[Carinal Reconstruction].

Carinoplasty can be divided into the one-stoma method, the montage method, the double-barrel method, and the Miyamoto method. The one-stoma method is usually performed with right upper sleeve lobectomy, and with an anastomosis of the intermediate trunk to a carina. On the other hand, in the montage method, the double-barrel method or the Miyamoto method, carina is completely resected and the trachea, left main bronchus and right bronchus are divided into three pieces.

Anti-Inflammatory Thrombolytic JX10 (TMS-007) in Late Presentation of Acute Ischemic Stroke.

Background: Contemporary thrombolytics in acute ischemic stroke are limited to administration within 4.5 hours of last known normal. JX10 (formerly TMS-007), a triprenyl phenol family member, may extend this therapeutic window.

Anti-angiogenic activity of a novel angiostatin-like plasminogen fragment produced by a bacterial metalloproteinase.

Tumor growth depends on angiogenesis, a process by which new blood vessel are formed from pre-existing normal blood vessels. Proteolytic fragments of plasminogen, containing varying numbers of plasminogen kringle domains, collectively known as angiostatin, are a naturally occurring inhibitor of angiogenesis and inhibit tumor growth. We have developed an "affinity-capture reactor" that enables a single-step method for the production/purification of an angiostatin-like plasminogen fragment from human plasma using an immobilized bacterial metalloproteinase.

Potent Efficacy of 3-Amino-4-hydroxy Benzoic Acid, a Small Molecule Having Anti-fibrotic Activity, in a Mouse Model of Non-alcoholic Steatohepatitis.

Non-alcoholic steatohepatitis (NASH), which is on the rise due to the increasing obese population and changing lifestyles, causes fibrosis over time and carries the risk of progression to cirrhosis and hepatocellular carcinoma. However, there are no approved effective treatments for NASH. Recent studies suggest that increased lipid metabolism and reduced nitric oxide content are responsible for NASH; 3-amino-4-hydroxy benzoic acid (AHBA) was identified as an inhibitor for the phosphatase activity of soluble epoxy hydrolase, which in turn inhibits lipid metabolism and endothelial nitric oxide synthase activity.

Preclinical safety, toxicokinetics and metabolism of BIIB131, a novel prothrombolytic agent for acute stroke.

BIIB131, a small molecule, is currently in Phase 2 for the treatment of acute ischemic stroke. Safety and metabolism of BIIB131 were evaluated following intravenous administration to rats and monkeys. Exposure increased dose-proportionally in rats up to 60 mg/kg and more than dose-proportionally in monkeys at greater than 10 mg/kg accompanied by prolonged half-life and safety findings.

Soluble epoxide hydrolase maintains steady-state lipid turnover linked with autocrine signaling in peritoneal macrophages.

Soluble epoxide hydrolase is a widely distributed bifunctional enzyme that contains N-terminal phosphatase (N-phos) and C-terminal epoxide hydrolase (C-EH) domains. C-EH hydrolyzes anti-inflammatory epoxy-fatty acids to corresponding diols and contributes to various inflammatory conditions. However, N-phos has been poorly examined.

Long-lasting complete remission in a patient with systemic metastases of recurrent breast cancer treated with cyclin-dependent kinases 4/6 inhibitors: a case report.

Background: The prognosis for recurrence cases of hormone receptor-positive HER2-negative breast cancer remains poor, and treatment strategies that emphasize quality of life have often been chosen, with few physicians aiming for a cure. Our objective is to assess the validity of such current treatment strategies.

Case Presentation: A 74-year-old Asian woman with multiple lung and liver metastases after local recurrence of breast cancer was treated with two different cyclin-dependent kinases 4/6 inhibitors sequentially in combination with endocrine therapy.

SMTP-44D Inhibits Atherosclerotic Plaque Formation in Apolipoprotein-E Null Mice Partly by Suppressing the AGEs-RAGE Axis.

SMTP-44D has been reported to have anti-oxidative and anti-inflammatory reactions, including reduced expression of receptor for advanced glycation end products (RAGE) in experimental diabetic neuropathy. Although activation of RAGE with its ligands, and advanced glycation end products (AGEs), play a crucial role in atherosclerotic cardiovascular disease, a leading cause of death in diabetic patients, it remains unclear whether SMTP-44D could inhibit experimental atherosclerosis by suppressing the AGEs-RAGE axis. In this study, we investigated the effects of SMTP-44D on atherosclerotic plaque formation and expression of AGEs in apolipoprotein-E null () mice.

Combined phospholipids adjuvant augments anti-tumor immune responses through activated tumor-associated dendritic cells.

Dendritic cells (DCs) can initiate both naïve and memory T cell activation, as the most potent antigen-presenting cells. For efficient anti-tumor immunity, it is essential to enhance the anti-tumoral activity of tumor-associated DCs (TADCs) or to potently restrain TADCs so that they remain immuno-stimulating cells. Combined phospholipids (cPLs) adjuvant may act through the activation of DCs.

Identification of aminobenzoic acids as selective inhibitors of the N-terminal phosphatase of soluble epoxide hydrolase.

Soluble epoxide hydrolase (EC 3.3.2.

A first-in-human study of the anti-inflammatory profibrinolytic TMS-007, an SMTP family triprenyl phenol.

Aims: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation.

Effect of SMTP-7 on Cisplatin-Induced Nephrotoxicity in Mice.

SMTP-7, a fungal metabolite, is reported to have a high degree of availability for the ischemia-reperfusion (IR)-induced acute kidney injury (AKI) model. Cisplatin, a widely used anticancer drug, has serious side effects, such as AKI. Hence, we aimed to examine the effect of SMTP-7 on cisplatin-induced AKI in this study.

A patient with stage IIIB advanced breast cancer who is still alive 24 years after surgery: a case report and remarks on the treatment strategies.

Background: In recent years, a number of agents possessing novel mechanisms, such as cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors and PIK3CA inhibitors, have been developed for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor type negative (HER2-) advanced or recurrent breast cancer. As a result, the treatment strategies for advanced or recurrent breast cancer have changed significantly. The combination of CDK 4/6 inhibitors administration and endocrine therapy is now widely used in the treatment of HR+ HER2- recurrent breast cancer with improved outcomes.

Direct cell-cell interaction regulates division of stem cells from PC-3 human prostate cancer cell line.

Cancer stem cells (CSCs) are a subpopulation that can drive recurrence and metastasis. Therefore, therapies targeting CSCs are required. Although previous findings have suggested that non-CSCs regulate the proliferation and differentiation of CSCs in the tumor microenvironment, the precise molecular mechanism is largely unknown.

Amine-Regulated pri-SMTP Oxidation in SMTP Biosynthesis in : Possible Implication in Nitrogen Acquisition.

SMTP (the name SMTP is derived from triprenyl phenol) is a family of triprenyl phenol secondary metabolites from a black mold, . Some SMTP congeners exhibit anti-inflammatory and profibrinolytic activities that, in combination, contribute to the treatment of ischemic stroke. The final step in the SMTP biosynthesis is a non-enzymatic amine conjugation with an -phthalaldehyde moiety of the precursor pre-SMTP, which can form adducts with proteins and nucleic acids.

SMTP-44D Exerts Antioxidant and Anti-Inflammatory Effects through Its Soluble Epoxide Hydrolase Inhibitory Action in Immortalized Mouse Schwann Cells upon High Glucose Treatment.

Diabetic neuropathy (DN) is a major complication of diabetes mellitus. We have previously reported the efficacy of triprenyl phenol-44D (SMTP-44D) for DN through its potential antioxidant and anti-inflammatory activities. However, the mechanisms underlying the antioxidant and anti-inflammatory activities of SMTP-44D remain unclear.

A One-Armed Phase I Dose Escalation Trial Design: Personalized Vaccination with IKKβ-Matured, RNA-Loaded Dendritic Cells for Metastatic Uveal Melanoma.

Uveal melanoma (UM) is an orphan disease with a mortality of 80% within one year upon the development of metastatic disease. UM does hardly respond to chemotherapy and kinase inhibitors and is largely resistant to checkpoint inhibition. Hence, further therapy approaches are urgently needed.

β-glucan from Aureobasidium pullulans augments the anti-tumor immune responses through activated tumor-associated dendritic cells.

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor.

Potent efficacy of Stachybotrys microspora triprenyl phenol-7, a small molecule having anti-inflammatory and antioxidant activities, in a mouse model of acute kidney injury.

Acute kidney injury (AKI) increases the risk of chronic kidney disease (CKD), complicates existing CKD, and can lead to the end-stage renal disease. However, there are no approved effective therapeutics for AKI. Recent studies have suggested that inflammation and oxidative stress are the primary causes of AKI.

Impact of SMTP Targeting Plasminogen and Soluble Epoxide Hydrolase on Thrombolysis, Inflammation, and Ischemic Stroke.

triprenyl phenol (SMTP) is a large family of small molecules derived from the fungus . SMTP acts as a zymogen modulator (specifically, plasminogen modulator) that alters plasminogen conformation to enhance its binding to fibrin and subsequent fibrinolysis. Certain SMTP congeners exert anti-inflammatory effects by targeting soluble epoxide hydrolase.

SMTP-44D improves diabetic neuropathy symptoms in mice through its antioxidant and anti-inflammatory activities.

Diabetic neuropathy (DN) is one of the major complications of diabetes. However, there are few approved effective therapies for painful or insensate DN. Recent studies have implicated oxidative stress and inflammation in the pathogenesis of DN, and suppressing these could be an important therapeutic strategy.