Analysis of cause of failure of new targeting peptide in PEGylated liposome: molecular modeling as rational design tool for nanomedicine.

Drug nanocarriers are often derivatized with targeting moieties to achieve site specific delivery, however, the results from this approach have, as yet, not reached expectations. We have tested a new phage display based targeting moiety, the activated endothelium targeting peptide (AETP), for its vascular endothelium directed targeting efficiency, when anchored to a PEGylated liposome via maleimide chemistry. Our results have, however, not shown any evidence of improved targeting.

Matrix metalloproteinase 9 targeting peptides: syntheses, 68Ga-labeling, and preliminary evaluation in a rat melanoma xenograft model.

Biopanning of tumor cells was used in order to identify matrix metalloproteinase 9 (MMP-9) targeting peptides. The tumor cell targeting peptide (TCTP-1) and two modified versions thereof were evaluated as imaging agents for positron emission tomography (PET) using a rat melanoma xenograft model. For the PET imaging purposes, the 3 peptides were 1,4,7,10-tetraazacyclo-dodecane-N',N'',N''',N''''-tetraacetic acid (DOTA) conjugated and labeled with Gallium-68 ((68)Ga) and preliminarily evaluated: (1) cyclic (68)Ga-DOTA-TCTP-1 with cystine bridge, (2) cyclic (68)Ga-DOTA-lactam-TCTP-1 with a lactam bridge, and (3) linear (68)Ga-DOTA-lin-TCTP-1.

Conserved hydrophobicity in the SH2-kinase linker is required for catalytic activity of Csk and CHK.

The crystal structure of full-length Csk (C-terminal Src kinase) molecules shows a hydrophobic interaction between the SH2-kinase linker residue Phe183 and the alphaC-helix of the catalytic domain. To study the possible involvement of this contact in the regulation of the activity of Csk and CHK (Csk homologous kinase), a Csk SH2-kinase linker deletion mutant, Csk Phe183 and CHK Leu223 point mutants were analyzed. It was observed that a residue with a long hydrophobic side chain in position 183 (Csk) and 223 (CHK) is required to sustain the catalytic activity of Csk and CHK.

Transcriptional regulation of the ornithine decarboxylase gene by c-Myc/Max/Mad network and retinoblastoma protein interacting with c-Myc.

c-Myc is an oncogenic transcription factor involved in the regulation of cell proliferation, differentiation and apoptosis. The direct targets of c-Myc mediating these various processes are slowly being unravelled. This study indicates that the ornithine decarboxylase (ODC) gene is a physiological transcriptional target of c-Myc in association with induction of cell proliferation and transformation, but not with induction of apoptosis.

Incipient angiogenesis in Barrett's epithelium and lymphangiogenesis in Barrett's adenocarcinoma.

Purpose: Barrett's esophagus (BE), a precancerous condition for Barrett's adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barrett's adenocarcinoma patients is the frequent development of lymph node metastases.