463 research outputs found
Anti-VEGF DNA-based aptamers in cancer therapeutics and diagnostics
The vascular endothelial growth factor (VEGF) family and its receptors play fundamental roles not only in physiological but also in pathological angiogenesis, characteristic of cancer progression. Aiming at finding putative treatments for several malignancies, various small molecules, antibodies, or protein-based drugs have been evaluated in vitro and in vivo as VEGF inhibitors, providing efficient agents approved for clinical use. Due to the high clinical importance of VEGF, also a great number of anti-VEGF nucleic acid-based aptamers-that is, oligonucleotides able to bind with high affinity and specificity a selected biological target-have been developed as promising agents in anticancer strategies. Notable research efforts have been made in optimization processes of the identified aptamers, searching for increased target affinity and/or bioactivity by exploring structural analogues of the lead compounds. This review is focused on recent studies devoted to the development of DNA-based aptamers designed to target VEGF. Their therapeutic potential as well as their significance in the construction of highly selective biosensors is here discussed
PLoS One
Mature HIV-1 viral particles assemble as a fullerene configuration comprising p24 capsid hexamers, pentamers and dimers. In this paper, we report the X-ray crystal structures of the p24 protein from natural HIV-1 strain (BMJ4) in complex with Fab A10F9, which recognizes a conserved epitope in the C-terminal domain of the BMJ4 p24 protein. Our structures reveal a novel shoulder-to-shoulder p24 dimerization mode that is mediated by an S-S bridge at C177. Consistent with these structures, the shoulder-to-shoulder dimer that was obtained from the BMJ4 strain was also observed in p24 proteins from other strains by the introduction of a cysteine residue at position 177. The potential biological significance was further validated by the introduction of a C177A mutation in the BMJ4 strain, which then displays a low infectivity. Our data suggest that this novel shoulder-to-shoulder dimer interface trapped by this unique S-S bridge could represent a physiologically relevant mode of HIV-1 capsid assembly during virus maturation, although Cys residue itself may not be critical for HIV-I replication
Radio-induced low-grade glioma: report of two cases and review of the literature
With the increasing number of cancer survivors,
we can observe a population that will present a higher
risk of developing secondary long-term toxicities related to
adjuvant chemo and radiotherapy regimens. Among these,
children surviving from acute lymphoblastic leukemia
(ALL) that were treated with prophylactic cranial irradiation
represent a group of patients at a high risk of
developing secondary brain tumors. Radiation-induced
intracranial tumors have been documented since 1950, and
today, more than one-hundred cases have been described.
We report our experience with two young patients who
were hospitalized for low grade gliomas and had a positive
anamnesis for ALL and consequent radiotherapy
Pathomechanisms of ulnar ligament lesions of the wrist in a cadaveric distal radius fracture model
Background and purpose: Mechanisms of injury to ulnar sided ligaments, stabilizing the distal radioulnar joint and the ulna to the carpus, associated with dorsally displaced distal radius fractures are poorly described. We investigated the injury patterns in a human cadaver fracture model. Methods: Fresh frozen human cadaver arms were used. A dorsal open wedge osteotomy was made in the distal radius. In 8 specimens pressure was applied to the palm with the wrist in dorsiflexion and ulnar sided stabilizing structures subsequently severed. Dorsal angulation was measured on digitized radiographs. In 8 more specimens the triangular fibrocartilage complex was forced into rupture by axially loading the forearm with the wrist in dorsiflexion. The ulnar side was dissected and injuries were recorded. Results: Intact ulnar soft tissues limited the dorsal angulation of the distal radius fragment to a median of 32o (16-34o). A combination of bending and shearing of the distal radius fragment was needed to create TFCC injuries. Both palmar and dorsal injuries were observed simultaneously in 6/8 specimens. Interpretation: A TFCC injury can be expected when dorsal angulation of a distal radius fracture exceeds 32o. The extensor carpi ulnaris subsheath may be a functionally integral part of the TFCC. Both dorsal and palmar structures can tear simultaneously. These findings may have implications for reconstruction of ulnar sided soft tissue injuries
Search for pentaquark in high statistics measurement of at CLAS
The exclusive reaction was studied in the
photon energy range between 1.6-3.8 GeV searching for evidence of the exotic
baryon . The decay to requires the assignment of
strangeness to any observed resonance. Data were collected with the CLAS
detector at the Thomas Jefferson National Accelerator Facility corresponding to
an integrated luminosity of 70 . No evidence for the
pentaquark was found. Upper limits were set on the production cross section as
function of center-of-mass angle and mass. The 95% CL upper limit on the
total cross section for a narrow resonance at 1540 MeV was found to be 0.8 nb.Comment: Submitted to Physical Review Letter
Deeply virtual and exclusive electroproduction of omega mesons
The exclusive omega electroproduction off the proton was studied in a large
kinematical domain above the nucleon resonance region and for the highest
possible photon virtuality (Q2) with the 5.75 GeV beam at CEBAF and the CLAS
spectrometer. Cross sections were measured up to large values of the
four-momentum transfer (-t < 2.7 GeV2) to the proton. The contributions of the
interference terms sigma_TT and sigma_TL to the cross sections, as well as an
analysis of the omega spin density matrix, indicate that helicity is not
conserved in this process. The t-channel pi0 exchange, or more generally the
exchange of the associated Regge trajectory, seems to dominate the reaction
gamma* p -> omega p, even for Q2 as large as 5 GeV2. Contributions of handbag
diagrams, related to Generalized Parton Distributions in the nucleon, are
therefore difficult to extract for this process. Remarkably, the high-t
behaviour of the cross sections is nearly Q2-independent, which may be
interpreted as a coupling of the photon to a point-like object in this
kinematical limit.Comment: 15 pages,19 figure
- …