for neurologic injury (sensitivity, 0.769; specificity, 0.851) and 43.56 ng/mL for PND (sensitivity, 1.000; specificity, 0.963). The NSE level significantly correlated with the extent of stroke (r = 0.61, p < 0.001).
CONCLUSION:
Serum NSE level is a significant predictor of adverse neurologic outcomes and extent of stroke after thoracic aortic surgery.博士（医学）旭川医科大
