• G- and GM-CSF.

      Middleton, Mark R; Thatcher, Nick; CRC Department of Medical Oncology, Manchester, UK. (1998-05)
    • The G-value for the ferrous sulphate dosemeter for 14 MeV neutrons.

      Greene, D; Major, D; Law, J; Christie Hospital and Holt Radium Institute, Manchester (1973)
    • The G-value for the ferrous sulphate dosemeter for the radiation from californium-252.

      Greene, D; Law, J; Major, D; Christie Hospital and Holt Radium Institute, Manchester (1973)
    • G1 control gene status is frequently altered in resectable non-small cell lung cancer.

      Betticher, Daniel C; White, Gavin R M; Vonlanthen, S; Liu, X; Kappeler, A; Altermatt, H J; Thatcher, Nick; Heighway, Jim; Institute of Medical Oncology, Inselspital, University of Bern, Switzerland. (1997-10-21)
      Progression through the mammalian cell cycle is controlled by a series of cyclins, cyclin-dependent kinases (cdks) and cdk inhibitors. Cyclin D1, cdk4 and the tumour suppressors p16 and retinoblastoma protein (pRb) are thought to comprise a linked system governing cell passage through the G1 phase of the cell cycle. Extending an earlier study on cyclin D1 expression, a series of resectable non-small cell lung carcinomas (NSCLCs) was examined for defects in other elements of this control system. Forty-six of fifty-one NSCLC specimens exhibited at least one alteration of these cell-cycle regulators. Immunohistochemical analysis revealed that 33% and 47% of the tumours failed to express pRb and p16, respectively. Failure to detect pRb did not correlate with loss of heterozygosity at the RB1 locus. Eleven of 12 tumours showing positive (normal) pRb staining over-expressed nuclear localised cyclin D1, including 8 with amplification of the cyclin D1 gene (CCNDI). However, in a number of lesions (n = 5) where cyclin D1 was over-expressed but localised to the cytoplasm, pRb expression was undetectable. Sequencing of exons 1 and 2 of the p16 gene (CDKN2) revealed 3/51 tumours with somatic mutations (in addition to 1 case with a germ-line alteration). All of these lesions were positive for p16 protein. No clear homozygous deletions of CDKN2 were observed by multiplex PCR. As assessed by immunostaining using a p16 monoclonal antibody, there was an inverse correlation of pRb and p16 down-regulation. Whilst patients with tumours over-expressing cyclin D1 had a significantly lower incidence of local relapse, the group whose tumours failed to express pRb had a significantly greater risk of local relapse and tended to have shortened event-free survival. Our data show that alteration of at least one cell cycle-regulator gene occurs in the majority of resectable NSCLCs.
    • Gamma-delta T-cell lymphoma of skin, eye and brain presenting with visual loss.

      Jones, N; Gibb, Adam; Irion, L; Coupland, S; Manchester Royal Eye Hospital, Manchester, UK (2017-06-15)
      A young man presented with rapid, predominantly right-sided visual loss with a background of multifocal skin lesions. Visual acuity was right hand movements, left 6/5 Snellen, deteriorating to 6/38. He showed panuveitis with bilateral multifocal retinal infiltrates and retinal vasculitis. Multifocal brain lesions were identified. Biopsy of both skin and vitreous showed atypical lymphocytes, and immunohistochemistry confirmed T-cell lymphoma of gamma-delta subtype. Management with the CODOX-M/IVAC polychemotherapy regimen achieved rapid response including resolution of intraocular changes and substantial improvement of visual acuity to right 6/7.5, left 6/6. However, he relapsed before planned stem cell transplantation. Salvage with the gemcitabine/dexamethasone/cisplatin regimen, although temporarily effective, was followed by further relapse including widespread brain involvement, and he succumbed 10 months after presentation.
    • The ganglioside GM(3) is raised in the sera and tissue of patients with bladder tumours.

      Slevin, M; Costello, B; Kumar, Shant; Gaffney, J; Christie Hospital, Wilmslow Road, Manchester, M20 4BX (1996)
    • Gap analysis of role definition and training needs for therapeutic research radiographers in the UK.

      Russell, Wanda; McNair, Helen A; Heaton, Angela; Ball, Kim; Routsis, Donna; Love, Kate; Miles, Elizabeth; Academic Clinical Oncology and Radiobiology Research Network (ACORRN), Christie Hospital NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK. (2007-09)
      In this study, we aimed to create a comprehensive register of UK research radiographers (RRs), identify perceived training needs and make recommendations for the forward planning of the RR community in 2007 and 2008. Radiotherapy departments in England were sent an Academic Clinical Oncology and Radiobiology Research Network (ACORRN) questionnaire on RR establishment, demographics, role descriptions, research responsibilities, funding, time allocations, research skills and barriers to research. ACORRN received 85 replies from 51 departments of which just 5 RRs had a 100% research role. 70 radiographers participated in research at some level. 13 departments did not have any RRs. The RR role was defined as both developmental and specialist in nature by 43% of respondents; the remainder had a more diverse role. The National Health Service Trusts were responsible for funding 40% of RRs; the rest were fully or part-funded by national or local cancer networks, charity appeals and industry. 61% of RRs did not have dedicated academic time despite 93% being required to teach or support others. Critical barriers reported in conducting research were time, funding and supporting others In conclusion, the ACORRN RR Working Party makes the following recommendations for the future development of the community: the role of research should be viewed as an integral feature, at least one RR should be employed per radiotherapy department, the RR community must work together, dedicated research time is required, along with stable funding, RRs require more training, RRs need more support to accomplish the diversity of roles.
    • Gap junctions and nerve terminals among stromal cells in human fallopian tube ampullary mucosa.

      Yamazaki, K; Eyden, Brian P; Department of Diagnostic Pathology, School of Medicine Keio University, Tokyo, Japan. yamazaki@med.keio.ac.jp (1998-07)
      The purpose of the present study is to investigate the ultrastructure and immunohistochemistry of the stromal cells and terminal nerve fibers in human fallopian tube ampullar mucosa to achieve a detailed characterization of this tissue to permit a better assessment of possible functions. Tissues were obtained during surgery or at autopsy from 26 patients. Specimens were studied by the conventional histologic technique, immunohistochemistry (Cx43, synaptophysin, neurofilament proteins, and S-100 protein), and electron microscopy. Gap junction and nerve terminal frequency between stromal cells were studied by direct assessment on ultrathin sections in the transmission electron microscope. Gap junctions were observed between the cytoplasmic processes of subepithelial stromal cells. There were approximately 23 gap junctions per 73 nucleated stromal spindle cells. Immunohistochemistry using Cx43 antibody confirmed the dot-like distribution of gap junctions. The frequent and intimate association of stromal cell processes with nerve terminals was also demonstrated. Nerve terminals were immunostained by antibodies to nerve-specific molecules and ultrastructurally as axonal profiles containing dense-cored granules or empty vesicles. Analysis of nerve terminal frequency revealed 18 nerve profiles containing 51 axonal profiles per 73 nucleated stromal spindle cells. The present paper documents the participation of autonomic nerve endings and gap junctions in the stromal cell network in human fallopian tube stroma. Similarities to the unique anatomical unit referred to as the 'neuro-reticular complex' in bone marrow tissue (Yamazaki and Allen, 1990) are discussed.
    • Gastro--oesophageal reflux in late pregnancy.

      Hey, V; Cowley, D; Ganguli, P; Skinner, L D; Ostick, D; Sharp, D (1977-04)
      Lower oesophageal sphincter pressure and fasting plasma gastrin and progesterone were measured in 31 women in the last trimester of pregnancy and in 10 healthy female control subjects. Eighteen of the pregnant women suffered from heartburn but 13 did not. All of the control subjects and 10 women from each of the two pregnant groups were tested for gastro--oesophageal reflux by direct measurement of intraluminal pH. The mean barrier pressure of the lower oesophageal sphincter was lower in both groups of pregnant women than in the controls (P less than 0-05) and the mean barrier pressure of the women with heartburn was lower than that of the pregnant women without heartburn, though this difference did not reach statistical significance. Eight of 10 of the pregnant women with heartburn had moderate or severe reflux, and3 of 10 of the pregnant women without heartburn also had moderate or severe reflux. Most women who reflux have heartburn, nevertheless, some asymptomatic women also reflux, and therefore all pregnant women must be considerered at risk from Mendelson's syndrome if subjected to a general anaesthetic for an emergency obstetric procedure.
    • Gastrointestinal autonomic nerve tumours: a report of nine cases.

      Shanks, Jonathan H; Harris, Martin; Banerjee, Saumitra S; Eyden, Brian P; Department of Histopathology, Christie Hospital NHS Trust, Manchester, UK. (1996-08)
      We describe the clinicopathological features of gastrointestinal autonomic nerve tumours in nine patients where the diagnosis was confirmed by electronmicroscopy. Most patients presented with abdominal pain. At laparotomy, large intra-abdominal tumour masses were found which tended to be cystic and haemorrhagic. The predominant histological patterns were nests, sheets and fascicles of spindle and epithelioid cells. Immunohistochemistry showed positive staining for neuron specific enolase (9/9), PGP 9.5 (9/9), NKI/C3 (7/9), vimentin (7/9), alpha-smooth muscle actin (5/9), vasoactive intestinal peptide (3/9) and CD34/QBend10 (2/9). Grimelius staining was positive in two of nine cases. All tumours were negative for CAM 5.2, chromogranin, synaptophysin, Leu 7, neurofilament protein, muscle-specific actin (HHF-35) and desmin (D33). Ultrastructural examination showed cellular processes and dense-core granules in all cases. Three tumours had microtubules and/or intermediate filaments, particularly in cell processes. Skeinoid fibres were seen in three cases. No convincing synapses or small (synaptic-type) vesicles were identified. There was no evidence of epithelial, smooth muscle or nerve sheath differentiation. Two patients died due to tumour, two died of unknown causes and the remainder are alive 2-44 months after presentation. Four of the five survivors have recurrent/residual intra-abdominal tumour. So-called gastrointestinal autonomic nerve tumours are apparently slow-growing malignant tumours showing neuronal differentiation. Four cases arose in the mesentery/retroperitoneum or omentum rather than bowel wall and therefore a more appropriate nomenclature might be intra-abdominal stromal tumour with neuronal differentiation.
    • Gastrointestinal involvement with myeloma.

      Benson, W J; Scarffe, J Howard; Houwen, B; Crowther, Derek; Cancer Research Campaign, Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester (1983)
      A patient with IgA-k multiple myeloma is presented. There was initially a good response to chemotherapy but the patient later developed small intestinal obstruction. This was due to multiple polypoid plasmacytomas. The mesenteric nodes were also involved, and were found on immunofluorescence microscopy and flow cytometry with double fluorescent labelling to be composed of two separate populations of cells (IgA-k and IgG-k), one population having a diploid content of DNA and the other tetraploid. These two distinct cell populations differed in both proliferative characteristics and size. The findings are discussed and the literature relating to gastrointestinal involvement in plasma cell dyscrasias reviewed.
    • Gastrointestinal stromal tumor with multiple primary tyrosine kinase mutations-clinicopathologic and molecular characterization.

      Wong, N; Taniere, P; Walsh, S; Wallace, A; Nonaka, Daisuke; Jones, T; Gonzalez, D; Department of Cellular Pathology, Southmead Hospital, Bristol (2018-05-04)
      A unique cohort of chemo-naive gastrointestinal stromal tumors (GISTs) with double-primary tyrosine kinase mutations was characterized particularly to determine whether coexistent mutations represent a single mutational event. Up to 2013, 4 UK centers reported 9 GISTs with 2 primary tyrosine kinase mutations. In each of 8 cases validated by next generation sequencing, both mutations were present in the same allele of the same exon (KIT exon 11 or 17, or PDGFRA exon 18). One case showed the second mutation only on some of the mutant alleles. Seven cases showed both mutations in all the reads, but in 2 cases, additional variants were found only in some reads. Clinicopathologic features of the 8 cases were similar to GISTs with single-primary mutations. When GIST genotyping rarely uncovers multiple tyrosine kinase variants in an exon, they occur in the same allele but are likely to represent separate mutational events and lack clinical significance.
    • Gastrointestinal stromal tumor with structures resembling intracytoplasmic lumina.

      Xu, X; Eyden, Brian P; Hou, W; Chen, T; Department of Pathology, Fudan University Cancer Center, Shanghai, China. Lilysh21@hotmail.com (2010-10)
      Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gut. It is characterized by positive immunostaining for CD117, and bears mutations in the c-kit or PDGFRA genes. Its origin remains uncertain. GISTs mainly possess primitive smooth muscle or neuronal differentiation. Although an epithelioid pattern of GIST is a common finding on light microscopy, true epithelial differentiation has never been demonstrated by either immunohistochemistry or ultrastructural study. Here the authors report an epithelioid GIST of the stomach, immunopositive for CD117, DOG1.1, CD34, and PDGFRA, with slight cytoplasmic staining for epithelial membrane antigen. One heterozygous mutation on codon 842 of exon 18 of the PDGFRA gene was also found. Ultrastructurally, tumor cells had plentiful organelles, including some membrane-bound, dense-core granules and cytoplasmic vacuoles. Intermingled thin cellular processes were also found. Unusually, there were many structures resembling glandular epithelial intracellular lumina with processes. The processes, although resembling microvilli, did not have filament cores, while the lumina were either empty or contained some dense or flocculent content of uncertain nature. True intracellular lumina are very rare in GIST and the authors present findings related to this issue, with a discussion on their nature, origin, and significance.
    • Gastrointestinal symptoms after pelvic radiotherapy: a national survey of gastroenterologists.

      Henson, Caroline C; Davidson, Susan E; Lalji, A; Symonds, R P; Swindell, Ric; Andreyev, H J; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK, caroline.henson@christie.nhs.uk. (2011-11-13)
      PURPOSE: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. Up to 50% develop significant gastrointestinal symptoms. The National Cancer Survivorship Initiative has identified access to specialist medical care for those with complications after cancer as one of their four key needs. We aimed to determine the current practice of British gastroenterologists with regards to chronic gastrointestinal symptoms after pelvic radiotherapy. METHODS: A questionnaire was developed and sent up to a maximum of five times to all UK consultant gastroenterologists. RESULTS: Eight hundred sixty-six gastroenterologists were approached and 165 (20%) responded. Sixty-one percent saw one to four patients annually with bowel symptoms after radiotherapy. Eighteen percent rate the current treatments as effective "often" or "most of the time". Forty-seven percent of gastroenterologists consider themselves "confident with basic cases", with 11% "confident in all cases". Fifty-nine percent thinks a gastroenterologist with a specialist interest should manage these patients. Although only 29% thinks a specific service is required for these patients, 34% rates the current service as inadequate. The ideal service was considered to be gastroenterology-led, multidisciplinary and regional. Low referral rates, poor evidence-base and poor funding are cited as reasons for the current patchy services. CONCLUSIONS: The low response rate contrasts with that from a parallel survey of clinical oncologists. This may reflect the opinion that radiation-induced bowel toxicity is not a significant issue, which may be because only a small proportion of patients are referred to gastroenterologists. The development of new, evidence-based gastroenterology-led services is considered the optimal way to meet the needs of these patients.
    • Gastrostomy insertion: comparing the options--PEG, RIG or PIG?

      Laasch, Hans-Ulrich; Wilbraham, L; Bullen, K; Marriott, Andrew S; Lawrance, Jeremy A L; Johnson, Richard J; Lee, S H; England, R E; Gamble, G E; Martin, D F; et al. (2003-05)
      AIM: To compare percutaneous endoscopic gastrostomy (PEG) with radiologically inserted gastrostomy (RIG) and assess a hybrid gastrostomy technique (per-oral image-guided gastrostomy, PIG). MATERIALS AND METHODS: Fifty PEGs and 50 RIGs performed in three centres were prospectively compared and the endoscopic findings of 200 PEGs reviewed. A fluoroscopy-guided technique was modified to place 20 F over-the-wire PEG-tubes in 60 consecutive patients. RESULTS: Technical success was 98%, 100% and 100% for PEG, RIG and PIG, respectively. Antibiotic prophylaxis significantly reduced stoma infection for orally placed tubes (p=0.02). Ten out of 50 (20%) small-bore RIG tubes blocked. Replacement tubes were required in six out of 50 PEGs (12%), 10 out of 50 RIGs (20%), but no PIGs (p<0.001). No procedure-related complications occurred. The function of radiologically placed tubes was significantly improved with the larger PIG (p<0.001), with similar wound infection rates. PIG was successful in 24 patients where endoscopic insertion could not be performed. Significant endoscopic abnormalities were found in 42 out of 200 PEG patients (21%), all related to peptic disease. Insignificant pathology was found in 8.5%. CONCLUSION: PIG combines advantages of both traditional methods with a higher success and lower re-intervention rate. Endoscopy is unlikely to detect clinically relevant pathology other than peptic disease. PIG is a very effective gastrostomy method; it has better long-term results than RIG and is successful where conventional PEG has failed.
    • GATA3 shows differential immunohistochemical expression across thyroid and parathyroid lesions.

      Betts, Guy N J; Beckett, Elizabeth; Nonaka, Daisuke (2014-02-07)
      Transcription factors have proved highly specific immunohistochemical markers e.g. TTF-1 (thyroid/lung) and CDX-2 (Gastro-intestinal). GATA3 is a transcription factor which is functionally involved with the development of breast, urothelial, epidermal, T lymphocyte and parathyroid tissue. Recent studies of GATA3 immunoprofile, including that by Miettinen et al. across 2040 epithelial malignancies and 460 mesenchymal or neuroectodermal neoplasms, demonstrated the specificity and potential clinical utility of GATA3 across urothelial, mammary and cutaneous squamous lesions(1, 2) . This article is protected by copyright. All rights reserved.
    • GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways.

      Burrows, N; Babur, M; Resch, Julia; Ridsdale, S; Mejin, M; Rowling, E; Brabant, Georg E; Williams, K; Hypoxia and Therapeutics Group, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom. (2011-12)
      Phosphoinositide 3-kinase (PI3K) regulates the transcription factor hypoxia-inducible factor-1 (HIF-1) in thyroid carcinoma cells. Both pathways are associated with aggressive phenotype in thyroid carcinomas.
    • GEC-ESTRO ACROP recommendations in skin brachytherapy.

      Guinot, J; Rembielak, Agata; Perez-Calatayud, J; Rodríguez-Villalba, S; Skowronek, J; Tagliaferri, L; Guix, B; Gonzalez-Perez, V; Valentini, V; Kovacs, G; et al. (2018-02-15)
      The aim of this publication is to compile available literature data and expert experience regarding skin brachytherapy (BT) in order to produce general recommendations on behalf of the GEC-ESTRO Group.
    • Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: subset analysis from the ISEL study.

      Chang, Alex; Parikh, Purvish; Thongprasert, Sumitra; Tan, Eng Huat; Perng, Reury-Perng; Ganzon, Domingo; Yang, Chih-Hsin; Tsao, Chao-Jung; Watkins, Claire; Botwood, Nicholas; et al. (2006-10)
      INTRODUCTION: The IRESSA Survival Evaluation in Lung Cancer (ISEL) phase III study compared the efficacy of gefitinib (IRESSA) versus placebo in patients with refractory advanced non-small cell lung cancer (NSCLC). Although a statistically significant difference in survival was not seen between gefitinib and placebo in the overall ISEL population, preplanned subset analyses demonstrated a significant survival benefit in patients who had never smoked and in patients of Asian origin. METHODS: In ISEL, 1692 patients who were refractory to or intolerant of their latest chemotherapy were randomized to receive either gefitinib (250 mg/day) or placebo, plus best supportive care. Preplanned subgroup analyses included an assessment of patients who were of Asian origin (n = 342).RESULTS: Two hundred thirty-five patients of Asian origin received gefitinib, and 107 received placebo. In these patients, treatment with gefitinib significantly improved survival compared with placebo (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.48, 0.91; p = 0.010; median survival, 9.5 versus 5.5 months). Patients of Asian origin also experienced statistically significant improvements in time to treatment failure with gefitinib compared with placebo (HR, 0.69; 95% CI, 0.52, 0.91; p = 0.0084; 4.4 versus 2.2 months), and objective response rates were higher with gefitinib than with placebo (12 versus 2%). Gefitinib was generally well tolerated in patients of Asian origin, with rash and diarrhea being the most common adverse events. No unexpected adverse events were observed. CONCLUSIONS: Treatment with gefitinib was associated with a significant improvement in survival in a subgroup of patients of Asian origin with previously treated refractory advanced NSCLC.