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Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer-related genes in hepatocarcinogenesis. However, the expensive and time-consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver-specific transgenic approach was developed, in which a hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor-suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.

The aim of this study was to develop a highly reliable radiofluorination method for the preparation of N-{2-[4-(2-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4-(18) F-fluoromethylcyclohexane)carboxamide ([(18) F]Mefway) by using a fully automated system. The optimal condition is composed of two parts. The extraction system of the trapped F-18 in the anion exchange resin (i.e., quaternary methylamine cartridge) is a complex of Kryptofix 2.2.2. (K222, 4 mg/0.9 mL methanol) and K2 CO3 (1 mg/0.1 mL H2 O). After removing the solvents, the trans-tosylated Mefway precursor (1 mg/0.5 mL acetonitrile) was reacted with dried K222-K[(18) F] at 100°C for 5 min. After purification and formulation, [(18) F]Mefway was obtained with 38 ± 2.4% (decay corrected, n = 34) radiochemical yield, a total synthesis time of 52 ± 3.4 min, specific activity was 120.6 ± 8.7 GBq/µmol at the end of synthesis and a radiochemical purity of 99%. According to the quality control tests, formulated [(18) F]Mefway is suitable to apply parenteral clinical application.

Aim Attention deficit has been reported in both schizophrenia patients and patients with major depressive disorder (MDD). The aim of this study was to elucidate the deficits in sustained attention and associated neural network dysfunctions in schizophrenia patients and MDD patients, and to investigate the difference between the two patient groups. Methods Twelve schizophrenia patients, 12 patients with non-psychotic MDD, and 12 healthy control subjects participated in this study. A sustained attention to response task (SART) was used to measure attention capacity. Cerebral blood flow (CBF) during attention tasks was measured using H215O positron emission tomography. Statistical parametric mapping and analysis of covariance were performed to compare the behavioral performance and CBF changes during SART among three groups. Results Behavioral performances were not significantly different among the three groups except for an increased commission error rate in the schizophrenia group. Regional CBF during SART was significantly reduced in the left inferior frontal gyrus, the left cuneus, and the right superior parietal lobule and increased in the right superior frontal gyrus and the right cuneus in the schizophrenia group compared to the healthy control group. In the MDD group, neither significant regional CBF difference nor behavioral deficit was found compared to the healthy control group. Conclusion Behavioral performance deficit and perfusion changes in the prefrontal and parietal cortices during SART were observed only in the schizophrenia group. Prefrontal and parietal network dysfunction for sustained attention may be involved in the pathophysiology of schizophrenia.

Aim: Liver transplantation (LT) is a curative treatment for localized hepatocellular carcinoma (HCC), but the recurrence rate after LT is about 10–20%, with a dismal prognosis. Little data exist as to the natural history, treatment outcome and optimal treatment of recurrent HCC after LT. We reviewed various treatment modalities given to patients with recurrent HCC after LT. Methods: Among 132 patients who underwent LT for localized HCC, we retrospectively reviewed medical records of 39 of the 132 patients who developed recurrent HCC after LT. We analyzed the clinical outcome of various treatment modalities and treatment-related adverse events. Results: A total of 39 (29%) of the original 132 patients had recurrent HCC, most recurrences (82%) having occurred within 1 year after LT and involved extrahepatic lesions. Only seven patients had recurrent disease limited to the liver. The median overall survival from the initial treatment of all relapsed patients was 6.9 months. There were various initial treatment modalities, namely palliative systemic chemotherapy, trans-catheter arterial chemo-embolization/infusion (TACE/I), radiation therapy (RT), surgical resection and no treatment. The median overall survival was 9.5 months for first-line chemotherapy, including those who had prior local therapy, 6.3 months TACE/I and 6.9 months for RT. Conclusion: Various clinical approaches have been used to treat patients with recurrent HCC after LT in a clinical setting. More effective strategies and clinical guidelines for recurrent HCC following LT must be established.

Background: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used 18F-2-fluoro-2-deoxyglucose (18F-FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC. Materials and methods: A total of 29 patients with HCC were included. Baseline 18F-FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient. Results: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0–12.0] and 3.8 months (95% CI: 1.4–6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α-fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors (P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too (P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax (n=10

BACKGROUND: Metabolic activity assessed by 18F-fluorodeoxyglocuse-positron emission tomography (18F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Over a 3-year period (2005-2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received 18F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated. RESULTS: The median maximal tumor SUV was 6.1 (range, 2.4-∼19.2). Patients with low maximal tumor SUVs (

Purpose This retrospective study was conducted to determine the characteristic imaging and histopathologic features of breast fibroadenomas in kidney-transplant recipients given chronic cyclosporin A immunosuppressive therapy after the transplantation and to compare these characteristics with those from a control group. Methods From January 1, 1990, through December 31, 1999, 486 women underwent renal transplantation at our institution. All patients subsequently received immunosuppressive therapy with cyclosporin A and prednisolone. Ten (2%) of these women had developed breast fibroadenomas during this chemotherapy. We compared the data obtained on this group's fibroadenomas with those obtained from those in the control group, which comprised 100 women with fibroadenomas but who had never undergone organ transplantation or immunosuppressive therapy. Results Twenty-two fibroadenomas developed in the 10 transplant recipients. Eight of those 10 had multiple lesions, and 7 were affected bilaterally. The mean diameter of the fibroadenomas was 4.2 ± 2.5 cm. Mammographically, the lesions were round or oval high-density masses with well-circumscribed margins and no calcification or spiculation. Sonographically, the lesions were relatively highly echogenic and had a lower ratio of the longitudinal to the anteroposterior diameter (L /AP) than did those in the control group. Histopathologically, the features of these lesions were generally typical of fibroadenomas, but some were more typical of malignant lesions. Among the 100 control patients, 146 fibroadenomas developed; 33 women had multiple lesions, and 12 were affected bilaterally. Their fibroadenomas had a mean diameter of 2.1 ± 1.5 cm, and the imaging features of these lesions were typical of fibroadenomas. Conclusions The fibroadenomas that developed in kidney-transplant recipients given chronic cyclosporin A and prednisolone immunosuppressive therapy had a tendency to be multiple, bilateral, and larger than those that developed in the control patients. These fibroadenomas also exhibited some imaging features that differed from those of typical fibroadenomas that develop in women who have not undergone organ transplantation or immunosuppressive therapy. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:69–77, 2004

In a 40-year-old man who had suffered from vague and generalized bone pains for 7 years due to oncogenic osteomalacia, the causative tumour was finally detected by Indium-111 octreotide scintigraphy. Some characteristics of the tumour associated with oncogenic osteomalacia, such as its size, growth rate, location and origin, often make the diagnosis difficult. However, the recent discovery of somatostatin receptors in mesenchymal tumours, which are the most common cause of oncogenic osteomalacia, has raised the possibility of early detection of this devastating disorder. Here, we report that radiolabelled octreotide scintigraphy has a potential role as a diagnostic tool in oncogenic osteomalacia. However, the exact role of somatostatin receptors in tumours associated with oncogenic osteomalacia still remains elusive.

The melt polycondensation reaction of the prepolymer prepared from N-(benzyloxycarbonyl)-L-aspartic acid anhydride (N-CBz-L-aspartic acid anhydride) and low molecular weight poly(ethylene glycol) (PEG) using titanium isopropoxide (TIP) as a catalyst produced the new biodegradable poly(L-aspartic acid-co-PEG). This new copolymer had pendant amine functional groups along the polymer backbone chain. The optimal reaction conditions for the preparation of the prepolymer were obtained by using a 0.12 mol % of p-toluenesulfonic acid with PEG 200 for 48 h. The weight-average molecular weight of the prepolymer increased from 1,290 to 31,700 upon melt polycondensation for 6 h at 130°C under vacuum using 0.5 wt % TIP as a catalyst. The synthesized monomer, prepolymer, and copolymer were characterized by FTIR, 1H- and 13C-NMR, and UV spectrophotometers. Thermal properties of the prepolymer and the protected copolymer were measured by DSC. The glass transition temperature (Tg) of the prepolymer shifted to a significantly higher temperature with increasing molecular weight via melt polycondensation reaction, and no melting temperature was observed. The in vitro hydrolytic degradation of these poly(L-aspartic acid-co-PEG) was measured in terms of molecular weight loss at different times and pHs at 37°C. This pH-dependent molecular weight loss was due to a simple hydrolysis of the backbone ester linkages and was characterized by more rapid rates of hydrolysis at an alkaline pH. These new biodegradable poly(L-aspartic acid-co-PEG)s may have potential applications in the biomedical field. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2949–2959, 1998

Signal-intensity characteristics of magnetic resonance (MR) images were assessed in five patients and in 10 rabbits with tuberculous arthritis. MR imaging findings were compared with histologic findings in the animal study. In both of clinical and experimental cases, tuberculous lesions showed both intermediate and high signal intensity on T2-weighted images, while they showed heterogeneously intermediate signal intensity on T1-weighted images. As T2-weighted images were compared with pathologic specimens, intermediate signal intensity corresponded to caseous necrosis, whereas high signal intensity related to granulomas or effusion. Postcontrast T1-weighted images showed enhancement at the peripheries rather than the centers of tuberculous lesions. These results indicate that tuberculous arthritis should be included in the differential diagnosis when intra-articular lesions with low or intermediate signal intensity are found on T2-weighted images.