The Influence of Total Fat Mass and Skeletal Muscle Mass Index on the Occurrence of Perioperative Hypothermia in Patients Undergoing Open Gastrectomy.

Background: Perioperative hypothermia, a common occurrence in patients undergoing general anesthesia, is defined as a core body temperature below 36°C. The relationship between patient body composition and the incidence of hypothermia remains underreported. This study aims to elucidate the association between body composition and perioperative hypothermia in patients undergoing open gastrectomy.

Efficacy and safety of carmustine wafers, followed by radiation, temozolomide, and bevacizumab therapy, for newly diagnosed glioblastoma with maximal resection.

Background: To improve the outcome in newly diagnosed glioblastoma patients with maximal resection, we aimed to evaluate the efficacy and safety of implantation of carmustine wafers (CWs), radiation concomitant with temozolomide and bevacizumab, and maintenance chemotherapy with six cycles of temozolomide and bevacizumab.

Method: This prospective phase II study enrolled glioblastoma patients considered candidates for complete resection (> 90%) of a contrast-enhanced lesion. The CWs were intraoperatively implanted into the resection cavity after achieving maximal resection.

CEP-1347 Boosts Chk2-Mediated p53 Activation by Ionizing Radiation to Inhibit the Growth of Malignant Brain Tumor Cells.

Radiation therapy continues to be the cornerstone treatment for malignant brain tumors, the majority of which express wild-type p53. Therefore, the identification of drugs that promote the ionizing radiation (IR)-induced activation of p53 is expected to increase the efficacy of radiation therapy for these tumors. The growth inhibitory effects of CEP-1347, a known inhibitor of MDM4 expression, on malignant brain tumor cell lines expressing wild-type p53 were examined, alone or in combination with IR, by dye exclusion and/or colony formation assays.

Neuroradiological, genetic and clinical characteristics of histone H3 K27-mutant diffuse midline gliomas in the Kansai Molecular Diagnosis Network for CNS Tumors (Kansai Network): multicenter retrospective cohort.

This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term "midline" areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings.

Association of ADC of hyperintense lesions on FLAIR images with TERT promoter mutation status in glioblastoma IDH wild type.

Background: Although mutations in telomerase reverse transcriptase () promoter (p) are the most common alterations in glioblastoma (GBM), predicting p mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing p mutation status using magnetic resonance imaging (MRI).

Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM.

The MDM2-p53 Axis Represents a Therapeutic Vulnerability Unique to Glioma Stem Cells.

The prevention of tumor recurrence by the successful targeting of glioma stem cells endowed with a tumor-initiating capacity is deemed the key to the long-term survival of glioblastoma patients. Glioma stem cells are characterized by their marked therapeutic resistance; however, recent evidence suggests that they have unique vulnerabilities that may be therapeutically targeted. We investigated MDM2 expression levels in glioma stem cells and their non-stem cell counterparts and the effects of the genetic and pharmacological inhibition of MDM2 on the viability of these cells as well as downstream molecular pathways.

CEP-1347 Dually Targets MDM4 and PKC to Activate p53 and Inhibit the Growth of Uveal Melanoma Cells.

Uveal melanoma (UM) is among the most common primary intraocular neoplasms in adults, with limited therapeutic options for advanced/metastatic disease. Since UM is characterized by infrequent p53 mutation coupled with the overexpression of MDM4, a major negative regulator of p53, we aimed to investigate in this study the effects on UM cells of CEP-1347, a novel MDM4 inhibitor with a known safety profile in humans. We also examined the impact of CEP-1347 on the protein kinase C (PKC) pathway, known to play a pivotal role in UM cell growth.

Antagonizing MDM2 Overexpression Induced by MDM4 Inhibitor CEP-1347 Effectively Reactivates Wild-Type p53 in Malignant Brain Tumor Cells.

The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses.

The Novel MDM4 Inhibitor CEP-1347 Activates the p53 Pathway and Blocks Malignant Meningioma Growth In Vitro and In Vivo.

A significant proportion of meningiomas are clinically aggressive, but there is currently no effective chemotherapy for meningiomas. An increasing number of studies have been conducted to develop targeted therapies, yet none have focused on the p53 pathway as a potential target. In this study, we aimed to determine the in vitro and in vivo effects of CEP-1347, a small-molecule inhibitor of MDM4 with known safety in humans.

Domatinostat Targets the FOXM1-Survivin Axis to Reduce the Viability of Ovarian Cancer Cells Alone and in Combination with Chemotherapeutic Agents.

The deregulation of the FOXM1 transcription factor is a key molecular alteration in ovarian cancer, contributing to the development and progression of ovarian cancer via activation of the target genes. As such, FOXM1 is a highly attractive therapeutic target in the treatment of ovarian cancer, but there has been no clinically tested FOXM1 inhibitor to date. We investigated in this study the effects of domatinostat, a class I-selective HDAC inhibitor currently in the clinical stage of development as a cancer therapeutic, on the expression of FOXM1 and viability of ovarian cancer cells.

Preoperative Risk Factors in Patients With Pancreatic Cancer.

Background: Pancreatic cancer is gastrointestinal cancer with a poor prognosis. Although surgical techniques and chemotherapy have improved treatment outcomes, the 5-year survival rate for pancreatic cancer is less than 10%. In addition, resection of pancreatic cancer is highly invasive and is associated with high rates of postoperative complications and hospital mortality.

Differences in Analgesia Methods for Open Gastrointestinal Surgery Are Not Associated With Initial Postoperative Ambulation.

Background: A characteristic of modern medical care is the reduction in the length of hospital stay, and several facilities across Japan are working towards this goal. The presence of postoperative pain is correlated with the number of days to hospital discharge. Therefore, this study investigated the relationship between the analgesic methods used in clinical practice and the initial ambulation of postoperative laparotomy patients with severe postoperative worked incisional pain to enable better analgesic management in the future.

Predictors of Catheter-Related Bladder Discomfort After Surgery: A Literature Review.

Background: Indwelling bladder catheters are routinely used in clinical practice. Patients may experience postoperative indwelling catheter-related bladder discomfort (CRBD). This study aimed to perform a literature review to identify predictors of postoperative CRBD.

Usefulness of Serum Soluble Interleukin-2 Receptor Levels for Differentiating between PCNSL and SCNSL.

Serum soluble interleukin-2 receptor (sIL-2R) is a practical tumor marker that is elevated in hematogenous tumors. The purpose of this study was to determine the usefulness of serum sIL-2R for differentiating among malignant brain tumors, including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL). This study retrospectively investigated the sIL-2R levels in 130 patients with various types of malignant brain tumors, including PCNSL patients (n = 48) and SCNSL (n = 8); metastatic brain tumors (MTs, n = 16); and glioblastoma (GBM, n = 58).

Perspectives on Collaboration between Physicians and Nurse Practitioners in Japan: A Cross-Sectional Study.

Background: Nurse practitioners (NPs) are known as effective healthcare providers worldwide. In Japan, nurse practitioner adoption is considered to be in a shaky period. Although nurse practitioners were introduced approximately 10 years ago at the initiative of educational institutions in Japan, the full extent of this trend is not known.

Changes in vascular supply pattern associated with growth of nonfunctioning pituitary adenomas.

Background: The vascular supply to nonfunctioning pituitary adenomas (NFPAs) differs compared with that of the anterior lobe of the normal pituitary gland. In this study, we aimed to identify feeding arteries and flow dynamics using 3.0 T magnetic resonance imaging (MRI) in NFPAs.

CEP-1347 Targets MDM4 Protein Expression to Activate p53 and Inhibit the Growth of Glioma Cells.

Background/aim: The development of pharmacological inhibitors targeting negative regulators of p53, such as murine double minute (MDM) 2 and, more recently, MDM4, has been actively pursued as a potential strategy to treat cancers with wild-type p53. We previously showed that CEP-1347, a small molecule kinase inhibitor originally developed for the treatment of Parkinson's disease, suppressed MDM4 expression and activated wild-type p53 in retinoblastoma cells. However, it remains unknown whether CEP-1347 acts as an MDM4 inhibitor and as such activates p53 in other types of human cancer cells.

Inhibition of the Phospholipase Cε-c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties.

Glioma stem cells (GSCs), the cancer stem cells of glioblastoma multiforme (GBM), contribute to the malignancy of GBM due to their resistance to therapy and tumorigenic potential; therefore, the development of GSC-targeted therapies is urgently needed to improve the poor prognosis of GBM patients. The molecular mechanisms maintaining GSCs need to be elucidated in more detail for the development of GSC-targeted therapy. In comparison with patient-derived GSCs and their differentiated counterparts, we herein demonstrated for the first time that phospholipase C (PLC)ε was highly expressed in GSCs, in contrast to other PLC isoforms.

HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny.

Cancer stem cells (CSCs) are in general characterized by higher resistance to cell death and cancer therapies than non-stem differentiated cancer cells. However, we and others have recently revealed using glioma stem cells (GSCs) as a model that, unexpectedly, CSCs have specific vulnerabilities that make them more sensitive to certain drugs compared with their differentiated counterparts. We aimed in this study to discover novel drugs targeting such Achilles' heels of GSCs as anti-GSC drug candidates to be used for the treatment of glioblastoma, the most therapy-resistant form of brain tumors.

Potential eating disorder exhibited with daytime functional vulnerabilities associated with sleep problems in Japanese adolescents: A cross-sectional study.

Objectives: Eating disorders (ED) are serious psychiatric disorders that affect individuals, especially adolescents. It has been suggested that nonclinical ED-like characteristics are related to sleep problems. We conducted a survey of Japanese adolescents to investigate this claim.

A Literature Review of Factors Related to Postoperative Sore Throat.

Postoperative sore throat can occur as a complication in patients who have undergone surgery under general anesthesia. The incidence of postoperative sore throat ranges from 12.1% to 70%, and its effects include damage to the epithelium and mucosal cells caused by airway securement, damage to the vocal cords, congestion, blood clots, and factors such as an inappropriately large tube, cuff shape, cuff pressure, and airway securement.

Optimal Skeletal Muscle Mass Index Cut-Off Values for Presarcopenia Evaluated by Computed Tomography against Dual-Energy X-ray Absorptiometry in Patients with Chronic Liver Disease.

Although dual-energy X-ray absorptiometry (DXA) and body impedance analysis are commonly used to measure skeletal muscle mass (SMM), a computed tomography (CT) scan is preferred in clinical practice. We aimed to propose the cut-off values of skeletal muscle mass index (SMI) calculated using CT scans, using DXA as the reference method. We retrospectively assessed 589 patients with chronic liver disease.