Efficacy and Safety of Transurethral Enucleation with Bipolar Energy for Treatment of Benign Prostatic Hyperplasia: Does Prostate Volume Matter?

Background: We evaluated the association of prostate volume (PV) with the efficacy and safety of transurethral enucleation with bipolar energy (TUEB) for treatment of benign prostatic hyperplasia (BPH).

Methods: We retrospectively evaluated data from 180 patients with symptomatic BPH who underwent TUEB between 2008 and 2015. Efficacy was assessed by perioperative changes in international prostate symptom score (IPSS), Quality of Life Score (QOLS), maximum flow rate on uroflowmetry (Qmax), and serum prostate-specific antigen level (PSA), which were recorded at 3 months postoperatively.

Neutron imaging with an inertial electrostatic confinement fusion neutron source.

A compact inertial electrostatic confinement (IEC) fusion neutron source was developed. Imaging tests using the cylindrical IEC neutron source were conducted with the indirect imaging plate (IP) method using dysprosium foil and an imaging plate. An array of powder contained in a stainless-steel blade and Cd pins was successfully imaged.

DS-7300a, a DNA Topoisomerase I Inhibitor, DXd-Based Antibody-Drug Conjugate Targeting B7-H3, Exerts Potent Antitumor Activities in Preclinical Models.

B7-H3 is overexpressed in various solid tumors and has been considered as an attractive target for cancer therapy. Here, we report the development of DS-7300a, a novel B7-H3-targeting antibody-drug conjugate with a potent DNA topoisomerase I inhibitor, and its in vitro profile, pharmacokinetic profiles, safety profiles, and in vivo antitumor activities in nonclinical species. The target specificity and species cross-reactivity of DS-7300a were assessed.

Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody-Drug Conjugate.

Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), which eventually lead to the development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-tyrosine kinase target in GIST, developed new GPR20 IHC, and assessed GPR20 expression in cell lines, patient-derived xenografts, and clinical samples from two institutes (United States and Japan). We studied GPR20 expression stratified by treatment line, KIT expression, GIST molecular subtype, and primary tumor location.

[Preoperative Metallic Stent Placement and Neoadjuvant Chemotherapy for Locally Advanced Sigmoid Colon Cancer with Obstruction and Invasion of the Psoas Muscle-A Case Report].

A 77-year-old man was diagnosed with obstructive sigmoid colon cancer invading the psoas major and iliac muscles. To avoid the postoperative paralysis of the lower limb, a self-expandable metallic stent(SEMS)was placed, and systemic chemotherapy was administered subsequently. After 4 courses of SOX, Hartmann's procedure was performed.

Mitigation of liquid-liquid phase separation of a monoclonal antibody by mutations of negative charges on the Fab surface.

Some monoclonal antibodies undergo liquid-liquid phase separation owing to self-attractive associations involving electrostatic and other soft interactions, thereby rendering monoclonal antibodies unsuitable as therapeutics. To mitigate the phase separation, formulation optimization is often performed. However, this is sometimes unsuccessful because of the limited time for the development of therapeutic antibodies.

Evaluation of Enhanced Lipid Oxidation and Compensatory Suppression using Natriuretic Peptide in Patients with Cardiovascular Diseases.

Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is recognized as a surrogate marker of lipid oxidation and is associated with arteriosclerosis. However, there are limited reports on the relationship between heart failure and MDA-LDL. Therefore, we aimed to determine whether MDA-LDL is activated in patients with left ventricular (LV) dysfunction and examine our hypothesis that the B-type natriuretic peptide (BNP) masks the enhancement of MDA-LDL in patients with LV dysfunction by its strong antioxidative action.

DS-7080a, a Selective Anti-ROBO4 Antibody, Shows Anti-Angiogenic Efficacy with Distinctly Different Profiles from Anti-VEGF Agents.

Purpose: Neovascular age-related macular degeneration (nAMD) results from choroidal neovascularization (CNV) and causes severe vision loss. Intravitreal anti-vascular endothelial growth factor (VEGF) therapies have significantly improved therapeutic outcomes; however, a substantial number of patients experience disease progression. Roundabout 4 (ROBO4) has been reported to be a vascular-specific protein that stabilizes vasculature in ocular pathological angiogenesis.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors.

Background: Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface in many cancers and predicts poor prognosis. DS-8895a is a humanized anti-EPHA2 IgG1 monoclonal antibody afucosylated to enhance antibody-dependent cellular cytotoxicity activity. We conducted a two-step, phase I, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of DS-8895a in patients with advanced solid tumors.

Relationship between blood coagulability and sense of burden among caregivers of patients with dementia.

Aim: This study aimed to examine the relationship between blood coagulability and sense of burden among caregivers of patients with senile dementia of the Alzheimer type.

Methods: A cross-sectional study was carried out involving healthy older caregivers who lived with their patients with senile dementia of the Alzheimer type. We evaluated the Zarit Burden Interview score, levels of von Willebrand factor antigen, D-dimer, thrombin-antithrombin III complex, tissue plasminogen activator/plasminogen activator inhibitor type 1 complex, number of chronic diseases, body mass index and number of medications.

Familial pulmonary thromboembolism with a prothrombin mutation and antithrombin resistance.

We describe the case of a 45-year-old man with congenital thrombophilia induced by antithrombin resistance. He had recurrent venous thrombosis without traditional risk factors or abnormal coagulation function and had a family history of venous thrombosis which included his mother, brother, and nephew. We suspected the association of hereditary antithrombin resistance, which has been reported in some cases of familial venous thromboses due to prothrombin mutations.

Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches.

Atrial natriuretic peptide (ANP) exerts beneficial pharmacological effects in the treatment of various cardiovascular disorders, such as acute congestive heart failure (ADHF). However, the clinical use of ANP is limited to the continuous intravenous infusion owing to its short half-life (2.4 ± 0.

Generation of efficient mutants of endoglycosidase from Streptococcus pyogenes and their application in a novel one-pot transglycosylation reaction for antibody modification.

The fine structures of Fc N-glycan modulate the biological functions and physicochemical properties of antibodies. By remodeling N-glycan to obtain a homogeneous glycoform or chemically modified glycan, antibody characteristics can be controlled or modified. Such remodeling can be achieved by transglycosylation reactions using a mutant of endoglycosidase from Streptococcus pyogenes (Endo-S) and glycan oxazoline.

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor: a case of a rare malignancy.

Background: A gastric adenosquamous carcinoma (ASC) that produces granulocyte-colony stimulating factor (G-CSF) is an uncommon malignancy with a poor prognosis. Due to the rarity of this lesion, a standard treatment for the disease has not been established.

Case Presentation: We describe a case of a 66-year-old male with a G-CSF-producing gastric ASC who presented with severe anemia and leukocytosis.

Novel anti-EPHA2 antibody, DS-8895a for cancer treatment.

Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors.

Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models with 89Zr-DS-8895a.

Unlabelled: Subtype A2 of the erythropoietin-producing hepatocellular tyrosine kinase (EphA2) cell surface receptor is expressed in a range of epithelial cancers. This study evaluated the molecular imaging of EphA2 expression in vivo in mouse tumor models using SPECT/MR and PET/MR and a humanized anti-EphA2 antibody, DS-8895a.

Methods: DS-8895a was labeled with (111)In, (125)I, and (89)Zr and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen-binding affinity (Scatchard analysis), and serum stability in vitro.

[Surgical Resection after Chemotherapy for Ampullary Carcinoma with Synchronous Liver Metastasis--Report of a Case].

A 63-year-old woman presented with abnormalities in liver enzyme levels on laboratory studies, which were detected during a routine medical check-up. She was diagnosed with carcinoma of the ampulla of Vater with a synchronous solitary liver metastasis (S7). She was treated with gemcitabine plus S-1.

Toxicological evaluation of acyl glucuronides utilizing half-lives, peptide adducts, and immunostimulation assays.

Chemical reactivity of acyl glucuronides (AGs) is believed to be involved in the toxicity of carboxylic acid-containing drugs. Both direct and immune-mediated toxicity have been suggested as possible mechanisms of toxicity; however, it remains unclear. In the present study, we performed assays of half-lives, peptide adducts, and immunostimulation to evaluate the potential risk of AGs of 21 drugs and analyzed the relationship to the toxic category.

Effects of Add-on Therapy Consisting of a Selective Mineralocorticoid Receptor Blocker on Arterial Stiffness in Patients with Uncontrolled Hypertension.

Objective: Aldosterone plays an important role in the pathogenesis of atherosclerosis; however, the significance of mineralocorticoid receptor blockade for atherosclerosis has not been fully elucidated. In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension.

Methods: Forty-seven uncontrolled hypertensive patients who had previously been treated with anti-hypertensive drugs were examined retrospectively.

[Routes of nutrition and types of diet among dependent community-dwelling older care recipients and the relevance to mortality and hospitalization].

Aim: To clarify the routes of nutrition and types of diet and their relevance to the risk of mortality and hospitalization among community-dwelling dependent elderly provided various home care services under the long-term care insurance program.

Methods: The present study consisted of the collection of baseline data of participants in the Nagoya Longitudinal Study of the Frail Elderly (NLS-FE) and data regarding mortality and hospitalization during a three-year follow-up period. The study population consisted of 1,872 subjects, and the baseline data included demographic characteristics, basic activities of daily living (ADLs), comorbidities, nutritional routes and types of diet, which were evaluated by trained visiting nurses.

Change in and long-term investigation of neuro-otologic disorders in disaster-stricken Fukushima prefecture: retrospective cohort study before and after the Great East Japan Earthquake.

On March 11, 2011, Japan's northeast Pacific coast was hit by a gigantic earthquake and subsequent tsunami. Soma City in Fukushima Prefecture is situated approximately 44 km north of Fukushima Daiichi Nuclear Power Plant. Soma General Hospital is the only hospital in Soma City that provides full-time otolaryngological medical care.

Real-time emulator for reproducing graded potentials in vertebrate retina.

In most parts of the retina, neuronal circuits process visual signals represented by slowly changing membrane potentials, or so-called graded potentials. A feasible approach to speculate about the functional roles of retinal neuronal circuits is to reproduce the graded potentials of retinal neurons in response to natural scenes. In this study, we developed a simulation platform for reproducing graded potentials with the following features: real-time reproduction of retinal neural activities in response to natural scenes, a configurable model structure, and compact hardware.

Clinical and bacteriological influence of diabetes mellitus on deep neck infection: Systematic review and meta-analysis.

Background: Diabetes mellitus has been recognized as the most common systemic disease associated with deep neck infection. We report the first systematic review and meta-analysis of the influence of diabetes on clinical and bacteriological characteristics of deep neck infection.

Methods: Articles were retrieved from PubMed, EMBASE, and the Japan Medical Abstracts Society database.

Phase I/II trial of irinotecan and S-1 combination chemotherapy as a second-line treatment for advanced colorectal cancer.

Background: This study attempted to determine the therapeutic dosage of irinotecan and S-1 (IRIS) as a second-line treatment for colorectal cancer (CRC).

Methods: S-1 was administered on days 1-14 of a 28-day cycle. Irinotecan was administered on days 1 and 15.