Mutations of bacteria from virus sensitivity to virus resistance
TL;DR: This article reported Luria and Delbruck's breakthrough study in which they established that viruses do not induce mutations in bacteria, but that virus-resisting mutations are spontaneous.
Abstract: This article reported Luria and Delbruck's breakthrough study in which they established that viruses do not induce mutations
in bacteria, but that virus-resisting mutations are spontaneous. Their "fluctuation test" theory demonstrated that
bacteria were ideal subjects for genetic research.
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TL;DR: It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis.
Abstract: Researchers have been studying metastasis for more than 100 years, and only recently have we gained insight into the mechanisms by which metastatic cells arise from primary tumours and the reasons that certain tumour types tend to metastasize to specific organs. Stephen Paget's 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the 'seeds') and specific organ microenvironments (the 'soil') still holds forth today. It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis. How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?
4,319 citations
Cites methods from "Mutations of bacteria from virus se..."
...This hypothesis was tested using the Luria and Delbruck fluctuation analysi...
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TL;DR: Metastases do not result from random survival of cells released from the primary tumour but from the selective growth of specialised subpopulations of highly metastatic cells endowed with specific properties that befit them to complete each step of the metastatic process.
Abstract: Metastases do not result from random survival of cells released from the primary tumour but from the selective growth of specialised subpopulations of highly metastatic cells endowed with specific properties that befit them to complete each step of the metastatic process.
1,724 citations
TL;DR: Northern analysis of strains containing plasmid inserts with various promoter mutations suggests that the stimulation in recombination is mediated by events initiating within the integrated plasmID sequences.
1,641 citations
TL;DR: The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.
Abstract: Neoplasms are microcosms of evolution. Within a neoplasm, a mosaic of mutant cells compete for space and resources, evade predation by the immune system and can even cooperate to disperse and colonize new organs. The evolution of neoplastic cells explains both why we get cancer and why it has been so difficult to cure. The tools of evolutionary biology and ecology are providing new insights into neoplastic progression and the clinical control of cancer.
1,586 citations
TL;DR: Results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner, which explains why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
Abstract: Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6 months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.
1,555 citations
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TL;DR: A bacteria-resistant-virus-resistant line is being developed from a cross between bacteria-susceptible-v virus-resistant and bacteria- resistant- virus-sUSceptible lines, which proved uniformly susceptible to a strain of mouse passage rabies virus.
Abstract: Under the conditions specified, there may be selected promptly from a hybrid stock of mice, of which 40 to 50 per cent die following a standard dose of B. enteritidis or St. Louis encephalitis virus, lines in which as high as 95 per cent and as low as 15 per cent succumb. Three lines,—one bacteria-susceptible-virus-susceptible, one bacteria-susceptible-virus-resistant, and one bacteria-resistant-virus-susceptible,—are regarded as remaining relatively stable after approximately twelve generations of selection and brother to sister or line inbreeding. Crossing susceptible with resistant lines and testing F1, F2, F3, and backcross progeny resulted in mortality percentages in the neighborhood of those expected on the basis that resistance to B. enteritidis and to encephalitis virus is each inherited independently on a single factor basis with resistance dominant over susceptibility. A bacteria-resistant-virus-resistant line is being developed from a cross between bacteria-susceptible-virus-resistant and bacteria-resistant-virus-susceptible lines. All selected lines proved uniformly susceptible to a strain of mouse passage rabies virus.
137 citations
73 citations
TL;DR: The work reported in this paper is of a preliminary nature and is concerned with the selection of a strain suitable for intensive study, the development of a special medium, and the recognition and characterization of specific variant types.
Abstract: Many workers have recognized the theoretical advantages to be derived from the use of a fast-growing, pigmented organism such as Serratia marcescens in the study of bacterial variation. Wasserzug (1888), Scheurlen (1896), Hefferan (1903), Rettger and Sherrick (1911), Eisenberg (1914), Breed and Breed (1927), Daddi (1932), Reed (1937) and others have reported observations on the appearance of more or less stable color variants of this species. These observations, however, have thrown little light on the mechanisms involved in the production of such variants. Some series or coincidence of events must be responsible for the cellular changes that are so conspicuous, but as yet so little is known concerning the rates at which variants arise, or the effects of environmental factors on rates of variation, that the nature of these events remains obscure. It has been the writer's object to approach the problem of color-variation in Serratia in a quantitative manner, and to attempt to measure the frequency with which variants are produced under different environmental conditions. The work reported in this paper' is of a preliminary nature and is concerned with the selection of a strain suitable for intensive study, the development of a special medium, and the recognition and characterization of specific variant types. Pigmented strains of Serratia were found to differ greatly both in color and in the frequency with which they produced paler variants. These differences proved so confusing that it was
54 citations