Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor.

The biologic mechanisms involved in the intratumoral heterogeneous distribution of 18F-FDG have not been fully investigated. To clarify factors inducing heterogeneous 18F-FDG distribution, we determined the intratumoral distribution of 18F-FDG by autoradiography (ARG) and compared it with the regional expression levels of glucose transporters Glut-1 and Glut-3 and hexokinase-II (HK-II) in a rat model of malignant tumor. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle (n = 7). Tumor tissues were excised 1 h after the intravenous injection of 18F-FDG and sectioned to obtain 2 adjacent slices for ARG and histochemical studies. The regions of interest (ROIs) were placed on ARG images to cover mainly the central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions. The radioactivity in each ROI was analyzed quantitatively using a computerized imaging analysis system. The expression levels of Glut-1, Glut-3, and HK-II were determined by immunostaining and semiquantitative evaluation. The hypoxia-inducible factor 1 (HIF-1) was also immunostained. RESULTS: ARG images showed that intratumoral 18F-FDG distribution was heterogeneous. The accumulation of 18F-FDG in the CT region was the highest, which was 1.6 and 2.3 times higher than those in the PT and NA regions, respectively (P < 0.001). The expression levels of Glut-1, Glut-3, and HK-II were markedly higher in the CT region (P < 0.001) compared with those in the PT region. The intratumoral distribution of 18F-FDG significantly correlated with the expression levels of Glut-1, Glut-3, and HK-II (r = 0.923, P < 0.001 for Glut-1; r = 0.829, P < 0.001 for Glut-3; and r = 0.764, P < 0.01 for HK-II). The positive staining of HIF-1 was observed in the CT region. CONCLUSION: These results demonstrate that intratumoral 18F-FDG distribution corresponds well to the expression levels of Glut-1, Glut-3, and HK-II. The elevated expression levels of Glut-1, Glut-3, and HK-II, induced by hypoxia (HIF-1), may be contributing factors to the higher 18F-FDG accumulation in the CT region.     

Geographic patterns of urban trauma according to mechanism and severity of injury

The purpose of this study was to investigate the distribution of various mechanisms of injury and the relative severity of such injury cases throughout the different geographic zones of a large urban area using a computerized emergency medical services (EMS) dispatch/patient record database. The study city (population, 2 million residents) was divided into 156 geographic grids (each 4.5 by 3 miles) and the incidence and relative severity of various injury mechanisms were determined for each zone. Results: In one year (1988), there were more than 115,000 separate EMS incidents involving more than 150,000 patients, 26,000 of whom were transported for injuries incurred in 10,064 motor vehicle accidents, 4,587 falls, 4,015 lacerations/stabwounds, 1,796 beatings, 1,270 gunshots, and 952 auto-pedestrian accidents. Analysis of the 156 zones showed a disproportionate number of EMS responses in the city center with two centralmost grids accounting for about 25% of all responses. Call volume then progressively diminished toward the periphery of the city. However, with some very minor exceptions, the relative incidence and severity of the various injury mechanisms remained proportionally uniform within each zone, regardless of geographic location. Therefore, contrary to popular notoriety, the incidence and associated severity of any given injury type generally was not necessarily predicted by any particular neighborhood predilection for it, but rather by the overall demand for EMS in that zone of the city.     

Synthesis and antiviral activity of sulfonamidobenzophenone oximes and sulfonamidobenzamides

To find antiviral agents, various sulfonamidobenzophenone oximes (II) were synthesized from the appropriate m-sulfonamidobenzophenones by hydroxylamine reaction. The reaction products were generally obtained as syn/anti mixtures which were separable by fractional crystallization. The anti isomer had more potent antipoliovirus activity than the syn isomer. Various sulfonamidobenzamides (III) which were structurally related to II were synthesized by the reactions of amino-substituted benzamides with sulfuryl chloride or amines with (aminosulfonyl)benzoyl chloride. Antiviral activity was examined by the plaque-inhibition test. Compounds 5, 36, and 69 exhibited strong antipicornavirus activity. The structure-activity relationships are discussed.     

Creatine kinase BB and neuron specific r-enolase as biomarkers for lung cancer

The serum concentrations of both CK-BB and NSE in patients with various lung carcinoma have been determined by the enzyme immunoassay. Serum CK-BB levels were found to be significantly increased (less than 1.0 ng/ml) in patients with a small cell carcinoma (51 cases, 74.5%), adenocarcinoma (77 cases, 36.5%), and a squamous cell carcinoma (68 cases, 39.7%). The serum NSE levels also were increased (less than 6.0 ng/ml) in cases of small cell carcinoma (72.5%), adenocarcinoma (27.3%), and squamous cell carcinoma (26.5%). Since the serum concentrations of bos CK-BB and NSE changed in parallel with the clinical course, they may be useful biomarkers for monitoring the clinical course of patients with lung cancer, especially in cases of small cell carcinoma.     

Right pneumonectomy syndrome: Report of two cases

We report herein the cases of two infants who developed right pneumonectomy syndrome, both of whom were born with gross C-type esophageal atresia (EA/TEF), and a hypoplastic right lung arising from the lower esophagus, being a bronchopulmonary foregut malformation (BPFM). Appropriate and well-timed treatments for a variety of sequelae primarily caused by the mediastinal shift must be considered after right pneumonectomy in early childhood.     

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991.     

Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

Video-assisted thoracoscopic wedge resection of solitary pulmonary metastasis from hepatocellular carcinoma

We report a metastatic pulmonary tumor resected by video-assisted thoracoscopic surgery. A 63-year-old female was found to have four nodules of hepatocellular carcinoma (HCC) in January 1991; after non-surgical treatment, the tumors had become necrotic. In June 1992, a new HCC nodule was found. After infusion chemotherapy, it became necrotic. In September 1993, a solitary lung tumor, 2.4 cm in diameter, appeared at the periphery of the right lung. Because the tumor was considered to be a metastatic HCC rather than a primary lung cancer, it was removed by thoracoscopic wedge resection. Although whether metastasectomy contributes to prolongation of survival is still controversial, thoracoscopic pulmonary resection may be indicated for solitary peripheral metastasis, if the primary HCC is well controlled by multidisciplinary treatment.