Improvement of Biophysical Properties and Affinity of a Human Anti-L1CAM Therapeutic Antibody through Antibody Engineering Based on Computational Methods.

The biophysical properties of therapeutic antibodies influence their manufacturability, efficacy, and safety. To develop an anti-cancer antibody, we previously generated a human monoclonal antibody (Ab417) that specifically binds to L1 cell adhesion molecule with a high affinity, and we validated its anti-tumor activity and mechanism of action in human cholangiocarcinoma xenograft models. In the present study, we aimed to improve the biophysical properties of Ab417.

Realistic Advantages of Early Surgical Drain Removal after Pancreatoduodenectomy: A Single-Institution Retrospective Study.

The latest guidelines from the Enhanced Recovery After Surgery (ERAS) Society stated that early drain removal after pancreatoduodenectomy (PD) is beneficial in decreasing complications including postoperative pancreatic fistulas (POPFs). This study aimed to ascertain the actual benefits of early drain removal after PD. The data of 450 patients who underwent PD between 2018 and 2020 were retrospectively reviewed.

Prognostic Role of in Clear Cell Renal Cell Carcinoma: A Retrospective Multi-Cohort Analysis.

Transmembrane p24 trafficking protein 3 (TMED3) is a metastatic suppressor in colon cancer and hepatocellular carcinoma. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that TMED3 could be a new prognostic marker for ccRCC.

Comparison analysis of left-side versus right-side resection in bismuth type III hilar cholangiocarcinoma.

Backgrounds/aims: Several studies report worse prognosis after left-side compared to right-side liver resection in patients with perihilar cholangiocarcinoma. In this study, we compared outcomes of left-side and right-side resections for Bismuth type III hilar cholangiocarcinoma and analyzed factors affecting survival.

Methods: From May 1995 to December 2012, 179 patients underwent surgery at Samsung Medical Center for type III hilar cholangiocarcinoma.

Zinc-mediated Reversible Multimerization of Hsp31 Enhances the Activity of Holding Chaperone.

Hsp31 protein, belonging to the DJ-1/ThiJ/PfpI superfamily, increases the survival of Escherichia coli under various stresses. While it was reported as a holding chaperone, Hsp31 was also shown to exhibit the glyoxalase III activity in subsequent study. Here, we describe our finding that Hsp31 undergoes a Zn-mediated multimerization (HMW), resulting in an enhanced chaperone activity.

Backbone resonance assignments of the Escherichia coli 62 kDa protein, Hsp31.

Dimeric Hsp31 protein was first characterized as a holding chaperone of Escherichia coli (E. coli), and has been suggested as having protease activity due to the presence of a potential catalytic triad, Cys185, His186, and Asp214. However, it has recently been reported that Hsp31 displays a relatively strong glyoxalase III activity that can decompose reactive carbonyl species (methylglyoxal and glyoxal) in the absence of additional cofactor.

Three-dimensional image transmission and reconstruction for multisensor imaging system using interleaver division multiple access.

In this paper, we present an optical image transmission and reconstruction system of 3D objects using a multisensor imaging system and interleaver division multiple access (IDMA) channel. When the 3D image data from the multisensor imaging system are transmitted over a wireless channel, loss or distortion of original data may occur by wireless channel environment, such as multiple access interference and channel noise. To solve this problem, an optical 3D image reconstruction scheme and IDMA technique can be used.

Stereospecific mechanism of DJ-1 glyoxalases inferred from their hemithioacetal-containing crystal structures.

Unlabelled: DJ-1 family proteins have recently been characterized as novel glyoxalases, although their cofactor-free catalytic mechanisms are not fully understood. Here, we obtained crystals of Arabidopsis thaliana DJ-1d (atDJ-1d) and Homo sapiens DJ-1 (hDJ-1) covalently bound to glyoxylate, an analog of methylglyoxal, forming a hemithioacetal that presumably mimics an intermediate structure in catalysis of methylglyoxal to lactate. The deuteration level of lactate supported the proton transfer mechanism in the enzyme reaction.

Pathologic T1 subclassification of ampullary carcinoma with perisphincteric or duodenal submucosal invasion: Is it T1b?

Context: In ampullary carcinoma staging, T1 is defined as a tumor limited to the ampulla of Vater or the sphincter of Oddi, and T2 is defined as invasion into the duodenal wall. However, the definition of duodenal wall invasion is vague. Ampullary carcinoma that invades beyond the sphincteric of Oddi (perisphincteric invasion) or into the duodenal submucosa could be considered pT1b because submucosal invasion is classified as pT1b in gastrointestinal tract tumors.

Glucagon/insulin ratio in preoperative screening before pancreatic surgery: correlation with hemoglobin A1C in subjects with and without pancreatic cancer.

Role of impaired suppression of glucagon secretion in the pathogenesis of pancreatic cancer-associated diabetes has been suggested. We examined the correlation between glucagon/insulin ratio (G/I) after glucose challenge and hemoglobin A1C (A1C) in subjects with and without pancreatic cancer. Data were gathered from a preoperative screening 75-g oral glucose tolerance test in patients who would eventually undergo pancreatic resection.

Novel glyoxalases from Arabidopsis thaliana.

We examined six Arabidopsis thaliana genes from the DJ-1/PfpI superfamily for similarity to the recently characterized bacterial and animal glyoxalases. Based on their sequence similarities, the six genes were classified into two sub-groups consisting of homologs of the human DJ-1 gene and the PH1704 gene of Pyrococcus horikoshii. Unlike the homologs from other species, all the A.

Structural alteration of Escherichia coli Hsp31 by thermal unfolding increases chaperone activity.

Escherichia coli Hsp31, encoded by hchA, is a heat-inducible molecular chaperone. We found that Hsp31 undergoes a conformational change via temperature-induced unfolding, generating a high molecular weight (HMW) form with enhanced chaperone activity. Although it has previously been reported that some subunits of the Hsp31 crystal structure show structural heterogeneity with increased hydrophobic surfaces, Hsp31 basically forms a dimer.

Long-term effects of pancreaticoduodenectomy on glucose metabolism.

Background:   To analyse the association between pancreatogenic diabetes and the volume of the remnant pancreas after pancreaticoduodenectomy and to identify clinicopathologic factors correlated with pancreatogenic diabetes.

Methods:   Among the patients who underwent pancreaticoduodenenctomy from 2003 to 2004, 55 patients who survived by 2009 and were able to measure the volume of the pancreas pre- and post-operatively by CT volumetry were included in this study. Twelve patients had diabetes before surgery.

Ablation of Rassf2 induces bone defects and subsequent haematopoietic anomalies in mice.

RASSF2 belongs to the Ras-association domain family (RASSF) of proteins, which may be involved in the Hippo signalling pathway. However, the role of RASSF2 in vivo is unknown. Here, we show that Rassf2 knockout mice manifest a multisystemic phenotype including haematopoietic anomalies and defects in bone remodelling.

The expression of phospho-AKT1 and phospho-MTOR is associated with a favorable prognosis independent of PTEN expression in intrahepatic cholangiocarcinomas.

AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry.

Hsp31 of Escherichia coli K-12 is glyoxalase III.

Hsp31 encoded by hchA is known as a heat-inducible molecular chaperone. Although structure studies revealed that Hsp31 has a putative catalytic triad consisting of Asp-214, His-186 and Cys-185, its enzymatic function, besides weak amino-peptidase activity, is still unknown. We found that Hsp31 displays glyoxalase activity that catalyses the conversion of methylglyoxal (MG) to d-lactate without an additional cofactor.

Male-like sexual behavior of female mouse lacking fucose mutarotase.

Background: Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM) was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated.

Carcinoma of the middle bile duct: is bile duct segmental resection appropriate?

Aim: To compare survival between bile duct segmental resection (BDSR) and pancreaticoduodenectomy (PD) for treating distal bile duct cancers.

Methods: Retrospective analysis was conducted for 45 patients in a BDSR group and for 149 patients in a PD group.

Results: The T-stage (P < 0.

Comparison of different pancreatic anastomosis techniques using the definitions of the International Study Group of Pancreatic Surgery: a single surgeon's experience.

Objectives: We aimed to compare different techniques using the definitions of the International Study Group of Pancreatic Surgery for postoperative complications after pancreaticoduodenectomy.

Methods: The perioperative data of 119 patients that underwent pancreaticoduodenectomy by a single surgeon were retrospectively analyzed. Pancreaticojejunal anastomosis was performed using the dunking method (n = 39), the duct-to-mucosa anastomosis method (n = 40), and the duct-to-mucosa adaptation (n = 40).

Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients.

The purpose of this study was to evaluate the effects of autologous islet transplantation (ITx) on glucose homeostasis and insulin secretory function after partial pancreatectomy (Px). Fourteen nondiabetic patients who underwent distal Px and autologous ITx for benign pancreatic tumors were enrolled in the study (Px + ITx group). Fourteen normal glucose-tolerant controls and 6 Px without ITx controls were recruited, and all groups were followed over a 24-month period.

Mutation analysis of p31comet gene, a negative regulator of Mad2, in human hepatocellular carcinoma.

Failure of mitotic checkpoint machinery leads to the chromosomal missegregation and nuclear endoreduplication, thereby driving the emergence of aneuploidy and tetraploidy population. Although abnormal nuclear ploidy and the resulting impairment of mitotic checkpoint function are typical physiological event leading to human hepatocellular carcinoma, any mutational change of mitotic checkpoint regulators has not yet been discovered. Therefore, we investigated the mutation of p31(comet), a recently identified mitotic checkpoint regulator, in human hepatocellular carcinoma.

Characterization and role of fucose mutarotase in mammalian cells.

L-Fucose for mammalian glycosylation contains an anomeric carbon atom generating alpha- and beta-L-fucoses. Based on sequence comparison of mouse and human homologs with the prokaryotic fucose mutarotases (FucU) characterized previously, we investigated their function in mammalian cells. By nuclear magnetic resonance (NMR) measurement with saturation difference analysis, the purified mammalian mutarotases were demonstrated to be involved in an interconversion between the two anomeric forms with comparable efficiency as that of the Escherichia coli FucU.

Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma.

Background: Erlotinib, in combination with gemcitabine, has shown clinical benefits in pancreatic adenocarcinoma patients. The presence of EGFR mutations and increased EGFR copy numbers in pancreatic adenocarcinoma was explored.

Methods: Sixty-six pancreatic cancer patients were included in the analysis.

Missing effect of glutamine supplementation on the surgical outcome after pancreaticoduodenectomy for periampullary tumors: a prospective, randomized, double-blind, controlled clinical trial.

Background: The effect of glutamine (Gln) supplementation in patients undergoing a major operation has not been conclusively established. This study was designed to elucidate the effect of Gln supplementation on the surgical outcome after a pancreaticoduodenectomy (PD) for periampullary tumors.

Methods: A prospective, randomized, double-blind, and controlled clinical trial was undertaken for patients who underwent a classical PD or a pylorus-preserving PD for periampullary tumors.

Feature genes of hepatitis B virus-positive hepatocellular carcinoma, established by its molecular discrimination approach using prediction analysis of microarray.

Recent introduction of a learning algorithm for cDNA microarray analysis has permitted to select feature set to accurately distinguish human cancers according to their pathological judgments. Here, we demonstrate that hepatitis B virus-positive hepatocellular carcinoma (HCC) could successfully be identified from non-tumor liver tissues by supervised learning analysis of gene expression profiling. Through learning and cross-validating HCC sample set, we could identify an optimized set of 44 genes to discriminate the status of HCC from non-tumor liver tissues.