• Nanofluidic allele-specific digital PCR method for quantifying IDH1 and IDH2 mutation burden in acute myeloid leukemia.

      Wiseman, Daniel H; Somervaille, Tim C P; Leukemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, M20 4BX, UK (2017)
      Precise quantitation of allelic burden for a pathogenic mutation has diverse clinical and research applications but can be difficult to achieve with conventional qPCR-based techniques, especially at lower mutant allele frequencies. Digital PCR overcomes many of the limitations of qPCR and can be highly quantitative even for single-nucleotide variants, with distinct advantages over next-generation sequencing approaches. Here we describe a method combining the principles of TaqMan(®)-chemistry SNP genotyping with microfluidic digital PCR to generate a highly sensitive, quantitative allele-specific digital PCR assay for the six most common IDH1 and IDH2 mutations encountered in myeloid malignancy. The concept and approach could easily be applied to other suitable SNVs.
    • Nanomedicine: photo-activated nanostructured titanium dioxide, as a promising anticancer agent

      Lagopati, N.; Evangelou, K.; Falaras, P.; Tsilibary, E. C.; Vasileiou, P. V. S.; Havaki, S.; Angelopoulou, A.; Pavlatou, E. A.; Gorgoulis, Vassilis G; Laboratory of Histology-Embryology, Molecular Carcinogenesis Group, Faculty of Medicine, School of Health Science, National and Kapodistrian University of Athens, 75, Mikras Asias Str., Goudi, GR 11527 Athens, Greece; (2020)
      The multivariate condition of cancer disease has been approached in various ways, by the scientific community. Recent studies focus on individualized treatments, minimizing the undesirable consequences of the conventional methods, but the development of an alternative effective therapeutic scheme remains to be held. Nanomedicine could provide a solution, filling this gap, exploiting the unique properties of innovative nanostructured materials. Nanostructured titanium dioxide (TiO2) has a variety of applications of daily routine and of advanced technology. Due to its biocompatibility, it has also a great number of biomedical applications. It is now clear that photo-excited TiO2 nanoparticles, induce generation of pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) that have been proven to damage cancer cells, triggering controlled cellular processes. The aim of this review is to provide insights into the field of nanomedicine and particularly into the wide context of TiO2-NP-mediated anticancer effect, shedding light on the achievements of nanotechnology and proposing this nanostructured material as a promising anticancer photosensitizer.
    • Nanosecond flash photolysis of rhodopsin.

      Bensasson, R; Land, Edward J; Truscott, T G; E.R. 98 Laboratoire de Chimie Physique de la Faculté des Sciences, Université de Paris VI, 91405-Orsay, France (1975-12-25)
    • Naptumomab estafenatox: targeted immunotherapy with a novel immunotoxin.

      Eisen, T; Hedlund, G; Forsberg, G; Hawkins, Robert E; Cambridge University Health Partners, Addenbrooke's Hospital, Cambridge, UK, tgqe2@medschl.cam.ac.uk. (2014-02)
      Improvement of cancer therapy by introducing new concepts is still urgent even though there have been major advancements lately. Immunotherapy is well on the way to becoming an established tool in the cancer treatment armory. It seems that a combination of (1) activation of immune effector cells and selective targeting of them to tumors and (2) the inhibition of immune suppression often induced by the tumor itself are necessary to achieve the therapeutic goal. The immunotoxin naptumomab estafenatox was developed in an effort to activate and target the patient's own T cells to their tumor, by fusing a superantigen (SAg) variant that activates T lymphocytes to the Fab moiety of a tumor-reactive monoclonal antibody. Naptumomab estafenatox targets the 5T4 tumor antigen, a 72-kDa oncofetal trophoblast protein expressed on many carcinomas, including renal cell carcinoma. The therapeutic effect is associated with activation of SAg-binding T cells. The SAg-binding T lymphocytes expand, differentiate to effector cells, and infiltrate the tumor. The therapeutic efficacy is most likely related to the dual mechanism of tumor cell killing: (1) direct lysis by cytotoxic T lymphocytes of tumor cells expressing the antigen recognized by the antibody moiety of the fusion protein and (2) secretion of cytokines eliminating antigen-negative tumor cell variants. Naptumomab estafenatox has been clinically tested in a range of solid tumors with focus on renal cell carcinoma. This review looks at the clinical experience with the new immunotoxin and its potential.
    • Natural cytotoxic reactivity of human lymphocyte subpopulations.

      Potter, M R; Moore, Michael; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester (1979-05)
      The spontaneous cytotoxicity of human peripheral blood lymphocyte preparations from normal donors for K562 target cells was examined. Effector cells were separated into SRBC rosette forming cell (RFC) and non-rosette forming cell (non-RFC) fractions using optimal and suboptimal rosetting procedures. RFC and non-RFC fractions both had high cytotoxic activity irrespective of the rosetting procedure. Owing to the larger size of the RFC fraction, it contained a higher proportion of the total activity in the preparation. Nylon fibre column adherent and non-adherent fractions also both produced cytotoxicity. Nylon fibre non-adherent cells separated by SRBC separation gave a RFC fraction with low activity and a non-RFC fraction with high activity. Separation of nylon fibre adherent cells gave RFC and non-RFC fractions with high cytotoxic activity. Therefore cytotoxic cells did not form a discrete subpopulation and either occur in several lymphocyte subsets or show a variable capacity to form SRBC rosettes and adhere to nylon fibre.
    • Natural cytotoxicity in humans: susceptibility of freshly isolatd tumor cells to lysis.

      Vose, Brent M; Moore, Michael; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, England (1980-08)
      The cytotoxic potential of blood lymphocyters from healthy donors was tested against freshly isolated lung cancer cells and the erythroleukemia K562 cell line in short-term 51Cr release assays conducted at an effector:target ratio of 50:1. Most donors exhibited significant activity against K6-562 cells. By contrast, fresh tumor cells were refractory, only 6 of 30 showing significant cytotoxicity. The low susceptibility of these tumor cells was confirmed in third-party cold inhibition assays in which they interfered minimally with killing of K562 targets under conditions in which unlabeled K562 cells efficiently blocked cytotoxicity. Cells prepared from normal lung tissue and Raji cells also failed to inhibit killing. Although in comparison to the K562 cell line freshly isolated tumor cells were resistant, their susceptibility may not be so low as to be biologically irrelevant, inasmuch as boosting of natural killing activity by interferon induced levels of cytotoxicity against both types of target cell that were unattainable by unstimulated effectors. Interferon-boosted killers were lytic for "normal" lung cells and the Raji cell line.
    • Natural cytotoxicity of human blood monocytes: Production of monocyte cytotoxic factors (MCF) during interaction with tumor cells

      Uchida, Atsushi; Yanagawa, Etsuro; Division of Immunology, Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, England. (1984)
    • Natural expression of the CD19 antigen impacts the long-term engraftment but not antitumor activity of CD19-specific engineered T cells.

      Cheadle, Eleanor J; Hawkins, Robert E; Batha, Hayley; O'Neill, Allison L; Dovedi, Simon J; Gilham, David E; Cellular Therapy Group, Department of Medical Oncology, Paterson Institute for Cancer Research, The University of Manchester, Manchester, UK. echeadle@picr.man.ac.uk (2010-02-15)
      T cells gene-modified to express chimeric Ag receptors (CARs) have shown potent antitumor activity in vivo and are in clinical trials at locations worldwide. However, CAR activity has been investigated in mouse models in which Ag expression is restricted to the tumor. To explore the impact of normal tissue expression of the target Ag, we developed a mouse CD19-specific CAR to investigate antitumor efficacy against a syngeneic B cell lymphoma cell line within a background of normal CD19(+) host B cells. Mouse T cells engrafted with the amCD19CD3zeta CAR specifically lysed A20 lymphoma targets and B cells in vitro. These T cells also eradicated a 12-d established disseminated A20 lymphoma in mice preconditioned with 6 Gy total body irradiation. In the short-term (7 d after adoptive transfer), amCD19z T cells underwent Ag-dependent proliferation in vivo with a concomitant depletion in host B cell levels. However, the levels of amCD19z CAR(+) T cells decreased significantly at later time points, at which point host B cells returned, eventually reaching normal levels. In contrast, CAR(+) T cells lacking a signaling domain or specificity for mCD19 persisted over extended periods in blood and spleen. Importantly, no overt clinical signs of autotoxicity were observed in tumor-free or tumor-bearing mice treated with amCD19z T cells over an extended period of time. These observations highlight the importance of studying the activity of CAR(+) T cells in autologous models that have the normal range of tissue expression of Ag.
    • The natural history of actinic keratoses in organ transplant recipients.

      Jiyad, Z; Marquart, L; O'Rourke, P; Green, Adèle C; Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia (2017-01)
    • The natural history of common melanocytic naevi: a systematic review of longitudinal studies in the general population.

      Plasmeijer, E; Nguyen, T; Olsen, C; Janda, M; Soyer, P; Green, Adèle C; QIMR Berghofer Medical Research Institute, Cancer and Population studies, Brisbane, QLD, Australia (2017-05-18)
    • Natural history of HLA expression during tumour development

      Garrido, F; Cabrera, T; Concha, A; Glew, Susan S; Ruiz-Cabello, F; Stern, Peter L; Dept of Analisis Clinicos e Immunologia, Hospital Virgen de las Nieves, Universidad de Granada 18014 Granada, Spain (1993)
    • Natural HPV immunity and vaccination strategies.

      Stern, Peter L; Brown, Michael D; Stacey, Simon N; Kitchener, Henry C; Hampson, Ian N; Abdel-Hady, El-Said; Moore, James V; Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, M20 4BX, Manchester, UK. (2000-10)
      BACKGROUND: the task of preventing premature death in women may be delivered by vaccinating against the high-risk papillomaviruses associated with various malignancies. OBJECTIVES: we will discuss the immune mechanisms likely to be relevant to the control of an HPV infection in the cervix and assess the limited evidence for such immune recognition in the natural history of infection. CONCLUSION: the next generation of vaccination strategies should include the use of HPV 16 early (E2 and/or E6 and/or E7) and late gene targets (L1 and L2) expressed as VLPs with their clinical and immunological evaluation aimed at therapy as well as prophylaxis. Important clinical efficacy assessment may be deliverable in relatively short-term studies by targeting patients with HPV 16 associated vulval intraepithelial neoplasia.
    • Natural immunity to tumours - theoretical predictions and biological observations

      Moore, Michael; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX (1985)
    • Natural killer cell activity and autologous tumor killing activity in cancer patients: overlapping involvement of effector cells as determined in two-target conjugate cytotoxicity assay.

      Uchida, Atsushi; Yanagawa, Etsuro; Paterson Institute for Cancer Research, Manchester, U.K. (1984-11)
      The relationship between natural killer (NK) cell activity and autologous tumor killing activity was examined in patients with carcinomatous pleural effusions (PE) by means of a two-target conjugate cytotoxicity assay. Enrichment of large granular lymphocyte(s) (LGL) by discontinuous Percoll gradient centrifugation resulted in an augmentation of cytotoxicity against both K562 cells and tumor cells freshly isolated from PE of the same patients in a 4-hour 51Cr release cytotoxicity assay. At the single-cell level, the LGL-enriched fraction contained an increased number of effector cells that bound to autologous tumor cells and to K562 cells, as well as an increased frequency of cells cytotoxic to these target cells. In the two-target conjugate cytotoxicity assay, a single lymphocyte in the LGL population simultaneously bound to both a fluorescein-labeled K562 cell and a nonfluorescent autologous tumor cell. A significant number of lymphocytes in these mixed two-target conjugates lysed both autologous tumor cells and K562 cells after 6 hours' incubation, although overall lysis of K562 cells was higher than that of autologous tumor cells. These results indicate that a single LGL is involved in the lysis of both autologous tumor cells and K562 cells and thus provide direct evidence of involvement of subsets of NK cells in autologous tumor cell killing.
    • Naturally cytotoxic tonsillar leukocytes: phenotypic characterization of the effector population

      Christmas, Stephen E; Allan G; Moore, Michael; Department of Immunology, Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom (1985)
    • The nature of ataxia-telangiectasia: problems and perspectives.

      Harnden, David G; Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 9BX, UK (1994-12)
    • The nature of inherited susceptibility to cancer.

      Harnden, David G; The Paterson Laboratories, Christie Hospital and Holt Radium Institute, Wilmslow Road, Manchester 20, UK (1984-12)
    • The nature of the ESR signal in lyophilized tissue and its relevance to malignancy.

      Dodd, Nicholas J F; Swartz, H M; Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester, U.K. (1984-01)
      Comparison of 9 and 35 GHz spectra, obtained from frozen and lyophilized tissues, with those from model systems containing ascorbic acid, confirm that the major component of the "lyophilization signal" of tissue is the ascorbyl radical, stabilized by adsorption on an inert matrix. The magnitude of the signal under anoxic conditions is shown to be a measure of cellular damage, which allows intracellular ascorbic acid to be oxidized. On exposure of lyophilized samples to air, the signal increases due to autoxidation of the available tissue ascorbic acid. Under moist atmospheric conditions the ascorbyl radicals readily decay, leaving other radicals, which appear to be formed by interaction of ascorbic acid or ascorbyl radicals with some tissue component. The results show that, although widely studied, the free radical ESR signal of lyophilized tissue is not unique to tumour and has no relevance to malignancy.
    • Necrosis of murine tail skin following photodynamic treatment with meso-tetra-(p-sulphophenyl) porphine (TPPS).

      Moore, James V; Paterson Institute for Cancer research, CHristie Hospital & Holt Radium Institute, Manchester M20 9BX, England, UK (1987-06)
    • The neoadjuvant approach in the treatment of patients with advanced epithelial ovarian carcinoma.

      Rosa, Daniela D; Ton, Nhuan C; Clamp, Andrew R; Mullamitha, Saifee A; Lau, Sin C; Clayton, Richard D; Kitchener, Henry C; Shanks, Jonathan H; McVey, Rhona J; Jayson, Gordon C; et al. (2007-03)
      AIMS: Ovarian cancer has a very poor prognosis, with 5-year survival rates of 5-20% for advanced-stage disease. This work was designed to verify whether the neoadjuvant approach had an effect on survival in patients with advanced-stage ovarian cancer. MATERIALS AND METHODS: Patients with stage III or IV disease who received neoadjuvant platinum-based chemotherapy (group 1) were compared with a group of conventionally treated patients (group 2). RESULTS: Most of the patients in group 1 (76%) had partial tumoral responses after chemotherapy. Patients from group 1 (n = 42) had a median survival that was not different from that in patients from group 2 (n = 348). Patients who received platinum-based chemotherapy with taxanes had the same survival of patients who received no taxanes. CONCLUSIONS: Our results showed similar responses and survival rates for patients with stage III or IV ovarian cancer treated with neoadjuvant platinum-based chemotherapy, when compared with patients who underwent primary suboptimal cytoreductive surgery. Our data therefore support the ongoing trials to determine the optimum timing of surgery for ovarian cancer.