Current Trends in Targeted Therapies for Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is one of the most frequently occurring tumors in the central nervous system and the most malignant tumor among gliomas. Despite aggressive treatment including surgery, adjuvant TMZ-based chemotherapy, and radiotherapy, GBM still has a dismal prognosis: the median survival is 14.6 months from diagnosis. To date, many studies report several determinants of resistance to this aggressive therapy: (1) O6-methylguanine-DNA methyltransferase (MGMT), (2) the complexity of several altered signaling pathways in GBM, (3) the existence of glioma stem-like cells (GSCs), and (4) the blood-brain barrier. Many studies aim to overcome these determinants of resistance to conventional therapy by using various approaches to improve the dismal prognosis of GBM such as modifying TMZ administration and combining TMZ with other agents, developing novel molecular-targeting agents, and novel strategies targeting GSCs. In this paper, we review up-to-date clinical trials of GBM treatments in order to overcome these 4 hurdles and to aim at more therapeutical effect than conventional therapies that are ongoing or are about to launch in clinical settings and discuss future perspectives

Ultrathin Platinum Film Hydrogen Sensors with a Twin-T Type Notch Filter Circuit

In recent years, hydrogen energy has garnered attention as a potential solution for mitigating greenhouse gas emissions. However, concerns regarding the inherent risk of hydrogen gas leakage and potential explosions have necessitated the development of advanced sensors. Within our research group, we have innovated an ultrathin platinum (Pt) film hydrogen sensor that gauges resistance changes in Pt thin films when exposed to hydrogen gas. Notably, the sensitivity of each sensor is contingent upon the thickness of the Pt film. To address the challenge of detecting hydrogen using multiple sensors, we integrated the ultrathin Pt film as a resistance element within a twin-T type notch filter. This filter exhibits a distinctive reduction in output signals at a specific frequency. The frequency properties of the notch filter dynamically alter with changes in the resistance of the Pt film induced by hydrogen exposure. Consequently, the ultrathin Pt film hydrogen sensor monitors output signal variations around the notch frequency, responding to shifts in frequency properties. This innovative approach enables the electrical control of sensor sensitivity by adjusting the operating frequency in proximity to the notch frequency. Additionally, the simultaneous detection of hydrogen by multiple sensors was successfully achieved by interconnecting sensors with distinct notch frequencies in series

Numerical analysis and measurement of glass flow in a small melting furnace

Control of glass flow in a glass tank is a key technology in the glass melting process. The flow and temperature distributions of the glass melt greatly affect the quality of glass products. However, these phenomena have not been well understood due to the difficulty involved in the measurement as a result of the high temperature of the glass melt. Α small melting furnace was developed that was heated by electrodes. The glass flow was measured and analyzed by 3-D computer simulation. The numerical results show good agreement with the experimentally measured values. It is shown that it is possible to control the glass convection using a variety of the electric boosting conditions, the heat loss through walls and the charged glass batch. The quality of glass melt was evaluated by analyzing the temperature histories of virtual particles the furnace was charged with. It is found that the temperature of the particles is high and stable near the throat, as shown by the experimental data

Production of 3π03\pi^{0} and η2π0\eta2\pi^{0} from π−p\pi^{-}p collision in GAMS experiment

The data on the pi- p --> M0 n, with M0 = pi0 pi0 pi0 or pi0 pi0 eta obtained in the GAMS experiment may be useful to study the sigma(400--700) and a_1^chi (1000), which can be taken as chiral partners of pi and rho, respectively. A preliminary analysis for 3pi0 invariant mass spectra gives a support for the assumed a_1^chi with a mass of 930 MeV and Gamma = 170 MeV

Biomechanical Analysis of a Pedicle Screw-Rod System with a Novel Cross-Link Configuration

Study DesignThe strength effects of a pedicle screw-rod system supplemented with a novel cross-link configuration were biomechanically evaluated in porcine spines.PurposeTo assess the biomechanical differences between a conventional cross-link pedicle screw-rod system versus a novel cross-link instrumentation, and to determine the effect of the cross-links.Overview of LiteratureTransverse cross-link systems affect torsional rigidity, but are thought to have little impact on the sagittal motion of spinal constructs. We tested the strength effects in pullout and flexion-compression tests of novel cross-link pedicle screw constructs using porcine thoracic and lumbar vertebrae.MethodsFive matched thoracic and lumbar vertebral segments from 15 porcine spines were instrumented with 5.0-mm pedicle screws, which were then connected with 6.0-mm rods after partial corpectomy in the middle vertebral body. The forces required for construct failure in pullout and flexion-compression tests were examined in a randomized manner for three different cross-link configurations: un-cross-link control, conventional cross-link, and cross-link passing through the base of the spinous process. Statistical comparisons of strength data were analyzed using Student's t-tests.ResultsThe spinous process group required a significantly greater pullout force for construct failure than the control group (p=0.036). No difference was found between the control and cross-link groups, or the cross-link and spinous process groups in pullout testing. In flexion-compression testing, the spinous processes group required significantly greater forces for construct failure than the control and cross-link groups (p<0.001 and p=0.003, respectively). However, there was no difference between the control and cross-link groups.ConclusionsA novel cross-link configuration that features cross-link devices passing through the base of the spinous processes increased the mechanical resistance in pullout and flexion-compression testing compared to un-cross-link constructs. This configuration provided more resistance to middle-column damage under flexion-compression testing than conventional cross-link configuration

Identification of novel biomarker candidates by proteomic analysis of cerebrospinal fluid from patients with moyamoya disease using SELDI-TOF-MS

<p>Abstract</p> <p>Background</p> <p>Moyamoya disease (MMD) is an uncommon cerebrovascular condition with unknown etiology characterized by slowly progressive stenosis or occlusion of the bilateral internal carotid arteries associated with an abnormal vascular network. MMD is a major cause of stroke, specifically in the younger population. Diagnosis is based on only radiological features as no other clinical data are available. The purpose of this study was to identify novel biomarker candidate proteins differentially expressed in the cerebrospinal fluid (CSF) of patients with MMD using proteomic analysis.</p> <p>Methods</p> <p>For detection of biomarkers, CSF samples were obtained from 20 patients with MMD and 12 control patients. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with an anion exchange chip in three different buffer conditions. After expression difference mapping was undertaken using the obtained protein profiles, a comparative analysis was performed.</p> <p>Results</p> <p>A statistically significant number of proteins (34) were recognized as single biomarker candidate proteins which were differentially detected in the CSF of patients with MMD, compared to the control patients (p < 0.05). All peak intensity profiles of the biomarker candidates underwent classification and regression tree (CART) analysis to produce prediction models. Two important biomarkers could successfully classify the patients with MMD and control patients.</p> <p>Conclusions</p> <p>In this study, several novel biomarker candidate proteins differentially expressed in the CSF of patients with MMD were identified by a recently developed proteomic approach. This is a pilot study of CSF proteomics for MMD using SELDI technology. These biomarker candidates have the potential to shed light on the underlying pathogenesis of MMD.</p

Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study

Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman\u27s correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression

Tokyo Guidelines 2018 management bundles for acute cholangitis and cholecystitis

Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 (TG13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 (TG18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: . Related clinical questions and references are also include

Tokyo Guidelines 2018 diagnostic criteria and severity grading of acute cholecystitis (with videos)

The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013. According to that revision, the TG13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG13 diagnostic criteria of acute cholecystitis. On the other hand, the TG13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG13 severity grading for acute cholecystitis was significantly associated with parameters including 30-day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG18/TG13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also include

TG18 management strategies for gallbladder drainage in patients with acute cholecystitis: Updated Tokyo Guidelines 2018 (with videos)

Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high-risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 (TG18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high-risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound-guided gallbladder drainage can be considered in high-volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso-gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound-guided gallbladder drainage studies. Free full articles and mobile app of TG18 are available at: . Related clinical questions and references are also include