17 research outputs found
Hypoxia-induced downregulation of microRNA-186-5p in endothelial cells promotes non-small cell lung cancer angiogenesis by upregulating protein kinase C alpha
The tumor microenvironment stimulates the angiogenic activity of endothelial cells (ECs) to facilitate tumor vascularization,
growth, and metastasis. The involvement of microRNA-186-5p
(miR-186) in regulating the aberrant activity of tumor-associated ECs has so far not been clarified. In the present study,
we demonstrated that miR-186 is significantly downregulated
in ECs microdissected from human non-small cell lung cancer
(NSCLC) tissues compared with matched non-malignant lung
tissues. In vitro analyses of primary human dermal microvascular ECs (HDMECs) exposed to different stimuli indicated
that this miR-186 downregulation is triggered by hypoxia
via activation of hypoxia-inducible factor 1 alpha (HIF1a).
Transfection of HDMECs with miR-186 mimic (miR-186m)
significantly inhibited their proliferation, migration, tube
formation, and spheroid sprouting. In contrast, miR-186
inhibitor (miR-186i) exerted pro-angiogenic effects. In vivo,
endothelial miR-186 overexpression inhibited the vascularization of Matrigel plugs and the initial growth of tumors
composed of NSCLC cells (NCI-H460) and HDMECs. Mechanistic analyses revealed that the gene encoding for protein
kinase C alpha (PKCa) is a bona fide target of miR-186. Activation of this kinase significantly reversed the miR-186mrepressed angiogenic activity of HDMECs. These findings
indicate that downregulation of miR-186 in ECs mediates hypoxia-stimulated NSCLC angiogenesis by upregulating PKCa
Effect of the 3q26-coding oncogene SEC62 as a potential prognostic marker in patients with ovarian neoplasia
With approximately 220,000 newly diagnosed cases per year, ovarian cancer is
among the most frequently occurring cancers among women and the second
leading cause of death from gynecological malignancies worldwide. About 70%
of these cancers are diagnosed in advanced stages (FIGO IIB–IV), with a 5-year
survival rate of 20–30%. Due to the poor prognosis of this disease, research has
focused on its pathogenesis and the identification of prognostic factors. One
possible approach for the identification of biological markers is the
identification of tumor entity-specific genetic “driver mutations”. One such
mutation is 3q26 amplification in the tumor driver SEC62, which has been
identified as relevant to the pathogenesis of ovarian cancer. This study was
conducted to investigate the role of SEC62 in ovarian malignancies. Patients
with ovarian neoplasias (borderline tumors of the ovary and ovarian cancer) who
were treated between January 2007 and April 2019 at the Department of
Gynecology and Obstetrics, Saarland University Hospital, were included in
this retrospective study. SEC62 expression in tumor tissue samples taken
during clinical treatment was assessed immunohistochemically, with the
calculation of immunoreactivity scores according to Remmele and Stegner,
Pathologe, 1987, 8, 138–140. Correlations of SEC62 expression with the TNM
stage, histological subtype, tumor entity, and oncological outcomes
(progression-free and overall survival) were examined. The sample
comprised 167 patients (123 with ovarian cancer and 44 with borderline
tumors of the ovary) with a median age of 60 (range, 15–87) years. At the
time of diagnosis, 77 (46%) cases were FIGO stage III. All tissue slides showed
SEC62 overexpression in tumor cells and no SEC62 expression in other cells.
Median immunoreactivity scores were 8 (range, 2–12) for ovarian cancer and 9
(range, 4–12) for borderline tumors of the ovary. Patients with borderline
tumors of the ovary as well as patients with ovarian cancer and an
immunoreactive score (IRS) ≤ 9 showed an improved overall survival compared to those presenting with an IRS score >9 (p = 0.03). SEC62 seems to
be a prognostic biomarker for the overall survival of patients with ovarian
malignancies
Polydispersity and ordered phases in solutions of rodlike macromolecules
We apply density functional theory to study the influence of polydispersity
on the stability of columnar, smectic and solid ordering in the solutions of
rodlike macromolecules. For sufficiently large length polydispersity (standard
deviation ) a direct first-order nematic-columnar transition is
found, while for smaller there is a continuous nematic-smectic and
first-order smectic-columnar transition. For increasing polydispersity the
columnar structure is stabilized with respect to solid perturbations. The
length distribution of macromolecules changes neither at the nematic-smectic
nor at the nematic-columnar transition, but it does change at the
smectic-columnar phase transition. We also study the phase behaviour of binary
mixtures, in which the nematic-smectic transition is again found to be
continuous. Demixing according to rod length in the smectic phase is always
preempted by transitions to solid or columnar ordering.Comment: 13 pages (TeX), 2 Postscript figures uuencode
Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells
Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins
Online training of TPACK skills of higher education scholars: a cross-institutional impact study
Higher education institutions should provide adequate training for teachers in order to increase their awareness of the complex interplay between technology, pedagogy and the cognitive knowledge in their disciplines. However, research has shown that providing effective staff development from teacher educators to support these teachers’ skills is not straightforward. An online teacher training programme created and implemented by a team of 14 teacher educators in a cross-institutional programme in the Netherlands was followed by 67 teachers. Data were gathered using a TPACK (Technological, Pedagogical, Content Knowledge) instrument in a pre-post test design. Furthermore, (perceived) learning satisfaction was measured in order to determine whether the design was appropriate. The results indicate that the teachers’ TPACK skills increased substantially. Furthermore, most participants were positive about the design and implementation of the online professionalisation programme. Nonetheless, not all teachers were able to effectively learn in this context, requiring further fine-tuning and research