RESUMEN
Sialosyl-Tn, a mucin-associated carbohydrate antigen, is not expressed by normal mucus-producing cells of the stomach but becomes expressed in metaplastic, pre-malignant and malignant gastric tissues. Reports vary as to the frequency of STn expression and its prognostic role in gastric cancer. To determine whether these differences might be due to inter-country variations in gastric cancer biology, we immunohistochemically analyzed 340 gastric cancers from 2 countries at high-risk (high incidence) for gastric cancer (Japan and Chile), one with intermediate risk (Brazil) and one with low-risk (USA). Expression of STn was correlated with clinico-pathological features of the tumors and with cancer-related survival. Regardless of country, the frequency of STn-positive tumors was lower in non-invasive ("early") than in advanced gastric cancer. Consequently, high-risk countries where early gastric cancer is more common demonstrated a lower overall frequency of STn-positive tumors. In all 4 countries, STn expression directly correlated with depth of invasion, stage, and lymph node involvement. In addition, STn expression correlated with a poor prognosis in all 4 countries, but the effect of STn on survival was not independent of tumor stage. Our findings indicate the need to consider the inherent gastric cancer risk and prevalence of early gastric cancer in the study population when reporting frequency of STn expression in gastric cancer. Regardless of country, however, STn expression is a marker of gastric cancer progression suggesting that cancer-associated mucins play a role in the malignant behavior of this tumor.
Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/análisis , Biomarcadores de Tumor/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , Anciano , Brasil/epidemiología , Chile/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Factores de Riesgo , Neoplasias Gástricas/mortalidad , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
A new macrolide antibiotic, PC-766B, was isolated from the cells of Nocardia brasiliensis SC-4710 by acetone extraction, and purified by gel filtration, silica gel chromatography, HPLC and TLC. The structure of PC-766B was determined by NMR spectral analysis to be a new class of the hygrolidin family antibiotics. PC-766B had a 16-membered macrocyclic lactone ring, a 6-membered hemiketal ring and a 2-deoxy-D-rhamnose moiety. DL-alpha-Tocopherol, known as an antioxidant agent, significantly improved the stability of PC-766B and prevented the decomposition of PC-766B during the storage of the antibiotic.
Asunto(s)
Antibacterianos , Macrólidos , Nocardia/metabolismo , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Fenómenos Químicos , Química Física , Estructura MolecularRESUMEN
An actinomycete strain SC-4710, a new soil isolate, was found to produce a new macrolide antibiotic, PC-766B. Chemotaxonomic analysis of the producing organism revealed that the cells of SC-4710 had type IV cell wall, type A whole cell sugar pattern, type PII phospholipids, menaquinone MK-8(H4), cellular fatty acids comprising straight-chain saturated, unsaturated and tuberculostearic acids, and mycolic acids. The strain was identified as Nocardia brasiliensis (Lindenberg) Pinoy. The antibiotic, PC-766B, was active against Gram-positive bacteria, and some fungi and yeasts, but inactive against Gram-negative bacteria. It also showed antitumor activity against murine tumor cells in vitro and in vivo, and a weak inhibitory activity against Na+, K(+)-ATPase in vitro.