No abstract

A consensus on the indications and contraindications for ALPPS and a standardized operative protocol are needed.

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II plays critical roles in the initiation, elongation and processing of primary transcripts. These activities are at least partially regulated by the phosphorylation of the CTD by three cyclin-dependent protein kinases (CDKs), namely CDK7, CDK8 and CDK9. In this study, we systematically compared the phosphorylation of different recombinant CTD substrates by recombinant CDK7/ CycH/MAT1, CDK8/CycC and CDK9/CycT1 kinases. We showed that CDK7, CDK8 and CDK9 produce different patterns of phosphorylation of the CTD. CDK7/CycH/ MAT1 generates mostly hyperphosphorylated full-length and truncated CTD peptides, while CDK8/CycC and CDK9/CycT1 generate predominantly hypophosphorylated peptides. Total activity towards different parts of the CTD also differs between the three kinases; however, these differences did not correlate with their ability to hyperphosphorylate the substrates. The last 10 repeats of the CTD can act as a suppressor of the activity of the kinases in the context of longer peptides. Our results indicate that the three kinases possess different biochemical properties that could reflect their actions in vivo.Keywords: carboxy-terminal domain; cyclin-dependent kinase; phosphorylation; RNA pol II.The C-terminus of the largest subunit of the eukaryotic RNA polymerase II consists of multiple repeats of a YSPTSPS consensus heptapeptide sequence [1,2]. This part of the polypeptide is referred to as CTD (C-terminal domain). In higher eukaryotes, the CTD consists of 52 heptapeptide repeats [1][2][3]. The N-terminal portion of the CTD contains mainly perfect YSPTSPS repeats; however, the repeats in the C-terminal portion significantly deviate from the consensus [2-5], probably reflecting a more specialized function of this part of the polypeptide. It has been demonstrated that the N-terminal half of the CTD supports RNA synthesis and capping of the primary transcript [6][7][8], whereas the C-terminal half supports splicing and 3¢ processing of the transcripts [6]. The importance of the C-terminal ISPDDSDEEN sequence of the CTD in the regulation of transcript processing has also been shown [9]. The CTD is phosphorylated at multiple sites, which leads to the production of two forms of RNA polymerase II in vivo: a hypophosphorylated form called IIa, and a hyperphosphorylated form called IIo [1,2,4,5]. It is well established that phosphorylation of the CTD regulates the transition of RNA polymerase II from initiation to elongation, the capping of primary transcripts and the efficiency of pol II elongation [1,2,10]. CTD phosphorylation has also been implicated in the cotranscriptional splicing and polyadenylation of nascent transcripts [1,2,10]. However, little is known about how the phosphorylation of different parts of the CTD contributes to these functions.At least three protein kinases are involved directly in the phosphorylation of the CTD and in the regulation of different stages of mRNA synthesis [1,2]. Cyclin dependent kinase (CDK)7, in conjunct...

FRS is robust and able to stratify the risk of developing CR-POPF following PD in diverse North American academic and non-academic institutions. The FRS should be used in research and to guide clinical management of patients post PD in these institutions.

Aim: To investigate whether the long-term outcomes of hepatocellular carcinoma (HCC) was adversely impacted by intermittent hepatic inflow occlusion (HIO) during hepatic resection.Methods: 1549 HCC patients who underwent hepatic resection between 1998 and 2008 were identified from a prospectively maintained database. Intermittent HIO was performed in 931 patients (HIO group); of which 712 patients had a Pringle maneuver as the mechanism for occlusion (PM group), and 219 patients had selective hemi-hepatic occlusion (SO group). There were 618 patients that underwent partial hepatectomy without occlusion (occlusion-free, OF group).Results: The 1-, 3-, and 5- year overall survival (OS) rates were 79%, 59%, and 42% in the HIO group, and 83%, 53%, and 35% in the OF group, respectively. The corresponding recurrence free survival (RFS) rates were 68%, 39%, and 22% in the HIO group, and 74%, 41%, and 18% in the OF group, respectively. There was no significant difference between the 2 groups in OS or RFS (P = 0.325 and P = 0.416). Subgroup analysis showed patients with blood loss over 3000 mL and those requiring transfusion suffered significantly shorter OS and RFS. Blood loss over 3000 mL and blood transfusion were independent risk factors to OS and RFS.Conclusions: The application of intermittent HIO (PM and SO) during hepatic resection did not adversely impact either OS or RFS in patients with HCC. Intermittent HIO is still a valuable tool in hepatic resection, because high intraoperative blood loss resulting in transfusion is associated with a reduction in both OS and RFS.