Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents

Aberrant signaling through protein-tyrosine kinase (PTK)-dependent pathways is associated with several proliferative diseases. Accordingly, PTK inhibitors are being developed as new approaches for the treatment of certain cancers. Growth factor receptor bound protein 2 (Grb2) is an important downstream mediator of PTK signaling that serves obligatory roles in many pathogenic processes. One of the primary functions of Grb2 is to bind to specific phosphotyrosyl (pTyr)-containing sequences through its Src homology 2 (SH2) domain. Agents that bind to the Grb2 SH2 domain and prevent its normal function could disrupt associated PTK signaling and serve as alternatives to kinase-directed inhibitors. Starting from the X-ray crystal structure of a lead peptide bound to the Grb2 SH2 domain, this review will summarize important contributions to these efforts. The presentation will be thematically arranged according to the region of peptide modified, proceeding from the N-terminus to the C-terminus, with a special section devoted to aspects of conformational constraint

From citizen journalism to alternative media: The case of 140journos

[No abstract available

THE EFFECTS OF THE HELIUM-NEON LASER ON WOUND-HEALING IN RABBITS AND ON HUMAN SKIN FIBROBLASTS IN-VITRO

Helium-neon laser irradiation was applied to the denuded dermis and full-thickness open wounds on rabbit skin and eel cultures of human skin fibroblasts to investigate its effects on the wound healing process. To determine the effects of He-Ne laser radiation on epithelialization rate, 3x3 cm denuded dermis areas on the flank of 16 rabbits were irradiated daily until complete epithelialization occurred. For histopathological evaluation biopsies were taken on the first day and on the day on which epithelialization was complete. As a second part of in vivo study, identical full-thickness skin wounds were created bilaterally on the middle flank area of 12 rabbits. He-Ne laser irradiation was applied daily to the wounds until complete healing occurred to determine the effects of the low-energy laser on the contraction of open wounds. The contralateral wounds were left untreated, serving as controls. In a separate in vitro study, the effect of single or multiple applications of He-Ne laser irradiation on normal human skin fibroblasts in cell cultures was evaluated using growth measurement. The mean epithelialization time was 11+/-0.63 days for the laser-treated wounds and 12+/-0.12 days for the control wounds. The difference was not significant. No significant difference was found between the contraction rates of the full-thickness wounds (e.g., on the seventh post operative day, the average wound area was 70.2+/-6.75% of original wound area in the laser-treated group and 66.5+/-8.75% in the control group). Histopathologically, epidermal thickening and an increase in dermal vascularity were observed in healed wounds of the laser-treated groups. However, in vitro, this low-energy laser promoted cell growth in human fibroblast cell cultures in 2- and 3-day treated groups (p<0.05)

A new posteriorly based chondrocutaneous flap for the repair of middle third marginal auricular defects

A new chrondrocutaneous flap raised from the posterior area was used to reconstruct composite marginal ear defects of two patients. In this technique, a posterior rectangular advancement flap with a cartilage strip was advanced into the defectly horizontal. Two weeks later, the pedicle was divided and the flap was tailored. The donor area was covered with a skin graft. This flap provides both ideal skin cover and support for the cartilaginous framework. It can be transferred without delay and can be used in immediate or secondary reconstructions. It is recommended as an alternative method for the reconstruction of the middle third marginal auricular defects