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TL;DR: It is demonstrated that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft.
Abstract: Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.
2,997 citations
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TL;DR: Transgenic mice that express high levels of human mutant APP support a primary role for APP/Aβ in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
Abstract: Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs.
2,669 citations
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TL;DR: It is proposed that the mutant versions of CFTR are recognized as abnormal and remain incompletely processed in the endoplasmic reticulum where they are subsequently degraded.
1,747 citations
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TL;DR: Cystic fibrosis is a regulated Cl- channel, for which structure-function relationships have begun to be established, and insight into the functions of individual domains has come from a number of studies.
1,446 citations
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TL;DR: Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.
1,428 citations
Authors
Showing all 3085 results
Name | H-index | Papers | Citations |
---|---|---|---|
George M. Whitesides | 240 | 1739 | 269833 |
Stephen J. O'Brien | 153 | 1062 | 93025 |
Robert B. Jackson | 132 | 458 | 91332 |
Glenn M. Chertow | 128 | 764 | 82401 |
Jon Clardy | 116 | 983 | 56617 |
John J. Fung | 115 | 1011 | 52924 |
Robert B. Colvin | 111 | 556 | 52034 |
Sergio Giralt | 109 | 1024 | 48513 |
Paul Saftig | 107 | 356 | 49929 |
Robert J. Desnick | 102 | 694 | 39698 |
Robert A. Soslow | 87 | 427 | 29014 |
Richard J. Roman | 84 | 461 | 23760 |
Diana W. Bianchi | 81 | 405 | 24554 |
Paolo Raggi | 80 | 439 | 33332 |
Helmut G. Rennke | 77 | 256 | 33959 |