23 research outputs found
Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor
Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution
Tumor Cells Upregulate Normoxic HIF-1 in Response to Doxorubicin
Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that controls cellular homeostasis. While its activation benefits normal tissue, HIF-1 activation in tumors is a major risk factor for angiogenesis, therapeutic resistance and poor prognosis. HIF-1 activity is usually suppressed under normoxic conditions because of rapid oxygen-dependent degradation of HIF-1α. Here we show that under normoxic conditions HIF-1α is upregulated in tumor cells in response to doxorubicin, a chemotherapy used to treat many cancers. Doxorubicin also enhanced VEGF secretion by normoxic tumor cells and stimulated tumor angiogenesis. Doxorubicin-induced accumulation of HIF-1α in normoxic cells was caused by increased expression and activation of STAT1, the activation of which stimulated expression of iNOS and its synthesis of NO in tumor cells. Mechanistic investigations established that blocking NO synthesis or STAT1 activation was sufficient to attenuate the HIF-1α accumulation induced by doxorubicin in normoxic cancer cells. To our knowledge, this is the first report that a chemotherapeutic drug can induce HIF-1α accumulation in normoxic cells, an efficacy-limiting activity. Our results argue that HIF-1α targeting strategies may enhance doxorubicin efficacy. More generally, they suggest a broader perspective on the design of combination chemotherapy approaches with immediate clinical impact
Plasmonics-enhanced and optically modulated delivery of gold nanostars into brain tumor
Plasmonics-active gold nanostars exhibiting strong imaging contrast and efficient photothermal transduction were synthesized for a novel pulsed laser-modulated plasmonics-enhanced brain tumor microvascular permeabilization. We demonstrate a selective, optically modulated delivery of nanoprobes into the tumor parenchyma with minimal off-target distribution
Health, education, and social care provision after diagnosis of childhood visual disability
Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
An Engineered Optogenetic Switch for Spatiotemporal Control of Gene Expression, Cell Differentiation, and Tissue Morphogenesis
The precise spatial and temporal
control of gene expression, cell differentiation, and tissue morphogenesis
has widespread application in regenerative medicine and the study
of tissue development. In this work, we applied optogenetics to control
cell differentiation and new tissue formation. Specifically, we engineered
an optogenetic “on” switch that provides permanent transgene
expression following a transient dose of blue light illumination.
To demonstrate its utility in controlling cell differentiation and
reprogramming, we incorporated an engineered form of the master myogenic
factor MyoD into this system in multipotent cells. Illumination of
cells with blue light activated myogenic differentiation, including
upregulation of myogenic markers and fusion into multinucleated myotubes.
Cell differentiation was spatially patterned by illumination of cell
cultures through a photomask. To demonstrate the application of the
system to controlling <i>in vivo</i> tissue development,
the light inducible switch was used to control the expression of VEGF
and angiopoietin-1, which induced angiogenic sprouting in a mouse
dorsal window chamber model. Live intravital microscopy showed illumination-dependent
increases in blood-perfused microvasculature. This optogenetic switch
is broadly useful for applications in which sustained and patterned
gene expression is desired following transient induction, including
tissue engineering, gene therapy, synthetic biology, and fundamental
studies of morphogenesis
Professionalisierung durch Fallarbeit für die inklusive Schule
Heinrich M, Blasse N, Budde J, et al. Professionalisierung durch Fallarbeit für die inklusive Schule. In: Ricken G, Degenhardt S, eds. Vernetzung, Kooperation, Sozialer Raum. Inklusion als Querschnittaufgabe. Perspektiven sonderpädagogischer Forschung . Bad Heilbrunn: Julius Klinkhardt; 2019: 159-181