Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans.

Adult intestinal stem cells (ISCs) possess both a long-term proliferation ability and differentiation capability into enterocytes. As a novel in vitro system for the evaluation of drug absorption, we characterized a human small intestinal epithelial cell (HIEC) monolayer that differentiated from adult ISCs. Continuous proliferation/differentiation from ISCs consistently conferred the capability of maturation of enterocytes to HIECs over 25 passages.

Concurrent chemoradiotherapy for patients with postoperative recurrence of surgically resected non-small-cell lung cancer.

Background: A few reports have evaluated the outcomes of concurrent chemoradiotherapy (CRT) for patients with postoperative recurrence of non-small cell lung cancer (NSCLC).

Patients And Methods: From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution. Of those, 280 patients had experienced postoperative recurrence by the end of 2012.

The contribution of epithelial-mesenchymal transition to renal fibrosis differs among kidney disease models.

The impact of the epithelial-mesenchymal transition (EMT) to the formation of renal fibrosis has been debated in several lineage-tracing studies, with conflicting findings. Such disparities may have arisen from varying experimental conditions such as different disease models, the mouse strain, and type of genetic alteration used. In order to determine the contribution of these factors to EMT, we generated four kidney disease models in several mouse strains genetically modified to express enhanced green fluorescence protein (EGFP) in cortical tubular epithelial cells under the control of the γ-glutamyl transpeptidase promoter.

Non-small cell lung cancer patients with EML4-ALK fusion gene are insensitive to cytotoxic chemotherapy.

Background: Although patients with the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene (EML4-ALK) re-arrangement and epidermal growth factor gene EGFR mutations have proven sensitive to specific inhibitors, there is currently no consensus regarding the sensitivity of non-small cell lung cancer (NSCLC) patients with such mutations to cytotoxic chemotherapy.

Patients And Methods: The responses to first-line cytotoxic chemotherapy were retrospectively compared between advanced or postoperative recurrent patients with non-squamous NSCLC who harbor the EML4-ALK fusion gene (ALK+), EGFR mutation (EGFR+), or neither abnormality (wild-type).

Results: Data for 22 ALK+, 30 EGFR+, and 60 wild-type patients were analyzed.

Impact of the epidermal growth factor receptor mutation status on the post-recurrence survival of patients with surgically resected non-small-cell lung cancer.

Objectives: The impact of epidermal growth factor receptor (EGFR) status and the use of EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy have not been well discussed only in recurrent non-small-cell lung cancer (NSCLC). The purpose of this study was to identify the prognostic factors associated with post-recurrence survival after surgical resection of NSCLC in terms of the EGFR mutation status and the use of EGFR-TKI therapy.

Methods: From 2000 through 2011, 1237 consecutive patients with NSCLC underwent pulmonary resection at our institution.

Electrophysiological measurement of interest during walking in a simulated environment.

A reliable neuroscientific technique for objectively estimating the degree of interest in a real environment is currently required in the research fields of neuroergonomics and neuroeconomics. Toward the development of such a technique, the present study explored electrophysiological measures that reflect an observer's interest in a nearly-real visual environment. Participants were asked to walk through a simulated shopping mall and the attractiveness of the shopping mall was manipulated by opening and closing the shutters of stores.

High-dose-rate interstitial brachytherapy in combination with androgen deprivation therapy for prostate cancer: are high-risk patients good candidates?

Background And Purpose: To evaluate the effectiveness of high-dose-rate interstitial brachytherapy (HDR-ISBT) as the only form of radiotherapy for high-risk prostate cancer patients.

Patients And Methods: Between July 2003 and June 2008, we retrospectively evaluated the outcomes of 48 high-risk patients who had undergone HDR-ISBT at the National Hospital Organization Osaka National Hospital. Risk group classification was according to the criteria described in the National Comprehensive Cancer Network (NCCN) guidelines.

Calcitriol supplementation improves endothelium-dependent vasodilation in rat hypertensive renal injury.

Background/aims: Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress.

Methods: In this study, we aimed to determine if vitamin D would suppress oxidative stress using 4 groups of hypertensive rats: uninephrectomized, stroke-prone, spontaneously hypertensive rats fed a high-salt (6%) diet (controls; C); those treated with irbesartan (I); those treated with calcitriol (V); and those treated with both irbesartan and calcitriol (I+V).

High-dose-rate interstitial brachytherapy for mobile tongue cancer: preliminary results of a dose reduction trial.

Purpose: To compare the outcome of our facility with another about the shortened schedule (60 Gy in 10 fractions to 54 Gy in 9 fractions) of high-dose-rate interstitial brachytherapy (HDR ISBT) for mobile tongue cancer.

Material And Methods: Eighteen patients were treated with HDR ISBT as a monotherapy in dose reduction schedule with some unique technique to determine the border of tumor accuracy (lugol's staining and metal marker), and to minimize adverse effect (lead-lined silicon block) at our facility.

Results: The 2-year local and regional control rates and cause-specific survival rate were 82%, 80%, and 83% and moderate to severe late complications occurred in five patients (28%), which were almost the same treatment results achieved by another facility.

Decline of Renal Function and Progression of Left Ventricular Hypertrophy Are Independently Determined in Chronic Kidney Disease Stages 3-5.

Unlabelled: Invasive and noninvasive methods for evaluating the effects of hemodynamics on progression of left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD) have been proposed. Central aortic pressure (CAP) has been reported to be the best among selected measures of hemodynamics for predicting LVH. However, there are few studies examining the relation between longitudinal changes in CAP and renal dysfunction in patients with CKD.

Role of Pulse Wave Velocity in Patients with Chronic Kidney Disease Stages 3-5 on Long-Term Follow-Up.

Background: The relationship between arterial stiffness and kidney function has not been clearly demonstrated although observations of higher arterial stiffness in patients with advanced stages of chronic kidney disease (CKD) were reported. In longitudinal analyses, there was no close association between basal arterial stiffness and progression of kidney function in the general population. In the present study, we assessed the relationship between arterial stiffness and progression of renal dysfunction in patients with CKD stages 3-5 using two types of measures of arterial stiffness, i.

A novel minimally invasive technique of high-dose rate image-based intracavitary brachytherapy for endometrial cancer using a single fine and soft, flexible applicator.

Aim: We report on a minimally invasive computed tomography (CT)/magnetic resonance imaging (MRI)-based image-guided intracavitary brachytherapy (ICBT) for an elder patient with endometrial cancer, who was unfit for anesthesia, using a fine and soft flexible applicator.

Patients And Methods: The patient was an 82-year-old female. She was identified as having T1bN0M0 (stage IB) tumor, and histological findings revealed grade 2 adenocarcinoma.

Isolated cardiac sarcoidosis requiring open-chest myocardial biopsy for differentiation from malignant lymphoma.

A 68-year-old woman with a history of hypertension was admitted to our hospital because of dyspnea during physical exertion. Echocardiography demonstrated impaired left ventricular systolic function, and her ejection fraction was reduced to 30%. Coronary angiography did not show significant stenosis.

Calcium channel blockers suppress daily variations of blood pressure in hypertensive patients with end-stage renal diseases.

Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension. Furthermore, daily variations of blood pressure are relatively large in patients treated with hemodialysis, partly due to ultrafiltration.

Split-dose cisplatin and vinorelbine as adjuvant chemotherapy for completely resected non-small cell lung cancer.

Aim: The aim of the present study was to evaluate the feasibility of, and compliance with a regimen using split-dose cisplatin and vinorelbine (split-CV) as adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC).

Patients And Methods: The treatment schedule included cisplatin at 40 mg/m(2) and vinorelbine at 25 mg/m(2) administered intravenously on days 1 and 8, every three weeks for four cycles.

Results: This study included 22 patients (male/female; 12/10) with a median age of 67 (range 50-76) years; 10 had clinical stage II and 12 stage III; 21 had ECOG 0 and 1 patient ECOG 1; 15 patients had adenocarcinoma, 5 squamous cell and 2 adenosquamous carcinoma; 18 patients had undergone lobectomy, 3 pneumonectomy and 1 segmentectomy.

Clinical science of calcium channel blocker to inhibit hypertensive vascular injury.

Calcium channel blockers are the strongest and most widely used antihypertensive drugs in Japan. Calcium channel blockers dilate both artery and arteriole that increases end-organ perfusion, thus possessing few side effects especially for the elderly hypertensive patients. The safety of calcium channel blockers was well established.

Statin improves flow-mediated vasodilation in chronic kidney diseases.

Background. Numbers of drugs are required to manage patients with chronic kidney disease (CKD). Drug adherence is relatively poor in this population.

Sequence-specific DNA alkylation targeting for Kras codon 13 mutation by pyrrole-imidazole polyamide seco-CBI conjugates.

Hairpin N-methylpyrrole-N-methylimidazole polyamide seco-CBI conjugates 2-6 were designed for synthesis by Fmoc solid-phase synthesis, and their DNA-alkylating activities against the Kras codon 13 mutation were compared by high-resolution denaturing gel electrophoresis with 225 base pair (bp) DNA fragments. Conjugate 5 had high reactivity towards the Kras codon 13 mutation site, with alkylation occurring at the A of the sequence 5'-ACGTCACCA-3' (site 2), including minor 1 bp-mismatch alkylation against wild type 5'-ACGCCACCA-3' (site 3). Conjugate 6, which differs from conjugate 5 by exchanging one Py unit with a β unit, showed high selectivity but only weakly alkylated the A of 5'-ACGTCACCA-3' (site 2).

Disturbed tumor necrosis factor system is linked with lower eGFR and chronic inflammation in hypertension.

Background: The relationship between tumor necrosis factor (TNF)-related parameters and cardiorenal metabolic factors is still controversial in clinical hypertension.

Methods: Normotensive men (NT, n=60) and treated stage 2 and 3 essential hypertensive men (HT, n=89) were enrolled in this study. The relationship between TNF-related parameters and cardiorenal metabolic factors was examined in NT and HT, separately.

Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy.

Background: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that responds poorly to chemotherapy. Although treatment with pemetrexed in combination with cisplatin serves as first-line chemotherapy for MPM, the optimal second-line and beyond therapy has not yet been fully examined.

Methods: Between March 2008 and October 2011, 17 consecutive Japanese patients pretreated with at least one regimen of platinum plus pemetrexed chemotherapy received gemcitabine and vinorelbine.

The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorable tolerability profile.

VEGF receptor (VEGFR) signaling plays a key role in tumor angiogenesis. Although some VEGFR signal-targeted drugs have been approved for clinical use, their utility is limited by associated toxicities or resistance to such therapy. To overcome these limitations, we developed TAS-115, a novel VEGFR and hepatocyte growth factor receptor (MET)-targeted kinase inhibitor with an improved safety profile.

Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

Introduction: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM). rTM has been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan, and is currently undergoing a phase III clinical trial in the United States.

Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer drugs to glioblastoma through the blood-brain tumor barrier.

Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules for targeting αvβ3/αvβ5 integrins, which are overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic Arg-Gly-Asp (cRGD) ligand molecules.