5 research outputs found
Soluble CD44 Interacts with Intermediate Filament Protein Vimentin on Endothelial Cell Surface
CD44 is a cell surface glycoprotein that functions as hyaluronan receptor. Mouse and human serum contain substantial amounts of soluble CD44, generated either by shedding or alternative splicing. During inflammation and in cancer patients serum levels of soluble CD44 are significantly increased. Experimentally, soluble CD44 overexpression blocks cancer cell adhesion to HA. We have previously found that recombinant CD44 hyaluronan binding domain (CD44HABD) and its non-HA-binding mutant inhibited tumor xenograft growth, angiogenesis, and endothelial cell proliferation. These data suggested an additional target other than HA for CD44HABD. By using non-HA-binding CD44HABD Arg41Ala, Arg78Ser, and Tyr79Ser-triple mutant (CD443MUT) we have identified intermediate filament protein vimentin as a novel interaction partner of CD44. We found that vimentin is expressed on the cell surface of human umbilical vein endothelial cells (HUVEC). Endogenous CD44 and vimentin coprecipitate from HUVECs, and when overexpressed in vimentin-negative MCF-7 cells. By using deletion mutants, we found that CD44HABD and CD443MUT bind vimentin N-terminal head domain. CD443MUT binds vimentin in solution with a Kd in range of 12â37 nM, and immobilised vimentin with Kd of 74 nM. CD443MUT binds to HUVEC and recombinant vimentin displaces CD443MUT from its binding sites. CD44HABD and CD443MUT were internalized by wild-type endothelial cells, but not by lung endothelial cells isolated from vimentin knock-out mice. Together, these data suggest that vimentin provides a specific binding site for soluble CD44 on endothelial cells
Incidental advanced-stage Hodgkin lymphoma diagnosed at the time of radical prostatectomy for prostatic cancer: a case report and review of literature
Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.
Purpose
Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.
Methods
The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative
process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.
Results
Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.
Conclusions
In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest
and most efficacious reconstruction techniques
Timing of Palaeozoic magmatism in the Maggia and Sambuco nappes and paleogeographic implications (Central Lepontine Alps)
Magmatic rocks from the pre-Mesozoic basements of the Sambuco and Maggia
nappes have been dated by U-Pb zircon ages with the LA-ICPMS technique.
Several magmatic events have been identified in the Sambuco nappe. The
mafic banded calc-alkaline suite of Scheggia is dated at 540 Ma, an age
comparable to that of mafic rocks in the Austroalpine Silvretta nappe.
The Sasso Nero peraluminous augengneiss has an age of 480-470 Ma, like
many other ``older orthogneisses'' in Alpine basement units. It hosts
a large proportion of inherited zircons, which were dated around 630 Ma,
a Panafrican age indicating the Gondwanan affiliation of the Sambuco
basement. The calc-alkaline Matorello pluton yielded ages around 300 Ma,
similar to numerous Late Carboniferous intrusions in other basement
units of the Lower Penninic (Monte Leone, Antigorio, Verampio) and
Helvetic domains (Gotthard and other External Crystalline Massifs).
Associated lamprophyric dykes are slightly younger (300-290 Ma), like
similar dykes sampled in gneiss blocks included in the sedimentary cover
of the underlying Antigorio nappe (290-285 Ma). The Cocco granodiorite
and Ruscada leucogranite, both intruding the basement of the
neighbouring Maggia nappe, yielded ages of ca. 300-310 Ma, identical
within errors to the age of the Matorello pluton. They are significantly
older than former age determinations. This age coincidence, coupled with
remarkable petrologic similarities between the Cocco and Matorello
granodiorites, strongly suggests paleogeographic proximity of the
Sambuco and Maggia nappes in Late Carboniferous times. In recent
publications these two nappes have been interpreted as belonging to
distinct Mesozoic paleogeographic domains: ``European'' for Sambuco
and ``Brian double dagger onnais'' for Maggia, separated by the
``Valais'' oceanic basin. In this case, the similarity of the
Matorello and Cocco intrusions would demonstrate the absence of any
significant transcurrent movement between these two continental domains.
Alternatively, according to a more traditional view, Sambuco and Maggia
might belong to a single large Alpine tectonic unit