Gene/Protein Disease Symptom Drug Enzyme Compound
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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystatins are protein inhibitors of cysteine proteinases, which are believed to play an important role in the pathogenesis of periodontal disease. In this study, we report a new sensitive method for the quantitative analysis of cystatin activity in a small amount of crude sample such as gingival crevicular fluid. Cystatin activity in the crude sample was determined by using active site-titrated papain, which is a cysteine proteinase from the plant Carica papaya. Crude samples usually contain endogenous cysteine proteinases. These competed with the added papain for the active sites of the cystatins. The cystatin-cysteine proteinase complex was able to be dissociated by the addition of papain. This competition and dissociation could interfere with the determination of cystatin activity, since some of the cysteine proteinases, such as cathepsin B, hydrolyzed the specific substrate for papain during titration with the papain. In order to exclude this interference and measure total cystatin activity, the crude sample must be alkalinized (pH 11.0) for 5 min at 4 degrees C followed by 10 min at 40 degrees C before titration with papain. The minimum detectable amount of cystatins was 20 fmol/assay when it was calculated per mole of papain inhibitory sites. Using this method, significant levels of cystatin activity were detected in all the samples of gingival crevicular fluid taken from periodontal disease patients. These results suggest that cystatins could regulate the cysteine proteinases in gingival crevicular fluid and that this new method could be useful to clarify the role of cystatins in the pathogenesis of periodontal disease.
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PMID:Cystatin activity in gingival crevicular fluid from periodontal disease patients measured by a new quantitative analysis method. 153 1

Platinum-based drugs have been widely used for the treatment of malignant tumors. However, their applications are limited by severe side effects for their lack of selectivity for cancer cells. The development of antibody drug conjugates (ADCs) have provided a platform to reduce drug toxicity and improve drug efficacy. Here we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and platinum drug via a cathepsin B cleavable dipetide for enhancing drug accumulation and HER2-positive cancer cell specific delivery. This conjugate is believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and activation of drug release. Herceptin-Pt(II) is evaluated to have approximately loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR-3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary, Herceptin-platinum (II) conjugate is a remarkable and potent platform for efficient and cancer cell specific delivery.
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PMID:Biological evaluation of a novel Herceptin-platinum (II) conjugate for efficient and cancer cell specific delivery. 2621 91