determined by light microscopy: the pit patterns in 100 glands were analysed. Results-Pit pattern was classified into seven principal types: (1) normal round pit; (2) small round pit; (3) small asteroid pit; (4) large asteroid pit; (5) oval pit; (6) gyrus-like pit; and (7) non-pit. There was a correlation between pit pattern and the structure of the underlying crypt or gland. Furthermore, there was an association between pit pattern and the histology of the cells in the gland.Macroscopically, types 3, 4, 5, and 6 were common in protruding lesions. Type 2 was common in depressed lesions. The non-pit pattern was recognised in both. The depressed lesions had invaded the deeper layers more rapidly than protruding lesions.
QR-32 tumor cells, a clone derived from a murine fibrosarcoma, are poorly tumorigenic and nonmetastatic when injected into syngeneic C57BL/6 mice. However, they are converted to highly malignant ones once they have grown in vivo after being co-implanted in a subcutaneous site with a foreign body, a gelatin sponge. Early phase of inflammation induced by the gelatin sponge participates in the conversion and histological analysis shows predominant infiltration of neutrophils. The objective of this study was to determine whether the depletion of the infiltrating neutrophils has any effect on the tumor progression. Intraperitoneal administration of a monoclonal anti-granulocyte antibody, RB6-8C5 (RB6), depleted neutrophils from both the peripheral blood circulation and the local inflamed site in mice with co-implantation of QR-32 tumor cells and gelatin sponge. The RB6 administration did not inhibit either tumor development or growth of QR-32 tumor cells. In contrast, tumor cell lines established from RB6-administered mice showed a significant decrease in metastatic incidence as compared with the tumor cell lines obtained from the mice with administration of control rat IgG or saline. Metastatic ability was significantly suppressed when RB6 had been administered in the early phase (from day -2 to day 6 after implantation); however, the administration in the middle (from day 6 to day 14) or late (from day 14 to day 22) phase did not affect the metastatic ability. We confirmed the phenomena by using integrin beta(2) knockout mice that had impaired neutrophil infiltration into inflamed sites. In the knockout mice, neutrophils hardly infiltrated into the gelatin sponge and the tumors showed dramatically suppressed metastatic phenotype as compared with those in wild-type mice or nude mice. Immunohistochemical analysis demonstrated that expressions of 8-hydroxy-2'-deoxyguanosine and nitrotyrosine were parallel to those in the presence of neutrophils. These results suggested that inflammation, especially when neutrophils infiltrate into tumor tissue, is primarily important for benign tumor cells to acquire metastatic phenotype.
We identified a thymosin-beta4 gene overexpression in malignant mouse fibrosarcoma cells (QRsP-30) that were derived from clonal weakly tumorigenic and nonmetastatic QR-32 cells by using a differential display method. Thymosin-beta4 is known as a 4.9-kd polypeptide that interacts with G-actin and functions as a major actin-sequestering protein in cells. All of the six malignant fibrosarcoma cell lines that have been independently converted from QR-32 cells expressed high levels of thymosin-beta4 mRNA and its expression in tumor cells was correlated with tumorigenicity and metastatic potential. Up-regulation of thymosin-beta4 in QR-32 cells (32-S) transfected with sense thymosin-beta4 cDNA converted the cells to develop tumors and formed numerous lung metastases in syngeneic C57BL/6 mice. In contrast, antisense thymosin-beta4 cDNA-transfected QRsP-30 (30-AS) cells reduced thymosin-beta4 expression, and significantly lost tumor formation and metastases to distant organs. Vector-alone transfected cells (32-V or 30-V cells) behaved like their parental cells. We observed that tumor cell motility, cell shape, and F-actin organization is regulated in proportion to the level of thymosin-beta4 expression. These findings indicate that thymosin-beta4 molecule regulates fibrosarcoma cell tumorigenicity and metastasis through actin-based cytoskeletal organization.
In the past two decades, the Argo Program has collected, processed, and distributed over two million vertical profiles of temperature and salinity from the upper two kilometers of the global ocean. A similar number of subsurface velocity observations near 1,000 dbar have also been collected. This paper recounts the history of the global Argo Program, from its aspiration arising out of the World Ocean Circulation Experiment, to the development and implementation of its instrumentation and telecommunication systems, and the various technical problems encountered. We describe the Argo data system and its quality control procedures, and the gradual changes in the vertical resolution and spatial coverage of Argo data from 1999 to 2019. The accuracies of the float data have been assessed by comparison with high-quality shipboard measurements, and are concluded to be 0.002 • C for temperature, 2.4 dbar for pressure, and 0.01 PSS-78 for salinity, after delayed-mode adjustments. Finally, the challenges faced by the vision of an expanding Argo Program beyond 2020 are discussed.
We propose to add dissolved oxygen sensors to the Argo (Global array of free-drifting profiling floats) float program in order to determine, on a global-scale, seasonal to decadal time-scale variations in dissolved oxygen concentrations throughout the upper ocean. Such observations are especially important to document the ocean's expected loss of oxygen as a result of ocean warming, but there are many other benefits including the opportunity to estimate net community and export production, the assessment of changes in low oxygen regions, and improved estimates of the oceanic uptake of anthropogenic C O2 .The proposed joint Argo-Oxygen program is made possible by the recent development of dissolved oxygen sensors that are both precise and stable over extended periods and can be easily integrated with the currently used Argo floats. Results from the more than 200 oxygen equipped Argo float have not only demonstrated the feasibility of the program, but also produced already many insights and discoveries. Achieving the main goal of the Argo-Oxygen program does not require any appreciable changes in the deployment and operating strategies of the current Argo program and can therefore be implemented without a significant impact on Argo's core mission.A two-phase implementation is proposed, consisting of a small set of regional pilot-studies, followed by a buildup toward a global implementation. The cost of adding oxygen sensors to all floats of the Argo program is estimated to be about USD 4.2 million per year. The proposed Argo-Oxygen program will add substantial value to Argo by expanding the number of Argo data users, as well as by creating new synergies between the physical and the biogeochemical ocean research communities. The new observations will also contribute to the activities of various international networks and partnerships for Earth Observing Systems.
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