Partial but significant overlap was revealed with
previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and CB-5083 manufacturer pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.”
“Integrin alpha(4)beta(1) (also called very late antigen-4 or VLA-4) plays an-important role in tumor growth, angiogenesis and metastasis, and there has been increasing interest in targeting this receptor for cancer imaging and therapy. In this study, we conjugated a peptidomimetic ligand known to have good DihydrotestosteroneDHT ic50 binding affinity for alpha(4)beta(1) integrin to a cross-bridged macrocyclic chelator with a methane phosphonic acid pendant arm, CB-TE1A1P. CB-TE1A1P-LLP2A was labeled with Cu-64 under mild conditions in high specific activity, in contrast to conjugates based on the “”gold standard”" di-acid cross-bridged chelator, CB-TE2A, which require high temperatures for efficient radiolabeling. Saturation
binding assays demonstrated that Cu-64-CB-TE1A1P-LLP2A had comparable binding affinity (1.2 nM vs 1.6 nM) but more binding sites (B-max = 471 fmol/mg) in B16F10 melanoma tumor cells than Cu-64-CB-TE1A1P-LLP2A (B-max = 304 fmol/mg, p<0.03). In biodistribution studies, Cu-64-CB-TE1A1P-LLP2A had less renal retention but higher uptake in tumor (11.4+/-2.3 %ID/g versus 3.1+/-0.6 %ID/g, p<0.001) and other receptor-rich tissues compared to Cu-64-CB-TE2A-LLP2A. At 2 h post-injection, 64Cu-CB-TE1A1P-LLP2A also had significantly higher tumor:blood and tumor:muscle ratios than Cu-64-CB-TE2A-LLP2A (CB-TE1A1P = 19.5+/-3.0 and 13.0+/-1.4, respectively, CB-TE2A = 4.2+/-1.4 and 5.5+/-0.9, respectively, p<0.001). These data demonstrate that Cu-64-CB-TE1A1P-LLP2A
and is an excellent PET radiopharmaceutical for the imaging of alpha(4)beta(1) positive tumors and also has potential for imaging other alpha(4)beta(1) positive cells such as those of the pre-metastatic niche. (C) 2013 Elsevier Inc. All rights reserved.”
“Purpose: Collagenase Clostridium histolyticum is an investigational nonsurgical treatment for Peyronie disease. In this phase 2b, double-blind, randomized, placebo controlled study we determined the safety and efficacy of collagenase C. histolyticum and assessed a patient reported outcome questionnaire.
Materials and Methods: A total of 147 subjects were randomized into 4 groups to receive collagenase C. histolyticum or placebo (3: 1) with or without penile plaque modeling (1: 1). Per treatment cycle 2 injections of collagenase C. histolyticum (0.58 mg) were given 24 to 72 hours apart.