Refine
Document Type
- Article (4)
Language
- English (4)
Has Fulltext
- yes (4)
Is part of the Bibliography
- no (4)
Keywords
- Ascites (1)
- Charged-particle density (1)
- Claudin 5 (1)
- Heavy-ion collisions (1)
- LHC (1)
- Ovarian cancer (1)
- VE-cadherin (1)
- VEGF (1)
- Vascular permeability (1)
- Wide rapidity coverage (1)
Institute
- Frankfurt Institute for Advanced Studies (FIAS) (2)
- Informatik (2)
- Physik (2)
- E-Finance Lab e.V. (1)
- Medizin (1)
Background: Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.
Methods: Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.
Results: VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.
Conclusions: Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
We present the first wide-range measurement of the charged-particle pseudorapidity density distribution, for different centralities (the 0-5%, 5-10%, 10-20%, and 20-30% most central events) in Pb-Pb collisions at sNN−−−√=2.76 TeV at the LHC. The measurement is performed using the full coverage of the ALICE detectors, −5.0<η<5.5, and employing a special analysis technique based on collisions arising from LHC "satellite" bunches. We present the pseudorapidity density as a function of the number of participating nucleons as well as an extrapolation to the total number of produced charged particles (Nch=17165±772 for the 0-5% most central collisions). From the measured dNch/dη distribution we derive the rapidity density distribution, dNch/dy, under simple assumptions. The rapidity density distribution is found to be significantly wider than the predictions of the Landau model. We assess the validity of longitudinal scaling by comparing to lower energy results from RHIC. Finally the mechanisms of the underlying particle production are discussed based on a comparison with various theoretical models.
We report on the first measurement of inclusive J/ψ elliptic flow, v2, in heavy-ion collisions at the LHC. The measurement is performed with the ALICE detector in Pb-Pb collisions at sNN−−−√=2.76 TeV in the rapidity range 2.5<y<4.0. The dependence of the J/ψ v2 on the collision centrality and on the J/ψ transverse momentum is studied in the range 0<pT<10 GeV/c. For semi-central Pb-Pb collisions at sNN−−−√=2.76 TeV, an indication of non-zero v2 is observed with a maximum value of v2=0.116±0.046(stat.)±0.029(syst.) for J/ψ in the transverse momentum range 2<pT<4 GeV/c. The elliptic flow measurement complements the previously reported ALICE results on the inclusive J/ψ nuclear modification factor and favors the scenario of a significant fraction of J/ψ production from charm quarks in a deconfined partonic phase.