RESUMEN
CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.
RESUMEN
The paper describes the characterization of proteases in the whole body homogenate of Moina macrocopa, which can possibly be inhibited by the extracts of Microcystis aeruginosa PCC7806. With the use of oligopeptide substrates and specific inhibitors, we detected the activities of trypsin, chymotrypsin, elastase and cysteine protease. Cysteine protease, the predominant enzyme behind proteolysis of a natural substrate, casein, was partially purified by gel filtration. The substrate SDS-polyacrylamide gel electrophoresis of body homogenate revealed the presence of nine bands of proteases (17-72 kDa). The apparent molecular mass of an exclusive cysteine protease was 60 kDa, whereas of trypsin, it was 17-24 kDa. An extract of M. aeruginosa PCC7806 significantly inhibited the activities of trypsin, chymotrypsin and cysteine protease in M. macrocopa body homogenate at estimated IC(50) of 6- to 79-microg dry mass mL(-1). Upon fractionation by C-18 solid-phase extraction, 60% methanolic elute contained all the protease inhibitors, and these metabolites could be further separated by reverse-phase liquid chromatography. The metabolites inhibitory to M. macrocopa proteases also inhibited the corresponding class of proteases of mammalian/plant origin. The study suggests that protease inhibition may contribute to chemical interaction of cyanobacteria and crustacean zooplankton.
Asunto(s)
Cladóceros/metabolismo , Cisteína Endopeptidasas/metabolismo , Microcystis/fisiología , Serina Endopeptidasas/metabolismo , Animales , Benzoilarginina-Nitroanilida/metabolismo , Caseínas/metabolismo , Quimotripsina/metabolismo , Cisteína Endopeptidasas/química , Inhibidores de Cisteína Proteinasa/farmacología , Concentración 50 Inhibidora , Peso Molecular , Elastasa Pancreática/metabolismo , Proteínas/efectos de los fármacos , Proteínas/metabolismo , Serina Endopeptidasas/química , Especificidad por Sustrato , Tripsina/metabolismo , ZooplanctonRESUMEN
Two major protease activities were present in gut homogenates of the cladoceran crustacean Daphnia magna: (i) a trypsin activity that hydrolysed the synthetic substrate N-benzoyl-dl-arginine p-nitroanilide and was strongly inhibited by N-p-tosyl-lysine chloroketone (TLCK) and 4-(amidinophenyl)methanesulfonyl fluoride (APMSF) and not inhibited by chymostatin; and (ii) a chymotrypsin activity that hydrolysed synthetic chymotrypsin substrates containing more than one amino acid, did not hydrolyse N-benzoyl-l-tyrosine p-nitroanilide, and was strongly inhibited by chymostatin and not by TLCK and APMSF. Both activities had alkaline pH optima (pH 7-10), but were shown to be due to distinct types of proteases. These two enzyme activities accounted for 75-83% of the proteolytic activity of gut contents. Substrate SDS-polyacrylamide gel electrophoresis revealed nine different proteases ranging from 15 to 73 kDa.