Renoprotective Effects of a Novel Receptor-Interacting Protein Kinase 2 Inhibitor, AS3334034, in Uninephrectomized Adriamycin-Induced Chronic Kidney Disease Rats.

Renal inflammation is a final common pathway of chronic kidney disease (CKD), and its progression can be used to effectively gauge the degree of renal dysfunction. Inflammatory mechanisms contribute to glomerulosclerosis and tubulointerstitial fibrosis, which are hallmarks of CKD leading to end-stage renal disease. Receptor-interacting protein kinase 2 (RIP2) is largely committed to nucleotide-binding oligomerization domain signaling as a direct effector and transmits nuclear factor-B (NF-B)-mediated proinflammatory cytokine production.

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma.

Background: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK.

Patients And Methods: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT.

[A Retrospective Evaluation of the Impact of Multi-disciplinary Approach for Improving the Quality of Anticoagulation Therapy in Ambulatory Patients with Non-valvular Atrial Fibrillation Receiving Warfarin].

While percent time within therapeutic range (%TTR) of international normalized ratio of prothrombin time (PT-INR) represents the quality of anticoagulation therapy with warfarin, it is often maintained less than 50% in patients with non-valvular atrial fibrillation (NVAF). We aimed to study if implementation of a multi-disciplinary ambulatory anticoagulation service (MAAS) may improve %TTR. Collaborating with cardiologists at Kanto Rosai Hospital, we conducted a MAAS for NVAF patients receiving warfarin from April 2013 to December 2015.

A phase II randomized trial of adjuvant chemotherapy with S-1 versus S-1 plus cisplatin for completely resected pathological stage II/IIIA non-small cell lung cancer.

Objectives: Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC.

Synthesis and structure activity relationships of carbamimidoylcarbamate derivatives as novel vascular adhesion protein-1 inhibitors.

Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted structural optimization of the glycine amide derivative 1, which we previously reported as a novel VAP-1 inhibitor, to improve stability in dog and monkey plasma, and aqueous solubility. By chemical modification of the right part in the glycine amide derivative, we identified the carbamimidoylcarbamate derivative 20c, which showed stability in dog and monkey plasma while maintaining VAP-1 inhibitory activity.

Synthesis and pharmacological evaluation of glycine amide derivatives as novel vascular adhesion protein-1 inhibitors without CYP3A4 and CYP2C19 inhibition.

Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted optimization studies of our lead compound 1, which we previously reported as a novel VAP-1 inhibitor, to enhance the inhibition of human VAP-1 and to reduce CYP3A4 and CYP2C19 inhibition. As a result, we identified 3-chloro-4-{4-[5-(3-{[glycyl(methyl)amino]methyl}phenyl)pyrimidin-2-yl]piperazin-1-yl}benzoic acid (17h) as a novel orally active VAP-1 inhibitor, with 14-fold increased human VAP-1 inhibitory activity compared to 1, without CYP3A4 and CYP2C19 inhibition.

Synthesis and structure activity relationships of glycine amide derivatives as novel Vascular Adhesion Protein-1 inhibitors.

Vascular Adhesion Protein-1 (VAP-1) is a promising therapeutic target for the treatment of several inflammatory-related diseases including diabetic microvascular complication. We identified glycine amide derivative 3 as a novel structure with moderate VAP-1 inhibitory activity. Structure-activity relationship studies of glycine amide derivatives revealed that the tertiary amide moiety is important for stability in rat blood and that the position of substituents on the left phenyl ring plays an important role in VAP-1 inhibitory activity.

A rare case of human pulmonary dirofilariasis with a growing pulmonary nodule after migrating infiltration shadows, mimicking primary lung carcinoma.

Introduction: Pulmonary dirofilariasis is a rare pulmonary parasitic infection by the nematode Dirofilaria immitis. It is characterized by an asymptomatic pulmonary nodule usually seen on chest X-ray. The differential diagnosis of pulmonary dirofilariasis includes other pulmonary diseases, primary lung carcinoma and metastatic lung tumor.

A rare case report of rib hemangioma mimicking a malignant bone tumor or metastatic tumor.

Hemangioma of the rib is a rare benign vascular tumor. This benign disease induces osteolytic changes, and must be distinguished from a malignant bone tumor or metastatic tumor. Definitive diagnosis is achieved by excision biopsy or histological examination after surgical resection in many cases.

Four-year natural clinical course of pulmonary epithelioid hemangioendothelioma without therapy.

Pulmonary epithelial hemangioendothelioma is a rare low to intermediate malignant vascular tumor originating from vascular endothelial cells. The therapy for this disease, if possible, is surgical resection. However, there is no standard treatment for patients with multiple unresectable lesions.

How should synchronous multiple primary adenocarcinomas of the lung be resected?

We often encounter patients with multiple primary lung cancers with ground-glass opacity. However, there are no established guidelines regarding the optimal extent of resection for multifocal lung adenocarcinoma, so it is necessary to determine the most suitable strategy for each case. A 62-year-old man visited our hospital with 7 lesions in the lung field.

Surgical treatment of catamenial pneumothorax: Report of three cases.

Catamenial pneumothorax (CP) is a rare entity of spontaneous, recurring pneumothorax in females. Although it has been known to be associated with thoracic endometriosis, varying clinical course and the lack of consistent intraoperative findings have led to conflicting etiological theories. We herein discuss the etiology, clinical course, and surgical treatment of three patients with CP.

Treatment of the postoperative recurrence of lung cancer in octogenarians.

Purpose: Guidelines for the treatment of postoperative recurrent lung cancer in octogenarians do not exist. In this study, we investigated the prognosis of patients with recurrence after the resection of lung cancer and discuss the management of recurrent tumors in octogenarians.

Methods: This study clinicopathologically evaluated 135 octogenarians who underwent resections for lung cancer at a single institution between 1992 and 2010.

Carcinoid tumors of the lung: a report of 11 cases.

Objective: Carcinoid tumors of the lung are rare, and account for 1% of all primary tumors of the lung. This study was undertaken to investigate the histological characteristics and clinical behavior of carcinoid tumors of the lung.

Methods: We have retrospectively reviewed the hospital records of 11 consecutive patients undergoing surgical treatment for carcinoid tumors of the lung between 1992 and 2007.

Aspergilloma mimicking a lung cancer.

Introduction: Pulmonary aspergillosis occurs in the parenchymal cavities or ectatic airways. It rarely affects healthy people with an intact immune response. There have been few reports describing an aspergilloma mimicking a lung cancer.

Novel 1H-imidazol-2-amine derivatives as potent and orally active vascular adhesion protein-1 (VAP-1) inhibitors for diabetic macular edema treatment.

Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although we previously identified a compound (2) with potent VAP-1 inhibitory activity in rats, the human activity was relatively weak. Here, to improve the human VAP-1 inhibitory activity of compound 2, we first evaluated the structure-activity relationships of guanidine bioisosteres as simple small molecules and identified a 1H-benzimidazol-2-amine (5) with potent activity compared to phenylguanidine (1).

Association between EGFR-TKI resistance and efficacy of radiotherapy for brain metastases from EGFR-mutant lung adenocarcinoma.

Aim: To clarify how patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) respond to radiotherapy (RT) for brain metastases.

Patients And Methods: Forty-seven patients were divided into the following three groups: a TKI-naïve group with EGFR mutation (n=11), a TKI-resistant group with EGFR mutation (n=10), and an EGFR-wild-type group (n=26). Patients received stereotactic RT (n=23) or whole-brain RT (n=24).

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema: part 2.

Novel thiazole derivatives were synthesized and evaluated as vascular adhesion protein-1 (VAP-1) inhibitors. Although our previous compound 1 showed potent VAP-1 inhibitory activity, the activity differed between humans and rats. This issue was overcome by a hybrid design using human VAP-1 specific inhibitor 2, which was found by high-throughput screening (HTS), a docking study of a human VAP-1 homology model, and an analysis of sequence information for humans and rats.

Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema.

Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats.

Analysis of the surgical treatment for superior sulcus tumors.

Purpose: This study was undertaken to assess the mortality, complication, and major morbidity rates of surgical treatment for superior sulcus tumors (SSTs), and to estimate the significance of prognostic factors.

Methods: We retrospectively reviewed the hospital records of 50 consecutive patients undergoing surgical treatment for SSTs between 1992 and 2007. The significance of risk factors for an adverse outcome was investigated.

Pneumonectomy for non-small cell lung cancer.

Purpose: To assess the mortality, complications and major morbidity of pneumonectomy for non-small cell lung cancer (NSCLC) and to establish the importance of various prognostic factors.

Methods: We reviewed retrospectively the hospital records of 71 consecutive patients who underwent pneumonectomy for NSCLC between 1992 and 2007 to evaluate the significance of risk factors for an adverse outcome. Patients were divided into two period groups according to the period when they were treated: early (1992-1999; n = 47) and late (2000-2007; n = 24).

Primary pulmonary Ewing's sarcoma: report of a case.

The Ewing's sarcoma family of tumors has been reported to originate in a variety of sites, most commonly in the extremities. We herein describe a rare case of primary pulmonary Ewing's sarcoma in a patient with a family history of sarcoma. The patient was a 42-year-old male, who presented with hemoptysis.

[Chest wall reconstruction with rectus abdominis musculocutaneous flap for sternum osteomyelitis after radiation].

We report a case of reconstruction of radiation ulcer on the chest wall and sternum osteomyelitis using a rectus abdominis musculocutaneous flap. A case of 67-year-old woman, Halsted operation was performed for right breast cancer, 23 years ago. After 4 years, transcatheter arterial injection and radiation therapy was performed to treat recurrence of parasternal lymph nodes.

Utility of preoperative visualization for intrapulmonary sequestration in video-assisted thoracoscopic surgery.

We herein report the case of a 59-year-old male suffering from severe cough. The patient had previously experienced several episodes of pneumonia beginning in childhood. A three dimensional multidetector computed tomography (3D-MDCT) scan revealed pulmonary sequestration with a left gastric artery blood supply, and clearly revealed the other pulmonary vessels.