Lysyl Oxidase Mediates Proliferation and Differentiation in the Esophageal Epithelium.

In homeostatic conditions, the basal progenitor cells of the esophagus differentiate into a stratified squamous epithelium. However, in the setting of acid exposure or inflammation, there is a marked failure of basal cell differentiation, leading to basal cell hyperplasia. We have previously shown that lysyl oxidase (LOX), a collagen crosslinking enzyme, is upregulated in the setting of allergic inflammation of the esophagus; however, its role beyond collagen crosslinking is unknown.

Pimitespib, a Novel Heat Shock Protein 90 Inhibitor, Is Effective in Treating Renal Cell Carcinoma by Anti-angiogenetic Signaling.

Background/aim: Most clear cell renal cell carcinomas (ccRCCs) have a dysfunctional von Hippel-Lindau tumor suppressor protein (VHL). Hypoxia-inducible factors 1 and 2 alpha (HIF1α and HIF2α) accumulate in ccRCC with dysfunctional VHL and up-regulate the vascular endothelial growth factor (VEGF) pathway and tumor angiogenesis. Recently, pimitespib (PIM), a potent ATP-competitive inhibitor of heat shock protein 90 (HSP90), was developed.

Pancreas-left gastric artery angle predicts difficulty of suprapancreatic lymph node dissection in gastrectomy for gastric cancer: a cross-sectional study.

Purpose: Suprapancreatic lymph node dissection is one of the most challenging procedures performed in the treatment of gastric cancer. This study aimed to investigate whether the pancreas-left gastric artery angle (PLA) can be used to predict the difficulty of the procedure.

Methods: This was a single-center cross-sectional study.

Spontaneous Overactivation of Frog Eggs Triggers Necrotic Cell Death.

The excessive activation of frog eggs, referred to as overactivation, can be initiated by strong oxidative stress, leading to expedited calcium-dependent non-apoptotic cell death. Overactivation also occurs spontaneously, albeit at a low frequency, in natural populations of spawned frog eggs. Currently, the cytological and biochemical events of the spontaneous process have not been characterized.

Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Background: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium.

Lysyl Oxidase Regulates Epithelial Differentiation and Barrier Integrity in Eosinophilic Esophagitis.

Background & Aims: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is up-regulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown.

The impact of contour maps on estimating the risk of gastrointestinal stromal tumor recurrence: indications for adjuvant therapy: an analysis of the Kinki GIST registry.

Introduction: Contour maps enable risk classification of GIST recurrence in individual patients within 10 postoperative years. Although contour maps have been referred to in Japanese guidelines, their usefulness and role in determining indications for adjuvant therapy is still unclear in Japanese patients. The aims of this study are to investigate the validity of contour maps in Japanese patients with GIST and explore the new strategy for adjuvant therapy.

Long-term survival and prognostic factors associated with curative conversion surgery for ct4b esophageal squamous cell carcinoma: Analysis of 200 consecutive cases.

Background: The optimal treatment strategy for cT4b esophageal cancer has not been established yet. Although curative surgery is sometimes performed after induction treatments, the prognostic factor of cT4b esophageal cancer cases who underwent R0 resection remains unknown.

Methods: A total of 200 patients with cT4b esophageal cancer who underwent R0 resection after induction treatments between 2001 and 2020 in our institute were included in the present study.

Long-term response to pimitespib in postoperative recurrent gastrointestinal stromal tumors with PDGFRA D842V mutation: a case report.

Background: Exon 18 D842V, which is a point mutation from aspartic acid to valine at codon 842, is the most frequent mutation in Platelet-Derived Growth Factor Receptor alpha (PDGFRA)-mutated gastrointestinal stromal tumor (GIST). In the Japanese GIST guidelines, no standard systematic therapy is available for this type of GIST, which is refractory after recurrence. Recently, pimitespib (PIMI), a novel heat shock protein 90 (HSP90) inhibitor, was approved for the treatment of advanced GIST in a phase III study.

Plasma trough concentration of imatinib and its effect on therapeutic efficacy and adverse events in Japanese patients with GIST.

Background: Imatinib mesylate (IM) is the standard chemotherapy for patients with gastrointestinal stromal tumors (GISTs) and has a favorable safety profile. Pharmacokinetics (PK), such as plasma trough concentration (Cmin), varies among patients, requiring the need for therapeutic drug monitoring (TDM) during IM administration. Despite some reports from overseas, the relationship between Cmin, adverse events (AEs), and treatment efficacy in Japanese patients with GIST has still been lacking.

Combination of pimitespib (TAS-116) with sunitinib is an effective therapy for imatinib-resistant gastrointestinal stromal tumors.

Despite the effectiveness of imatinib, most gastrointestinal stromal tumors (GISTs) develop resistance to the treatment, mainly due to the reactivation of KIT tyrosine kinase activity. Sunitinib, which inhibits the phosphorylation of KIT and vascular endothelial growth factor (VEGF) receptor, has been established as second-line therapy for GISTs. The recently-developed heat shock protein 90 (HSP90) inhibitor pimitespib (PIM; TAS-116) demonstrated clinical benefits in some clinical trials; however, the effects were limited.

Oxidative Stress-Induced Overactivation of Frog Eggs Triggers Calcium-Dependent Non-Apoptotic Cell Death.

Excessive activation of frog eggs (overactivation) is a pathological process that renders eggs unfertilizable. Its physiological inducers are unknown. Previously, oxidative stress was shown to cause time- and dose-dependent overactivation of frog eggs.

Mathematical modelling for antimicrobial photodynamic therapy mediated by 5-aminolaevulinic acid: An in vitro study.

Background: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect.

Laparoscopic resection for recurrent gastrointestinal stromal tumors and paraganglioma in a patient with Carney-Stratakis syndrome: A case report.

Carney-Stratakis syndrome (CSS) is a familial syndrome characterized by gastrointestinal stromal tumors (GISTs) and paragangliomas, often at multiple sites. A 34-year-old woman who had undergone resection of gastric GISTs, liver metastases, and a retroperitoneal paraganglioma in her previous hospital was referred to our hospital due to recurrence after 5 years. She presented with two gastric GISTs, a liver tumor, and a peritoneal tumor.

Characterizing Profiles of TBI Severity: Predictors of Functional Outcomes and Well-Being.

Objective: To identify profiles of acute traumatic brain injury (TBI) severity and relate profiles to functional and well-being outcomes.

Setting: Acute inpatient rehabilitation and general community settings.

Participants: Three hundred and seventy-nine individuals with moderate-severe TBI participating in the Traumatic Brain Injury Model Systems.

Robotic Distal Gastrectomy Reduces Drain Amylase Values in Patients With a Small Pancreas-left Gastric Artery Angle.

Purpose: Pancreatic fistula is a severe complication after laparoscopic distal gastrectomy (LDG). We previously evaluated the pancreas-left gastric artery angle (PLA) as a risk indicator for developing a pancreatic fistula after LDG. This study evaluated the incidence of pancreatic fistula with robotic distal gastrectomy (RDG) in comparison to LDG from the view of the PLA.

Cardiovascular Characteristics of Zucker Fatty Diabetes Mellitus Rats, an Animal Model for Obesity and Type 2 Diabetes.

Zucker fatty diabetes mellitus (ZFDM) rats harboring the missense mutation (fa) in a leptin receptor gene have been recently established as a novel animal model of obesity and type 2 diabetes (T2D). Here, we explored changes in cardiovascular dynamics including blood pressure and heart rate (HR) associated with the progression of obesity and T2D, as well as pathological changes in adipose tissue and kidney. There was no significant difference in systolic blood pressure (SBP) in ZFDM-Lepr (Homo) compared with ZFDM-Lepr (Hetero) rats, while HR and plasma adrenaline in Homo were significantly lower than Hetero.

Efficacy and safety of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors.

Background: Regorafenib is an oral multi-kinase inhibitor that has been established as third-line treatment for patients after the failure of imatinib and sunitinib. However, since clinical data of regorafenib in the Japanese population are still lacking, the management of regorafenib is mainly based on the clinical experience of each oncologist. The aim of this study was to evaluate the efficacy and safety of regorafenib in a Japanese population.

Targeted therapy for drug-tolerant persister cells after imatinib treatment for gastrointestinal stromal tumours.

Background: Despite the effectiveness of tyrosine kinase inhibitors (TKI), gastrointestinal stromal tumours (GIST) develop after the withdrawal of TKI. Based on previous studies, a subpopulation of drug-tolerant cells called "persister cells" may be responsible for the recurrence and have thus, gained attention as a novel target in cancer therapy.

Methods: The metabolic changes were investigated in imatinib-derived persister GIST cells.

Pancreas-left gastric artery angle is associated with postoperative inflammation and drain amylase after laparoscopic gastrectomy.

Introduction: The pancreas often interferes with the surgical field during laparoscopic gastrectomy (LG) and its disorders cause severe postoperative complications. This study aimed to evaluate the association between the anatomical location of the pancreas and surgical outcome and to investigate the optimal surgical position in LG.

Methods: We newly defined the angle formed between the supra-pancreatic region and the root of the left gastric artery (LGA) as the pancreas-LGA angle (PLA).

Plan-view characterization of intergranular precipitates on grain boundaries by combination of FIB lift out method and TEM analyses: A case study in austenitic stainless steel.

A new characterization method is proposed to study intergranular precipitates of polycrystalline material in the planar manner. A dual beam focused ion beam (FIB) - scanning electron microscopy (SEM) was applied to fabricate thin FIB lamella with a grain boundary parallel to the lamella to investigate for transmission electron microscopy (TEM). Distributions, microstructures and compositions of intergranular precipitates of austenitic stainless steel were then examined by TEM, scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS).

Lung donation after medical assistance in dying at home.

Organ donation after medical assistance in dying (MAID) has only been possible for patients having the MAID procedure performed at a hospital facility due to prohibitive warm ischemic times. Herein, we describe a protocol for lung donation following MAID at home and demonstrate excellent postoperative outcomes. Lung donation following MAID at home is possible and should be considered by transplant programs.