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Keratinocyte Growth Factor Receptor Restores 5-Fluorouracil and Tamoxifen Efficacy on Resp

Silencing of Keratinocyte Growth Factor Receptor Restores 5-Fluorouracil and Tamoxifen Efficacy on Responsive Cancer Cells.Sabrina Rotolo 1, Simona Ceccarelli 1, Ferdinando Romano 1, Luigi Frati 1,2, Cinzia Marchese 1, Antonio Angeloni 1* 1 Dipartimento di Medicina Sperimentale, Universita` Sapienza di Roma, Roma, Italy, 2 Istituto Neurologico Mediterraneo ‘‘Neuromed, Pozzilli, ItalyAbstract : BackgroundKeratinocyte growth factor receptor (KGFR) is a splice variant of the FGFR2 gene expressed in epithelial cells. Activation of KGFR is a key factor in the regulation of physiological processes in epithelial cells such as proliferation, differentiation and wound healing. Alterations of KGFR signaling have been linked to the pathogenesis of different epithelial tumors. It has been also hypothesized that its specific ligand, KGF, might contribute to the development of resistance to 5-fluorouracil (5-FU) in epithelial cancers and tamoxifen in estrogen-positive breast cancers.Abstract : Methodology/Principal FindingsSmall interfering RNA was transfected into a human keratinocyte cell line (HaCaT), a breast cancer derived cell line (MCF-7) and a keratinocyte primary culture (KCs) to induce selective downregulation of KGFR expression. A strong and highly specific reduction of KGFR expression was observed at both RNA (reduction = 75.7%, P = 0.009) and protein level. KGFR silenced cells showed a reduced responsiveness to KGF treatment as assessed by measuring proliferation rate (14.2% versus 39.0% of the control cells, P

Loss of the Otx2-Binding Site in the Nanog Promoter Affects the Integrity of Embryonic Stem Cell Subtypes and Specification of Inner Cell Mass-Derived Epiblast

• Otx2 binds to the promoter/enhancer region of Oct4, Sox2, and Nanog in ESCs and EpiSCs • Otx2 binding to the Nanog promoter helps maintain the integrity of ESC compartments • Loss of this Otx2-binding site induces primed-like features in ESCs • Otx2 regulation of Nanog contributes to ICM differentiation of the epiblast Mouse embryonic stem cells (ESCs) and the inner cell mass (ICM)-derived epiblast exhibit naive pluripotency. ESC-derived epiblast stem cells (EpiSCs) and the postimplantation epiblast exhibit primed pluripotency. Although core pluripotency factors are well-characterized, additional regulators, including Otx2, recently have been shown to function during the transition from naive to primed pluripotency. Here we uncover a role for Otx2 in the control of the naive pluripotent state. We analyzed Otx2-binding activity in ESCs and EpiSCs and identified Nanog, Oct4, and Sox2 as direct targets. To unravel the Otx2 transcriptional network, we targeted the strongest Otx2-binding site in the Nanog promoter, finding that this site modulates the size of specific ESC-subtype compartments in cultured cells and promotes Nanog expression in vivo, predisposing ICM differentiation to epiblast. Otx2-mediated Nanog regulation thus contributes to the integrity of the ESC state and cell lineage specification in preimplantation development.

Direct evidence for grain boundary passivation in Cu(In,Ga)Se2 solar cells through alkali-fluoride post-deposition treatments

BioSentinel

BioSentinel’s microfluidics card, designed at NASA Ames, will be used to study the impact of interplanetary space radiation on yeast. Once in orbit, the growth and metabolic activity of the yeast will be measured using a 3-color LED detection system and a metabolic indicator dye. Here, pink wells contain actively growing yeast cells that have turned the metabolic dye from blue to pink color.

THE CITY WHICH IS INSIDE YOU

You live in your own inner city, which you bought in a silent auction. You were again unable to cancel your debts. Under your blackening eyelids you try to feel certain things. Without noticing your withdrawal from self, you leave for distant parts by using your ropes of thought like a ski-lift. Your shudders increase as you touch the numberless elements. In your screams at the moment when you feel the jolts from the echoes of your words crossing the threshold of your thought, you send birds fleeing before you. As you breathe, your roses wither. In your moments of madness, crystals fall from your roof. As your field of thought shrinks, your city expands. You exhaust yourself from running down the streets and avenues. As the lamps of your voltage machines alight upon your nights, your humans robotize themselves. The toads in your dirty waters frighten even the crocodiles. Your inner journey makes you grow older. Your internal cries amplify themselves. You manifest difficulties with forty paws. The auxiliary cells of your laboratories do not give you the opportunity to live any pleasurable moments. While the fear indicator inside you slackens you through and through, you have not even the possibility of speaking. With each movement of the clock, the seasons rip themselves out of your heart. Your solitude traverses your spirit without cease. by Ãœzeyir Lokman É¡AYCI Mantes la Ville - 22.09.2002 Traduit par by Yakup YURT en français French free verse translated into English free verse by F.J. Bergmann - 16.02.2003

Stem-cell 'secret of youth' found

Chemical might help human cells reach clinic. ERIKA CHECK

CLOT-BUSTERS ATTACK CELLS FROM WITHIN