MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated signaling.

MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines.

Rosiglitazone increases endothelial cell migration and vascular permeability through Akt phosphorylation.

Background: Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, exhibit anti-inflammatory and antioxidant properties and inhibit endothelial inflammation and dysfunction, which is anti-atherogenic. However, fluid retention, which may lead to congestive heart failure and peripheral edema, is also a concern, which may result from endothelial cell leakage. In the current study, we examined the effects of PPAR-γ agonists on vascular endothelial cell migration and permeability in order to determine its underlying mechanisms.

Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo.

Even with aggressive treatment involving radiation therapy plus temozolomide (TMZ), the prognosis for glioblastoma remains poor. We investigated the potential for targeting signal transducer and activator of transcription-3 (STAT3) to improve the therapeutic outcome in glioblastoma. We evaluated the preclinical potential of a STAT3 inhibitor, Cpd188, combined with temozolomide and radiation using in vitro assays with two established glioblastoma cell lines (U251 and U87) and two patient-derived glioblastoma cell lines (GBL12 and GBL28) as well as in vivo studies with nude mice bearing intracranial U251 xenografts.

Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells.

Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification.

Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization.

Purpose: Histone deacetylase (HDAC) inhibitors radiosensitize tumor cells. To elucidate mechanisms underlying radiosensitization by HDAC inhibition, understanding of differential contributions of HDAC isotypes is needed. The aim of this study was to investigate involvement of known HDAC isotypes in modulation of cellular radiosensitivity.

The Effect of Chemoradiotherapy with SRC Tyrosine Kinase Inhibitor, PP2 and Temozolomide on Malignant Glioma Cells In Vitro and In Vivo.

Purpose: We investigated the effect of chemoradiotherapy with PP2 and temozolomide (TMZ) on malignant glioma cells using clonogenic assays and in vivo brain tumor model.

Materials And Methods: The effect of PP2 on radiosensitivity of U251 and T98G cells was investigated using clonogenic assays. The expression of E-cadherin, matrix metalloproteinases 2 (MMP2), Ephrin type-A receptor 2 (EphA2), and vascular endothelial growth factor (VEGF) was measured by Western blotting and an accumulation of γH2AX foci 6 hours after radiotherapy was measured after PP2 treatment.

Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) shows aggressive clinical behavior, but the treatment options are limited due to lack of a specific target. TNBC shares many clinical and pathological similarities with BRCA-deficient breast cancer, for which poly(ADP-ribose) polymerase (PARP) inhibitor is effective, but PARP inhibitor alone failed to show clinical effects in patients with sporadic TNBC. Radiation induces DNA double-strand breaks, and the phosphoinositide 3-kinase (PI3K) signaling pathway has been known to regulate steady-state levels of homologous recombination.

Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases.

Background: Despite aggressive treatment with radiation therapy and concurrent adjuvant temozolomide (TMZ), glioblastoma multiform (GBM) still has a dismal prognosis. We aimed to identify strategies to improve the therapeutic outcome of combined radiotherapy and TMZ in GBM by targeting pro-survival signaling from the epidermal growth factor receptor (EGFR).

Methods: Glioma cell lines U251, T98G were used.

Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level.

Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.

The effects of chronic exercise on the inflammatory cytokines interleukin-6 and tumor necrosis factor-α are different with age.

Aging is associated with chronic low-grade inflammation, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are key mediators of the inflammatory process. IL-6, especially muscle-derived IL-6, is expected to mediate the beneficial metabolic effects of exercise. There was no report that directly compares the effects of chronic endurance exercise on cytokine responses between old and young subjects in the same situation.

Effect of a dipeptidyl peptidase-IV inhibitor, des-fluoro-sitagliptin, on neointimal formation after balloon injury in rats.

Background: Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms.

Methods And Findings: Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group).

Differential effects of trimetazidine on vascular smooth muscle cell and endothelial cell in response to carotid artery balloon injury in diabetic rats.

Background: Treatment with trimetazidine (TMZ), 1-[2,3,4-trimethoxybenzyl] piperazine, dihydrochloride, improves cardiac function and ameliorates endothelial dysfunction. However, its potential efficacy against restenosis after balloon injury has not been addressed. We investigated the effect of TMZ on reducing the occurrence of restenosis in the carotid artery in response to balloon injury and explored potential mechanisms for the effects.

EGb761, a Ginkgo biloba extract, is effective against atherosclerosis in vitro, and in a rat model of type 2 diabetes.

Background: EGb761, a standardized Ginkgo biloba extract, has antioxidant and antiplatelet aggregation and thus might protect against atherosclerosis. However, molecular and functional properties of EGb761 and its major subcomponents have not been well characterized. We investigated the effect of EGb761 and its major subcomponents (bilobalide, kaemferol, and quercetin) on preventing atherosclerosis in vitro, and in a rat model of type 2 diabetes.

Serum fibroblast growth factor-21 concentration is associated with residual renal function and insulin resistance in end-stage renal disease patients receiving long-term peritoneal dialysis.

Fibroblast growth factor-21 (FGF-21) is a new metabolic regulator, which is related to antiobesity and insulin sensitivity in vivo. However, the clinical implication of FGF-21 is poorly understood. To investigate whether FGF-21 may play a role as a metabolic regulator in patients with end-stage renal disease, we measured serum concentrations of FGF-21, inflammatory markers, and metabolic parameters in healthy people (n = 63) and nondiabetic patients receiving peritoneal dialysis (PD, n = 72).

Effect of a peroxisome proliferator-activated receptor gamma sumoylation mutant on neointimal formation after balloon injury in rats.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor regulating inflammation, atherosclerosis, insulin sensitivity and adipogenesis. Recently, it has been discovered that modification by the small ubiquitin-like modifier (SUMO) plays an important role in PPARgamma activity. In the present study, we investigated the effect of sumoylation on the antiatherogenic property of PPARgamma.

Effect of ginsam, a vinegar extract from Panax ginseng, on body weight and glucose homeostasis in an obese insulin-resistant rat model.

Extracts of ginseng species show antihyperglycemic activity. We evaluated the antihyperglycemic and antiobesity effects of ginsam, a component of Panax ginseng produced by vinegar extraction, which is enriched in the ginsenoside Rg3. Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, were assigned into 1 of 3 groups (n = 8 each): controls (isotonic sodium chloride solution, 5 mL/d), rats given 300 mg/(kg d) ginsam, and rats given 500 mg/(kg d) ginsam.

Berberine inhibits the production of lysophosphatidylcholine-induced reactive oxygen species and the ERK1/2 pathway in vascular smooth muscle cells.

Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity.