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Selected AbstractsMetastatic melanoma to lymph nodes in patients with unknown primary sitesCANCER, Issue 9 2006Janice N. Cormier M.D., M.P.H. Abstract BACKGROUND The natural history of metastatic melanoma in lymph nodes in the absence of a known primary site (MUP) has been defined poorly; thus, treatment guidelines for patients with MUP are not clear-cut. METHODS The authors conducted a retrospective analysis of consecutive patients with melanoma (from 1990 to 2001) who underwent surgical resection for melanoma metastatic to regional lymph nodes. Among those patients, 71 patients with MUP and 466 control patients who had regional lymph node metastases of similar stage with a known primary site were identified. Associations between clinicopathologic factors and survival were estimated by using the Cox proportional hazards model. RESULTS After they underwent lymph node dissection, patients with MUP were classified with N1b disease (47%), N2b disease (14%), or N3 disease (39%). With a median follow-up of 7.7 years, the 5-year and 10-year overall survival rates were 55% and 44%, respectively, for patients with MUP, compared with 42% and 32%, respectively, for the control group (P = .04). In multivariate analyses, age 50 years or older, male gender, and N2b or N3 disease status were identified as adverse prognostic factors, and MUP was identified as a favorable prognostic factor (hazard ratio, 0.61; 95% confidence interval, 0.42,0.86; P = .006) for overall survival. CONCLUSIONS The relatively favorable long-term survival of patients with MUP in the current study suggested that patients with MUP have a natural history that is similar to (if not better than) the survival of many patients with Stage III disease. Therefore, patients with MUP should be treated with an aggressive surgical approach with curative intent and should be considered for Stage III adjuvant therapy protocols. Cancer 2006. © 2006 American Cancer Society. [source] THE IMPORTANCE OF PREADAPTED GENOMES IN THE ORIGIN OF THE ANIMAL BODYPLANS AND THE CAMBRIAN EXPLOSIONEVOLUTION, Issue 5 2010Charles R. Marshall The genomes of taxa whose stem lineages branched early in metazoan history, and of allied protistan groups, provide a tantalizing outline of the morphological and genomic changes that accompanied the origin and early diversifications of animals. Genome comparisons show that the early clades increasingly contain genes that mediate development of complex features only seen in later metazoan branches. Peak additions of protein-coding regulatory genes occurred deep in the metazoan tree, evidently within stem groups of metazoans and eumetazoans. However, the bodyplans of these early-branching clades are relatively simple. The existence of major elements of the bilaterian developmental toolkit in these simpler organisms implies that these components evolved for functions other than the production of complex morphology, preadapting the genome for the morphological differentiation that occurred higher in metazoan phylogeny. Stem lineages of the bilaterian phyla apparently required few additional genes beyond their diploblastic ancestors. As disparate bodyplans appeared and diversified during the Cambrian explosion, increasing complexity was accommodated largely through changes in cis -regulatory networks, accompanied by some additional gene novelties. Subsequently, protein-coding genic richness appears to have essentially plateaued. Some genomic evidence suggests that similar stages of genomic evolution may have accompanied the rise of land plants. [source] The A-type cyclins and the meiotic cell cycle in mammalian male germ cellsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 4 2004Debra J. Wolgemuth Summary There are two mammalian A-type cyclins, cyclin Al and A2. While cyclin A1 is limited to male germ cells, cyclin A2 is widely expressed. Cyclin A2 promotes both Gl/S and G2/M transitions in somatic cells and cyclin A2-deficient mice are early embryonic lethal. We have shown that cyclin Al is essential for passage of spermatocytes into meiosis I (MI) by generating mice null for the cyclin A1 gene Ccna1. Both Ccna1,/, males and females were healthy but the males were sterile because of a cell cycle arrest before MI. This arrest was associated with desynapsis abnormalities, low M-phase promoting factor activity, and apoptosis. We have now determined that human cyclin A1 is expressed in similar stages of spermatogenesis and are exploring its role in human male infertility and whether it may be a novel target for new approaches for male contraception. [source] An ontology of human developmental anatomyJOURNAL OF ANATOMY, Issue 4 2003Amy Hunter Human developmental anatomy has been organized as structured lists of the major constituent tissues present during each of Carnegie stages 1,20 (E1,E50, ,8500 anatomically defined tissue items). For each of these stages, the tissues have been organized as a hierarchy in which an individual tissue is catalogued as part of a larger tissue. Such a formal representation of knowledge is known as an ontology and this anatomical ontology can be used in databases to store, organize and search for data associated with the tissues present at each developmental stage. The anatomical data for compiling these hierarchies comes from the literature, from observations on embryos in the Patten Collection (Ann Arbor, MI, USA) and from comparisons with mouse tissues at similar stages of development. The ontology is available in three versions. The first gives hierarchies of the named tissues present at each Carnegie stage (http://www.ana.ed.ac.uk/anatomy/database/humat/) and is intended to help analyse both normal and abnormal human embryos; it carries hyperlinked notes on some ambiguities in the literature that have been clarified through analysing sectioned material. The second contains many additional subsidiary tissue domains and is intended for handling tissue-associated data (e.g. gene-expression) in a database. This version is available at the humat site and at http://genex.hgu.mrc.ac.uk/Resources/intro.html/), and has been designed to be interoperable with the ontology for mouse developmental anatomy, also available at the genex site. The third gives the second version in GO ontology syntax (with standard IDs for each tissue) and can be downloaded from both the genex and the Open Biological Ontology sites (http://obo.sourceforge.net/) [source] |