Predictability of the response to tyrosine kinase inhibitors via in vitro analysis of Bcr-Abl phosphorylation.
ABSTRACT It would be of great value to predict the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of individual CML patients. We propose an immunoblot system for detecting the phosphorylation of Crkl, a major target of Bcr-Abl, in blood samples after in vitro incubation with TKIs. When the remaining phosphorylated Crkl after treatment with imatinib was evaluated as the "residual index (RI)", high values were found in accordance with imatinib resistance. Moreover, RI reflected the outcome of imatinib- as well as second generation TKIs with a high sensitivity and specificity. Therefore, this system should be useful in the selection of TKIs.
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ABSTRACT: Southern California's many large harbors form an important coastal ecosystem, yet they are also a␣major destination for thousands of pleasure craft and cargo vessels that have often traveled great distances. Many groups of marine organisms, including ascidians, have now been documented as undergoing range extensions as a consequence of rapid ship-transport between distant harbors phenomenon. This has resulted in a rapid increase in the rate of introductions of non-indigenous species worldwide, yet these effects of boat traffic remain largely unstudied in southern California. Ascidians are sessile marine filter-feeders, hermaphroditic, and often self-fertilizing; many species are tolerant of a wide range of environmental conditions, can reach sexual maturity in just a few weeks, and have a long breeding season. This paper documents the arrival of 14␣non-indigenous species in southern California harbors␣during this century, 13 of which have persisted:␣four prior to the 1960s (Cionaintestinalis, Styelaclava, S.␣plicata, Botryllusschlosseri), another by 1972 (S.␣canopus, formerly S. partita), and 8 since 1983 [C.␣savignyi, Ascidia zara, Ascidia sp., Polyandrocarpa zorritensis, Symplegma brakenhielmi (formerly S. oceania, and S. reptans, Microcosmus squamiger, and Molgula␣manhattensis)]. We estimate the relative abundance and seasonal fluctuations of both non-indigenous and native ascidians in all harbors in southern California from San Diego to Santa Barbara based upon the historical record, our 35 yr of field notes, and our recent surveys carried out during fall 1994, spring and fall 1995, fall 1996 and spring 1997. Possible points of origin of the exotics and predictions on further U.S. Pacific coast range-extensions are included. The concomitant decline in numbers and species of native ascidians in the harbors of southern California during this century is also reviewed.Marine Biology 02/1998; 130(4):675-688. · 2.47 Impact Factor
- Journal of Zoology 08/2009; 125(1):169 - 221. · 2.04 Impact Factor
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ABSTRACT: The Mediterranean mussel Mytilus galloprovincialis invaded the shores of South Africa in about the mid-1970s. It was first detected at a harbour in Saldanha on the west coast and apparently arrived accidentally. From there, it spread at a rate of about 115 km·year−1 and now occupies the whole of the west coast of South Africa and at least the southern half of Namibia. It was deliberately introduced from the west coast to the south coast for mariculture. In this case study, we record its effects on intertidal rocky shores, cast in terms of predictions based on (a) the history of its invasions elsewhere, (b) its mode of dispersal, (c) its physiological performance relative to indigenous mussels, (d) the role of wave action as a moderator of competition, (e) the influence of relative body sizes, (f) the projected effects of the mussel on infauna, (g) consumption by higher trophic levels, and (h) rates of parasitism.Several properties of M. galloprovincialis itself, and of the recipient community, conspired to favour the spread and establishment of this alien mussel, including high productivity on the west coast of South Africa, prevalently strong wave action, a sparsity of predators, an absence of parasites, the mussel's fast growth and high reproductive output, and its possession of a planktotrophic larva. It competitively displaces several species because of its physiological performance. Some of the species gain a substitute substratum on the mussels themselves, but only if they are small enough to live and reproduce on the mussels. M. galloprovincialis has had little effect on infauna, but has provided an additional source of food for higher predators, including the rare and endangered African Black Oystercatcher (Haematopus moquini).Nearly all these effects and conditions were forecasted (or, at the least, explainable with hindsight), but despite these successes in predicting the impacts of M. galloprovincialis, its spread was not only unavoidable but was encouraged by its transfer to the south coast for mariculture. Moreover, there was one completely unpredictable effect of M. galloprovincialis—which led to mass mortalities of a swimming crab. Given the failure of even quite detailed and accurate predictions to allow control of M. galloprovincialis once it arrived, prevention rather than cure must be the prime means of avoiding future unwanted introductions of invasive species.Journal of Experimental Marine Biology and Ecology. 01/2004;