A patient with octopus pot-shaped cardial cancer that metastasized to multiple organs

A 71-year-old male was admitted for abdominal fullness. The condition rapidly deteriorated in a short period (3weeks), and the patient died. Autopsy revealed a protruding lesion measuring about 3 cm with erosion measuring 5mmin diameter immediately below the esophago-gastric conjugation site, suggesting primary cardial undifferentiated adenocarcinoma. In the primary focus, changes on the mucosal surface were almost normal. However, below the mucosa, infiltration of cancer cells was observed in an approximately 3 cm area along the gastric wall. Simultaneously, the site of infiltration was markedly increased in deep areas. Extra serous infiltration was observed. The morphology was special, and resembled an octopus pot, a trap used to catch octopuses in Japan, with a narrow top and a broad base. In our patient, metastatic lesions were detected in multiple organs, including the stomach

A novel organic-rich meteoritic clast from the outer solar system

The Zag meteorite which is a thermally-metamorphosed H ordinary chondrite contains a primitive xenolitic clast that was accreted to the parent asteroid after metamorphism. The cm-sized clast contains abundant large organic grains or aggregates up to 20μm in phyllosilicate-rich matrix. Here we report organic and isotope analyses of a large (~10μm) OM aggregate in the Zag clast. The X-ray micro-spectroscopic technique revealed that the OM aggregate has sp2 dominated hydrocarbon networks with a lower abundance of heteroatoms than in IOM from primitive (CI,CM,CR) carbonaceous chondrites, and thus it is distinguished from most of the OM in carbonaceous meteorites. The OM aggregate has high D/H and 15N/14N ratios (δD=2,370±74‰ and δ15N=696±100‰), suggesting that it originated in a very cold environment such as the interstellar medium or outer region of the solar nebula, while the OM is embedded in carbonate-bearing matrix resulting from aqueous activities. Thus, the high D/H ratio must have been preserved during the extensive late-stage aqueous processing. It indicates that both the OM precursors and the water had high D/H ratios. Combined with 16O-poor nature of the clast, the OM aggregate and the clast are unique among known chondrite groups. We further propose that the clast possibly originated from D/P type asteroids or trans-Neptunian Objects

Methylation pattern of CDH13 gene in digestive tract cancers

Recently, the loss of CDH13 (T-cadherin, H-cadherin) gene expression accompanied by CDH13 promoter methylation was identified in colon cancers. We examined CDH13 methylation in oesophageal and gastric carcinomas. Five of 37 oesophageal cancers (14%) and 23 of 66 gastric cancers (35%) demonstrated abnormal methylation of the CDH13 promoter. Abnormal methylation was frequently found in gastric cancers of patients at all clinical stages just as in E-cadherin, another of the cadherin family, suggesting that these cancers could be methylated at an early stage. These results suggested that CDH13 might play a variety of roles depending on the tissue type

A D- and N-15-Rich Micrometer-Sized Aggregate of Organic Matter in a Xenolithic Clast from the Zag Ordinary Chondrite

The nature and origin of extraterrestrial organic matter are still under debate despite the significant progress in the analyses and experimental approaches in this field over the last five decades. Xenolithic clasts are often found in a wide variety of meteorite groups, some of which contain exotic organic matter (OM). The Zag meteorite is a thermally-metamorphosed H ordinary chondrite. It contains a primitive xenolithic clast that has been proposed to have originated from Ceres, which was accreted to the Zag host asteroid after metamorphism. The cm-sized clast contains abundant large carbon-rich (mostly organic) grains or aggregates up to 20 microns. Such large OM grains are unique among astromaterials with respect to the size. Here we report organic and isotope analyses of a large (approx.10 microns) aggregate of solid OM in the Zag clast. The X-ray micro-spectroscopic technique revealed that the OM has sp2 bonded carbon with no other functional groups nor graphitic feature (1s-sigma exciton), and thus it is distinguished from most of the OM in carbonaceous meteorites. The apparent absence of functional groups in the OM suggests that it is composed of hydrocarbon networks with less heteroatoms, and therefore the OM aggregate is similar to hydrogenated amorphous carbon (HAC). The OM aggregate has high D/H and 15N/14N ratios, suggesting that it originated in a very cold environment such as the interstellar medium or outer region of the solar nebula, while the OM is embedded in carbonate-bearing matrix resulting from aqueous activities. Thus the high D/H ratio must have survived the extensive late-stage aqueous processing. It is not in the case for OM in carbonaceous chondrites of which the D/H ratio was reduced by the alteration via the D-H exchange of water. It indicates that both the OM precursors and the water had high D/H ratios, similar to the water in Enceladus. Our results support the idea that the clast originated from Ceres, or at least, a hydrovolcanically active body similar to Ceres, and further imply that Ceres originally formed in the outer Solar System and migrated to the main belt asteroid region as suggested by the "Grand tack" scenario

Organic Aggregates with (delta)D and delta(sup 15)N Anomalies in the Zag Clast Revealed by STXM and NanoSIMS

Xenolithic clasts are often found in a wide variety of meteorite groups. Some ordinary chondrite clasts are interesting since these clasts might have originated from Ceres which shares crossing orbits with a possible ordinary chondrite parent body, Hebe. The Zag meteorite contains a dark clast dominated by saponite, serpentine, carbonates, sulfides, magnetite, minor olivine and pyroxene, which is consistent with formation on a large, carbonaceous, aqueously active body, e.g., Ceres. Abundant large C-rich grains up to 20 microns were found in the Zag clast as well. Such large C-rich grains are unique among any other meteorites in our knowledge, and will provide important clues to decipher the origin of the clast and accretion history. C-rich grains were selected in the Zag dark clast using SEM and approximately 100 nm-thick sections were prepared using a focused ion beam (FIB) at NASA-JSC. The sections were analyzed using the scanning transmission X-ray microscope (STXM) on beamline 5.3.2.2 at Advanced Light Source, LBNL, and BL-13A at the Photon Factory, KEK. Subsequently, the FIB section was analyzed for H, C and N isotopic compositions using a CAMECA NanoSIMS 50L ion microprobe at Kochi Institute for Core Sample Research, JAMSTE

Engineering biomolecular microenvironments for cell instructive biomaterials

Engineered cell instructive microenvironments with the ability to stimulate specific cellular responses is a topic of high interest in the fabrication and development of biomaterials for application in tissue engineering. Cells are inherently sensitive to the in vivo microenvironment that is often designed as the cell “niche”. The cell “niche” comprising the extracellular matrix and adjacent cells, influences not only cell architecture and mechanics, but also cell polarity and function. Extensive research has been performed to establish new tools to fabricate biomimetic advanced materials for tissue engineering that incorporate structural, mechanical and biochemical signals that interact with cells in a controlled manner and to recapitulate the in vivo dynamic microenvironment. Bioactive tunable microenvironments using micro and nanofabrication have been successfully developed and proven to be extremely powerful to control intracellular signaling and cell function. This review is focused in the assortment of biochemical signals that have been explored to fabricate bioactive cell microenvironments and the main technologies and chemical strategies to encode them in engineered biomaterials with biological information.The authors thank Fundacao para a Ciencia e Tecnologia for C.A.C.'s PhD grant (SFRH/BD/61390/2009). This work was carried out under the scope of the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS

Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture

INTRODUCTION: Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells. METHOD: To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips. RESULTS: HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing cells compared to empty vector control cells. The expression of a functionally inactive Cx43 chimeric protein in HBL100 cells failed to increase migration efficiency, suggesting that the observed up-regulation of diapedesis in Cx43 expressing cells required heterocellular GJIC. This finding is further supported by the observation that blocking homocellular and heterocellular GJIC with carbenoxolone in co-cultures also reduced diapedesis of Cx43 expressing HBL100 tumor cells. CONCLUSION: Collectively, our results suggest that heterocellular GJIC between breast tumor cells and endothelial cells may be an important regulatory step during metastasis