Exploring the role of endothelium in the tumour response to anti-angiogenic therapy

2014 ◽  
Vol 42 (6) ◽  
pp. 1569-1575 ◽  
Author(s):  
Yi-Chao He ◽  
Michael M. Halford ◽  
Marc G. Achen ◽  
Steven A. Stacker
Keyword(s):  
Human Cancer ◽  
Tumour Response ◽  
Tumour Microenvironment ◽  
Hallmarks Of Cancer ◽  
Patient Response ◽  
Angiogenic Therapy ◽  
Wide Range ◽  
Cancer Inhibition ◽  
Insight Into

A chronic hyperactivated angiogenic state in cancer plays an important role in tumour growth and metastasis and has been identified as one of the hallmarks of cancer. Inhibition of this process has been associated with tumour suppression in many pre-clinical contexts using different animal tumour models. Anti-angiogenic therapeutics were subsequently developed and used to treat several prevalent types of human cancer. However, recent clinical experience has revealed limitations of this approach in treating cancer as patient response varies over a wide range. Given that there are complex underlying molecular and cellular changes provoked by anti-angiogenic treatment within the tumour microenvironment (TME), it is not surprising that modest effectiveness and resistance have been observed in the clinical setting. This article discusses these issues in the context of VEGF-A-targeted anti-angiogenic treatment of cancer and provides insight into the importance of tumour endothelium for understanding the tumour response to anti-angiogenic therapy. Special consideration is also given to possible approaches for investigating how endothelium contributes to the tumour response to anti-angiogenic agents and for exploring the therapeutic and biomarker potential of targeting tumour endothelium.

scholarly journals The role of B-Cell Lymphoma-3 (BCL-3) in enabling the hallmarks of cancer: implications for the treatment of colorectal carcinogenesis

2020 ◽  
Vol 41 (3) ◽  
pp. 249-256 ◽  
Author(s):  
Danny N Legge ◽  
Adam C Chambers ◽  
Christopher T Parker ◽  
Penny Timms ◽  
Tracey J Collard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Lymphocytic Leukaemia ◽  
Tumour Response ◽  
B Cell Lymphoma ◽  
Hallmarks Of Cancer ◽  
Wide Range ◽  
The Impact

Abstract With its identification as a proto-oncogene in chronic lymphocytic leukaemia and central role in regulating NF-κB signalling, it is perhaps not surprising that there have been an increasing number of studies in recent years investigating the role of BCL-3 (B-Cell Chronic Lymphocytic Leukaemia/Lymphoma-3) in a wide range of human cancers. Importantly, this work has begun to shed light on our mechanistic understanding of the function of BCL-3 in tumour promotion and progression. Here, we summarize the current understanding of BCL-3 function in relation to the characteristics or traits associated with tumourigenesis, termed ‘Hallmarks of Cancer’. With the focus on colorectal cancer, a major cause of cancer related mortality in the UK, we describe the evidence that potentially explains why increased BCL-3 expression is associated with poor prognosis in colorectal cancer. As well as promoting tumour cell proliferation, survival, invasion and metastasis, a key emerging function of this proto-oncogene is the regulation of the tumour response to inflammation. We suggest that BCL-3 represents an exciting new route for targeting the Hallmarks of Cancer; in particular by limiting the impact of the enabling hallmarks of tumour promoting inflammation and cell plasticity. As BCL-3 has been reported to promote the stem-like potential of cancer cells, we suggest that targeting BCL-3 could increase the tumour response to conventional treatment, reduce the chance of relapse and hence improve the prognosis for cancer patients.

scholarly journals The use of ceramics as an aesthetic element in Durban architecture (1914-2012)

2013 ◽  
Author(s):  
◽  
Raksha Padaruth
Keyword(s):  
Historical Background ◽  
Art Practice ◽  
Local Identity ◽  
Architectural Elements ◽  
Architectural Element ◽  
Wide Range ◽  
Research Questions ◽  
Contemporary Practice ◽  
Insight Into

This paper documents and evaluates the use of ceramics as an aesthetic architectural element in Durban from 1914-2012 with special reference to James Hall (1916-2006), Andrew Walford (b.1942) and Jane du Rand (b.1969). These artists were selected because their work demonstrates a wide range of the use of decorative tiles and mosaics as aesthetic elements in Durban architecture over a period of more than fifty years. Reference is made to the historical use of tiles and mosaics as aesthetic architectural elements in Durban from 1914-1955 in order to provide a context to an investigation and evaluation of the contribution of Hall, Walford and du Rand to the use of tiles and mosaics as an aesthetic architectural element in Durban. The paper begins by highlighting the importance of this study, discusses the role of ceramic architectural adornment and defines terminology for the purpose of this research. In addition an explanation of the research methodology used, research questions and literature review is provided. The study is contextualised through an overview of the historical background of the use of ceramics (tiles and mosaics) as an aesthetic element in architecture. The importance of the use of ceramic elements in relation to architecture, as well as the different techniques and methods of production, are highlighted and related to contemporary practice. The overview provides insight into how the use of ceramic elements in the past has influenced the approach of contemporary practice. My contribution to the use of mosaics as an aesthetic architectural element in Durban and my art practice, in the form of an installation titled passage is discussed and evaluated. The paper concludes by noting that the historical use of tiles and mosaics as aesthetic elements in architecture persists in contemporary art practice. However, the methods of tiled mosaic production and tiled mosaic techniques have been revolutionised extensively. It is evident that, the use of ceramics as an aesthetic element in Durban architecture reflects, both a strong European design influence and a distinctive local identity.

scholarly journals Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond

2019 ◽  
Vol 20 (18) ◽  
pp. 4507 ◽  
Author(s):  
Lang ◽  
Guerrero-Giménez ◽  
Prince ◽  
Ackerman ◽  
Bonorino ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Stress Proteins ◽  
De Novo ◽  
Human Cancer ◽  
Essential Components ◽  
Wide Range ◽  
Cancer Types ◽  
Shock Proteins

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.

Robots in recycling and disassembly

2019 ◽  
Vol 46 (4) ◽  
pp. 461-466 ◽  
Author(s):  
Robert Bogue
Keyword(s):  
Research Effort ◽  
Electronic Waste ◽  
Waste Recycling ◽  
Content Type ◽  
Research Activities ◽  
Wide Range ◽  
Electronic Waste Recycling ◽  
Product Disassembly ◽  
Insight Into

Purpose This paper aims to illustrate the growing role robots are playing in recycling and product disassembly and provide an insight into recent research activities. Design/methodology/approach Following a short introduction, this first considers robotic waste sorting systems and then describes two systems for the disassembly of electronic products. It then provides details of some recent research activities. Finally, brief conclusions are drawn. Findings Robotic systems exploiting artificial intelligence combined with various sensing and machine vision technologies are playing a growing role in the sorting of municipal and industrial waste, prior to recycling. These are mostly based on delta robots and can achieve pick rates of 60-70 items/min and be configured to recognise and select a wide range of different materials and items from moving conveyors. Electronic waste recycling is yet to benefit significantly from robotics although a limited number of systems have been developed for product disassembly. Disassembly techniques are the topic of a concerted research effort which often involves robots and humans collaborating and sharing disassembly tasks. Originality/value This provides an insight into the present-day uses and potential future role of robots in recycling which has traditionally been a highly labour-intensive industry.

scholarly journals The Role of the Fibronectin IGD Motif in Stimulating Fibroblast Migration

2007 ◽  
Vol 282 (49) ◽  
pp. 35530-35535 ◽  
Author(s):  
Christopher J. Millard ◽  
Ian R. Ellis ◽  
Andrew R. Pickford ◽  
Ana M. Schor ◽  
Seth L. Schor ◽  
...  
Keyword(s):  
Fibroblast Migration ◽  
Wide Range ◽  
Migration Stimulating Factor ◽  
Function Relationship ◽  
Relationship Of ◽  
Stimulating Factor ◽  
Insight Into ◽  
Stimulation Of

The motogenic activity of migration-stimulating factor, a truncated isoform of fibronectin (FN), has been attributed to the IGD motifs present in its FN type 1 modules. The structure-function relationship of various recombinant IGD-containing FN fragments is now investigated. Their structure is assessed by solution state NMR and their motogenic ability tested on fibroblasts. Even conservative mutations in the IGD motif are inactive or have severely reduced potency, while the structure remains essentially the same. A fragment with two IGD motifs is 100 times more active than a fragment with one and up to 106 times more than synthetic tetrapeptides. The wide range of potency in different contexts is discussed in terms of cryptic FN sites and cooperativity. These results give new insight into the stimulation of fibroblast migration by IGD motifs in FN.

scholarly journals Short-Term Effects of Pacifier Texture on NNS in Neurotypical Infants

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Austin L. Oder ◽  
David L. Stalling ◽  
Steven M. Barlow
Keyword(s):  
Short Term ◽  
Compression Pressure ◽  
Term Infants ◽  
Wide Range ◽  
Postmenstrual Age ◽  
Array Density ◽  
Insight Into ◽  
Dense Representation ◽  
Short Term Effects

The dense representation of trigeminal mechanosensitive afferents in the lip vermilion, anterior tongue, intraoral mucosa, and temporomandibular joint allows the infant’s orofacial system to encode a wide range of somatosensory experiences during the critical period associated with feed development. Our understanding of how this complex sensorium processes texture is very limited in adults, and the putative role of texture encoding in the infant is unknown. The purpose of this study was to examine the short-term effects of a novel textured pacifier experience in healthy term infants (N=28). Nonnutritive suck (NNS) compression pressure waveforms were digitized in real time using a variety of custom-molded textured pacifiers varying in spatial array density of touch domes. MANCOVA, adjusted for postmenstrual age at test and sex, revealed that infants exhibited an increase in NNS burst attempts at the expense of a degraded suck burst structure with the textured pacifiers, suggesting that the suck central pattern generator (sCPG) is significantly disrupted and reorganized by this novel orocutaneous experience. The current findings provide new insight into oromotor control as a function of the oral somatosensory environment in neurotypically developing infants.

Qualitative perspectives: through a methodological lens

2014 ◽  
Vol 11 (1) ◽  
pp. 13-28 ◽  
Author(s):  
Lee Parker
Keyword(s):  
Qualitative Research ◽  
Significant Contribution ◽  
Research Literature ◽  
Management Research ◽  
Content Type ◽  
Wide Range ◽  
Qualitative Methodologies ◽  
Insight Into ◽  
Management Scholarship

Purpose – This paper aims to offer an insight into the emergent qualitative methodological profile and its distinctive contribution to accounting and management scholarship, particularly reflecting upon the contribution of Qualitative Research in Accounting & Management (QRAM). Design/methodology/approach – It examines the range of qualitative methodologies employed in the research published across the ten years of QRAM and analyses the methodological discourse and its contribution to the armoury available to qualitative researchers. In association with these methodological developments, the paper offers a critique of the articulated role of theory in contemporary accounting and management qualitative research. Findings – A wide range of qualitative methodologies are found to be in evidence, with considerable scope for further adoption and development of some. Methodological exposition papers are found to be a significant contribution in the past decade and include methodological framework building, methodological applications, methodological critiques, and methodological development exemplars. Alongside methodology, the dual role of theory as either informing or reflecting methodology is presented. Originality/value – The paper provides a critical analysis and consideration of qualitative methodological literature development in the last ten years of accounting and management research literature, particularly reflected in QRAM. It identifies dominant methodologies in use, as well as opportunities for expanding the methodological menu in accounting and management research. Furthermore, it classifies groups of methodological papers and their contributing perspectives, as well as addressing the often-vexed relationship between theory and methodology.

scholarly journals The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

2014 ◽  
Vol 21 (4) ◽  
pp. R331-R344 ◽  
Author(s):  
Eric Monsalves ◽  
Kyle Juraschka ◽  
Toru Tateno ◽  
Sameer Agnihotri ◽  
Sylvia L Asa ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Human Cancer ◽  
Tumor Biology ◽  
Pituitary Tumors ◽  
Mass Effect ◽  
Therapeutic Approaches ◽  
Hormone Production ◽  
New Therapeutic Approaches ◽  
Wide Range

Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.

scholarly journals INDOLEAMINE 2,3 DIOXYGENASE AS AN IMMUNOTHERAPEUTIC TARGET BRINGS A NEW HOPE FOR CANCER PATIENTS

2018 ◽  
Vol 4 (3) ◽  
Author(s):  
Kashif Asghar ◽  
Asif Loya
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cancer Colorectal ◽  
Immune Escape ◽  
Mammalian Target Of Rapamycin ◽  
Tumour Microenvironment ◽  
Indoleamine 2,3 Dioxygenase ◽  
Wide Range ◽  
Ido Inhibitors

Therapeutic manipulation of immune system in cancer has been an extensive area of research in the field of oncoimmunology. Immunotherapy helps the immune system to combat against cancer. Tumour cells take an edge of immunosuppressive mechanisms and inhibit antitumour immune responses. Indoleamine 2,3 dioxygenase (IDO) is an immunosuppressive enzyme which is involved in tumour immune escape mechanism in various cancers. IDO can degrade the tryptophan into kynurenines and has an ability to enhance the immune tolerance through mammalian target of rapamycin pathway general control nonderepressible 2 (GCN2) pathway and induction of regulatory T (T-regs) cells. IDO-induced T-regs suppress the local immune responses in the tumour microenvironment and promote metastasis. IDO overexpression in various cancers is associated with poor prognosis. Several preclinical and clinical trials have been proceeding and recommend that IDO inhibitor may be an influential tool against a wide range of cancers. IDO inhibitors as adjuvant therapeutic agents may also have clinical implications. Thus, IDO has the potential to be used as an immunotherapeutic target. This review discusses the promising role of IDO in cancer and its implication in immunotherapy.Key words: Breast cancer, colorectal cancer, haematological malignancies, immunotherapy, indoleamine 2,3-dioxygenase, pancreatic cancer, prostate cancer

Sign in / Sign up

Export Citation Format

Share Document