Molecular biomarkers for prognosis of gastrointestinal stromal tumor.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. However, the development of molecular markers, especially circulating biomarkers, remains largely undone for the prognosis of GIST. We discussed the clinical-pathological characteristics of GIST and identified potential biomarkers for guidance of therapy and prognosis of GIST. Around 90% of GISTs contain mutations in KIT or PDGFRA and the remaining 10% of GISTs are wild-type. Recent studies have indicated that various DNAs and miRNAs could serve as potential biomarkers for prognosis of GIST, including KIT, PDGFRA, other DNAs (such as BRAF, SDH, SETD2 and ROR2), and microRNAs (miRNAs). The pressing need and challenges in the development of circulating prognostic biomarkers for GIST are also discussed. Although challenges remain, DNAs and miRNAs are promising circulating biomarkers for surveillance and prognosis of GIST. Advances in clarification of aberrant molecular alterations may open new avenues for exploration of reliable and robust biomarkers to improve the management of GIST.

Application of Sartwell's model (lognormal distribution of incubation periods) to age at onset and age at death of foals with Rhodococcus equi pneumonia as evidence of perinatal infection.

The distributions of the incubation periods for infectious and neoplastic diseases originating from point-source exposures, and for genetic diseases, follow a lognormal distribution (Sartwell's model). Conversely, incubation periods in propagated outbreaks and diseases with strong environmental components do not follow a lognormal distribution. In this study Sartwell's model was applied to the age at onset and age at death of foals with Rhodococcus equi pneumonia. The age at onset of clinical signs and age at death were compiled for 107 foals that had been diagnosed with R. equi pneumonia at breeding farms in Argentina and Japan. For each outcome (disease and death), these data followed a lognormal distribution. A group of 115 foals with colic from the University of California were used as a comparison group. The age at onset of clinical signs for these foals did not follow a lognormal distribution. These results were consistent with the hypothesis that foals are infected with R. equi during the 1st several days of life, similar to a point-source exposure.

Molecular, cellular and functional characterizations of a novel ICAM-like molecule of the immunoglobulin superfamily from Leishmania mexicana amazonensis.

A molecule with two immunoglobulin (Ig) domains cloned from Leishmania mexicana amazonensis was characterized to have a sequence homology to the Ig domains of an ICAM-like molecule telencephalin, cloned from the brain of mammals, as well as to the variable domains of human immunoglobulin lambda light chain. The molecule therefore appears to be an ICAM-like molecule as well as a member of the immunoglobulin superfamily. We thus named it ICAM-L for Leishmania ICAM. The gene was coamplified with the ribonucleotide reductase M(2) subunit gene responsible for hydroxyurea resistance from hydroxyurea (Hu)-resistant Leishmania variants. As expected, an increase of the ICAM-L protein as well as an increase of the specific ICAM-L transcript of 2.1 kb was detected in the Hu-resistant variants with increasing doses of the drug used for resistance selection. Structurally, ICAM-L is more similar to the secretory adhesive molecules, such as 1Bgp and the link protein of the immunoglobulin superfamily, in that it lacks a transmembrane region and a GPI anchor sequence. Although ICAM-L was mainly localized in the nucleus of the parasite by confocal microscopy, however, detailed studies by electron microscopy and FACS analysis indicated that the protein was also localized on the surface of the parasite. The surface localization of the protein was furthered strengthened by the observations that anti-ICAM-L or ICAM-L itself can significantly block the binding of the parasite to macrophages. The blocking of the attachment of parasite to macrophages may indicate that ICAM-L functions as an intercellular adhesive molecule.