Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma

BACKGROUND: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma. METHODS: In this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data. RESULTS: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. In particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis. CONCLUSION: In this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker

Global burden of disease attributable to diabetes mellitus in Brazil Carga global de doença devida e atribuível ao diabetes mellitus no Brasil

Type II diabetes mellitus accounts for 90% of all cases of diabetes, and its inclusion in health evaluation has shown that its complications have a considerable impact on the population's quality of life. The current article presents the results of the Global Burden of Disease Study in Brazil for the year 1998, with an emphasis on diabetes mellitus and its complications. The indicator used was disability-adjusted life years (DALY), using a discount rate of 3%. In Brazil, ischemic heart disease, stroke, and diabetes accounted for 14.7% of total lost DALYs. Brazil showed a higher proportion of years lived with disability (YLDs) among total DALYs for diabetes as compared to other countries. Retinopathy and neuropathy were the complications that contributed most to YLDs. According to forecasts, diabetes mellitus will have an increasing impact on years of life lost due to premature death and disability in the world, shifting from the 11th to 7th cause of death by 2030. It is thus urgent to implement effective measures for prevention, early diagnosis, counseling, and adequate follow-up of patients with diabetes mellitus.<br>O diabetes mellitus tipo II é responsável por 90% de todos os casos de diabetes, e sua inclusão na avaliação de saúde evidencia que as suas complicações têm um considerável impacto na qualidade de vida de uma população. O presente artigo apresenta os resultados do Estudo de Carga Global de Doença, realizado no Brasil para o ano de 1998, com ênfase no diabetes mellitus e suas complicações. O indicador utilizado foi o disability-adjusted life years (DALY), ao qual aplicou-se a taxa de desconto de 3%. No Brasil, doenças isquêmicas do coração, doenças cardiovasculares e diabetes contribuíram com 14,7% do total de DALY. Observou-se uma maior participação do years lived with disability (YLD) no total de DALY para o diabetes quando comparado a outros países. As complicações retinopatias e neuropatias foram as que mais contribuíram para o YLD. Projeções indicam que o diabetes mellitus terá crescente impacto sobre a perda de anos de vida por morte prematura e incapacidade no mundo, e que se deslocará de 11ª para 7ª causa de morte em 2030. Faz-se urgente a implantação e implementação de medidas efetivas para prevenção, diagnóstico precoce, aconselhamento e adequado acompanhamento dos pacientes com diabetes mellitus

Validation of the Scientific Program for the Dark Energy Spectroscopic Instrument

Abstract The Dark Energy Spectroscopic Instrument (DESI) was designed to conduct a survey covering 14,000 deg2 over 5 yr to constrain the cosmic expansion history through precise measurements of baryon acoustic oscillations (BAO). The scientific program for DESI was evaluated during a 5 month survey validation (SV) campaign before beginning full operations. This program produced deep spectra of tens of thousands of objects from each of the stellar Milky Way Survey (MWS), Bright Galaxy Survey (BGS), luminous red galaxy (LRG), emission line galaxy (ELG), and quasar target classes. These SV spectra were used to optimize redshift distributions, characterize exposure times, determine calibration procedures, and assess observational overheads for the 5 yr program. In this paper, we present the final target selection algorithms, redshift distributions, and projected cosmology constraints resulting from those studies. We also present a One-Percent Survey conducted at the conclusion of SV covering 140 deg2 using the final target selection algorithms with exposures of a depth typical of the main survey. The SV indicates that DESI will be able to complete the full 14,000 deg2 program with spectroscopically confirmed targets from the MWS, BGS, LRG, ELG, and quasar programs with total sample sizes of 7.2, 13.8, 7.46, 15.7, and 2.87 million, respectively. These samples will allow exploration of the Milky Way halo, clustering on all scales, and BAO measurements with a statistical precision of 0.28% over the redshift interval z &lt; 1.1, 0.39% over the redshift interval 1.1 &lt; z &lt; 1.9, and 0.46% over the redshift interval 1.9 &lt; z &lt; 3.5.</jats:p