Metformin induces apoptosis in TRAIL-resistant colorectal cancer cells.

Resistance to chemotherapy drugs, which commonly occurs during the treatment of colorectal cancer (CRC), can lead to tumor recurrence and metastasis, so combinational treatment strategies according to the cancer cell type are urgently needed to overcome drug resistance and increase therapeutic efficiency. To this end, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer strategy. Some CRC cell lines such as SW620 have low sensitivity to TRAIL, so additional sensitizers are required to make the strategy effective.

Transport of Golgi-localized β-catenin p-S47 by KIF11 or KIFC3 induces primary ciliogenesis.

Primary cilium is an important hub for cell signaling and dysregulation of primary cilia assembly and disassembly is associated with the development of cancer and chemotherapeutic drug resistance, as well as the genetic disorders collectively known as ciliopathy. β-catenin plays a major role in canonical Wnt signaling; however, its association with primary cilia has only recently been highlighted in reports of β-catenin-mediated primary ciliogenesis. In this study, we found that β-catenin p-S47 was localized to the Golgi apparatus and the nucleus, and the amount of β-catenin p-S47 at these locations was significantly higher during primary ciliogenesis compared with asynchronous cell growth conditions.

FRMD6 determines the cell fate towards senescence: involvement of the Hippo-YAP-CCN3 axis.

Cellular senescence, a hallmark of aging, is pathogenically linked to the development of aging-related diseases. This study demonstrates that FRMD6, an upstream component of the Hippo/YAP signaling cascade, is a key regulator of senescence. Proteomic analysis revealed that FRMD6 is upregulated in senescent IMR90 fibroblasts under various senescence-inducing conditions.

The TGFβ→TAK1→LATS→YAP1 Pathway Regulates the Spatiotemporal Dynamics of YAP1.

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1.

Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain.

p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity.

Automated 3D Segmentation of Intraretinal Surfaces in SD-OCT Volumes in Normal and Diabetic Mice.

Purpose: To describe an adaptation of an existing graph-theoretic method (initially developed for human optical coherence tomography [OCT] images) for the three-dimensional (3D) automated segmentation of 10 intraretinal surfaces in mice scans, and assess the accuracy of the method and the reproducibility of thickness measurements.

Methods: Ten intraretinal surfaces were segmented in repeat spectral domain (SD)-OCT volumetric images acquired from normal ( = 8) and diabetic ( = 10) mice. The accuracy of the method was assessed by computing the border position errors of the automated segmentation with respect to manual tracings obtained from two experts.

A combined machine-learning and graph-based framework for the segmentation of retinal surfaces in SD-OCT volumes.

Optical coherence tomography is routinely used clinically for the detection and management of ocular diseases as well as in research where the studies may involve animals. This routine use requires that the developed automated segmentation methods not only be accurate and reliable, but also be adaptable to meet new requirements. We have previously proposed the use of a graph-theoretic approach for the automated 3-D segmentation of multiple retinal surfaces in volumetric human SD-OCT scans.

Chemokine expression of intraocular lymphocytes in patients with Behçet uveitis.

Background: To compare the expression of chemokines in the aqueous humor and chemokine receptors in intraocular lymphocytes from Behçet and non-Behçet uveitis patients.

Methods: A total of 95 uveitis patients were included in this study. We studied 39 Behçet and 56 non-Behçet uveitis patients.

Inhibitory effect of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, on experimental choroidal neovascularization in rat.

Purpose: It was the aim of this study to evaluate the effects of YC-1, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, one of the hypoxia-inducible factor 1 (HIF-1) inhibitors, on laser-induced choroidal neovascularization (CNV) in rats.

Methods: Thirty female Brown Norway rats underwent laser photocoagulation to induce CNV. Twenty of them (treatment group) were treated with a single intravitreal injection of 5 microg YC-1, and the remaining 10 (control) were sham-treated with a single intravitreal injection of 2.

Multifocal electroretinogram responses of the clinically normal retinal areas in diabetes.

Aims: To investigate the degree of implicit time delay in aretinopathic hexagons according to the grading of diabetic retinopathy and factors that affect the mfERG responses of aretinopathic areas.

Methods: MfERG was recorded using the RETIscan system (Roland consult, Brandenbrug, Germany) in 40 eyes of 20 nondiabetic controls, 32 eyes of 16 diabetic patients without retinopathy, and 96 eyes of 48 diabetic patients with nonproliferative diabetic retinopathy (NPDR). Hexagons are divided into retinopathic and aretinopathic hexagons, which were selected using fundus photographs and fluorescence angiography.

The mitochondrial Ca2+-activated K+ channel activator, NS 1619 inhibits L-type Ca2+ channels in rat ventricular myocytes.

We examined the effects of the mitochondrial Ca(2+)-activated K(+) (mitoBK(Ca)) channel activator NS 1619 on L-type Ca(2+) channels in rat ventricular myocytes. NS 1619 inhibited the Ca(2+) current in a dose-dependent manner. NS 1619 shifted the activation curve to more positive potentials, but did not have a significant effect on the inactivation curve.

Endogenous angiotensin II enhances atherogenesis in apoprotein E-deficient mice with renovascular hypertension through activation of vascular smooth muscle cells.

Renovascular hypertension is one of the most important risk factors in the development of atherosclerosis. However, very little is known about the role of angiotensin II (AII), a key regulator of blood pressure homeostasis, on renovascular hypertension-associated atherogenesis. To study a possible role of AII on atherogenesis, we generated apoE-deficient hypertensive mice with either normal or increased AII production by applying 1-kidney, 1-clip (1K1C) or 2-kidney, 1-clip (2K1C) operation, respectively.

Delayed apoptosis and modulation of phospholipase D activity by plasmid containing mammalian cDNA in human neutrophils.

Phospholipase D (PLD) has been reported to have an anti-apoptotic role in neutrophils. This study examined the effects of plasmids containing the cDNA of PLD on the apoptosis of neutrophils. The apoptotic rate of neutrophils treated with the pCDNA3.

Placental superoxide dismutase, genetic polymorphism, and neonatal birth weight.

Background: The roles of antioxidants in the placenta and genetic susceptibility to oxidant chemicals in relation to neonatal birth weight have not been elucidated. We determined whether the level of placental manganese superoxide dismutase (MnSOD) and its genetic polymorphism plays any role in oxidative stress and neonatal birth weight.

Methods: We measured placental MnSOD and determined MnSOD genetic polymorphism among 108 pregnant women who were hospitalized for delivery and their singleton live births in Korea.

Phase I study of weekly docetaxel and cisplatin concurrent with thoracic radiotherapy in Stage III non-small-cell lung cancer.

Purpose: This is the first report of a Phase I study on concomitant weekly cisplatin and docetaxel chemotherapy with thoracic radiation for Stage III non-small-cell lung cancer (NSCLC). The study objectives were to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of docetaxel used in this regimen, and to evaluate the feasibility of weekly concurrent chemoradiotherapy.

Methods And Materials: Patients with histologically proven and unresectable Stage III NSCLC were the subjects of this study.

Long-lasting sonographic and histopathological findings in cured clonorchiasis of rabbits.

To ascertain residual sonographic and histopathological findings of clonorchiasis after treatment, the present study evaluated sonographic findings in rabbits which were infected with 500 metacercariae of C. sinensis every 6 months for 18 months after treatment with praziquantel. The sonographic findings were analyzed in terms of intrahepatic bile duct dilatation and periductal echogenicity, and histopathological findings were observed after the last sonographic examination.