Glycolysis inhibitors as a potential therapeutic option to treat aggressive neuroblastoma expressing GLUT1

Background/PurposeIncreased glycolysis is among the biochemical characteristics of cancerous tissue. The glucose transporter isoform 1 (GLUT1) gene encodes a key factor for glucose transport into cancerous tissue. However, the expression and functional significance of GLUT1 in neuroblastoma have not been fully characterized. Therefore, we investigated the association of GLUT1 expression with clinical outcomes in patients with neuroblastoma using immunohistochemical staining for GLUT1 in neuroblastoma tissues. We also assessed the efficacy of glycolysis inhibition as an anticancer treatment in neuroblastoma cell lines with altered expression of GLUT1.MethodsWe obtained total RNA from cancerous tissue by microdissection in 47 patients with neuroblastoma. GLUT1 expression levels were evaluated by quantitative real-time polymerase chain reaction. We analyzed the association of GLUT1 expression levels with clinical outcomes. We also examined changes in GLUT1 expression and proliferative responses in vitro using 4 neuroblastoma cell lines treated with a glycolysis inhibitor, 3-Bromopyruvate acid.ResultsElevated GLUT1 expression was associated with poor prognosis. Moreover, elevated GLUT1 expression independently predicted overall survival. Immunohistochemical analysis showed that GLUT1 expression tended to be localized to the centers of neuroblastoma cell nests. Our in vitro studies showed that 3-Bromopyruvate acid significantly suppressed the proliferation of neuroblastoma cells with high GLUT1 gene expression compared with those with low expression.ConclusionGlycolysis inhibitors are a potential therapeutic option for treating aggressive tumors expressing GLUT1.     

Impact of an inflammation-based prognostic system on patients undergoing surgery for hepatocellular carcinoma: a retrospective study of 398 Japanese patients

BackgroundFew studies have investigated the Glasgow Prognostic Score (GPS) in patients with hepatocellular carcinoma (HCC).MethodsThis study compared the prognostic value of the GPS and Cancer of the Liver Italian Program (CLIP) score in patients undergoing surgery for HCC.ResultsA total of 398 patients were evaluated retrospectively. Kaplan–Meier analyses revealed that GPS (P < .001) and CLIP score (P < .001) were associated with overall survival. GPS could classify patients with low CLIP score (0 or 1) into 3 independent groups (P < .001). Univariate analyses selected GPS (P = .006) and CLIP score (P = .002) as the predictive factors associated with overall survival. Multivariate analysis using these 2 scoring systems disclosed that both GPS (P = .025) and CLIP score (P = .010) were associated with overall survival.ConclusionsGPS is not only an important predictor of overall survival after surgical treatment of HCC as well as CLIP score, but also is able to clearly divide patients with low CLIP score into 3 independent groups.     

Triangle target principle for the placement of trocars during video-assisted thoracic surgery.

OBJECTIVE: The baseball-diamond principle is generally used for trocar placement during video-assisted thoracic surgery; however, we are unable to treat all peripheral lung lesions using this principle. Therefore, we have developed another method for determining trocar placement based on a modification of the conventional principle. We have termed this method the triangle target principle. This report describes the instrument positioning that we now use for many video-assisted thoracic surgical procedures. METHODS: We position 3 trocars in an equilateral triangle, with the target lesion at the apex. One vertex of the base becomes the site of the first trocar placement for introduction of the thoracoscopic camera. Another vertex of the base becomes the site for the second trocar for forceps or the endoscopic stapler. The third trocar is for forceps and is inserted to create the vicinity of target lesion. Four types of the triangle target principle were developed according to sites of the target lesion. RESULTS: Between January 2000 and December 2002, we used this principle for 161 patients who underwent video-assisted thoracic surgery and all intrathoracic lesions were accessible except in 3 patients requiring intraoperative modifications. CONCLUSIONS: We conclude that video-assisted thoracic surgery by this principle is more effective and easier than the conventional principle to treat intrathoracic disease.     

Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy hyperbilirubinemia in patients with biliary cancer

Background and aims Hyperbilirubinemia is a critical complication following hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a bilirubin transporter, is shown to be down-regulated by acute biliary obstruction in rats. However, little is known about the effect of chronic obstruction by malignancy on the MRP2 expression in patients or the association of MRP2 expression with posthepatectomy hyperbilirubinemia.Materials and Methods The MRP2 expression before hepatectomy was determined by immunostaining and Western blotting in patients with biliary cancer. To directly determine the effect of chronic bile duct obstruction on the MRP2 expression, the expression levels were compared between the cholestatic and noncholestatic lobes in each of seven patients. In another 39 patients, the correlation of the MRP2 expression of the anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia, defined as a serum total bilirubin concentration200 mol/l, was evaluated.Results The MRP2 staining in the cholestatic lobes was weak and not restricted to the canalicular membrane, unlike the noncholestatic lobes. The expression levels in the cholestatic lobes were 45% of those in the noncholestatic lobes. Postoperative maximum bilirubin levels were significantly correlated with MRP2 expression of the anticipated remnant liver. The MRP2 expression had been already impaired before hepatectomy in all patients who eventually developed severe hyperbilirubinemia.Conclusions Decreased MRP2 expression, caused by biliary obstruction due to cancer, is a possible risk factor for posthepatectomy severe hyperbilirubinemia.     

Rectovaginal fistulas after rectal cancer surgery: Incidence and operative repair by gluteal-fold flap repair

BACKGROUND: We investigated the correlation between operative procedures for rectal carcinoma and postoperative rectovaginal fistulas (RVF), and treatment for RVF. METHODS: The medical records of 161 female patients with rectal carcinoma were examined retrospectively with respect to the cause, incidence, and methods of treatment for RVF occurring after rectal cancer operations, and to the outcomes of gluteal-fold flap repairs for RVF. RESULTS: Of the 161 patients, 16 developed RVF clinically. The incidence of RVF was significantly higher in patients who were anastomosed by the double stapling technique (DST) and had concomitant resection of the vaginal wall. No statistical difference was found between the established diverting ostomy group and the no-stoma group. Six patients recovered by the establishment of a diverting ostomy only. The gluteal-fold flap technique was performed for 5 patients. No RVF recurrences were noted in these 5 patients. CONCLUSIONS: The incidence of RVF was higher in the patients who were anastomosed by DST or had concomitant resection of the vaginal wall. Although some RVFs heal with only fecal diversion, for patients in whom RVF is caused by involvement of the vaginal wall in the circular staple or intersphincteric resection, good results are obtained with the gluteal-fold flap repair technique.     

Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura

PURPOSE: Vascular endothelial growth factor (VEGF) is known as a multifunctional protein with roles in angiogenesis stimulation and apoptosis inhibition. We hypothesized that intracavernous administration of VEGF would recover erectile dysfunction due to diabetes by protection from apoptosis in the penile cavernosum. MATERIALS AND METHODS: A total of 30, 6-month-old male Sprague-Dawley rats were divided into 2 large groups, namely 20 with diabetes and 10 healthy controls. The diabetic group received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Intracavernous injection of VEGF was administered to randomly selected STZ diabetic rats 6 weeks after STZ injections. Erectile functional studies were performed in 10 STZ and 10 STZ plus VEGF rats at 12 weeks. After completion of the functional study the penile crura were collected for molecular and immunohistochemical studies. RESULTS: Mean intracavernous pressure in the diabetic group was significantly lower than in controls and low pressure was significantly recovered by VEGF treatment. Gene expression of pro-apoptotic and anti-apoptotic factors were present in the control, diabetic and VEGF treated groups. However, anti-apoptotic protein expression was lacking in the diabetic group and it was recovered by VEGF treatment. The apoptotic index in the diabetic group was significantly higher than in controls and this index was significantly decreased in the VEGF treated group. CONCLUSIONS: The decrease in and recovery of intracavernous pressure correlated significantly with a variation in anti-apoptotic protein expression in the diabetic and VEGF treated groups. To our knowledge this is the first study to show that intracavernous injection of VEGF restores erectile dysfunction through the inhibition of apoptosis in diabetic rats.     

Cardioprotective Effect of Succinate Against Ischemia/Reperfusion Injury

(Received for publication on Sept. 12, 1996; accepted on May 12, 1997)     

Quantitative assessment of right ventricular function and pulmonary regurgitation in surgically repaired tetralogy of Fallot using 256-slice CT: comparison with 3-Tesla MRI

Objectives

To compare 256-slice cardiac computed tomography (CCT) with cardiac magnetic resonance (CMR) imaging to assess right ventricular (RV) function and pulmonary regurgitant fraction (PRF) in patients with repaired tetralogy of Fallot (TOF).

Methods

Thirty-three consecutive patients with repaired TOF underwent retrospective ECG-gated CCT and 3-Tesla CMR. RV and left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were measured using CCT and CMR. PRF-CCT (%) was defined as (RVSV???LVSV)/RVSV. PRF-CMR (%) was measured by the phase-contrast method. Repeated measurements were performed to determine intra- and interobserver variability.

Results

CCT measurements, including PRF, correlated highly with the CMR reference (r?=?0.71–0.96). CCT overestimated RVEDV (mean difference, 17.1?±?2.9 ml), RVESV (12.9?±?2.1 ml) and RVSV (4.2?±?2.0 ml), and underestimated RVEF (?2.6?±?1.0 %) and PRF (?9.1?±?2.0 %) compared with CMR. The limits of agreement between CCT and CMR were in a good range for all measurements. The variability in CCT measurements was lower than those in CMR. The estimated effective radiation dose was 7.6?±?2.6 mSv.

Conclusions

256-slice CCT can assess RV function and PRF with relatively low dose radiation exposure in patients with repaired TOF, but overestimates RV volume and underestimates PRF.

Key points

? 256-slice CT assessment of RV function is highly reproducible in repaired TOF. ? Pulmonary regurgitation can be evaluated by biventricular systolic volume difference. ? CT overestimates RV volume and underestimates pulmonary regurgitation, compared with MRI.