Ja Turri

Prognostic value of ADAMTS proteases and their substrates in epithelial ovarian cancer

Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied.

The transcription factor chicken Scratch2 is expressed in a subset of early postmitotic neural progenitors

Scratch proteins are members of the Snail superfamily which have been shown to regulate invertebrate neural development. However, in vertebrates, little is known about the function of Scratch or its relationship to other neural transcription factors. We report the cloning of chicken Scratch2 (cScrt2) and describe its expression pattern in the chick embryo from HH15 through HH29. cScrt2 was detected in cranial ganglia, the nasal placode and neural tube. At all stages examined, cScrt2 expression is only detected within a subregion of the intermediate zone of the neural tube. cScrt2 is also expressed in the developing dorsal root ganglia from HH22-23 onwards and becomes limited to its dorsal medial domain at HH29. phospho-Histone H3 and BrdU-labeling revealed that the cScrt2 expression domain is located immediately external to the proliferative region. In contrast, cScrt2 domain overlapped almost completely with that of the postmitotic neural transcription factor NeuroM/Ath3/NEUROD4. Together, these data define cScrt2-positive cells as a subset of immediately postmitotic neural progenitors. Previous data has shown that Scrt2 is a repressor of E-box-driven transcription whereas NeuroM is an E-box-transactivator. In light of these data, the co-localization detected here suggests that Scrt2 and NeuroM may have opposing roles during definition of neural subtypes.

Economic evaluations in gastroenterology in Brazil: A systematic review

AIMnTo systematically review economic evaluations in gastroenterology, relating to Brazil, published between 1980 and 2013.nnnMETHODSnWe selected full and partial economic evaluations from among those retrieved by searching the following databases: MEDLINE (PubMed); Excerpta Medica; the Latin American and Caribbean Health Sciences Literature database; the Scientific Electronic Library Online; the database of the Centre for Reviews and Dissemination; the National Health Service (NHS) Economic Evaluation Database; the NHS Health Technology Assessment database; the Health Economics database of the Brazilian Virtual Library of Health; Scopus; Web of Science; and the Brazilian Network for the Evaluation of Health Technologies. Two researchers, working independently, selected the studies and extracted the data.nnnRESULTSnWe identified 535 health economic evaluations relating to Brazil and published in the 1980-2013 period. Of those 535 articles, only 40 dealt with gastroenterology. Full and partial economic evaluations respectively accounted for 23 (57.5%) and 17 (42.5%) of the 40 studies included. Among the 23 full economic evaluations, there were 11 cost-utility analyses, seven cost-effectiveness analyses, four cost-consequence analyses, and one cost-minimization analysis. Of the 40 studies, 25 (62.5%) evaluated medications; 7 (17.5%) evaluated procedures; and 3 (7.5%) evaluated equipment. Most (55%) of the studies were related to viral hepatitis, and most (63.4%) were published after 2010. Other topics included gastrointestinal cancer, liver transplantation, digestive diseases and hernias. Over the 33-year period examined, the number of such economic evaluations relating to Brazil, especially of those evaluating medications for the treatment of hepatitis, increased considerably.nnnCONCLUSIONnFurther studies are needed in order to ensure that expenditures on health care in Brazil are made as fairly and efficiently as possible.

Gene Expression in Embryonic Neural Development and Stem Cell Differentiation

The concept of neural induction, i.e. the definition of the neural plate domain in the ectoderm, was first proposed by Spemman and Mangold after the classic experiment in which transplantation of the frog embryo’s dorsal blastopore lip induced a complete neural axis from the acceptor embryo’s ectoderm. Since then, much effort has been made aimed at identify the signals that confer the neural bias to the ectoderm. The resulting picture clearly indicates that neural induction is a multi-step process that requires the interplay of various pathways. The result of neural induction is the definition of a neural plate composed by proliferating neuroepithelial cells expressing pan-neural genes.