The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK checklist consists of 20 items to report for published tumor marker prognostic studies. A detailed paper was published explaining the rationale behind checklist items, providing positive examples and giving empirical evidence of the quality of reporting. REMARK provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. Despite support for REMARK from major cancer journals, prognostic factor research studies remain poorly reported. To encourage dissemination and uptake of REMARK, we have produced this considerably abridged version of the detailed explanatory manuscript, which may also serve as a brief guide to key issues for investigators planning tumor marker prognostic studies. To summarize the current situation, more recent papers investigating the quality of reporting and related reporting guidelines are cited, but otherwise the literature is not updated. Another important impetus for this paper is that it serves as a basis for literal translations into other languages. Translations will help to bring key information to a larger audience world-wide. Many more details can be found in the original paper.

Subcellular distributions of the five human Arf proteins were examined, using a set of isoform-specific polyclonal and a pan-Arf monoclonal antibodies. Subcellular fractionation of cultured mammalian cells allowed the demonstration that Arf6 is uniquely localized to the plasma membranes of Chinese hamster ovary cells. The plasma membrane distrubution was unaffected by either GTP␥S (guanosine 5-O-(3-thio)triphosphate) or brefeldin A, an activator and inhibitor of Arf activities, respectively. In contrast, Arf proteins 1, 3, 4, and 5 were predominantly cytosolic but could be recruited to a variety of intracellular membranes, but not plasma membranes, upon incubation in the presence of GTP␥S. The GTP␥S-promoted binding of the cytosolic Arf proteins to membranes was blocked by brefeldin A. The stable association of Arf6 with plasma membranes and the insensitivity of its localization to either GTP␥S or brefeldin A revealed a clear distinction between Arf6 and the other Arf isoforms. Localization of Arf6 to the plasma membrane suggests a unique cellular role for this isoform at the plasma membrane, but failure to find endogenous Arf6 on endocytic structures, including clathrin-coated vesicles, appears inconsistent with the proposed role of Arf6 in assembly of coat structures or endosomes in transfected fibroblasts (1, 2).The ADP-ribosylation factor (Arf) 1 family is a group of structurally related proteins that form a subset of the Ras superfamily of regulatory GTP-binding proteins (for a recent review, see Ref. 3). In addition to serving as cofactors for cholera toxin-catalyzed ADP-ribosylation, Arf proteins have more recently been associated with a wide array of functions. These include acting as regulators of the binding of coat proteins and adaptins to intracellular membranes (4, 5), activators of phospholipase D (6, 7), regulators of ER and Golgi morphology and function (8, 9), and cytosolic factors conferring sensitivity to GTP␥S in cell-free assays of intra-Golgi (10 -12) and ER-Golgi transport (13), and endosome (14) and nuclear membrane fusion (15, 16).The importance of Arf proteins in both membrane traffic and organelle organization was manifest due to the sensitivities of most Arf proteins to both GTP␥S, a slowly hydrolyzable GTP analog, and to brefeldin A (BFA), a fungal metabolite capable of inhibiting guanine nucleotide exchange on Arf in a crude system (17-19). The activation (GTP binding) and deactivation (GTP hydrolysis) cycle of Arf action in cells is thought to coincide with its binding and release, respectively, from intracellular membranes. In this model, activation of a soluble Arf protein results in its translocation to a membrane and the recruitment, through unknown mechanisms, of coat proteins or adaptor complexes to that membrane. It remains unclear how, or even if, Arf-mediated activation of phospholipase D or cholera toxin relate to mechanisms of regulation of membrane transport by Arf proteins.

Ran is a small GTPase required for nuclear transport in eukaryotic cells [

The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to ‘omics’-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests forguiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy.