No abstract

SP-free survival can be regarded as an end-point for TACE refractoriness. Development of progression or need for three sessions of TACE within the first 6 months could be predictive of TACE refractoriness.

No abstract

No abstract

CP score was more important than CP class in predicting the outcome of sorafenib therapy in patients with advanced HCC. Among the CP score components, presence of ascites was a significant prognostic factor, especially in CPB7 patients.

The envelope protein of hepatitis C virus (HCV) is composed of two membrane-associated glycoproteins, E1 and E2. To obtain HCV E2 protein as a secretory form at a high level, we constructed a recombinant chinese hamster ovary (CHO) cell line expressing a C-terminal truncated E2 (E2t) fused to human growth hormone (hGH), CHO/hGHE2t. The hGHE2t fusion protein was purified from the culture supernatant using anti-hGH mAb affinity chromatography at approximately 80% purity. The purified hGHE2t protein appeared to be assembled into oligomers linked by intermolecular disulfide bond(s) when density gradient centrifugation and SDSpolyacrylamide gel electrophoresis were employed. When the purified fusion protein was used for testing its ability to bind to antibodies specific for HCV by enzymelinked immunosorbent assay, the protein was recognized by antibodies in sera from 90% of HCV-positive patients. Treatment of hGHE2t protein by ␤-mercaptoethanol, but not by heat and SDS, significantly reduced its reactivity to the antibodies of patient sera, suggesting that intermolecular and/or intramolecular disulfide bonds are important for its ability to recognize its specific antibody and that the E2 protein contains discontinuous antigenic epitope(s). Hepatitis C virus (HCV)1 is a major causative agent of posttransfusion and sporadic non-A, non-B hepatitis throughout the world (1, 2). In most cases, the virus appears to cause a persistent infection. Previous studies indicate that the development of chronic liver diseases, cirrhosis, and hepatocellular carcinoma is associated with chronic HCV infection (3).Comparative analyses of the genomes from several HCV strains indicate that HCV is a member of the family Flaviviridae, which includes flaviviruses and pestiviruses (4). The HCV genome is a 9.5-kilobase positive-strand RNA from which a single polypeptide is expressed and processed by cellular and viral proteinases to produce the putative viral structural and nonstructural proteins (4 -6). It was previously shown that structural proteins were composed of the core protein of 18 -22 kDa and two glycosylated envelope proteins, E1 of 31-35 kDa and E2 of 58 -74 kDa (5, 7-11). Although some lymphocyte cell lines have shown to support the limited replication of HCV, there has not been in vitro cell culture system efficiently enough to be used for viral propagation and for detailed virological studies (12). Expression studies using recombinant cDNA templates are the only means for identifying individual HCV proteins and to study their roles in the pathogenesis of HCV infection.The hydrophobicity profile of HCV polyprotein suggested that the HCV E2 protein corresponds to the flavivirus NS1 glycoprotein and the major pestivirus envelope protein gp53/ gp55 (E2; gp53 in bovine viral diarrhea virus and gp55 in hog cholera virus), which were reported to induce protective immunity in experimental animals (13,14). HCV envelope proteins are of considerable interest, because experimentally challenged chimpanzees were either protected or shown to a...

Cell death-inducing DFF45-like effector (CIDE) domains, initially identified in apoptotic nucleases, form a family with diverse functions ranging from cell death to lipid homeostasis. Here we show that the CIDE domains of Drosophila and human apoptotic nucleases Drep2, Drep4, and DFF40 all form head-to-tail helical filaments. Opposing positively and negatively charged interfaces mediate the helical structures, and mutations on these surfaces abolish nuclease activation for apoptotic DNA fragmentation. Conserved filamentous structures are observed in CIDE family members involved in lipid homeostasis, and mutations on the charged interfaces compromise lipid droplet fusion, suggesting that CIDE domains represent a scaffold for higher-order assembly in DNA fragmentation and other biological processes such as lipid homeostasis.CIDE family | higher-order structure | DNA fragmentation | apoptosis | lipid homeostasis A hallmark of apoptosis is the fragmentation of cellular genomic DNA into a laddered pattern composed of multiples of 180-to 200-bp pieces, which correspond to the DNA length in a nucleosome. Two decades ago, the enzyme responsible for regulated DNA fragmentation was identified from human HeLa cells as a heterodimeric complex of the nuclease DNA fragmentation factor (DFF) of 40 kDa (DFF40), and the inhibitor of 45 kDa (DFF45) (1). Independently, a heterodimeric complex of caspase-activated DNase (CAD) and its inhibitor (ICAD) was identified from mouse lymphoma cells (2, 3). DFF45 and ICAD chaperone the folding of DFF40 and CAD, respectively, and also trap them in inactive states through complex formation. On induction of apoptosis, DFF45 and ICAD are cleaved by activated caspases to release DFF40 and CAD for nuclear translocation and digestion of genomic DNA through large-scale chromatin fragmentation and internucleosomal DNA cleavage (1, 4).DNA fragmentation is the basis for the classical apoptotic TUNEL assay that detects DNA double-strand breaks (5). Because apoptotic cells display "eat-me" signals and are phagocytosed, DNA fragmentation has been proposed as a mechanism for avoiding the transformation of recipient cells by the activated oncogenes or viral genes and reduce the autoimmune response from the strong autoantigenic DNA (6). Clinically, sperm DNA fragmentation is used as a correlative to male infertility (7), and circulating fragmented cellfree DNA is detected as a disease biomarker (8).Human DFF40 and DFF45 and mouse CAD and ICAD contain a conserved N-terminal region known as the cell death-inducing DFF45-like effector (CIDE) domain (9) (Fig. S1A). In Drosophila, four DFF-related proteins (Drep1-4) are critical for apoptotic DNA fragmentation (10-12) (Fig. S1A), and Drep2 also acts as a unique synaptic protein important in learning and behavioral adaptation (13). Biochemical characterization of CIDE-CIDE interactions from Drep1 to Drep4 has revealed that the Drep2 and Drep4 nucleases interact with and are inhibited by . In addition to DNA fragmentation, the CIDE domain-containing proteins CIDEA...

Summary Hepatocellular carcinoma (HCC) has become one of the main indications for liver transplantation. To keep abreast of the times, a comprehensive cancer center may have to perform liver transplantation as a treatment option for HCC. We introduce a learning curve for living‐donor liver transplantation (LDLT) and present our initial experience in a new cancer center as an example to any center considering LDLT. A total of 51 consecutive adult right liver LDLTs performed from January 2005 to January 2008 were analyzed by comparing the first 17 transplants performed with the help of an outside experienced team (group 1) with the middle 17 (group 2) and the last 17 cases (group 3) performed in our center independently. There was no hospital mortality in donors and recipients. In a mean follow‐up of 34 months (range: 12–48 months), there was only one case of late mortality in donor and recipient, respectively. A total of four donors and 12 recipients underwent re‐operations. The warm ischemic time was significantly longer in group 2 than that in groups 1 and 3. Otherwise, there was no significant difference in the operative outcomes among the three groups. Thorough preparation and the assistance of an experienced liver transplantation team at the beginning can facilitate a more rapid learning curve and bring about a good outcome even in a small, newly established institution.