Adoptive transfer of genetically engineered WT1-specific cytotoxic T lymphocytes does not induce renal injury.

Because WT1 is expressed in leukemia cells, the development of cancer immunotherapy targeting WT1 has been an attractive translational research topic. However, concern of this therapy still remains, since WT1 is abundantly expressed in renal glomerular podocytes. In the present study, we clearly showed that WT1-specific cytotoxic T lymphocytes (CTLs) certainly exerted cytotoxicity against podocytes in vitro; however, they did not damage podocytes in vivo.

Determination of HEL (Hexanoyl-lysine adduct): a novel biomarker for omega-6 PUFA oxidation.

Published evidences indicate that reactive oxygen species (ROS) can induce lipid peroxidation, which plays important role in the pathophysiology of numerous diseases including atherosclerosis, diabetes, cancer and aging process. Monitoring of oxidative modification or oxidative damages of biomolecules may therefore be essential for the understanding of aging, and age-related diseases. N-epsilon-Hexanoyl-lysine (HEL) is a novel lipid peroxidation biomarker which is derived from the oxidation of omega-6 unsaturated fatty acid.

Glycemic variability is an independent predictive factor for development of hepatic fibrosis in nonalcoholic fatty liver disease.

Unlabelled: Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) often have metabolic disorders including insulin resistance and type 2 diabetes mellitus (T2DM). We clarified the predictive factors in glucose metabolism for progression of hepatic fibrosis in patients with NAFLD by the 75-g oral glucose tolerance test (75gOGTT) and a continuous glucose monitoring system (CGMS). One hundred sixty-nine patients (68 female and 101 male patients) with biopsy-proven NAFLD with performance with 75gOGTT were enrolled and divided into four groups according to the stage of hepatic fibrosis (F0-3).

Effects of transport stress on serum alkaline phosphatase activity in beagle dogs.

Here, to determine the effects of transport stress on blood parameters in dogs, we investigated the changes in hematologic and serum chemical parameters in healthy beagle dogs transported from Beijing, China, to Osaka, Japan, to obtain the background data. Only the activity of serum alkaline phosphatase increased clearly upon arrival, a change attributed to transport stress, but the activity gradually reduced afterward. No marked changes in levels of other blood parameters were noted.

Volume-based parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography improve disease recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive axillary lymph nodes.

Purpose: To determine whether volume-based parameters on pretreatment (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence.

Methods And Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes.

Effects of auditory stimuli in the horizontal plane on audiovisual integration: an event-related potential study.

This article aims to investigate whether auditory stimuli in the horizontal plane, particularly originating from behind the participant, affect audiovisual integration by using behavioral and event-related potential (ERP) measurements. In this study, visual stimuli were presented directly in front of the participants, auditory stimuli were presented at one location in an equidistant horizontal plane at the front (0°, the fixation point), right (90°), back (180°), or left (270°) of the participants, and audiovisual stimuli that include both visual stimuli and auditory stimuli originating from one of the four locations were simultaneously presented. These stimuli were presented randomly with equal probability; during this time, participants were asked to attend to the visual stimulus and respond promptly only to visual target stimuli (a unimodal visual target stimulus and the visual target of the audiovisual stimulus).

Lateral lymph-node dissection for rectal cancer: meta-analysis of all 944 cases undergoing surgery during 1975-2004.

Background: Colorectal cancer is the third most common cancer and leading cause of cancer-related death in Japan. One of the major problems in rectal cancer surgery is local recurrence. Pelvic sidewall dissection (PSD) has the potential to reduce local recurrence.

Development of a novel redirected T-cell-based adoptive immunotherapy targeting human telomerase reverse transcriptase for adult T-cell leukemia.

Although adult T-cell leukemia (ATL) has a poor prognosis, successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) in some cases suggests that a cellular immune-mediated strategy can be effective. So far, however, no effective target for anti-ATL immunotherapy has been defined. Here we demonstrated for the first time that human telomerase reverse transcriptase (hTERT) is a promising therapeutic target for ATL, and we developed a novel redirected T-cell-based immunotherapy targeting hTERT.

Hepatocyte destruction with enhanced collagen synthesis: characteristic feature of chronic hepatitis C patients on haemodialysis.

Hepatitis C virus (HCV) infection is frequent among patients with end-stage renal disease on haemodialysis and is considered to be an independent risk factor for mortality in this setting. However, only a few of these patients are treated with anti-hepatitis virus treatment before the development of end-stage renal disease. Recent guidelines recommend identification of patients with good prognoses who are in need of interferon treatment, but we know little of patients who must be treated urgently.

Structure of the catalytic region of DNA ligase IV in complex with an Artemis fragment sheds light on double-strand break repair.

Nonhomologous end joining (NHEJ) is central to the repair of double-stranded DNA breaks throughout the cell cycle and plays roles in the development of the immune system. Although three-dimensional structures of most components of NHEJ have been defined, those of the catalytic region of DNA ligase IV (LigIV), a specialized DNA ligase known to work in NHEJ, and of Artemis have remained unresolved. Here, we report the crystal structure at 2.

Co-introduced functional CCR2 potentiates in vivo anti-lung cancer functionality mediated by T cells double gene-modified to express WT1-specific T-cell receptor.

Background And Purpose: Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR) or chimeric antigen receptor (CAR) has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor.

Methodology/principal Findings: Human lung cancer cells variously express a tumor antigen, Wilms' Tumor gene product 1 (WT1), and an inflammatory chemokine, CCL2.

Safety and feasibility for single-incision laparoscopic cholecystectomy in local community hospital: a retrospective comparison with conventional 4-port laparoscopic cholecystectomy.

Background: The aim of this study was to evaluate the safety and feasibility for single-incision laparoscopic cholecystectomy (SILC) by retrospective comparison with conventional laparoscopic cholecystectomy (CLC) in a local community hospital.

Methods: SILC was introduced and performed in 57 patients for benign gallbladder diseases. Their clinical data were compared with those of 62 patients treated with CLC.

Differentiation of tumor recurrence from radiation-induced pulmonary fibrosis after stereotactic ablative radiotherapy for lung cancer: characterization of 18F-FDG PET/CT findings.

Objective: Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is now a standard treatment option for patients with stage I non-small cell lung cancer or oligometastatic lung tumor who are medically inoperable or medically operable but refuse surgery. When mass-like consolidation is observed on follow-up CT after SABR, it is sometimes difficult to differentiate tumor recurrence from SABR-induced pulmonary fibrosis. In this study, we evaluated the role of (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) in differentiating tumor recurrence from radiation fibrosis after SABR.

Factors affected by surgical technique when treating total colonic aganglionosis: laparoscopy-assisted versus open surgery.

Introduction: We compared laparoscopy-assisted Duhamel (Lap-D) with open surgery (Duhamel or Soave = D/S) for treating total colonic aganglionosis (TCA) in children to establish what factors may affect outcome.

Methods: Fourteen TCA cases treated between 1990 and 2010 were reviewed. Open D/S (O-D/S) through a vertical midline abdominal incision was routine from 1990 to 2005, whereupon Lap-D became routine.

Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test.

The leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan (SN-38; FOLFIRI) regimens with or without molecularly-targeted drugs are widely used as first-line chemotherapy in the treatment of advanced colorectal cancer (CRC). Whether FOLFOX or FOLFIRI is administered first is not significant, however, it is essential that full administration of the targeted dosages of all 3 drugs, 5-FU, l-OHP and SN-38, is achieved. However, this is not always possible and second-line chemotherapy must be abandoned in certain cases.

Serial block-face scanning electron microscopy combined with double-axis electron beam tomography provides new insight into cellular relationships.

To evaluate the advantages of combination of two advanced electron microscopic technologies such as serial block-face scanning electron microscopy and double-axis electron beam tomography, we analyzed the three-dimensional morphology of cellular relationships between dendritic and plasma cells in the synovial membrane from patients with rheumatoid arthritis, using the combined approach.

Rapid growth hormone measurement during transsphenoidal surgery: analysis of 252 acromegalic patients.

The usefulness of rapid growth hormone (GH) measurement was retrospectively evaluated as an indicator of total tumor removal during surgery and compared with several reported criteria in 252 acromegalic patients who underwent transsphenoidal surgery at Toranomon Hospital between 2006 and 2008. GH levels were measured in blood samples obtained before surgery, at the start of tumor removal, and every 20 minutes thereafter until 20 minutes after total tumor removal as judged by the operator. Intraoperative GH dynamics were compared between 201 patients fulfilling the Cortina consensus criteria (successful group) and 37 patients who did not (unsuccessful group).

Thoracoscopic plication for diaphragmatic eventration in a neonate.

Background: Currently, thoracoscopic surgery is replacing thoracotomy for an ever increasing number of indications, even in pediatric surgery. However, there are few reports describing thoracoscopic plication (TP) for diaphragmatic eventration in children, particularly in neonates. We report a case of TP under single-lung ventilation in a neonate with diaphragmatic eventration.

Prognosis of primary central nervous system lymphoma treated with radiotherapy alone.

Purpose: Standard treatment for patients with primary central nervous system (CNS) lymphoma involves combining high-dose methotrexate-based chemotherapy and radiation. However, chemotherapy is sometimes contraindicated, and radiotherapy alone becomes the only option. We retrospectively investigated the clinical outcomes of primary CNS lymphoma patients treated with radiotherapy alone.

Good response to leucovorin and fluorouracil plus oxaliplatin and cetuximab therapy in a patient with metastatic ascending colon cancer harboring a KRAS p.G13D mutation.

The effectiveness of cetuximab (Cmab) against KRAS p.G13D mutant-type tumors has been reported. In this study, we report a case of metastatic ascending colon cancer harboring a KRAS p.

Accuracy for predicting adhesion between meningioma and the brain by using brain surface motion imaging: comparison between single and double acquisition methods.

Introduction: The presence of adhesions between the brain and the meningioma is an important factor that determines the success of total surgical removal. Brain surface motion imaging enables assessment of the dynamics of brain surface motion. A subtraction image of pulse-gated heavily T2-weighted images in different phases of the cardiac cycle provides a stripe pattern on the surface of the pulsating brain.

HLA-restricted presentation of WT1 tumor antigen in B-lymphoblastoid cell lines established using a maxi-EBV system.

Lymphoblastoid cell lines (LCLs), which are established by in vitro infection of peripheral B-lymphocytes with Epstein-Barr virus (EBV), are effective antigen-presenting cells. However, the ability of LCLs to present transduced tumor antigens has not yet been evaluated in detail. We report a single-step strategy utilizing a recombinant EBV (maxi-EBV) to convert B-lymphocytes from any individuals into indefinitely growing LCLs expressing a transgene of interest.

Structural insights into the role of domain flexibility in human DNA ligase IV.

Knowledge of the architecture of DNA ligase IV (LigIV) and interactions with XRCC4 and XLF-Cernunnos is necessary for understanding its role in the ligation of double-strand breaks during nonhomologous end joining. Here we report the structure of a subdomain of the nucleotidyltrasferase domain of human LigIV and provide insights into the residues associated with LIG4 syndrome. We use this structural information together with the known structures of the BRCT/XRCC4 complex and those of LigIV orthologs to interpret small-angle X-ray scattering of LigIV in complex with XRCC4 and size exclusion chromatography of LigIV, XRCC4, and XLF-Cernunnos.