R C Rees

Nottingham Trent University, Nottigham, England, United Kingdom

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Publications (248)785.08 Total impact

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    ABSTRACT: Under normal conditions the detachment of anchorage-dependant cells from their extracellular matrix typically induces programmed cell death which is mediated through a pathway referred to as anoikis. However, a resistance to anoikis in cancer enables the migration of cells from the primary tumour and the establishment of aggressive metastatic disease. Although cancer cell aggregation is known to be an important mechanism within anoikis resistance, research into the underlying mechanisms that govern this process remain problematic as commercially available tissue culture material can only sustain 2D monolayer or 3D aggregate/spheroid cultures. This necessitates the development of a system that can accommodate for cancer cell aggregation–disaggregation as a single dynamic process, without the disruption of passaging cells between alternate substrates. This study describes a procedure for modifying tissue culture polystyrene (TCP) to produce a fluoro-silica (FS) surface which preferentially promotes the deposition of a distinct profile of proteins/factors from serum which mediate the transient aggregation of human breast cancer cell lines. This modified surface therefore provides an experimental platform for better understanding cancer cell aggregation–disaggregation events in vitro, and their influence on the establishment of metastatic disease in patients with cancer.
    Biomater. Sci. 07/2014;
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    ABSTRACT: Background:HAGE protein is a known immunogenic cancer-specific antigen.Methods:The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated.Results:Eight percent of patients with EP-BC exhibited high HAGE expression (HAGE+) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGE+expression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+residual disease (P=0.0003).Conclusions:This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC.British Journal of Cancer advance online publication, 22 April 2014; doi:10.1038/bjc.2014.168 www.bjcancer.com.
    British Journal of Cancer 04/2014; · 5.08 Impact Factor
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    ABSTRACT: A stage III ovarian cancer diagnosis yields a 22% 5-year survival rate, this applies to over half of the 7000 new cases diagnosed each year in the UK. Stratification of patients with this heterogeneous disease, based on active molecular pathways in their cancer, would aid a targeted treatment and improve prognosis. Hundreds of genes have been significantly associated with ovarian cancer, few have yet been verified. Exploration of published microarray data sets using Artificial Neural Networks confirmed the robustness of PRELP as a biomarker for survival time from stage III ovarian cancer, and generated a new panel of 44 genes that significantly predicted survival length of a blind valida-tion set (p=0.00073).
    Proceedings of the international work-conference on Bioinformatics and Biomedical Engineering (IWBBIO 2014), Granada Spain; 04/2014
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    ABSTRACT: The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5+ malignant melanoma-initiating cells (ABCB5+ MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro. Finally, using a stem cell proliferation assay and tumour xenotransplantation assay in non-obese diabetic/severe combined immunodeficiency mice, we show that HAGE promotes MMICs-dependent tumour initiation and tumour growth by preventing the anti-proliferative effects of interferon-α (IFNα). Our results suggest that the helicase HAGE has a key role in the resistance of ABCB5+ MMICs to IFNα treatment and that cancer therapies targeting HAGE may have broad implications for the treatment of malignant melanoma.
    Cell Death & Disease 01/2014; 5:e1061. · 6.04 Impact Factor
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    ABSTRACT: Oestrogen receptor (ER) positive (luminal) tumours account for the largest proportion of females with breast cancer. Theirs is a heterogeneous disease presenting clinical challenges in managing their treatment. Three main biological luminal groups have been identified but clinically these can be distilled into two prognostic groups in which Luminal A are accorded good prognosis and Luminal B correlate with poor prognosis. Further biomarkers are needed to attain classification consensus. Machine learning approaches like Artificial Neural Networks (ANNs) have been used for classification and identification of biomarkers in breast cancer using high throughput data. In this study, we have used an artificial neural network (ANN) approach to identify DACH1 as a candidate luminal marker and its role in predicting clinical outcome in breast cancer is assessed. A reiterative ANN approach incorporating a network inferencing algorithm was used to identify ER-associated biomarkers in a publically available cDNA microarray dataset. DACH1 was identified in having a strong influence on ER associated markers and a positive association with ER. Its clinical relevance in predicting breast cancer specific survival was investigated by statistically assessing protein expression levels after immunohistochemistry in a series of unselected breast cancers, formatted as a tissue microarray. Strong nuclear DACH1 staining is more prevalent in tubular and lobular breast cancer. Its expression correlated with ER-alpha positive tumours expressing PgR, epithelial cytokeratins (CK)18/19 and 'luminal-like' markers of good prognosis including FOXA1 and RERG (p<0.05). DACH1 is increased in patients showing longer cancer specific survival and disease free interval and reduced metastasis formation (p<0.001). Nuclear DACH1 showed a negative association with markers of aggressive growth and poor prognosis. Nuclear DACH1 expression appears to be a Luminal A biomarker predictive of good prognosis, but is not independent of clinical stage, tumour size, NPI status or systemic therapy.
    PLoS ONE 01/2014; 9(1):e84428. · 3.53 Impact Factor
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    ABSTRACT: Treatment options for patients with advanced prostate cancer remain limited and rarely curative. Prostatic acid phosphatase (PAP) is a prostate-specific protein over-expressed in 95% of prostate tumours. An FDA-approved vaccine for the treatment of advanced prostate disease, PROVENGE® (sipuleucel-T), has been shown to prolong survival, however the precise sequence of the PAP protein responsible for the outcome is unknown. As the PAP antigen is one of the very few prostate-specific antigens for which there is a rodent equivalent with high homology, pre-clinical studies using PAP have the potential to be directly relevant to clinical setting. Here we show three PAP epitopes naturally processed and presented in the context of HHDII/DR1 (114-128, 299-313, and 230-244). The PAP-114-128 epitope elicits CD4(+) and CD8(+) T-cell-specific responses in C57BL/6 mice. Furthermore, when immunised in a DNA vector format (ImmunoBody®), PAP-114-128 prevents and reduces the growth of TRAMP-C1 prostate cancer cell-derived tumours in both prophylactic and therapeutic settings. This anti-tumour effect is associated with infiltration of CD8(+) tumour-infiltrating lymphocytes (TILs) and the generation of high avidity T cells secreting elevated levels of IFN-γ. PAP-114-128 therefore appears to be a highly relevant peptide on which to base vaccines for the treatment of prostate cancer. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 12/2013; · 4.97 Impact Factor
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    ABSTRACT: The effect of alterations in virulence and transformation by long term in vitro culture of L. mexicana promastigotes on infectivity and immune responses was investigated. Fresh parasite cultures harvested from Balb/c mice were passaged 20 times in vitro. Infectivity was decreased and was completely avirulent after 20 passages. The qPCR results showed a down regulation of GP63, LPG2, CPC, CPB2, CPB2.8, CHT1, LACK and LDCEN3 genes after passage 7 concomitant with a reduced and absence of infectivity by passages 7 and 20, respectively. Parasites at passages 1 and 20 are referred to as virulent and avirulent, respectively. The growth of avirulent and virulent parasite was affected by conditioned media derived from macrophages or monocytes infected with parasites for 2 hours. Giemsa staining showed the failure of avirulent but not virulent parasites to transform to the amastigote stage in infected host cells. with both virulent and avirulent modulating the expression of CCL-22, Tgad51, Cox2, IL-1, IL-10, TGF-β, TNF-α, Rab7, Rab9 and A2 genes; virulent but not avirulent L. mexicana significantly up regulated Th2 associated cytokines, but down regulated Rab7and Rab9 gene expression. In conclusion, a model for L. mexicana is reported, which is of potential value in studying host- parasite interaction. This article is protected by copyright. All rights reserved.
    Parasite Immunology 07/2013; · 2.21 Impact Factor
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    ABSTRACT: BACKGROUND: Conditions for maintaining hematopoietic progenitor cells (HPCs) before cryopreservation remain controversial. An understanding of the impact of time and temperature during nonfrozen storage can contribute to the maintenance of the quality of products, improving transplantation outcomes. The objective of this study was to determine the influence on cell potency of thawed products from three sources of HPCs after prolonged storage at different temperatures before cryopreservation. STUDY DESIGN AND METHODS: Viable cell counts by flow cytometry and colony-forming unit (CFU) recoveries were assessed on cord blood (CB), mobilized peripheral blood stem cell (PBSC), and bone marrow (BM) samples over 72 hours using two different storage conditions, refrigerated (4-8°C) or room temperature (19-22°C). To determine the effects of delayed freezing on progenitor recoveries, paired samples were evaluated before and after cryopreservation. RESULTS: All samples maintained at refrigerated temperatures resulted in higher recoveries than those at room temperature in all variables assessed. Specifically, when assessing for CFU yields after thawing, the impact of time on BM resulted in a significant loss as soon as 24 hours (n = 10, 36.4 ± 28.0%, p = 0.003). This decrease was also observed for PBSCs and CB but at 48 hours of fresh storage (PBSCs n = 11, 32.7 ± 26.2%, p = 0.006; CB n = 10, 39.6 ± 26.4%, p = 0.001). CONCLUSION: Our data suggest that HPC products are better maintained at refrigerated temperatures before cryopreservation. Delaying cryopreservation should be minimized to avoid significant losses in cell potency.
    Transfusion 12/2012; · 3.53 Impact Factor
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    ABSTRACT: Breast cancer is a heterogeneous and complex disease. Although the use of tumor biomarkers has improved individualized breast cancer care, i.e., assessment of risk, diagnosis, prognosis, and prediction of treatment outcome, new markers are required to further improve patient clinical management. In the present study, a search for novel breast cancer-associated genes was performed by mining the UniGene database for expressed sequence tags (ESTs) originating from human normal breast, breast cancer tissue, or breast cancer cell lines. Two hundred and twenty-eight distinct breast-associated UniGene Clusters (BUC1-228) matched the search criteria. Four BUC ESTs (BUC6, BUC9, BUC10, and BUC11) were subsequently selected for extensive in silico database searches, and in vitro analyses through sequencing and RT-PCR based assays on well-characterized cell lines and tissues of normal and cancerous origin. BUC6, BUC9, BUC10, and BUC11 are clustered on 10p11.21-12.1 and showed no homology to any known RNAs. Overall, expression of the four BUC transcripts was high in normal breast and testis tissue, and in some breast cancers; in contrast, BUC was low in other normal tissues, peripheral blood mononuclear cells (PBMCs), and other cancer cell lines. Results to-date suggest that BUC11 and BUC9 translate to protein and BUC11 cytoplasmic and nuclear protein expression was detected in a large cohort of breast cancer samples using immunohistochemistry. This study demonstrates the discovery and expression analysis of a tissue-restricted novel transcript set which is strongly expressed in breast tissue and their application as clinical cancer biomarkers clearly warrants further investigation. © 2012 Wiley Periodicals, Inc..
    Genes Chromosomes and Cancer 12/2012; · 3.55 Impact Factor
  • Robert C. Rees
    Cancer Immunology and Immunotherapy 09/2012; 61(11). · 3.64 Impact Factor
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    ABSTRACT: Malignant melanoma-initiating cells (MMIC) are a subpopulation of cells responsible for melanoma tumor growth and progression. They are defined by the expression of the ATP-binding cassette (ABC) subfamily B member 5 (ABCB5). Here, we identified a critical role for the DEAD-box helicase antigen (HAGE) in ABCB5+ MMIC-dependent tumorigenesis and show that HAGE-specific inactivation inhibits melanoma tumor growth mediated by this tumor-initiating population. Knockdown of HAGE led to a significant decrease in RAS protein expression with a concomitant decrease in activation of the AKT and ERK signaling pathways implicated to play an important role in melanoma progression. To confirm that the reduction in NRAS (Neuroblastoma RAS) expression was dependent on the HAGE helicase activity, we showed that NRAS, effectively silenced by siRNA, could be rescued by reintroduction of HAGE in cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes NRAS unwinding in vitro. We also observed using tumor transplantation in Non-obese diabetic/severe combined immunodeficiency mice that the HAGE knockdown in a ABCB5+ melanoma cell line displayed a significant decrease in tumor growth and compared with the control. Our results suggest that the helicase HAGE is required for ABCB5+ MMIC-dependent tumor growth through promoting RAS protein expression and that cancer therapies targeting HAGE helicase may have broad applications for treating malignant melanoma and potentially other cancer types.
    Journal of Biological Chemistry 03/2012; 287(17):13633-43. · 4.65 Impact Factor
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    H Rezvan, R Rees, Sa Ali
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    ABSTRACT: Leishmania is an intracellular parasite infecting humans and many wild and domestic animals. Recent studies have suggested an important role for cytotoxic T cells against Leishmania. Peptide-based vaccines targeting short sequences derived from known immunogenic proteins have been shown to elicit cellular immune responses against disparate pathogens. We predicted four HLA-A2 peptides derived from L. mexican/major gp63 and tested these in HHD II mice, as well as four peptides for mouse MHC class I from the same proteins tested in BALB/ mice. The results revealed immunogenicity for three of the four peptides predicted for HLA-A2. Immunisation with these peptides, along with IFA, induced CTL responses detected by standard 4-hour cytotoxicity assay and significantly upregulated the production of IFN-γ. When HHDII mice were injected IM with L. mexicana gp63 cDNA and splenocytes were restimulated with blasts loaded with the immunogenic peptides, two of the peptides were able to induce significant level of IFN-γ detected by ELISA. None of the peptides predicted for Balb/c mouse MHC class I elicited CTL activity or significantly upregulated the IFN-γ. The results may help in developing a peptide-based vaccine, which can be applied alone or in combination with drugs against Leishmania.
    Iranian Journal of Parasitology 01/2012; 7(4):27-40. · 0.33 Impact Factor
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    ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.
    Journal of Translational Medicine 12/2011; 9(1):214. · 3.46 Impact Factor
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    H Rezvan, R Rees, Sa Ali
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    ABSTRACT: Leishmaniasis is a worldwide disease prevalent in tropical and sub tropical countries. Many attempts have been made and different strategies have been approached to develop a potent vaccine against Leishmania. DNA immunisation is a method, which is shown to be effective in Leishmania vaccination. Leishmania Soluble Antigen (SLA) has also recently been used Leishmania vaccination. The immunity generated by SLA and L. mexicana gp63 cDNA was compared in groups of 6 mice, which were statistically analysed by student t- test with the P-value of 0.05. SLA was administered by two different methods; intramuscular injection and injection of dendritic cells (DCs) loaded with SLA. L. mexicana gp63 cDNA was administered by the gene gun. Immunisation of BALB/c mice with L. mexicana gp63 resulted in high levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity, which were accompanied with protection induced by the immunisation against L. mexicana infection. In contrast, administration of SLA, produced a mixed Th1/Th2-type immune responses as well as a high level of CTL activity but did not protect mice from the infection. The results indicate higher protection by DNA immunisation using L. mexicana gp63 cDNA compared to SLA, which is accompanied by a high level of Th1 immune response. However, the CTL activity does not necessarily correlate with the protection induced by the vaccine. Also, gene gun immunisation is a potential approach in Leishmania vaccination. These findings would be helpful in opening new windows in Leishmania vaccine research.
    Iranian journal of parasitology. 12/2011; 6(4):60-75.
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    ABSTRACT: The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process.
    Amino Acids 11/2011; · 3.91 Impact Factor
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    ABSTRACT: We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically-diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) patients (n = 10) were used to obtain proteomic profiles, followed by bioinformatic analysis that generated a set of potential biomarkers in CSF samples that could discriminate AD cases from controls. The identity of the biomarker ions was determined using mass spectroscopy. The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). When this model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The panel were identified, in order of predictive ability, as SPARC-like 1 protein, fibrinogen alpha chain precursor, amyloid-β, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin. The 7 ion ANN model was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort which was from postmortem confirmed AD patients (n = 17).
    Journal of Alzheimer's disease: JAD 11/2011; 28(3):625-36. · 4.17 Impact Factor
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    ABSTRACT: ABSTRACT: Raw spectral data from matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) with MS profiling techniques usually contains complex information not readily providing biological insight into disease. The association of identified features within raw data to a known peptide is extremely difficult. Data preprocessing to remove uncertainty characteristics in the data is normally required before performing any further analysis. This study proposes an alternative yet simple solution to preprocess raw MALDI-TOF-MS data for identification of candidate marker ions. Two in-house MALDI-TOF-MS data sets from two different sample sources (melanoma serum and cord blood plasma) are used in our study. Raw MS spectral profiles were preprocessed using the proposed approach to identify peak regions in the spectra. The preprocessed data was then analysed using bespoke machine learning algorithms for data reduction and ion selection. Using the selected ions, an ANN-based predictive model was constructed to examine the predictive power of these ions for classification. Our model identified 10 candidate marker ions for both data sets. These ion panels achieved over 90% classification accuracy on blind validation data. Receiver operating characteristics analysis was performed and the area under the curve for melanoma and cord blood classifiers was 0.991 and 0.986, respectively. The results suggest that our data preprocessing technique removes unwanted characteristics of the raw data, while preserving the predictive components of the data. Ion identification analysis can be carried out using MALDI-TOF-MS data with the proposed data preprocessing technique coupled with bespoke algorithms for data reduction and ion selection.
    Clinical Proteomics 09/2011; 8:14.
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    ABSTRACT: • To define the expression pattern of the tumour antigen T21 at the protein level in prostate tissues, prostate cell lines and a panel of normal tissues. • To correlate the expression pattern of T21 in prostate cancer with clinical parameters. • Tissue samples were collected from 79 patients presenting at clinic with either prostate cancer (63 patients) or benign prostatic hyperplasia (BPH, 16 patients). • A tissue microarray (TMA) was constructed from 44 of the prostate cancer tissues and areas of benign disease (43 patients) from these tissues were also included on the TMA. The remaining tissues (prostate cancer 19 patients and BPH 16 patients) were mounted fresh frozen onto cork boards and sectioned. • Full ethical approval was granted for all aspects of the study and informed patient consent was taken before tissue collection. • Immunohistochemistry was used on the prostate tumour TMA, the normal tissue TMA and the fresh-frozen prostate tissues. Fluorescent microscopy and flow cytometry was performed on prostate cell lines. • Expression of T21 was highly restricted within normal tissues with only the stomach, ovary, breast and prostate having detectable T21 expression. • T21 was significantly over-expressed in prostate cancer glands compared with benign tissue and was present in >80% of the malignant specimens analysed. • Increased expression was positively correlated to pathological stage of prostate tumours. • Additionally, T21 was associated with Gleason grade and prostate-specific antigen recurrence, although statistical significance was not reached in this restricted cohort of patients. • Taken together these results show that T21 is a potential new biomarker for advanced disease and that elevated levels of T21 appear relevant to prostate cancer development.
    BJU International 08/2011; 109(5):796-805. · 3.05 Impact Factor
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    ABSTRACT: Cancer stem cells have been implicated in a number of solid malignancies including prostate cancer. In the case of localised prostate cancer, patients are often treated with surgery (radical prostatectomy) and/or radiotherapy. However, disease recurrence is an issue in about 30% of patients, who will then go on to receive hormone ablation therapy. Hormone ablation therapy is often palliative in a vast proportion of individuals, and for hormone-refractory patients, there are several immunotherapies targeting a number of prostate tumour antigens which are currently in development. However, clinical responses in this setting are inconsistent, and it is believed that the failure to achieve full and permanent tumour eradication is due to a small, resistant population of cells known as 'cancer stem cells' (CSCs). The stochastic and clonal evolution models are among several models used to describe cancer development. The general consensus is that cancer may arise in any cell as a result of genetic mutations in oncogenes and tumour suppressor genes, which consequently result in uncontrolled cell growth. The cancer stem cell theory, however, challenges previous opinion and proposes that like normal tissues, tumours are hierarchical and only the rare subpopulation of cells at the top of the hierarchy possess the biological properties required to initiate tumourigenesis. Furthermore, where most cancer models infer that every cell within a tumour is equally malignant, i.e. equally capable of reconstituting new tumours, the cancer stem cell theory suggests that only the rare cancer stem cell component possess tumour-initiating capabilities. Hence, according to this model, cancer stem cells are implicated in both tumour initiation and progression. In recent years, the role of epithelial--mesenchymal transition (EMT) in the advancement of prostate cancer has become apparent. Therefore, CSCs and EMT are both likely to play critical roles in prostate cancer tumourigenesis. This review summarises the current immunotherapeutic strategies targeting prostate tumour antigens taking into account the need to consider treatments that target cancer stem cells and cells involved in epithelial--mesenchymal transition.
    Cancer Immunology and Immunotherapy 06/2011; 60(8):1181-93. · 3.64 Impact Factor
  • Adam J Linley, Murrium Ahmad, Robert C Rees
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    ABSTRACT: Since their discovery, tumour-associated antigens (TAA) have provided highly inviting targets for cancer therapy, especially immunotherapy. Evidence now points to their involvement in the malignant phenotype of transformed cells and heightens their importance for being targeted by different treatments. TAA vary in their nature and pattern of expression and this influences the way therapy is directed towards them. While large numbers of these antigens have been isolated from solid tumours, fewer are linked with haematological malignancies. Those TAA found in this latter group of cancers, referred to as leukaemia-associated antigens (LAA), also appear to have significant potential for promoting the malignant phenotype and have been described in detail in terms of expression and therapy. Interestingly, the action of some of LAA in blood cancers, which are stem cell derived, could act as model for solid tumours, which are increasingly thought to be also derived from a cancer stem cell origin. In this review, TAA and their use in immunotherapy will be discussed. The nature and expression of these antigens will be described together with the events that provide tumours, including haematological cancers, with the ability to avoid immune deletion.
    International journal of hematology 03/2011; 93(3):263-73. · 1.17 Impact Factor

Publication Stats

4k Citations
785.08 Total Impact Points


  • 1997–2014
    • Nottingham Trent University
      • School of Science and Technology
      Nottigham, England, United Kingdom
  • 2008
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1973–2008
    • The University of Sheffield
      • • Medical School
      • • Institute for Cancer Studies
      Sheffield, England, United Kingdom
  • 2004–2006
    • University of Nottingham
      • Division of Pre-Clinical Oncology
      Nottingham, ENG, United Kingdom
  • 2003
    • University of Tuebingen
      • Department of Internal Medicine
      Tübingen, Baden-Wuerttemberg, Germany
  • 2002
    • University of Latvia
      • Biomedical Research and Study Centre
      Riga, Riga, Latvia
  • 1995–1997
    • National Institute of Arthritis and Musculoskeletal and Skin Diseases
      Maryland, United States
  • 1990
    • MRC Clinical Sciences Centre
      London Borough of Harrow, England, United Kingdom