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A letter from Anne Walker Cragg to the Carlos F. Truan.
No full textA letter from Anne Walker Cragg to the Carlos F. Truan regarding the gifting a a reproduced Lorenzo de Zavala flag, copied to Dr. Hector P. Garcia
Mitotic death: a mechanism of survival? A review
No full textMitotic death is a delayed response of p53 mutant tumours that are resistant to genotoxic damage. Questions surround why this response is so delayed and how its mechanisms serve a survival function. After uncoupling apoptosis from G1 and S phase arrests and adapting these checkpoints, p53 mutated tumour cells arrive at the G2 compartment where decisions regarding survival and death are made. Missed or insufficient DNA repair in G1 and S phases after severe genotoxic damage results in cells arriving in G2 with an accumulation of point mutations and chromosome breaks. Double strand breaks can be repaired by homologous recombination during G2 arrest. However, cells with excessive chromosome lesions either directly bypass the G2/M checkpoint, starting endocycles from G2 arrest, or are subsequently detected by the spindle checkpoint and present with the features of mitotic death. These complex features include apoptosis from metaphase and mitosis restitution, the latter of which can also facilitate transient endocycles, producing endopolyploid cells. The ability of cells to initiate endocycles during G2 arrest and mitosis restitution most likely reflects their similar molecular environments, with down-regulated mitosis promoting factor activity. Resulting endocycling cells have the ability to repair damaged DNA, and although mostly reproductively dead, in some cases give rise to mitotic progeny. We conclude that the features of mitotic death do not simply represent aberrations of dying cells but are indicative of a switch to amitotic modes of cell survival that may provide additional mechanisms of genotoxic resistance
Mitotic catastrophe and endomitosis in tumour cells: An evolutionary key to a molecular solution
No full textFollowing genotoxic insult, p53 mutated tumour cells undergo mitotic catastrophe. This is characterised by a switch from mitosis to the endocycle. The essential difference between mitosis and the endocycle is that in the latter, DNA synthesis is uncoupled from cell division, which leads to the formation of endopolyploid cells. Recent data suggests that a return from the endocycle into mitosis is also possible. Furthermore, our observations indicate that a particular type of endocycle known as endomitosis may be involved in this return. Here we review the role of endomitosis in the somatic reduction of polyploidy during development and its postulated role in the evolution of meiosis. Finally, we incorporate these evolutionary data to help interpret our most recent observations in the tumour cell system, which indicate a role for endomitosis and meiotic regulators, in particular p39mos in the segregation of genomes (somatic reduction) of these endopolyploid cells
Cancer: A matter of life cycle?
No full textIn the last decade, the concept of "cancer stem cells" has emerged, recognised by the fact that only a small fraction of tumour cells appears to retain the stem cell properties of self-renewal and unlimited proliferation. At the same time, it is well known that cancer is an age-related disease developing at the limit of proliferating cell senescence. The apparent need to link senescence and the capacity for self-renewal has lead some authors to suggest that cancers develop from amongst senescing stem cells. However, an alternative solution has recently been proffered by Sundaram M, Guernsey DL, Rajaraman MM, Rajaraman R [Neosis: a novel type of cell division in cancer. Cancer Biol Ther 2004;3:207-18], who suggest that sternness may be a transient, cyclic property afforded by de-polyploidisation of senescing cells which have undergone polyploidisation. In this mini-review, we attempt to reconcile both of these views by the idea that cycling polyploidy intermitting senescence and rejuvenation may be features of a life cycle analogous to the life cycles of certain unicellular organisms. Furthermore, we suggest that mitotic catastrophe may represent a mechanism through which the cell can switch from the usual mitotic cell-cycle to this evolutionarily conserved life cycle. Intriguingly, some most recent data suggest that cell senescence may be reversible and that stem cells are tolerant to polyploidy caused by genotoxic stress
Resistance of modified wood to marine borers
No full textThe resistance of differently modified wood to the common shipworm, Teredo navalis, and the wood boring crustacean, Limnoria quadripunctata, was assessed in a field trial and by means of a short term laboratory assay, respectively. Scots pine (Pinus sylvestris) sapwood was treated with TEOS (tetra-ethoxy-ortho-silane) and different thermosetting resins, namely phenol formaldehyde (PF) and methylated melamine formaldehyde (MMF). Additionally, acetylated and untreated Radiata pine (Pinus radiata) was included. In the field trial according to EN 275 in the Baltic Sea over a period of six years the specimens were exclusively attacked by T. navalis. For the laboratory assay, matchstick-sized samples cut from spare panels prepared for the field trial were subjected to individuals of L. quadripunctata; faecal pellet production served as a measure of feeding rate. Treatments that prevented shipworm attack in the field also reduced feeding of L quadripunctata in the laboratory assay: efficacy of resin treatments was enhanced by parameters that increase the amount of resin in the cell wall (i.e. high WPG and dry curing conditions); acetylation resulted in high resistance; and TEOS treatment was not effective. The results suggest that modification on cell wall level is required to impart marine borer resistance. (c) 2015 Elsevier Ltd. All rights reserved
Treatment with the anti-CD20 antibody (B1) and irradiation result in synergistic cytotoxicity that is dependent on MAPK activation
No full textRadioimmunotherapy using radiolabeled anti-CD20 antibodies (mAb) is an effective new treatment in non-Hodgkin lymphoma with high response rates. However, the molecular mechanisms behind these impressive clinical responses are poorly understood. To elucidate these mechanisms we studied the signaling events evoked in a panel of lymphoma cell lines following treatment with anti-CD20 mAb alone or in combination with irradiation. In all three lymphoma cell-lines tested a synergistic cytotoxic effect was observed when the anti-CD20 mAb B1 was combined with irradiation. The additive effect seen with B1 mAb and radiation was not observed with Rituximab and could be reversed with MEK inhibitors U0126 and PD98059 as well as siRNA targeting MEK1 or 2. Moreover, addition of U0126 reversed the decrease in clonogenic survival triggered by treatment with B1 and irradiation. To further probe the mechanism of this synergistic cell death we used cell lines over-expressing BCL2 or crmA, to block mitochondrial and death receptor pathways, respectively. Although BCL2 and crmA over-expression mediated protection against radiation alone, it had no impact on the increased cytotoxicity induced by B1+irradiation. Morphological studies revealed gross vacuolization of the cytoplasm, yet relatively well preserved nuclei in cells treated with B1+irradiation. Taken together our data indicate that activation of the MAPK cascade is an important factor that contributes to the synergistic effect of anti-CD20 (B1) antibody and irradiation and provides important new insights into how this treatment may work in the clinic
FcγR requirements leading to successful immunotherapy
No full textMonoclonal antibody (mAb) immunotherapy is currently experiencing an unprecedented amount of success, delivering blockbuster sales for the pharmaceutical industry. Having experienced several false dawns and overcoming technical issues which limited progress, we are now entering a golden period where mAbs are becoming a mainstay of treatment regimes for diseases ranging from cancer to autoimmunity. In this review, we discuss how these mAbs are most likely working and focus in particular on the key receptors that they interact with to precipitate their therapeutic effects. Although their targets may vary, their engagement with Fcγ receptors (FcγRs) on numerous immune effector cells is almost universal, and here we review their roles in delivering successful immunotherapy
Distinguishing ten sympatric species of fiddler crab (Decapoda: Ocypodidae) using a suite of phenotypic characteristics
No full textMichie, Laura A., Barnes, R. S. K., Clark, Paul F., Bennett, Wayne A., Cragg, Simon M. (2021): Distinguishing ten sympatric species of fiddler crab (Decapoda: Ocypodidae) using a suite of phenotypic characteristics. Zootaxa 5026 (4): 480-506, DOI: 10.11646/zootaxa.5026.4.
Anthony Cragg. Le prime stagioni (1970-2000)
No full textThe essay reconstructs the development of Anthony Cragg's research form the early minimalist-conceptual works to the works from the 1990s, from fragmentary forms to whole forms, from two-dimensionality to compact volumes, and from occupying space through installation to sculpture isolated in space
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