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Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma 下载免费PDF全文
The lack of advanced animal models of human cancers is considered a barrier to developing effective therapeutics. Canine and human melanomas are histologically disparate but show similar disease progression and response to therapies. The purpose of these studies was to compare human and canine melanoma tumours and cell lines regarding MAPK and PI3K/AKT signalling dysregulation, and response to select molecularly targeted agents. Pathway activation was investigated via microarray and mutational analysis. Growth inhibition and cell cycle effects were assessed for pathway inhibitors AZD6244 (MAPK) and rapamycin (PI3K/AKT) in human and canine melanoma cells. Human and canine melanoma share similar differential gene expression patterns within the MAPK and PI3K/AKT pathways. Constitutive pathway activation and similar sensitivity to AZD6244 and rapamycin was observed in human and canine cells. These results show that human and canine melanoma share activation and sensitivity to inhibition of cancer‐related signalling pathways despite differences in activating mutations. 相似文献
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Two hundred feral cats from the inner suburbs of Sydney were examined post mortem for adult Dirofilaria immitis and circulating microfilariae, and 101 of these cats were tested for heartworm antigens by an ELISA. Only 2 cats (1%) had adult heartworms, the blood sample from another cat contained a single microfilaria. The blood of a further three cats contained small amounts of D immitis antigen. Although D immitis occurs in cats in Sydney, the prevalence is not high enough to warrant prophylactic treatment. 相似文献
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W. W. Miller D. W. Johnson C. Denton P. S. J. Verburg G. L. Dana R. F. Walker 《Water, air, and soil pollution》2005,163(1-4):3-17
It is generally held that surface runoff in heavily forested ecosystems is minimal and therefore nutrient fluxes via runoff are unimportant. This is based in large measure on the absence of direct observation or remnant physical evidence. It is further held that protected forests with heavy understory and litter serve as a nutrient sink due to maximum uptake and interception. Our Sierran studies have detected the presence of surface runoff at several sites in the form of both overland and litter interflow with concentrations of NH4-N as high as 87.2 mg L?1, NO3-N as high as 95.4 mg L?1, and PO4-P as high as 24.4 mg L?1. Data suggest that nutrients are derived from the mature O-horizons, and that there has been little contact with the mineral soil or root zone where strong retention and/or uptake of these ions would be expected. Such contributions from overland/interflow could be particularly important in areas where ultra-oligotrophic lakes (e.g., Lake Tahoe) are now trending towards meso-oligotrophic status. We believe that fire exclusion in these systems may have exacerbated N and P inputs to Lake Tahoe and elsewhere by allowing unnatural buildups of O-horizons that are apparently a source of nutrients to surface runoff. 相似文献
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Pliocene paleoclimate and East antarctic ice-sheet history from surficial ash deposits 总被引:1,自引:0,他引:1
The preservation, age, and stratigraphic relation of an in situ ashfall layer with an underlying desert pavement in Arena Valley, southern Victoria Land, indicate that a cold-desert climate has persisted in Arena Valley during the past 4.3 million years. These data indicate that the present East Antarctic Ice Sheet has endured for this time and that average temperatures during the Pliocene in Arena Valley were no greater than 3 degrees C above present values. One implication is that the collapse of the East Antarctic Ice Sheet due to greenhouse warming is unlikely, even if global atmospheric temperatures rise to levels last experienced during mid-Pliocene times. 相似文献
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PC Sereno DB Dutheil M Iarochene HCE Larsson GH Lyon PM Magwene CA Sidor DJ Varricchio JA Wilson 《Science (New York, N.Y.)》1996,272(5264):986-991
Late Cretaceous (Cenomanian) fossils discovered in the Kem Kem region of Morocco include large predatory dinosaurs that inhabited Africa as it drifted into geographic isolation. One, represented by a skull approximately 1.6 meters in length, is an advanced allosauroid referable to the African genus Carcharodontosaurus. Another, represented by a partial skeleton with slender proportions, is a new basal coelurosaur closely resembling the Egyptian genus Bahariasaurus. Comparisons with Cretaceous theropods from other continents reveal a previously unrecognized global radiation of carcharodontosaurid predators. Substantial geographic differentiation of dinosaurian faunas in response to continental drift appears to have arisen abruptly at the beginning of the Late Cretaceous. 相似文献