William A H Wallace

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (71)448.63 Total impact

  • Gehad Youssef · William A H Wallace · Mark P Dagleish · Chris Cousens · David J Griffiths ·
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    ABSTRACT: Lung cancer is the leading cause of cancer deaths worldwide. Recent progress in understanding the molecular pathogenesis of this disease has resulted in novel therapeutic strategies targeting specific groups of patients. Further studies are required to provide additional advances in diagnosis and treatment. Animal models are valuable tools for studying oncogenesis in lung cancer, particularly during the early stages of disease where tissues are rarely available from human cases. Mice have traditionally been used for studying lung cancer in vivo, and a variety of spontaneous and transgenic models are available. However, it is recognized that other species may also be informative for studies of cancer. Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by retrovirus infection and has several features in common with adenocarcinoma of humans, including a similar histological appearance and activation of common cell signaling pathways. Additionally, the size and organization of human lungs are much closer to those of sheep lungs than to those of mice, which facilitates experimental approaches in sheep that are not available in mice. Thus OPA presents opportunities for studying lung tumor development that can complement conventional murine models. Here we describe the potential applications of OPA as a model for human lung adenocarcinoma with an emphasis on the various in vivo and in vitro experimental systems available. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    ILAR journal / National Research Council, Institute of Laboratory Animal Resources 05/2015; 56(1):99-115. DOI:10.1093/ilar/ilv014 · 2.39 Impact Factor
  • R. Mills · A. Mathur · L. Nicol · I. Dransfield · W. Wallace · S. Howie · N. Hirani ·

    Immunology 12/2014; 143:170-170. · 3.80 Impact Factor
  • Tim Andrews · William A.H. Wallace ·
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    ABSTRACT: Lung and pleural malignancy is a major cause of morbidity and mortality. Approaches to diagnosis and management are evolving, based on both technological and scientific advances. A basic understanding of the classification of lung and pleural tumours and approaches to their pathological diagnosis is important for all those involved in managing these patients. To this end, we present an overview of the current classification of lung tumours, briefly discuss their aetiology and pathogenesis, describe pathological aspects of the diagnosis and staging of bronchial carcinoma (including an outline of the developing role of molecular approaches to refining oncological management), and finally review the pathology of mesothelioma and it differential diagnosis.
    Surgery (Oxford) 05/2014; 32(5). DOI:10.1016/j.mpsur.2014.02.011
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    American Journal of Respiratory and Critical Care Medicine 02/2014; 189(4):500-1. DOI:10.1164/rccm.201309-1725LE · 13.00 Impact Factor
  • C. D. Bingle · B. Araujo · W. A. Wallace · H. M. Marriott · N. Hirani · L. Bingle ·

    Thorax 11/2013; 68(Suppl 3):A139-A139. DOI:10.1136/thoraxjnl-2013-204457.290 · 8.29 Impact Factor
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    ABSTRACT: Small cell lung cancer (SCLC) kills at least one person every 2 hr in the United Kingdom. Some patients do relatively well but most have rapidly progressive disease. There is no effective treatment and overall 2-year survival is less than 5%. Patients with SCLC have poorly understood local and systemic immune defects and can be immunocompromised. As CD4(+) T lymphocytes coordinate and regulate immunity, a better understanding of interactions between SCLC tumour cells and CD4(+) T cells may lead to effective molecular immunotherapy. We show that some, but not all, SCLC tumour cell lines secrete molecules that induce IL-10 secretion by and de novo differentiation of functional CD4(+)CD25(+)FOXP3(+)CD127(lo)Helios(-) regulatory T (Treg) cells in healthy blood lymphocytes. FOXP3(+) T cells were found in SCLC tumour biopsies, and patients with higher ratios of FOXP3(+) cells in tumour infiltrates have a worse survival rate. The inhibitory effect of SCLC tumour cells was not affected by blocking IL-10 receptor or TGF-β signalling but was partially reversed by blocking IL-15, which is reported to be involved in human Treg cells induction. IL-15 was secreted by SCLC cells that inhibited CD4(+) T-cell proliferation and was present in SCLC biopsy tumour cells. These novel findings demonstrate that SCLC tumour cells can induce CD4(+) T-cell-mediated immunosuppression. This gives a potential mechanism by which SCLC tumour cells may downregulate local and systemic immune responses and contribute to poor patient survival. Our data suggest that IL-15 and Treg cells are potential new therapeutic targets to improve immune response and patient survival in SCLC.
    International Journal of Cancer 09/2012; 131(6):E928-37. DOI:10.1002/ijc.27613 · 5.09 Impact Factor
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    ABSTRACT: Background: Small cell lung carcinoma (SCLC) continues to have a poor prognosis, with a 2-year survival of < 20%. Studies have suggested that SCLC may affect the immune system to allow it to evade immunologic responses. We hypothesized that any such effect would be characterized by a decrease in the lymphoid cells associated with the tumor in biopsy specimens and that this might relate to patient outcome. Methods: Sixty-four SCLC biopsy specimens were immunohistochemically stained with anti-CD45 antibody to identify immune cells associated with the tumor. A mean CD45 count per high-power field for each case was obtained, and the results were correlated with age, sex, stage, performance status (PS), treatment with chemotherapy/radiotherapy, and overall survival. Results: The median CD45 count for all cases was taken as 40 (CD45(40)). Kaplan-Meier plots demonstrated better survival for patients with a CD45(40) > 40 ( P < .009). No relationship between CD45 40 and age, sex, stage, or treatment by chemotherapy or radiotherapy was identified. Although PS was a significant predictor of survival ( P = .014), it did not correlate with CD45 40. In patients with better Eastern Cooperative Oncology Group PS (≤ 2), the CD45(40) demonstrated a highly significant survival advantage for those with CD45(40) > 40 ( P < .0001). Conclusions: The data indicate that (1) simple immunohistochemical assessment of immune cell infiltrates in routinely processed and stained biopsy specimens of primary tumors can provide prognostic information in SCLC and (2) tumor-associated CD45(+) cells in SCLC biopsy specimens may be a good clinical marker to identify patients with poor prognosis despite good PS.
    Chest 07/2012; 143(1). DOI:10.1378/chest.12-0681 · 7.48 Impact Factor
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    ABSTRACT: Rationale: Acute lung injury (ALI) is an important cause of morbidity and mortality, with no currently effective pharmacological therapies. Neutrophils have been specifically implicated in the pathogenesis of ALI, and there has been significant research into the mechanisms of early neutrophil recruitment, but those controlling the later phases of neutrophil emigration that characterize disease are poorly understood. Objectives: To determine the influence of peripheral blood monocytes (PBMs) in established ALI. Methods: In a murine model of LPS-induced ALI, three separate models of conditional monocyte ablation were used: systemic liposomal clodronate (sLC), inducible depletion using CD11b diphtheria toxin receptor (CD11b DTR) transgenic mice, and antibody-dependent ablation of CCR2(hi) monocytes. Measurements and Main Results: PBMs play a critical role in regulating neutrophil emigration in established murine LPS-induced lung injury. Gr1(hi) and Gr1(lo) PBM subpopulations contribute to this process. PBM depletion is associated with a significant reduction in measures of lung injury. The specificity of PBM depletion was demonstrated by replenishment studies in which the effects were reversed by systemic PBM infusion but not by systemic or local pulmonary infusion of mature macrophages or lymphocytes. Conclusions: These results suggest that PBMs, or the mechanisms by which they influence pulmonary neutrophil emigration, could represent therapeutic targets in established ALI.
    American Journal of Respiratory and Critical Care Medicine 07/2012; 186(6):514-24. DOI:10.1164/rccm.201112-2132OC · 13.00 Impact Factor
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    Andreas Alber · Sarah E M Howie · William A H Wallace · Nikhil Hirani ·
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    ABSTRACT: Acute tissue injury is often considered in the context of a wound. The host response to wounding is an orchestrated series of events, the fundamentals of which are preserved across all multicellular organisms. In the human lung, there are a myriad of causes of injury, but only a limited number of consequences: complete resolution, persistent and/or overwhelming inflammation, a combination of resolution/remodelling with fibrosis or progressive fibrosis. In all cases where complete resolution does not occur, there is the potential for significant ongoing morbidity and ultimately death through respiratory failure. In this review, we consider the elements of injury, resolution and repair as they occur in the lung. We specifically focus on the role of the macrophage, long considered to have a pivotal role in regulating the host response to injury and tissue repair.
    International Journal of Experimental Pathology 07/2012; 93(4):243-51. DOI:10.1111/j.1365-2613.2012.00833.x · 2.17 Impact Factor

  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012

  • Thorax 12/2011; 66(Suppl 4):A63-A63. DOI:10.1136/thoraxjnl-2011-201054b.137 · 8.29 Impact Factor
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    C A Parisinos · C W Lees · W A H Wallace · J Satsangi ·
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    ABSTRACT: Natalizumab is a humanised monoclonal antibody targeting the lymphocyte adhesion molecule a4 integrin, with proven efficacy in multiple sclerosis (MS) and Crohn's disease (CD). The development of sarcoidosis with extrapulmonary involvement is reported in two patients with refractory CD who had received maintenance therapy with natalizumab. This complication has not been previously reported. It is hypothesised that the effect of natalizumab in altering lymphocyte mucosal trafficking may underlie the development of sarcoidosis in these patients.
    Thorax 11/2011; 66(12):1109-10. DOI:10.1136/thx.2010.155762 · 8.29 Impact Factor
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    ABSTRACT: Large production volumes of zinc oxide nanoparticles (ZnONP) might be anticipated to pose risks, of accidental inhalation in occupational and even in consumer settings. Herein, we further investigated the pathological changes induced by ZnONP and their possible mechanism of action. Two doses of ZnONP (50 and 150 cm2/rat) were intratracheally instilled into the lungs of rats with assessments made at 24 h, 1 wk, and 4 wks after instillation to evaluate dose- and time-course responses. Assessments included bronchoalveolar lavage (BAL) fluid analysis, histological analysis, transmission electron microscopy, and IgE and IgA measurement in the serum and BAL fluid. To evaluate the mechanism, alternative ZnONP, ZnONP-free bronchoalveolar lavage exudate, and dissolved Zn2+ (92.5 μg/rat) were also instilled to rats. Acridine orange staining was utilized in macrophages in culture to evaluate the lysosomal membrane destabilization by NP. ZnONP induced eosinophilia, proliferation of airway epithelial cells, goblet cell hyperplasia, and pulmonary fibrosis. Bronchocentric interstitial pulmonary fibrosis at the chronic phase was associated with increased myofibroblast accumulation and transforming growth factor-β positivity. Serum IgE levels were up-regulated by ZnONP along with the eosinophilia whilst serum IgA levels were down-regulated by ZnONP. ZnONP are rapidly dissolved under acidic conditions (pH 4.5) whilst they remained intact around neutrality (pH 7.4). The instillation of dissolved Zn2+ into rat lungs showed similar pathologies (eg., eosinophilia, bronchocentric interstitial fibrosis) as were elicited by ZnONP. Lysosomal stability was decreased and cell death resulted following treatment of macrophages with ZnONP in vitro. We hypothesise that rapid, pH-dependent dissolution of ZnONP inside of phagosomes is the main cause of ZnONP-induced diverse progressive severe lung injuries.
    Particle and Fibre Toxicology 09/2011; 8(1):27. DOI:10.1186/1743-8977-8-27 · 7.11 Impact Factor
  • E C McLean · H Monaghan · D M Salter · WA Wallace ·
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    ABSTRACT: Morphological sub-classification of non-small cell carcinoma in small biopsy specimens presents difficulties for pathologists and recent advances in chemotherapy have resulted in increased pressure to more robustly differentiate between squamous carcinoma and adenocarcinoma. The results of audits examining classification of non-small cell lung carcinoma by pathologists working in a specialist team within a regional centre and the effect of introducing adjunct immunohistochemistry into the reporting pathway are presented. It is concluded that the use of a limited immunohistochemical panel substantially reduces the number of cases when a specific cell type cannot be identified or 'favoured' (34% to 6%) and that the classification obtained correlates well with that found in subsequent resection specimens. In addition the introduction of immunohistochemistry substantially reduces the variability in reporting practice between pathologists.
    Journal of clinical pathology 06/2011; 64(12):1136-8. DOI:10.1136/jcp.2011.090571 · 2.92 Impact Factor
  • W A H Wallace · D M Rassl ·
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    ABSTRACT: Endoscopic ultrasound-guided transbronchial or transoesophageal lymph node aspiration is increasingly used as a method of diagnosing nonsmall cell carcinoma. Data validating the accuracy of cell typing of nonsmall cell carcinoma using these cytological samples has not been assessed. 23 samples were identified in Edinburgh, UK and a further 25 in Cambridge, UK, with matching histological samples. The morphological cell type, as assessed on the cytological preparations and cell blocks, was recorded and immunohistochemical staining was performed, where possible, as an adjunct. The final cell type, as assessed by morphology with or without immunohistochemistry, was correlated with that reported in the paired histological samples. Cell blocks with tumour were available in 39 out of 48 cases. The accuracy of cell typing when no cell block was available was four out of nine cases. This increased to 25 out of 39 when a cell block was available, increasing to 33 out of 39 with the addition of immunohistochemistry. The overall accuracy of classification was 37 out of 48 cases. Accurate cell typing of nonsmall cell carcinomas can be performed using endoscopically derived fine-needle aspirates. The importance of obtaining sufficient material for the production of cell blocks is critical in allowing optimal assessment.
    European Respiratory Journal 03/2011; 38(4):911-7. DOI:10.1183/09031936.00176410 · 7.64 Impact Factor
  • I Wilkinson · K S Cuschieri · M Monaghan · D M Salter · W A Wallace ·
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    ABSTRACT: Cytological features suggesting herpes simplex virus (HSV) infection in samples obtained at bronchoscopy have been described only very rarely in routinely processed samples. We report four cases where evidence of HSV infection was identified morphologically in samples processed using thin-layer techniques, with polymerase chain reaction confirmation of the presence of virus in three cases. We suggest that the increased morphological clarity provided by this technique for processing these cytology samples may result in the morphological features of viral infection being seen more frequently. Pathologists reporting such samples need to be aware of this possibility in order to avoid potential misinterpretations. In addition, however, respiratory and intensive care physicians unused to receiving cytology reports indicating 'HSV infection' need to be aware that the significance is uncertain and in most cases it is likely to indicate the reactivation of a latent infection.
    The journal of the Royal College of Physicians of Edinburgh 03/2011; 41(1):26-8. DOI:10.4997/JRCPE.2011.107
  • Timothy D Andrews · Jan W Baird · William A H Wallace · David J Harrison ·
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    ABSTRACT: Therapeutic approaches to lung cancer are evolving, with personalized therapy, based on "molecular analysis" of tumors being developed. Given that approximately 90% of patients will not undergo surgery for their disease, an ability to apply these tests to small samples obtained at the time of initial pathological diagnosis is desirable. Studies in this area have produced variable results, and the minimum area of tumor tissue required for analysis has not been defined. Furthermore, such assays have not been widely applied to cytology specimens, which may be the only source of diagnostic material in many cases. Routinely processed biopsy and cytology specimens were microdissected to enrich for tumor cells, followed by RNA extraction using QIAGEN RNeasy kit and cDNA synthesis/reverse-transcriptase polymerase chain reaction for genes including beta-actin, ERCC-1, and RRM-1, according to standard laboratory protocols. Paired biopsy and resection specimens were similarly analyzed. As little as 1 mm² of tumor tissue, from a 10-μm-thick section, may be used to produce RNA suitable for analysis. RNA of adequate quality and quantity for analysis may be obtained from residual, routinely processed biopsy and cytology specimens. There is good correlation between the result obtained on the tumor biopsy specimen and paired blocks from the surgical resection with respect to clinical decision making. Routinely processed clinical diagnostic samples provide a suitable source of RNA for polymerase chain reaction-based molecular analyses, potentially providing personalized medicine to all lung cancer patients.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2011; 6(5):884-8. DOI:10.1097/JTO.0b013e3182106d48 · 5.28 Impact Factor
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    ABSTRACT: A proportion of human pulmonary adenocarcinomas has been shown previously to express an antigen related to the Gag protein of a betaretrovirus, Jaagsiekte sheep retrovirus, that causes ovine pulmonary adenocarcinoma. To investigate further the hypothesis that a retrovirus might be present in human lung adenocarcinoma, we examined specimens from patients with lung cancer for evidence of retroviral infection by immunohistochemistry, reverse transcriptase-polymerase chain reaction, immunoblotting and cDNA library screening. Thirty-eight percent of the tumor samples analyzed were positive by immunohistochemistry for Gag-related antigen of Jaagsiekte sheep retrovirus. However, this antigen was not detected by immunoblotting using the same antiserum. In addition, plasma samples from the patients did not contain antibodies reacting with Gag proteins from Jaagsiekte sheep retrovirus or other betaretroviruses on immunoblots. Reverse transcriptase-polymerase chain reaction identified the expression of endogenous betaretroviruses in tumor tissue and in normal lung tissue, but no specific provirus was associated with tumor. Expression library screening did not identify the Gag-reactive antigen. This study has confirmed the expression of a Jaagsiekte sheep retrovirus Gag-related antigen in some human lung tumors but additional evidence of betaretroviral infection was not obtained. While these data do not rule out a role for a retrovirus in human pulmonary adenocarcinomas, they suggest that, if such a virus is present, it is unrelated to known betaretroviruses.
    Human pathology 11/2010; 41(11):1631-40. DOI:10.1016/j.humpath.2010.05.013 · 2.77 Impact Factor
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    Paul M Fitch · Sarah E M Howie · William A H Wallace ·
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    ABSTRACT: Idiopathic interstitial lung diseases (iILDs) are characterized by inflammation, hyperplasia of Type-II alveolar epithelial cells (AECs) and lung remodelling often with progressive fibrosis. It remains unclear which signals initiate iILD and/or maintain the disease processes. Using real-time RT-PCR and immunohistochemistry on archival biopsies of three patterns of iILD (usual interstitial pneumonitis/UIP, non-specific interstitial pneumonitis/NSIP and cryptogenic organizing pneumonia/COP) we investigated whether hedgehog signalling (previously associated with lung damage and repair) was functional and whether the damage associated extracellular matrix protein tenascin-C was present in activated Type-II AECs in all three iILDs. Using tissue culture, protein and mRNA detection we also determined how two signals (oxidative damage and TGF-β) associated with iILD pathogenesis affected Sonic hedgehog (SHH) and tenascin-C production by a Type-II AEC cell line. We report that SHH pathway and tenascin-C mRNA and proteins were found in UIP, NSIP and COP. SHH signalling was most active at sites of immature organizing fibrous tissue (fibroblastic foci) in UIP. In vitro Type-II AECs constitutively secrete SHH but not tenascin-C. Oxidative injury stimulated SHH release whereas TGF-β inhibited it. TGF-β and oxidative damage both upregulated tenascin-C mRNA but only TGF-β induced synthesis and release of a distinct protein isoform. SHH signalling is active in Type-II AECs from three types of ILD and all three express tenascin-C.
    International Journal of Experimental Pathology 10/2010; 92(1):8-17. DOI:10.1111/j.1365-2613.2010.00743.x · 2.17 Impact Factor
  • T.D. Andrews · W.A.H. Wallace ·
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    ABSTRACT: Malignant diseases of the lungs and pleura are common causes of morbidity and mortality throughout the developed world. Determining the appropriate treatment strategies for an individual patient requires a multidisciplinary approach integrating input from many disciplines including pathology. In this overview, we discuss diagnosis of lung and pleural malignancy from the pathologist's perspective, placing particular emphasis on methods available to obtain material for pathological assessment, and their implications for diagnosis and provision of information to guide patient management.
    Clinical Oncology 06/2009; 21(6):451-63. DOI:10.1016/j.clon.2009.03.006 · 3.40 Impact Factor

Publication Stats

3k Citations
448.63 Total Impact Points


  • 1991-2014
    • The University of Edinburgh
      • • Queen's Medical Research Institute
      • • Centre for Molecular Medicine
      • • Division of Pathology
      • • MRC Centre for Inflammation Research
      Edinburgh, Scotland, United Kingdom
  • 2009
    • University of Oxford
      Oxford, England, United Kingdom
  • 2001-2003
    • The University of Sheffield
      Sheffield, England, United Kingdom
  • 2001-2002
    • Sheffield Teaching Hospitals NHS Foundation Trust
      Sheffield, England, United Kingdom