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Search Results: 1 - 10 of 402143 matches for " Gillian M. Howell "
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Epigenetic Targeting of Transforming Growth Factor β Receptor II and Implications for Cancer Therapy
Sanjib Chowdhury,Sudhakar Ammanamanchi,Gillian M. Howell
Molecular and Cellular Pharmacology , 2009,
Abstract: The transforming growth factor (TGF) β signaling pathway is involved in many cellular processes including proliferation, differentiation, adhesion, motility and apoptosis. The loss of TGFβ signaling occurs early in carcinogenesis and its loss contributes to tumor progression. The loss of TGFβ responsiveness frequently occurs at the level of the TGFβ type II receptor (TGFβRII) which has been identified as a tumor suppressor gene (TSG). In keeping with its TSG role, the loss of TGFβRII expression is frequently associated with high tumor grade and poor patient prognosis. Reintroduction of TGFβRII into tumor cell lines results in growth suppression. Mutational loss of TGFβRII has been characterized, particularly in a subset of colon cancers with DNA repair enzyme defects. However, the most frequent cause of TGFβRII silencing is through epigenetic mechanisms. Therefore, re-expression of TGFβRII by use of epigenetic therapies represents a potential therapeutic approach to utilizing the growth suppressive effects of the TGFβ signaling pathway. However, the restoration of TGFβ signaling in cancer treatment is challenging because in late stage disease, TGFβ is a pro-metastatic factor. This effect is associated with increased expression of the TGFβ ligand. In this Review, we discuss the mechanisms associated with TGFβRII silencing in cancer and the potential usefulness of histone deacetylase (HDAC) inhibitors in reversing this effect. The use of HDAC inhibitors may provide a unique opportunity to restore TGFβRII expression in tumors as their pleiotropic effects antagonize many of the cellular processes, which mediate the pro-metastatic effects associated with increased TGFβ expression.
Ron Knockdown and Ron Monoclonal Antibody IMC-RON8 Sensitize Pancreatic Cancer to Histone Deacetylase Inhibitors (HDACi)
Yi Zou, Gillian M. Howell, Lisa E. Humphrey, Jing Wang, Michael G. Brattain
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069992
Abstract: Recepteur d’origine nantais (Ron) is overexpressed in a panel of pancreatic cancer cells and tissue samples from pancreatic cancer patients. Ron can be activated by its ligand macrophage stimulating protein (MSP), thereby activating oncogenic signaling pathways. Crosstalk between Ron and EGFR, c-Met, or IGF-1R may provide a mechanism underlying drug resistance. Thus, targeting Ron may represent a novel therapeutic strategy. IMC-RON8 is the first Ron monoclonal antibody (mAb) entering clinical trial for targeting Ron overexpression. Our studies show IMC-RON8 downmodulated Ron expression in pancreatic cancer cells and significantly blocked MSP-stimulated Ron activation, downstream Akt and ERK phosphorylation, and survivin mRNA expression. IMC-RON8 hindered MSP-induced cell migration and reduced cell transformation. Histone deacetylase inhibitors (HDACi) are reported to target expression of various genes through modification of nucleosome histones and non-histone proteins. Our work shows HDACi TSA and Panobinostat (PS) decreased Ron mRNA and protein expression in pancreatic cancer cells. PS also reduced downstream signaling of pAkt, survivin, and XIAP, as well as enhanced cell apoptosis. Interestingly, PS reduced colony formation in Ron knockdown cells to a greater extent than Ron scramble control cells in colony formation and soft agarose assays. IMC-RON8 could also sensitize pancreatic cancer cells to PS, as reflected by reduced colony numbers and size in combination treatment with IMC-RON8 and PS compared to single treatment alone. The co-treatment further reduced Ron expression and pAkt, and increased PARP cleavage compared to either treatment alone. This study suggests the potential for a novel combination approach which may ultimately be of value in treatment of pancreatic cancer.
Identification of a Novel TGFβ/PKA Signaling Transduceome in Mediating Control of Cell Survival and Metastasis in Colon Cancer
Sanjib Chowdhury,Gillian M. Howell,Ashwani Rajput,Carol A. Teggart,Lisa E. Brattain,Hannah R. Weber,Aparajita Chowdhury,Michael G. Brattain
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019335
Abstract: Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown.
A.B. Mulder-Bakker, J. Wogan-Browne: Household, Women and Christianities in Late Antiquity and the Middle Ages
M. Howell
BMGN : Low Countries Historical Review , 2008,
Open questions: missing pieces from the immunological jigsaw puzzle
Griffiths Gillian M
BMC Biology , 2013, DOI: 10.1186/1741-7007-11-10
Global Diversity and Review of Siphonophorae (Cnidaria: Hydrozoa)
Gillian M. Mapstone
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087737
Abstract: In this review the history of discovery of siphonophores, from the first formal description by Carl Linnaeus in 1785 to the present, is summarized, and species richness together with a summary of world-wide distribution of this pelagic group within the clade Hydrozoa discussed. Siphonophores exhibit three basic body plans which are briefly explained and figured, whilst other atypical body plans are also noted. Currently, 175 valid siphonophore species are recognized in the latest WoRMS world list, including 16 families and 65 genera. Much new information since the last review in 1987 is revealed from the first molecular analysis of the group, enabling identification of some new morphological characters diagnostic for physonect siphonophores. Ten types of nematocysts (stinging cells) are identified in siphonophores, more than in any other cnidarian; these are incorporated into batteries in the side branches of the tentacles in most species (here termed tentilla), and tentilla are reviewed in the last section of this paper. Their discharge mechanisms are explained and also how the tentilla of several physonect siphonophores are modified into lures. Of particular interest is the recent discovery of a previously unknown red fluorescent lure in the tentilla of the deep sea physonect Erenna, the first described example of emission of red light by an invertebrate to attract prey.
Temporal Changes in the Lesser Flamingos Population (Phoenicopterus minor) in Relation to Phytoplankton Abundance in Lake Manyara, Tanzania  [PDF]
Emilian Samwel Kihwele, Charles Lugomela, Kim M. Howell
Open Journal of Ecology (OJE) , 2014, DOI: 10.4236/oje.2014.43016

A study on seasonal variations in the abundance of Lesser Flamingo (Phoenicopterus minor) in relation to phytoplankton abundance in lake Manyara was conducted for a period of fourteen consecutive months (July 2007 to August 2008). The aim was to relate the temporal variability in the phytoplankton species abundance and diversity of the lake to the population size of the Lesser Flamingo. Lesser Flamingo population numbers were obtained from monthly ground surveys whereby the lake was subdivided into defined counting vantage points. Water samples for phytoplankton species composition and biomass analyses were taken to the University of Dar es Salaam for laboratory analysis. The flamingo population estimates ranged from 9319 in August 2007 to 640,850 in August 2008. The Lesser Flamingo populations showed that temporal fluctuations were related to the changes in the abundance and diversity of phytoplankton species. The occurrence of Arthrospira associated with the increase in the abundance of Lesser Flamingo. It was observed that changes in the Lesser Flamingo numbers were influenced by the changes in the abundance and availability of their preferred food. The results indicated that microalgae assemblage positively correlated with ammonium and nitrate which were also related to the abundance of lesser flamingo. The phytoplankton community was dominated by cyanobacteria particularly Arthrosipira fusiformis likely due to the high lake salinity and pH that limited the growth of other microalgae. Correlation analysis showed strong correlation between the Lesser Flamingo abundance with the concentration of nitrate and ammonium and between the number of Lesser Flamingo and the cyanobacterium Arthrospira.

Land of a Couple of Dances: Global and Local Influences on Freestyle Play in Dance Dance Revolution
Fibreculture Journal , 2006,
Abstract: This paper traces successful and unsuccessful attempts to shape the meanings of the video game Dance Dance Revolution, specifically with reference to what "dancing" means in this context, as the game moves between various interested parties - game developers, players, Internet forum participants, and other media producers. Drawing on Actor-Network Theory and the network analyses of Manuel Castells, the paper reconstructs the forces shaping players' stylistic decisions through an analysis of dance game machines and software, and of a single forum thread on DDRFreak.com, a major website in the dance game community. The paper asks who decides how DDR players dance and at what times? Are the decisions about play made in the development meeting, the arcade, competitions, online or around the home console? Globally, how do some regions or groups emerge as experts or leaders in play style? Analysis indicates that within the United States, Californian players from major cities dominate discussion, supported by the global flows of people, resources, and capital through the state. The dominant players support their stated norms for play through recourse to mainstream conceptions of masculinity, rap music and associated styles of dance.
Prolactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity
Sacha J Howell, Elizabeth Anderson, Tom Hunter, Gillian Farnie, Robert B Clarke
Breast Cancer Research , 2008, DOI: 10.1186/bcr2129
Abstract: The effects of doxorubicin, paclitaxel and Δ1–9 on the growth of breast cancer cell lines (MCF-7, T47D, MDA-MB-453, MDA-MB-468 and SK-BR-3) in monolayer culture were assessed by the sulphorhodamine B assay. Effects on clonogenicity were assessed by soft agar assay for the cell lines and by the mammosphere assay for disaggregated primary ductal carcinoma in situ samples. Dual-fluorescence immunocytochemistry was used to identify subpopulations of cells expressing the prolactin receptor and autocrine prolactin.Δ1–9 as a single agent had no effect on the cell number in monolayer culture, but potentiated the cytotoxic effects of doxorubicin and paclitaxel. Doxorubicin accordingly induced expression of prolactin mRNA and protein in all five breast cancer cell lines tested. Δ1–9 alone inhibited the clonogenicity in soft agar of cell lines by ~90% and the mammosphere forming efficiency of six disaggregated primary ductal carcinoma in situ samples by a median of 56% (range 32% to 88%). Subpopulations of cells could be identified in the cell lines based on the prolactin receptor and prolactin expression.Autocrine prolactin appears to act as an inducible survival factor in a clonogenic subpopulation of breast cancer cells. The rational combination of cytotoxics and Δ1–9 may therefore improve outcomes in breast cancer therapy by targeting this cell population.Exogenous prolactin has been shown to induce the proliferation, survival, migration and invasion of breast cancer cell lines in vitro and to increase the clonogenicity of primary human breast cancer samples in soft agar [1-5]. A prolactin excess reduces the tumour latency and increases the tumour incidence and growth rate in multiple rodent models of spontaneous and carcinogen-induced mammary tumours [6-8]. In humans, prospective case–control studies show that women with high versus low blood prolactin levels have an increased risk of preinvasive and invasive breast cancer [9,10]. Furthermore, the majority of human breast
Lifestyle in adults aged 35 years who were born with open spina bifida: prospective cohort study
Gillian M Hunt, Pippa Oakeshott
Fluids and Barriers of the CNS , 2004, DOI: 10.1186/1743-8454-1-4
Abstract: Ascertainment was 100%. There had been 63 deaths, mainly of the most severely affected. The mean age of the 54 survivors was 35 years. The outcome in terms of disability ranged from apparent normality to total dependency. It reflected both the neurological deficit, which had been recorded in infancy in terms of sensory level, and events in the CSF shunt history. Overall about 2 in 5 of the survivors lived independently in the community, 2 in 5 drove a car, 1 in 5 was in competitive employment and 1 in 5 could walk 50 metres.Although those who survived to age 35 years tended to be less disabled, 2 in 5 continued to need daily care.Neurosurgical intervention in babies with open spina bifida had dramatic results in terms of survival. However, the disability and the complications of the survivors were often severe [1-5]. Many efforts were made to enable them to walk, to control their urinary incontinence while safeguarding renal function, and to overcome problems associated with the shunt treatment of hydrocephalus. Promising new methods of management, such as the psoas transplant, urinary diversion and artificial urinary sphincters, which seemed highly successful in the short term, lost favour after 10 or 15 years because of disappointing long-term results. In this unsteady course of progress it is helpful to have a long term follow up of a complete cohort of patients with open spina bifida as a realistic basis for helping parents facing the difficult decisions about termination of an affected pregnancy or treatment after birth.In 1963 the Regional Neurosurgical Unit at Addenbrooke's Hospital, Cambridge, England offered treatment to all cases of open spina bifida, without any attempt at selection. Between 1963 and 1971, after a detailed neurological examination, 117 babies (50 male, 67 female) had their open spinal defects closed within 48 hours of birth. A ventriculo-atrial cerebrospinal fluid (CSF) shunt was inserted for hydrocephalus when required.In 2002 all surviv
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