Ectopic Overexpression of Coiled-Coil Domain Containing 110 Delays G2/M Entry in U2-OS Cells.

Coiled-coil domain containing 110 (CCDC110, KM-HN-1) is a protein containing C-terminal coiled-coil domain (CCD) which was previously discovered as a member of the human cancer/testis antigen (CTA). In addition, CCDC110 has both nuclear localization signal sequence and the leucine zipper motif. Although the functional role of CCDC110 has yet to be fully identified, the mRNA expression levels of CCDC110 are known to be highly elevated in various cancer types including testis, implying its relevance to cancer pathogenesis.

Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth factor signaling and resistance to inhibitors for epidermal growth factor receptor (EGFR), despite the overexpression of EGFR protein, and this is associated with a malignant behavior and a poor prognosis. In this study, to elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify inhibitors that exert a synergistic effect with EGFR inhibition, we examined the inhibitory effects of selected protein kinase inhibitors (PKIs) in combination with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC cell line. MK‑2206, an AKT inhibitor, and a group of mammalian target of rapamycin (mTOR) inhibitors were found to exert synergistic lethal effects in combination with gefitinib in MDA‑MB‑231 cells.

Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells.

Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2), a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy.

Co-treatment with BEZ235 Enhances Sensitivity of BRCA1-negative Breast Cancer Cells to Olaparib.

The poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib has been reported as having preferential anti-proliferative effects on breast cancer 1 (BRCA1)-deficient breast and ovarian cancer cells and was recently approved by the US Food and Drug Administration (FDA) for advanced, BRCA1-mutated ovarian cancer. Herein, we show that BEZ235, a protein kinase inhibitor, enhanced the tumor cell-killing effect of olaparib in BRCA1-mutated breast cancer cells in vitro. BEZ235 reduced olaparib-induced phosphorylation of p53 binding protein 1 (53BP1) and 53BP1 foci formation, as well as phosphorylation of AKT (S473).

Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative breast cancer cells through downregulation of ribosomal protein S6.

Triple-negative breast cancer (TNBC) exhibits innate resistance to the EGFR inhibition despite high level expression of EGFR. Recently, we found that the proliferation of basal-like (BL) subtype TNBC cells is synergistically inhibited by combination of EGFR and PI3K/AKT inhibitors. On the contrary, TNBC cells of mesenchymal stem-like (MSL) subtype are resistant to these combinations.

Non-muscle myosin II regulates neuronal actin dynamics by interacting with guanine nucleotide exchange factors.

Background: Non-muscle myosin II (NM II) regulates a wide range of cellular functions, including neuronal differentiation, which requires precise spatio-temporal activation of Rho GTPases. The molecular mechanism underlying the NM II-mediated activation of Rho GTPases is poorly understood. The present study explored the possibility that NM II regulates neuronal differentiation, particularly morphological changes in growth cones and the distal axon, through guanine nucleotide exchange factors (GEFs) of the Dbl family.

Combination of dasatinib and gemcitabine reduces the ALDH1A1 expression and the proliferation of gemcitabine-resistant pancreatic cancer MIA PaCa-2 cells.

Gemcitabine-based chemotherapy is the standard for treatment of pancreatic cancer; however, intrinsic and acquired resistance to gemcitabine commonly occurs. Aldehyde dehydrogenase 1A1 (ALDH1A1), one of the characteristic features of tumor-initiating and/or cancer stem cell (CSC) properties, is important in both intrinsic and acquired resistance to gemcitabine. In this study, we investigated the effectiveness of dasatinib, an SRC inhibitor, and gemcitabine combination to inhibit the survivals of parental (MIA PaCa-2/P) and gemcitabine-resistant (MIA PaCa-2/GR) cell lines.

cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells.

Background: The ataxia-telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells.

p90 ribosomal S6 kinase 1 (RSK1) isoenzyme specifically regulates cytokinesis progression.

The p90 ribosomal S6 kinase family (RSK1-4) of Ser/Thr kinases is a downstream component of the Ras-MAPK cascade responsible for regulating various cellular processes. Here, we examined the potential involvement of RSKs in regulating mitosis by transfecting HeLa cells with siRNAs targeting RSK1 and -2, which are the major isoforms. Depletion of RSK1 but not RSK2 triggered a significant accumulation of binucleated cells compared to control cells (0.

Respiratory effects of the hebei spirit oil spill on children in taean, Korea.

Purpose: The oil spill from the Heibei Spirit in December 2007 contaminated the Yellow Coast of South Korea. We evaluated the respiratory effects of that spill on children who lived along the Yellow Coast.

Methods: Of 662 children living in the area exposed to the oil spill, 436 (65.

A novel balanced-lethal host-vector system based on glmS.

During the last decade, an increasing number of papers have described the use of various genera of bacteria, including E. coli and S. typhimurium, in the treatment of cancer.

First report of human infection with Gynaecotyla squatarolae and first Korean record of Haplorchis pumilio in a patient.

Gynaecotyla squatarolae (Digenea: Microphallidae) is a minute intestinal trematode whose natural hosts are aves. We conducted a feces screening survey in a coastal village of Muan-gun, where the residents routinely consume brackish water crabs as a food. Through this survey, a 50-year-old female was found to shed gymnophallid and heterophyid eggs in her stool, and 845 adult flukes were collected from her purged stool.

Evacuated calcium phosphate spherical microcarriers for bone regeneration.

Microparticulates are an effective three-dimensional (3D) matrix for the culture of stem cells to be used in tissue engineering of bone. Herein, bioactive calcium phosphate microparticles with an evacuated morphology were prepared, and their potential to support stem cells for bone tissue engineering was addressed. Spherical particles with sizes of hundreds of micrometers were produced using the emulsification method, during which the internal portion was evacuated with the aid of solvent evaporation.

Involvement of betaPIX in angiotensin II-induced migration of vascular smooth muscle cells.

Angiotensin II (Ang II) stimulates migration of vascular smooth muscle cell (VSMC) in addition to its contribution to contraction and hypertrophy. It is well established that Rho GTPases regulate cellular contractility and migration by reorganizing the actin cytoskeleton. Ang II activates Rac1 GTPase, but its upstream guanine nucleotide exchange factor (GEF) remains elusive.

Mechanisms of mammalian polo-like kinase 1 (Plk1) localization: self- versus non-self-priming.

Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key element in regulating diverse mitotic events during M-phase progression. Plk1 is spatially regulated through the targeting activity of the conserved polo-box domain (PBD) present in the C-terminal non-catalytic region. Over the years, studies have demonstrated that the PBD forms a phospho-epitope binding module and the PBD-dependent interaction is critical for proper subcellular localization of Plk1.

Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts.

Background: Adipose-derived stem cells (ADSCs) are a population of pluripotent cells, which have characteristics similar to bone marrow-derived mesenchymal stem cells. Whereas ADSCs have potential applications for the repair and regeneration of various damaged tissues, few studies have dealt with the effect of ADSCs on fibroblasts, which play a key role in skin biology.

Objective: In this study, we investigated the possible roles of ADSCs in skin wound healing process, especially in the aspect of fibroblast activation-proliferation, collagen synthesis and migratory properties.

COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder cancer cells.

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor development and progression as well as to protect cells from apoptosis induced by various cellular stresses. Through a tetracycline-regulated COX-2 overexpression system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a human bladder cancer cell line, EJ. We also found that the inhibition of anoikis by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by suppression of the COX-2 effect on anoikis by a PI-3K inhibitor, LY294002.

Increased caveolin-1, a cause for the declined adipogenic potential of senescent human mesenchymal stem cells.

Mesenchymal stem cell (MSC) has drawn much attention in the aspect of tissue renewal and wound healing because of its multipotency. We initially observed that bone marrow-derived human MSCs (hMSCs) divided poorly and took flat and enlarged morphology after expanded in culture over a certain number of cell passage, which resembled characteristic features of senescent cells, well-studied in human diploid fibroblasts (HDFs). More interestingly, adipogenic differentiation potential of hMSCs sharply declined as they approached the end of their proliferative life span.

NF-kappaB is involved in the TNF-alpha induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARgamma expression.

TNF-alpha, a trimeric cytokine, was known to inhibit differention of preadipocytes to adipocytes. In the present study, we investigated signal mediators working downstream of TNF-alpha using murine 3T3-L1 cells. TNF-alpha induced activation of both c-jun NH(2)-terminal kinase (JNK) and nuclear transcription factor-kappaB (NF-kappaB) in 3T3-L1 cells.

Coordinate expression of the alpha and beta subunits of heterotrimeric G proteins involves regulation of protein degradation in CHO cells.

Individual cell types express a characteristic balance between heterotrimeric G protein alpha and betagamma subunits, but little is known about the regulatory mechanism. We systemically examined the regulatory mechanism in CHO cells. We found that expression of Galphas, Galphai2, and Galphaq proteins increased in direct proportion to the increase of Gbeta1gamma2 overexpressed transiently.

Src/ERK but not phospholipase D is involved in keratinocyte growth factor-stimulated secretion of matrix metalloprotease-9 and urokinase-type plasminogen activator in SNU-16 human stomach cancer cell.

Purpose: We investigated the signaling pathway for keratinocyte growth factor (KGF)-induced invasion using human stomach cancer cell line, SNU-16.

Methods: Alterations in the activities of Src, extracellular signal-regulated kinase (ERK), and phospholipase D (PLD) were measured using [gamma-(32)P] ATP for autophosphorylation of Src, phospho-specific ERK antibody, and [9,10-(3)H] myristic acid, respectively, while herbimycin A, PD98059 and butan-1-ol were used to inhibit their activities. Matrix metalloproteases (MMPs) and urokinase-type plasminogen activator (uPA) were quantified with zymography and Matrigel-coated Transwell was employed to estimate the invasiveness of SNU-16 cells.

Basic fibroblast growth factor-induced translocation of p21-activated kinase to the membrane is independent of phospholipase C-gamma1 in the differentiation of PC12 cells.

p21-activated kinase (PAK) targeting to the plasma membrane is essential for PC12 cell neurite outgrowth. Phospholipase C-gamma1 (PLC-gamma1) can mediate the PAK translocation in response to growth factors, since PLC-gamma1 binds to both tyrosine-phosphorylated receptor tyrosine kinases and PAK through its SH2 and SH3 domain, respectively. In the present study, we examined a potential role for PLC-gamma1 in the basic fibroblast growth factor (bFGF)-induced PAK translocation using stable PC12 cell lines that overexpress in a tetracycline-inducible manner either the wild-type FGFR-1 or the Y766F FGFR-1 mutant.