Association of taurine intake with changes in physical fitness among community-dwelling middle-aged and older Japanese adults: an 8-year longitudinal study.

Introduction: Taurine has diverse valuable biological functions, including antioxidant activity and regulation of osmotic pressure. Maintaining physical fitness from middle age is important for healthy life expectancy. Although taurine administration improves muscle endurance and strength, its role in maintenance remains unclear.

Glycogen synthase kinase 3β: the nexus of chemoresistance, invasive capacity, and cancer stemness in pancreatic cancer.

The treatment of pancreatic cancer remains a significant clinical challenge due to the limited number of patients eligible for curative (R0) surgery, failures in the clinical development of targeted and immune therapies, and the pervasive acquisition of chemotherapeutic resistance. Refractory pancreatic cancer is typified by high invasiveness and resistance to therapy, with both attributes related to tumor cell stemness. These malignant characteristics mutually enhance each other, leading to rapid cancer progression.

Deactivation of glycogen synthase kinase-3β by heat shock‑inducible tumor small protein attenuates hyperthermia‑induced pro‑migratory activity in colorectal cancer cells.

Hyperthermia is a promising approach for improving cancer treatment in combination with chemotherapy, radiotherapy and/or immunotherapy; however, its molecular mechanisms remain unclear. Although heat shock proteins (HSPs) are involved in hyperthermia via antigen presentation and immune activation, major HSPs including HSP90 are associated with cancer progression via tumor cell migration and metastasis. The present study showed that heat shock‑inducible tumor small protein (HITS) could counteract the pro‑migratory effects of HSPs in colorectal cancer (CRC) cells, which represents a novel function.

Expression status of p53 and organic cation transporter 1 is correlated with poor response to preoperative chemotherapy in esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. DNA-damaging drugs, such as cisplatin (CDDP) and 5-fluorouracil (5-FU), are most frequently used in preoperative chemotherapy for ESCC. However, the response to preoperative chemotherapy varies among patients.

Discovery of a Novel Aminocyclopropenone Compound That Inhibits BRD4-Driven Nucleoporin NUP210 Expression and Attenuates Colorectal Cancer Growth.

Epigenetic deregulation plays an essential role in colorectal cancer progression. Bromodomains are epigenetic "readers" of histone acetylation. Bromodomain-containing protein 4 (BRD4) plays a pivotal role in transcriptional regulation and is a feasible drug target in cancer cells.

Glycogen synthase kinase-3β participates in acquired resistance to gemcitabine in pancreatic cancer.

Acquisition of resistance to gemcitabine is a challenging clinical and biological hallmark property of refractory pancreatic cancer. Here, we investigated whether glycogen synthase kinase (GSK)-3β, an emerging therapeutic target in various cancer types, is mechanistically involved in acquired resistance to gemcitabine in human pancreatic cancer. This study included 3 gemcitabine-sensitive BxPC-3 cell-derived clones (BxG30, BxG140, BxG400) that acquired stepwise resistance to gemcitabine and overexpressed ribonucleotide reductase (RR)M1.

Potential therapeutic effect of targeting glycogen synthase kinase 3β in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal cancer and is often refractory to current therapies. Development of efficient therapeutic strategies against ESCC presents a major challenge. Glycogen synthase kinase (GSK)3β has emerged as a multipotent therapeutic target in various diseases including cancer.

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment.

Glycogen synthase kinase (GSK)3β is a multifunctional serine/threonine protein kinase with more than 100 substrates and interacting molecules. GSK3β is normally active in cells and negative regulation of GSK3β activity via phosphorylation of its serine 9 residue is required for most normal cells to maintain homeostasis. Aberrant expression and activity of GSK3β contributes to the pathogenesis and progression of common recalcitrant diseases such as glucose intolerance, neurodegenerative disorders and cancer.

Stepwise surgery with variable adjustments for severe blepharochalasis with multiple chemical sensitivity: a case report.

We report a 29-year-old man with blepharochalasis and multiple chemical sensitivity (MCS). Although standard blepharoplasty with aponeurotic fixation was performed, palpebral ptosis recurred after 3 months. Eyelid function and appearance improved after additional operations.

Glycogen synthase kinase 3β as a potential therapeutic target in synovial sarcoma and fibrosarcoma.

Soft tissue sarcomas (STSs) are a rare cancer type. Almost half are unresponsive to multi-pronged treatment and might therefore benefit from biologically targeted therapy. An emerging target is glycogen synthase kinase (GSK)3β, which is implicated in various diseases including cancer.

Identification of GSK3β inhibitor kenpaullone as a temozolomide enhancer against glioblastoma.

Cancer stem cells are associated with chemoresistance and rapid recurrence of malignant tumors, including glioblastoma (GBM). Although temozolomide (TMZ) is the most effective drug treatment for GBM, GBM cells acquire resistance and become refractory to TMZ during treatment. Therefore, glioma stem cell (GSC)-targeted therapy and TMZ-enhancing therapy may be effective approaches to improve GBM prognosis.

Colorectal cancer cells require glycogen synthase kinase-3β for sustaining mitosis via translocated promoter region (TPR)-dynein interaction.

Glycogen synthase kinase (GSK) 3β, which mediates fundamental cellular signaling pathways, has emerged as a potential therapeutic target for many types of cancer including colorectal cancer (CRC). During mitosis, GSK3β localizes in mitotic spindles and centrosomes, however its function is largely unknown. We previously demonstrated that translocated promoter region (TPR, a nuclear pore component) and dynein (a molecular motor) cooperatively contribute to mitotic spindle formation.

Sutureless Microvascular Anastomosis using Intravascular Stenting and Cyanoacrylate Adhesive.

Background:  Microvascular anastomosis using cyanoacrylate adhesive has a reputation among researchers as an alternative to conventional sutures. However, a degree of ingenuity is required to avoid the collapse of the vascular lumen for the duration of the anastomosis. The aim of this study was to determine the feasibility of intravascular stenting (IVaS) as a temporary stent during sutureless microvascular anastomosis with cyanoacrylate adhesive.

Phaeoacremonium Tenosynovitis of the Wrist.

A 79-year-old man presented with a painless, soft, subcutaneous mass lesion of the right volar wrist that had been slowly growing for 3 years. A cloudy, yellow serous effusion was aspirated from the punctured mass, from which Phaeoacremonium spp., an extremely rare cause of tenosynovitis, was isolated in culture.

Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy.

Tumor cell invasion and resistance to therapy are the most intractable biological characteristics of cancer and, therefore, the most challenging for current cancer research and treatment paradigms. Refractory cancers, including pancreatic cancer and glioblastoma, show an inextricable association between the highly invasive behavior of tumor cells and their resistance to chemotherapy, radiotherapy and targeted therapies. These aggressive properties of cancer share distinct cellular pathways that are connected to each other by several molecular hubs.

Efficacy of glycogen synthase kinase-3β targeting against osteosarcoma via activation of β-catenin.

Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3β (GSK- 3β) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3β inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model.

Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway.

A histone acetyltransferase Tat-interacting protein 60 kDa (Tip60) regulates the DNA damage response by acetylating histone and remodeling chromatin. In addition to histone acetyltransferase activity, Tip60 is known to regulate a variety of cellular functions, including gene expression, DNA damage response, cell migration and apoptosis. Lower expression of Tip60 is observed in lymphomas, melanomas, breast, colon, and lung cancer.

Modification of the Nuss Procedure: The Single-incision Technique.

The Nuss procedure is a prevalent minimally invasive surgery for pectus excavatum. Although the Nuss procedure has the advantage of leaving less obtrusive scars, the standard technique requires at least 3 skin incisions to insert several instruments. We experienced 7 cases of the modified Nuss procedure using a single incision during a 7-year period.

Glycogen synthase kinase 3β sustains invasion of glioblastoma via the focal adhesion kinase, Rac1, and c-Jun N-terminal kinase-mediated pathway.

The failure of current treatment options for glioblastoma stems from their inability to control tumor cell proliferation and invasion. Biologically targeted therapies offer great hope and one promising target is glycogen synthase kinase-3β (GSK3β), implicated in various diseases, including cancer. We previously reported that inhibition of GSK3β compromises the survival and proliferation of glioblastoma cells, induces their apoptosis, and sensitizes them to temozolomide and radiation.

Vinculin negatively regulates transcription of MT1-MMP through MEK/ERK pathway.

Vinculin regulates a variety of cellular functions partly through stabilization of tumor suppressor PTEN. In order to study the role of vinculin in tumor progression other than PTEN stabilization, vinculin was knocked down in PTEN-deficient squamous cell carcinoma HSC-4 cells. Knockdown of vinculin induced phenotypical change by reducing cell-cell and cell-extracellular matrix adhesions, and enhanced MT1-MMP expression at transcription level and subsequent cell migration.

Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly and N-cadherin adhesion.

Fibronectin matrix formation requires the increased cytoskeletal tension generated by cadherin adhesions, and is suppressed by membrane-type 1 matrix metalloproteinase (MT1-MMP). In a co-culture of Rat1 fibroblasts and MT1-MMP-silenced HT1080 cells, fibronectin fibrils extended from Rat1 to cell-matrix adhesions in HT1080 cells, and N-cadherin adhesions were formed between Rat1 and HT1080 cells. In control HT1080 cells contacting with Rat1 fibroblasts, cell-matrix adhesions were formed in the side away from Rat1 fibroblasts, and fibronectin assembly and N-cadherin adhesions were not formed.

Effect on blood pressure of daily lemon ingestion and walking.

Background. Recent studies suggest that the daily intake of lemon (Citrus limon) has a good effect on health, but this has not been confirmed in humans. In our previous studies, it was observed that people who are conscious of their health performed more lemon intake and exercise.

[Effect of variation of lemon intake and walking in daily life on various indicators of muscle mass and blood biochemistry in menopausal middle-aged and elderly women].

Objectives: We examined the factors considered to change body composition and blood biochemistry indicators in menopausal middle-aged and elderly women. These changes result from exercise by walking as part of their daily activities and lemon consumption by women who live on the small islands of the Seto Inland Sea, Japan's largest citrus fruit (lemon)-producing region.

Methods: Between September 2011 and March 2012, we recorded the daily lemon consumption and the number of steps taken by 101 middle-aged and elderly female lemon farmers.

MT1-MMP prevents growth inhibition by three dimensional fibronectin matrix.

The extracellular microenvironment plays a key role in regulation of cellular functions and growth control. We show here that membrane-type 1 matrix metalloproteinase (MT1-MMP) acts as a growth promoter in confluent culture. When MT1-MMP was silenced in HT1080 fibrosarcoma cells, cells created three dimensional (3D) fibronectin matrix in a confluent culture, and growth of cells embedded within it was retarded.

Shedding of kidney injury molecule-1 by membrane-type 1 matrix metalloproteinase.

Co-expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) with kidney injury molecule-1 (KIM-1) in HEK293T cells resulted in cleavage and shedding of KIM-1 ectodomain. Analysis of cleavage products using KIM-1 mutants localized cleavage site at the juxtamembrane region. HT1080 cells were stably transfected with expression plasmid for KIM-1 or its mutant with deletion of the juxtamembrane region (Asp(261)-Gly(295)) to establish HT/KIM-1 or HT/ΔKIM-1 cells, respectively.