The Tyrosine Kinase Inhibitor TAS-115 Attenuates Bleomycin-induced Lung Fibrosis in Mice.

The signaling pathways of growth factors, including platelet-derived growth factor, can be considered specific targets for overcoming the poor prognosis of idiopathic pulmonary fibrosis. Nintedanib, the recently approved multiple kinase inhibitor, has shown promising antifibrotic effects in patients with idiopathic pulmonary fibrosis; however, its efficacy is still limited, and in some cases, treatment discontinuation is necessary owing to toxicities such as gastrointestinal disorders. Therefore, more effective agents with less toxicity are still needed.

Systemic Sarcoidosis Presenting with Renal Involvement Caused by Various Sarcoidosis-associated Pathophysiological Conditions.

A 61-year-old man was diagnosed with sarcoidosis involving the lungs, eyes, parotid gland and extrathoracic lymph nodes complicated by chronic kidney injury and hypercalcemia. Kidney biopsy showed non-specific interstitial nephritis and nephrosclerosis. However, immunohistochemical staining of cell surface markers revealed a multinucleated giant macrophage surrounded by T-cells, suggesting granulomatous interstitial nephritis.

The clinical features of older patients with lung cancer in comparison with their younger counterparts.

Background: Older patients with lung cancer have increased over the past decades. Several standard treatments for older patients were established, but their clinical features in real world clinics remain unknown. Thus, we performed a retrospective study to clarify the clinical features of them.

A multicenter, open-label, phase II trial of S-1 plus carboplatin in advanced non-small cell lung cancer patients with interstitial lung disease.

Objectives: The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remain unclear. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of S-1 in combination with carboplatin (CBDCA) in NSCLC patients with ILD.

Materials And Methods: A total of 33 advanced or recurrent NSCLC patients with ILD were prospectively enrolled in this multicenter, open-label, phase II study.

Effect of Janus kinase inhibition by tofacitinib on body composition and glucose metabolism.

Tofacitinib is the first Janus Kinase (JAK) inhibitor to treat moderately to severely active RA. In this study, we investigated whether the effect of tofacitinib have any effects on body composition in mice and female patients with RA. Female C57BL/6 mice fed with a high-fat diet were treated with 30 mg/kg/day tofacitinib or vehicle for 70 days.

Detection of Autoreactive Type II NKT Cells: A Pilot Study of Comparison Between Healthy Individuals and Patients with Vasculitis.

NKT cells are defined as T cells that recognize hydrophobic antigens presented by class I MHC-like molecules, including CD1d. Among CD1d-restricted NKT cells, type I and type II subsets have been noted. CD1d-restricted type I NKT cells are regarded as pro-inflammatory cells in general.

Neutrophils induce smooth muscle hyperplasia via neutrophil elastase-induced FGF-2 in a mouse model of asthma with mixed inflammation.

Background: Bronchial asthma is traditionally characterized by chronic allergic inflammation, including eosinophilia and elevated Th2 cytokines. Recently, IL-17-derived neutrophil infiltration was shown to correlate with asthma severity and airway remodelling.

Objective: To investigate the role of IL-17-derived neutrophils in airway remodelling in chronic bronchial asthma.

Investigating the effects of nintedanib on biomarkers of extracellular matrix turnover in patients with IPF: design of the randomised placebo-controlled INMARK®trial.

Introduction: A feature of the pathogenesis of idiopathic pulmonary fibrosis (IPF) is the excess accumulation of extracellular matrix (ECM) in the lungs. Cleavage of the ECM by metalloproteinases (MMPs) generates free-circulating protein fragments known as neoepitopes. The PROFILE study suggested that changes in ECM turnover proteins may be of value as markers of disease progression in patients with IPF.

A case of pulmonary pleomorphic carcinoma with malignant phenotypes induced by ZEB1-associated epithelial-mesenchymal transition.

A 60-year-old man was admitted to our hospital with non-small cell lung cancer (NSCLC). Imaging and pathological studies revealed NSCLC, not otherwise specified (NOS), at clinical stage T3N1M0 stage IIIA. We started radiotherapy alone because of obstructive pneumonia and end-stage renal disease, but the tumors progressed rapidly and resulted in death due to air obstruction by pharyngeal metastasis.

Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC.

EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of β-catenin in EGFR TKI resistance has been previously reported, however, the precise mechanism by which β-catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of β-catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call "adaptive persisters".

Japanese guideline for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology which accounts for a large proportion of cases of idiopathic interstitial pneumonia. It has a very poor prognosis with a 5-year survival rate of 30% or below, and so far there has been no guideline in Japan offering an established effective therapy based on evidence. In addition to the establishment of basic therapies, there is also an urgent need to establish therapies to deal with complications, as death occurs in many cases due to acute exacerbation or comorbid lung cancer.

Host MICA Polymorphism as a Potential Predictive Marker in Response to Chemotherapy for Colorectal Liver Metastases.

Background: Understanding the genetic background of a tumor is important to better stratify patient prognosis and select optimal treatment. For colorectal liver metastases (CLM), however, clinically available biomarkers remain limited.

Methods: After a comprehensive sequencing of 578 cancer-related genes in 10 patients exhibiting very good/poor responses to chemotherapy, the A5.

Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma.

Podocalyxin (PODXL) overexpression is associated with progression, metastasis, and poor outcomes in cancers. We recently produced the novel anti-PODXL monoclonal antibody (mAb) PcMab-47 (IgG, kappa). Herein, we engineered PcMab-47 into 47-mG, a mouse IgG-type mAb, to add antibody-dependent cellular cytotoxicity (ADCC).

Possibility of Interstitial Lung Disease as a Phlebosclerotic Colitis Manifestation.

Phlebosclerotic colitis presents with ischemic bowels and calcification of the mesenteric veins. Owing to its rarity, we have little information on the complications of this disease. Herein, we report on a 77-year-old woman with phlebosclerotic colitis and interstitial lung disease.

Thymidine catabolism promotes NADPH oxidase-derived reactive oxygen species (ROS) signalling in KB and yumoto cells.

Thymidine phosphorylase (TP) is a rate-limiting enzyme in the thymidine catabolic pathway. TP is identical to platelet-derived endothelial cell growth factor and contributes to tumour angiogenesis. TP induces the generation of reactive oxygen species (ROS) and enhances the expression of oxidative stress-responsive genes, such as interleukin (IL)-8.

[A Case of HER2 Positive Occult Breast Cancer Presenting as Swollen Axillary Lymph Nodes].

Occult breast cancer, which develops as a metastatic lesion with no primary tumor detected in the breast, is a rare breast cancer. A 68-year-old female patient particularly complained of the presence of a right axillary mass. The mass in the right axilla was palpable, but no tumor was found in both the breasts on palpation, ultrasound examination, or MRI.

[Gallbladder Carcinoma That Occurred 50 Years after Cholecystojejunostomy].

Creation of a cholecystojejunostomy has been recommended as one option in the palliation of biliary obstruction due to pancreatic carcinoma.However, it was a technique used for biliary drainage for acute cholecystitis a long time ago.We describe a patient who underwent a cholecystojejunostomy for acute cholecystitis 50 years prior to presentation, and then revealed a gallbladder carcinoma.

[Hepatocellular Carcinoma with Bile Duct Thrombosis - A Case Report].

Hepatocellular carcinoma(HCC)is not commonly observed with bile duct thrombosis.Here, we report a case of HCC with bile thrombi that extended to the liver hilum.The patient was a 61-year-old man who visited us due to untreated type B hepatitis.

MRI Detection of Intratumoral Fat in Colorectal Liver Metastases After Preoperative Chemotherapy.

Objective: The objective of this study was to investigate the incidence and clinical significance of intratumoral fat deposition in colorectal liver metastases (CLMs) after preoperative chemotherapy using dual-echo gradient-recalled echo MRI.

Materials And Methods: Our institutional review board approved this retrospective radiographic study and waived the requirement for informed patient consent. Fifty-nine patients (33 men, 26 women; median age, 62 years old) who underwent preoperative MRI and curative hepatic resection for colorectal liver metastases after chemotherapy were selected.

CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides.

NKT cells belong to a distinct subset of T cells that recognize hydrophobic antigens presented by major histocompatibility complex class I-like molecules, such as CD1d. Because NKT cells stimulated by antigens can activate or suppress other immunocompetent cells through an immediate production of a large amount of cytokines, they are regarded as immunological modulators. CD1d-restricted NKT cells are classified into two subsets, namely, type I and type II.

A case of interstitial pneumonia associated with anti-PL-7 antibody in a patient with rheumatoid arthritis.

A 65-year-old female had been treated rheumatoid arthritis (RA), interstitial pneumonia (IP) and nephrotic syndrome with prednisolone and cyclosporine. She was emergently admitted to our hospital due to the worsening exertional dyspnea and severe hypoxemia. Chest computed tomography (CT) showed new diffuse ground-glass opacities (GGOs) with slight consolidations along with bronchovascular bundle were observed in addition to pre-existing reticular shadows in both lungs with lower lobe-predominance.

Brain-derived neurotrophic factor induces angiogenin secretion and nuclear translocation in human umbilical vein endothelial cells.

Brain-derived neurotrophic factor (BDNF) is a well-known humoral protein that induces growth of neurons. Recent studies have suggested that BDNF could act as an angiogenesis inducer similar to vascular endothelial growth factor (VEGF). Angiogenin is a strong mediator of angiogenesis.

Postoperative low hepatitis C virus load predicts long-term outcomes after hepatectomy for hepatocellular carcinoma.

Background: Preoperative hepatitis C virus (HCV) viral load is known to predict long-term outcomes after hepatectomy for HCV-related hepatocellular carcinoma (HCC). This study sought to examine the hypothesis that postoperative and preoperative HCV viral-load have similar prognostic implications, as well as determine a target viral-load that will improve long-term postoperative outcomes.

Method: One hundred and eighty-one patients who underwent curative hepatectomy for HCV-related HCC were divided into five groups according to time-weighted average viral load.

Bone marrow-derived fibrocytes promote stem cell-like properties of lung cancer cells.

Cancer stem cells (CSCs) represent a minor population that have clonal tumor initiation and self-renewal capacity and are responsible for tumor initiation, metastasis, and therapeutic resistance. CSCs reside in niches, which are composed of diverse types of stromal cells and extracellular matrix components. These stromal cells regulate CSC-like properties by providing secreted factors or by physical contact.

Changes in CT morphology can be an independent response marker for patients receiving regorafenib for colorectal liver metastases: retrospective pilot study.

Background: Regorafenib is a multi-kinase inhibitor, which was shown to be effective for patients with metastatic colorectal cancer refractory to standard therapies. However, its patterns of response has not yet been fully understood.

Methods: Clinical records of 10 patients who received regorafenib for evaluable colorectal liver metastases were reviewed.