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Califano R.,Christie NHS Foundation Trust | Landi L.,Instituto Toscano Tumori | Cappuzzo F.,Instituto Toscano Tumori
Drugs | Year: 2012

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, caused by the presence of different clinically relevant molecular subtypes. Genetic mutations are emerging as potential biomarkers of response and treatment selection in patients with NSCLC. Over the past few years, activating mutations of epidermal growth factor receptor (EGFR) have been recognized as the most important predictor of response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib and also as a favourable prognostic factor. The RAS genes, including H-RAS, K-RAS and N-RAS, encode a family of proteins regulating cell growth, differentiation and apoptosis. Mutations in the K-RAS gene, mainly in codons 12 and 13, have been found in 20-30% of NSCLC tumor samples and occur most commonly, but not exclusively, in adenocarcinoma histology and in heavy smokers. In NSCLC, the presence of K-RAS mutations has generally been considered to be associated with worse prognosis and resistance to systemic therapy in the adjuvant as well as the metastatic setting. In early stage NSCLC, the prognostic role of K-RAS mutations has been evaluated in several studies without definitive conclusion. On the other hand, in advanced NSCLC, the presence of K-RAS mutations identifies a subgroup of patients who do not respond to EGFR-TKI therapy but, at the same time, a positive survival effect from EGFR-TKIs cannot be excluded in these patients. Similarly, K-RAS mutational status does not predict benefit from the anti-EGFR monoclonal antibody cetuximab, high-lighting the biological difference between lung cancer and colorectal cancer. As a result of the lack of conclusive data, K-RAS mutations do not represent a validated biomarker for the negative selection of patients who are candidates for anti-EGFR therapy. The aim of this article is to review and discuss the data on the prognostic and predictive value of K-RAS mutations in NSCLC. Adis © 2012 Springer International Publishing AG. All rights reserved.


News Article | December 15, 2016
Site: www.eurekalert.org

Manchester is set to receive a major cash injection from Cancer Research UK. The charity plans to invest around £39 million over the next five years into the Cancer Research UK Manchester Centre, a partnership between Cancer Research UK, The University of Manchester and the Christie NHS Foundation Trust. The grant will fund ground-breaking work as part of the development of a unique chain of cutting-edge research hubs around the UK focusing on translational research. A further £2.75 million investment is planned for the Manchester Experimental Cancer Medicine Centre, from Cancer Research UK and the National Institute for Health Research. Funding will also support training of the next generation of cancer researchers - including 45 PhD students - to ensure the brightest scientists are attracted and supported in their career in cancer research. Professor Nic Jones, Director of the Cancer Research UK Manchester Centre, based at The University of Manchester, said: "This funding award is fantastic news for the city and for our Centre and we are especially honoured to be selected as a Major Centre. The award represents a critical investment in the research infrastructure that will equip us with the tools needed to advance the understanding and treatment of cancer. "This investment will boost efforts to transform treatments through the development of new approaches in personalised medicine. "Our aim is to transform cancer treatment by optimising the delivery of radiotherapy, and by developing new approaches to treatment where decisions are guided by the specific characteristics of a patient's tumour. This includes studying and characterising blood samples taken from patients at diagnosis and throughout their journey. We do this to look for markers released from the tumour that can provide key information to help doctors pick the right drug for the right patient. "We also aim to detect early warning signs of cancer to provide earlier diagnosis, or to give a clear indication if a patient's cancer has come back after treatment." Manchester has been chosen, by an international panel of experts, as one of just 13 locations to secure funding in the latest review of the Cancer Research UK Centres network of excellence and one of two to receive major centre status - the highest award. These research centres draw together world class research and medical expertise to provide the best possible results for cancer patients - getting cutting edge discoveries from the laboratory to patients and learning as much as possible from them to initiate new research ideas and programmes. Additionally, the panel chose Manchester as one of 18 Experimental Cancer Medicine Centres (ECMCs). The ECMCs aim to bring better treatments faster to cancer patients in the UK through both the adult and children's network of Centres. They are hubs where promising cancer treatments - including small molecule drugs, surgery, immunotherapy, and vaccines - are safely tested through clinical trials. These Centres help give people with cancer access to cutting-edge treatments by testing new ways of detecting and monitoring the disease and how it responds to treatment. Every year, 41,700 of people are diagnosed with cancer in the North West. Sir Harpal Kumar, chief executive at Cancer Research UK, said: "This is an exciting time for cancer research. "Cancer Research UK's projections are that we will reach more than 500,000 new diagnoses of cancer a year in the UK by 2035. By that time, our goal is that three in four people will survive their cancer. Funding these Centres, like the ones in Manchester, is one of the charity's most important strategic priorities and one which will help us reach this ambition. This huge investment is only made possible through generous donations from the public and the tireless fundraising of our supporters." Professor Dame Nancy Rothwell, President and Vice-Chancellor of The University of Manchester said: "Manchester is now one of the world's leading research centres for cancer and this funding represents an important step forward in finding new treatments, carrying out more trials and training the brightest minds to continue this work. Working with our partners at The Christie and Cancer Research UK gives us great strength, bringing together researchers and doctors to make new discoveries that benefit of people here and around the world." Roger Spencer, Chief Executive at The Christie said: "This investment in research and development of new cancer medicines will be vital to the Manchester partnership achieving its ambition to become one of the largest centres for experimental cancer medicine trials worldwide. "Patients are at the heart of everything we do at The Christie and this funding will enable us to deliver personalised treatments to even more patients. This in turn will translate into better outcomes for our patients." Professor Andrew Hughes, Joint Lead at Manchester's Experimental Cancer Medicine Centre and Strategic Director of the Experimental Cancer Medicine Team at The Christie, said: "This funding boost will enable us to deliver more novel clinical trials right here in Manchester - this will mean cancer patients from the North West will have access to new pioneering drugs as quickly as possible across all major cancer types. "Specifically, the funding will be used to treat an additional 200 patients per year with the goal that by 2020 over 500 patients each year will have access to pioneering new drugs in experimental cancer medicine clinical trials." Nicola Blackwood, Minister for Public Health and Innovation, said: "We want to lead the world in fighting cancer. The work of Experimental Cancer Medicine Centres is crucial in this fight. This next phase of funding from the National Institute for Health Research will help our world-leading researchers to continue to make new discoveries. "The collaboration between universities, NHS Trusts and the research community is a key reason these centres are successful, and illustrates why the UK is the best place in the world to be a researcher. "I hope this funding will ultimately lead to more life-saving treatments for patients."


Monaghan P.J.,Christie NHS Foundation Trust | Keevil B.G.,University of Manchester | Trainer P.J.,Christie NHS Foundation Trust
Reviews in Endocrine and Metabolic Disorders | Year: 2013

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is becoming a standard analytical tool in the clinical laboratory for the measurement of small molecules, including steroid hormones. Endocrinologists are coming to acknowledge the superior quality of measurement that is achievable by LC-MS/MS through the enhanced analytical specificity and high sensitivity that this technique offers over conventional immunoassay (IA) methodologies. Additionally, LC-MS/MS overcomes many of the problems encountered in immunoassays, such as anti-reagent antibody interferences and cross-reactivity with structurally related compounds. The potential benefits of applying LC-MS/MS for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis are beginning to be realised. This review critically evaluates recent developments in the application of LC-MS/MS for measurement of glucocorticoids and mineralocorticoids towards the diagnosis and management of HPA axis disorders and aims to address the current unmet need in this expanding field of endocrinology for which future studies into the potential applications of LC-MS/MS should be directed. © 2013 Springer Science+Business Media New York.


Hill S.,Christie NHS Foundation Trust
British Journal of Nursing | Year: 2015

Implanted ports (IPs) are an essential device for many patients who require long-term vascular access. IPs offer some advantages over other central venous access devices, such as lifestyle, body image benefits and lower infection rates. A typical implantation site for a port is the anterior chest wall. For some patients with breast cancer who have metastatic chest wall disease this site may lead to problems with the function of the device if disease spreads to the port site. One option for this patient group is to place the implanted port over the trapezius muscle. This article discusses six patients, all of whom had metastatic breast cancer with some degree of subcutaneous disease on the anterior chest wall. Three patients had received trapezius port placements and three had anterior chest wall placements. A retrospective review of the patients' medical records was undertaken from the time of insertion until removal or until the patient died. The anterior chest wall group of patients had their devices in for an average of 368 days vs 214 in the trapezius group. The total complications were higher in the anterior chest wall group (7 vs 2 in the trapezius group). Disease spread to two of the devices in the anterior chest wall group meaning the devices could no longer be used. The trapezius approach appears to be a safe and a reliable form of vascular access and may offer fewer complications than the traditional method of anterior chest wall placement when standard anterior chest wall approach is not suitable.


Bhaskar A.K.,Christie NHS Foundation Trust
Current Opinion in Supportive and Palliative Care | Year: 2012

Purpose of review Interventional techniques were the mainstay for cancer pain management before the WHO ladder and opioids were freely available. The three-step WHO ladder has its limitations, and cancer pain is often under treated. Advances in treatment options mean that cancer patients are living longer and pain interventions may have a role to play even early in the cancer diagnosis for better quality of analgesia. The role of high doses of opioids in pain management is also currently under scrutiny. Recent findings Recent advances in intrathecal analgesia, radiofrequency techniques, both in tumour ablation and neurotomies, are being widely used for palliation. Vertebroplasty techniques have been used not only for pain relief, but also for stabilization. Improved imaging and thoracoscopic techniques have made coeliac plexus and splanchnic blockade safer and more efficacious. There has been recent interest in percutaneous cordotomy with newer techniques using computed tomography/MRI and endoscopy guidance. Percutaneous electrical nerve stimulation and 8% capsaicin patches have been successfully used for managing neuropathic pain in cancer. Summary Interventions form an integral part in providing pain relief in complex cancer pains. Oncologists and palliative care physicians are to be educated on the usefulness and timing of interventions in the management of complex cancer pain. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Nonaka D.,Christie NHS Foundation Trust
American Journal of Surgical Pathology | Year: 2011

Glial cells missing 2 (Gcm2) is a master regulatory gene of parathyroid gland development, and it is exclusively expressed in the parathyroid gland. Diagnostic application of anti-Gcm2 antibody has not been reported yet. In this study, a total of 58 cases of parathyroid lesions including 40 adenomas, 2 atypical adenomas, 2 carcinomas, 9 hyperplastic lesions, 4 parathyroid cysts, and 1 case of recurrent hyperplasia of an autograft gland were stained with anti-Gcm2 antibody. Anti-Gcm2 was also applied to a variety of endocrine tumors, including thyroid tumors and nonendocrine tumors, and normal tissues from a variety of organs, including the parathyroid and thyroid glands. Gcm2 nuclear expression was seen in all the normal parathyroid glands, and cystic, hyperplastic, and neoplastic parathyroid lesions in a diffuse manner, whereas no Gcm2 expression was seen in any other normal tissues and tumors, including those of the thymus and thyroid gland. Anti-Gcm2 antibody is a highly sensitive and specific marker for parathyroid lesions. Although the immunohistochemistry stain for parathyroid hormone is a useful marker, its reaction tends to be variable in extent and intensity in parathyroid neoplasia, and it is often negative in parathyroid cysts, and Gcm2 would serve as a useful adjunct marker. © 2010 by Lippincott Williams & Wilkins.


Howell M.,Christie NHS Foundation Trust | Valle J.W.,Christie NHS Foundation Trust | Valle J.W.,University of Manchester
Best Practice and Research: Clinical Gastroenterology | Year: 2015

Abstract Cholangiocarcinomas are rare cancers arising from the epithelia of the biliary tract. The only prospect of curative therapy is with surgery. However, relapse rates are high with five-year survival rates typically around 20-30%. Involved resection margins and spread to local lymph nodes are associated with a higher risk of relapse. Such poor outcomes provide a rationale for adjuvant strategies to improve survival. However, there is little randomised data to support the use of adjuvant therapy; the available evidence base is based mostly on retrospective case series and results are often conflicting. This review evaluates the available evidence. Adjuvant therapy may be considered on an individual patient basis after discussion of the limitations of our knowledge. The results of prospective, randomised clinical trials of adjuvant therapy are eagerly awaited. Progress will require collaboration of basic science and clinical oncology and the execution of well-designed clinical trials. © 2015 Elsevier Ltd.


Craciunas L.,Worthing Hospital | Sajid M.S.,Worthing Hospital | Ahmed A.S.,Christie NHS Foundation Trust
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2014

Background The incidence of postoperative ileus (POI) after gynaecological surgery is 10-15% Chewing gum following general surgery improves outcomes, including early flatus, early bowel sounds, and shortening of hospitalisation periods. There is currently no guideline that supports the use of chewing gum after caesarean sections. Objectives To systematically analyse the published randomised controlled trials regarding the effectiveness of chewing gum in preventing POI in women undergoing caesarean sections. Search strategy Systematic search of medical databases up to March 2013. Selection criteria Randomised controlled trials that reported the role of chewing gum in preventing POI in women undergoing caesarean sections. Data collection and analysis Two authors independently identified the relevant studies for inclusion, extracted outcome-related data, and analysed it systematically using revman ®. The combined outcome was expressed as an odds ratio and standardised mean difference. Main results Seven randomised controlled trials involving 1462 women (728 in the chewing gum group, 734 controls) were systematically analysed. There was significant heterogeneity (χ2 = 29.02, df = 7; P < 0.0001; I2 = 76%) among the included trials. Among women undergoing caesarean sections, chewing gum reduced the risk of POI (odds ratio 0.36; 95% confidence interval 0.19-0.69; z = 3.08; P < 0.002) but did not affect duration of hospitalisation (P = 0.32). Conclusions Chewing gum for 30-60 minutes at least three times a day appears to be effective in reducing the incidence and consequences of POI following caesarean sections. © 2014 Royal College of Obstetricians and Gynaecologists.


Dean E.,Christie NHS Foundation Trust | Lorigan P.,Christie NHS Foundation Trust
Expert Review of Anticancer Therapy | Year: 2012

Metastatic melanoma is an aggressive, immunogenic and molecularly heterogeneous disease for which most patients require systemic treatment. Recently, significant clinical breakthroughs have revolutionized the treatment of advanced melanoma, leading to the licensing of ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4, and vemurafenib, a BRAF inhibitor used in patients whose tumors contain a V600 mutation in the BRAF gene. This recent success has led to optimism and momentum has gathered with updated trial results from these therapies, next-generation compounds that target validated molecular pathways and novel agents that are mechanistically distinct. This review summarizes the recent advances and updated results since the licensing of vemurafenib and ipilimumab, the benefits and limitations of these agents, future strategies to improve upon existing treatments and overcome acquired resistance, in-progress and future clinical trials, as well as novel therapeutic targets, pathways and therapies that hold promise in advancing clinical benefit. © 2012 2012 Expert Reviews Ltd.


Recurrent tumour after radical pancreaticoduodenectomy may cause obstruction of the small bowel loop draining the liver. Roux-loop obstruction presents a particular therapeutic challenge, since the postsurgical anatomy usually prevents endoscopic access. Careful multidisciplinary discussion and multimodality preprocedure imaging are essential to accurately demonstrate the cause and anatomical location of the obstruction. Transhepatic or direct percutaneous stent placement should be possible in most cases, thereby avoiding long-term external biliary drainage. Gastropexy T-fasteners will secure the percutaneous access and reduce the risk of bile leakage. The static bile is invariably contaminated by gut bacteria, and systemic sepsis is to be expected. Enteral stents are preferable to biliary stents, and compound covered stents in a sandwich construction are likely to give the best long-term results. Transhepatic and direct percutaneous enteral stent insertion after jejunopexy is illustrated and the literature reviewed.

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