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Sample records for lymphoma tumour growth

  1. VEGF-A promotes lymphoma tumour growth by activation of STAT proteins and inhibition of p27(KIP1) via paracrine mechanisms

    NARCIS (Netherlands)

    Roorda, Berber D.; ter Elst, Arja; Scherpen, Frank J. G.; Meemusen-de Boer, Tiny G. J.; Kamps, Willem A.; de Bont, Eveline S. J. M.

    Increased levels of circulating VEGF-A have been demonstrated in patients with non-Hodgkin lymphoma (NHL) and are associated with progressive disease and poor clinical outcome. We investigated the role of VEGF-A in lymphoma tumour growth on a molecular level in order to identify the mechanism of

  2. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients

    International Nuclear Information System (INIS)

    Meignan, Michel; Sasanelli, Myriam; Itti, Emmanuel; Casasnovas, Rene Olivier; Luminari, Stefano; Fioroni, Federica; Coriani, Chiara; Masset, Helene; Gobbi, Paolo G.; Merli, Francesco; Versari, Annibale

    2014-01-01

    The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on 18 F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Data were processed by two nuclear medicine physicians in Reggio Emilia and Creteil. Nineteen phantoms filled with 18 F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm 3 with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41 % SUVmax threshold (TMTV 41 ) and a variable visually adjusted SUVmax threshold (TMTV var ). In phantoms, the 41 % threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV 41 measurement was substantial (ρ c = 0.986, CI 0.97 - 0.99) and the difference between the means was not significant (212 ± 218 cm 3 for Creteil vs. 206 ± 219 cm 3 for Reggio Emilia, P = 0.65). By contrast the agreement was poor for TMTV var . There was a significant direct correlation between TMTV 41 and normalized LDH (r = 0.652, CI 0.42 - 0.8, P 41 , but high TMTV 41 could be found in patients with stage 1/2 or nonbulky tumour. Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation. It should be evaluated in prospective studies. (orig.)

  3. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients

    Energy Technology Data Exchange (ETDEWEB)

    Meignan, Michel [Hopital Henri Mondor and Paris-Est University, Department of Nuclear Medicine, Creteil (France); Paris-Est University, Service de Medecine Nucleaire, EAC CNRS 7054, Hopital Henri Mondor AP-HP, Creteil (France); Sasanelli, Myriam; Itti, Emmanuel [Hopital Henri Mondor and Paris-Est University, Department of Nuclear Medicine, Creteil (France); Casasnovas, Rene Olivier [CHU Le Bocage, Department of Hematology, Dijon (France); Luminari, Stefano [University of Modena and Reggio Emilia, Department of Diagnostic, Clinic and Public Health Medicine, Modena (Italy); Fioroni, Federica [Santa Maria Nuova Hospital-IRCCS, Department of Medical Physics, Reggio Emilia (Italy); Coriani, Chiara [Santa Maria Nuova Hospital-IRCCS, Department of Radiology, Reggio Emilia (Italy); Masset, Helene [Henri Mondor Hospital, Department of Radiophysics, Creteil (France); Gobbi, Paolo G. [University of Pavia, Department of Internal Medicine and Gastroenterology, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy); Merli, Francesco [Santa Maria Nuova Hospital-IRCCS, Department of Hematology, Reggio Emilia (Italy); Versari, Annibale [Santa Maria Nuova Hospital-IRCCS, Department of Nuclear Medicine, Reggio Emilia (Italy)

    2014-06-15

    The presence of a bulky tumour at staging on CT is an independent prognostic factor in malignant lymphomas. However, its prognostic value is limited in diffuse disease. Total metabolic tumour volume (TMTV) determined on {sup 18}F-FDG PET/CT could give a better evaluation of the total tumour burden and may help patient stratification. Different methods of TMTV measurement established in phantoms simulating lymphoma tumours were investigated and validated in 40 patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Data were processed by two nuclear medicine physicians in Reggio Emilia and Creteil. Nineteen phantoms filled with {sup 18}F-saline were scanned; these comprised spherical or irregular volumes from 0.5 to 650 cm{sup 3} with tumour-to-background ratios from 1.65 to 40. Volumes were measured with different SUVmax thresholds. In patients, TMTV was measured on PET at staging by two methods: volumes of individual lesions were measured using a fixed 41 % SUVmax threshold (TMTV{sub 41}) and a variable visually adjusted SUVmax threshold (TMTV{sub var}). In phantoms, the 41 % threshold gave the best concordance between measured and actual volumes. Interobserver agreement was almost perfect. In patients, the agreement between the reviewers for TMTV{sub 41} measurement was substantial (ρ {sub c} = 0.986, CI 0.97 - 0.99) and the difference between the means was not significant (212 ± 218 cm{sup 3} for Creteil vs. 206 ± 219 cm{sup 3} for Reggio Emilia, P = 0.65). By contrast the agreement was poor for TMTV{sub var}. There was a significant direct correlation between TMTV{sub 41} and normalized LDH (r = 0.652, CI 0.42 - 0.8, P <0.001). Higher disease stages and bulky tumour were associated with higher TMTV{sub 41}, but high TMTV{sub 41} could be found in patients with stage 1/2 or nonbulky tumour. Measurement of baseline TMTV in lymphoma using a fixed 41% SUVmax threshold is reproducible and correlates with the other parameters for tumour mass evaluation

  4. 3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

    KAUST Repository

    Perfahl, H.

    2012-11-01

    We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

  5. 3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

    KAUST Repository

    Perfahl, H.; Byrne, H. M.; Chen, T.; Estrella, V.; Alarcó n, T.; Lapin, A.; Gatenby, R. A.; Gillies, R. J.; Lloyd, M. C.; Maini, P. K.; Reuss, M.; Owen, M. R.

    2012-01-01

    We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

  6. Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice.

    Science.gov (United States)

    Jauch, Dominik; Martin, Maria; Schiechl, Gabriela; Kesselring, Rebecca; Schlitt, Hans Jürgen; Geissler, Edward K; Fichtner-Feigl, Stefan

    2011-12-01

    Colitis-associated tumorigenesis is a balance between proliferation of tumour cells and tumour immunosurveillance. The role of T-helper-cell-derived cytokines in tumour growth is not fully understood. In this study the authors investigated the influence of interleukin (IL) 21 on intestinal tumorigenesis. Chronic colitis was induced in IL-21(-/-) and littermate control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS) over 7 days followed by 7 days of drinking water. Mice received an azoxymethane injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry was performed on inflamed and tumour-bearing areas of colons. Cytokine expression of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of isolated colonic CD8 T cells targeting tumour cells was evaluated by flow cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was determined by TUNEL assay of colonic sections. Increasing expression of IL-21 was observed in chronic colitis, which showed functional importance, since IL-21 deficiency prevented chronic DSS-colitis development. Further, in the absence of IL-21, significantly fewer tumour nodules were detected, despite a similar extent of intestinal inflammation. In wild-type mice, 8.6±1.9 tumour nodules were found compared with 1.0±1.2 in IL-21-deficient mice. In tumour-bearing IL-21-deficient mice, intestinal inflammation was restored and partly dependent on interferon (IFN)-γ, whereas the inflammation in wild-type mice showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice, tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was increased, compared with wild-type mice. Increased IFNγ expression in tumour-bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated by cytotoxic CD8CD103 T cells targeting E-cadherin(+) colonic tumour cells and therefore limited tumour growth. These results indicate that IL-21

  7. Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kanoun, Salim; Berriolo-Riedinger, Alina; Dygai-Cochet, Inna; Cochet, Alexandre; Humbert, Olivier; Toubeau, Michel; Brunotte, Francois [Centre G.F. Leclerc, Medecine nucleaire, Dijon (France); Rossi, Cedric; Ferrant, Emmanuelle [Hopital Le Bocage - CHU Dijon, Hematologie Clinique, Dijon Cedex (France); Casasnovas, Rene-Olivier [Hopital Le Bocage - CHU Dijon, Hematologie Clinique, Dijon Cedex (France); Universite de Bourgogne, Inserm U866, Labex team, Faculte de medecine, Dijon (France)

    2014-09-15

    The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p = 0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p = 0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = <71 % or TMTV0 >225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = <71 % and TMTV0 >225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively. TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may

  8. Anti-apoptotic A1 is not essential for lymphoma development in Eµ-Myc mice but helps sustain transplanted Eµ-Myc tumour cells.

    Science.gov (United States)

    Mensink, Mark; Anstee, Natasha S; Robati, Mikara; Schenk, Robyn L; Herold, Marco J; Cory, Suzanne; Vandenberg, Cassandra J

    2018-03-01

    The transcription factor c-MYC regulates a multiplicity of genes involved in cellular growth, proliferation, metabolism and DNA damage response and its overexpression is a hallmark of many tumours. Since MYC promotes apoptosis under conditions of stress, such as limited availability of nutrients or cytokines, MYC-driven cells are very much dependent on signals that inhibit cell death. Stress signals trigger apoptosis via the pathway regulated by opposing fractions of the BCL-2 protein family and previous genetic studies have shown that the development of B lymphoid tumours in Eµ-Myc mice is critically dependent on expression of pro-survival BCL-2 relatives MCL-1, BCL-W and, to a lesser extent, BCL-X L , but not BCL-2 itself, and that sustained growth of these lymphomas is dependent on MCL-1. Using recently developed mice that lack expression of all three functional pro-survival A1 genes, we show here that the kinetics of lymphoma development in Eµ-Myc mice and the competitive repopulation capacity of Eµ-Myc haemopoietic stem and progenitor cells is unaffected by the absence of A1. However, conditional loss of a single remaining functional A1 gene from transplanted A1-a -/- A1-b fl/fl A1-c -/- Eµ-Myc lymphomas slowed their expansion, significantly extending the life of the transplant recipients. Thus, A1 contributes to the survival of malignant Eµ-Myc-driven B lymphoid cells. These results strengthen the case for BFL-1, the human homologue of A1, being a valid target for drug development for MYC-driven tumours.

  9. Protective Effect of Zingiber officinale Against Dalton's Lymphoma Ascites Tumour by Regulating Inflammatory Mediator and Cytokines.

    Science.gov (United States)

    Rubila, Sundararaj; Ranganathan, Thottiam Vasudevan; Sakthivel, Kunnathur Murugesan

    2016-12-01

    The aim of the present investigation was to evaluate Zingiber officinale paste against Dalton's lymphoma ascites (DLA)-induced tumours in Swiss albino mice. Experimental animals received Z. officinale paste (low dose 100 mg/kg bw and high dose 500 mg/kg bw) orally for eight alternative days. Treatment with Z. officinale paste showed significant increase in haemoglobin level and decrease in aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (γ-GT) level. Z. officinale paste reduced the inflammatory mediators and cytokine levels, such as inducible nitric oxide (iNOS), tumour necrosis factor level (TNF-α) and interleukin-1β (IL-1β). Treatment with Z. officinale paste also significantly increased the antioxidant enzyme level, such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione transferase (GST), and decreased the lipid peroxidation. Treatment also increased the vitamin C and E levels in treated animals compared with the DLA-bearing host. Histopathological studies also confirmed the protective influence of Z. officinale paste against DLA. The present study suggested that Z. officinale paste could be used as natural spice and a potent antitumour agent.

  10. Multiphase modelling of vascular tumour growth in two spatial dimensions

    KAUST Repository

    Hubbard, M.E.

    2013-01-01

    In this paper we present a continuum mathematical model of vascular tumour growth which is based on a multiphase framework in which the tissue is decomposed into four distinct phases and the principles of conservation of mass and momentum are applied to the normal/healthy cells, tumour cells, blood vessels and extracellular material. The inclusion of a diffusible nutrient, supplied by the blood vessels, allows the vasculature to have a nonlocal influence on the other phases. Two-dimensional computational simulations are carried out on unstructured, triangular meshes to allow a natural treatment of irregular geometries, and the tumour boundary is captured as a diffuse interface on this mesh, thereby obviating the need to explicitly track the (potentially highly irregular and ill-defined) tumour boundary. A hybrid finite volume/finite element algorithm is used to discretise the continuum model: the application of a conservative, upwind, finite volume scheme to the hyperbolic mass balance equations and a finite element scheme with a stable element pair to the generalised Stokes equations derived from momentum balance, leads to a robust algorithm which does not use any form of artificial stabilisation. The use of a matrix-free Newton iteration with a finite element scheme for the nutrient reaction-diffusion equations allows full nonlinearity in the source terms of the mathematical model.Numerical simulations reveal that this four-phase model reproduces the characteristic pattern of tumour growth in which a necrotic core forms behind an expanding rim of well-vascularised proliferating tumour cells. The simulations consistently predict linear tumour growth rates. The dependence of both the speed with which the tumour grows and the irregularity of the invading tumour front on the model parameters is investigated. © 2012 Elsevier Ltd.

  11. Modelling breast cancer tumour growth for a stable disease population.

    Science.gov (United States)

    Isheden, Gabriel; Humphreys, Keith

    2017-01-01

    Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

  12. Adaptation to statins restricts human tumour growth in Nude mice

    International Nuclear Information System (INIS)

    Follet, Julie; Rémy, Lionel; Hesry, Vincent; Simon, Brigitte; Gillet, Danièle; Auvray, Pierrick; Corcos, Laurent; Le Jossic-Corcos, Catherine

    2011-01-01

    Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years

  13. Giant growth-hormone secreting pituitary tumour with etracranial extension

    Energy Technology Data Exchange (ETDEWEB)

    Ip Taipang; Chan Fuluk; Kung Annie Waichee; Lam Karen Siuling [Univ. of Hong Kong, Queen Mary Hospital (Hong Kong). Depts. of Medicine and Diagnostic Radiology

    1996-02-01

    A 19 year old female patient with typical features of acromegaly was found to have an extensive pituitary tumour with suprasellar, lateral and inferior extensions. Magnetic resonance imaging (MRI) also showed a portion of the tumour extending from the right cavernous sinus through the foramen ovale to become extracranial. Serum growth hormone (GH) was 52.6 mU/L basally and remained elevated after oral glucose, confirming the diagnosis of acromegaly. Treatment with the long-acting somatostatin analogue, octreotide, for 6 months led to a 30% reduction in tumour volume of the intracranial portion but no effect on the extracranial and sphenoidal extensions. She was subsequently treated with trans-sphenoidal surgery followed by external irradiation. The possibility of perineural spread of the tumour was considered. 9 refs., 1 tab., 1 fig.

  14. Giant growth-hormone secreting pituitary tumour with etracranial extension

    International Nuclear Information System (INIS)

    Ip Taipang; Chan Fuluk; Kung Annie Waichee; Lam Karen Siuling

    1996-01-01

    A 19 year old female patient with typical features of acromegaly was found to have an extensive pituitary tumour with suprasellar, lateral and inferior extensions. Magnetic resonance imaging (MRI) also showed a portion of the tumour extending from the right cavernous sinus through the foramen ovale to become extracranial. Serum growth hormone (GH) was 52.6 mU/L basally and remained elevated after oral glucose, confirming the diagnosis of acromegaly. Treatment with the long-acting somatostatin analogue, octreotide, for 6 months led to a 30% reduction in tumour volume of the intracranial portion but no effect on the extracranial and sphenoidal extensions. She was subsequently treated with trans-sphenoidal surgery followed by external irradiation. The possibility of perineural spread of the tumour was considered. 9 refs., 1 tab., 1 fig

  15. Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

    International Nuclear Information System (INIS)

    Oliveira, Soraya I de; Andrade, Luciana NS; Onuchic, Ana C; Nonogaki, Sueli; Fernandes, Patrícia D; Pinheiro, Mônica C; Rohde, Ciro BS; Chammas, Roger; Jancar, Sonia

    2010-01-01

    Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma. Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the

  16. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    International Nuclear Information System (INIS)

    Peres, Elodie A.; Valable, Samuel; Guillamo, Jean-Sebastien; Marteau, Lena; Bernaudin, Jean-Francois; Roussel, Simon; Lechapt-Zalcman, Emmanuele; Bernaudin, Myriam; Petit, Edwige

    2011-01-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  17. Stochastic modelling of avascular tumour growth and therapy

    International Nuclear Information System (INIS)

    Sahoo, S; Sahoo, A; Shearer, S F C

    2011-01-01

    In this paper, a generalized stochastic model for the growth of avascular tumours is presented. This model captures the dynamical evolution of avascular tumour cell subpopulations by incorporating Gaussian white noise into the growth rate of the mitotic function. This work generalizes the deterministic model proposed by Sherratt and Chaplain (2001 J. Math. Biol. 43 291) where they formulated a tumour model in an in vivo setting, in terms of continuum densities of proliferating, quiescent and necrotic cells. Detailed simulations of our model show that the inclusion of Gaussian noise in the original model of Sherratt and Chaplain substantially distorts the overall structure of the density profiles in addition to reducing the speed of tumour growth. Within this stochastic carcinogenesis framework the action of therapy is also investigated by replacing Gaussian white noise with a therapy term. We compare a constant therapy protocol with a logarithmic time-dependent protocol. Our results predict that a logarithmic therapy is more effective than the constant therapy protocol.

  18. Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas

    International Nuclear Information System (INIS)

    Schramm, Peter; Xyda, Argyro; Knauth, Michael; Klotz, Ernst; Tronnier, Volker; Hartmann, Marius

    2010-01-01

    Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data. PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (K Trans ). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests. In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p > 0.05), whereas high-grade gliomas demonstrated significantly higher values (p Trans , p Trans values compared with unaffected cerebral parenchyma (p = 0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p = 0.0078). PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and K Trans . (orig.)

  19. Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

    Science.gov (United States)

    Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

    2016-12-01

    Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. © 2016 John Wiley & Sons Ltd.

  20. Notch3 signalling promotes tumour growth in colorectal cancer.

    Science.gov (United States)

    Serafin, Valentina; Persano, Luca; Moserle, Lidia; Esposito, Giovanni; Ghisi, Margherita; Curtarello, Matteo; Bonanno, Laura; Masiero, Massimo; Ribatti, Domenico; Stürzl, Michael; Naschberger, Elisabeth; Croner, Roland S; Jubb, Adrian M; Harris, Adrian L; Koeppen, Hartmut; Amadori, Alberto; Indraccolo, Stefano

    2011-08-01

    Increased Notch1 activity has been observed in intestinal tumours, partially accomplished by β-catenin-mediated up-regulation of the Notch ligand Jagged-1. Whether further mechanisms of Notch activation exist and other Notch receptors might be involved is unclear. Microarray data indicated that Notch3 transcript levels are significantly up-regulated in primary and metastatic CRC samples compared to normal mucosa. Moreover, Notch3 protein was expressed at strong/moderate levels by 19.7% of 158 CRC samples analysed, and at weak levels by 51.2% of the samples. Intrigued by these findings, we sought to investigate whether Notch3 modulates oncogenic features of CRC cells. By exploiting xenografts of CRC cells with different tumourigenic properties in mice, we found that the aggressive phenotype was associated with altered expression of components of the Notch pathway, including Notch3, Delta-like 4 (DLL4), and Jagged-1 ligands. Stimulation with immobilized recombinant DLL4 or transduction with DLL4-expressing vectors dramatically increased Notch3 expression in CRC cells, associated with accelerated tumour growth. Forced expression of an active form of Notch3 mirrored the effects of DLL4 stimulation and increased tumour formation. Conversely, attenuation of Notch3 levels by shRNA resulted in perturbation of the cell cycle followed by reduction in cell proliferation, clonogenic capacity, and inhibition of tumour growth. Altogether, these findings indicate that Notch3 can modulate the tumourigenic properties of CRC cells and contributes to sustained Notch activity in DLL4-expressing tumours. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Primary pancreatic lymphoma – pancreatic tumours that are potentially curable without resection, a retrospective review of four cases

    International Nuclear Information System (INIS)

    Grimison, Peter S; Chin, Melvin T; Harrison, Michelle L; Goldstein, David

    2006-01-01

    Primary pancreatic lymphomas (PPL) are rare tumours of the pancreas. Symptoms, imaging and tumour markers can mimic pancreatic adenocarcinoma, but they are much more amenable to treatment. Treatment for PPL remains controversial, particularly the role of surgical resection. Four cases of primary pancreatic lymphoma were identified at Prince of Wales Hospital, Sydney, Australia. A literature review of cases of PPL reported between 1985 and 2005 was conducted, and outcomes were contrasted. All four patients presented with upper abdominal symptoms associated with weight loss. One case was diagnosed without surgery. No patients underwent pancreatectomy. All patients were treated with chemotherapy and radiotherapy, and two of four patients received rituximab. One patient died at 32 months. Three patients are disease free at 15, 25 and 64 months, one after successful retreatment. Literature review identified a further 103 patients in 11 case series. Outcomes in our series and other series of chemotherapy and radiotherapy compared favourably to surgical series. Biopsy of all pancreatic masses is essential, to exclude potentially curable conditions such as PPL, and can be performed without laparotomy. Combined multimodality treatment, utilising chemotherapy and radiotherapy, without surgical resection is advocated but a cooperative prospective study would lead to further improvement in treatment outcomes

  2. Lymphoma and the control of B cell growth and differentiation.

    Science.gov (United States)

    Rui, Lixin; Goodnow, Christopher C

    2006-05-01

    It is now widely accepted that lymphomagenesis is a multistep transformation process. A number of genetic changes and environmental and infectious factors contributing to the development and malignant progression of B-cell lymphoproliferative disorders are well documented. Reciprocal chromosomal translocations involving the immunoglobulin loci are a hallmark of most mature B cell lymphomas and lead to dysregulated expression of proto-oncogenes (c-myc) important for cell proliferation or genes involved in cell cycle progression (cyclin D1), differentiation block (bcl-6, PAX5) and cell survival (bcl-2, NF-kappaB). In addition, genetic alterations that inactivate tumor suppressor genes (p53, p16) have been frequently detected in some lymphoma tissues. Many of these genes are normally regulated by signals from the B cell antigen receptor. The high prevalence of bacterial and viral infection in lymphoma patients supports the hypothesis that infectious agents may play a contributory role in the development and evolution of B cell lymphoproliferative disorders by either directly inducing polyclonal B cell hyperactivation (EBV, HCV), or providing a chronic antigenic stimulus (EBV, HCV, HBV, H. pylori), or mimicking B cell antigen receptor signaling (EBV, HCV, HHV8), although whether these are causative factors or they are secondary to genetic changes in lymphomagenesis remains to be defined. Stimulatory signals from reactive T cells, local cytokines and growth factors can also contribute, to some extent, to the progression of transformation. Modulation of B cell antigen receptor signaling therefore emerges as a potentially powerful strategy for controlling the growth of certain B cell lymphomas.

  3. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Sasanelli, Myriam; Meignan, Michel; Haioun, Corinne; Itti, Emmanuel [Paris-Est University, Nuclear Medicine and Lymphoid Malignancies Unit, Henri Mondor Hospital, Creteil (France); Berriolo-Riedinger, Alina; Casasnovas, Rene-Olivier [Nuclear Medicine and Hematology, Georges-Francois Leclerc Center, Le Bocage Hospital, Dijon (France); Biggi, Alberto; Gallamini, Andrea [Nuclear Medicine and Hematology, Santa Croce e Carle Hospital, Cuneo (Italy); Siegel, Barry A.; Cashen, Amanda F. [Washington University School of Medicine, Nuclear Medicine and Oncology, Siteman Cancer Center, St. Louis, MO (United States); Vera, Pierre; Tilly, Herve [Nuclear Medicine and Hematology, Henri Becquerel Center, Rouen (France); Versari, Annibale [Nuclear Medicine, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia (Italy)

    2014-11-15

    We investigated the prognostic value of total metabolic tumour volume (TMTV) in diffuse large B-cell lymphoma (DLBCL). TMTV was measured in 114 patients with newly diagnosed DLBCL who underwent {sup 18}F-FDG PET/CT at baseline before immunochemotherapy. TMTV was computed by summing the volumes of all lymphomatous lesions after applying the local SUVmax threshold of 41 % using semiautomatic software. Prognostic value was assessed by Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Median follow-up was 39 months. Average pretherapy TMTV was 509 ± 568 cm{sup 3}. The 3-year estimates of PFS were 77 % in the low metabolic burden group (TMTV ≤550 cm{sup 3}) and 60 % in the high metabolic burden group (TMTV >550 cm{sup 3}, p = 0.04), and prediction of OS was even better (87 % vs. 60 %, p = 0.0003). Cox regression showed independence of TMTV for OS prediction (p = 0.002) compared with other pretherapy indices of tumour burden, such as tumour bulk and the International Prognostic Index. Pretherapy TMTV is an independent predictor of outcome in patients with DLBCL. (orig.)

  4. Low expression of Mda-7/IL-24 and high expression of C-myb in tumour tissues are predictors of poor prognosis for Burkitt lymphoma patients.

    Science.gov (United States)

    Ma, Ming; Zhao, Riyang; Yang, Xingxiao; Zhao, Lianmei; Liu, Lihua; Zhang, Cong; Wang, Xuexiao; Shan, Baoen

    2018-02-08

    Burkitt lymphoma is one of the most common types of haematopoietic malignancy in children and adolescents. Mda-7/IL-24 had been identified as a differentiation inducer of Burkitt lymphoma cells. Previous studies have revealed that knockdown of C-myb can also lead to the terminal differentiation of Burkitt lymphoma cells. The aim of the present study was to investigate the correlation between the expression of Mda-7/IL-24 and C-myb, as well as their prognostic significance, for Burkitt lymphoma patients. The tumour tissues were collected from 59 cases of Burkitt lymphoma patients and detected with Western blotting and immunohistochemistry. The results showed that the expression of Mda-7/IL-24 was lower, whereas the expression of C-myb was higher in Burkitt lymphoma tissues compared to specimens of normal lymph node tissues. Furthermore, C-myb expression was negatively correlated with Mda-7/IL-24 expression at the protein level in Burkitt lymphoma tissues and cell lines. Both the expression of Mda-7/IL-24 and C-myb in Burkitt lymphoma tissues was associated with some clinicopathological parameters, such as clinical stage, infiltration in the bone marrow, Ki67 and overall survival rates. These results indicated that low expression of Mda-7/IL-24 along with high expression of C-myb are predictors for poor prognosis of Burkitt lymphoma patients; this outcome suggests that Mda-7/IL-24 and C-myb might be potential targets for clinical treatment of Burkitt lymphoma. Mda-7/IL-24: melanoma differentiation associated gene7/interleukin 24; FCM: flow cytometry; Ecog: Eastern Cooperative Oncology Group; IPI: International lymphoma prognosis index.

  5. Haematogenous tumour growth in the inferior vena cava in a patient with a nonseminomatous testicular tumour

    NARCIS (Netherlands)

    Ham, S J; Koops, H Schraffordt; Sleijfer, D T; Freling, N M; Molenaar, W M

    1991-01-01

    The case history is reported of a patient with an invasion of the inferior vena cava by metastases of a non-seminomatous testicular tumour. He was treated with combination chemotherapy, followed by laparotomy and resection of residual tumour tissue. Fourteen months after this operation he is in good

  6. Mathematical modeling of liver metastases tumour growth and control with radiotherapy

    International Nuclear Information System (INIS)

    Campbell, Adrienne; Sivakumaran, Thiru; Wong, Eugene; Davidson, Melanie; Lock, Michael

    2008-01-01

    Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

  7. The role of gallium-67 tumour scintigraphy in patients with small, non-cleaved cell lymphoma

    International Nuclear Information System (INIS)

    Sandrock, D.; Lastoria, S.; Neumann, R.D.; Magrath, I.T.

    1993-01-01

    Two hundred and thirty-four scintigraphic studies were performed in 34 patients (27 men, 7 women, age 17.3±7.7 years) with small, non-cleaved cell lymphoma who had follow-up for 3-96 months (mean 21.6±21.7 months). Whole-body scintigraphy was performed 48-72 h following i.v. injection of 370 MBq gallium-67 citrate. 'Gold standards' for truth determinations were surgery, autopsy, histology, axial X-ray computed tomography, magnetic resonance imaging, ultrasonography and clinical follow-up. Overall, 181 of 234 studies were true negative. Eighty proven sites of disease had true positive 67 Ga uptake (in 21 patients/37 studies). Nineteen sites (in 12 patients/15 studies) were false positive. In addition, 31 benign lesions were detected and interpreted correctly in terms of non-malignancy. Ten lymphoma sites (in 6 patients/10 studies) were missed by scintigraphy. Overall, sensitivity of gallium scintigraphy was 89% when calculated by sites and 79% when calculated by studies. Corresponding specificities were 91% and 92%, respectively. Positive predictive values were 81% (sites) and 71% (studies), and negative predictive values 95% (sites and studies). Thus, gallium scintigraphy proved to be a sensitive and specific method for staging and follow-up in patients with small, non-cleaved cell lymphoma. (orig.)

  8. Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.

    Science.gov (United States)

    Gururajan, Murali; Dasu, Trivikram; Shahidain, Seif; Jennings, C Darrell; Robertson, Darrell A; Rangnekar, Vivek M; Bondada, Subbarao

    2007-01-01

    Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

  9. Renal space-occupying solid growth of uncertain tumour status in metastasising tumour of the testicles

    International Nuclear Information System (INIS)

    Engelhard, K.; Sarmiento-Garcia, G.; Worlicek, H.; Krankenhaus Martha-Maria, Nuernberg

    1988-01-01

    On the basis of a particular case of 'atypical' hypernephroma the main differential diagnosis of solid renal masses are described with reference to the basis disease: testicle tumour causing metastasis. The problems of determining the dignity of the disease by methods of sonography, pyelogram and CT are pointed out as well as the differences between those characteristics of the said tumour revealed by X-ray diagnosis and the known characteristics of substantial kidney deformations as described in medical literature. (orig.) [de

  10. Adenoviral gene transfer of angiostatic ATF-BPTI inhibits tumour growth

    International Nuclear Information System (INIS)

    Lefesvre, Pierre; Attema, Joline; Bekkum, Dirk van

    2002-01-01

    The outgrowth of new vessels – angiogenesis – in the tumour mass is considered to be a limiting factor of tumour growth. To inhibit the matrix lysis that is part of the tumour angiogenesis, we employed the chimeric protein mhATF-BPTI, composed of the receptor binding part of the urokinase (ATF) linked to an inhibitor of plasmin (BPTI). For delivery, recombinant adenovirus encoding the transgene of interest was injected intravenously or locally into the tumour. The anti tumour effect of this compound was compared to that of human endostatin and of mhATF alone in two different rat bronchial carcinomas growing either as subcutaneous implants or as metastases. Significant inhibition of the tumour growth and decrease of the number of lung metastasis was achieved when the concentration of mhATF-BPTI at the tumour site was above 400 of ng / g tissue. This concentration could be achieved via production by the liver, only if permissive to the recombinant adenovirus. When the tumour cells could be transduced, local delivery of the vector was enough to obtain a response. In the case of metastasis, the capacity of the lung tissue to concentrate the encoded protein was essential to reach the required therapeutic levels. Further, endostatin or mhATF could not reproduce the effects of mhATF-BPTI, at similar concentrations (mhATF) and even at 10-fold higher concentration (endostatin). The ATF-BPTI was shown to inhibit tumour growth of different rat lung tumours when critical concentration was reached. In these tumour models, endostatin or ATF induce almost no tumour response

  11. Multiphase modelling of vascular tumour growth in two spatial dimensions

    KAUST Repository

    Hubbard, M.E.; Byrne, H.M.

    2013-01-01

    the (potentially highly irregular and ill-defined) tumour boundary. A hybrid finite volume/finite element algorithm is used to discretise the continuum model: the application of a conservative, upwind, finite volume scheme to the hyperbolic mass balance equations

  12. Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors.

    Science.gov (United States)

    Butler, Jason M; Kobayashi, Hideki; Rafii, Shahin

    2010-02-01

    The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

  13. Sources of information on lymphoma associated with anti-tumour necrosis factor agents: comparison of published case reports and cases reported to the French pharmacovigilance system.

    Science.gov (United States)

    Théophile, Hélène; Schaeverbeke, Thierry; Miremont-Salamé, Ghada; Abouelfath, Abdelilah; Kahn, Valentine; Haramburu, Françoise; Bégaud, Bernard

    2011-07-01

    Anti-tumour necrosis factor (TNF) agents, through their intense immunoregulatory effect, have been suspected to increase the risk of malignant lymphoma. However, the classical epidemiological approaches conducted over about the last 10 years have not totally succeeded in addressing the question of a causal or artifactual association. Therefore, the analysis of a substantial set of case reports, although usually considered as poorly generalizable to the general population, could be particularly informative. Two main sources of case reports in postmarketing settings are available; publications in medical journals and reports to pharmacovigilance systems. The aim of the study was to compare the characteristics of case reports from both these sources in order to understand whether they provided the same information for the investigation of the causal link between lymphoma and anti-TNF agents. All case reports of malignant lymphoma in patients treated with an anti-TNF agent published in MEDLINE and all reports to the French pharmacovigilance system up to 1 February 2010 were identified. Cases of malignant lymphoma identified in postmarketing surveillance from both sources were compared regarding the following variables: age, sex, anti-TNF agent involved, indication for use, type of lymphoma, prior or concomitant immunosuppressive drugs and time to onset of lymphoma. A total of 81 published case reports and 61 cases reported to the French pharmacovigilance system were compared. In published reports, patients were younger (p = 0.03) and more frequently receiving a first anti-TNF treatment (p = 0.03), particularly infliximab (p = 0.03). Conversely, in the pharmacovigilance system reports, a succession of different anti-TNFs (p = 0.03) and adalimumab (p French pharmacovigilance system differed markedly for all characteristics tested, except sex and the use of prior or concomitant immunosuppressive drugs. Published case reports favoured convincing arguments

  14. Oscillatory dynamics in a model of vascular tumour growth - implications for chemotherapy

    Directory of Open Access Journals (Sweden)

    Maini PK

    2010-04-01

    Full Text Available Abstract Background Investigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth. Results By analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one of λ-ω type dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls. Conclusions We have developed a mathematical model of vascular tumour growth formulated as a system of partial

  15. On the relationship between tumour growth rate and survival in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hitesh B. Mistry

    2017-11-01

    Full Text Available A recurrent question within oncology drug development is predicting phase III outcome for a new treatment using early clinical data. One approach to tackle this problem has been to derive metrics from mathematical models that describe tumour size dynamics termed re-growth rate and time to tumour re-growth. They have shown to be strong predictors of overall survival in numerous studies but there is debate about how these metrics are derived and if they are more predictive than empirical end-points. This work explores the issues raised in using model-derived metric as predictors for survival analyses. Re-growth rate and time to tumour re-growth were calculated for three large clinical studies by forward and reverse alignment. The latter involves re-aligning patients to their time of progression. Hence, it accounts for the time taken to estimate re-growth rate and time to tumour re-growth but also assesses if these predictors correlate to survival from the time of progression. I found that neither re-growth rate nor time to tumour re-growth correlated to survival using reverse alignment. This suggests that the dynamics of tumours up until disease progression has no relationship to survival post progression. For prediction of a phase III trial I found the metrics performed no better than empirical end-points. These results highlight that care must be taken when relating dynamics of tumour imaging to survival and that bench-marking new approaches to existing ones is essential.

  16. Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth

    NARCIS (Netherlands)

    Lamers, Fieke; Schild, Linda; den Hartog, Ilona J. M.; Ebus, Marli E.; Westerhout, Ellen M.; Ora, Ingrid; Koster, Jan; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.

    2012-01-01

    Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is

  17. Reduction of Myeloid-derived Suppressor Cells and Lymphoma Growth by a Natural Triterpenoid

    Science.gov (United States)

    Radwan, Faisal F. Y.; Hossain, Azim; God, Jason M.; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2016-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A’s anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen presentation and CD4+ T cell recognition of lymphoma in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. PMID:25142864

  18. Investigation of various growth mechanisms of solid tumour growth within the linear-quadratic model for radiotherapy

    International Nuclear Information System (INIS)

    McAneney, H; O'Rourke, S F C

    2007-01-01

    The standard linear-quadratic survival model for radiotherapy is used to investigate different schedules of radiation treatment planning to study how these may be affected by different tumour repopulation kinetics between treatments. The laws for tumour cell repopulation include the logistic and Gompertz models and this extends the work of Wheldon et al (1977 Br. J. Radiol. 50 681), which was concerned with the case of exponential re-growth between treatments. Here we also consider the restricted exponential model. This has been successfully used by Panetta and Adam (1995 Math. Comput. Modelling 22 67) in the case of chemotherapy treatment planning.Treatment schedules investigated include standard fractionation of daily treatments, weekday treatments, accelerated fractionation, optimized uniform schedules and variation of the dosage and α/β ratio, where α and β are radiobiological parameters for the tumour tissue concerned. Parameters for these treatment strategies are extracted from the literature on advanced head and neck cancer, prostate cancer, as well as radiosensitive parameters. Standardized treatment protocols are also considered. Calculations based on the present analysis indicate that even with growth laws scaled to mimic initial growth, such that growth mechanisms are comparable, variation in survival fraction to orders of magnitude emerged. Calculations show that the logistic and exponential models yield similar results in tumour eradication. By comparison the Gompertz model calculations indicate that tumours described by this law result in a significantly poorer prognosis for tumour eradication than either the exponential or logistic models. The present study also shows that the faster the tumour growth rate and the higher the repair capacity of the cell line, the greater the variation in outcome of the survival fraction. Gaps in treatment, planned or unplanned, also accentuate the differences of the survival fraction given alternative growth

  19. Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts

    International Nuclear Information System (INIS)

    Tuomela, Johanna; Solin, Olof; Minn, Heikki; Härkönen, Pirkko L; Grönroos, Tove J; Valta, Maija P; Sandholm, Jouko; Schrey, Aleksi; Seppänen, Jani; Marjamäki, Päivi; Forsback, Sarita; Kinnunen, Ilpo

    2010-01-01

    Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([ 18 F]FDG) and hypoxia ([ 18 F]EF5), and intratumoral polarographic measurements of pO 2 . Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO 2 measurements, [ 18 F]EF5 and [ 18 F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts

  20. Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.

    Science.gov (United States)

    Nguyen, Hoang-Yen T; Vo, Bach-Hue T; Nguyen, Lac-Thuy H; Bernad, Jose; Alaeddine, Mohamad; Coste, Agnes; Reybier, Karine; Pipy, Bernard; Nepveu, Françoise

    2013-08-26

    Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear. To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages. The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages). The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not

  1. Investigating the effect of longitudinal micro-CT imaging on tumour growth in mice

    Energy Technology Data Exchange (ETDEWEB)

    Foster, W Kyle; Ford, Nancy L, E-mail: nlford@ryerson.ca [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada)

    2011-01-21

    The aim of this study is to determine the impact of longitudinal micro-CT imaging on the growth of B16F1 tumours in C57BL/6 mice. Sixty mice received 2 x 10{sup 5} B16F1 cells subcutaneously in the hind flank and were divided into control (no scan), 'low-dose' (80 kVp, 70 mA, 8 s, 0.07 Gy), 'medium-dose' (80 kVp, 50 mA, 30 s, 0.18 Gy) and 'high-dose' (80 kVp, 50 mA, 50 s, 0.30 Gy) groups. All imaging was performed on a fast volumetric micro-CT scanner (GE Locus Ultra, London, Canada). Each mouse was imaged on days 4, 8, 12 and 16. After the final imaging session, each tumour was excised, weighed on an electronic balance, imaged to obtain the final tumour volume and processed for histology. Final tumour volume was used to evaluate the impact of longitudinal micro-CT imaging on the tumour growth. An ANOVA indicated no statistically significant difference in tumour volume (p = 0.331, {alpha} = {beta} = 0.1) when discriminating against a treatment-sized effect. Histological samples revealed no observable differences in apoptosis or cell proliferation. We conclude that four imaging sessions, using standard protocols, over the course of 16 days did not cause significant changes in final tumour volume for B16F1 tumours in female C57BL/6 mice (ANOVA, {alpha} = {beta} = 0.1, p = 0.331).

  2. Investigating the effect of longitudinal micro-CT imaging on tumour growth in mice

    International Nuclear Information System (INIS)

    Foster, W Kyle; Ford, Nancy L

    2011-01-01

    The aim of this study is to determine the impact of longitudinal micro-CT imaging on the growth of B16F1 tumours in C57BL/6 mice. Sixty mice received 2 x 10 5 B16F1 cells subcutaneously in the hind flank and were divided into control (no scan), 'low-dose' (80 kVp, 70 mA, 8 s, 0.07 Gy), 'medium-dose' (80 kVp, 50 mA, 30 s, 0.18 Gy) and 'high-dose' (80 kVp, 50 mA, 50 s, 0.30 Gy) groups. All imaging was performed on a fast volumetric micro-CT scanner (GE Locus Ultra, London, Canada). Each mouse was imaged on days 4, 8, 12 and 16. After the final imaging session, each tumour was excised, weighed on an electronic balance, imaged to obtain the final tumour volume and processed for histology. Final tumour volume was used to evaluate the impact of longitudinal micro-CT imaging on the tumour growth. An ANOVA indicated no statistically significant difference in tumour volume (p = 0.331, α = β = 0.1) when discriminating against a treatment-sized effect. Histological samples revealed no observable differences in apoptosis or cell proliferation. We conclude that four imaging sessions, using standard protocols, over the course of 16 days did not cause significant changes in final tumour volume for B16F1 tumours in female C57BL/6 mice (ANOVA, α = β = 0.1, p = 0.331).

  3. Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Darendeliler, F.; Livesey, E.A.; Hindmarsh, P.C.; Brook, C.G.D. (Endocrine Unit, The Middlesex Hospital, London (UK))

    1990-01-01

    We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n=20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n=36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whome were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m{sup 2}/week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. (authors).

  4. Growth and growth hormone secretion in children following treatment of brain tumours with radiotherapy

    International Nuclear Information System (INIS)

    Darendeliler, F.; Livesey, E.A.; Hindmarsh, P.C.; Brook, C.G.D.

    1990-01-01

    We have studied the growth of 144 children after treatment of brain tumours distant from the hypothalamo-pituitary axis. All had cranial irradiation and 87 spinal irradiation. In 56 patients observed without intervention for 3 years, height SDS in the cranial (CR) group (n=20) declined from 0.02 to -0.44 and in the craniospinal (CS) group (n=36) from -0.28 to -1.11. Failure of spinal growth had a marked effect in the CS group. The onset of puberty was slightly but not significantly advanced; median ages at onset of puberty were 10.3 years in girls and 12.1 years in boys. Of the total group 86.4% had clinical and biochemical evidence of growth hormone insufficiency. Fifty-two children, 33 (28 CS; 5 CR) of whome were prepubertal, received biosynthetic human growth hormone, in a dose of 15 mU/m 2 /week by daily injection for a period of one year. Height velocity SDS increased significantly in both groups from -2.74 to +1.90 (CS) and from -1.0 to +4.26 (CR). Spinal response to GH treatment was restricted in the craniospinal group. (authors)

  5. Regulation of Id2 expression in EL4 T lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A

    2009-01-01

    In previous studies, we have shown that overexpression of growth hormone (GH) in cells of the immune system upregulates proteins involved in cell growth and protects from apoptosis. Here, we report that overexpression of GH in EL4 T lymphoma cells (GHo) also significantly increased levels of the inhibitor of differentiation-2 (Id2). The increase in Id2 was suggested in both Id2 promoter luciferase assays and by Western analysis for Id2 protein. To identify the regulatory elements that mediate transcriptional activation by GH in the Id2 promoter, promoter deletion analysis was performed. Deletion analysis revealed that transactivation involved a 301-132bp region upstream to the Id2 transcriptional start site. The pattern in the human GHo Jurkat T lymphoma cell line paralleled that found in the mouse GHo EL4 T lymphoma cell line. Significantly less Id2 was detected in the nucleus of GHo EL4 T lymphoma cells compared to vector alone controls. Although serum increased the levels of Id2 in control vector alone cells, no difference was found in the total levels of Id2 in GHo EL4 T lymphoma cells treated with or without serum. The increase in Id2 expression in GHo EL4 T lymphoma cells measured by Id2 promoter luciferase expression and Western blot analysis was blocked by the overexpression of a dominant-negative mutant of STAT5. The results suggest that in EL4 T lymphoma cells overexpressing GH, there is an upregulation of Id2 protein that appears to involve STAT protein activity.

  6. Three-dimensional reconstruction of prostate cancer architecture with serial immunohistochemical sections: hallmarks of tumour growth, tumour compartmentalisation, and implications for grading and heterogeneity.

    Science.gov (United States)

    Tolkach, Yuri; Thomann, Stefan; Kristiansen, Glen

    2018-05-01

    Conventional morphology of prostate cancer considers only the two-dimensional (2D) architecture of the tumour. Our aim was to examine the feasibility of three-dimensional (3D) reconstruction of tumour morphology based on multiple consecutive histological sections and to decipher relevant features of prostate cancer architecture. Seventy-five consecutive histological sections (5 μm) of a typical prostate adenocarcinoma (Gleason score of 3 + 4 = 7) were immunostained (pan-cytokeratin) and scanned for further 3D reconstructions with fiji/imagej software. The main findings related to the prostate cancer architecture in this case were: (i) continuity of all glands, with the tumour being an integrated system, even in Gleason pattern 4 with poorly formed glands-no short-range migration of cells by Gleason pattern 4 (poorly formed glands); (ii) no repeated interconnections between the glands, with a tumour building a tree-like branched structure with very 'plastic' branches (maximal depth of investigation 375 μm); (iii) very stark compartmentalisation of the tumour related to extensive branching, the coexistence of independent terminal units of such branches in one 2D slice explaining intratumoral heterogeneity; (iv) evidence of a craniocaudal growth direction in interglandular regions of the prostate and for a lateromedial growth direction in subcapsular posterolateral regions; and (v) a 3D architecture-based description of Gleason pattern 4 with poorly formed glands, and its continuum with Gleason pattern 3. Consecutive histological sections provide high-quality material for 3D reconstructions of the tumour architecture, with excellent resolution. The reconstruction of multiple regions in this typical case of a Gleason score 3 + 4 = 7 tumour provides insights into relevant aspects of tumour growth, the continuity of Gleason patterns 3 and 4, and tumour heterogeneity. © 2018 John Wiley & Sons Ltd.

  7. Vascular endothelial growth factor in prognosis of splenic malignant tumours in dogs

    Directory of Open Access Journals (Sweden)

    Sobczyńska-Rak Aleksandra

    2014-06-01

    Full Text Available The aim of the study was to determine the levels of the vascular endothelial growth factor (VEGF in the serum of dogs suffering from splenic malignant tumours, prior to splenectomy, as well as three and six months after the surgery. Tumours and blood samples were collected from 10 dogs of various breeds, aged between 7 and 13 years, and from 10 control animals. Tumour sections were fixed in 10% buffered formalin for 24 h. The type of tumour was determined according to the WHO classification. Blood samples were centrifuged and the obtained sera were subjected to immunoenzymatic assays to determine the VEGF levels. The median of VEGF levels in the serum of dogs suffering from splenic malignant tumours was 37.85 pg/mL (15.40-107.18 pg/mL. The highest values were observed in dogs with confirmed metastases (107.18 pg/mL and 65.43 pg/mL. The VEGF values in control group were between 0.1 pg/mL and 13.04 pg/mL. A comparative analysis of the VEGF levels against the animals' survival time indicated that VEGF overexpression may serve as a prognostic factor in cases of malignant tumours of the spleen.

  8. Complement-mediated tumour growth: implications for cancer nanotechnology and nanomedicines

    DEFF Research Database (Denmark)

    Moghimi, S. M.; Andresen, Thomas Lars

    2009-01-01

    The recent unexpected observation that complement activation helps turnout growth and progression has an important bearing on the future development of cancer nanomedicines for site-specific tumour targeting as these entities are capable of triggering complement. These issues are discussed and su...

  9. Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth

    Directory of Open Access Journals (Sweden)

    Hiroaki Haga

    2015-01-01

    Full Text Available The contributions of mesenchymal stem cells (MSCs to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs. We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth.

  10. Early growth of tumour cells in lung tissue

    International Nuclear Information System (INIS)

    Poll, P.H.A.

    1981-01-01

    As the treatment of metastases is a very important problem in human and veterinary medicine (for instance osteosarcoma is notorious for its high deathrate due to this problem), proof was sought for the hypothesis that the doubling time of early metastases is shorter than that of tumor cells of an older age. This is of fundamental importance for the therapeutic problem: is a favourable effect to be expected from a limited dose of radiation on the lungs when metastases are still very small or even invisible. If the hypothesis holds true, it would be justified to treat patients, even though a small group of patients will be treated unnecessarily; clinical experience shows that some patients have not developed metastases without adjuvant treatment. The interest was directed at the very early (1-cell, 2-cell etc.) stages. Obviously these are not detectable in patients and therefore an experimental study with tumourcells in the lungs of mice was devised. The expectation is that the theoretical approach may produce an additional basis for the radiotherapeutic and chemotherapeutic treatment of patients, in whom the tumourload has been diminished by treatment of the primary tumour but where metastases, although frequently not detectable must be expected. (Auth.)

  11. Reduction of myeloid-derived suppressor cells and lymphoma growth by a natural triterpenoid.

    Science.gov (United States)

    Radwan, Faisal F Y; Hossain, Azim; God, Jason M; Leaphart, Nathan; Elvington, Michelle; Nagarkatti, Mitzi; Tomlinson, Stephen; Haque, Azizul

    2015-01-01

    Lymphoma is a potentially life threatening disease. The goal of this study was to investigate the therapeutic potential of a natural triterpenoid, Ganoderic acid A (GA-A) in controlling lymphoma growth both in vitro and in vivo. Here, we show that GA-A treatment induces caspase-dependent apoptotic cell death characterized by a dose-dependent increase in active caspases 9 and 3, up-regulation of pro-apoptotic BIM and BAX proteins, and a subsequent loss of mitochondrial membrane potential with release of cytochrome c. In addition to GA-A's anti-growth activity, we show that lower doses of GA-A enhance HLA class II-mediated antigen (Ag) presentation and CD4+ T cell recognition of lymphoma cells in vitro. The therapeutic relevance of GA-A treatment was also tested in vivo using the EL4 syngeneic mouse model of metastatic lymphoma. GA-A-treatment significantly prolonged survival of EL4 challenged mice and decreased tumor metastasis to the liver, an outcome accompanied by a marked down-regulation of STAT3 phosphorylation, reduction myeloid-derived suppressor cells (MDSCs), and enhancement of cytotoxic CD8+ T cells in the host. Thus, GA-A not only selectively induces apoptosis in lymphoma cells, but also enhances cell-mediated immune responses by attenuating MDSCs, and elevating Ag presentation and T cell recognition. The demonstrated therapeutic benefit indicates that GA-A is a candidate for future drug design for the treatment of lymphoma. © 2014 Wiley Periodicals, Inc.

  12. A study of tumour growth based on stoichiometric principles: a continuous model and its discrete analogue.

    Science.gov (United States)

    Saleem, M; Agrawal, Tanuja; Anees, Afzal

    2014-01-01

    In this paper, we consider a continuous mathematically tractable model and its discrete analogue for the tumour growth. The model formulation is based on stoichiometric principles considering tumour-immune cell interactions in potassium (K (+))-limited environment. Our both continuous and discrete models illustrate 'cancer immunoediting' as a dynamic process having all three phases namely elimination, equilibrium and escape. The stoichiometric principles introduced into the model allow us to study its dynamics with the variation in the total potassium in the surrounding of the tumour region. It is found that an increase in the total potassium may help the patient fight the disease for a longer period of time. This result seems to be in line with the protective role of the potassium against the risk of pancreatic cancer as has been reported by Bravi et al. [Dietary intake of selected micronutrients and risk of pancreatic cancer: An Italian case-control study, Ann. Oncol. 22 (2011), pp. 202-206].

  13. Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in cancer biology-Involvement in tumour suppression, tumour growth, multidrug resistance and target for chemotherapy.

    Science.gov (United States)

    Rabbani, Naila; Xue, Mingzhan; Weickert, Martin O; Thornalley, Paul J

    2018-04-01

    Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all human cells. It catalyses the glutathione-dependent removal of the endogenous reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side product of anaerobic glycolysis. It modifies protein and DNA to form mainly hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal accumulation of MG, dicarbonyl stress, increases adduct levels which may induce apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a tumour suppressor protein and small molecule inducers of Glo1 expression may find use in cancer prevention. Increased Glo1 expression is permissive for growth of tumours with high glycolytic activity and is thereby a biomarker of tumour growth. High Glo1 expression is a cause of multi-drug resistance. It is produced by over-activation of the Nrf2 pathway and GLO1 amplification. Glo1 inhibitors are antitumour agents, inducing apoptosis and necrosis, and anoikis. Tumour stem cells and tumours with high flux of MG formation and Glo1 expression are sensitive to Glo1 inhibitor therapy. It is likely that MG-induced cell death contributes to the mechanism of action of current antitumour agents. Common refractory tumours have high prevalence of Glo1 overexpression for which Glo1 inhibitors may improve therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.

    Science.gov (United States)

    Varano, Gabriele; Raffel, Simon; Sormani, Martina; Zanardi, Federica; Lonardi, Silvia; Zasada, Christin; Perucho, Laura; Petrocelli, Valentina; Haake, Andrea; Lee, Albert K; Bugatti, Mattia; Paul, Ulrike; Van Anken, Eelco; Pasqualucci, Laura; Rabadan, Raul; Siebert, Reiner; Kempa, Stefan; Ponzoni, Maurilio; Facchetti, Fabio; Rajewsky, Klaus; Casola, Stefano

    2017-06-08

    Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR - ) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR + ) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR + tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR - tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR - lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR - tumour cells.

  15. Bayesian Calibration, Validation and Uncertainty Quantification for Predictive Modelling of Tumour Growth: A Tutorial.

    Science.gov (United States)

    Collis, Joe; Connor, Anthony J; Paczkowski, Marcin; Kannan, Pavitra; Pitt-Francis, Joe; Byrne, Helen M; Hubbard, Matthew E

    2017-04-01

    In this work, we present a pedagogical tumour growth example, in which we apply calibration and validation techniques to an uncertain, Gompertzian model of tumour spheroid growth. The key contribution of this article is the discussion and application of these methods (that are not commonly employed in the field of cancer modelling) in the context of a simple model, whose deterministic analogue is widely known within the community. In the course of the example, we calibrate the model against experimental data that are subject to measurement errors, and then validate the resulting uncertain model predictions. We then analyse the sensitivity of the model predictions to the underlying measurement model. Finally, we propose an elementary learning approach for tuning a threshold parameter in the validation procedure in order to maximize predictive accuracy of our validated model.

  16. The influence of elevated levels of platelet-derived endothelial cell growth factor/thymidine phosphorylase on tumourigenicity, tumour growth, and oxygenation

    International Nuclear Information System (INIS)

    Griffiths, L.; Stratford, I.J.

    1998-01-01

    Purpose: Investigation of the effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on various aspects of tumour growth in a xenograft model, including growth rate, tumourigenicity and oxygenation levels. Methods and Materials: MDA 231 breast cancer cells overexpressing PD-ECGF/TP protein were made by retroviral transduction. These cells were grown in vitro and in vivo as xenografts. Direct measurement of tumours was used to record growth parameters, while the comet assay with the bioreductive drug RSU 1069 was used to assess tumour cell oxygenation. Results: We report that MDA 231 breast tumour cell lines expressing an increased range of levels of PD-ECGF/TP have increased tumourigenicity positively related to the level of PD-ECGF/TP when implanted in nude mice. As previously reported, tumours grown from these overexpressing cell lines grew faster than the parental line. These tumours expressed higher levels of TP activity and showed increased immunocytochemical staining for PD-ECGF. In addition, the rate of growth was found to be positively related to the level of PD-ECGF/TP expressed by the tumour cells. When the comet assay was used to compare the oxygenation status of cells between the parental and PD-ECGF/TP overexpressing tumours, the latter were found to have a larger proportion of well oxygenated cells. This is consistent with these tumours having an increased and functionally competent vascular supply in response to the expression of PD-ECGF/TP. Conclusion: PD-ECGF/TP appears to be capable of influencing tumourigenicity, angiogenesis and tumour growth in a proportional manner and can directly influence tumour oxygenation levels via its role in formation of functional vasculature

  17. Isthmin is a novel secreted angiogenesis inhibitor that inhibits tumour growth in mice

    Science.gov (United States)

    Xiang, Wei; Ke, Zhiyuan; Zhang, Yong; Ho-Yuet Cheng, Grace; Irwan, Ishak Darryl; Sulochana, K N; Potturi, Padma; Wang, Zhengyuan; Yang, He; Wang, Jingyu; Zhuo, Lang; Kini, R Manjunatha; Ge, Ruowen

    2011-01-01

    Abstract Anti-angiogenesis represents a promising therapeutic strategy for the treatment of various malignancies. Isthmin (ISM) is a gene highly expressed in the isthmus of the midbrain–hindbrain organizer in Xenopus with no known functions. It encodes a secreted 60 kD protein containing a thrombospondin type 1 repeat domain in the central region and an adhesion-associated domain in MUC4 and other proteins (AMOP) domain at the C-terminal. In this work, we demonstrate that ISM is a novel angiogenesis inhibitor. Recombinant mouse ISM inhibited endothelial cell (EC) capillary network formation on Matrigel through its C-terminal AMOP domain. It also suppressed vascular endothelial growth factor (VEGF)-basic fibroblast growth factor (bFGF) induced in vivo angiogenesis in mouse. It mitigated VEGF-stimulated EC proliferation without affecting EC migration. Furthermore, ISM induced EC apoptosis in the presence of VEGF through a caspase-dependent pathway. ISM binds to αvβ5 integrin on EC surface and supports EC adhesion. Overexpression of ISM significantly suppressed mouse B16 melanoma tumour growth through inhibition of tumour angiogenesis without affecting tumour cell proliferation. Knockdown of isthmin in zebrafish embryos using morpholino antisense oligonucleotides led to disorganized intersegmen-tal vessels in the trunk. Our results demonstrate that ISM is a novel endogenous angiogenesis inhibitor with functions likely in physiological as well as pathological angiogenesis. PMID:19874420

  18. Isthmin is a novel secreted angiogenesis inhibitor that inhibits tumour growth in mice.

    Science.gov (United States)

    Xiang, Wei; Ke, Zhiyuan; Zhang, Yong; Cheng, Grace Ho-Yuet; Irwan, Ishak Darryl; Sulochana, K N; Potturi, Padma; Wang, Zhengyuan; Yang, He; Wang, Jingyu; Zhuo, Lang; Kini, R Manjunatha; Ge, Ruowen

    2011-02-01

    Anti-angiogenesis represents a promising therapeutic strategy for the treatment of various malignancies. Isthmin (ISM) is a gene highly expressed in the isthmus of the midbrain-hindbrain organizer in Xenopus with no known functions. It encodes a secreted 60 kD protein containing a thrombospondin type 1 repeat domain in the central region and an adhesion-associated domain in MUC4 and other proteins (AMOP) domain at the C-terminal. In this work, we demonstrate that ISM is a novel angiogenesis inhibitor. Recombinant mouse ISM inhibited endothelial cell (EC) capillary network formation on Matrigel through its C-terminal AMOP domain. It also suppressed vascular endothelial growth factor (VEGF)-basic fibroblast growth factor (bFGF) induced in vivo angiogenesis in mouse. It mitigated VEGF-stimulated EC proliferation without affecting EC migration. Furthermore, ISM induced EC apoptosis in the presence of VEGF through a caspase-dependent pathway. ISM binds to αvβ(5) integrin on EC surface and supports EC adhesion. Overexpression of ISM significantly suppressed mouse B16 melanoma tumour growth through inhibition of tumour angiogenesis without affecting tumour cell proliferation. Knockdown of isthmin in zebrafish embryos using morpholino antisense oligonucleotides led to disorganized intersegmental vessels in the trunk. Our results demonstrate that ISM is a novel endogenous angiogenesis inhibitor with functions likely in physiological as well as pathological angiogenesis. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  19. The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

    Science.gov (United States)

    Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

    2016-08-01

    Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice. Copyright © 2016 Norwegian Institute of Public Health. Published by Elsevier Ltd.. All rights reserved.

  20. Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo.

    Directory of Open Access Journals (Sweden)

    Jason R Sutherland

    Full Text Available Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2, cytokines interleukin (IL -6, and -11 and vascular endothelial growth factor-A (VEGF-A. To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.

  1. 2008 update of standards, options: recommendations for management of patients with salivary gland malignant tumours (excluding lymphoma, sarcoma and melanoma), summary report

    International Nuclear Information System (INIS)

    Bensadoun, R.J.; Dassonville, O.; Rousmans, S.

    2008-01-01

    Context: An update of the S.O.R.-C.P.G. for management of patients with salivary gland malignant tumours has been initiated by the French National Federation of Cancer Centres (F.N.C.L.C.C.) in collaboration with French league against cancer, specialists from university or general hospitals and private clinics, and with the French National Cancer Institute. This work performed is based on the methodology developed and used in the 'Standards, Options: Recommendations' program (S.O.R.). Objectives. To update the S.O.R. guideline for the management of patients with salivary gland malignant tumors (excluding lymphoma, sarcoma and melanoma) previously validated in 1997 and 2003. Method: The guideline development process is based on literature review and critical appraisal by a multidisciplinary group of experts. The methodological approach combines systematic review with expert judgement. Recommendations take into account the effectiveness and toxicity of the different therapeutic alternatives and the levels of evidence. Following their development and prior to publication, S.O.R.-guidelines are reviewed by independent practitioners in cancer care delivery. Results: This paper is a summary version of the full clinical practice guideline presenting the updated recommendations. Recommendations on radiotherapy have been updated to underline new Options on more and more accessible emerging techniques including 'intensity-modulated radiotherapy', '3-D conformational radiotherapy', 'Cyber-knife', 'Tomotherapy', 'Proton therapy' and 'particle accelerators producing carbon ions' (e.g. last generation hadron therapy). Therapeutical modalities have also been specified. (authors)

  2. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo

    Science.gov (United States)

    Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M.; Brennan, Patrick J.; Banerjee, Pinaki P.; Wiener, Susan J.; Orange, Jordan S.; Brenner, Michael B.; Grupp, Stephan A.; Nichols, Kim E.

    2013-01-01

    Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we find that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially-induced by iNKT cell agonists of varying TCR affinities, such as OCH, α-galactosyl ceramide and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of T cell receptor (TCR) signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell-deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T-lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T-lymphoma. PMID:24563871

  3. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo .

    Science.gov (United States)

    Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M; Brennan, Patrick J; Banerjee, Pinaki P; Wiener, Susan J; Orange, Jordan S; Brenner, Michael B; Grupp, Stephan A; Nichols, Kim E

    2014-01-01

    Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we found that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially induced by iNKT cell agonists of varying T-cell receptor (TCR) affinities, such as OCH, α-galactosyl ceramide, and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell–deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma. ©2013 AACR.

  4. The effect of mixed fractionation with X rays and neutrons on tumour growth delay and skin reactions in mice

    International Nuclear Information System (INIS)

    Carl, U.M.

    1987-01-01

    The authors have compared the effects of mixed fractionation schedules with X rays and neutrons on growth delay of a murine tumour and skin reactions in mice. The schedules were five daily fractions of X rays, neutrons or mixtures (NNXXX, XXXNN or NXXXN). For clamped tumours or skin all three mixed schedules had the same effect. In contrast, for unclamped tumours giving the neutrons first (NNXXX) was more effective than the other two mixed schedules. This represented a true therapeutic gain and implies that if neutrons are used clinically as only part of a course of fractionated radiotherapy, they should be given at the beginning rather than at the end of treatment. (author)

  5. Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo.

    Science.gov (United States)

    Ahn, Jin-Ok; Chae, Ji-Sang; Coh, Ye-Rin; Jung, Woo-Sung; Lee, Hee-Woo; Shin, Il-Seob; Kang, Sung-Keun; Youn, Hwa-Young

    2014-09-01

    Human mesenchymal stem cells (hMSCs) are thought to be one of the most reliable stem cell sources for a variety of cell therapies. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on EL4 murine T-cell lymphoma in vitro and in vivo. The growth-inhibitory effect of hAT-MSCs on EL4 tumor cells was evaluated using a WST-1 cell proliferation assay. Cell-cycle arrest and apoptosis were investigated by flow cytometry and western blot. To evaluate an anti-tumor effect of hAT-MSCs on T-cell lymphoma in vivo, CM-DiI-labeled hAT-MSCs were circumtumorally injected in tumor-bearing nude mice, and tumor size was measured. hAT-MSCs inhibited T-cell lymphoma growth by altering cell-cycle progression and inducing apoptosis in vitro. hAT-MSCs inhibited tumor growth in tumor-bearing nude mice and prolonged survival time. Immunofluorescence analysis showed that hAT-MSCs migrated to tumor sites. hAT-MSCs suppress the growth of T-cell lymphoma, suggesting a therapeutic option for T-cell lymphoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Acromegaly caused by a growth hormonereleasing hormone secreting carcinoid tumour of the lung : the effect of octreotide treatment

    NARCIS (Netherlands)

    De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.

    2007-01-01

    in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the

  7. Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

    Science.gov (United States)

    Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

    2018-05-01

    Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

  8. [Secondary orbital lymphoma].

    Science.gov (United States)

    Basanta, I; Sevillano, C; Álvarez, M D

    2015-09-01

    A case is presented of an 85 year-old Caucasian female with lymphoma that recurred in the orbit (secondary ocular adnexal lymphoma). The orbital tumour was a diffuse large B-cell lymphoma according to the REAL classification (Revised European-American Lymphoma Classification). Orbital lymphomas are predominantly B-cell proliferations of a variety of histological types, and most are low-grade tumours. Patients are usually middle-aged or elderly, and it is slightly more common in women. A palpable mass, proptosis and blepharoptosis are the most common signs of presentation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Growth Pattern of Follicles in Mice after X-Ray or DMBA Induction of Ovarian Tumours

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, T.; Krarup, T.; Peters, H.; Faber, M. [Finsen Institute, Copenhagen (Denmark)

    1969-11-15

    Whole-body X-irradiation of mice as well as treatment with the carcinogenic hydrocarbon 9:10-dimethyl-1:2 benzanthracene results in the formation of ovarian tumours. After both experimental procedures an immediate destruction of the small oocytes is initiated. Tumours arise in ovaries totally depleted of oocytes. The question arises how the two carcinogenic stimuli, besides destroying small oocytes, will influence the only cell population in the ovary that proliferates, namely granulosa cells in medium and large follicles. This was investigated by autoradiographs prepared at different time intervals after intraperitoneal injection of {sup 3}H-thymidine. Two parameters were determined in the autoradiographs, i. e. the labelling index of the granulosa cells and the duration of the DNA-synthesis phase. From these parameters the doubling times of the granulosa cells and the growth rate of whole follicles were calculated. It was shown that immediately after X-irradiation and after treatment with DMBA, the labelling index of the granulosa cells increases, which is most marked in the medium follicles. This increase reaches a maximum about 48 hours after both types of treatment and is still recognizable 7 days later. The duration of the S-phase of the individual cells is not significantly affected after DMBA treatment, but in X-irradiated animals it is shortened in the medium follicles 48 hours after irradiation. Simultaneously with the increase in the labelling index there is a shortening of the doubling times of the granular cells and thereby an acceleration of the growth rate of whole follicles. It seems most likely that the increase in labelling index is due partly to an increase in the growth fraction of the granulosa cells and partly to a shortening of the generation time of the proliferating cells. (author)

  10. Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

    Science.gov (United States)

    Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

    2004-01-01

    In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

  11. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Manpreet S. Chahal

    2010-07-01

    Full Text Available Phospholipase D2 (PLD2 generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  12. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Brauner, Daniel J; Meier, Kathryn E

    2010-07-02

    Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.

  13. Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study

    International Nuclear Information System (INIS)

    Spoudeas, H.A.; Hindmarsh, P.C.; Brook, C.G.D.; Matthews, D.R.

    1996-01-01

    To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1.5-11.8 years, with brain tumours in the posterior foss (n = 25) or cerebral hemispheres (n 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR 9n 9); Group 2: ≥ 30 Gy DXR only (n = 22); Group 3: ≥ 30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. (author)

  14. A bi-paratopic anti-EGFR nanobody efficiently inhibits solid tumour growth

    Science.gov (United States)

    Roovers, Rob C.; Vosjan, Maria J.W.D.; Laeremans, Toon; el Khoulati, Rachid; de Bruin, Renée C.G.; Ferguson, Kathryn M.; Verkleij, Arie J.; van Dongen, Guus A.M.S.; van Bergen en Henegouwen, Paul M. P.

    2014-01-01

    The epidermal growth factor receptor (EGFR) has been shown to be a valid cancer target for antibody-based therapy. At present, several anti-EGFR monoclonal antibodies (mAbs) have been successfully used, among which cetuximab and matuzumab. X-ray crystallography data show that these antibodies bind to different epitopes on the ecto-domain of EGFR, providing a rationale for the combined use of these two antibody specificities. We have previously reported on the successful isolation of antagonistic anti-EGFR nanobodies. In the present study, we aimed to improve on these molecules by combining nanobodies with specificities similar to both cetuximab and matuzumab into a single bi-paratopic molecule. Carefully designed phage nanobody selections resulted in two sets of nanobodies that specifically blocked the binding of either matuzumab or of cetuximab to EGFR and that did not compete for each others binding. A combination of nanobodies from both epitope groups into the bi-paratopic nanobody CONAN-1 was shown to block EGFR activation more efficiently than monovalent or bivalent (monospecific) nanobodies. In addition, this bi-paratopic nanobody potently inhibited EGF-dependent cell proliferation. Importantly, in an in vivo model of athymic mice bearing A431 xenografts, CONAN-1 inhibited tumour outgrowth with an almost similar potency as the whole mAb cetuximab, despite the fact that CONAN-1 is devoid of an Fc portion that could mediate immune effector functions. Compared to therapy using bivalent, mono-specific nanobodies, CONAN-1 was clearly more potent in tumour growth inhibition. These results show that the rational design of bi-paratopic nanobody-based anti-cancer therapeutics may yield potent lead molecules for further development. PMID:21520037

  15. Mantle-cell lymphoma.

    Science.gov (United States)

    Barista, I; Romaguera, J E; Cabanillas, F

    2001-03-01

    During the past decade, mantle-cell lymphoma has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small to medium-sized nuclei, are commonly indented or cleaved, and stain positively with CD5, CD20, cyclin D1, and FMC7 antibodies. Because of its morphological appearance and a resemblance to other low-grade lymphomas, many of which grow slowly, this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the BCL1 oncogene was identified as a marker for this disease. Mantle-cell lymphoma is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas.

  16. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

    DEFF Research Database (Denmark)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara

    2007-01-01

    Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades......, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine...... phosphatase Shp2 as a candidate substrate. We found that NPM-ALK was able to bind Shp2 in coprecipitation experiments and to induce its phosphorylation in the tyrosine residues Y542 and Y580 both in HEK293 cells and ALCL cell lines. In primary lymphomas, antibodies against the phosphorylated tyrosine Y542...

  17. Imaging of sacral tumours

    International Nuclear Information System (INIS)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S.; Leclere, J.; Vanel, D.; Missenard, G.; Pinieux, G. de

    2008-01-01

    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  18. Imaging of sacral tumours

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S. [Institut Curie, Department of Radiology, Paris (France); Leclere, J. [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Vanel, D. [The Rizzoli Institute, Department of Radiology, Bologna (Italy); Missenard, G. [Institut Gustave Roussy, Comite de pathologie tumorale de l' appareil locomoteur, Villejuif (France); Pinieux, G. de [CHRU de Tours, Department of Pathology, Hopital Trousseau, Tours (France)

    2008-04-15

    All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

  19. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial

    DEFF Research Database (Denmark)

    Salles, Gilles; Seymour, John Francis; Offner, Fritz

    2011-01-01

    Patients with follicular lymphoma can have long survival times, but disease progression typically occurs 3-5 years after initial treatment. We assessed the potential benefit of 2 years of rituximab maintenance after first-line treatment in patients with follicular lymphoma receiving a rituximab...... plus chemotherapy regimen....

  20. World Health Organisation Classification of Lymphoid Tumours in Veterinary and Human Medicine: a Comparative Evaluation of Gastrointestinal Lymphomas in 61 Cats.

    Science.gov (United States)

    Wolfesberger, B; Fuchs-Baumgartinger, A; Greß, V; Hammer, S E; Gradner, G; Knödl, K; Tichy, A; Rütgen, B C; Beham-Schmid, C

    2018-02-01

    To diagnose and classify the various entities of lymphomas, the World Health Organisation (WHO) classification is applied in human as well as in veterinary medicine. We validated the concordance of these classification systems by having a veterinary and human pathologist evaluate gastrointestinal lymphoma tissue from 61 cats. In 59% of all cases, there was a match between their respective diagnoses of the lymphoma subtype. A complete consensus between the two evaluators was obtained for all samples with a diagnosis of diffuse large B-cell lymphoma, T-cell anaplastic large cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. A corresponding diagnosis was also made in the majority of samples with enteropathy associated T-cell lymphoma (EATL) type II, although this subtype in cats has similarities to the 'indolent T-cell lymphoproliferative disorder of the gastrointestinal tract', a provisional entity newly added to the revised human WHO classification in 2016. Very little consensus has been found with cases of EATL type I due to the fact that most did not meet all of the criteria of human EATL I. Hence, the human pathologist assigned them to the heterogeneous group of peripheral T-cell lymphomas (not otherwise specified). Consequently, concrete guidelines and advanced immunophenotyping based on the model of human medicine are essential to differentiate these challenging entities in veterinary medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Farmer, John T; Weigent, Douglas A

    2006-03-01

    Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.

  2. Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics.

    Directory of Open Access Journals (Sweden)

    Chryso Kanthou

    Full Text Available Vascular endothelial growth factor-A (VEGF is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120 on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188 or wild type controls (fswt were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine

  3. Expression of insulin-like growth factor-2 receptors on EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Farmer, John T; Weigent, Douglas A

    2007-01-01

    In the present study, we report the upregulation of functional IGF-2Rs in cells overexpressing growth hormone (GH). EL4 lymphoma cells stably transfected with an rGH cDNA overexpression vector (GHo) exhibited an increase in the binding of (125)I-IGF-2 with no change in the binding affinity compared to vector alone controls. An increase in the expression of the insulin-like growth factor-2 receptor (IGF-2R) in cells overexpressing GH was confirmed by Western blot analysis and IGF-2R promoter luciferase assays. EL4 cells produce insulin-like growth factor-2 (IGF-2) as detected by the reverse transcription-polymerase chain reaction (RT-PCR); however, no IGF-2 protein was detected by Western analysis. The increase in the expression of the IGF-2R resulted in greater levels of IGF-2 uptake in GHo cells compared to vector alone controls. The data suggest that one of the consequences of the overexpression of GH is an increase in the expression of the IGF-2R.

  4. The inhibition of apoptosis in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2004-01-01

    The antiapoptotic action of exogenous growth hormone (GH) has been reported for several lymphoid cell lines; however, the potential role of endogenous GH in apoptosis has not been thoroughly investigated. This study was designed to investigate the effects of endogenous GH on apoptosis induced by methyl methanesulfonate (MMS) in a T cell lymphoma overexpressing GH (GHo). The results of these experiments have shown that in EL4 lymphoma cells, overexpression of GH sustained viability after exposure to MMS compared to control cells. The extent of DNA fragmentation measured by ladder formation on agarose gels was reduced in GHo cells following treatment with MMS, when compared to control cells. Adding exogenous GH to control cells and treatment of GHo cells with antibodies to GH had no effect on MMS-induced DNA ladder formation. In further studies, DNA microarray analysis suggested a marked decrease in the constitutive expression of bax, BAD, and caspases 3, 8, and 9 in GHo cells compared to controls. In addition, after treatment with MMS, the activities of caspases 2, 3, 6, 8, and 9 were all lower than control in GHo cells. Western blot analysis detected an increase in Bcl-2 while the levels of nuclear factor kappa B (NFkappaB) remained unchanged in GHo cells. Treatment of EL4 cells with antisense deoxyoligonucleotides to GH and specific inhibitors of NFkappaB (SN-50) increased DNA fragmentation. GHo cells show increased levels of phosphorylated Akt and GSK-3, suggesting inactivation of this proapoptotic protein. The results, taken together with our previous data which showed increased nitric oxide formation in GHo cells, suggest a possible mechanism for the antiapoptotic effects of endogenous GH through the production of nitric oxide and support the idea that endogenous GH may play an important role in the survival of lymphocytes exposed to stressful stimuli. Copyright 2004 S. Karger AG, Basel

  5. Radiation leukemia virus and x-irradiation induce in C57BL/6 mice two distinct T-cell neoplasms: a growth factor-dependent lymphoma and a growth factor-independent lymphoma

    International Nuclear Information System (INIS)

    Haas, Martin; Rothenberg, Ellen; Bogart, M.H.; Jones, O.W.

    1987-01-01

    Two different classes of neoplastic T cells were isolated from radiation leukemia virus (RadLV)-inoculated and from X-ray-treated C57BL/6 mice. One consisted of growth factor-dependent T-cell lymphoma (FD-TCL) lines which were established from the spleens and thymuses of treated mice within a day of lymphoma detection. Non-thymic, factor-dependent TCL cells produced interleukin-2 upon lectin stimulation, and were autostimulatory because they secreted growth factor(s) constitutively. In vivo, FD-TCL cells that were injected intraperitoneally or intravenously homed to the spleen, proliferated in it and killed the injected mice. The isolation and study of FD-TCL cells was facilitated by their cultivation on stromal hematopoietic monolayers in supplemented ''lymphocyte medium'', until an autostimulating, self-sustaining concentration of FD-TCL cells was obtained. FD-TCL cells could not be grown from lymphoid tissue of normal, control mice. In contrast, T-cell lymphoma (TCL) lines, which were established from virus-induced thymomas which had been kept in situ for 4-6 weeks after detection, consisted of factor-independent cells that possessed an aneuploid karyotype. The phenotypic markers of TCL cells differed from those of FD-TCL cells, suggesting heterogeneity in the stages of differentiation at which cells can give rise to growth factor-independent (TCL) and to growth factor-dependent (FD-TCL) lines. (author)

  6. Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer.

    Science.gov (United States)

    Yu, Huixin; Hendrikx, Jeroen J M A; Rottenberg, Sven; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

    2016-03-01

    In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

  7. Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model.

    Directory of Open Access Journals (Sweden)

    Araceli Tobío

    Full Text Available Yessotoxins (YTXs are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.

  8. Cymbopogon citratus and Camellia sinensis extracts selectively induce apoptosis in cancer cells and reduce growth of lymphoma xenografts in vivo

    Science.gov (United States)

    Philion, Cory; Ma, Dennis; Ruvinov, Ivan; Mansour, Fadi; Pignanelli, Christopher; Noel, Megan; Saleem, Ammar; Arnason, John; Rodrigues, Mark; Singh, Inderpal; Ropat, Jesse; Pandey, Siyaram

    2017-01-01

    Cancer cells are reported to have elevated levels of reactive oxygen species (ROS) and are highly dependent on cellular defense mechanisms against oxidative stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide range of abilities to alter cellular redox states with potential implications in various diseases. Furthermore, therapeutic options for cancers are mostly nonselective treatments including genotoxic or tubulin-targeting compounds. Some of the natural extracts, containing multiple bioactive compounds, could target multiple pathways in cancer cells to selectively induce cell death. Cymbopogon citratus (lemongrass) and Camellia sinensis (white tea) extracts have been shown to have medicinal properties, however, their activity against lymphoma and leukemia, as well as mechanistic details, have not been fully characterized. Herein, we report potent anti-cancer properties in dose and time-dependent manners of ethanolic lemongrass and hot water white tea extracts in lymphoma and leukemia models. Both extracts were able to effectively induce apoptosis selectively in these human cancer cell types. Interestingly, ethanolic lemongrass extract induces apoptosis primarily by the extrinsic pathway and was found to be dependent on the generation of ROS. Conversely, apoptotic induction by hot water white tea extract was independent of ROS. Furthermore, both of these extracts caused mitochondrial depolarization and decreased rates of oxygen consumption in lymphoma and leukemia cells, leading to cell death. Most importantly, both these extracts were effective in reducing tumor growth in human lymphoma xenograft models when administered orally. Thus, these natural extracts could have potential for being nontoxic alternatives for the treatment of cancer. PMID:29340014

  9. Treatment of transplanted CT26 tumour with dendritic cell vaccine in combination with blockade of vascular endothelial growth factor receptor 2 and CTLA-4

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Buus, S; Claesson, M H

    2005-01-01

    We investigated the anti CT26 tumour effect of dendritic cell based vaccination with the MuLV gp70 envelope protein-derived peptides AH1 and p320-333. Vaccination lead to generation of AH1 specific cytotoxic lymphocytes (CTL) and some decrease in tumour growth of simultaneously inoculated CT26...... cells. After combination with an antibody against VEGF receptor 2 (DC101), a significant increase in survival of the tumour cell recipients was observed. Also, monotherapy with an antibody against CTLA-4 (9H10), led to approximately 100% survival of tumour cell recipients. However, effective treatment...

  10. The inhibition of superoxide production in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2003-05-01

    A substantial body of research exists to support the production of growth hormone by cells of the immune system. However, the function and mechanism of action of lymphocyte-derived growth hormone remain largely unelucidated. Since, it has been found that exogenous growth hormone (GH) primes neutrophils for the production of reactive oxygen intermediates (ROI) and in particular superoxide (O2-), we investigated the role of GH on the production of O2- in T cells. Furthermore, we examined whether endogenous and exogenous GH act similarly. Our studies show that overexpression of GH in EL4, a T-cell lymphoma cell line, results in a decrease in the production of O2- compared to control cells, as detected using the fluorescent dye, dihydroethidium. O2- production in control cells was not affected by treatment with inhibitors of xanthine oxidase or a non-specific NADPH-oxidase inhibitor. However, treatment with diallyl sulfide, an inhibitor of cytochrome P450 2E1 mimicked the reduction in O2- production seen in cells overexpressing GH. Although no significant change could be detected in CYP2E1 protein levels, CYP2E1 activity was found to be greater in control EL4 than in cells overexpressing GH. Both the decrease in O2- production and the lower CYP2E1 activity in GH overexpressing cells could be abrogated by treatment with N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide synthase. The overexpression of GH protects cells from apoptosis induced by isoniazid, a CYP2E1 inducer, suggesting a role for nitric oxide as a mediator in the regulation of xenobiotic metabolism and apoptosis-protection by lymphocyte GH.

  11. ESMO Consensus conferences : guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma

    NARCIS (Netherlands)

    Dreyling, M.; Thieblemont, C.; Gallamini, A.; Arcaini, L.; Campo, E.; Hermine, O.; Kluin-Nelemans, J. C.; Ladetto, M.; Le Gouill, S.; Iannitto, E.; Pileri, S.; Rodriguez, J.; Schmitz, N.; Wotherspoon, A.; Zinzani, P.; Zucca, E.

    To complement the existing treatment guidelines for all tumour types, ESMO organizes consensus conferences to focus on specific issues in each type of tumour. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, next to the 11th International

  12. Growth of extrapulmonary tumours after inhalation of small doses of plutonium oxide by rats

    International Nuclear Information System (INIS)

    Nolibe, D.; Masse, R.; L'Hullier, I.; Metivier, H.; Lafuma, J.

    1983-01-01

    After inhalation of plutonium oxide ( 239 PuO 2 ) involving initial lung burdens ranging from 74 to 103 Bq, male rats of the Wistar strain are kept in conditions allowing maximum survival; tumour incidences for the target organ (lung) and for the rest of the organs are calculated separately after the death of the animals. In the outbred Wistar rat the incidence of lung tumours is 18.5% for an initial lung burden of 74 Bq. The mean survival time of animals having such tumours is 973 days after inhalation. For an initial burden of 103 Bq syngenetic Wistar AG rats show a lower frequency of lung tumours (6.1%), but also a much reduced mean survival time, namely 757 days. Compared with the frequencies observed in the corresponding control groups, the frequency of non-pulmonary tumours is twice as high (12%) in consanguineous rats and six times as high (25.9%) in conventional rats. A supralinear dose-effect relationship at very low doses seems improbable in view of the dose delivered ( -3 Gy in the most exposed organs, such as the liver) and, in particular, because there is no correlation between the dose delivered to the organs and the location of the tumours. The exposed animals show, on the one hand, no specificity of organs for the surplus extrapulmonary tumours observed, and on the other, an inhibition by about 45% in the natural cytotoxic activity (natural killers) measured one year after inhalation. These observations suggest the hypothesis that an anti-tumour control mechanism is affected, perhaps as a result of the irradiation experienced during the circulation of blood cells in the lung capillaries. The failure of this system would in that case allow the expression of neoplastic characters as ageing progresses. A non-specific BCG immunotherapy does not restore this anti-tumour control system. (author)

  13. Sialic acid changes in Dalton's lymphoma-bearing mice after cyclophosphamide and cisplatin treatment

    Directory of Open Access Journals (Sweden)

    Nicol B.M.

    2002-01-01

    Full Text Available Sialic acid changes in Dalton's lymphoma cells and other tissues of 10-12-week-old Swiss albino mice were investigated in relation to tumour growth in vivo and following cyclophosphamide (ip, 200 mg/kg body weight or cisplatin (ip, 8 mg/kg body weight treatment. Three to four animals of both sexes were used in each experimental group. The sialic acid level of tumour cells (0.88 µmol/g increased with tumour progression (1.44-1.59 µmol/g; P<=0.05 in mice. Sialic acid concentration in other tissues (liver, kidney, testes and brain also increased (~40, 10, 30 and 58%, respectively in the tumour-bearing hosts as compared with that in the respective tissues of normal mice. In vivo cyclophosphamide or cisplatin treatment resulted in an overall decrease of sialic acid contents in the tissues. Cyclophosphamide was more efficient in lowering tissue sialic acid than cisplatin (P<=0.01, ANOVA. It is suggested that sialic acid residues could be an important factor contributing to the manifestation of malignant properties in cancer cells in general and Dalton's lymphoma cells in particular. A significant decrease in the sialic acid content of Dalton's lymphoma cells after cisplatin or cyclophosphamide treatment may bring about specific changes in tumour cells which could be associated with tumour regression.

  14. The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2003-01-01

    Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

  15. Radiological diagnosis of malignant tumours in patients with renal transplants

    Energy Technology Data Exchange (ETDEWEB)

    Raaijmakers, P A.M.; Rosenbusch, G; Hoitsma, A J; Boetes, C; Strijk, S P; Koene, R A.P.

    1984-12-01

    17 of 400 patients with a total of 537 renal transplantations developed a malignant tumour (4,2%). 3 patients had a tumour of the skin or lips, 5 a solid lymphoma, 2 a hepatocellular carcinoma and 7 each another tumour. The radiologic findings of the patients are described. The problems around the diagnostics of malignant tumours in patients with renal transplantations are discussed.

  16. Growth arrest line mimicking lymphoma involvement: The findings of {sup 99m}Tc-MDP bone SPECT/CT and serial bone scan in a child with non-Hodgkin's lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chan Woo; Kim, Ji Young; Choi, Yun Young; Lee, Seung Hun; Lee, Young Ho [Hanyang University Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on {sup 99m}Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth.

  17. Growth arrest line mimicking lymphoma involvement: The findings of 99mTc-MDP bone SPECT/CT and serial bone scan in a child with non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Kim, Chan Woo; Kim, Ji Young; Choi, Yun Young; Lee, Seung Hun; Lee, Young Ho

    2016-01-01

    Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on 99m Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth

  18. Influence of Coloured Correlated Noises on Probability Distribution and Mean of Tumour Cell Number in the Logistic Growth Model

    Institute of Scientific and Technical Information of China (English)

    HAN Li-Bo; GONG Xiao-Long; CAO Li; WU Da-Jin

    2007-01-01

    An approximate Fokker-P1anck equation for the logistic growth model which is driven by coloured correlated noises is derived by applying the Novikov theorem and the Fox approximation. The steady-state probability distribution (SPD) and the mean of the tumour cell number are analysed. It is found that the SPD is the single extremum configuration when the degree of correlation between the multiplicative and additive noises, λ, is in -1<λ ≤ 0 and can be the double extrema in 0<λ<1. A configuration transition occurs because of the variation of noise parameters. A minimum appears in the curve of the mean of the steady-state tumour cell number, 〈x〉, versus λ. The position and the value of the minimum are controlled by the noise-correlated times.

  19. Down-regulation of DNA mismatch repair enhances initiation and growth of neuroblastoma and brain tumour multicellular spheroids.

    Directory of Open Access Journals (Sweden)

    Samuel L Collins

    Full Text Available Multicellular tumour spheroid (MCTS cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. One mechanism linked to tumourigenesis in a number of cancers is genetic instability arising from impaired DNA mismatch repair (MMR. This study aimed to determine the role of MMR in MCTS initiation and development. Using surface-associated N2a and CHLA-02-ATRT culture systems we have investigated the impact of impaired MMR on MCTS growth. Analysis of the DNA MMR genes MLH1 and PMS2 revealed both to be significantly down-regulated at the mRNA level compared with non-spheroid-forming cells. By using small interfering RNA (siRNA against these genes we show that silencing of MLH1 and PMS2 enhances both MCTS initiation and subsequent expansion. This effect was prolonged over several passages following siRNA transfection. Down-regulation of DNA MMR can contribute to tumour initiation and progression in N2a and CHLA-02-ATRT MCTS models. Studies of surface-associated MCTS differentiation may have broader applications in studying events in the initiation of cancer foci.

  20. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.

    Science.gov (United States)

    Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

    2016-02-25

    The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody (99m)Tc-D10 for visualizing small tumour lesions with volumes below 100 mm(3) by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody (99m)Tc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm(3) ± 21.2 and 26.6 mm(3) ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of (99m)Tc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody (99m)Tc-D10.

  1. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

    Science.gov (United States)

    Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

    2016-01-01

    The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

  2. Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

    2015-01-01

    Background: Understanding the biological properties of potential drug targets are important. This is especially true for anti-angiogenic therapies in the search for potential biomarkers. The aim of the present descriptive study was to analyse the intra-tumoural expressions of epidermal growth...

  3. Analysis of a time-delayed mathematical model for tumour growth with an almost periodic supply of external nutrients.

    Science.gov (United States)

    Xu, Shihe; Bai, Meng; Zhang, Fangwei

    2017-12-01

    In this paper, the existence, uniqueness and exponential stability of almost periodic solutions for a mathematical model of tumour growth are studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a delay in the cell proliferation process. Using a fixed-point theorem in cones, the existence and uniqueness of almost periodic solutions for different parameter values of the model is proved. Moreover, by the Gronwall inequality, sufficient conditions are established for the exponential stability of the unique almost periodic solution. Results are illustrated by computer simulations.

  4. Lennert's Lymphoma

    International Nuclear Information System (INIS)

    Narayanrao, Suresh T.; Pillai, R.; Nada, Aymen; Hasan, Suhel

    2005-01-01

    Lymphoepithelioid cell lymphoma (Lennert's lymphoma) is a rare morphological variant of peripheral T-cell lymphoma characterized by the presence of numerous clusters of epithelioid histiocytes without formation of discrete granulomas and the intervening atypical lymphocytes. Lennert's lymphoma is often misinterpreted as granulomatous lymphadenitis or Hodgkin's disease. This report describes fine needle aspiration cytology and histological findings in a case of Lennert's lymphoma. (author)

  5. HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression.

    Science.gov (United States)

    Keith, Brian; Johnson, Randall S; Simon, M Celeste

    2011-12-15

    Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.

  6. Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A; Arnold, Robyn E

    2005-03-01

    Almost all of the previous studies with growth hormone (GH) have been done with exogenously supplied GH and, therefore, involve actions of the hormone through its receptor. However, the actions of endogenous or lymphocyte GH are still unclear. In a previous study, we showed that overexpression of GH (GHo) in a lymphoid cell line resulted in protection of the cells to apoptosis mediated by nitric oxide (NO). In the present study, we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1) or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis detected significantly higher levels of IGF-1 in cells overexpressing GH. An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R mutant construct blocked the generation of NO and activation of Akt seen in GHo cells compared to vector alone control EL4 cells. The results suggest that one of the consequences of the overexpression of GH, in cells lacking the GH receptor, is an increase in the expression of IGF-1 and the IGF-1R which mediate the protection of EL4 lymphoma cells from apoptosis.

  7. Lymphoma of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2014-01-01

    Full Text Available Background. Lymphoma of the urinary bladder (LUB is rare. Aims. To review the literature on LUB. Methods. Various internet databases were used. Results. LUB can be either primary or secondary. The tumour has female predominance; most cases occur in middle-age women. Secondary LUB occurs in 10% to 25% of leukemias/lymphomas and in advanced-stage systemic lymphoma. Less than 100 cases have been reported. MALT typically affects adults older than 60 years; 75% are female. Diffuse large B-cell lymphoma is also common and may arise from transformation of MALT. LUB presents with haematuria, dysuria, urinary frequency, nocturia, and abdominal or back pain. Macroscopic examination of LUBs show large discrete tumours centred in the dome or lateral walls of the bladder. Positive staining of LUB varies by the subtype of lymphoma; B-cell lymphomas are CD20 positive. MALT lymphoma is positively stained for CD20, CD19, and FMC7 and negatively stained for CD5, CD10, and CD11c. LUB stains negatively with Pan-keratin, vimentin, CK20, and CK7. MALT lymphoma exhibits t(11; 18(q21: 21. Radiotherapy is an effective treatment for the MALT type of LUB with no recurrence. Conclusions. LUB is diagnosed by its characteristic morphology and immunohistochemical characteristics. Radiotherapy is a useful treatment.

  8. Unusual presentation of rare primary lymphoma of bone ...

    African Journals Online (AJOL)

    Primary bone lymphoma is a distinct disease. It represents only 3% of all malignant bone tumours and less than 1% of non-Hodgkin's lymphoma. It is essential to differentiate it from other tumours because of its good prognosis. We report a case of 45 years old male who presented one year ago with a painful left arm.

  9. Modeling growth and dissemination of lymphoma in a co-evolving lymph node: a diffuse-domain approach

    Science.gov (United States)

    Chuang, Yao-Li; Cristini, Vittorio; Chen, Ying; Li, Xiangrong; Frieboes, Hermann; Lowengrub, John

    2013-03-01

    While partial differential equation models of tumor growth have successfully described various spatiotemporal phenomena observed for in-vitro tumor spheroid experiments, one challenge towards taking these models to further study in-vivo tumors is that instead of relatively static tissue culture with regular boundary conditions, in-vivo tumors are often confined in organ tissues that co-evolve with the tumor growth. Here we adopt a recently developed diffuse-domain method to account for the co-evolving domain boundaries, adapting our previous in-vitro tumor model for the development of lymphoma encapsulated in a lymph node, which may swell or shrink due to proliferation and dissemination of lymphoma cells and treatment by chemotherapy. We use the model to study the induced spatial heterogeneity, which may arise as an emerging phenomenon in experimental observations and model analysis. Spatial heterogeneity is believed to lead to tumor infiltration patterns and reduce the efficacy of chemotherapy, leaving residuals that cause cancer relapse after the treatment. Understanding the spatiotemporal evolution of in-vivo tumors can be an essential step towards more effective strategies of curing cancer. Supported by NIH-PSOC grant 1U54CA143907-01.

  10. Primary intracerebral lymphoma: Case report

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2012-09-01

    Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

  11. Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of bacterial toxins

    DEFF Research Database (Denmark)

    Woetmann, Anders; Lovato, Paola; Eriksen, Karsten W

    2007-01-01

    Bacterial toxins including staphylococcal enterotoxins (SEs) have been implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). Here, we investigate SE-mediated interactions between nonmalignant T cells and malignant T-cell lines established from skin and blood of CTCL patients....... The malignant CTCL cells express MHC class II molecules that are high-affinity receptors for SE. Although treatment with SE has no direct effect on the growth of the malignant CTCL cells, the SE-treated CTCL cells induce vigorous proliferation of the SE-responsive nonmalignant T cells. In turn, the nonmalignant...... T cells enhance proliferation of the malignant cells in an SE- and MHC class II-dependent manner. Furthermore, SE and, in addition, alloantigen presentation by malignant CTCL cells to irradiated nonmalignant CD4(+) T-cell lines also enhance proliferation of the malignant cells. The growth...

  12. Inhibitory effect of magnolol on tumour metastasis in mice.

    Science.gov (United States)

    Ikeda, Koji; Sakai, Yoshimichi; Nagase, Hisamitsu

    2003-09-01

    It has previously been reported that magnolol, a phenolic compound isolated from Magnolia obovata, inhibited tumour cell invasion in vitro. The purpose of this study was to investigate the antimetastatic effect of magnolol on tumour metastasis in vivo with experimental and spontaneous metastasis models and to clarify the mechanism. The antimetastatic effects of magnolol were evaluated by an experimental liver and spleen metastasis model using L5178Y-ML25 lymphoma, or an experimental and spontaneous lung metastasis model using B16-BL6 melanoma. Intraperitoneal (i.p.) administration of 2 or 10 mg/kg of magnolol significantly suppressed liver and spleen metastasis or lung metastasis. As for the spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.p. administrations of 10 mg/kg of magnolol after and before tumour inoculation significantly suppressed lung metastasis and primary tumour growth. In addition, magnolol significantly inhibited B16-BL6 cell invasion of the reconstituted basement membrane (Matrigel, MG) without affecting cell growth. These data from the in vivo experiments suggest that magnolol possesses strong antimetastatic ability and that it may be a lead compound for drug development. The antimetastatic action of magnolol is considered to be due to its ability to inhibit tumour cell invasion. Copyright 2003 John Wiley & Sons, Ltd.

  13. Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses human mesothelioma tumour growth in mouse xenograft models.

    Directory of Open Access Journals (Sweden)

    Mohamed A Alfaleh

    Full Text Available Human malignant mesothelioma is a chemoresistant tumour that develops from mesothelial cells, commonly associated with asbestos exposure. Malignant mesothelioma incidence rates in European countries are still rising and Australia has one of the highest burdens of malignant mesothelioma on a population basis in the world. Therapy using systemic delivery of free cytotoxic agents is associated with many undesirable side effects due to non-selectivity, and is thus dose-limited which limits its therapeutic potential. Therefore, increasing the selectivity of anti-cancer agents has the potential to dramatically enhance drug efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV are antibody-targeted nanocells which can be loaded with cytotoxic drugs and delivered to specific cancer cells via bispecific antibodies (BsAbs which target the EDV and a cancer cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin-loaded EDVs to cancer cells via cell surface mesothelin (MSLN. Flow cytometry was used to investigate cell binding and induction of apoptosis, and confocal microscopy to visualize internalization. Mouse xenograft models were used to assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs were able to bind to and internalize within mesothelioma cells in vitro via MSLN receptors and induce apoptosis. In mice xenografts, the BsAb-targeted, doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated doxorubicin can provide a novel and alternative modality for treatment of mesothelioma.

  14. Primary vertebral tumours in children

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Masel, J.; Diard, F.; Ferrari-Ciboldi, F.; Le Dosseur, P.; Labatut, J.

    1984-03-01

    20 cases of primary benign and malignant bone tumours in children were reported. The most common tumours were Ewing's sarcoma, aneurismal bone cyst, benign osteoblastoma and osteoid osteoma. Some rare primary bone tumours in children (osteochondroma, chondroblastoma 6F, primary lymphoma of bone and neurofibromatosis with unusual cervical spinal changes) were also reported. The authors believe that radiographic findings together with clinical history and clinical examination may yield a high percentage of accurate diagnoses. Although microscopy is essential in the final diagnosis, the microscopic report should be also accepted with caution.

  15. Composite lymphoma: Mycosis fungoides with hodgkin′s lymphoma

    Directory of Open Access Journals (Sweden)

    Mehta Jalpa

    2005-01-01

    Full Text Available Mycosis fungoides (MF is a malignant lymphoma, primarily of the skin and is characterized by infiltration of the skin by atypical T-cells which have a tendency for epidermotropism. Hodgkins disease (HD is considered to be a malignant lymphoma affecting predominantly the lymph nodes and characterized by presence of Reed- Sternberg cells on histopathology, though, the exact origin of the Reed Sternberg cell and the nature of the malignant cell is not known yet. Few cases of association of mycosis fungoides with Hodgkin′s lymphoma have been reported in the literature. It was reported in the past that when mycosis fungoides spreads to the lymph nodes and other viscera it frequently gets transformed into a more common lymphoma like Hodgkin′s lymphoma. However it has now been proved that the two malignancies are distinct and that such patients probably have a tumour diathesis.

  16. How effective is external pituitary irradiation for growth hormone-secreting pituitary tumours

    International Nuclear Information System (INIS)

    Feek, C.M.; McLelland, J.; Seth, J.; Toft, A.D.; Irvine, W.J.; Padfield, P.L.; Edwards, C.R.W.

    1984-01-01

    Forty-six patients with GH-secreting pituitary tumours were treated with external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment; 16 received radiotherapy combined with pituitary surgery. The mean (+- SD) serum GH in the former group was 74.3 +- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+- SD) serum GH in the latter group was 265.4 +- 209.3 mU/l before treatment, falling by 76% in the first year-a direct result of surgery-then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages are the time taken to achieve a cure and the high incidence of hypopituitarism. (author)

  17. An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma.

    Science.gov (United States)

    Verma, Sonal; Kumar, Madhu; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

    2017-07-01

    Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients.

  18. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Perez-Cornago, Aurora; Appleby, Paul N.; Tipper, Sarah; Key, Timothy J.; Allen, Naomi E.; Nieters, Alexandra; Vermeulen, Roel; Roulland, Sandrine; Casabonne, Delphine; Kaaks, Rudolf; Fortner, Renee T.; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Klinaki, Eleni; Hansen, Louise; Tjønneland, Anne; Bonnet, Fabrice; Fagherazzi, Guy; Boutron-Ruault, Marie Christine; Pala, Valeria; Masala, Giovanna; Sacerdote, Carlotta; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Dorronsoro, Miren; Quirós, J. Ramón; Barricarte, Aurelio; Gavrila, Diana; Agudo, Antonio; Borgquist, Signe; Rosendahl, Ann H.; Melin, Beatrice; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Riboli, Elio; Vineis, Paolo; Travis, Ruth C.

    2017-01-01

    Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested

  19. Therapy of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Coffey, J.; Hodgson, D.C.; Gospodarowicz, M.K.

    2003-01-01

    Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas

  20. Fertility preservation in women--a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkin's lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT.

    Science.gov (United States)

    von Wolff, Michael; Montag, Markus; Dittrich, Ralf; Denschlag, Dominik; Nawroth, Frank; Lawrenz, Barbara

    2011-08-01

    Fertility preservation methods are playing an increasing role in women up to the age of 40 years because of rising survival rates in those affected by cancer. However, balanced practical recommendations concerning all relevant fertility preservation, to support doctors in counselling and treating patients, are still rare. These recommendations were prepared by the network FertiPROTEKT ( http://www.fertiprotect.eu ), a collaboration of around 70 centres in Germany, Switzerland and Austria. The recommendations were developed by specialists in reproductive medicine, reproductive biology and oncology, which gave a comprehensive overview of all named techniques as well as their benefits and risks. Furthermore, practice-orientated recommendations for the individual use of fertility preservation methods for various indications such as breast cancer, Hodgkin's lymphoma and borderline ovarian tumours are given. Various options such as ovarian stimulation and cryopreservation of unfertilised or fertilised oocytes, cryopreservation and transplantation of ovarian tissue, GnRH-agonist administration and transposition of the ovaries can be offered. All the techniques can be performed alone or in combination within a maximum of 2 weeks with low risk and different success rates. Fertility preservation in women has become an option with realistic chances to become pregnant after cytotoxic therapies. The information provided allows a well balanced and realistic counselling and treatment.

  1. Management of parapharyngeal space tumours

    International Nuclear Information System (INIS)

    Ahmad, F.; Waqar-Uddin; Khan, M.S.; Khawar, A.; Bangush, W.; Aslam, J.

    2006-01-01

    Objective: To determine the role of clinical features, fine needle aspiration cytology (FNAC) and computed tomography (CT) scan in diagnosing Para pharyngeal space (PPS) tumours and treatment options. Design: A descriptive study. Place and Duration of Study: From July 2000 to July 2002 at Pakistan Institute of Medical Sciences, Islamabad. Patients and Methods: Patients diagnosed as having PPS tumours were studied. The medical record of patients was reviewed for their age, gender, clinical features, investigations (FNAC and CT scan) and treatment. The mean age, percentage of different clinical features and the sensitivity and specificity of FNAC was determined. Results: The mean age of patients presenting with PPS tumours was 33.6 years. The most common clinical features were neck mass (93%) and bulge in lateral pharyngeal wall (80%). The CT scan showed exact location and extent of tumour in 11 out of 15 cases. The sensitivity and specificity of FNAC was 70% and 85% respectively. The most common tumours were neurogenic tumours and salivary gland tumours. Surgery was performed in all except 2 patients with lymphoma in whom radiation and chemotherapy was recommended. Conclusion: This study indicates that PPS tumours are usually benign neurosurgeon and salivary gland tumours presenting with neck mass and bulge in or oropharynx. FNAC and CT scan are important in diagnostic work up and treatment planning. Surgery has the best results in most cases. (author)

  2. Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Šímová, Jana; Indrová, Marie; Bieblová, Jana; Přibylová, Hana; Moravcová, Simona; Jandlová, Táňa; Bubeník, Jan

    2007-01-01

    Roč. 30, č. 4 (2007), s. 1011-1017 ISSN 1019-6439 R&D Projects: GA MZd NR7807 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * MHC class I-deficient tumours * immunologic crossreaction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.295, year: 2007

  3. Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Fu, J.

    2002-03-01

    CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding

  4. Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

    International Nuclear Information System (INIS)

    Fu, J.

    2002-03-01

    CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding. Finally, I

  5. Evaluation of the prognostic role of tumour-associated macrophages in newly diagnosed classical Hodgkin lymphoma and correlation with early FDG-PET assessment.

    Science.gov (United States)

    Cencini, Emanuele; Fabbri, Alberto; Rigacci, Luigi; Lazzi, Stefano; Gini, Guido; Cox, Maria Christina; Mancuso, Salvatrice; Abruzzese, Elisabetta; Kovalchuk, Sofia; Goteri, Gaia; Di Napoli, Arianna; Bono, Roberto; Fratoni, Stefano; Di Lollo, Simonetta; Bosi, Alberto; Leoncini, Lorenzo; Bocchia, Monica

    2017-03-01

    In Hodgkin Lymphoma (HL), about 20% of patients still have relapsed/refractory disease and late toxic effects rate continue to rise with time. 'Early FDG-PET' and tissue macrophage infiltration (TAM) emerged as powerful prognostic predictors. The primary endpoint was to investigate the prognostic role of both early FDG-PET and TAM; the secondary endpoint was to test if early FDG-PET positivity could correlate with high TAM score. A cohort of 200 HL patients was analysed. Induction treatment plan consisted of two to six courses of ABVD and, if indicated, involved field radiation therapy. All patients repeated CT scan and FDG-PET after two cycles and after the completion of therapy. TAM in diagnostic specimens was determined by immunohistochemistry with a monoclonal antibody (anti-CD68 KP1). Overall, early FDG-PET was negative in 163 patients (81.5%) and positive in 37 patients (18.5%), showing a significant correlation with the achievement of CR (p PET negative patients (p PET result. This study confirms that early FDG-PET has a high prognostic power, while TAM score does not seem to influence the outcome; in contrast to our original hypothesis, it does not correlate with FDG-PET assessment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Alternative splicing of TIA-1 in human colon cancer regulates VEGF isoform expression, angiogenesis, tumour growth and bevacizumab resistance.

    Science.gov (United States)

    Hamdollah Zadeh, Maryam A; Amin, Elianna M; Hoareau-Aveilla, Coralie; Domingo, Enric; Symonds, Kirsty E; Ye, Xi; Heesom, Katherine J; Salmon, Andrew; D'Silva, Olivia; Betteridge, Kai B; Williams, Ann C; Kerr, David J; Salmon, Andrew H J; Oltean, Sebastian; Midgley, Rachel S; Ladomery, Michael R; Harper, Steven J; Varey, Alexander H R; Bates, David O

    2015-01-01

    The angiogenic capability of colorectal carcinomas (CRC), and their susceptibility to anti-angiogenic therapy, is determined by expression of vascular endothelial growth factor (VEGF) isoforms. The intracellular protein T-cell Intracellular Antigen (TIA-1) alters post-transcriptional RNA processing and binds VEGF-A mRNA. We therefore tested the hypothesis that TIA-1 could regulate VEGF-A isoform expression in colorectal cancers. TIA-1 and VEGF-A isoform expression was measured in colorectal cancers and cell lines. We discovered that an endogenous splice variant of TIA-1 encoding a truncated protein, short TIA-1 (sTIA-1) was expressed in CRC tissues and invasive K-Ras mutant colon cancer cells and tissues but not in adenoma cell lines. sTIA-1 was more highly expressed in CRC than in normal tissues and increased with tumour stage. Knockdown of sTIA-1 or over-expression of full length TIA-1 (flTIA-1) induced expression of the anti-angiogenic VEGF isoform VEGF-A165b. Whereas flTIA-1 selectively bound VEGF-A165 mRNA and increased translation of VEGF-A165b, sTIA-1 prevented this binding. In nude mice, xenografted colon cancer cells over-expressing flTIA-1 formed smaller, less vascular tumours than those expressing sTIA-1, but flTIA-1 expression inhibited the effect of anti-VEGF antibodies. These results indicate that alternative splicing of an RNA binding protein can regulate isoform specific expression of VEGF providing an added layer of complexity to the angiogenic profile of colorectal cancer and their resistance to anti-angiogenic therapy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.

    Science.gov (United States)

    Schöffski, Patrick; Sufliarsky, Jozef; Gelderblom, Hans; Blay, Jean-Yves; Strauss, Sandra J; Stacchiotti, Silvia; Rutkowski, Piotr; Lindner, Lars H; Leahy, Michael G; Italiano, Antoine; Isambert, Nicolas; Debiec-Rychter, Maria; Sciot, Raf; Van Cann, Thomas; Marréaud, Sandrine; Nzokirantevye, Axelle; Collette, Sandra; Wozniak, Agnieszka

    2018-06-01

    An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK). Eligible participants were patients aged at least 15 years with a local diagnosis of advanced or metastatic IMFT deemed incurable with surgery, radiotherapy, or systemic therapy; measurable disease; an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, renal, and liver function. Central reference pathology was done for confirmation of the diagnosis, and ALK positivity or negativity was assessed centrally using immunohistochemistry and fluorescence in-situ hybridisation based on archival tumour tissue and defined as ALK immunopositivity or rearrangements in at least 15% of tumour cells. Eligible ALK-positive and ALK-negative patients received oral crizotinib 250 mg twice per day administered on a continuous daily dosing schedule (the duration of each treatment cycle was 21 days) until documented disease progression, unacceptable toxicity, or patient refusal. If at least two of the first 12 eligible and assessable ALK-positive patients achieved a confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, a maximum of 35 patients were to be enrolled. If at least six ALK-positive patients achieved a confirmed response, the trial would be deemed successful. The primary endpoint was the proportion of patients who achieved

  8. Hodgkin lymphoma

    Science.gov (United States)

    Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... to 70 years old. Past infection with the Epstein-Barr virus ( EBV ) is thought to contribute to some cases. People with HIV infection are at increased risk compared to the general population.

  9. Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on {sup 18}F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Choon-Young; Hong, Chae Moon; Kim, Do-Hoon; Son, Seung Hyun; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol [Kyungpook National University School of Medicine and Hospital, Department of Nuclear Medicine, Daegu (Korea, Republic of)

    2013-09-15

    The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment {sup 18}F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment {sup 18}F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV > 3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG). During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm{sup 3} and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS. Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes. (orig.)

  10. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  11. Tumoural Expression of Connective Tissue Growth Factor (CTGF) Impacts on Survival in Patients Diagnosed with Hepatocellular Carcinoma (HCC).

    Science.gov (United States)

    Lamarca, Angela; Mendiola, Marta; Bernal, Elsa; Heredia, Victoria; Díaz, Esther; Miguel, María; Pastrian, Laura G; Burgos, Emilio; Feliu, Jaime; Barriuso, Jorge

    2015-01-01

    Hepatocellular carcinoma (HCC) tends to develop in the liver when there is a high level of background inflammation (cirrhosis). Treatment options are limited and mainly based on systemic therapies such as anti-angiogenic drugs (e.g. sorafenib). Connective tissue growth factor (CTGF) is a matricellular protein involved in inflammation, tumour growth and angiogenesis. The aim of this study is to determine the expression of CTGF and hypoxia inducible factors (HIF) in HCC and to clarify its impact on relapse and survival. Eligibility criteria for the study consisted of patients with a diagnosis of HCC, formalin-fixed and paraffin-embedded (FFPE) biopsy tissue, as well as relapse and available survival data. A tissue microarray was constructed from ≥ 70% tumoural sections. The expressions of CTGF, HIF1α and HIF2α were analysed by immunohistochemistry. The relationship between expression of CTGF/HIF1α and CTGF/HIF2α were analysed. Univariate and multivariate analyses were performed. Fifty-three patients were screened; 39 patients were eligible for this study. Patients were treated with radical intent. At the end of follow up, 59% patients relapsed (28.2% locally, 10.3% multicentric liver relapse and 7.7% distant metastases). Estimated median disease-free survival (DFS) and overall survival (OS) were 23.4 (95%CI 7.18-39.66) and 38.6 months (95%CI 30.7-46.6), respectively. Expression of CTGF was: negative 23.1%, focal 48.7% and diffuse 23.1%. A non-statistically significant relationship between expression of CTGF and HIF was shown supporting an alternative pathway for CTGF expression in HCC. In multivariate analysis CTGF expression was an independent factor related to OS, with shorter survival in those patients with focal/diffuse CTGF expression (HR 2.46; 95%CI 1.18-5.15). Our results support that expression of CTGF is an independent factor associated with shorter OS in HCC. Further analysis of CTGF expression in a larger series of HCC patients is required to confirm

  12. Coarse-graining and hybrid methods for efficient simulation of stochastic multi-scale models of tumour growth

    Science.gov (United States)

    de la Cruz, Roberto; Guerrero, Pilar; Calvo, Juan; Alarcón, Tomás

    2017-12-01

    The development of hybrid methodologies is of current interest in both multi-scale modelling and stochastic reaction-diffusion systems regarding their applications to biology. We formulate a hybrid method for stochastic multi-scale models of cells populations that extends the remit of existing hybrid methods for reaction-diffusion systems. Such method is developed for a stochastic multi-scale model of tumour growth, i.e. population-dynamical models which account for the effects of intrinsic noise affecting both the number of cells and the intracellular dynamics. In order to formulate this method, we develop a coarse-grained approximation for both the full stochastic model and its mean-field limit. Such approximation involves averaging out the age-structure (which accounts for the multi-scale nature of the model) by assuming that the age distribution of the population settles onto equilibrium very fast. We then couple the coarse-grained mean-field model to the full stochastic multi-scale model. By doing so, within the mean-field region, we are neglecting noise in both cell numbers (population) and their birth rates (structure). This implies that, in addition to the issues that arise in stochastic-reaction diffusion systems, we need to account for the age-structure of the population when attempting to couple both descriptions. We exploit our coarse-graining model so that, within the mean-field region, the age-distribution is in equilibrium and we know its explicit form. This allows us to couple both domains consistently, as upon transference of cells from the mean-field to the stochastic region, we sample the equilibrium age distribution. Furthermore, our method allows us to investigate the effects of intracellular noise, i.e. fluctuations of the birth rate, on collective properties such as travelling wave velocity. We show that the combination of population and birth-rate noise gives rise to large fluctuations of the birth rate in the region at the leading edge of

  13. Coarse-graining and hybrid methods for efficient simulation of stochastic multi-scale models of tumour growth

    International Nuclear Information System (INIS)

    Cruz, Roberto de la; Guerrero, Pilar; Calvo, Juan; Alarcón, Tomás

    2017-01-01

    The development of hybrid methodologies is of current interest in both multi-scale modelling and stochastic reaction–diffusion systems regarding their applications to biology. We formulate a hybrid method for stochastic multi-scale models of cells populations that extends the remit of existing hybrid methods for reaction–diffusion systems. Such method is developed for a stochastic multi-scale model of tumour growth, i.e. population-dynamical models which account for the effects of intrinsic noise affecting both the number of cells and the intracellular dynamics. In order to formulate this method, we develop a coarse-grained approximation for both the full stochastic model and its mean-field limit. Such approximation involves averaging out the age-structure (which accounts for the multi-scale nature of the model) by assuming that the age distribution of the population settles onto equilibrium very fast. We then couple the coarse-grained mean-field model to the full stochastic multi-scale model. By doing so, within the mean-field region, we are neglecting noise in both cell numbers (population) and their birth rates (structure). This implies that, in addition to the issues that arise in stochastic-reaction diffusion systems, we need to account for the age-structure of the population when attempting to couple both descriptions. We exploit our coarse-graining model so that, within the mean-field region, the age-distribution is in equilibrium and we know its explicit form. This allows us to couple both domains consistently, as upon transference of cells from the mean-field to the stochastic region, we sample the equilibrium age distribution. Furthermore, our method allows us to investigate the effects of intracellular noise, i.e. fluctuations of the birth rate, on collective properties such as travelling wave velocity. We show that the combination of population and birth-rate noise gives rise to large fluctuations of the birth rate in the region at the leading edge

  14. Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line

    International Nuclear Information System (INIS)

    Hirata, Y.; Uchihashi, M.; Nakashima, H.; Fujita, T.; Matsukura, S.; Matsui, K.

    1984-01-01

    Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E 2 , a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125 I-labelled EGF: the apparent dissociation constant was approximately 4-10 x 10 -10 M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125 I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE 2 into medium, while no significant amount of PGE 2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE 2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE 1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGFsub(2α) PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 of G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE 2 -mediated process in human osseous tissues. (author)

  15. Effect of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on the growth and radiotherapeutic sensitivity of human lymphoma cell lines

    International Nuclear Information System (INIS)

    Yu Zeyang; Fan Wo; Li Dongqing; Zhu Ran; Wang Yongqing; Wu Jinchang

    2008-01-01

    Objective: To explore the inhibitory effect and radiation sensitization of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) on human lymphoma cell lines. Methods: Human lymphoma cell lines Raji and Daudi were treated with rAd-p53, radiation therapy and combined treatment, respectively. The cell growth inhibition was assessed by MTT. The p53 protein expression was detected by Western blotting, and p53 mRNA was detected by BT-PCB. Results: The MTT results showed that the inhibitory effect and radiosensitivity enhancement of rAd-p53 on human lymphoma cell lines were not obvious [Raji: (27.5±4.1)%; Daudi: (28.1±1.6)%]. The results of Western blotting and BT-PCB showed that extrinsic p53 protein and p53 mRNA were expressed to some degree, but not at high-level. In addition, the results didn't demonstrate obvious radiosensitivity enhancement. Conclusions: The role of inhibition and radiosensitivity enhancement of rAd-p53 was not significant on human lymphoma cell lines. (authors)

  16. Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

    Science.gov (United States)

    Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

    2015-10-01

    Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without

  17. Tumour-induced osteomalacia.

    Science.gov (United States)

    Minisola, Salvatore; Peacock, Munro; Fukumoto, Seijii; Cipriani, Cristiana; Pepe, Jessica; Tella, Sri Harsha; Collins, Michael T

    2017-07-13

    Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone mineralization). The diagnosis of TIO is usually suspected when serum phosphate levels are chronically low in the setting of bone pain, fragility fractures and muscle weakness. Locating the offending tumour can be very difficult, as the tumour is often very small and can be anywhere in the body. Surgical removal of the tumour is the only definitive treatment. When the tumour cannot be located or when complete resection is not possible, medical treatment with phosphate salts or active vitamin D is necessary. One of the most promising emerging treatments for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody KRN23. The recent identification of a fusion of fibronectin and fibroblast growth factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds light on the pathophysiology of TIO but also opens the door to a better understanding of the transcription, translocation, post-translational modification and secretion of FGF23, as well as suggesting approaches to targeted therapy. Further study will reveal if the FGFR1 pathway is also involved in tumours that do not harbour the translocation.

  18. Malignant lymphoma in african lions (panthera leo).

    Science.gov (United States)

    Harrison, T M; McKnight, C A; Sikarskie, J G; Kitchell, B E; Garner, M M; Raymond, J T; Fitzgerald, S D; Valli, V E; Agnew, D; Kiupel, M

    2010-09-01

    Malignant lymphoma has become an increasingly recognized problem in African lions (Panthera leo). Eleven African lions (9 male and 2 female) with clinical signs and gross and microscopic lesions of malignant lymphoma were evaluated in this study. All animals were older adults, ranging in age from 14 to 19 years. Immunohistochemically, 10 of the 11 lions had T-cell lymphomas (CD3(+), CD79a(-)), and 1 lion was diagnosed with a B-cell lymphoma (CD3(-), CD79a(+)). The spleen appeared to be the primary site of neoplastic growth in all T-cell lymphomas, with involvement of the liver (6/11) and regional lymph nodes (5/11) also commonly observed. The B-cell lymphoma affected the peripheral lymph nodes, liver, and spleen. According to the current veterinary and human World Health Organization classification of hematopoietic neoplasms, T-cell lymphoma subtypes included peripheral T-cell lymphoma (4/11), precursor (acute) T-cell lymphoblastic lymphoma/leukemia (2/11), chronic T-cell lymphocytic lymphoma/leukemia (3/11), and T-zone lymphoma (1/11). The single B-cell lymphoma subtype was consistent with diffuse large B-cell lymphoma. Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing by immunohistochemistry on sections of malignant lymphoma was negative for all 11 lions. One lion was seropositive for FeLV. In contrast to domestic and exotic cats, in which B-cell lymphomas are more common than T-cell lymphomas, African lions in this study had malignant lymphomas that were primarily of T-cell origin. Neither FeLV nor FIV, important causes of malignant lymphoma in domestic cats, seems to be significant in the pathogenesis of malignant lymphoma in African lions.

  19. Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human b lymphoma cell line bl36

    Directory of Open Access Journals (Sweden)

    Joubert-Caron Raymonde

    2001-12-01

    Full Text Available Abstract Background 5-AzaCytidine (AzaC is a DNA demethylating drugs that has been shown to inhibit cell growth and to induce apoptosis in certain cancer cells. Induced expression of the galectin1 (Gal1 protein, a galactoside-binding protein distributed widely in immune cells, has been described in cultured hepatoma-derived cells treated with AzaC and this event may have a role in the effect of the drug. According to this hypothesis, we investigated the effect of AzaC and Gal1 on human lymphoid B cells phenotype. Methods The effect of AzaC and Gal1 on cell growth and phenotype was determined on the Burkitt lymphoma cell line BL36. An immunocytochemical analysis for detection of Gal1 protein expression was performed in AzaC-treated cells. To investigate the direct effects of Gal1, recombinant Gal1 was added to cells. Results Treatment of lymphoid B cells with AzaC results in: i a decrease in cell growth with an arrest of the cell cycle at G0/G1 phase, ii phenotypic changes consistent with a differentiated phenotype, and iii the expression of p16, a tumor-suppressor gene whose expression was dependent of its promoter demethylation, and of Gal1. A targeting of Gal 1 to the plasma membrane follows its cytosolic expression. To determine which of the effects of AzaC might be secondary to the induction of Gal1, recombinant Gal1 was added to BL36 cells. Treated cells displayed growth inhibition and phenotypic changes consistent with a commitment toward differentiation. Conclusions Altered cell growth and expression of the cell surface plasma cell antigen, CD138 are detectable in BL36 cells treated by AzaC as well as by Gal1. It seems that AzaC-induced Gal1 expression and consequent binding of Gal1 on its cell membrane receptor may be, in part, involved in AzaC-induced plasmacytic differentiation.

  20. Can exercise suppress tumour growth in advanced prostate cancer patients with sclerotic bone metastases? A randomised, controlled study protocol examining feasibility, safety and efficacy.

    Science.gov (United States)

    Hart, Nicolas H; Newton, Robert U; Spry, Nigel A; Taaffe, Dennis R; Chambers, Suzanne K; Feeney, Kynan T; Joseph, David J; Redfern, Andrew D; Ferguson, Tom; Galvão, Daniel A

    2017-05-30

    Exercise may positively alter tumour biology through numerous modulatory and regulatory mechanisms in response to a variety of modes and dosages, evidenced in preclinical models to date. Specifically, localised and systemic biochemical alterations produced during and following exercise may suppress tumour formation, growth and distribution by virtue of altered epigenetics and endocrine-paracrine activity. Given the impressive ability of targeted mechanical loading to interfere with metastasis-driven tumour formation in human osteolytic tumour cells, it is of equal interest to determine whether a similar effect is observed in sclerotic tumour cells. The study aims to (1) establish the feasibility and safety of a combined modular multimodal exercise programme with spinal isometric training in advanced prostate cancer patients with sclerotic bone metastases and (2) examine whether targeted and supervised exercise can suppress sclerotic tumour growth and activity in spinal metastases in humans. A single-blinded, two-armed, randomised, controlled and explorative phase I clinical trial combining spinal isometric training with a modular multimodal exercise programme in 40 men with advanced prostate cancer and stable sclerotic spinal metastases. Participants will be randomly assigned to (1) the exercise intervention or (2) usual medical care. The intervention arm will receive a 3-month, supervised and individually tailored modular multimodal exercise programme with spinal isometric training. Primary endpoints (feasibility and safety) and secondary endpoints (tumour morphology; biomarker activity; anthropometry; musculoskeletal health; adiposity; physical function; quality of life; anxiety; distress; fatigue; insomnia; physical activity levels) will be measured at baseline and following the intervention. Statistical analyses will include descriptive characteristics, t-tests, effect sizes and two-way (group × time) repeated-measures analysis of variance (or analysis of

  1. Anaplastic Large Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  2. Mantle Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  3. Marginal Zone Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  4. The HLJ1-targeting drug screening identified Chinese herb andrographolide that can suppress tumour growth and invasion in non-small-cell lung cancer.

    Science.gov (United States)

    Lai, Yi-Hua; Yu, Sung-Liang; Chen, Hsuan-Yu; Wang, Chi-Chung; Chen, Huei-Wen; Chen, Jeremy J W

    2013-05-01

    HLJ1 is a novel tumour suppressor and is a potential druggable target for non-small-cell lung cancer (NSCLC). In this report, using a promoter-containing enhancer region as the HLJ1-targeting drug-screening platform, we identified several herbal compounds from a Chinese herbal bank with the capacity to enhance HLJ1 promoter activity and suppress tumour growth and invasion of NSCLC. Among the herbal drugs identified, the andrographolide (from Andrographis paniculata [Burm. f.] Nees.) most significantly induced HLJ1 expression and suppressed tumorigenesis both in vitro and in vivo. The andrographolide upregulates HLJ1 via JunB activation, which modulates AP-2α binding at the MMP-2 promoter and represses the expression of MMP-2. In addition, silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. Microarray transcriptomic analysis was performed to comprehensively depict the andrographolide-regulated signalling pathways. We showed that andrographolide can affect 939 genes (analysis of variance, false discovery rate andrographolide on anticancer invasion and proliferation. In conclusion, the HLJ1-targeting drug-screening platform is useful for screening of novel anticancer compounds. Using this platform, we identified andrographolide is a promising new anticancer agent that could suppress tumour growth and invasion in NSCLC.

  5. Primary effusion lymphomas in AIDS: CT findings in two cases

    International Nuclear Information System (INIS)

    Ferrozzi, F.; Tognini, G.; Mulonzia, N.W.; Pavone, P.; Bova, D.

    2001-01-01

    Primary effusion lymphomas represent an unusual subset of AIDS-related non-Hodgkin's lymphomas. They are associated with herpes virus 8 and Epstein-Barr virus and characterized by predominant involvement of the serous body cavities (pleura, pericardium, peritoneum) as lymphomatous effusion without any identifiable tumour mass. We report herein CT findings in two patients with primary effusion lymphoma emphasizing the possible neoplastic nature of a pleural effusion in a patient with AIDS. (orig.) (orig.)

  6. Primary effusion lymphomas in AIDS: CT findings in two cases

    Energy Technology Data Exchange (ETDEWEB)

    Ferrozzi, F.; Tognini, G.; Mulonzia, N.W.; Pavone, P. [Ist. di Scienze Radiologiche, Univ. di Parma (Italy); Bova, D.

    2001-04-01

    Primary effusion lymphomas represent an unusual subset of AIDS-related non-Hodgkin's lymphomas. They are associated with herpes virus 8 and Epstein-Barr virus and characterized by predominant involvement of the serous body cavities (pleura, pericardium, peritoneum) as lymphomatous effusion without any identifiable tumour mass. We report herein CT findings in two patients with primary effusion lymphoma emphasizing the possible neoplastic nature of a pleural effusion in a patient with AIDS. (orig.) (orig.)

  7. VEGF(121)b, a new member of the VEGF(xxx)b family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo.

    Science.gov (United States)

    Rennel, E S; Varey, A H R; Churchill, A J; Wheatley, E R; Stewart, L; Mather, S; Bates, D O; Harper, S J

    2009-10-06

    The key mediator of new vessel formation in cancer and other diseases is VEGF-A. VEGF-A exists as alternatively spliced isoforms - the pro-angiogenic VEGF(xxx) family generated by exon 8 proximal splicing, and a sister family, termed VEGF(xxx)b, exemplified by VEGF(165)b, generated by distal splicing of exon 8. However, it is unknown whether this anti-angiogenic property of VEGF(165)b is a general property of the VEGF(xxx)b family of isoforms. The mRNA and protein expression of VEGF(121)b was studied in human tissue. The effect of VEGF(121)b was analysed by saturation binding to VEGF receptors, endothelial migration, apoptosis, xenograft tumour growth, pre-retinal neovascularisation and imaging of biodistribution in tumour-bearing mice with radioactive VEGF(121)b. The existence of VEGF(121)b was confirmed in normal human tissues. VEGF(121)b binds both VEGF receptors with similar affinity as other VEGF isoforms, but inhibits endothelial cell migration and is cytoprotective to endothelial cells through VEGFR-2 activation. Administration of VEGF(121)b normalised retinal vasculature by reducing both angiogenesis and ischaemia. VEGF(121)b reduced the growth of xenografted human colon tumours in association with reduced microvascular density, and an intravenous bolus of VEGF(121)b is taken up into colon tumour xenografts. Here we identify a second member of the family, VEGF(121)b, with similar properties to those of VEGF(165)b, and underline the importance of the six amino acids of exon 8b in the anti-angiogenic activity of the VEGF(xxx)b isoforms.

  8. Tofacitinib induces G1 cell-cycle arrest and inhibits tumor growth in Epstein-Barr virus-associated T and natural killer cell lymphoma cells.

    Science.gov (United States)

    Ando, Shotaro; Kawada, Jun-Ichi; Watanabe, Takahiro; Suzuki, Michio; Sato, Yoshitaka; Torii, Yuka; Asai, Masato; Goshima, Fumi; Murata, Takayuki; Shimizu, Norio; Ito, Yoshinori; Kimura, Hiroshi

    2016-11-22

    Epstein-Barr virus (EBV) infects not only B cells, but also T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoma. These lymphoid malignancies are refractory to conventional chemotherapy. We examined the activation of the JAK3/STAT5 pathway in EBV-positive and -negative B, T and NK cell lines and in cell samples from patients with EBV-associated T cell lymphoma. We then evaluated the antitumor effects of the selective JAK3 inhibitor, tofacitinib, against these cell lines in vitro and in a murine xenograft model. We found that all EBV-positive T and NK cell lines and patient samples tested displayed activation of the JAK3/STAT5 pathway. Treatment of these cell lines with tofacitinib reduced the levels of phospho-STAT5, suppressed proliferation, induced G1 cell-cycle arrest and decreased EBV LMP1 and EBNA1 expression. An EBV-negative NK cell line was also sensitive to tofacitinib, whereas an EBV-infected NK cell line was more sensitive to tofacitinib than its parental line. Tofacitinib significantly inhibited the growth of established tumors in NOG mice. These findings suggest that tofacitinib may represent a useful therapeutic agent for patients with EBV-associated T and NK cell lymphoma.

  9. Primary cutaneous peripheral T-cell lymphoma, unspecified with an indolent clinical course: a distinct peripheral T-cell lymphoma?

    LENUS (Irish Health Repository)

    Ryan, A J A

    2012-02-01

    Primary cutaneous peripheral T-cell lymphomas (PTL), unspecified, are rare lymphomas, with a poor prognosis. They grow and disseminate rapidly, leading to widespread disease. We report a case of PTL, unspecified occurring on the nose. Despite its aggressive histology, this tumour behaved indolently. It is remarkably similar, clinically and histologically, to four recently described cases that occurred on the ear.

  10. Primary lymphocytic lymphoma of lacrimal gland.

    Science.gov (United States)

    Romero-Caballero, M D; Lozano-García, I; Gómez-Molina, C; Gil-Liñán, A I; Arcas, I

    2017-02-01

    We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo.

    Science.gov (United States)

    Murray, Jayne; Valli, Emanuele; Yu, Denise M T; Truong, Alan M; Gifford, Andrew J; Eden, Georgina L; Gamble, Laura D; Hanssen, Kimberley M; Flemming, Claudia L; Tan, Alvin; Tivnan, Amanda; Allan, Sophie; Saletta, Federica; Cheung, Leanna; Ruhle, Michelle; Schuetz, John D; Henderson, Michelle J; Byrne, Jennifer A; Norris, Murray D; Haber, Michelle; Fletcher, Jamie I

    2017-09-01

    The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

    Directory of Open Access Journals (Sweden)

    Levy Laura S

    2007-02-01

    Full Text Available Abstract Background AIDS-related non-Hodgkin's lymphoma (AIDS-NHL is the second most frequent cancer associated with AIDS, and is a frequent cause of death in HIV-infected individuals. Experimental analysis of AIDS-NHL has been facilitated by the availability of an excellent animal model, i.e., simian Acquired Immunodeficiency Syndrome (SAIDS in the rhesus macaque consequent to infection with simian immunodeficiency virus. A recent study of SAIDS-NHL demonstrated a lymphoma-derived cell line to be sensitive to the growth inhibitory effects of the ubiquitous cytokine, transforming growth factor-beta (TGF-beta. The authors concluded that TGF-beta acts as a negative growth regulator of the lymphoma-derived cell line and, potentially, as an inhibitory factor in the regulatory network of AIDS-related lymphomagenesis. The present study was conducted to assess whether other SAIDS-NHL and AIDS-NHL cell lines are similarly sensitive to the growth inhibitory effects of TGF-beta, and to test the hypothesis that interleukin-6 (IL-6 may represent a counteracting positive influence in their growth regulation. Methods Growth stimulation or inhibition in response to cytokine treatment was quantified using trypan blue exclusion or colorimetric MTT assay. Intracellular flow cytometry was used to analyze the activation of signaling pathways and to examine the expression of anti-apoptotic proteins and distinguishing hallmarks of AIDS-NHL subclass. Apoptosis was quantified by flow cytometric analysis of cell populations with sub-G1 DNA content and by measuring activated caspase-3. Results Results confirmed the sensitivity of LCL8664, an immunoblastic SAIDS-NHL cell line, to TGF-beta1-mediated growth inhibition, and further demonstrated the partial rescue by simultaneous treatment with IL-6. IL-6 was shown to activate STAT3, even in the presence of TGF-beta1, and thereby to activate proliferative and anti-apoptotic pathways. By comparison, human AIDS-NHL cell lines

  13. Putting tumours in context.

    Science.gov (United States)

    Bissell, M J; Radisky, D

    2001-10-01

    The interactions between cancer cells and their micro- and macroenvironment create a context that promotes tumour growth and protects it from immune attack. The functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses. Investigation of this process might provide new insights into the mechanisms of tumorigenesis and could also lead to new therapeutic targets.

  14. Tocopherol in irradiation of temporary hypoxic tumours

    International Nuclear Information System (INIS)

    Kaagerud, A.; Lund, N.; Peterson, H.I.

    1981-01-01

    The influence of tocopherol on the effect of local irradiation under induced ischaemia by temporary tourniquet of two rat tumours transplanted intramuscularly into one hindleg was evaluated. An impaired retardation of growth rate occurred in tumours irradiated under ischaemia. This effect was eliminated by pretreatment of animals with tocopherol. In separate experiments the method of inducing ischaemia was investigated by MDO-electrode measurements of tumour tissue oxygen pressure. A significant tumour hypoxia was found under tourniquet of the tumour-bearing leg of the animals. Pretreatment with tocopherol did not influence the tumour pO 2 . (Auth.)

  15. Angiogenesis and expression of vascular endothelial growth factor, tumour necrosis factor-α and hypoxia inducible factor-1α in canine renal cell carcinoma.

    Science.gov (United States)

    Yhee, J Y; Yu, C H; Kim, J H; Im, K S; Kim, N H; Brodersen, B W; Doster, A R; Sur, J-H

    2012-01-01

    The aim of the present study was to determine the distribution and characteristics of microvessels in various histological types of canine renal cell carcinoma (RCC). The study compared microvessel density (MVD) and distribution of blood vessels according to histological type and evaluated the presence of angiogenesis-related proteins. Nine archival samples of canine RCC were studied. MVD was calculated as the mean number of blood vessels per mm(2). The diameter of blood vessels was calculated by determining either the length of the long axis of blood vessels (diameter(max)) or the mean distance from the centre of each blood vessel to the tunica adventia (diameter(mean)). A significant difference in MVD was evident between RCCs and normal kidneys (46.6 ± 28.0 versus 8.4 ± 2.2 microvessels/mm(2)). Diameter(max) in canine RCCs (34.1 ± 14.7 μm) was also significantly different from normal canine kidney (23.2 ± 3.4 μm). Vascular endothelial growth factor (VEGF) was expressed by tumour cells and vascular endothelial cells and tumour necrosis factor (TNF)-α expression was observed in vascular endothelial cells in both neoplastic and normal kidney. Although VEGF is involved in angiogenesis and correlates with tumour stage of development, no correlation was found between VEGF expression and MVD. Tumour-associated macrophages expressing TNF-α and hypoxia inducible factor 1α were identified in peritumoural tissue and may play an important role in angiogenesis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Conjunctival Lymphoma

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M; Rasmussen, Peter K; Coupland, Sarah E

    2016-01-01

    IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS...... age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse...... large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were...

  17. Lymphoma: Immune Evasion Strategies

    International Nuclear Information System (INIS)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul; Brown, Brian; Merad, Miriam; Brody, Joshua D.

    2015-01-01

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care

  18. Lymphoma: Immune Evasion Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Ranjan; Hammerich, Linda; Peng, Paul [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brown, Brian [Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Merad, Miriam [Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Brody, Joshua D., E-mail: joshua.brody@mssm.edu [Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

    2015-04-30

    While the cellular origin of lymphoma is often characterized by chromosomal translocations and other genetic aberrations, its growth and development into a malignant neoplasm is highly dependent upon its ability to escape natural host defenses. Neoplastic cells interact with a variety of non-malignant cells in the tumor milieu to create an immunosuppressive microenvironment. The resulting functional impairment and dysregulation of tumor-associated immune cells not only allows for passive growth of the malignancy but may even provide active growth signals upon which the tumor subsequently becomes dependent. In the past decade, the success of immune checkpoint blockade and adoptive cell transfer for relapsed or refractory lymphomas has validated immunotherapy as a possible treatment cornerstone. Here, we review the mechanisms by which lymphomas have been found to evade and even reprogram the immune system, including alterations in surface molecules, recruitment of immunosuppressive subpopulations, and secretion of anti-inflammatory factors. A fundamental understanding of the immune evasion strategies utilized by lymphomas may lead to better prognostic markers and guide the development of targeted interventions that are both safer and more effective than current standards of care.

  19. [Antitumor effect of recombinant Xenopus laevis vascular endothelial growth factor (VEGF) as a vaccine combined with adriamycin on EL4 lymphoma in mice].

    Science.gov (United States)

    Niu, Ting; Liu, Ting; Jia, Yong-Qian; Liu, Ji-Yan; Wu, Yang; Hu, Bing; Tian, Ling; Yang, Li; Kan, Bing; Wei, Yu-Quan

    2005-09-01

    To explore the antitumor effect of immunotherapy with recombinant Xenopus laevis vascular endothelial growth factor (xVEGF) as a vaccine combined with adriamycin on lymphoma model in mice. EL4 lymphoma model was established in C57BL/6 mice. Mice were randomized into four groups: combination therapy, adriamycin alone, xVEGF alone and normal saline (NS) groups, and then were given relevant treatments. The growth of tumor, the survival rate of tumor-bearing mice, and the potential toxicity of regimens above were observed. Anti-VEGF antibody-producing B cells (APBCs) were detected by enzyme-linked immunospot (ELISPOT) assay. In addition, microvessel density (MVD) of tumor was detected by immunohistochemistry, and tumor cell apoptosis was also detected by TUNEL staining. The tumor volumes of mice were significantly smaller in combination group than those in other three groups (P < 0.05). Complete regression of tumor was observed in 3 of 10 mice in combination group. Forty-eight days after inoculation of tumor cells, the survival rate of mice was significantly higher in combination group than in NS group (P < 0.01). The anti-VEGF APBC count in combination group or xVEGF group was significantly higher, compared with that in adriamycin group or NS group (P < 0.01). MVD in tumor tissues was significantly lower in combination group than those in other three groups (P < 0.05). Moreover, tumor cell apoptosis was significantly higher in combination group than those in other three groups (P < 0.05). In this experimental study, the use of xVEGF vaccine and adriamycin as a combination of immunotherapy with chemotherapy has sucessfully produced synergistic antitumor effect on lymphoma in mice.

  20. Ovarian lymphoma

    International Nuclear Information System (INIS)

    Bonet Fonseca, Ivan; Diaz Anaya, Amnia; Francis, Tabu

    2012-01-01

    50 % of pediatric oncologic pathology corresponds to mass or solid tumors, reaching about 20 % of total abdomen. The tumors that most frequently occur in the abdomen are nephroblastoma or Wilms tumor, Burkitts lymphoma, neuroblastoma, and ovarian germ cell tumors

  1. Diagnostic challenges and management of a patient with acromegaly due to ectopic growth hormone-releasing hormone secretion from a bronchial carcinoid tumour

    Directory of Open Access Journals (Sweden)

    Nikolaos Kyriakakis

    2017-01-01

    Full Text Available A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed.

  2. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  3. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Heegaard, Steffen

    2017-01-01

    Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B......-cell lymphoma (18 cases-9%). T-cell lymphomas are most frequently mycosis fungoides (25 cases-13%), extranodal natural killer/T-cell, nasal-type lymphoma (12 cases-6%), and primary cutaneous anaplastic large-cell lymphoma (12 cases-6%). This distribution differs from the distribution of ocular adnexal lymphoma...... and that of cutaneous lymphoma. The majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and adolescents. Several subtypes have a male predominance, including peripheral T-cell lymphoma and Burkitt lymphoma. Only...

  4. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  5. Intra-tumoural vessel area estimated by expression of epidermal growth factor-like domain 7 and microRNA-126 in primary tumours and metastases of patients with colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, T. F.; Nielsen, Boye Schnack; Jakobsen, Anders

    2015-01-01

    factor-like domain 7 (EGFL7) and microRNA-126 (miRNA-126) in primary tumours from patients with stage II-IV colorectal cancer (CRC) and in paired samples of primary tumours, regional lymph node metastases and distant metastases. Methods: A total of 126 patients were included. Analyses were performed...

  6. Tumours of the head and neck induced by ionizing radiation

    International Nuclear Information System (INIS)

    Daal, W.A.J. van.

    1979-01-01

    Reference is made to the cases of two patients who between 20 and 45 years after irradiation for tuberculous lymphomas in the neck developed malignant and benign tumours in the skin, the thyroid and the larynx-hypopharynx. The literature on induction of tumours by ionizing radiation is reviewed. So far, only one patient has been described in whome tumours in three organs may have been induced by irradiation. In the course of the examination of patients who have been irradiated for benign conditions, the possibility of tumours developing in several organs should be kept in mind. (Auth.)

  7. Emerging diagnostic tests for vitreoretinal lymphoma.

    Science.gov (United States)

    Dawson, Abby C; Williams, Keryn A; Appukuttan, Binoy; Smith, Justine R

    2018-04-19

    Vitreoretinal lymphoma, which most commonly is diffuse large B cell non-Hodgkin in type, is a rare cancer with high morbidity and high mortality. Making a tissue diagnosis of vitreoretinal lymphoma is a major challenge for clinicians due to biological and technical factors. Yet, the delay in start of treatment may have vision- and life- threatening consequences, and there is considerable interest in the application of molecular assays to improve the accuracy of the diagnostic process: detection of a clonal immunoglobulin heavy chain rearrangements in lymphoma cells by polymerase chain reaction; measurement of vitreous or aqueous interleukin-10 protein levels in ocular fluids; and identification of mutations in the myeloid differentiation primary response gene 88 in tumour cells. In this article, we review the historical development and current application of each of these molecular methods. We also discuss future opportunities for the molecular diagnosis of vitreoretinal lymphoma through next generation sequencing technologies. This article is protected by copyright. All rights reserved.

  8. Orbital and conunctival lymphoma treatment and prognosis

    International Nuclear Information System (INIS)

    Bessell, E.M.; Henk, J.M.; Whitelocke, R.A.F.; Wright, J.E.

    1988-01-01

    115 patients with lymphoid tumours presenting in the orbit were seen between 1970 and 1984. The histological types were high-grade malignant lymphoma - 18, low-grade malignant lymphoma - 43, and indeterminate lymphocytic lesions - 54. Eighteen patients were found to have disseminated lymphoma at presentation. The majority of the patients received radiotherapy to the orbit; local control was achieved in all cases and the ocular morbidity from radiotherapy was low with 11 patients developing lens opacities and 5 a dry eye. Survival of patients with stage I low-grade lymphoma adn indeterminate lymphocytic lesions was similar to that of a normal population of the same age distribution. The clinic features and dissemination pattern of the low-grade malignant lymphomata and the indeterminate lymphocytic lesions were identical, suggesting that most, if not all, lymphoid masses presenting in the orbit are neoplastic rather than reactive in nature. 28 refs.; 4 figs.; 5 tabs

  9. Orbital and conunctival lymphoma treatment and prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Bessell, E M; Henk, J M; Whitelocke, R A.F.; Wright, J E

    1988-12-01

    115 patients with lymphoid tumours presenting in the orbit were seen between 1970 and 1984. The histological types were high-grade malignant lymphoma - 18, low-grade malignant lymphoma - 43, and indeterminate lymphocytic lesions - 54. Eighteen patients were found to have disseminated lymphoma at presentation. The majority of the patients received radiotherapy to the orbit; local control was achieved in all cases and the ocular morbidity from radiotherapy was low with 11 patients developing lens opacities and 5 a dry eye. Survival of patients with stage I low-grade lymphoma adn indeterminate lymphocytic lesions was similar to that of a normal population of the same age distribution. The clinic features and dissemination pattern of the low-grade malignant lymphomata and the indeterminate lymphocytic lesions were identical, suggesting that most, if not all, lymphoid masses presenting in the orbit are neoplastic rather than reactive in nature. 28 refs.; 4 figs.; 5 tabs.

  10. Longitudinal growth in children with non-Hodgkin's lymphoma and children with acute lymphoblastic leukemia: Comparison between unirradiated and irradiated patients

    International Nuclear Information System (INIS)

    Marky, I.; Samuelsson, B.O.; Mellander, L.; Karlberg, J.

    1991-01-01

    Longitudinal growth was studied in children treated for non-Hodgkin's lymphoma (NHL). The aim of the study was to compare these children's growth velocity with findings in a previous study we performed on age-matched children with acute lymphoblastic leukemia (ALL) who received cranial irradiation. Nine children with NHL with an onset time of treatment between 4 and 9 years of age (mean 6.5 years) were studied with annual body measurements taken from the time of the diagnosis and thereafter annually during the following 4 years. None of the children received cranial irradiation. During the first treatment year a significantly low mean height velocity was observed (-1.4 standard deviation score [SDS]) for the NHL group. The consecutive two 1 year periods showed a normalization of the mean height velocity. For the group of children with ALL, there was a more prominent negative effect on height during the first 2 years of treatment than for the NHL group in the present study. After the cessation of therapy, the children with NHL showed a reduced catch-up growth compared with the children with ALL. The explanation offered is that cranial irradiation has a heavier impact on growth than chemotherapy during the first 2 years of treatment, but an intense chemotherapy during the maintenance period could have a considerable impact in blunting growth

  11. Comparison of metastatic disease after local tumour treatment with radiotherapy or surgery in various tumour models

    International Nuclear Information System (INIS)

    Ruiter, J. de; Cramer, S.J.; Lelieveld, P.; Putten, L.M. van

    1982-01-01

    Spontaneous metastases in lymph nodes and/or the lung were obtained after tumour cell inoculation of four mouse tumours and one rat tumour into the foot-pads of syngeneic animals or their F 1 hybrids. Following local radiotherapy with doses of 45-80 Gy, significantly more mice died with metastases than following local amputation of the tumour-bearing foot when the 2661 carcinoma was involved. No significant difference was observed after these treatments for the other tumours. The enhancement of metastatic growth after local radiotherapy in the 2661 carcinoma seems not to be due to incomplete killing of tumour cells in the foot. The presence of irradiated normal structures and tumour tissue after radiotherapy promoted the outgrowth of 2661 carcinoma cells which were outside the radiation field at the time of treatment. Evidently, even under similar experimental conditions, radiotherapy may enhance the growth of metastases from some tumours and not from others. (author)

  12. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Directory of Open Access Journals (Sweden)

    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  13. [Primary non-Hodgkin's lymphoma of the breast. A case report].

    Science.gov (United States)

    Villalón-López, José Sebastián; Souto-Del Bosque, Rosalía; Méndez-Sashida, Pedro Gonzalo

    Primary breast lymphomas, a rare subtype of non-Hodgkin's lymphoma, represent 0.04 to 0.5% of all breast cancers, 0.38 to 0.7% of all lymphomas, and 1.7 to 2.2% of extranodal lymphomas. The treatment choice is based on chemotherapy containing anthracycline and rituximab. Surgery is limited to being less invasive and only for diagnostic purposes. Radiotherapy has an important role as consolidation therapy, particularly in patients with negative nodes. A 70 year old woman with a breast nodule in the left upper outer quadrant, with slow growth, expansive, painless, and accompanied by skin changes, malaise, weight loss, fatigue, chill, and sweating. There was tissue replacement by the mammary gland tumour, skin changes due to invasion, and a 5cm axillary lymphadenopathy. The mammography showed skin thickening and a dense pattern of 80% of breast tissue replacement, and the lymphadenopathy with loss of radiolucent centre and soft tissue invasion. The biopsy confirmed a diffuse high grade large cell lymphoma. She received an Rituximab (R-CHOP) chemotherapy scheme and radiotherapy with tangential and supraclavicular and axillary fields. After completing the chemotherapy, the patient is on follow-up, and at 15 months she is alive without disease activity. Primary lymphoma of the breast is a rare entity. Multimodal treatment with combined chemo-radiotherapy is the cornerstone. Surgery is reserved only for diagnostic purposes. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Lymphoma cytogenetics.

    Science.gov (United States)

    Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

    2011-12-01

    Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

  15. Paediatric laryngeal granular cell tumour

    Directory of Open Access Journals (Sweden)

    Dauda Ayuba

    2009-01-01

    Full Text Available Granular cell tumour (GCT affecting the larynx is not common, especially in children. Most cases are apt to be confused with respiratory papilloma and may even be mistaken for a malignant neoplasia. We present a case of laryngeal GCT in a 12-year-old child to emphasize that the tumour should be regarded in the differential of growths affecting the larynx in children.

  16. The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mi-Ae Lyu

    2010-05-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB are expected to be of therapeutic value in those tumors where NF-κB seems to play a unique survival role such as activated B-cell (ABC-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-κB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-κB (IκB-α, inhibition of NF-κB DNA-binding activity, and accumulation of IκB-α. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-κB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05 in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-κB and are resistant to conventional chemotherapeutic regimens.

  17. Studies on a transplantable C57BL/6 mouse lymphoma

    International Nuclear Information System (INIS)

    Kendall, C.E.

    1977-01-01

    A C57BL/6 mouse lymphoma was demonstrated to be of T cell origin by treating the lymphoma cells with anti-Thy 1.2 antisera in a complement-dependent cytotoxicity test. The lymphoma's growth pattern was described using flow microfluorometric determinations and spleen weight progression. C-type particles were identified in electron micrographs of the lymphoma. C57BL/6 mice were immunized against the lymphoma by injecting x-ray inactivated lymphoma cells into the mice. Protection of immunized mice against live lymphoma cells demonstrated tumor antigens on the lymphoma cells. The success of immunization was found to depend on: route of injection, antigen dosage, state of the antigen, number of injections and the vaccination-challenge interval. Attempts were made to passively transfer immunity from immunized C57BL/6 mice which had survived lymphoma challenge to non-treated, syngeneic mice. The route of immunization in the donors influenced the success of passively transferred immunity in the recipients. Serum from days 1 to 3 and days 11 to death (day 17) had an enhancing effect on lymphoma growth. However, sera from days 5 to 9 retarded lymphoma growth. The C57BL/6 lymphoma cells were injected into rabbits and other strains of mice to demonstrate tumor specificity. The lymphoma did not grow in rabbits and only grew in one mouse strain. This strain had the same major histocompatibility loci as C57BL/6 mice. Crosses were made between C57BL/6 mice and a resistant strain of mice (DBA/2 mice). The F 1 hybrids were found to be less susceptible to the lymphoma than the C57BL/6 strain. Sublethal x-irradiation of the F 1 mice decreased its ability to resist the C57BL/6 lymphoma. Immunization with x-ray inactivated C57BL/6 lymphoma cells increased survival after challenge with lymphoma in the F 1 mice

  18. A database survey of equine tumours in the United Kingdom.

    Science.gov (United States)

    Knowles, E J; Tremaine, W H; Pearson, G R; Mair, T S

    2016-05-01

    Survey data on equine tumours are sparse compared with other species and may have changed over time. To describe the most frequently diagnosed equine tumours recorded by a diagnostic pathology laboratory over 29 years, to identify background factors associated with tumour type, and to identify any changes in the tumours diagnosed or the background of cases submitted during the study period. Observational; cross-sectional analysis of records of a diagnostic pathology laboratory. The records of all neoplastic equine histology submissions to the University of Bristol (January 1982-December 2010) were accessed from a database, and a list of diagnoses compiled. The 6 most commonly diagnosed tumour types were analysed using logistic regression to identify background factors associated with tumour type. The overall population of equine tumour submissions and the relative frequency of diagnosis of the most common tumour types were compared between decades. There were 964 cases included. The most frequently diagnosed tumours were: sarcoid (24% cases), squamous cell carcinoma (SCC) (19%), lymphoma (14%), melanoma (6%), gonadal stromal tumour (6%) and mast cell tumour (MCT) (4%). With sarcoid, Thoroughbred/Thoroughbred cross and gelding as reference categories: increasing age was significantly associated with the odds of each of the other tumour types, mares were at reduced risk of SCC, Arab/Arab cross had a higher risk of MCT, Cob/Cob cross had an increased risk of SCC and MCT, and ponies had an increased risk of melanoma. The mean age of submissions increased in each successive decade and the breed composition became broader. Sarcoids and lymphoma formed a smaller proportion of diagnoses in later decades. The types of tumours submitted to this laboratory have changed over the last 3 decades. Current data inform clinicians and researchers and further studies are warranted to follow trends. © 2015 EVJ Ltd.

  19. Intraocular lymphoma

    Directory of Open Access Journals (Sweden)

    Li-Juan Tang

    2017-08-01

    Full Text Available Intraocular lymphoma (IOL is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL is mainly a sub-type of primary central nervous system lymphoma (PCNSL. Alternatively, IOL can originate from outside the central nervous system (CNS by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL. The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1, and polymerase chain reaction (PCR amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.

  20. Breast lymphoma

    African Journals Online (AJOL)

    To fulfil the criteria for primary breast lymphoma, the following characteristics were reqUired: (I) technically adequate specimens; (iI) mammary tissue and lymphomatous infiltrate in close association; (iil) no evidence of concurrent widespread disease; and (iv) no previous. Haematology/Oncology Division, Department of ...

  1. Testicular lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; d'Amore, F; Christensen, Bjarne Egelund

    1994-01-01

    In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases...

  2. Hodgkin's Lymphoma

    Science.gov (United States)

    ... People who have had illnesses caused by the Epstein-Barr virus, such as infectious mononucleosis, are more likely to develop Hodgkin's lymphoma than are people who haven't had Epstein-Barr infections. By Mayo Clinic Staff . Mayo Clinic Footer ...

  3. Primary pleuro-pulmonary malignant germ cell tumours.

    Directory of Open Access Journals (Sweden)

    Vaideeswar P

    2002-01-01

    Full Text Available Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

  4. The effect of BW12C on radiosensitivity and necrosis of murine tissues and tumours

    International Nuclear Information System (INIS)

    Stevens, G.; Hill, S.A.; Joiner, M.C.; Joiner, B.; Johns, H.; Williams, K.; Denekamp, J.

    1994-01-01

    BW12C is a drug that has the potential to induce normal tissue and tumour hypoxia by binding to haemoglobin, increasing its affinity for oxygen and thereby reducing oxygen availability to tissues. Initial results suggested that BW12C administration caused significant radioprotection of normal tissues and induced tumour necrosis, but variable results have been reported subsequently. This work was carried to extend the range of observations concerning the ability of BW12C to radioprotect normal tissues and tumours and to induce necrosis of tumours of the mouse. BW12C was administered as 70 mg/kg intravenous 15 min before irradiation of jejunum in CBA mice and of foot skin in WHT mice with single doses of 240 kVp X-rays while mice breathed gases of varying oxygen tensions. The radiosensitivities of these tissues were assessed by the crypt survival assay and the acute skin reaction, respectively. The radiosensitivity of CaNT tumours to single fraction irradiation was assessed by the regrowth delay assay following administration of single or multiple does of BW12C at varying times to air-breathing CBA mice. The radiation response was compared to the radiosensitivity of clamped tumours. The effect of BW12C alone on tumours was assessed by regrowth delay and histological examination for necrosis. Single or multiple doses of BW12C did not influence the radiosensitivity of CaNT tumours, although marked radioprotection could be induced by clamping the tumours during irradiation. Multiple doses of BW12C alone led to a slight increase in necrosis of the CaNT tumour but did not alter its growth rate. BW12C alone did not induce necrosis of the murine JT lymphoma. The results shown that BW12C did not have a significant effect as a radioprotective or necrotizing agent in these experimental systems. The reported differences in the radiomodifying effects of BW12C are probably tissue-specific and relate to complex biochemical and physiological interactions. 18 refs., 4 figs

  5. Angioimmunoblastic T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  6. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  7. Non-Hodgkin's lymphoma - the role of radiation therapy

    International Nuclear Information System (INIS)

    Gospodarowicz, Mary K.

    1995-01-01

    Objective: To review the approach to the diagnosis, assessment, treatment and continuing management of patients with Non-Hodgkin's lymphoma with the emphasis on the role of radiation therapy in this group of diseases. The entity of 'Non-Hodgkin's Lymphoma' encompasses a diverse group of disorders involving almost any part of the body. This diversity bedevils any attempt to unify the approach to this disease on a rational basis. Nevertheless, some broad principles can be applied to almost any presentation of Non-Hodgkin's lymphoma. The approach to the management of Non-Hodgkin's lymphoma is based on the histologic type, localization and extent of disease and other disease and patient related prognostic factors. The accurate pathologic diagnosis of lymphoma has been greatly facilitated by availability of markers, molecular and genetic techniques. The newly proposed revised classification of lymphomas and its impact on these of RT will be discussed. Although the Ann Arbor staging classification has been shown to provide important prognostic information, other factors have equivalent, if not greater, influence on outcome in patients with Non-Hodgkin's lymphomas. The management of lymphomas is based primarily on the histologic type and extent of the disease including stage, tumour bulk, number of sites involved and location of the disease. The success of curative radiation therapy is contingent upon the presence of localized disease, normal tissue tolerance allowing the delivery of RT curative dose (30-35 Gy) and the tumour bulk. The current evidence suggests that locoregional RT for stage I and II low grade lymphoma results in approximately 50% prolonged (10-15 years) failure free rate and possible cure. Radiation alone is no longer used for intermediate and high grade lymphomas. The standard management of stage I and II intermediate grade large cell and mixed lymphomas is with doxorubicin based chemotherapy (e.g. CHOP) followed by involved field radiation. The

  8. Extranodal diffuse non hodgkin lymphoma in the thigh

    Directory of Open Access Journals (Sweden)

    Bölke E

    2010-08-01

    Full Text Available Abstract Diffuse large B-cell lymphoma usually starts as a rapidly growing mass in an internal lymph node and can grow in other areas such as the bone or intestines. About 1/3 of these lymphomas are confined to one part of the body when they are localized. In the case of a 78-year-old man, an extensive tumour was located on the right thigh. Biopsies of the tumour revealed diffuse proliferation of large lymphoid cells which have totally affected the normal architecture of striated muscle. The patient received multimodality treatment including chemotherapy of the CHOP regimen and adjuvant radiotherapy. Despite this being a fast growing lymphoma, about 3 out of 4 people will have no signs of disease after initial treatment, and about half of all people with this lymphoma are cured with therapy.

  9. Response and recovery kinetics of a solid tumour after irradiation

    International Nuclear Information System (INIS)

    Rowley, R.; Hopkins, H.A.; Ritenour, E.R.; Looney, W.B.

    1980-01-01

    The effects of local tumour radiation over the dose range 7.5-30 Gy on the growth and cell kinetics of rat hepatoma H-4-II-E have been investigated. A plot of growth delays against log surviving fraction was linear below a fraction of 0.03, but failed to extrapolate to the origin. Following a single dose of 15 Gy to the tumour, DNA-precursor incorporation, labelling and mitotic indices were depressed for 7 days. Tumour cellularity, measured as DNA/g tumour was reduced and the rate of increase of total clonogenic cells slower than after complete tumour recovery. From Day 7 to Day 9 all indices of proliferation recovered to about control levels, clonogenic cell numbers increased more rapidly and tumour cellularity was restored. Repopulation of the tumour therefore appeared to take place mainly after Day 7. Incorporation of [ 3 H]-TdR into tumour DNA reached twice the control values on Day 9. The rate of tumour growth accelerated after the initial decrease, and maximum tumour growth rate was also twice the control values on Day 13. Accelerated growth rates in irradiated tumours, above those of control tumours, occurred 10-16 days after treatment. The effectiveness of sequential therapy may therefore be improved if given during this period of accelerated tumour growth. (author)

  10. [Biotherapy of neuroendocrine tumours of the gastrointestinal tract and pancreas

    DEFF Research Database (Denmark)

    Hansen, C.P.; Knigge, U.

    2008-01-01

    Biotherapy of hormonal symptoms and tumour growth is a mainstay in the therapy of metastatic neuroendocrine tumours of the gastrointestinal tract and pancreas. Symptomatic relief can be achieved by somatostatin analogues and interferon, either alone or in combination. The effect on tumour growth...

  11. Hodgkin lymphoma - children

    Science.gov (United States)

    ... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... Cancer Institute website. Childhood Hodgkin lymphoma treatment (PDQ) - health professional ...

  12. Primary Breast Burkitt’s Lymphoma in an HIV-Infected Woman

    Directory of Open Access Journals (Sweden)

    Bangaly Traoré

    2015-01-01

    Full Text Available A 30-year-old HIV positive woman presented with a multifocal mass tumour associated with axillary and lateral-cervical lymphadenopathy in the right breast. Laboratory examination of the biopsy confirmed a case of mammary Burkitt’s lymphoma with a nodular infiltration of the breast. Antiretroviral treatment and chemotherapy were effective to control the tumour. Although Burkitt’s lymphoma rarely involves the breasts, it should be considered during routine breast examination of African woman.

  13. Gastric Calcifying Fibrous Tumour

    Directory of Open Access Journals (Sweden)

    Tan Attila

    2006-01-01

    Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

  14. [Plasmablastic lymphoma].

    Science.gov (United States)

    Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

    2016-11-04

    Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  15. Adiponectin deficiency suppresses lymphoma growth in mice by modulating NK cells, CD8 T cells, and myeloid-derived suppressor cells.

    Science.gov (United States)

    Han, Sora; Jeong, Ae Lee; Lee, Sunyi; Park, Jeong Su; Kim, Kwang Dong; Choi, Inpyo; Yoon, Suk Ran; Lee, Myung Sok; Lim, Jong-Seok; Han, Seung Hyun; Yoon, Do Young; Yang, Young

    2013-05-01

    Previously, we found that adiponectin (APN) suppresses IL-2-induced NK cell activation by downregulating the expression of the IFN-γ-inducible TNF-related apoptosis-inducing ligand and Fas ligand. Although the antitumor function of APN has been reported in several types of solid tumors, with few controversial results, no lymphoma studies have been conducted. In this study, we assessed the role of APN in immune cell function, including NK cells, CTLs, and myeloid-derived suppressor cells, in EL4 and B16F10 tumor-bearing APN knockout (KO) mice. We observed attenuated EL4 growth in the APNKO mice. Increased numbers of splenic NK cells and splenic CTLs were identified under naive conditions and EL4-challenged conditions, respectively. In APNKO mice, splenic NK cells showed enhanced cytotoxicity with and without IL-2 stimulation. Additionally, there were decreased levels of myeloid-derived suppressor cell accumulation in the EL4-bearing APNKO mice. Enforced MHC class I expression on B16F10 cells led to attenuated growth of these tumors in APNKO mice. Thus, our results suggest that EL4 regression in APNKO mice is not only due to an enhanced antitumor immune response but also to a high level of MHC class I expression.

  16. Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma.

    Science.gov (United States)

    Fanale, Michelle A; Younes, Anas

    2007-01-01

    Antibody-based therapeutic approaches have had a significant impact in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab's development as an anti-CD20 antibody heralded a new era in treatment approaches for NHL. While rituximab was first shown to be effective in the treatment of relapsed follicular lymphoma, it is now standard monotherapy for front-line treatment of follicular lymphoma, and is also used in conjunction with chemotherapy for other indolent, intermediate and aggressive B-cell lymphomas. The development of rituximab has led to intense interest in this type of therapeutic approach and to development and approval of the radioimmunoconjugates of rituximab, (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, which have added to the repertoire of treatments for relapsed follicular lymphoma and increased interest in developing other conjugated antibodies. Since rituximab is a chimeric antibody, there is a need to develop fully humanised antibodies, such as IMMU-106 (hA20), in order to minimise infusion reactions and eliminate the development of human antibodies against the drug. Further clinical evaluation of antibodies has been based largely on our knowledge of antigen expression on the surface of lymphoma cells and has led to the development of antibodies against CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD52 (alemtuzumab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab]), and CD40 (SGN-40). Furthermore, the VEGF (vascular endothelial growth factor) inhibitor bevacizumab, which was first approved for the treatment of colon cancer is currently under investigation in NHL, and agonists rather than antibodies to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) [rApo2L/TRAIL, HGS-ETR1{mapatumumab}, HGS-ETR2] are currently being investigated as treatments for both advanced solid tumours and NHL. Knowledge of the ability of cancer cells to become

  17. Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

    Science.gov (United States)

    Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

    2018-06-08

    Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER

  18. Treatment options for Primary CNS Lymphoma.

    Science.gov (United States)

    Laghari, Altaf Ali; Ahmed, Syed Ijlal; Jabbar, Adnan; Shamim, Muhammad Shahzad

    2018-03-01

    Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

  19. Antigen-specific primed cytotoxic T cells eliminate tumour cells in vivo and prevent tumour development, regardless of the presence of anti-apoptotic mutations conferring drug resistance.

    Science.gov (United States)

    Jaime-Sánchez, Paula; Catalán, Elena; Uranga-Murillo, Iratxe; Aguiló, Nacho; Santiago, Llipsy; M Lanuza, Pilar; de Miguel, Diego; A Arias, Maykel; Pardo, Julián

    2018-05-09

    Cytotoxic CD8 + T (Tc) cells are the main executors of transformed and cancer cells during cancer immunotherapy. The latest clinical results evidence a high efficacy of novel immunotherapy agents that modulate Tc cell activity against bad prognosis cancers. However, it has not been determined yet whether the efficacy of these treatments can be affected by selection of tumoural cells with mutations in the cell death machinery, known to promote drug resistance and cancer recurrence. Here, using a model of prophylactic tumour vaccination based on the LCMV-gp33 antigen and the mouse EL4 T lymphoma, we analysed the molecular mechanism employed by Tc cells to eliminate cancer cells in vivo and the impact of mutations in the apoptotic machinery on tumour development. First of all, we found that Tc cells, and perf and gzmB are required to efficiently eliminate EL4.gp33 cells after LCMV immunisation during short-term assays (1-4 h), and to prevent tumour development in the long term. Furthermore, we show that antigen-pulsed chemoresistant EL4 cells overexpressing Bcl-X L or a dominant negative form of caspase-3 are specifically eliminated from the peritoneum of infected animals, as fast as parental EL4 cells. Notably, antigen-specific Tc cells control the tumour growth of the mutated cells, as efficiently as in the case of parental cells. Altogether, expression of the anti-apoptotic mutations does not confer any advantage for tumour cells neither in the short-term survival nor in long-term tumour formation. Although the mechanism involved in the elimination of the apoptosis-resistant tumour cells is not completely elucidated, neither necroptosis nor pyroptosis seem to be involved. Our results provide the first experimental proof that chemoresistant cancer cells with mutations in the main cell death pathways are efficiently eliminated by Ag-specific Tc cells in vivo during immunotherapy and, thus, provide the molecular basis to treat chemoresistant cancer cells with CD8 Tc

  20. Synchronous Epithelioid Stromal Tumour and Lipoma in the Stomach

    Directory of Open Access Journals (Sweden)

    Nabeel Al-Brahim

    2003-01-01

    Full Text Available An 82-year-old man presented with upper gastrointestinal bleeding. A polypoid lesion of the distal stomach with focal ulceration was seen at endoscopy. This was treated by a partial gastrectomy. The resected stomach contained two separate tumours near the pylorus: a gastrointestinal stromal tumour (GIST and an adjacent lipoma. The literature includes case reports of synchronously occurring GIST and adenocarcinoma, GIST and mucosa-associated lymphoid tissue lymphoma and GIST and carcinoid tumour. Herein is the first case report of two distinct mesenchymal tumors coexisting in the stomach.

  1. Paraspinal primitive neuroectodermal tumour (PNET) of the chest ...

    African Journals Online (AJOL)

    neural crest cells1-5 and may occur in the central or peripheral nervous system.4 PNET must be distinguished from other small round cell tumours like Ewing's sarcoma (ES), extraosseous Ewing's sarcoma, neuroblastoma, lymphoma, rhabdomyosarcoma and small-cell carcinoma. 3,4,6,7 Although it can occur at any age, ...

  2. MRI characteristics of midbrain tumours

    International Nuclear Information System (INIS)

    Sun, B.; Wang, C.C.; Wang, J.

    1999-01-01

    We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases. (orig.) (orig.)

  3. Synergistic suppression of the PI3K inhibitor CAL-101 with bortezomib on mantle cell lymphoma growth

    International Nuclear Information System (INIS)

    Qu, Fu-Lian; Xia, Bing; Li, Su-Xia; Tian, Chen; Yang, Hong-Liang; Li, Qian; Wang, Ya-Fei; Yu, Yong; Zhang, Yi-Zhuo

    2015-01-01

    To investigate the effects of CAL-101, particularly when combined with bortezomib (BTZ) on mantle cell lymphoma (MCL) cells, and to explore its relative mechanisms. MTT assay was applied to detect the inhibitory effects of different concentrations of CAL-101. MCL cells were divided into four groups: control group, CAL-101 group, BTZ group, and CAL-101/BTZ group. The expression of PI3K-p110σ, AKT, ERK, p-AKT and p-ERK were detected by Western blot. The apoptosis rates of CAL-101 group, BTZ group, and combination group were detected by flow cytometry. The location changes of nuclear factor kappa-B (NF-κB) of 4 groups was investigated by NF-κB Kit exploring. Western blot was applied to detect the levels of caspase-3 and the phosphorylation of AKT in different groups. CAL-101 dose- and time-dependently induced reduction in MCL cell viability. CAL-101 combined with BTZ enhanced the reduction in cell viability and apoptosis. Western blot analysis showed that CAL-101 significantly blocked the PI3K/AKT and ERK signaling pathway in MCL cells. The combination therapy contributed to the inactivation of NF-κB and AKT in MCL cell lines. However, cleaved caspase-3 was up-regulated after combined treatment. Our study showed that PI3K/p110σ is a novel therapeutic target in MCL, and the underlying mechanism could be the blocking of the PI3K/AKT and ERK signaling pathways. These findings provided a basis for clinical evaluation of CAL-101 and a rationale for its application in combination therapy, particularly with BTZ

  4. RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.

    Science.gov (United States)

    Yu, W; Sanders, B G; Kline, K

    1997-01-01

    RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

  5. Nuclear medicine in childhood tumours

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    2004-01-01

    Full text: In recent years the contribution of nuclear medicine has been of increasing interest to paediatric oncology, in particular in imaging for diagnosis, staging and follow-up, in quantitative function analysis of organs at risk during oncological therapy, as well as in radionuclide therapy. For tumour imaging a great number of tumour-seeking radiopharmaceuticals are available, exploiting various metabolic and biological properties of individual tumours; several of these agents can also be applied for radionuclide therapy. More recent tracers allow the characterization of tumours, highlighting features like hormone receptors, hypoxia, MDR and apoptosis. New techniques in paediatric oncology include PET and probe-guided surgery. As a functional modality, nuclear medicine is well suited to monitor the function of organs at risk during treatment in paediatric oncology, in particular cardiac, pulmonary, renal and salivary gland function. A summary of applications and major Indications will be presented. Osteosarcoma: In differentiated osteosarcoma bone scintigraphy/SPECT using 99m Tc-diphosphonate may, as a result of Its targeting the tumour-produced osteoid, visualize not only the primary bone tumour and skeletal metastases, but also the extraosseous metastases. For preoperative therapy nd palliation of metastases beta-emitting bone-seeking agents, such as 89 Sr-chloride, 186 Re-HEDP and 153 Sm-EDTMP, are available. Lymphoma: 67 Ga-citrate has been used for decades in the detection, staging and follow up of lymphoma, as well as for early recognition of response to therapy. 201 TI-chloride scintigraphy/SPECT and PET using 18 F-deoxyglucose can also be used for this purpose. 99m Tc- sestamibi and 99m Tc-tetrofosmin are associated with p-glycoprotein, playing a role in multidrug resistance. In adults with recurrent non Hodgkin lymphoma treatment with 131 l- or 90 Y labelled anti-CD20 antibodies is highly effective. Thyroid carcinoma. 201 TI-chloride scintigraphy

  6. Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

    Science.gov (United States)

    Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

    2014-09-01

    Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

  7. Oxidative stress by ascorbate/menadione association kills K562 human chronic myelogenous leukaemia cells and inhibits its tumour growth in nude mice.

    Science.gov (United States)

    Verrax, Julien; Stockis, Julie; Tison, Aurélie; Taper, Henryk S; Calderon, Pedro Buc

    2006-09-14

    The effect of oxidative stress induced by the ascorbate/menadione-redox association was examined in K562 cells, a human erythromyeloid leukaemia cell line. Our results show that ascorbate enhances menadione redox cycling, leading to the formation of intracellular reactive oxygen species (as shown by dihydrorhodamine 123 oxidation). The incubation of cells in the presence of both ascorbate/menadione and aminotriazole, a catalase inhibitor, resulted in a strong decrease of cell survival, reinforcing the role of H(2)O(2) as the main oxidizing agent killing K562 cells. This cell death was not caspase-3-dependent. Indeed, neither procaspase-3 and PARP were processed and only a weak cytochrome c release was observed. Moreover, we observed only 23% of cells with depolarized mitochondria. In ascorbate/menadione-treated cells, DNA fragmentation was observed without any sign of chromatin condensation (DAPI and TUNEL tests). The cell demise by ascorbate/menadione is consistent with a necrosis-like cell death confirmed by both cytometric profile of annexin-V/propidium iodide labeled cells and by light microscopy examination. Finally, we showed that a single i.p. administration of the association of ascorbate and menadione is able to inhibit the growth of K562 cells by about 60% (in both tumour size and volume) in an immune-deficient mice model. Taken together, these results reinforced our previous claims about a potential application of the ascorbate/menadione association in cancer therapy.

  8. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    International Nuclear Information System (INIS)

    Illidge, T.M.

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti-CD40

  9. Direct astatination of a tumour-binding protein, human epidermal growth factor, using nido-carborane as a prosthetic group

    International Nuclear Information System (INIS)

    Sjoestroem, A.; Carlsson, J.; Lundqvist, H.; Koziorowski, J.

    2003-01-01

    A method for direct astatine labeling of proteins has been investigated. Binding sites for astatine were created by coupling of a nido-carborane derivative to a protein, the human epidermal growth factor (hEGF), using two different conjugation methods - by glutaraldehyde cross-linking or by introduction of sulfohydryl groups by Traut's reagent with subsequent linking of ANC-1 with m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester. The conjugates were astatinated using the Chloramine-T method in high yield. The best labeling was obtained by the glutaraldehyde conjugate with an average yield of 68 ± 9%. In vitro stability tests indicated that the glutaraldehyde conjugated label was as stable as hEGF labeled with astatobenzoate. (author)

  10. Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

    2016-01-01

    AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

  11. Tumour sleuths

    International Nuclear Information System (INIS)

    Beyers, M.; Springolo, E.; Conradie, J.D.

    1986-01-01

    Hepatocellular carcinoma is a common disease in South Africa and its identification difficult. Methods for the diagnosis of this disease includes the production of hybridoma cell lines by inoculating laboratory mice with a purified human tumour-associated antigen or the antigen-containing surface membranes or the intact cells. In the diagnosis of hepatocellular carcinoma, high concentrations of serum alpha fetoprotein (AFP) can be measured by means of radioimmunoassay techniques. The need for specific methods of diagnosis and treatment of hepatocellular carcinoma led to the investigation by the Isotope Production Centre at Pelindaba into the possibility of using radiolabelled monoclonal anti-AFP for diagnosis, and later, therapy of hepatocellular carcinoma. The monoclonal antibodies can also be labelled with 131 I. Recently the Department of Nuclear Medicine of the University of the Witwatersrand is conducting diagnostic trials on patients who have given their informed consent, to assess the specificity of 131 I radiolabelled anti-AFP monoclonal antibodies to hepatocellular carcinoma cells in humans. Although the investigation is still in its infancy, monoclonal antibodies may prove to be successful non-invasive agents for detecting tumors in early stages

  12. Adnexal Tumours Of Skin

    Directory of Open Access Journals (Sweden)

    Parate Sanjay N

    1998-01-01

    Full Text Available A total 120 cases of epidermal appendage tumours of skin were analysed and classified according to the classification provided by WHO’. Epidermal appendage tumours accounted for 12.87% of all skin tumours, of which 29.17% were benign and 70.83% were malignant. Most of the tumours (75.83% were in the head and face region. The most common tumour was basal cell epithelioma (55%.

  13. Tumours associated with medical X-ray therapy exposure in childhood

    International Nuclear Information System (INIS)

    Colman, M.; Kirsch, M.; Creditor, M.

    1978-01-01

    A total of 5166 persons who were exposed to limited field (80-100 cm 2 ) X-ray irradiation to the head, neck and upper chest region during childhood and adolescence have provided an outstanding opportunity for the study of tumour incidence following medical X-ray therapy. More than 3254 subjects have been traced, 3108 have completed questionnaires eliciting information on tumour incidence, and 1539 of these were subjected to a thorough clinical screening procedure that included a thyroid scintigram. The prevalence of thyroid tumours in the 1539 clinically screened subjects and the prevalence of all other tumours in the 3254 subjects traced can therefore be assumed to reflect the risks in the group of irradiated subjects as a whole. Median age at irradiation was 3.5 years, and median radiation dose 790 rads (7.9 Gy). Thyroid tumour was diagnosed in 413 subjects. Of those undergoing surgery (273) 30.3% were found to have thyroid cancer. A total of 366 surgical pathology specimens of the thyroid, including 93 from subjects who were diagnosed at other hospitals, were examined revealing 73 papillary carcinomas, 12 follicular carcinomas and 26 microscopic papillary carcinomas. One hundred and eighty-seven other (non-thyroid) neoplasmas identified included 27 benign and 10 malignant salivary gland tumours, 16 benign and seven malignant tumours of neural origin (brain, spinal cord, cranial and peripheral nerves), 37 skin tumours, 9 lymphomas, 8 gonadal tumours, 45 breast tumours and 28 tumours of miscellaneous sites. The incidence of thyroid tumours, salivary gland tumours and primary brain tumours was considerably in excess of the expected incidence (p values<0.0001), and a radiation dose-effect correlation was observed for thyroid and brain tumours. Gonadal tumours and lymphomas did not occur in excess of the expected incidence

  14. Periaortic lymphoma in a cat

    Directory of Open Access Journals (Sweden)

    Laura Bree

    2017-09-01

    Full Text Available Case summary A 14-year-old neutered male Siamese cat was presented with a 3 month history of lethargy, inappetence, dehydration, hindlimb ataxia and intermittent proprioceptive deficits in the hindlimbs. Physical examination revealed low body condition score (1.75/5, pallor and bilateral basilar grade II/VI systolic heart murmur. Neurological examination revealed hindlimb ataxia, severe atrophy of the hindlimb musculature, intermittent hindlimb proprioceptive deficits and normoreflexia. Clinicopathological investigations revealed non-regenerative anaemia (haematocrit 0.17 l/l; reference interval [RI] 0.24–0.45 l/l and increased feline pancreatic lipase concentration (Spec fPL test [IDEXX] 8.3 μg/l; RI 0.1–3.5 μg/l. Feline leukaemia virus antigen and feline immunodeficiency virus antibody tests were negative. Thoracic and abdominal imaging revealed a soft tissue structure in the area of the thoracoabdominal aorta. CT confirmed a periaortic contrast-enhancing mass extending from the level of T9–L2, with associated intervertebral infiltration at the level of T11–T12. Post-mortem examination confirmed the presence of a solid, white, multinodular, well-demarcated mass encircling the aorta extending from T9–L2. Based on histopathology and immunohistochemistry, a diagnosis of B-cell lymphoma was made. Lymphoma was also identified histopathologically within the kidneys and spleen. Evidence of mild Wallerian degeneration was present within the spinal cord, indicating compression at the level of the periaortic mass. Relevance and novel information To our knowledge, this is the first report of periaortic lymphoma in the cat. Although periaortic tumours are exceptionally rare in veterinary medicine, lymphoma should be considered as a differential in cats.

  15. The uPA/uPAR system regulates the bioavailability of PDGF-DD: implications for tumour growth.

    Science.gov (United States)

    Ehnman, M; Li, H; Fredriksson, L; Pietras, K; Eriksson, U

    2009-01-29

    Members of the platelet-derived growth factor (PDGF) family are mitogens for cells of mesenchymal origin and have important functions during embryonic development, blood vessel maturation, fibrotic diseases and cancer. In contrast to the two classical PDGFs, the novel and less well-characterized members, PDGF-CC and PDGF-DD, are latent factors that need to be processed extracellularly by activating proteases, before they can mediate PDGF receptor activation. Here, we elucidate the structural requirements for urokinase plasminogen activator (uPA)-mediated activation of PDGF-DD, as well as the intricate interplay with uPA receptor (uPAR) signalling. Furthermore, we show that activated PDGF-DD, in comparison to latent, more potently transforms NIH/3T3 cells in vitro. Conversely, xenograft studies in nude mice demonstrate that cells expressing latent PDGF-DD are more tumorigenic than those expressing activated PDGF-DD. These findings imply that a fine-tuned proteolytic activation, in the local milieu, controls PDGF-DD bioavailability. Moreover, we suggest that proteolytic activation of PDGF-DD reveals a retention motif mediating interactions with pericellular components. Our proposed mechanism, where uPA not only generates active PDGF-DD, but also regulates its spatial distribution, provides novel insights into the biological function of PDGF-DD.

  16. Malignant lymphoma of the conjunctiva

    DEFF Research Database (Denmark)

    Kirkegaard, Marina M.; Coupland, Sarah E.; Prause, Jan U.

    2015-01-01

    Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed...... by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%), and mantle cell lymphoma (3%). Extranodal marginal zone lymphoma occurs slightly more often in women and, along with follicular lymphoma, presents late in the seventh decade of life, whereas diffuse large B-cell lymphoma and especially mantle cell...... lymphoma have a predilection for the male gender and typically present in the eighth decade. Extranodal marginal zone lymphoma and follicular lymphoma present most frequently in the forniceal and bulbar conjunctiva. Conjunctival diffuse large B-cell lymphoma, mantle cell lymphoma and T-cell NHLs...

  17. Imaging of primary central nervous system lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Y.Z., E-mail: yenzhitang@doctors.net.uk [Royal Free Hospital, London (United Kingdom); Booth, T.C.; Bhogal, P.; Malhotra, A.; Wilhelm, T. [Royal Free Hospital, London (United Kingdom)

    2011-08-15

    Primary central nervous system lymphoma (PCNSL) comprises 5% of all primary brain tumours. PCNSL demonstrates a variety of well-documented imaging findings, which can vary depending on immune status and histological type. Imaging features of PCNSL may overlap with other tumours and infection making definitive diagnosis challenging. In addition, several rare variants of PCNSL have been described, each with their own imaging characteristics. Advanced imaging techniques including 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}FDG) and {sup 11}C positron-emission tomography (PET), {sup 201}Tl single-photon emission computed tomography (SPECT), {sup 1}H-magnetic resonance spectroscopy (MRS), and MR perfusion, have been used to aid differentiation of PCNSL from other tumours. Ultimately, no imaging method can definitively diagnose PCNSL, and histology is required.

  18. Non-Hodgkin's lymphoma of the spermatic cord

    DEFF Research Database (Denmark)

    Møller, Michael Boe

    1994-01-01

    Primary lymphomas of the spermatic cord (LSC) are rare and have only been described in 10 cases in the literature. The present study is a review of the clinicopathological features of LSC described in the cases reported in the literature and presents a new case. LSC is a tumour affecting middle...

  19. [Gastric perforation by MALT lymphoma. Case report].

    Science.gov (United States)

    López-Zamudio, José; Ramírez-González, Luis Ricardo; Núñez-Márquez, Julia; Fuentes Orozco, Clotilde; González Ojeda, Alejandro; Leonher-Ruezga, Karla Lisseth

    2015-01-01

    Gastric non-Hodgkin lymphoma is a rare tumour that represents approximately 7% of all stomach cancers and 2% of all lymphomas. The most frequent location of gastric MALT (mucosa associated lymphoid tissue) lymphomas is in the antrum in 41% of the cases, and 33% can be multifocal. The risk of spontaneous perforation of a gastric MALT lymphoma is 4-10%. 24 year old male patient carrying the Human Immunodeficiency Virus, who began with signs and symptoms of acute abdomen and fever 72 hours before arriving in the emergency room. A computed tomography was performed that showed free fluid in the cavity, and gastric wall thickening. The patient underwent a laparotomy, finding absence of the anterior wall of the stomach, sealed with the left lobe of the liver, colon and omentum. Total gastrectomy, with oesophagosty and jejunostomy tube, was performed. Gastric perforation secondary to a MALT lymphoma is rare, with high mortality. There is limited information reported of this complication and should be highly suspected in order to provide appropriate treatment for a complication of this type. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  20. Primary Malignant Lymphoma of the Uterus: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Margriet Samama

    2011-12-01

    Full Text Available Primary malignant lymphomas in the female genital tract are rare. Most cases are non-Hodgkin lymphomas of which diffuse large B-cell lymphomas are most commonly seen. Symptoms are associated with other, more common diseases; therefore, a doctors’ delay can be expected. In this case a woman presented with complaints of urinary obstruction due to a large tumour in the pelvic area. A laparotomy was performed. A very large tumour of the uterus was found with adherence to the pelvic wall and urinary bladder. Diagnostic histological examination showed a diffuse large B-cell lymphoma. Treatment with R-CHOP chemotherapy was started shortly after the operation. The treatment of patients with a primary malignant lymphoma of the uterus should be individualized with the following options: surgery, radiotherapy and/or chemotherapy.

  1. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    Energy Technology Data Exchange (ETDEWEB)

    Fell, A.H.; Preston, P.M. (Edinburgh Univ. (United Kingdom))

    1992-07-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author).

  2. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    International Nuclear Information System (INIS)

    Fell, A.H.; Preston, P.M.

    1992-01-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author)

  3. HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Lundgren, Jens Dilling

    1991-01-01

    (6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0...

  4. Association between simian virus 40 and non-Hodgkin lymphoma

    Science.gov (United States)

    Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

    2002-01-01

    BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

  5. Lymphoma of the Eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Rasmussen, Peter Kristian; Coupland, Sarah E.

    2017-01-01

    Purpose To document subtype-specific clinical features of lymphoma of the eyelid, and their effect on patient outcome. Design Retrospective observational case series. Methods Patient data were collected from 7 international eye cancer centers from January 1, 1980 through December 31, 2015....... The cases included primary and secondary lymphomas affecting the eyelid. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary endpoints. Results Eighty-six patients were included. Mean age was 63 years and 47 (55%) were male. Non-Hodgkin B-cell lymphomas...... constituted 83% (n = 71) and T-cell lymphomas constituted 17% (n = 15). The most common subtypes were extranodal marginal-zone lymphoma (EMZL) (37% [n = 32]), follicular lymphoma (FL) (23% [n = 20]), diffuse large B-cell lymphoma (DLBCL) (10% [n = 9]), mantle cell lymphoma (MCL) (8% [n = 7]), and mycosis...

  6. International Lymphoma Epidemiology Consortium

    Science.gov (United States)

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  7. Radiotherapy of malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Kujawska, J [Instytut Onkologii, Krakow (Poland)

    1979-01-01

    The paper discusses current views on the role of radiotherapy in the treatment of patients with malignant lymphomas. Principles of radiotherapy employed in the Institute of Oncology in Cracow in case of patients with malignant lymphomas are also presented.

  8. Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

    Directory of Open Access Journals (Sweden)

    Marina Rios Araújo

    2012-08-01

    Full Text Available This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes are required for definitive diagnosis of round cell tumours in dogs.

  9. Lymphoma Research Foundation

    Science.gov (United States)

    ... Follow LRF Watch LRF Contact Us National Headquarters Wall Street Plaza 88 Pine Street, Suite 2400 | New York, NY 10005 212-349-2910 | 212-349-2886 Fax LRF@lymphoma.org LRF Helpline 800-500-9976 Helpline@lymphoma.org © 2012 Lymphoma Research Foundation | Privacy Policy

  10. of brain tumours

    African Journals Online (AJOL)

    outline of the important clinical issues related to brain tumours and psychiatry. ... Left-sided, frontal tumours also seem to be associated with higher rates of depression, while those in the frontal lobe of the right .... Oxford: Blackwell Science,.

  11. Immunity to tumour antigens.

    Science.gov (United States)

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  12. Spectrum of central nervous system tumours-a single center histopathological review of 761 cases over 5 years

    International Nuclear Information System (INIS)

    Ahsan, J.; Hashmi, S.N.; Din, H.U.; Masood, A.

    2015-01-01

    The incidence of central nervous system (CNS) tumours has rapidly increased over the past few years. There is no accurate nationwide CNS tumour epidemiology in Pakistan that makes policy making for tumour screening and early treatment difficult. The purpose of this study was to provide the spectrum of CNS tumours in a premier diagnostic and referral centre of Pakistan. Methods: This cross-sectional study was carried out at Histopathology Department, Armed Forces Institute of Pathology over a period of 5 years. A total of 761 cases patients who were diagnosed with CNS tumours on histopathology, both benign and malignant, belonging to both genders, between the ages of 1-85 years, from 11.2009 to 31.12.2013 were included in the study. Results: Seven CNS tumour categories were as follows; tumours of neuroepithelial tissue (56.0%), tumours of the meninges (28.3%), tumour of the sellar region (2.6%), germ cell tumour (0.1), tumour of cranial and paraspinal nerves (5.4%), lymphomas and haematopoietic neoplasm (2.4%), metastatic tumours (4.9%), where histological types by age and gender showed great variability. Astrocytic tumours were the commonest neuroepithelial tumours (69.4%). Glioblastoma multiform forming the largest subtype of neuroepithelial tumours (40.4%) with a mean age at diagnosis being 47.1 years. Overall, males exceeded females in number of most of the CNS tumour types, however meningeal tumours were more frequently noted in females. Conclusions: Neuroepithelial tumours are commonest tumour and comprise more than half of all operated CNS tumours in our setup, followed by meningeal tumours. Glioblastoma multiforme is largest subtype of neuroepithelial tumour, and comprising 40.4% of all. (author)

  13. The emergence of non-cytolytic NK1.1+ T cells in the long-term culture of murine tumour-infiltrating lymphocytes: a possible role of transforming growth factor-beta.

    Science.gov (United States)

    Tamada, K; Harada, M; Ito, O; Takenoyama, M; Mori, T; Matsuzaki, G; Nomoto, K

    1996-12-01

    The mechanism by which murine tumour-infiltrating lymphocytes (TIL) decreased their anti-tumour activity during an in vitro culture with interleukin-2 (IL-2) was investigated. A phenotype analysis revealed that the TIL cultured for 7 days (TIL-d7) were exclusively NKI.1- CD4- CD8+ CD3+ cells and that this population was replaced by natural killer (NK)1.1+ CD4- CD8 CD3+ cells by day 27 (TIL-d27) during the culture of TIL. The TIL-d7 cells showed a cytolytic activity against B16 melanoma, whereas the TIL-d27 cells had lost this activity, suggesting that the decrease in the anti tumour effect of TIL during the culture with IL-2 was due to their populational change. Analysis on the characteristics of the TIL-d27 cells revealed that they expressed skewed T-cell receptor (TCR) V beta 5 and increased mRNA expression of V alpha 14. In addition, they expressed transforming growth factor beta (TGF-beta) mRNA. Interestingly, TGF-beta augmented the proliferation of TIL-d27 cells under the presence of IL-2, but suppressed that of TIL-d7 cells. Moreover, the proliferation of TIL-d27 cells was suppressed by anti-TGF-beta monoclonal antibody. Collectively, these results suggest that, in contrast to its suppressive effect on anti-tumour effector T cells. TGF-beta could be an autocrine growth factor for NKL1.1+ T cells and thereby induce non-cytolytic NK1.1+ T cells in the long-term culture of TIL.

  14. Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies

    International Nuclear Information System (INIS)

    Meyn, R.E.; Stephens, L.C.; Ang, K.K.; Hunter, N.R.; Brock, W.A.; Milas, L.; Peters, L.J.

    1993-01-01

    Fifteen murine tumours were evaluated with respect to the degree of apoptosis development that occurs in the tumour tissue in the first few hours following irradiation in vivo. Animals were killed at 3 or 6 h following irradiation with 0, 2.5, 10 or 25 Gy. Apoptotis was scored as percent aberrant nuclei by microscopic examination of histological sections made from tumour specimens. Results showed that three of four mammary adenocarconomas, one ovarian adenocarcinoma, and one lymphoma displayed at least 10% apoptotic cells after 25 Gy, whereas five sarcomas, three squamous cell carcinomas, and a hepatocarcinoma did not. Time courses and dose responses were similar in those tumours that responded. (author)

  15. Heterogeneity in the development of apoptosis in irradiated murine tumours of different histologies

    Energy Technology Data Exchange (ETDEWEB)

    Meyn, R E; Stephens, L C; Ang, K K; Hunter, N R; Brock, W A; Milas, L; Peters, L J [Anderson (M.D.) Cancer Center, Houston, TX (United States)

    1993-11-01

    Fifteen murine tumours were evaluated with respect to the degree of apoptosis development that occurs in the tumour tissue in the first few hours following irradiation in vivo. Animals were killed at 3 or 6 h following irradiation with 0, 2.5, 10 or 25 Gy. Apoptotis was scored as percent aberrant nuclei by microscopic examination of histological sections made from tumour specimens. Results showed that three of four mammary adenocarconomas, one ovarian adenocarcinoma, and one lymphoma displayed at least 10% apoptotic cells after 25 Gy, whereas five sarcomas, three squamous cell carcinomas, and a hepatocarcinoma did not. Time courses and dose responses were similar in those tumours that responded. (author).

  16. CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.

    Science.gov (United States)

    Megaptche, Amelie Pajip; Erb, Ulrike; Büchler, Markus Wolfgang; Zöller, Margot

    2014-09-01

    Blockade of CD44 is considered a therapeutic option for the elimination of leukemia-initiating cells. However, the application of anti-panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4-v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti-CD44v10 prolonged the survival time twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation. Taken together, in hematological malignancies expressing CD44v, anti-panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy. Furthermore, CD44v10-specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.

  17. Plasma Cell-Free DNA in Paediatric Lymphomas

    Science.gov (United States)

    Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

    2013-01-01

    Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

  18. PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model.

    Directory of Open Access Journals (Sweden)

    Shi-Dong Ma

    2016-05-01

    Full Text Available Epstein-Barr virus (EBV infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types of human lymphomas. T cells directed against viral antigens play a critical role in controlling EBV infection, and EBV-positive lymphomas are particularly common in immunocompromised hosts. We previously showed that EBV induces B cell lymphomas with high frequency in a cord blood-humanized mouse model in which EBV-infected human cord blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rγnull (NSG mice. Since our former studies showed that it is possible for T cells to control the tumors in another NSG mouse model engrafted with both human fetal CD34+ cells and human thymus and liver, here we investigated whether monoclonal antibodies that block the T cell inhibitory receptors, PD-1 and CTLA-4, enhance the ability of cord blood T cells to control the outgrowth of EBV-induced lymphomas in the cord-blood humanized mouse model. We demonstrate that EBV-infected lymphoma cells in this model express both the PD-L1 and PD-L2 inhibitory ligands for the PD-1 receptor, and that T cells express the PD-1 and CTLA-4 receptors. Furthermore, we show that the combination of CTLA-4 and PD-1 blockade strikingly reduces the size of lymphomas induced by a lytic EBV strain (M81 in this model, and that this anti-tumor effect requires T cells. PD-1/CTLA-4 blockade markedly increases EBV-specific T cell responses, and is associated with enhanced tumor infiltration by CD4+ and CD8+ T cells. In addition, PD-1/CTLA-4 blockade decreases the number of both latently, and lytically, EBV-infected B cells. These results indicate that PD-1/CTLA-4 blockade enhances the ability of cord blood T cells to control outgrowth of EBV-induced lymphomas, and suggest that PD-1/CTLA-4 blockade might be useful for treating certain EBV-induced diseases in humans.

  19. Ligand-free, protein-bound technetium-99m iron-dextran enhancement of technetium pyrophosphate uptake in tumours

    International Nuclear Information System (INIS)

    Pojer, P.M.; Jakovljevic, A.C.; Wise, K.N.

    1985-01-01

    The biodistribution of technetium-99m was studied in T-cell lymphoma and selected organs of iron-dextran treated and control mice given technetium-99m pyrophosphate. The results showed that high serum iron levels increased tumour uptake of technetium pyrophosphate. This supports the hypothesis that technetium, in common with other metal-based tumour seeking radiopharmaceuticals, is transported to tumours as a ligand-free protein-bound cation. (U.K.)

  20. Imaging of MALT lymphomas

    International Nuclear Information System (INIS)

    Rodallec, M.; Guermazi, A.; Attal, P.; Zagdanski, A.M.; Frija, J.; De Kerviler, E.; Brice, P.

    2002-01-01

    The broad category of non-Hodgkin's lymphoma includes a large variety of different diseases including indolent as well as aggressive lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphoma arises in the extranodal mucosal lymphoid tissue and has only been recognised as a distinct entity in recent years. It affects one or several extranodal structures such as the stomach, the lung, the eye and salivary glands. The lymphoma is generally of low grade and has indolent course. The aim of this article is to exemplify the most common radiological patterns of MALT lymphoma. (orig.)

  1. Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin's lymphoma?

    International Nuclear Information System (INIS)

    Champion, P.E.; Groshar, D.; Hooper, H.R.; Palmer, M.; Catz, Z.; Belch, A.; McEwan, A.

    1992-01-01

    67 Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management. (Author)

  2. Nuclear medicine procedures to diagnose endocrine pancreatic tumours

    International Nuclear Information System (INIS)

    Bares, R.; Besenfelder, H.; Eschmann, S.M.; Pfannenberg, C.

    2003-01-01

    The typical clinical features of endocrine pancreatic tumours are either symptoms caused by excessive hormone production or progressive tumour growth. In several prospective studies it has been shown that somatostatin receptor scintigraphy is the most accurate imaging technique currently available to detect endocrine pancreatic tumours. Therefore it should be used whenever curative surgical treatment appears to be feasible. Furthermore it should be applied if a radionuclide treatment of inoperable tumours is considered. In this situation scintigraphy with 123 I-mIBG might be useful, too. Future developments include the use of PET with labelled somatostatin analogues or DOPA derivatives as well as image fusion techniques to optimize preoperative tumour localization. (orig.) [de

  3. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.

    Science.gov (United States)

    Teoh, Seong Lin; Das, Srijit

    2016-11-01

    Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

  4. CT findings in primary pulmonary lymphomas

    International Nuclear Information System (INIS)

    Cardinale, Luciano; Allasia, Marco; Cataldi, Aldo; Ferraris, Fabrizio; Fava, Cesare; Parvis, Guido

    2005-01-01

    Purpose. To describe the CT findings of pathologically confirmed primary pulmonary lymphomas. Materials and methods. The CT examinations of 11 patients with pathologically proven primary pulmonary lymphoma (9 BALT lymphomas and 2 non-BALT lymphomas) were retrospectively reviewed by three radiologists. Evaluated findings included morphology (consolidation, mass, nodule), number and distribution of lesions. Other CT findings such as air bronchogram, lymphadenopathy atelectasis and pleural effusion were also assessed. Results. Pulmonary lesions were depicted as air-space consolidation (pneumonia-like) in 5 patients (45%), tumour-like rounded opacity in 4 (36%), and nodules in 4 (36%). Multiple and bilateral long lesions were seen in 3 patients (27%). Air bronchogram was present in 7 patients (63%), lymphadenopathy in 3 (27%), atelectasis in 4 (36%) and pleural effusion in only 1 (9%). Conclusions. Our results agree with previous studies regarding lesion patterns and their relative frequency. A smaller number of nodules and of multiple lesions were found compared with some previous studies. The most frequent pattern was airspace consolidation [it

  5. Molecular diagnosis of Burkitt's lymphoma

    NARCIS (Netherlands)

    Dave, SS; Fu, K; Wright, GW; Lam, LT; Kluin, P; Boerma, EJ; Greiner, TC; Weisenburger, DD; Rosenwald, A; Ott, G; Muller-Hermelink, H; Gascoyne, RD; Delabie, J; Rimsza, LM; Braziel, RM; Grogan, TM; Campo, E; Jaffe, ES; Dave, BJ; Sanger, W; Bast, M; Vose, JM; Armitage, JO; Connors, JM; Smeland, EB; Kvaloy, S; Holte, H; Fisher, RI; Miller, TP; Montserrat, E; Wilson, WH; Bahl, M; Zhao, H; Yang, LM; Powell, J; Simon, R; Chan, WC; Staudt, LM

    2006-01-01

    Background: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

  6. In vitro effects of substance P analogue [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P on human tumour and normal cell growth.

    OpenAIRE

    Everard, M. J.; Macaulay, V. M.; Miller, J. L.; Smith, I. E.

    1992-01-01

    Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide receptors, and are reported to inhibit growth of small cell lung cancer cell lines (SCLC CLs). We found [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D-Phe5SP) significantly inhibited DNA synthesis by 10/10 human tumour CLs; six SCLC, one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma, with inhibition to 50% control levels (IC50) of 20-50 microM. There was dose dependent inhibition of colony...

  7. Some aspects of the endocrine tumours of the digestive tract

    International Nuclear Information System (INIS)

    Sassolas, G.

    1996-01-01

    Endocrine tumours of digestive tract (GEP) synthesize many hormonal products which are responsible for clinical expression in relation with their nature, amount and biological activity, some of these tumours being non-functioning or silent. Moreover these tumours have some characteristics related to neuroendocrine differentiation, which provide tumour markers in addition to hormonal markers, such as chromogranin. A which is of special interest in non-functioning tumours. Pancreatic tumours are the most frequently recognized tumours in systematic screening procedures performed in MEN 1 patients. They are multi-secreting and multifocal, and they exhibit a loss of heterozygosity in the 11q13 locus. Growth factors such as IGF-1 and PDGF and their specific receptors are expressed in GEP tumours but their role in tumour growth remains to be determined. Somatostatin receptors are present on most endocrine digestive tumours, conditioning the therapeutic effects of somatostatin analogues that reduce hormonal tumoral production and alleviate the related symptoms. In addition, in vivo visualization of somatostatin receptor positive tumours by scintigraphy using radiolabelled somatostatin analogues is of clinical interest. (author)

  8. Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

    Science.gov (United States)

    Rofstad, E K; Fenton, B M; Sutherland, R M

    1988-05-01

    Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

  9. Adult T-Cell Leukemia/Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  10. EVALUATION OF BRAIN TUMOURS USING COMPUTED TOMOGRAPHY

    Directory of Open Access Journals (Sweden)

    B. Vinod Kumar

    2016-07-01

    Full Text Available BACKGROUND The brain is basically formed by the neurons and the supporting cells. Tumours arising of neurons are almost impossible because the neurons never divide. Tumours arising from the supporting cells are almost frequently seen. The tumour characteristics depend upon the cell of origin. The brain is covered by meninges and the vascular tissue supplies the essential nutrients to all these components of the brain. Unfortunately, the brain is placed in a rigid box called as neurocranium. According to Monro–Kellie principle, if any of the one component increases in a rigid box, the other components will be compensated. So in a limited space if any of the catastrophes occur i.e. space occupying lesions, then the other components will be compensated and as a result the effects will be seen in a very small amount of time. A sincere effort has been put in this study to understand and evaluate the Brain Tumours using a CT scan. This study is intended to be useful to the diagnosing radiologists, internal medicine practitioners and general practitioners and surgeons. METHODS The aim of the study is to evaluate the brain tumours using CT and to confirm the diagnosis by sending to the Histopathology Department. The study is a cross-sectional study and is done in the Department of Radiology, Fathima Medical College, Kadapa, Andhra Pradesh. The study was done from December 2014 to May 2016. The study was done using thirty cases who were believed to have brain tumour and were studied in the Department of Radiology after initial clinical evaluation. First, the plain CT was done and was checked for the location, size, characteristics of the lesion and the surrounding characteristics were observed. RESULT In the present study, the most common of all tumours were those of the neuroepithelial groups. Next in frequency were the tumours of meninges of all intracranial tumours. This was followed by tumours of cranial nerves, metastatic tumour, one lymphoma case

  11. Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus.

    Science.gov (United States)

    Okabe, Atsushi; Funata, Sayaka; Matsusaka, Keisuke; Namba, Hiroe; Fukuyo, Masaki; Rahmutulla, Bahityar; Oshima, Motohiko; Iwama, Atsushi; Fukayama, Masashi; Kaneda, Atsushi

    2017-08-11

    Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis. We performed ChIP sequencing on H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K9me3 in gastric epithelial cells infected or not with EBV. We showed that repressive marks were redistributed after EBV infection, resulting in aberrant enhancer activation and repression. Enhancer dysfunction led to the activation of pathways related to cancer hallmarks (e.g., resisting cell death, disrupting cellular energetics, inducing invasion, evading growth suppressors, sustaining proliferative signalling, angiogenesis, and tumour-promoting inflammation) and inactivation of tumour suppressive pathways. Deregulation of cancer-related genes in EBV-infected gastric epithelial cells was also observed in clinical EBV(+) gastric cancer specimens. Our analysis showed that epigenetic alteration associated with EBV-infection may contribute to tumorigenesis through enhancer activation and repression.

  12. A reproducible brain tumour model established from human glioblastoma biopsies

    International Nuclear Information System (INIS)

    Wang, Jian; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Ø; Miletic, Hrvoje; Sakariassen, Per Ø; Huszthy, Peter C; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre

    2009-01-01

    Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression

  13. Perinatal tumours: the contribution of radiology to management

    Energy Technology Data Exchange (ETDEWEB)

    Donoghue, Veronica; Ryan, Stephanie; Twomey, Eilish [Children' s University Hospital, Radiology Department, Dublin (Ireland)

    2008-06-15

    A formal classification does not exist and they are probably best classified by their location. Overall the most common neoplasms are - Extracranial teratoma - Neuroblastoma - Soft-tissue tumours - Brain tumours - Leukaemia - Renal tumours - Liver tumours - Retinoblastoma. The prognosis is generally poor, although there are some exceptions such as congenital neuroblastoma and hepatoblastoma. These tumours have a tendency to regress and have a benign clinical course despite a clear malignant histological picture. Other tumours, though histologically benign, may be fatal because of their size and location. Large benign masses may cause airway or cardiovascular compromise and death. Others may cause significant mass effect preventing normal organ development. As normal embryonic cells have a high mitotic rate it is not surprising that perinatal tumours may have a rapid growth rate and become enormous in size. (orig.)

  14. The role of long-chain polyunsaturated fatty acids in the treatment of cancer Cachexia and tumour growth in patients with malignant diseases: A review

    Directory of Open Access Journals (Sweden)

    Elizabeth A Symington

    2008-11-01

    Full Text Available Recent studies show that ω-3 polyunsaturated fatty acids (PUFAs have the capacity to modulate cancer outcomes. The body responds to cancer in the same way that it responds to inflammation and wound healing. Nutrients with anti-inflammatory effects could therefore be expected to play a role in cancer treatment. This review focuses on the role of ω-3 PUFAs in tumourigenesis and cancer cachexia. Studies indicate that eicosapentaenoic acid (EPA supplementation may promote arrest of tumour growth and reduce cell proliferation. Patients need to consume at least 2 g of EPA per day for it to have a therapeutic effect. Positive outcomes related to cachexia include diminished weight loss, increased appetite, improved quality of life and prolonged survival, although there is controversy regarding these clinical outcomes. The effects of ω-3 PUFAs on tumourigenesis and cachexia are viewed in the context of altered lipid and protein metabolism. This altered metabolism usually experienced by cancer patients results in increased formation of proinflammatory eicosanoids and cytokines. Cytokines play an indirect role by stimulating the production of arachidonic acid-derived eicosanoids, which support inflammation, cell proliferation and angiogenesis, and inhibit apoptosis. It can be concluded that ω-3 PUFA supplementation offers a means of augmenting cancer therapy, inhibiting tumourigenesis and possibly contributing to cachexia alleviation. Opsomming Onlangse studies toon dat ω-3-poli-onversadigde vetsure (POVSe oor die vermoë beskik om kankeruitkomste te moduleer. Die liggaam reageer op kanker op dieselfde wyse as wat dit op inflammasie en wondgenesing reageer. Daar kan dus verwag word dat voedingstowwe met ‘n anti-inflammatoriese uitwerking ‘n rol in die behandeling van kanker kan speel. In hierdie oorsig word daar op die rol van ω-3-POVSe in tumorigenese en kankerkageksie gefokus. Studies dui daarop dat eikosapentanoënsuur- (EPS

  15. Radioimmunotherapy of Non-Hodgkin's Lymphoma. The interaction of radiation and antibody with lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Illidge, T.M

    1999-06-01

    Whilst many patients with indolent Non-Hodgkin's Lymphoma (NHL) can achieve clinical remissions to first-line chemotherapy and/or radiotherapy, most will relapse. Current treatment options for relapsing patients are limited since most patients become resistant to repeated chemotherapy. Death usually occurs within 10 years of diagnosis. Overall, these disappointing results have not changed significantly in a quarter of a century and clearly advocate the urgent priority to research into potential new therapeutic approaches into this diverse and increasingly prevalent group of human tumours. Radioimmunotherapy (RIT) is currently under investigation as a new approach for the treatment of this disease. In this form of treatment, radionuclide-labeled monoclonal antibodies are able to deliver selective systemic irradiation by recognising tumour-associated antigens. The use of RIT with radiolabeled anti-CD20 antibodies in patients with recurrent B-cell lymphoma has resulted in extremely high rates of durable complete remissions. The optimal approach and mechanisms of action of successful RIT remain however largely unknown. The work described in this thesis has focused on clarifying some of the important determinants and mechanisms of effective RIT of syngeneic B-cell lymphoma, both in vivo and in vitro. A successful animal model of RIT in B cell lymphomas was established by initially generating a panel of antibodies against mouse B cell antigens. The in vitro characteristics of these antibodies have been compared with their subsequent performance, in biodistribution studies and RIT in vivo. For the first time in an in vivo model the relative contributions of antibody and irradiation are described. Some antibodies including anti-MHC Class II were shown to be effective delivery vehicles of low doses of Iodine-131. These antibodies, which appear to be inactive delivery vehicles can cure animals with low burdens of tumour. However antibodies such as anti-idiotype and anti

  16. Extracellular matrix in tumours as a source of additional neoplastic lesions - a review

    Directory of Open Access Journals (Sweden)

    Madej Janusz A.

    2014-03-01

    Full Text Available The review describes the role of cells of extracellular matrix (ECM as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog. Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST, which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue, which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna, currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading are more important factors than the histogenesis of the tumour.

  17. Activation of TAK1 by MYD88 L265P drives malignant B-cell Growth in non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Ansell, S M; Hodge, L S; Secreto, F J; Manske, M; Braggio, E; Price-Troska, T; Ziesmer, S; Li, Y; Johnson, S H; Hart, S N; Kocher, J-P A; Vasmatzis, G; Chanan-Kahn, A; Gertz, M; Fonseca, R; Dogan, A; Cerhan, J R; Novak, A J

    2014-01-01

    Massively parallel sequencing analyses have revealed a common mutation within the MYD88 gene (MYD88 L265P ) occurring at high frequencies in many non-Hodgkin lymphomas (NHLs) including the rare lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia (WM). Using whole-exome sequencing, Sanger sequencing and allele-specific PCR, we validate the initial studies and detect the MYD88 L265P mutation in the tumor genome of 97% of WM patients analyzed (n=39). Due to the high frequency of MYD88 mutation in WM and other NHL, and its known effects on malignant B-cell survival, therapeutic targeting of MYD88 signaling pathways may be clinically useful. However, we are lacking a thorough characterization of the role of intermediary signaling proteins on the biology of MYD88 L265P -expressing B cells. We report here that MYD88 L265P signaling is constitutively active in both WM and diffuse large B-cell lymphoma cells leading to heightened MYD88 L265P , IRAK and TRAF6 oligomerization and NF-κB activation. Furthermore, we have identified the signaling protein, TAK1, to be an essential mediator of MYD88 L265P -driven signaling, cellular proliferation and cytokine secretion in malignant B cells. Our studies highlight the biological significance of MYD88 L265P in NHL and reveal TAK1 inhibition to be a potential therapeutic strategy for the treatment of WM and other diseases characterized by MYD88 L265P

  18. Primary Lymphoma of the Liver: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    Franzjosef Schweiger

    2000-01-01

    Full Text Available The case of a previously healthy man who developed primary non-Hodgkin’s lymphoma of the liver is presented. Biopsy confirmed that the tumour was of the diffuse large cell type and was of apparent T-cell origin. The diagnosis of these rare tumours is suggested by the presence of a hepatic mass without lymphadenopathy, splenomegaly or bone marrow involvement, as well as normal carcinoembryonic antigen and alpha-fetoprotein levels. However, histological examination of tissue is essential to confirm the diagnosis. The response to treatment varies, but surgical resection and/or chemotherapy can result in prolonged remissions. The literature on this topic is briefly reviewed.

  19. Authentication of Primordial Characteristics of the CLBL-1 Cell Line Prove the Integrity of a Canine B-Cell Lymphoma in a Murine In Vivo Model

    OpenAIRE

    Rütgen, Barbara C.; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E.; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Escobar, Hugo Murua

    2012-01-01

    Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stabilit...

  20. Wilms' tumour (nephroblastoma)

    African Journals Online (AJOL)

    Wilms' tumour or nephroblastoma is a cancer of the kidney that ... It may be noticed by parents or it may be an incidental finding ... patients. It may lead to iron deficiency anaemia. Rarely Wilms' tumour may present with acquired von Willebrand's ... the best treatment approach. ... with multimodality therapy in paediatric.

  1. Detection of the Epstein-Barr virus genome in the radiation-associated malignant lymphomas

    International Nuclear Information System (INIS)

    Butenko, Z.A.; Kindzel's'kij, L.P.; Butenko, A.K.

    1993-01-01

    The genomic and ultrastructural peculiarities of malignant lymphoma cells in the patients living in the radiation unfavourable regions have been examined. The specific viral genomic sequences of EBV are revealed in the lymphoma cells in 3 of 4 patients. The described EBV-associated lymphomas are correlated with a significant decrease of natural anti tumour immunity in all the patients. The obtained data can serve as an evidence of the important role of the Epstein-Barr herpes virus in the mechanism of lymphoid cells malignant transformation

  2. Therapy for minimal residual tumour disease: beta-galactosylceramide inhibits growth of recurrent HPV16-associated neoplasms after surgery and chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Indrová, Marie; Bieblová, Jana; Mikyšková, Romana; Bubeník, Jan; Reiniš, Milan

    2010-01-01

    Roč. 126, č. 12 (2010), s. 2997-3004 ISSN 0020-7136 R&D Projects: GA ČR GA301/06/0774; GA AV ČR IAA500520807; GA ČR GA301/07/1410; GA ČR GA301/09/1024 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : beta-galactosylceramide * tumour immunotherapy * NKT cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.926, year: 2010

  3. Anti-tumour action of 64Cu-bleomycin on Ehrlich ascites tumour cells in vivo

    International Nuclear Information System (INIS)

    Maki, Hirotoshi; Kawai, Kenichi; Akaboshi, Mitsuhiko

    1979-01-01

    The anti-tumor action of the complex of Bleomycin (BLM) with high specific-radioactivity 64 Cu on Ehrlich ascites tumour (EAT) was studied in vivo. The 64 Cu-BLM was administered into intraperitoneal cavity of mice from 1 to 4 days after inoculation of EAT cells. The effect of 64 Cu-BLM to suppress the tumour growth as demonstrated by prolonging life span was observed. The amounts of 64 Cu-BLM (800 μCi-8 mg/Kg) were administered at 4, 8 and 16 times separately. Then, the shorter the time interval and the less the amounts of drugs at a time, the higher the suppressing effect for the tumour growth was. It was confirmed that anti-tumour action of 64 Cu-BLM was in all the cases higher than that of BLM alone. (author)

  4. Primary malignant intramedullary lymphoma

    International Nuclear Information System (INIS)

    Orrego P, E.; Heinicke Y, H.; Arbaiza A, D.; Yepez R, V.

    1999-01-01

    A case of primary malignant intramedullary lymphoma, localized in the dorsal part of the spinal cord is presented. The clinical symptoms were associated with motor and sensitive deficit. Clinical investigations excluded the presence of lymphoma in other locations in the central nervous system and the extra neural organs. Postoperative radiotherapy and chemotherapy improved relict neurological symptoms. (authors)

  5. PET CT and lymphomas

    International Nuclear Information System (INIS)

    Castro, R.

    2012-01-01

    This presentation is about Tc and lymphomas. Classification and clinical cases of various cancer such as gastro duodenal or ulcer, mama, medullary, lymph and neck, leukemia, nodular sclerosis. Metabolic information, anatomical nature of lymphoma and its clinical presentation determine the extent that PET should be used in the patient.

  6. Hodgkin Lymphoma (For Kids)

    Science.gov (United States)

    ... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

  7. CARDIAC LYMPHOMA IN DOG

    Directory of Open Access Journals (Sweden)

    G. D. Cruz

    2016-11-01

    Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

  8. Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.

    Science.gov (United States)

    Bolkun, Lukasz; Lemancewicz, Dorota; Piszcz, Jaroslaw; Moniuszko, Marcin; Bolkun-Skornicka, Urszula; Szkiladz, Malgorzata; Jablonska, Ewa; Kloczko, Janusz; Dzieciol, Janusz

    2015-12-01

    Tumour necrosis factor-alfa (TNF-α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro-angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF-α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro-angiogenic cytokines and significant increase of TRAIL concentration after anti-angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro-angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro-angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan-1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.

  9. Proton magnetic resonance spectroscopy (1H-MRS) for the evaluation of treatment of brain tumours

    International Nuclear Information System (INIS)

    Houkin, K.; Kamada, K.; Sawamura, Y.; Iwasaki, Y.; Abe, H.; Kashiwaba, T.

    1995-01-01

    We investigated metabolic changes in brain tumours following treatment, using proton magnetic resonance spectroscopy. In meningiomas, effective therapeutic embolisation led to an acute increase in lactate. In radiosensitive tumours such as malignant lymphoma, a decrease in lactate and in increase in N-acetyl-aspartate occurred after radiotherapy, which preceded changes observed on magnetic resonance imaging. On the other hand, no significant changes in spectral patterns were observed in malignant gliomas resistant to therapy. Tissue characterisation of brain tumours by spectral patterns on proton magnetic resonance spectroscopy remains controversial. However, we have shown it to be sensitive to metabolic changes following treatment, which may reflect the efficacy of the therapy. (orig.)

  10. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

    Science.gov (United States)

    Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

    2015-02-27

    ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

  11. MicroRNAs in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Husby, Simon; Geisler, Christian; Grønbæk, Kirsten

    2013-01-01

    Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. New treatment modalities, including intensive induction regimens with immunochemotherapy and autologous stem cell transplant, have improved survival. However, many patients still relapse, and there is a need...... for novel therapeutic strategies. Recent progress has been made in the understanding of the role of microRNAs (miRNAs) in MCL. Comparisons of tumor samples from patients with MCL with their normal counterparts (naive B-cells) have identified differentially expressed miRNAs with roles in cellular growth...

  12. Primary malignant head and neck tumours in Ghana: a survey of ...

    African Journals Online (AJOL)

    McRoy

    Results: 2,041 of 4,546 reports were malignant. 1342 were ... Conclusion: We observed a rising incidence of head and neck .... head and neck cancer rose from 44 cases in ... Carcinosarcoma. 1. Clear cell tumour. 0. 1. Cutaneous lymphoma. 1.

  13. Ligand-free, protein-bound technetium-99m. Evidence for tumour localisation

    International Nuclear Information System (INIS)

    Jakovljevic, A.C.; Pojer, P.M.

    1984-11-01

    An hypothesis that cations accumulate in tumours independent of ligand is tested. A preparation of technetium-99m known to be ligand-free (that is, the technetium is protein bound and no other ligand is injected) has been shown to accumulate in a T-cell lymphoma

  14. Electrochemotherapy of tumours

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Rudolf, Z.; Miklavcic, D.

    2006-01-01

    Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

  15. Epstein-Barr virus-associated lymphomas.

    Science.gov (United States)

    Shannon-Lowe, Claire; Rickinson, Alan B; Bell, Andrew I

    2017-10-19

    Epstein-Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  16. Carcino-embryonic antigen in monitoring the growth of human colon adenocarcinoma tumour cells SK-CO-1 and HT-29 in vitro and in nude mice

    DEFF Research Database (Denmark)

    Sölétormos, G; Fogh, J M; Sehested-Hansen, B

    1997-01-01

    A set of experimental model systems were designed to investigate (a) the inter-relationship between growth of two human cancer cell lines (SK-CO-1, HT-29) and carcino-embryonic antigen (CEA) kinetics; and (b) whether neoplastic growth or CEA concentration is modulated by human growth hormone (hGH...

  17. Malignant thyroid tumours

    International Nuclear Information System (INIS)

    Boerner, W.; Reiners, C.

    1987-01-01

    The subjects dealt with at the symposium cover all topical aspects of pathology, epidemiology, diagnosis, therapy, and aftercare of the malignant thyroid tumours. A survey of the histological classification of the thyroid tumours and a review of the latest findings concerning the radiocarcinogenesis are followed by a detailed discussion of the most significant tumours. There are also papers dealing with controversial aspects of the histological classification, the value of diagnostic methods, radicality of the therapy, or after care. For five conference papers, separate records are available in the database. (orig./ECB) With 59 figs.; 57 tabs [de

  18. Acetyltransferases and tumour suppression

    International Nuclear Information System (INIS)

    Phillips, A C; Vousden, Karen H

    2000-01-01

    The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

  19. Tumour-induced osteomalacia: An emergent paraneoplastic syndrome.

    Science.gov (United States)

    Alonso, Guillermo; Varsavsky, Mariela

    2016-04-01

    Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  20. Life history, immunity, Peto's paradox and tumours in birds.

    Science.gov (United States)

    Møller, A P; Erritzøe, J; Soler, J J

    2017-05-01

    Cancer and tumours may evolve in response to life-history trade-offs between growth and duration of development on one hand, and between growth and maintenance of immune function on the other. Here, we tested whether (i) bird species with slow developmental rates for their body size experience low incidence of tumours because slow development allows for detection of rapid proliferation of cell lineages. We also test whether (ii) species with stronger immune response during development are more efficient at detecting tumour cells and hence suffer lower incidence of tumours. Finally, we tested Peto's paradox, that there is a positive relationship between tumour incidence and body mass. We used information on developmental rates and body mass from the literature and of tumour incidence (8468 birds) and size of the bursa of Fabricius for 7659 birds brought to a taxidermist in Denmark. We found evidence of the expected negative relationship between incidence of tumours and developmental rates and immunity after controlling for the positive association between tumour incidence and body size. These results suggest that evolution has modified the incidence of tumours in response to life history and that Peto's paradox may be explained by covariation between body mass, developmental rates and immunity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  1. Cranial irradiation for cerebral and nasopharyngeal tumours in children: evidence for the production of a hypothalmic defect in growth hormone release

    International Nuclear Information System (INIS)

    Blacklay, A.; Grossman, A.; Ross, R.J.M.; Savage, M.O.; Davies, P.S.W.; Plowman, P.N.; Besser, G.M.; Coy, D.H.

    1986-01-01

    A synthetic 29-amino acid analogue of human pancreatic GH-releasing hormone (GHRH(1-29)NH 2 ) has recently been shown to stimulate the release of GH in normal subjects. The authors have studied the GH reponse to GHRH(1-29)NH 2 in nine children irradiated for brain and nasopharyngeal tumours, who were not growing and were deficient in GH as assessed by insulin-induced hypoglycaemia. Serum GH rose in response to GHRH(1-29)NH 2 in all the children, and in five the peak serum GH response was > 20 mu./1. The data suggest that when hypothalamo-pituitary irradiation results in GH deficiency, this is due to a failure of the synthesis or delivery of endogenous GHRH from the hypothalamus to the pituitary cells. It also suggests that it may be possible to treat such children using synthetic GHRH in place of exogenous GH. (author)

  2. Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-23

    Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  3. Ocular Adnexal Follicular Lymphoma

    DEFF Research Database (Denmark)

    Rasmussen, Peter K; Coupland, Sarah E; Finger, Paul T

    2014-01-01

    that involved 6 eye cancer centers from January 1, 1980, through December 31, 2010. A total of 105 patients with follicular OAL were identified, of which 7 patients were excluded because of missing clinical data. The median follow-up time was 52 months (range, 13-118 months). MAIN OUTCOMES AND MEASURES Overall...... in conjunction with a concurrent systemic lymphoma, and 10 (10%) presented with an ocular adnexal relapse. The lacrimal gland (28%), conjunctiva (28%), and orbit (28%) were the most frequently involved sites. Of the 69 patients with primary follicular lymphoma, 38 (55%) presented with Ann Arbor stage IE lymphoma...

  4. Rare transformation to double hit lymphoma in Waldenstrom's macroglobulinemia.

    Science.gov (United States)

    Okolo, Onyemaechi N; Johnson, Ariel C; Yun, Seongseok; Arnold, Stacy J; Anwer, Faiz

    2017-08-01

    Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL. The paper also broadens to include discussions on current topics in the classification, diagnosis, possible causes of transformation, and treatment of WM, including transformation to double hit lymphoma. The significance of this case lies in that the presence of double hit lymphoma-like genetic mutations in WM have not been previously described in the literature and potentially such changes are harbinger of extra-nodal presentation, aggressive growth, and possibly poor prognosis, if data from other double-hit lymphoma are extrapolated.

  5. Head and neck tumours: combined MRI assessment based on IVIM and TIC analyses for the differentiation of tumors of different histological types

    International Nuclear Information System (INIS)

    Sumi, Misa; Nakamura, Takashi

    2014-01-01

    We evaluated the combined use of intravoxel incoherent motion (IVIM) and time-signal intensity curve (TIC) analyses to diagnose head and neck tumours. We compared perfusion-related parameters (PP) and molecular diffusion values (D) determined from IVIM theory and TIC profiles among 92 tumours with different histologies. IVIM parameters (f and D values) and TIC profiles in combination were distinct among the different types of head and neck tumours, including squamous cell carcinomas (SCCs), lymphomas, malignant salivary gland tumours, Warthin's tumours, pleomorphic adenomas and schwannomas. A multiparametric approach using both IVIM parameters and TIC profiles differentiated between benign and malignant tumours with 97 % accuracy and diagnosed different tumour types with 89 % accuracy. Combined use of IVIM parameters and TIC profiles has high efficacy in diagnosing head and neck tumours. (orig.)

  6. Targeting radiation to tumours

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

    1994-01-01

    Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

  7. [Gastric mesenchymal tumours (GIST)].

    Science.gov (United States)

    Spivach, Arrigo; Fezzi, Margherita; Sartori, Alberto; Belgrano, Manuel; Rimondini, Alessandra; Cuttin-Zernich, Roberto; Covab, Maria Assunta; Bonifacio, Daniela; Buri, Luigi; Pagani, Carlo; Zanconati, Fabrizio

    2008-01-01

    The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.

  8. [Occurrence of associated tumours in chronic lymphocytic leukemia].

    Science.gov (United States)

    Szerafin, László; Jakó, János; Varju, Lóránt

    2016-10-01

    Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

  9. Primary cardiac lymphoma: diagnostic tools and treatment challenges.

    LENUS (Irish Health Repository)

    Bambury, R

    2011-03-01

    Primary cardiac lymphoma (PCL) is a rare malignancy and the optimal treatment strategy remains uncertain. It appears to respond much better to systemic chemotherapy than to surgery and it should be considered in the differential diagnosis of all cardiac tumours before definitive management is undertaken. We report a case of this rare disorder treated successfully with a combination of rituximab and cyclophosphamide, adriamycin, vincristine and prednisolone. The patient developed recurrent unstable ventricular tachycardia (VT) post-chemotherapy secondary to extensive scarring at the tumour site. The tumour as well as the post-treatment scarring is well illustrated by cardiac magnetic resonance imaging highlighting its usefulness in this setting. An implantable cardioverter defibrillator (ICD) was placed. This is only the second case in the literature of PCL to have an ICD placed for recurrent VT. A brief literature review is included.

  10. Mucosa associated lymphoid tissue (MALT lymphoma) of the urinary bladder: a case report

    International Nuclear Information System (INIS)

    Tsang, T.; Masters, J.; Chan, K.; Jose, C.

    2003-01-01

    Full text: Mucosa associated lymphoid tissue (MALT lymphoma) of the urinary bladder is a rare condition. The best treatment approach for this disease is controversial. A case report on a patient with MALT lymphoma of the urinary bladder. The relevant current literature was reviewed. A 79 year old lady presented with haematuria in 2002. Ultrasound of the pelvis showed a large tumour in the bladder. Cystoscopy revealed a mass arising from the bladder. Transurethral resection of the tumour was performed. Histology showed Non Hodgkin's lymphoma of MALT type. CT showed a 8.9 X 7.6 cm solid tumour involving almost whole of the bladder. The patient could not tolerate anti helicobacter treatment and was then treated with radiotherapy. The pelvis was treated with 18 MV photons with a 3 field technique in 2 phases, with CT planning. In phase 1, the pelvis was treated to 24 Gy in 12 fractions, over 2.5 weeks. Phase 2 was treated to a reduced pelvic field, to a dose of 16 Gy in 8 fractions over 1.5 weeks. Five months after radiotherapy, repeat cystoscopy and biopsy of bladder base showed no evidence of malignancy. MALT lymphoma of the urinary bladder responds well to radiotherapy and permits bladder preservation. The current literature in management of MALT lymphoma of urinary bladder is reviewed

  11. Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay

    NARCIS (Netherlands)

    Kuijper, Arno; Buerger, H.; Simon, R.; Schaefer, K-L.; Croonen, A.; Boecker, W.; Wall, E. van der; Diest, P.J. van

    2002-01-01

    Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A

  12. Selective activation of TCR-G¿ cells in endemic Burkitt's lymphoma

    DEFF Research Database (Denmark)

    Futagbi, Godfred; Welbeck, Jennifer E; Tetteh, John Kweku A

    2007-01-01

    BACKGROUND: The overlap in geographical distribution of Plasmodium falciparum malaria and endemic Burkitt's lymphoma (eBL)--an aggressive Epstein-Barr virus (EBV)-associated B-cell tumour occurring almost exclusively in the tropics--strongly suggests a link between the two diseases. It is suspect...

  13. Primary Lymphoma of the Testis in Remission for more than Ten ...

    African Journals Online (AJOL)

    It is the most common testicular tumour in males between 60 and 80 years old OBJECTIVE: To report a case of primary testicular lymphoma in a young man who has done very well on surgery and chemotherapy. METHODS: The patient a Nigerian male civil servant who was single and aged 31 years presented to us with a ...

  14. 2-d spectroscopic imaging of brain tumours

    International Nuclear Information System (INIS)

    Ferris, N.J.; Brotchie, P.R.

    2002-01-01

    Full text: This poster illustrates the use of two-dimensional spectroscopic imaging (2-D SI) in the characterisation of brain tumours, and the monitoring of subsequent treatment. After conventional contrast-enhanced MR imaging of patients with known or suspected brain tumours, 2-D SI is performed at a single axial level. The level is chosen to include the maximum volume of abnormal enhancement, or, in non-enhancing lesions. The most extensive T2 signal abnormality. Two different MR systems have been used (Marconi Edge and GE Signa LX); at each site, a PRESS localisation sequence is employed with TE 128-144 ms. Automated software is used to generate spectral arrays, metabolite maps, and metabolite ratio maps from the spectroscopic data. Colour overlays of the maps onto anatomical images are produced using manufacturer software or the Medex imaging data analysis package. High grade gliomas showed choline levels higher than those in apparently normal brain, with decreases in NAA and creatine. Some lesions showed spectral abnormality extending into otherwise normal appearing brain. This was also seen in a case of CNS lymphoma. Lowgrade lesions showed choline levels similar to normal brain, but with decreased NAA. Only a small number of metastases have been studied, but to date no metastasis has shown spectral abnormality beyond the margins suggested by conventional imaging. Follow-up studies generally show spectral heterogeneity. Regions with choline levels higher than those in normal-appearing brain are considered to represent recurrent high-grade tumour. Some regions show choline to be the dominant metabolite, but its level is not greater than that seen in normal brain. These regions are considered suspicious for residual / recurrent tumour when the choline / creatine ratio exceeds 2 (lower ratios may represent treatment effect). 2-D SI improves the initial assessment of brain tumours, and has potential for influencing the radiotherapy treatment strategy. 2-D SI also

  15. Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; Josefsson, Pär; Jørgensen, Judit

    2016-01-01

    AIM OF DATABASE: The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. STUDY POPULATION: The LYFO database was established in 1982 as a seminational database including...... all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. MAIN VARIABLES: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each......-100 years) and a male/female ratio of 1.23:1. Patients can be registered with any of 42 different subtypes according to the World Health Organization classifications. CONCLUSION: LYFO is a nationwide database for all lymphoma patients in Denmark and includes detailed information. This information is used...

  16. Non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Glatstein, E.; Wasserman, T.H.

    1987-01-01

    Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

  17. Differential diagnosis of benign intrahepatic tumours

    International Nuclear Information System (INIS)

    Koenig, R.; Herter, M.; Deutsches Krebsforschungszentrum, Heidelberg

    1983-01-01

    Differential diagnosis of benign intrahepatic tumours can be very difficult despite numerous non-invasive diagnostic approaches, as is evident from two case reports presented here. The problem appears particularly intricate if two or more masses or space-occupying growths are present at the same time, the diagnostic aspects being different. In the first case, echinococcus alveolaris occurred simultaneously with a cavernous haemangioma and a focal nodular hyperplasia (FNH). In the second case, FNH as a pendulating tumour was combined with a second focus in the superior part of the liver. These two examples are used as basis for discussing various diagnostic approaches, such as sonography, computed tomography and scintiscanning. (orig.) [de

  18. Differential diagnosis of benign intrahepatic tumours

    Energy Technology Data Exchange (ETDEWEB)

    Koenig, R.; Herter, M.

    1983-01-01

    Differential diagnosis of benign intrahepatic tumours can be very difficult despite numerous non-invasive diagnostic approaches, as is evident from two case reports presented here. The problem appears particularly intricate if two or more masses or space-occupying growths are present at the same time, the diagnostic aspects being different. In the first case, echinococcus alveolaris occurred simultaneously with a cavernous haemangioma and a focal nodular hyperplasia (FNH). In the second case, FNH as a pendulating tumour was combined with a second focus in the superior part of the liver. These two examples are used as basis for discussing various diagnostic approaches, such as sonography, computed tomography and scintiscanning.

  19. Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours

    DEFF Research Database (Denmark)

    Paiva, C E; Drigo, S A; Rosa, F E

    2010-01-01

    BACKGROUND: The clinical relevance of transforming growth factor-beta (TGF-beta)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-beta1 and transforming growth factor-beta type II receptor (TGF-betaRII) expression levels in t...

  20. Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism.

    Science.gov (United States)

    Fais, S

    2010-05-01

    This review presents a possible new approach against cancer, as represented by inhibition of proton pumps, a mechanism used by tumour cells to avoid intracellular accumulation of toxic substances. Proton pump inhibitors (PPIs) belong to a family of pro-drugs that are currently used in the treatment of peptic diseases needing acidity to be activated. PPIs target the acidic tumour mass, where they are metabolized, thus blocking proton traffic. Proton pump inhibition triggers a rapid cell death as a result of intracellular acidification, caspase activation and early accumulation of reactive oxygen species into tumour cells. As a whole, the devastating effect of PPIs on tumour cells suggest the triggering of a fatal cell toxification. Many human tumours, including melanoma, osteosarcoma, lymphomas and various adenocarcinomas are responsive to PPIs. This appears highly conceivable, in as much as almost all human tumours are acidic and express high levels of proton pumps. Paradoxically, metastatic tumours appear to be more responsive to PPIs being more acidic than the majority of primary tumours. However, two clinical trials test the effectiveness of PPIs in chemosensitizing melanoma and osteosarcoma patients. Indeed, tumour acidity represents a very potent mechanism of chemoresistance. A majority of cytotoxic agents, being weak bases, are quickly protonated outside and do not enter the cells, thus preventing drugs to reach specific cellular targets. Clinical data will provide the proof of concept on the use of PPIs as a new class of antitumour agent with a very low level of systemic toxicity as compared with standard chemotherapeutic agents.

  1. Binding of peanut lectin to germinal-centre cells: a marker for B-cell subsets of follicular lymphoma?

    OpenAIRE

    Rose, M. L.; Habeshaw, J. A.; Kennedy, R.; Sloane, J.; Wiltshaw, E.; Davies, A. J.

    1981-01-01

    The binding of horseradish-peroxidase-labelled peanut lectin (HRP-PNL) to cryostat sections of tonsil, lymphoma lymph nodes, reactive lymph nodes and miscellaneous tumours demonstrated that PNL binds selectively to lymphocytes in germinal centres. Lymph nodes from 21 patients with non-Hodgkin's lymphomas were phenotyped as cell suspensions for PNL binding, and the following surface markers: E rosetting, C3d, SIg, OK markers of T-cell subsets, Ig heavy-chain and light-chain classes. There was ...

  2. Salivary gland anlage tumour

    African Journals Online (AJOL)

    developmental midline nasal lesions such as a meningo-encephalocele or glioma. Neoplastic lesions are usually benign, and include dermoids, hamartomas, teratomas and haemangiomas. Malignant lesions such as neuroblastoma, rhabdomyosarcoma or lymphoma may be seen, but are extremely rare, and metastatic ...

  3. MALT LYMPHOMA OF PALATE AND ORBIT

    Directory of Open Access Journals (Sweden)

    VIVIANA ANDREA CIFUENTES NAVAS

    2018-05-01

    acquires a tumour morphology of 4x4x2.2 cm, well defined that does not infiltrate adjacent tissues. It enhances intensely and homogeneously with contrast.  There are bilateral laterocervical ganglionic images ,with predominance in right side, nonspecific.Orbit MRI: It demostrates mixed orbital mass intra and extraconal on the left side, oval morfology, Its limits are partially well-defined, with transverse diameters 2.3x1.1 cm and craniocaudal 2cm approximately, it show a  moderate and diffuse enhance after endovenous contrast. The result of the biopsy of both lesions indicated infiltration of "B" lymphoma type MALT lymphoma. The patient was referred to the service of hematology, found no adenopathies or visceromegalies.  It was cataloged like a lymphoma NO HODGKIN B malt type STAGE IV-A (two extranodal sites, orbit and palate, He is currently with chemotherapy treatment, and he is followed up by this department.  CONCLUSIONS MALT lymphoma affects adults older than 60 years mainly, showing a slight female predominance, and more probably for gastric locations. The clinical characteristics and the presentation of the symptoms are mainly related to the primary location of the tomour. Approximately 6% of the non-hodgkin lymphomas that affect Waldeyer's ring are MALT lymphomas, affecting most of them to the palatine amygdala. However, according to the reviewed bibliography, the affectation of the palate is rare, being more frequent the orbital location MALT lymphomas follow a relatively indolent clinical course and generally remain localized in their primary extranodal site. Tumors are sensitive to radiation therapy and local treatment. However, dissemination at multiple sites is not infrequent, it may involve extra-ganglionic sites, such as bone marrow, spleen and liver.  Early diagnosis is the basis of a better prognosis, this allows a more adequate treatment. The role of the in-depth clinical study is emphasized and confirmed by a biopsy. It is important the

  4. Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

    Science.gov (United States)

    Smina, T P; Mathew, J; Janardhanan, K K

    2016-04-30

    G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities.

  5. Experimental tumour treatment

    International Nuclear Information System (INIS)

    1985-08-01

    This report of 1984 is the seventh in a series and presents that year's results of continuous studies in the domain of experimental tumour radiotherapy. In the year under review, more personnel has been available for the studies, and the scientific programmes for the assessment of acute and chronic side effects of radiotherapies have been extended. New models have been developed, among them a first system based on animal experiments, for quantifying the mucositis of the oral and pharyngeal mucosa, a limiting condition in the radiotherapy of head and throat tumours. Another significant advancement is a model for quantification of chronical damage to the ureter, which still is a serious problem in the radiotherapy of gynaecological tumours. The 1984 experimental tumour studies have been mainly devoted to the repopulation and split-dose recovery in various tumours, concentrating on dose fractionation as one of the major problems studies. Particular interest has been attached to the processes involved in treatments over several weeks with a daily effective dose of 2 Gy. (orig./MG) [de

  6. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

    2016-03-15

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

  7. Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade.

    Directory of Open Access Journals (Sweden)

    Sylwia Libard

    Full Text Available Human cytomegalovirus (HCMV has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

  8. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    International Nuclear Information System (INIS)

    Sernbo, Sandra; Gustavsson, Elin; Brennan, Donal J; Gallagher, William M; Rexhepaj, Elton; Rydnert, Frida; Jirström, Karin; Borrebaeck, Carl AK; Ek, Sara

    2011-01-01

    The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. SOX11 expression and clinicopathological data was compared using χ 2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours

  9. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    LENUS (Irish Health Repository)

    Sernbo, Sandra

    2011-09-24

    Abstract Background The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods SOX11 expression and clinicopathological data was compared using χ2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5\\'-Aza-2\\'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.

  10. Stages of Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

  11. Stages of Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... Version Key Points Childhood Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system. There are two types of childhood Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin ...

  12. The Danish National Lymphoma Registry

    DEFF Research Database (Denmark)

    Arboe, Bente; El-Galaly, Tarec Christoffer; Clausen, Michael Roost

    2016-01-01

    BACKGROUND: The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. AIM: To test the coverage and data...... of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive...... was good with high PPVs (87% to 100%), and high completeness (92% to 100%). CONCLUSION: The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research....

  13. A reproducible brain tumour model established from human glioblastoma biopsies

    Directory of Open Access Journals (Sweden)

    Li Xingang

    2009-12-01

    Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

  14. Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice.

    Science.gov (United States)

    Hu, Jingtao; Wang, Chunfeng; Ye, Liping; Yang, Wentao; Huang, Haibin; Meng, Fei; Shi, Shaohua; Ding, Zhuang

    2015-06-01

    Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN-gamma (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

  15. Somatostatin receptor imaging in intracranial tumours

    International Nuclear Information System (INIS)

    Schmidt, M.; Scheidhauer, K.; Voth, E.; Schicha, H.; Luyken, C.; Hildebrandt, G.; Klug, N.

    1998-01-01

    The somatostatin analogue [ 111 In-DTPA-d-Phe 1 ]-octreotide ( 111 In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and 111 In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of 111 In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), 111 In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq 111 In-octreotide. Planar images of the head in four views with a 128 x 128 matrix and single-photon emission tomographic images (64 x 64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed 111 In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show 111 In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and

  16. Somatostatin receptor imaging in intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, M.; Scheidhauer, K.; Voth, E.; Schicha, H. [Department of Nuclear Medicine, University of Koeln (Germany); Luyken, C.; Hildebrandt, G.; Klug, N. [Department of Neurosurgery, University of Kolen (Germany)

    1998-07-01

    The somatostatin analogue [{sup 111}In-DTPA-d-Phe{sup 1}]-octreotide ({sup 111}In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and {sup 111}In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of {sup 111}In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), {sup 111}In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq {sup 111}In-octreotide. Planar images of the head in four views with a 128 x 128 matrix and single-photon emission tomographic images (64 x 64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed {sup 111}In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show {sup 111}In-octreotide uptake. The results demonstrate that a large variety of intracranial

  17. Value of skeletal scintiscanning in cases of primary bone tumours and tumourous alterations

    International Nuclear Information System (INIS)

    Sokolowski, U.

    1982-01-01

    In the course of an investigation on the storage behaviour of primary bone tumours and tumourous bone alterations the skeletal scintigrams of a total of 26 patients were evaluated. Bone scintiscanning was done according to current practice after injection of an average amount of 10mCi sup(99m)Tc-MDP, followed by a semiquantitative evaluation. In all cases of malignant bone tumours there was fond to be increased storage of radionuclide; with benign bone alterations this was so in 70 per cent of cases. To differentiate between benign and malignant tumours respectively inflammatory bone diseases was not as a rule possible; however, the investigation yielded additional information completing the X-ray findings essentially. Thus very high storage of radioactivity was established for all osteosarcomas, whereas benign bone growths exhibited more circumscribed accumulations of activity. Skeletal scintiscanning for diagnostical purposes is particularly informative as to the early detection of bone foci evading X-ray diagnosis, more accurate delimitation of tumourous processes, and course control of tumours tending to degenerate. (orig./MG) [de

  18. Nodular breast lymphoma

    International Nuclear Information System (INIS)

    Rodriguez, M.; Sahagun, E.; Pena, J.; Mendez, J.

    1996-01-01

    We attempt to correlate the histological types [in three cases of B-cell non-Hodgkin's lymphoma (NHL), one case of T-cell NHL and one of Hodgkin's disease] with the radiological presentation and compare our findings with the literature reviewed. Among the mammographic studies, performed over and 18-month period, we have assessed five patients (four women and one man, aged as having lymphoma. the man presented bilateral involvement. Both mammography and a broader study with ultrasound and chest and abdominal CT scan were performed in every case. Four patients underwent breast ultrasound. The definitive diagnosis was based on biopsy in all cases. Three of the five cases involved primary lymphomas and the other two were secondary. Four patients presented NHL and the remaining patient had Hodgkin's disease. In mammography, the nodules showed different degrees of margin definition. In ultrasound, all the lesion were hypoechoic. The radiological diagnosis of breast lymphoma is difficult in the absence of a previous diagnosis of lymphoma. This lesion should be included in the differential diagnosis in the presence of a breast nodule associated with axillary lymph nodes, especially when the latter are bilateral. (Author)

  19. Classification of malignant lymphomas

    International Nuclear Information System (INIS)

    Schneider, M.; Thyss, A.

    1986-01-01

    Malignant lymphomas, primary tumors of the lymphoid tissues, were first described in 1832 by Thomas Hodgkin. The histological characteristics were later defined by Sternberg and Reed, and Virchow introduced the concept of lymphosarcoma in 1863. Today, these pathologies are grouped together under the synonymous terms hematosarcoma or malignant lymphoma, which are in turn divided into Hodgkin's disease (HD) and non-Hodgkin's malignant lymphomas (NHL). The therapy of lymphomas is controversial. The validity of treatment for asymptomatic patients is questioned, owing to the indolent course of many lymphomas. Results for histologically unfavorable forms are highly disparate. Exclusive radiotherapy has occasionally produced up to 78% disease-free survival at 5 years for truly localized stages. Today, however, use of chemotherapy/radiotherapy combinations is almost universal, with chemotherapy occasionally being used alone and providing 90% disease-free survival at 5 years. Chemotherapy is the main treatment for disseminated forms; the major associations include doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate, methotrexate, and prednisone. Radiotherapy is used more for adjuvant purposes. Synthesis of recent studies allows us to reasonably expect 40% relapse-free survival at 10 years and the establishment of a cure plateau in the near future

  20. HIV-associated lymphoma: histopathology and association with Epstein-Barr virus genome related to clinical, immunological and prognostic features

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Lundgren, Jens Dilling

    1991-01-01

    (6)/l, P less than 0.05), and more often a history of previous AIDS-defining illnesses (50% vs. 0%, P less than 0.005), compared with patients with Burkitt-type lymphomas. Epstein-Barr virus (EBV) DNA was demonstrated in 14 of 19 immunoblast-rich tumours, and in 2 of 7 Burkitt-type lymphomas (P = 0......-rich morphology, and may be linked to EBV, whereas the other may occur in the absence of immunosuppression, is often of Burkitt-type morphology, and is probably not linked to EBV. In addition to these two main types, other non-Hodgkin lymphomas and Hodgkin's disease do occur....

  1. Immunohistochemical Characterization of Canine Lymphomas

    Directory of Open Access Journals (Sweden)

    Roxana CORA

    2017-11-01

    Full Text Available Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania, in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T. Most of multicentric (80%, mediastinal (60% and primary central nervous system lymphomas (100% had B immunophenotype, while the majority of cutaneous (80% and digestive (100% lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

  2. Familial Aggregation of Non-Hodgkin's Lymphoma (NHL. A Case Report

    Directory of Open Access Journals (Sweden)

    Loves Sandra SCM

    2006-08-01

    Full Text Available Abstract A family is reported in which three male siblings of Asian descent developed non-Hodgkin's lymphoma (NHL. Case 1 was diagnosed with indolent follicular lymphoma stage IIIA at age 45. Case 2 presented with large B-cell lymphoma stage IIB at age 56. Chromosomal investigation of the peripheral blood did not show abnormalities. Chemotherapy induced a complete remission. However, after a period of nearly ten years he developed acute myeloid leukaemia. Case 3 developed large B-cell lymphoma stage IVA at age 52. Cytogenetic analysis in peripheral blood was normal. Shared genetic and environmental risk factors remain to be identified in this family. Familial aggregation of NHL is uncommon. In some families, various forms of immunodeficiency have been found. In addition to coincidental clustering of cases, and rare cases explained by known tumour syndromes such as Li-Fraumeni (like syndrome, other familial cases may share as yet unknown genetic and/or environmental risk factors.

  3. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Scally John

    2003-12-01

    Full Text Available Abstract Background Mantle cell lymphoma (MCL is a rare variety of non-Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph nodes with invasive breast cancers without prior history of adjuvant chemotherapy or radiotherapy has not been previously reported in literature. Case report We report a rare case of breast cancer co-existing with stage I mantle cell lymphoma of the ipsilateral axillary lymph node detected fortuitously by population screening. Conclusion Though some studies have tried to prove breast carcinomas and lymphomas to share a common molecular or viral link, more research needs to be done to establish whether such a link truly exists.

  4. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

    2015-04-01

    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  5. Lymphatic vessels assessment in feline mammary tumours

    International Nuclear Information System (INIS)

    Sarli, Giuseppe; Sassi, Francesco; Brunetti, Barbara; Rizzo, Antonio; Diracca, Laura; Benazzi, Cinzia

    2007-01-01

    The lymphatic vessels play a crucial role in a variety of human cancers since tumour cell lymphatic invasion significantly influences prognosis. It is not known if pre-existing lymphatics are enough for tumour dissemination or de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both lymphatic and blood vessels during embryonic development, and only for lymphatics after birth. VEGF is a mediator of both vasculogenesis and angiogenesis, regulates the growth of lymphatics in various experimental models, and is produced in many solid tumours. CD44 mediates hyaluronic acid (HA)-dependent cell adhesion: besides promoting invasion, this interaction also supports neoangiogenesis that indirectly stimulates tumour cell proliferation. The expression of VEGF-C (Vascular Endothelial Growth Factor – C), its receptor VEGFR-3 and CD44, were studied on feline mammary samples to assess the importance of lymphangiogenesis and lymphangiotrophism in neoplasia. Samples were taken from six normal mammary glands (NMG), ten benign (BT) and 32 malignant (MT) tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains were applied to 4 μm-thick sections, and their expression evaluated in intratumoral/extratumoral and intramammary/extramammary fields. All groups revealed a higher number of lymphatics in the extratumoral/extramammary areas. VEGF-C expression in the epithelium paralleled the number of positive vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral than intratumoral fields in tumours and showed a significant increase in extramammary/extratumoral fields from NMG to MT. Pearson test showed a significant and inversely proportional correlation between CD44 expression and the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours. The number of both VEGFR-3 positive and negative lymphatics in the extratumoral

  6. Tumour model with intrusive morphology, progressive phenotypical heterogeneity and memory

    Science.gov (United States)

    Atangana, Abdon; Alqahtani, Rubayyi T.

    2018-03-01

    The model of a tumour, taking into account invasive morphology, progressive phenotypical heterogeneity and also memory, is developed and analyzed in this paper. Three models are investigated: first we consider the model describing the proliferation concentrates in proximity of tumour boundaries, in which the oxygen levels are pronounced. Then we consider the model where the oxygen around the tumour is considered to be unchanged by the vascular system. Finally, we investigate the model of growth of tumours using the concept of non-local operators with the Mittag-Leffler kernel. We provide the numerical solution using the extended 3/8 Simpson method for the new trends of fractional integration for the proliferation concentrates in the proximity of the tumour model. Then we provide the exact solutions of the Gompertz model with three different fractional differentiations involving power law, exponential decay law and the Mittag-Leffler law.

  7. Genetically modified tumour vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2005-01-01

    Roč. 3, Suppl. 1 (2005), S7 ISSN 1214-021X. [Cells VI - Biological Days /18./. 24.10.2005-26.10.2005, České Budějovice] Institutional research plan: CEZ:AV0Z50520514 Keywords : tumour vaccines * HPV16 Subject RIV: EC - Immunology

  8. Transformation of Follicular Lymphoma

    Science.gov (United States)

    Lossos, Izidore S.; Gascoyne, Randy D.

    2011-01-01

    Histological transformation of follicular lymphoma (FL) to a more aggressive non-Hodgkin's lymphomas is a pivotal event in the natural history of FL and is associated with poor outcome. While commonly observed in clinical practice and despite multiple studies designed to address its pathogenesis, the biology of this process represents an enigma. In this chapter we present a state of the art review summarizing the definition of histologic transformation, its incidence, pathogenesis, clinical manifestations, treatment and outcome. Furthermore, we specifically emphasize gaps in our knowledge that should be addressed in future studies. PMID:21658615

  9. Lymphoma of the Cervix

    Directory of Open Access Journals (Sweden)

    Juanita Parnis

    2012-01-01

    Full Text Available Primary non-Hodgkins lymphoma of the uterine cervix is a very rare diagnosis. A 54-year-old woman presented with a 3-month history of postmenopausal bleeding per vaginum. On examination, a friable, fungating lesion was seen on the cervix. Histology revealed a CD 20 positive high-grade non-Hodgkin’s diffuse large B cell lymphoma from cervical biopsies and endometrial curettage. She was diagnosed as stage IE after workup and subsequently treated with six cycles of R-CHOP chemotherapy followed by radiotherapy of the involved field.

  10. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  11. High-mobility group B1 (HMGB1) and receptor for advanced glycation end-products (RAGE) expression in canine lymphoma.

    Science.gov (United States)

    Sterenczak, Katharina A; Joetzke, Alexa E; Willenbrock, Saskia; Eberle, Nina; Lange, Sandra; Junghanss, Christian; Nolte, Ingo; Bullerdiek, Jörn; Simon, Daniela; Murua Escobar, Hugo

    2010-12-01

    Canine lymphoma is a commonly occurring, spontaneously developing neoplasia similar to human non-Hodgkin's lymphoma and, thus, is used as a valuable model for human malignancy. HMGB1 and RAGE are strongly associated with tumour progression and vascularisation. Consequently, deregulated RAGE and HMGB1 may play an important role in the mechanisms involved in lymphoma progression. Expression patterns of HMGB1 and RAGE were analysed in 22 canine lymphoma and three canine non-neoplastic control samples via real time PCR and canine beta-glucuronidase gene (GUSB) as endogenous control. HMGB1 was up-regulated in the neoplastic samples, while RAGE expression remained inconspicuous. This study demonstrated similar mechanisms in lymphoma progression in humans and dogs due to overexpression of HMGB1, which was described in human lymphomas. RAGE remained stable in terms of expression indicating that the extracellular HMGB1-induced effects are regulated by HMGB1 itself.

  12. 18F-FDG PET/CT in the clinical management of patients with lymphoma.

    Science.gov (United States)

    Tamayo, P; Martín, A; Díaz, L; Cabrero, M; García, R; García-Talavera, P; Caballero, D

    The aim of this work was to review the current recommendations for staging and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) in routine clinical practice after chemotherapy and/or stem cell transplantation. A five-point scale (5-PS) from the First International Workshop on PET in Lymphoma in Deauville, France, in 2009, was recommended as the standard tool to score imaging to assess treatment response in patients with lymphoma using 18 F-Fluorodeoxyglucose (FDG) PET/CT. Following the recommendations of the 11th and 12th International Conferences on Malignant Lymphoma held in Lugano (Switzerland), in 2011 and 2013, respectively, a consensus (the so-called Lugano Classification) was reached regarding the use of PET/CT for staging and response assessment in FDG-avid lymphomas. As a result, 18 F-FDG PET/CT was formally incorporated into standard staging for FDG-avid lymphomas. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. PET/CT will be used to assess response in FDG-avid histologies using the 5-point scale. The recent introduction of biological agents with immune mechanisms requires flexibility in interpretations of the Lugano criteria due to tumour flare or a pseudo-progression effect produced by these agents. Provisional criteria have been proposed (Lymphoma Response to Immunomodulatory Therapy Criteria) with the introduction of the term 'Indeterminate Response' in order to identify this phenomenon until confirmed as flare/pseudoprogression or true progression. All these recommendations will improve evaluations of patients with lymphoma, and allow comparison of results from clinical practice and trials. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  13. Vitamin E - its status and role in leukemia and lymphoma

    International Nuclear Information System (INIS)

    Dasgupta, J.; Das, S.; Sanyal, U.

    1993-01-01

    A comparative study has been performed on the relationship between vitamin E and immuno-function in normal and malignant condition in human and murine systems. Further, the effects of supplemental vitamin E on tumor take, host survival and tumor growth has been studied in a transplantable lymphoma in mice. Vitamin E was assayed in serum samples from normal subjects and from patient with leukemia and lymphoma by high performance liquid chromatography (HPLC) The murine group included Dalton's ascite lymphoma (DL), Schwartz lymphoblastic leukemia (SVL) and Moloney lymphoblastic leukemia (MVL). Serum vitamin E was found to be lower than that of the normal controls in all cases of leukemia and lymphoma both in human and lymphoma. Supplementary vitamin E administered at the initial phase of development of murine lymphomas reduced the rate of tumor growth, improved host survival and elevated serum vitamin E level. Vitamin E supplementation also activated specific induced blastogenesis of peripheral blood lymphocytes (PBL) and elevated serum IgG level. IgM remained unaltered and and macrophage activity did not seem to be affected. The present findings indicated a low status of vitamin E in tumor bearing host and beneficial effect of supplemental vitamin E on the host which was mediated by the host immune system. (author)

  14. Swiss Canine Cancer Registry 1955-2008: Occurrence of the Most Common Tumour Diagnoses and Influence of Age, Breed, Body Size, Sex and Neutering Status on Tumour Development.

    Science.gov (United States)

    Grüntzig, K; Graf, R; Boo, G; Guscetti, F; Hässig, M; Axhausen, K W; Fabrikant, S; Welle, M; Meier, D; Folkers, G; Pospischil, A

    2016-01-01

    This study is based on the Swiss Canine Cancer Registry, comprising 121,963 diagnostic records of dogs compiled between 1955 and 2008, in which 63,214 (51.83%) animals were diagnosed with tumour lesions through microscopical investigation. Adenoma/adenocarcinoma (n = 12,293, 18.09%) was the most frequent tumour diagnosis. Other common tumour diagnoses were: mast cell tumour (n = 4,415, 6.50%), lymphoma (n = 2,955, 4.35%), melanocytic tumours (n = 2,466, 3.63%), fibroma/fibrosarcoma (n = 2,309, 3.40%), haemangioma/haemangiosarcoma (n = 1,904, 2.80%), squamous cell carcinoma (n = 1,324, 1.95%) and osteoma/osteosarcoma (n = 842, 1.24%). The relative occurrence over time and the most common body locations of those tumour diagnoses are presented. Analyses of the influence of age, breed, body size, sex and neutering status on tumour development were carried out using multiple logistic regression. In certain breeds/breed categories the odds ratios (ORs) for particular tumours were outstandingly high: the boxer had higher ORs for mast cell tumour and haemangioma/haemangiosarcoma, as did the shepherd group for haemangioma/haemangiosarcoma, the schnauzer for squamous cell carcinoma and the rottweiler for osteoma/osteosarcoma. In small dogs, the risk of developing mammary tumours was three times higher than in large dogs. However, small dogs were less likely to be affected by many other tumour types (e.g. tumours of the skeletal system). Examination of the influence of sex and neutering status on tumour prevalence showed that the results depend on the examination method. In all sampling groups the risk for female dogs of developing adenoma/adenocarcinoma was higher than for male dogs. Females had a lower risk of developing haemangioma/haemangiosarcoma and squamous cell carcinoma than males. Neutered animals were at higher risk of developing specific tumours outside the genital organs than intact animals. The sample size allows detailed insight into the

  15. Primitive Neuroectodermal Tumour in Young Adults - A Report of two Rare Cases and Review of Literature

    Directory of Open Access Journals (Sweden)

    Vidhya Lakshmi S

    2017-10-01

    Full Text Available Primitive Neuro Ectodermal Tumours’ (PNET are highly aggressive embryonal tumours of presumed neural crest origin. They are derived from neoplastic transformation of common progenitor cells in the sub ependymal matrix layer. They are more common in children. They are small round cell tumours affecting the central nervous system (CNS, others being Ewing’s sarcoma, medullobalstoma, lymphomas etc. They are classified based on their immune histochemical characteristics- neuronal, astrocytic, ependymal, retinal photo receptor, undifferentiated. Undifferentiated variety carries better prognosis. GFAP expression is an important prognostic factor. Presence of p53 germ line mutation indicates an increased risk for developing PNET. Spinal PNET are secondary to CSF metastasis from cranium commonly. Primary spinal PNET tumours are rare and extradural location is extremely rare. PNET needs multimodality approach but carries poor prognosis when compared to other CNS tumours.

  16. Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours.

    Science.gov (United States)

    Ujvari, Beata; Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; Pyecroft, Stephen; Taylor, Robyn; Hamede, Rodrigo; Jones, Menna; Belov, Katherine; Madsen, Thomas

    2014-02-01

    The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.

  17. Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Aoyagi, Tomoyoshi; Shuto, Kiyohiko; Okazumi, Shinichi; Hayano, Kohichi; Satoh, Asami; Saitoh, Hiroshige; Shimada, Hideaki; Nabeya, Yoshihiro; Matsubara, Hisahiro [Chiba University, Department of Frontier Surgery, Graduate School of Medicine, Chiba (Japan); Kazama, Toshiki [Chiba University, Department of Radiology, Graduate School of Medicine, Chiba (Japan)

    2012-06-15

    Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. circle Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen circle There is also negative correlation between ADCs and vascular endothelial growth factor circle ADC values may contribute to the treatment of oesophageal cancer. (orig.)

  18. Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis

    International Nuclear Information System (INIS)

    Aoyagi, Tomoyoshi; Shuto, Kiyohiko; Okazumi, Shinichi; Hayano, Kohichi; Satoh, Asami; Saitoh, Hiroshige; Shimada, Hideaki; Nabeya, Yoshihiro; Matsubara, Hisahiro; Kazama, Toshiki

    2012-01-01

    Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. circle Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen circle There is also negative correlation between ADCs and vascular endothelial growth factor circle ADC values may contribute to the treatment of oesophageal cancer. (orig.)

  19. [Fluctuant pulmonary nodules as presentation of a MALT lymphoma].

    Science.gov (United States)

    Dolz Aspas, R; Toyas Miazza, C; Ruiz Ruiz, F; Morales Rull, J L; Pérez Calvo, J I

    2003-11-01

    Mucosa associated lymphoid tissue (MALT) lymphomas are a group of non- Hodgkin"s lymphomas of low malignancy degree. The most frequent location is the gastrointestinal tract. Its primary pulmonary presentation is unusual and heterogeneous from point of view radiological. Woman 61 years old with antecedents of vitiligo, gastric ulcus, cirrhosis by VHC, that go into the hospital by sudden disnea, thoracic paint with pleural characterises and fever of 38.5 degrees C, Her thorax radiography and thoracic TAC showed nodes that affect to different pulmonary lobes. The cytology by PAAF confirms their malignant nature. In subsequent radiological controls it was notice the nodels took away completely and returns in different pulmonary place in each recurrence. The presentation like fluctuant pulmonary nodes is exceptional in a MALT lymphoma. It was described a higher incidence of VHC infection and tumour. The evidence of chronic hepatitis by virus C disease, and local chronic inflammatory process as well as autoimmune disorders may be considerate like a factor that contribute to MALT lymphoma.

  20. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2017-04-17

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  1. Lymphoma classification update: B-cell non-Hodgkin lymphomas.

    Science.gov (United States)

    Jiang, Manli; Bennani, N Nora; Feldman, Andrew L

    2017-05-01

    Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. A 2016 revision to the WHO classification of lymphoid neoplasms recently was reported. The present review focuses on B-cell non-Hodgkin lymphomas, the most common group of lymphomas, and summarizes recent changes most relevant to hematologists and other clinicians who care for lymphoma patients. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revision of the WHO classification particularly impact the subclassification and genetic stratification of diffuse large B-cell lymphoma and high-grade B-cell lymphomas, and reflect evolving criteria and nomenclature for indolent B-cell lymphomas and lymphoproliferative disorders.

  2. Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

    Science.gov (United States)

    Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

    2015-04-29

    A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

  3. Small Intestinal Tumours: An Overview on Classification, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Chiara Notaristefano

    2014-12-01

    Full Text Available The small intestinal neoplasia group includes different types of lesions and are a relatively rare event, accounting for only 3-6% of all gastrointestinal (GI neoplasms and 1-3% of all GI malignancies. These lesions can be classified as epithelial and mesenchymal, either benign or malignant. Mesenchymal tumours include stromal tumours (GIST and other neoplasms that might arise from soft tissue throughout the rest of the body (lipomas, leiomyomas and leiomyosarcomas, fibromas, desmoid tumours, and schwannomas. Other lesions occurring in the small bowel are carcinoids, lymphomas, and melanomas. To date, carcinoids and GIST are reported as the most frequent malignant lesions occurring in the small bowel. Factors that predispose to the development of malignant lesions are different, and they may be hereditary (Peutz-Jeghers syndrome, familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, neuroendocrine neoplasia Type 1, von Hippel-Lindau disease, and neurofibromatosis Type 1, acquired (sporadic colorectal cancer and small intestine adenomas, coeliac disease, Crohn’s disease, or environmental (diet, tobacco, and obesity. Small bowel tumours present with different and sometimes nonspecific symptoms, and a prompt diagnosis is not always so easily performed. Diagnostic tools, that may be both radiological and endoscopic, possess specificity and sensitivity, as well as different roles depending on the type of lesion. Treatment of these lesions may be different and, in recent years, new therapies have enabled an improvement in life expectancy.

  4. Primary splenic lymphoma

    International Nuclear Information System (INIS)

    Aslam, M.; Salamat, N.; Mamoon, N.; Ahmed, M.

    2006-01-01

    A middle-aged lady presented with fever and splenomegaly and had been provisionally treated for malaria, typhoid and tuberculosis. Diagnostic splenectomy was performed which revealed diffuse large cell lymphoma, B type, localized to spleen. Patient had remission of disease after splenectomy. (author)

  5. Primary splenic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Aslam, M [Combined Military Hospital, Multan (Pakistan). Dept. of Surgery; Salamat, N [Combined Military Hospital, Multan (Pakistan). Dept. of Pathology; Mamoon, N [Armed Forces Inst. of Pathology, Rawalpindi (Pakistan). Dept. of Histopathology; Ahmed, M [Combined Military Hospital, Multan (Pakistan). Dept. of Medicine

    2006-04-15

    A middle-aged lady presented with fever and splenomegaly and had been provisionally treated for malaria, typhoid and tuberculosis. Diagnostic splenectomy was performed which revealed diffuse large cell lymphoma, B type, localized to spleen. Patient had remission of disease after splenectomy. (author)

  6. Leukemia & Lymphoma Society

    Science.gov (United States)

    ... be the exclusive property of The Leukemia & Lymphoma Society which in its sole discretion may use this material as it sees fit. I agree to the terms of the Standard Photography Release.* Submit * This field is required * Please fix the validation error messages in the Form Your story was ...

  7. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Zhanshan [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Qian, Guangfang [Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200 (China); Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Song, Haihan [Emergency Center, East Hospital, Shanghai 200120 (China); Qian, Baohua, E-mail: qianbhl963@163.com [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5{sup +} CD4{sup +} T cells, in DLBCL. Data showed that compared to CXCR5{sup -} CD4{sup +} T cells, CXCR5{sup +} CD4{sup +} T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5{sup +} CD4{sup +} T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5{sup -} CD4{sup +} T cells, while the level of IL-10 secretion was significant elevated in the CXCR5{sup +} compartment compared to the CXCR5{sup -} compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5{sup +} CD4{sup +} T cell coculture compromised the CXCR5{sup +} CD4{sup +} T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5{sup +} compartment also contained significantly lower frequencies of cytotoxic CD4{sup +} T cells than the CXCR5{sup -} compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4{sup +} T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  8. Eyelid lymphoma in a patient with a gold weight implant.

    Science.gov (United States)

    Di Nisio, L A; Croxatto, J O; Mansur, M C; Aldecoa, J P; Weil, D

    2017-04-01

    A male patient with an exposure keratopathy caused by lagophthalmos. A gold weight was implanted in the right upper eyelid. Eight months later, he presented with erythema and swelling of right upper eyelid. An incisional biopsy was performed, reporting extranodal marginal zone B cell lymphoma. when a tumour at the site of a gold weight implant is refractory to treatment, it is essential to perform an incisional biopsy to establish the histopathological diagnosis. Ocular adnexal lymphomas are relatively common. The presence of foreign material can cause chronic inflammation that could be the stimulus for the development of a lymphoproliferative disorder. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. FDG PET/CT imaging as a biomarker in lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Meignan, Michel; Itti, Emmanuel [Hopitaux Universitaires Henri Mondor, Paris-Est Creteil University, LYSA Imaging, Department of Nuclear Medicine, Creteil (France); Gallamini, Andrea [Nice University, Research, Innovation and Statistic Department, Antoine Lacassagne Cancer Center, Nice (France); Scientific Research Committee, S. Croce Hospital, Cuneo (Italy); Younes, Anas [Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York, NY (United States)

    2015-04-01

    FDG PET/CT has changed the management of FDG-avid lymphoma and is now recommended as the imaging technique of choice for staging and restaging. The need for tailoring therapy to reduce toxicity in patients with a favourable outcome and for improving treatment in those with high-risk factors requires accurate diagnostic methods and a new prognostic algorithm to identify different risk categories. New drugs are used in relapsed/refractory patients. The role of FDG PET/CT as a biomarker in this context is summarized in this review. New trends in FDG metabolic imaging in lymphoma are addressed including metabolic tumour volume measurement at staging and integrative PET which combines PET data with clinical and molecular markers or other imaging techniques. The quantitative approach for response assessment which is under investigation and is used in large ongoing trials is compared with visual criteria. The place of FDG in the era of targeted therapy is discussed. (orig.)

  10. Primary B-cell Lymphoma of the Thyroid Featuring the Different Ultrasonographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Na; Choi, Yoon Jung; Kim, Dong Hoon [Kangbuk Samsung Medical Center, Seoul (Korea, Republic of)

    2009-06-15

    We review here 3 cases of primary thyroid lymphoma that we experienced during the past 5 years (age range: 39-55, all of the patients were female). The clinical and various ultrasonographic characteristics together with the other imaging modalities of primary thyroid lymphomas are described. The clinical features at presentation for one patient were a goiter with rapid growth and this was accompanied by compressive symptoms. The tumors of the other 2 patients were incidentally found during screening thyroid ultrasound exams. The pathologic studies of 2 cases showed a diffuse B-cell lymphoma with associated Hashimoto's thyroiditis and one case was a B-cell lymphoma of the MALT type. An extra-thyroid extension was shown in one case. The treatments included surgery alone for two cases, and chemotherapy and radiation therapy for one case. A US exam of thyroid lymphoma can show various morphological features, and US-CNB is helpful for diagnosing thyroid lymphoma.

  11. Targeting Tumour Vasculature as a Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Christopher A. Honstvet

    2007-01-01

    Full Text Available Modelling blood flow and capillary growth in tumours has been the focus of several research groups with the aim of generating theoretical models that can be used to predict biological behaviour within these systems. Since dysfunctional angiogenesis is seen in a wide range of pathological conditions ranging from cardiovascular, to arthritis, to diabetes, it is easy to see how these models may have a far-reaching influence on future therapeutic strategies.

  12. Haemorrhagic pituitary tumours

    International Nuclear Information System (INIS)

    Lazaro, C.M.; Philippine General Hospital, Manila; Guo, W.Y.; Sami, M.; Hindmarsch, T.; Ericson, K.; Hulting, A.L.; Wersaell, J.

    1994-01-01

    In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI. (orig.)

  13. Tumours following retinoblastoma radiotherapy

    International Nuclear Information System (INIS)

    Mollot, J.-P.

    1978-01-01

    Radioinduced tumours in young patients irradiated in childhood for retinoblastoma take on a particularly deadly aspect. The onset of this true clinical entity characterized by a long post-irradiation latency period induced by a dose above 6000 rads is a real tragedy. The vast majority of patients then enter into a long martyrdom ending in death. The only cure is surgical, but seldom possible. Treatment is limited to palliative radiotherapy, effective for a while, and chemiotherapy as a last resort but often difficult to prescribe. Prevention alone is the answer. The quality and reliability of the radiotherapeutic treatment depend not only on the personal talent of the radiotherapist but above all on the standard of the equipment. A strong reduction in the doses employed as well as recent technological progress improving the material, its precision and reproducibility appear already to have lowered the frequency curve of these fatal radioinduced tumours [fr

  14. Skull base tumours

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil, Servico de Radiologia, Rua Professor Lima Basto, 1093 Lisboa Codex (Portugal)], E-mail: borgesalexandra@clix.pt

    2008-06-15

    With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base.

  15. Skull base tumours

    International Nuclear Information System (INIS)

    Borges, Alexandra

    2008-01-01

    With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base

  16. Malignant salivary gland tumours

    International Nuclear Information System (INIS)

    Thompson, S.H.

    1982-01-01

    The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy

  17. Malignant salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, S.H. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Oral Pathology)

    1982-08-01

    The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy.

  18. Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

    Science.gov (United States)

    Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

    2004-09-09

    OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.

  19. Imaging brain tumour microstructure.

    Science.gov (United States)

    Nilsson, Markus; Englund, Elisabet; Szczepankiewicz, Filip; van Westen, Danielle; Sundgren, Pia C

    2018-05-08

    Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging. Copyright © 2018. Published by Elsevier Inc.

  20. [Adrenal tumours in childhood].

    Science.gov (United States)

    Martos-Moreno, G A; Pozo-Román, J; Argente, J

    2013-09-01

    This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  1. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-Term ...

  2. Nasosinusal Lymphoma of T Natural Killer Cells: Case Report

    Directory of Open Access Journals (Sweden)

    Castro, Victor Labres da Silva

    2011-01-01

    Full Text Available Introduction: The primary nasal lymphoma is an uncommon extranodal tumor and represents 0.44% of all Extranodal lymphomas in this region. The primary nasal lymphoma derives from the T-lineage in nearly 75% of the cases. Objective: To describe a case of nasosinusal lymphoma of T Natural Killer cells, attended in the Clinical Hospital of the Federal University of Goiás. Case Report: 48-year-old female patient with diffuse tumefaction in the left hemiface of firm-elastic consistency and painful upon digital compression. Face sinuses tomography identified a total maxillary veiling to the left and some posterior ethmoidal cells. With the diagnostic hypothesis of a tumor affection, we opted for the surgical removal via a transmaxillary approach and the material was sent for biopsy. The histopathological exam diagnosed a highly necrotic tumor of angiocentric pattern, polymorphic and atypical lymphoid population (T /NK Lymphoma; with the prognosis, the patient was submitted to chemical therapy with total regression of the facial edema. Final Comments: The otorhinolaryngologist must be attentive as regards the existence of lymphomas among the nasosinusal diseases, because the early diagnosis improves the survival as it prevents metastases, growth and local destruction.

  3. The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.

    Science.gov (United States)

    Han, Zhi-Yan; Richer, Wilfrid; Fréneaux, Paul; Chauvin, Céline; Lucchesi, Carlo; Guillemot, Delphine; Grison, Camille; Lequin, Delphine; Pierron, Gaelle; Masliah-Planchon, Julien; Nicolas, André; Ranchère-Vince, Dominique; Varlet, Pascale; Puget, Stéphanie; Janoueix-Lerosey, Isabelle; Ayrault, Olivier; Surdez, Didier; Delattre, Olivier; Bourdeaut, Franck

    2016-01-28

    Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin.

  4. Langerhans cell sarcoma following marginal zone lymphoma: expanding the knowledge on mature B cell plasticity.

    Science.gov (United States)

    Ambrosio, Maria Raffaella; De Falco, Giulia; Rocca, Bruno Jim; Barone, Aurora; Amato, Teresa; Bellan, Cristiana; Lazzi, Stefano; Leoncini, Lorenzo

    2015-10-01

    The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.

  5. Radiolabelled aptamers for tumour imaging and therapy

    International Nuclear Information System (INIS)

    Perkins, A.C.; Missailidis, S.

    2005-01-01

    Full text: The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers. The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by normal glandular epithelial cells, however this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers. Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer. The aptamer selection process was performed on affinity chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expressing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes

  6. Multimodality imaging of cardiothoracic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Brett W., E-mail: bcarter2@mdanderson.org [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Wu, Carol C. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Khorashadi, Leila [Department of Radiology, Mount Auburn Hospital, Cambridge, MA 02138 (United States); Godoy, Myrna C.B.; Groot, Patricia M. de [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Abbott, Gerald F. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Lichtenberger III, John P. [Department of Radiology, David Grant Medical Center, Travis AFB, CA 94535 (United States)

    2014-08-15

    Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and {sup 18}F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response.

  7. PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

    Science.gov (United States)

    Hung, Yin P; Lee, John P; Bellizzi, Andrew M; Hornick, Jason L

    2017-11-01

    Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases. © 2017 John Wiley & Sons Ltd.

  8. Abdominal Burkitt lymphoma

    International Nuclear Information System (INIS)

    Alvarez, Romina J.; Villavicencio, Roberto L.; Oxilia, Hector G.

    2004-01-01

    Purpose: As scarce information is available, in this research we have tried to describe the imaging findings of the Burkitt's lymphoma. Retrospective analysis of the clinical and imaging presentation of a 4 years old boy, is given. Biopsy confirmed the BL. Different imaging techniques were combined. The X-rays were negative. The US revealed a moderate hepatomegaly with multiple hypoechoic nodules and free fluid in the abdominal cavity. The CT showed the hepatomegaly as well as solid nodules in great number and different sizes(due to the densitometric behaviour and to post contrast enhancement), a scarce amount of ascites and a density increase of the mesentery fat. The MRI characterized and revealed in detail the US and the CT findings. The Burkitt's lymphoma is a rare entity; several methods are needed to approach the diagnosis. It represents a great clinical and imaging challenge. (author)

  9. Malignant lymphomas of the stomach

    International Nuclear Information System (INIS)

    Drgona, L.

    2011-01-01

    Primary gastric lymphomas are the most common extra nodal lymphomas. They can be presented as aggressive or indolent, majority of indolent lymphomas are associated to H. pylori infection. The basic diagnostic procedures are endoscopy, endo sonography and biopsy of gastric tissue. Therapy is related to the histological subtype, stage, H. pylori positivity, clinical symptoms and condition of patient. The aim of the treatment is remission as well as good quality of life. The prognosis of patients with primary gastric lymphomas is relatively good. (author)

  10. Vaginal haemangioendothelioma: an unusual tumour.

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

    Vaginal tumours are uncommon and this is a particularly rare case of a vaginal haemangioendothelioma in a 38-year-old woman. Initial presentation consisted of symptoms similar to uterovaginal prolapse with "something coming down". Examination under anaesthesia demonstrated a necrotic anterior vaginal wall tumour. Histology of the lesion revealed a haemangioendothelioma which had some features of haemangiopericytoma. While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma. Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our "knowledge bank" to guide management of these unusual tumours.

  11. Pathology of spontaneous tumour lesions in pullets and adult chickens in commercial farms - Short communication.

    Science.gov (United States)

    Ikezawa, Mitsutaka; Sasaki, Jun; Goryo, Masanobu

    2012-09-01

    Twenty pullets and adult chickens, aged 100 to 403 days, from several commercial chicken farms were examined by gross and histopathology. Grossly, all chickens had white-greyish masses in the visceral organs with or without enlargement of the peripheral nerves. Histopathological examination revealed Marek's disease (MD) lymphoma, lymphoid leukosis (LL) and myeloid leukosis (ML) in 14/20, 5/20 and 1/20 of the chickens, respectively. Lesions of the sciatic nerves in chickens diagnosed as having MD lymphoma were various. No neoplastic and/or inflammatory cells were noted in the peripheral nerves of chickens diagnosed as having LL and ML. These results indicated that MD lymphoma could also develop in older chickens; thus, microscopic examination is needed to identify MD in older chickens showing lymphocyte-derived tumours.

  12. Primary bone tumours in infants

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Cohen, D.H.; Padovani, J.; Tamaela, L.; Azouz, M.; Bale, P.; Martin, H.C.; Nayanar, V.V.; Arico, M.

    1985-09-01

    Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomastosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the auhtors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

  13. Radiological diagnosis of liver tumours

    International Nuclear Information System (INIS)

    Lundstedt, C.

    1987-01-01

    Sixty patients treated with an intra-arterial cytostatic drug for metastases from colo-rectal carcinoma were evaluated with angiography to determine prognostic parameters. The extent of tumour in the liver and an unchanged or diminished tumour volume following treatment, as demonstrated with angiography, were associated with significant prolongation of survival. Patients who developed occlusion of the hepatic artery or of branches of the portal vein, also survived longer. 189 patients examined with angiography, 161 with computed tomography (CT), 95 with computed tomographic arteriography (CTA) and 71 with ultrasound (US) were subjected to liver evaluation at laparotomy consisting of inspection and palpation. The result of this surgical liver evaluation was for the purpose of the study regarded as completely accurate and was used to assess the accuracy of the different radiological methods. The location of tumour in the liver lobes or segments was analysed, with a separate evaluation of the right and left liver lobes. The rate of detection of individual tumour nodules was also determined. Angiography detected 55% of liver areas affected by tumour and 47% of individual tumour nodules. CT detected 83% of liver lobes or segments containing tumour, and 70% of the tumour nodules. US detected 69% of the portions of liver holding tumour, and also 69% of the tumour nodules. CTA detected 85% of tumours areas and 74% of separate tumour nodules. Some lesions detected with CT were not seen with CTA and vice versa. More false-positive results were recorded with CTA than with CT using intravenous contrast enhancement. (orig.)

  14. Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours

    International Nuclear Information System (INIS)

    Barrande, G.; Kujas, M.; Gancel, A.; Turpin, G.; Bruckert, E.; Kuhn, J.M.; Luton, J.P.

    1995-01-01

    Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab

  15. Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas.

    Science.gov (United States)

    Zucca, Emanuele; Bertoni, Francesco; Vannata, Barbara; Cavalli, Franco

    2014-10-15

    Extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The most frequently affected organ is the stomach, where MALT lymphoma is incontrovertibly associated with a chronic gastritis induced by a microbial pathogen, Helicobacter pylori. Gastric MALT lymphoma therefore represents a paradigm for evaluating inflammation-associated lymphomagenesis, which may lead to a deeper understanding of a possible etiologic association between other microorganisms and nongastric marginal zone lymphomas. Besides infectious etiology, chronic inflammation caused by autoimmune diseases, such as Sjögren syndrome or Hashimoto thyroiditis, can also carry a significant risk factor for the development of marginal zone lymphoma. In addition to the continuous antigenic drive, additional oncogenic events play a relevant role in lymphoma growth and progression to the point at which the lymphoproliferative process may eventually become independent of antigenic stimulation. Recent studies on MALT lymphomas have in fact demonstrated genetic alterations affecting the NF-κB) pathway, a major signaling pathway involved in many cancers. This review aims to present marginal zone lymphoma as an example of the close pathogenetic link between chronic inflammation and tumor development, with particular attention to the role of infectious agents and the integration of these observations into everyday clinical practice. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma." ©2014 American Association for Cancer Research.

  16. Askin Tumour: Case Report

    International Nuclear Information System (INIS)

    Gomez, Carolina; Ramirez, Sandra Milena; Quesada, Diana Constanza; Unigarro Luz Adriana

    2011-01-01

    In this article we report a case of a 19 year-old woman with a final diagnosis of an extra skeletal Primitive Neuroectodermal Tumor/Ewing sarcoma of the chest, also known as Askin tumour. The histologic features and the immunohistochemical profile were consistent with this aggressive malignancy of the chest wall that affects young people. Because the low incidence of this entity, as well as the clear radiological findings, we considered it interesting to describe this documented case and undertake a review of the literature.

  17. Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

    Science.gov (United States)

    Anniko, M; Ritzén, E M

    1986-01-01

    True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

  18. Prognosticating and pharmacological prophylaxis of radiogenic malignant tumours

    International Nuclear Information System (INIS)

    Muksinova, K.N.; Kirillova, E.N.; Rabinovich, E.I.; Mushkacheva, G.S.; Revina, E.S.; Lemberg, V.K.

    1996-01-01

    Cancerogenic effect risks due to ionizing radiation, that impacted on large population groups because of Chernobyl and other accidents, cause the actuality of early diagnosis problems and of radiogenic tumour prevention. Since canceroembryonic antigen and α-fetoprotein had been found, the tumour markers began to be frequently used by oncologists. However, attempt to use onco-markers, as test for earlier pre-clinic determination, have been unsuccessful. The secondary messengers of hormonal signal, cyclic nucleotides, that take the leading place in system of organism self-regulation, had attracted our attention. As known, the increase of cell division number and suppression of morphological and biochemical developments of differentiation are the fundamental characteristics of tumour growth and are proceeding together with participating of cyclic nucleotide system. The including of both nucleotides in neoplastic transformation and at the same time their constant presence in extracellular fluid (blood serum, urine) makes the perspective use of these compounds as indicators of tumour growth before the appearance of clinic signs of diseases. This coincides with the modern viewpoints on the developments of optimum programs for pre-clinic diagnosing of tumours, that needs to base on the change in homeostasis preceded the malignant tumour development. (author)

  19. Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Chronic Lymphocytic Leukemia; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  20. Primary cutaneous lymphoma

    International Nuclear Information System (INIS)

    Nguyen, M. Connie; Cleary, Sean F.; Hoppe, Richard T.

    1995-01-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  1. Primary cutaneous lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, M Connie; Cleary, Sean F; Hoppe, Richard T

    1995-07-01

    Purpose: A retrospective review analyzed the survival and freedom from relapse of patients with stage IE or IIE primary cutaneous lymphoma (non mycosis fungoides) after treatments with radiation therapy alone (XRT), chemotherapy alone (RX) or combined modality therapy (CMT). Methods and Materials: Fifty two patients with stage IE-IIE cutaneous lymphoma treated at Stanford University Hospital were reviewed. The median age was 57, with a range of 26 to 94 and a male to female ratio of 1.21:1. Patients were staged according to the Ann Arbor System. Pathology was classified according to the Working Formulation. Treatment outcomes were compared using Kaplan-Meier survival curves with a Gehan p-value test. Results: The follow up range was 6 months to 22 years (median 7 years.) Twenty one percent of patients had low grade, 63% had intermediate grade and 15% had high grade lymphoma. The most common histologic subtype was diffuse large cell lymphoma Thirty two patients received radiation alone as initial treatment and sixteen patients received combined modality as initial treatment. Four patients received chemotherapy alone. The only significant prognostic factor for survival was the stage at diagnosis. Patients with stage IE disease had a longer actuarial survival (5-yr=79%, 10-yr=71%), as compared to those with stage IIE (5-yr=49%, 10-yr=33%), (p=0.029). The only significant prognostic factor for freedom from relapse was the initial treatment. Initial combined modality treatment lead to a longer freedom from relapse compared to patients treated with radiation alone (p=0.002), (median 5 years vs. 1.2 years). Despite this, the actuarial overall survival in the combined modality group and the radiation alone group are similar (median survival 7.7 and 8 years). The efficacy of either radiation or chemotherapy as salvage treatment after radiation failure was equivalent and both salvage treatments lead to equally long survival and freedom from second relapse. Conclusion

  2. President's categorical course on lymphoma

    International Nuclear Information System (INIS)

    Hoppe, Richard T.

    1997-01-01

    Improvements in the classification, staging, and treatment of the lymphomas, complemented by an improved understanding of the biology of these diseases, has led to an improved outcome of therapy for both Hodgkin's disease and many of the non-Hodgkin's lymphomas. The rapid changes that have occurred in this field in the last decade make it timely to review this subject for radiation oncologists in a comprehensive fashion. This course is designed to meet broad educational needs required for understanding these diseases and providing effective care for patients with lymphoma. The faculty includes many leaders from both laboratory and clinical disciplines dealing with lymphomas, who will address a variety of scientific and clinical topics. The morning session will be devoted to Hodgkin's disease, including new concepts in its biology, a review of clinical trials for early stage disease, a discussion of the role of high dose therapy, and description of long term complications of treatment. The afternoon sessions will be devoted to the non-Hodgkin's lymphomas, including new concepts in pathology and biology, a description of specific entities including the low grade lymphomas, MALT lymphomas, extranodal lymphomas, intermediate grade lymphomas, mantle cell lymphomas, and summary discussions of the role of radioimmuno-therapy and high dose therapy. Although the role of radiation therapy in the management of patients with lymphoma has changed dramatically in the past two decades, radiation remains the most effective single agent for the treatment of these diseases and it is especially important for radiation onologists to keep abreast of these new concepts. This course has been designed to achieve that goal

  3. Spatio-temporal cell dynamics in tumour spheroid irradiation

    International Nuclear Information System (INIS)

    Kempf, H.; Bleicher, M.; Meyer-Hermann, M.; Kempf, H.; Bleicher, M.; Kempf, H.; Meyer-Hermann, M.

    2010-01-01

    Multicellular tumour spheroids are realistic in vitro systems in radiation research that integrate cell-cell interaction and cell cycle control by factors in the medium. The dynamic reaction inside a tumour spheroid triggered by radiation is not well understood. Of special interest is the amount of cell cycle synchronization which could be triggered by irradiation, since this would allow follow-up irradiations to exploit the increased sensitivity of certain cell cycle phases. In order to investigate these questions we need to support irradiation experiments with mathematical models. In this article a new model is introduced combining the dynamics of tumour growth and irradiation treatments. The tumour spheroid growth is modelled using an agent-based Delaunay/Voronoi hybrid model in which the cells are represented by weighted dynamic vertices. Cell properties like full cell cycle dynamics are included. In order to be able to distinguish between different cell reactions in response to irradiation quality we introduce a probabilistic model for damage dynamics. The overall cell survival from this model is in agreement with predictions from the linear-quadratic model. Our model can describe the growth of avascular tumour spheroids in agreement to experimental results. Using the probabilistic model for irradiation damage dynamics the classic 'four Rs' of radiotherapy can be studied in silico. We found a pronounced reactivation of the tumour spheroid in response to irradiation. A majority of the surviving cells is synchronized in their cell cycle progression after irradiation. The cell synchronization could be actively triggered and should be exploited in an advanced fractionation scheme. Thus it has been demonstrated that our model could be used to understand the dynamics of tumour growth after irradiation and to propose optimized fractionation schemes in cooperation with experimental investigations. (authors)

  4. Transformation of marginal zone lymphoma (and association with other lymphomas).

    Science.gov (United States)

    Casulo, Carla; Friedberg, Jonathan

    Marginal zone lymphomas (MZL) are a diverse group of indolent lymphoproliferative disorders that comprise three subtypes: nodal, splenic and mucosal associated marginal zone lymphomas (MALT). Histologic transformation (HT) to an aggressive lymphoma is a rare event that can occur in any subtype, and at lower frequency compared to other indolent non Hodgkin lymphomas (NHL) like follicular lymphoma. There are few data directly associated with risk and prognosis of transformation in MZL. However, recent advances in the understanding of molecular and genetic features of MALT have contributed to an evolving appreciation of HT in this disease. Optimal treatment of HT of MZL remains unknown. Much of the approach to managing transformed MZL is extrapolated from other indolent NHLs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Gastric neuroendocrine tumours.

    Science.gov (United States)

    Crosby, David A; Donohoe, Claire L; Fitzgerald, Louise; Muldoon, Cian; Hayes, Brian; O'Toole, Dermot; Reynolds, John V

    2012-01-01

    Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment. Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs. Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted. Copyright © 2012 S. Karger AG, Basel.

  6. Radiotherapy in ocular tumours

    International Nuclear Information System (INIS)

    Pinto, J.M.

    1982-01-01

    Ocular tumours at the Tata Memorial Hospital, Bombay, form about 0.14% of all the proved cancer cases. In case of unilateral retinoblastoma with the other eye being not non-seeing for any reason, enucleation is advised, as the diagnosis may sometimes be in doubt. If after enucleation, optic nerve and/or peribulbar tissues are found to be involved, post-operative irradiation is given to the whole orbit. In bilateral retinoblastoma the more affected eye is enucleated and an attempt is made to preserve vision in the other eye. A tumour dose of 3500 to 4000 rad in about 4 weeks is given with a cobalt beam using a direct anterior field. A cataract that may develop has to be taken care of. Lateral and/or medial fields are used with deep X-rays. In certain cases, an implant of cobalt-60 or gold-198 grain is done. For carcinoma of conjuctiva, small lesions or early lesions are excised and a beta radiation dose of 2000 rad weekly for about 4 to 5 weeks is given; larger lesions require enucleation or exenteration followed by irradiation with super-voltage radiation. Post-irradiation sarcomas may develop many years later. Irradiation is repeated for recurrences. (M.G.B.)

  7. Is cell survival a determinant of the in situ response of 9L tumours

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Wallen, C.A.

    1980-01-01

    The influence of growth rate, location, size and potential lethal damage (PLD) recovery on the cellular radiosensitivity and the tumour response was studied in 9L/Ro and 9L/SF rat tumours. The median day of death of rats bearing the intracerebral (i.c.) 9L/Ro tumours was 16-18 days; for i.c. 9L/SF tumours it was 23-25 days. The doubling time of 9L/Ro cells was slightly faster than for 9L/SF cells both in culture and in the brain. The cellular radiosensitivity of both i.c. tumour cell sublines was identical. However, subcutaneous (s.c.) 9L/Ro tumour cells were more resistant. There was no evidence of a substantial hypoxic fraction in either site. When i.c. 9L/Ro and 9L/SF tumours of similar size were treated with fractionated doses of BCNU, X-rays or combinations of the two, the responses of the two tumours were essentially identical. The rate of recovery from radiation-induced PLD was identical in the two sublines and the two sites. Increase in life-span of rats bearing i.c. 9L/Ro tumours appeared to be correlated with the tumour cell kill measured after completion of PLD recovery rather than with the tumour cell kill determined immediately after irradiation. (author)

  8. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade.

    Science.gov (United States)

    Ouzounova, Maria; Lee, Eunmi; Piranlioglu, Raziye; El Andaloussi, Abdeljabar; Kolhe, Ravindra; Demirci, Mehmet F; Marasco, Daniela; Asm, Iskander; Chadli, Ahmed; Hassan, Khaled A; Thangaraju, Muthusamy; Zhou, Gang; Arbab, Ali S; Cowell, John K; Korkaya, Hasan

    2017-04-06

    It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced 'metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.

  9. Immune Dysfunction and the Pathogenesis of AIDS-associated non-Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Martínez-Maza Otoniel

    1998-01-01

    Full Text Available Much has been learned about how HIV-induced immune dysfunction contributes to B cell hyperactivation, and potentially, to the pathogenesis of AIDS-lymphoma. However, further studies are needed to fully understand how HIV infection and immune dysfunction promote B cell hyperactivation and the development/growth of AIDS-lymphoma. In particular, studies are needed to define the role of HHV8 vIL6, IL6 receptor-expression, and lymphocyte surface stimulatory molecules, in promoting B cell hyperactivation or lymphoma cell growth.

  10. Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Ludvigsen, Maja; Bendix, Knud

    2016-01-01

    . Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. A tissue microarray, containing diagnostic HIV-lymphoma tissue samples (N = 40), was used to investigate immunohistochemical expression of markers in tumoural lesions. RESULTS: Fourteen differentially expressed...... protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (P ... with subsequent lymphoma compared with patients without subsequent lymphoma. In the tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). CONCLUSION: We identified several differentially expressed protein spots present already...

  11. MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

    Science.gov (United States)

    2014-05-22

    Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  12. Hodgkin's Lymphoma of the Breast

    African Journals Online (AJOL)

    TNHJOURNALPH

    RESULT. A tissue diagnosis of Hodgkin's lymphoma with typical ... It was the first cancer to be cured ... ultrasonography showed enlarged liver. The .... McMillan A, Horning S. Non-Hodgkins lymphoma of the Breast. Cancer. 2007;110:25-30. 5.

  13. Tyrosine phosphorylation in human lymphomas

    NARCIS (Netherlands)

    Haralambieva, E; Jones, M.; Roncador, GM; Cerroni, L; Lamant, L; Ott, G; Rosenwald, A; Sherman, C; Thorner, P; Kusec, R; Wood, KM; Campo, E; Falini, B; Ramsay, A; Marafioti, T; Stein, H; Kluin, PM; Pulford, K; Mason, DY

    2002-01-01

    In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated

  14. Lymphoma risk in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence

    2014-01-01

    OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated...

  15. Plasmacytoid lymphoma within a left atrial myxoma: a rare coincidental dual pathology.

    Science.gov (United States)

    White, Ralph W; Hirst, Natalie A; Edward, Sara; Nair, Unnikrishnan R

    2010-01-01

    Primary malignant cardiac neoplasms are extremely rare. The occurrence of a malignant lymphoid tumour within a left atrial myxoma is highly atypical, with only one such case previously reported. Here, we describe a patient who presented with symptoms and signs of a left atrial myxoma. Subsequent specimen histology demonstrated the presence of lymphoma within the myxoma. We discuss the importance of histological diagnosis in order to best direct treatment and prognosis of such cases.

  16. Lymphoma imaging with a new technetium-99m labelled antibody, LL2

    International Nuclear Information System (INIS)

    Murthy, S.; Sharkey, R.M.; Goldenberg, D.M.; Lee, R.E.; Pinsky, C.M.; Hansen, H.J.; Burger, K.; Swayne, L.C.

    1992-01-01

    The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with ∝925 MBq (25 mCi) of 99m Tc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99m Tc-LL2 study. However, these initial results suggest that this new 99m Tc-labelled antibody imaging kit should be further investigated for its potential role in the staging and follow-up of lymphoma patients. (orig.)

  17. Beneficial Effect of Fluoxetine and Sertraline on Chronic Stress-Induced Tumor Growth and Cell Dissemination in a Mouse Model of Lymphoma: Crucial Role of Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    María Emilia Di Rosso

    2018-06-01

    Full Text Available Clinical data and experimental studies have suggested a relationship between psychosocial factors and cancer prognosis. Both, stress effects on the immune system and on tumor biology were analyzed independently. However, there are few studies regarding the stress influence on the interplay between the immune system and tumor biology. Moreover, antidepressants have been used in patients with cancer to alleviate mood disorders. Nevertheless, there is contradictory evidence about their action on cancer prognosis. In this context, we investigated the effect of chronic stress on tumor progression taking into account both its influence on the immune system and on tumor biology. Furthermore, we analyzed the action of selective serotonin reuptake inhibitors, fluoxetine and sertraline, in these effects. For this purpose, C57BL/6J mice submitted or not to a chronic stress model and treated or not with fluoxetine or sertraline were subcutaneously inoculated with EL4 cells to develop solid tumors. Our results indicated that chronic stress leads to an increase in both tumor growth and tumor cell dissemination. The analysis of cell cycle regulatory proteins showed that stress induced an increase in the mRNA levels of cyclins A2, D1, and D3 and a decrease in mRNA levels of cell cycle inhibitors p15, p16, p21, p27, stimulating cell cycle progression. Moreover, an augment of mRNA levels of metalloproteases (MMP-2 and MMP-9, a decrease of inhibitors of metalloproteases mRNA levels (TIMP 1, 2, and 3, and an increase in migration ability were found in tumors from stressed animals. In addition, a significant decrease of antitumor immune response in animals under stress was found. Adoptive lymphoid cell transfer experiments indicated that the reduced immune response in stressed animals influenced both the tumor growth and the metastatic capacity of tumor cells. Finally, we found an important beneficious effect of fluoxetine or sertraline treatment on cancer

  18. Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.

    Science.gov (United States)

    Kaneko, Hitomi; Hori, Toshiyuki; Yanagita, Soshi; Kadowaki, Norimitsu; Uchiyama, Takashi

    2005-03-01

    OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice. Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared. While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4. The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.

  19. Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

  20. Carcinoid Tumour of the Ovary

    African Journals Online (AJOL)

    Abstract. A case of bilateral carcinoid tumour of the ovary, with benign cystic teratoma in one ovary, in a 38 year old woman is presented. She had total abdominal hysterectomy, bilateral salpingoophorectomy, infracolic omentectomy and appendectomy. There was no macroscopic tumour in the vermiform appendix and the ...

  1. Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2013-12-13

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  2. [Neonatal tumours and congenital malformations].

    Science.gov (United States)

    Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

    2008-06-01

    The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

  3. Adapting radiotherapy to hypoxic tumours

    Science.gov (United States)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  4. Adapting radiotherapy to hypoxic tumours

    International Nuclear Information System (INIS)

    Malinen, Eirik; Soevik, Aste; Hristov, Dimitre; Bruland, Oeyvind S; Olsen, Dag Rune

    2006-01-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO 2 -related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO 2 -related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO 2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO 2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure

  5. FDG-PET in lymphomas

    International Nuclear Information System (INIS)

    Knapp, W. H.

    2009-01-01

    Lymphomas are a heterogeneous group of neoplasms in which two major subtypes are distinguished, Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The incidence of lymphomas is about 20 per 100000 inhabitants (Jemal et al 2002) and 7-8 times higher than that of HD. Since NHL has a worse prognosis, the death rates of NHL are 14 times higher than those for HD. Lymphomas account for about 4 % of all cancer incidences. In USA, lymphomas are the fifth most frequent cancer type diagnosed and the third most frequent form of cancer death (Jemal et al 2002). Concerning HD, there is a preponderance for males with a gender ratio of 1.33 for incidence and 1.12 for mortality. For NHL incidences and mortality rates of genders are almost equal. HL comprises different subtypes among which nodular sclerosis is the most frequent one (60-70 %). Other histopathologic subtypes are those of mixed cellularity, lymphocyte reach and lymphocyte depleted characteristics. The most frequent subgroup of NHL are B-cell lymphomas (80-90 % of all NHL). Two thirds of this subgroup are diffuse large B-cell lymphomas, one third follicular lymphomas. Other (less frequent) subtypes are mantle cell, peripheral T-cell, anaplastic large-cell-lymphomas etc. For NHL increasing incidence has been observed in the last decades. Within 15 years the incidence increased by 50 % in the USA (Jemal et al 2002). Etiology of lymphomas is still unknown. In a certain proportion of NHL viral causes are assumed. Diagnosis is based on histology (needle biopsy) with consecutive sub typing. Prognosis depends on stage, expansion state, histology and proliferation rates. (author)

  6. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    International Nuclear Information System (INIS)

    Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

    2008-01-01

    High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically

  7. Psoriasis and risk of malignant lymphoma

    DEFF Research Database (Denmark)

    Kamstrup, M R; Skov, L; Zachariae, C

    2018-01-01

    In patients with psoriasis, the risk of lymphoma has been a subject of controversy and data from larger studies are limited1-4 . We therefore investigated the 5-year risk of new-onset Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) (excluding cutaneous T-cell lymphoma [CTCL]), and CTCL...

  8. Improving tumour response

    International Nuclear Information System (INIS)

    Bentzen, S.

    2003-01-01

    Radiation oncology is in the middle of the most exciting developments in its 100-year history. Progress in treatment planning and delivery, in medical imaging and in basic cancer and normal tissue biology is likely to change the indication for radiotherapy as well as the way it is prescribed and delivered. Technological and conceptual advances, in particular the development of the multi-leaf collimator and the concept of inverse treatment planning, have led to the introduction of intensity modulated radiation therapy (IMRT) with its capability to plan and deliver non-uniform dose distributions in the clinic. This has forced us to re-think radiation oncology: refining the indication for radiotherapy, optimizing the prescription of dose distributions and considering how, based on clinical evidence, radiation can best be combined with other treatment modalities, surgery, cytotoxic chemotherapy and biologically targeted therapies. The attraction of radiation therapy as an element of multi-modality cancer therapy is that it induces DNA damage that can be modulated in space and time. Progress in basic cancer biology, genomics and proteomics, as well as biological imaging provides novel avenues for individualization of cancer therapy and for biological optimization of radiotherapy. In improving cancer care, it is the therapeutic ratio, rather than tumour control per se, that must be optimised. Interestingly, the two main avenues for improving the effectiveness of radiotherapy currently being actively pursued in the clinic generally aim at different sides of the therapeutic ratio: 3D conformal radiotherapy and IMRT predominantly aim to reduce normal-tissue side effects - and by doing this, open the way for dose escalation that may lead to increased tumour control rates - whereas combined radio-chemotherapy aims to improve tumour response - while keeping the fingers crossed that this will not increase normal-tissue complications to the same extent. In parallel with these

  9. Primary intracranial malignant lymphoma

    International Nuclear Information System (INIS)

    Matsumoto, Mikiro; Ohtsuka, Takatsugu; Kuroki, Takao; Shibata, Iekado; Terao, Hideo; Kudo, Motoshige

    1988-01-01

    Nine cases of primary intracranial malignant lymphoma, which accounts for 3.3 % of all intracranial tumors seen in the authors' institution, were studied in terms of diagnostic computed tomographic (CT) features, the tumors' histologic appearance, treatment, post-treatment blood immunologic and cerebrospinal fluid (CSF) characteristics, and outcome. The patients were seven males and two females aged 42 to 67 years. Their chief signs and symptoms on admission were intracranial hypertension, focal signs, and disturbance of consciousness. CT, which proved the most useful preoperative diagnostic technique, demonstrated multiple lesions in seven cases and, in all cases, regions of isodensity or slight high density that were enhanced by contrast medium. According to the patterns of enhancement, the tumors were classed as diffuse (three cases) or nodular (six cases). The former is considered typical of malignant lymphoma, whereas the latter type was sometimes indistinguishable from metastatic tumor and meningioma. At surgery, one patient underwent radical tumor excision, two partial removal, and six biopsy only. Histologic examination revealed one tumor to be of the diffuse small cell type, three of the medium cell type, and five of the large cell type (Lymphoma Study Group classification). Of seven tumors in which lymphocytes were examined by peroxidase-antiperoxidase staining, four were of the B cell type. Postoperatively, whole brain irradiation with 29 to 46 Gy was followed by local irradiation with 15 to 50 Gy. If the tumor persisted, one of three chemotherapies was administered. In one case, methotrexate was given intrathecally. Seven patients were divided into two groups: long remission (three) and recurrence (four). These two groups were compared in terms of serum immunoglobulin levels, T and B cell ratios, CSF characteristics, CT features, tumor cell type, and treatment. No clear differences were found. (author)

  10. Differential diagnosis of extra-axial intracranial tumours by dynamic spin-echo MRI

    International Nuclear Information System (INIS)

    Joo, Y.G.; Korogi, Y.; Hirai, T.; Sakamoto, Y.; Sumi, M.; Takahashi, M.; Ushio, Y.

    1995-01-01

    Dynamic MRI was performed on 22 patients with extra-axial intracranial tumours. Serial images were obtained every 30 s for 3 min using a spin-echo sequence (TR 200, TE 15 ms) after rapid injection of Gd-DTPA, 0.1 mmol/kg body weight. The contrast medium enhancement ratio (CER) was correlated with the histology of the tumours. Meningiomas and extra-axial metastases showed a sharp rise, then a gradual decline. Although both had a definite early peak of CER, metastases showed a more rapid decline. Neuromas and extra-axial lymphoma showed a slow, steady increase with no peak within 180 s. This study indicates that the CER is helpful in the differentiation of extra-axial tumours. (orig.)

  11. Region of the eye. Strategy for the management of malignant tumours of the orbit

    International Nuclear Information System (INIS)

    Freeman, J.E.

    1984-01-01

    The strategy for the management of the various malignant tumours of the orbit was tabulated and also illustrated in diagrams. Table 1. Strategy for retinoblastoma; Table 2. Strategy for malignant melanoma: (a) intra-ocular, (b) epibulbar; Table 3. Strategy for squamous cell carcinoma: (a) conjunctival, (b) palpebral; Table 4. Strategy for basal cell carcinoma: (a) palpebral, (b) intra-orbital; Table 5. Strategy for rhabdomyosarcoma (and embryoma) of the orbit; Table 6. Strategy for lymphosarcoma of the orbit; Table 7. Strategy for other tumours of the orbit or adnexa: (A) hystiocytosis X, (B) adenocarcinoma of the lachrymal gland, (C) optic nerve glioma, (D) para-nasal sinus tumours involving orbit; Table 8. Strategy for systemic or metastatic disease involving the orbit or contents: (a) intra-ocular [(i) leukaemia, (ii) carcinoma of the breast or of the bronchus], (b) orbital or peri-orbital [(i) leukaemia, (ii) neuroblastoma, (iii) histiocytosis X, (iv) lymphoma

  12. Sarcoidosis-lymphoma syndrome.

    Science.gov (United States)

    Brandy-García, Anahy M; Caminal-Montero, Luis; Fernández-García, María Soledad; Saiz Ayala, Angel; Cabezas-Rodríguez, Ivan; Morante-Bolado, Isla

    A 65 year-old female with a history of sarcoidosis with pulmonary and joint involvement, who after 5 years of diagnosis begins with central nervous system involvement manifesting as diplopia. She presents normal analysis results. In imaging results, a mass is identified in the right intraconal space; it depends of right optic nerve, and shows multiple lymph node involvement. Biopsy was performed diagnosed with large B-cell lymphoma, an atypical form of tumor associated with sarcoidosis. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  13. Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Warissara Rongthong

    2017-05-01

    Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

  14. Curcuma Contra Cancer? Curcumin and Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Stefanie Kewitz

    2013-01-01

    Full Text Available Curcumin, a phytochemical isolated from curcuma plants which are used as coloring ingredient for the preparation of curry powder, has several activities which suggest that it might be an interesting drug for the treatment or prevention of cancer. Curcumin targets different pathways which are involved in the malignant phenotype of tumor cells, including the nuclear factor kappa B (NFKB pathway. This pathway is deregulated in multiple tumor entities, including Hodgkin's lymphoma (HL. Indeed, curcumin can inhibit growth of HL cell lines and increases the sensitivity of these cells for cisplatin. In this review we summarize curcumin activities with special focus on possible activities against HL cells.

  15. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-11-15

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  16. Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2018-06-13

    CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

  17. Cancer and tumour markers

    International Nuclear Information System (INIS)

    Osifo, B.

    1999-02-01

    Cancer has been a major cause of death world wide and in Nigeria there are six commonest forms of manifestation of cancer known. Of these prostrate cancer is the highest with 16% occurrence of all known cancers according to a study by the Histopathology Department of the UCH. Many factors, amongst them dietary, environmental, lifestyle, age and sedentary work are possible causes. With the global rise in incidents, the IAEA initiated the Tumour Marker Project as a means of screening cancers in 15 African countries including Nigeria. In Nigeria, 4 groups of the commonest cancers have been chosen for screening. These are prostrate cancer, primary liver cancer, cancer of the GI tract and trophoblastic cancer

  18. Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

    Science.gov (United States)

    Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

    2017-07-01

    Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2018-04-10

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  20. Genomic aberrations in spitzoid tumours and their implications for diagnosis, prognosis and therapy

    Science.gov (United States)

    Wiesner, Thomas; Kutzner, Heinz; Cerroni, Lorenzo; Mihm, Martin J.; Busam, Klaus J.; Murali, Rajmohan

    2016-01-01

    Summary Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas conventional naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET. In Spitz naevi, which lack significant histological atypia, all of these mitogenic driver aberrations trigger rapid cell proliferation, but after an initial growth phase, various tumour suppressive mechanisms stably block further growth. In some tumours, additional genomic aberrations may abrogate various tumour suppressive mechanisms, such as cell-cycle arrest, telomere shortening, or DNA damage response. The melanocytes then start to grow in a less organised fashion, may spread to regional lymph nodes, and are termed atypical Spitz tumours. Upon acquisition of even more aberrations, which often activate additional oncogenic pathways or reduce and alter cell differentiation, the neoplastic cells become entirely malignant and may colonise and take over distant organs (spitzoid melanoma). The sequential acquisition of genomic aberrations suggests that Spitz tumours represent a continuous biological spectrum, rather than a dichotomy of benign versus malignant, and that tumours with ambiguous histological features (atypical Spitz tumours) might be best classified as low-grade melanocytic tumours. The number of genetic aberrations usually correlates with the degree of histological atypia and explains why existing ancillary genetic

  1. Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

    Science.gov (United States)

    Hernandez-Pando, R; Orozco, H; Arriaga, K; Sampieri, A; Larriva-Sahd, J; Madrid-Marina, V

    1997-01-01

    A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages

  2. Quantifying heterogeneity in human tumours using MRI and PET.

    Science.gov (United States)

    Asselin, Marie-Claude; O'Connor, James P B; Boellaard, Ronald; Thacker, Neil A; Jackson, Alan

    2012-03-01

    Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity. In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Tumour induction by small doses of ionised radiation

    International Nuclear Information System (INIS)

    Putten, L.M. van

    1980-01-01

    The effect of low doses of ionised radiation on tumour induction in animals is discussed. It is hypothesised that high doses of radiation can strongly advance tumour induction from the combination of a stimulated cell growth, as a reaction to massive cell killing, and damage to DNA in the cell nuclei. This effect has a limit below which the radiation dose causes a non-significant amount of dead cells. However in animals where through other reasons, a chronic growth stimulation already exists, only one effect, the damage of DNA, is necessary to induce tumours. A linear dose effect without a threshold level applies in these cases. Applying this hypothesis to man indicates that calculating low dose effects by linear extrapolation of high dose effects is nothing more than a reasonable approximation. (C.F.)

  4. Splenic marginal zone lymphoma.

    Science.gov (United States)

    Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

    Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Haemorrhage and intestinal lymphoma

    Directory of Open Access Journals (Sweden)

    Attilia M. Pizzini

    2013-04-01

    Full Text Available Background: The prevalence of coeliac disease is around 1% in general population but this is often unrecognised. The classical presentation of adult coeliac disease is characterized by diarrhoea and malabsorption syndrome, but atypical presentations are probably more common and are characterized by iron deficiency anaemia, weight loss, fatigue, infertility, arthralgia, peripheral neuropathy and osteoporosis. Unusual are the coagulation disorders (prevalence 20% and these are due to vitamin K malabsorption (prolonged prothrombin time. Clinical case: A 64-year-old man was admitted to our Department for an extensive spontaneous haematoma of the right leg. He had a history of a small bowel resection for T-cell lymphoma, with a negative follow-up and he didn’t report any personal or familiar history of bleeding. Laboratory tests showed markedly prolonged prothrombin (PT and partial-thromboplastin time (PTT, corrected by mixing studies, and whereas platelet count and liver tests was normal. A single dose (10 mg of intravenous vitamin K normalized the PT. Several days before the patient had been exposed to a superwarfarin pesticide, but diagnostic tests for brodifacoum, bromadiolone or difenacoum were negative. Diagnosis of multiple vitamin K-dependent coagulationfactor deficiencies (II, VII, IX, X due to intestinal malabsorption was made and coeliac disease was detected. Therefore the previous lymphoma diagnosis might be closely related to coeliac disease. Conclusions: A gluten free diet improves quality of life and restores normal nutritional and biochemical status and protects against these complications.

  6. Lymphoma Caused by Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Mitsuko L. Yamamoto

    2014-09-01

    Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

  7. VIP secreting tumours in infancy

    International Nuclear Information System (INIS)

    Davies, R.P.; Slavotinek, J.P.; Dorney, S.F.A.

    1990-01-01

    Vasoactive intestinal polypeptide (VIP) secreting neural crest tumours are an uncommon but important treatable cause of intractable childhood diarrhoea. The radiological appearances of two cases are presented with a review of radiological findings in childhood VIP secreting neural crest tumours. Twenty eight cases of childhood VIP secreting neural crest tumours were reviewed. Nineteen (68%) were ganglioneuroblastomas and nine (32%) were ganglioneuromas. The majority of tumours (66%) were in a paravertebral location in the abdomen indicating that a search for such a tumour should be initiated at this site. Eighteen of the twenty eight cases reviewed discussed relevant radiological investigations. Calcification was detected in 50% of abdominal radiographs. Gut dilatation was often a prominent feature. A mass was detected in 5 of 5 cases where ultrasound findings were reported, and seven of seven cases with CT findings reported. Prior to the availability of CT and ultrasound the most useful investigation was IVU which demonstrated evidence of a mass in 5 of 9 cases. The presence of paravertebral calcification and gut dilatation on the plain radiograph of a child with intractable diarrhoea suggests the presence of a VIP secreting neural crest tumour. If an abdominal tumour is not found in the appropriate clinical setting and VIP levels are elevated, a widespread search of the paravertebral region is indicated. (orig.)

  8. Sialyl-Tn vaccine induces antibody-mediated tumour protection in a relevant murine model

    DEFF Research Database (Denmark)

    Julien, S; Picco, G; Sewell, R

    2009-01-01

    challenge. We show that synthetic STn coupled to keyhole limpet haemocyanin (Theratope), induced antibodies to STn that recognised the glycan carried on a number of glycoproteins and in these mice a significant delay in tumour growth was observed. The protection was dependent on STn being expressed...... by the tumour and was antibody mediated. Affinity chromatography of the STn-expressing tumour cell line, followed by mass spectrometry, identified osteopontin as a novel STn-carrying glycoprotein which was highly expressed by the tumours. These results suggest that if antibodies can be induced to a number...

  9. Anaesthetic management for caesarean section in a case of previously operated with residual pituitary tumour

    Directory of Open Access Journals (Sweden)

    Prerana N Shah

    2011-01-01

    Full Text Available Successful anaesthetic management for caesarean section in a case with previous pituitary tumour resection, with residual tumour, is reported. The pituitary gland undergoes global hyperplasia during pregnancy. Functional pituitary tumours may exhibit symptomatic enlargement during pregnancy. Growth hormone secreting tumour is associated with acromegaly which has associated anaesthetic implications of difficult airway, systemic hypertension, and diabetes and electrolyte imbalance. Intracranial space occupying lesions can increase intra cranial pressure and compromise cerebral perfusion or cause herniation. We report management of this case.

  10. L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Rosilio, C.; Nebout, M.; Imbert, V.; Griessinger, E.; Neffati, Z.; Benadiba, J.; Hagenbeek, T.; Spits, H.; Reverso, J.; Ambrosetti, D.; Michiels, J.-F.; Bailly-Maitre, B.; Endou, H.; Wempe, M. F.; Peyron, J.-F.

    2015-01-01

    The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute

  11. Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

    Science.gov (United States)

    2018-01-02

    HIV Infection; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Plasmablastic Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Follicular Lymphoma; Stage III Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  12. An experimental study of tumour size and radiosensitivity

    International Nuclear Information System (INIS)

    Hill, S.A.; Denekamp, J.

    1989-01-01

    When designing experimental studies of tumours, it is considered important to control all variables that might alter the radiosensitivity and hence influence the variability of the data. One such variable is tumour size. We have studied the regrowth delay of a mammary carcinoma treated at 2-10 mm mean diameter (a 125-fold change of volume) with X-rays alone or X-rays plus misonidazole (MISO). The data were analysed to give dose-response curves, using four endpoints. Regrowth to a fixed size (4.5 mm larger than treatment size), or by a fixed increment (4 times the original volume) was expressed either as absolute delay, or as specific growth delay to allow for the changes in volume doubling time as the tumour grows. The method of analysis made no difference to the measured sensitizer enhancement ratio (SER) for MISO. The SER was dose-dependent, being higher doses, but was not different in tumours of 2 or 10 mm diameter. However, when comparing response to X-rays alone, the method of analysis made a very big difference to the conclusions. Regrowth to R + 4.5 mm showed no change in radiosensitivity with tumour size, but regrowth to 4 times the original volume (the most logical endpoint) indicated that large tumours were more sensitive than small. We conclude that regrowth delay may be an inappropriate method for comparing absolute sensitivities of tumours of different sizes. However, for studying the effectiveness of a radiomodifier the constraints of tumour size at irradiation seem to be less severe than previously believed. (author). 8 refs.; 8 figs

  13. The potential role of cyclooxygenase-2 inhibitors in the treatment of experimentally-induced mammary tumour: does celecoxib enhance the anti-tumour activity of doxorubicin?

    Science.gov (United States)

    Awara, Wageh M; El-Sisi, Alaa E; El-Sayad, Magda E; Goda, Ahmed E

    2004-11-01

    The potential anti-tumour activity of non-steroidal anti-inflammatory drugs (NSAIDS) has been previously discussed. This study was undertaken to assess the possible anti-tumour activity of the cyclooxygenase-2 (COX-2) inhibitor; celecoxib in an animal model of mammary carcinoma; the solid Ehrlich carcinoma (SEC). The possibility that celecoxib may modulate the anti-tumour activity of doxorubicin on the SEC was also studied. Some of the possible mechanisms underlying such modulation were investigated. The anti-tumour activity of celecoxib (25 mg kg(-1)), diclofenac (12.5 mg kg(-1)) and doxorubicin (2 mg kg(-1)) either alone or in combination were investigated on SEC in vivo through the assessment of tumour growth delay (TGD) and tumour volume (TV), changes in tumour DNA content and nitric oxide (NO) levels, immunohistochemical staining of the tumour suppressor gene product; p53 histopathological examination and determination of apoptotic index of SEC. In addition, the influence of these drugs on the DNA fragmentation pattern of Ehrlich carcinoma cells (ECC) was studied. It was found that both celecoxib and diclofenac lack the anti-tumour activity on SEC. In addition there was a significant increase in doxorubicin anti-tumour activity when administered in combination with celecoxib. Moreover, it was found that both celecoxib and diclofenac have the potential to inhibit the function of P-glycoprotein (P-gp) in ECC using rhodamine uptake and efflux assays. Therefore, the current study suggested the chemosensitizing potential of celecoxib in the SEC animal model of mammary tumour, which could be explained in part on the basis of inhibition of P-gp function, with possible enhancement of doxorubicin anti-tumour activity.

  14. Modulation of tumour spectra in C 57 black mice following fast-neutron versus Co irradiation at low dosage

    International Nuclear Information System (INIS)

    Mewissen, D.J.; Rust, J.H.

    1976-01-01

    A total of 7109 C 57 Black mice of either sex were either sham-, neutron- or cobalt-irradiated at the age of 33+-3 days. The dose range extended from 3.2 to 47.2 rads for neutrons and from 18 to 141 rads for γ rays. This experiment was aimed at assessing relative biological effectiveness (RBE) and its possible dose dependence from radiation mortality and morbidity data, using actuarial statistics. The primary goal was to define the spontaneous or basic tumour spectrum in control animals of either sex, which included a major proportion of lymphocytic lymphomas, followed by reticulum cell lymphomas. A variety of other tumours were observed, among them various adenocarcinomas, squamous cell carcinomas and leiomyosarcomas of the gastrointestinal tract, liver and spleen hemangiomas, micro- and macrofollicular hyperplasia as well as papillary adenomas of the thyroid, fibromas and fibrosarcomas of connective tissue, muscles and bones, myomas and fibrosarcomas of uterus, luteomas and cysts of the ovary, papillary and transitional cell carcinomas of kidneys and an occasional mammary adenocarcinoma or skin epithelioma. Modulation of the basic tumour pattern by neutrons or cobalt was primarily operative on the reticular tissue. Age-specific incidence rates for combined mature and immature lymphocytic lymphomas decreased following neutron or cobalt irradiation at higher dose levels. In reticulum cell sarcomas, however, the tumour type evidently shifted almost entirely from the mature to the immature type. Furthermore, all rates increased markedly following irradiation at all dose levels. One major finding in all groups was the non-linearity of tumour response. Furthermore, it appeared that the control as well as the radiation-modulated tumour spectra were likely to proceed from intercompetitive stochastic processes rather than from some probabilistic random distribution. Some implications of these primary results are discussed

  15. Dual role of delay effects in a tumour-immune system.

    Science.gov (United States)

    Yu, Min; Dong, Yueping; Takeuchi, Yasuhiro

    2017-08-01

    In this paper, a previous tumour-immune interaction model is simplified by neglecting a relatively weak direct immune activation by the tumour cells, which can still keep the essential dynamics properties of the original model. As the immune activation process is not instantaneous, we now incorporate one delay for the activation of the effector cells (ECs) by helper T cells (HTCs) into the model. Furthermore, we investigate the stability and instability regions of the tumour-presence equilibrium state of the delay-induced system with respect to two parameters, the activation rate of ECs by HTCs and the HTCs stimulation rate by the presence of identified tumour antigens. We show the dual role of this delay that can induce stability switches exhibiting destabilization as well as stabilization of the tumour-presence equilibrium. Besides, our results reveal that an appropriate immune activation time delay plays a significant role in control of tumour growth.

  16. Diverse effects of combined radiotherapy and EGFR inhibition with antibodies or TK inhibitors on local tumour control and correlation with EGFR gene expression

    International Nuclear Information System (INIS)

    Gurtner, Kristin; Deuse, Yvonne; Buetof, Rebecca; Schaal, Katja; Eicheler, Wolfgang; Oertel, Reinhard; Grenman, Reidar; Thames, Howard; Yaromina, Ala; Baumann, Michael; Krause, Mechthild

    2011-01-01

    Purpose: To compare functional effects of combined irradiation and EGFR inhibition in different HNSCC tumour models in vivo with the results of molecular evaluations, aiming to set a basis for the development of potential biomarkers for local tumour control. Material and methods: In five HNSCC tumour models, all wild-type for EGFR and KRAS, the effect of radiotherapy alone (30 fractions/6 weeks) and with simultaneous cetuximab or erlotinib treatment on local tumour control were evaluated and compared with molecular data on western blot, immunohistochemistry and fluorescence-in situ-hybridisation (FISH). Results: Erlotinib and cetuximab alone significantly prolonged tumour growth time in 4/5 tumour models. Combined irradiation and cetuximab treatment significantly improved local tumour control in 3/5 tumour models, whereas erlotinib did not alter local tumour control in any of the tumour models. The amount of the cetuximab-effect on local tumour control significantly correlated with the EGFR/CEP-7 ratios obtained by FISH. Conclusion: Both drugs prolonged growth time in most tumour models, but only application of cetuximab during irradiation significantly improved local tumour control in 3/5 tumour models. The significant correlation of this curative effect with the genetic EGFR expression measured by FISH will be further validated in preclinical and clinical studies.

  17. MRI findings in primary brain lymphoma in immunocompetent patients

    Directory of Open Access Journals (Sweden)

    Saeed Nadhim Younis

    2017-08-01

    Full Text Available Background and objective: Primary brain lymphoma is an extranodal aggressive intracranial neoplasm of lymphocytic origin originating and confined to the brain parenchyma and meninges. It is rare in immune competent patients, but its incidence is increasing. This retrospective study was conducted to record the MRI features of primary brain lymphoma at the time of diagnosis in immunocompetent patients. Methods: Of the 450 patients diagnosed with the brain tumor during a period of five years from 2008 to 2013, the clinical features and MRI findings of 16 cases of pathologically proven to be non-Hodgkin’s lymphoma were studied. All the patients were tested negative for HIV and there was no history of immune suppression drugs or any other chronic illness. All the patients were examined with MRI observing the tumor location, multifocality, signal intensity in different sequences, enhancement patterns, peritumoral edema, the presence of hemorrhage and calcification. Results: Of the 16 patients, including the monofocal and multifocal cases, 30 lesions exhibited. The mean age at diagnosis was 53 years. Nine patients (56.25% found to have a multifocal disease. In more than 75% of lesions, MRI was hypo to iso signal on T1 and T2. Mild to moderate perilesional edema, strong contrast enhancement and restricted diffusion were seen in all cases. The hemorrhagic tumor was noticed in four lesions (13.3%. No calcification and no leptomeningeal lesions were noted. The MRI images in post steroid therapy were studied within one month of treatment. Tumour regression was noticed in 21/30 (70%, stable in 3/30 (10% and progressing in 6/30 (20%. Conclusion: MRI is a reliable imaging technique in the management of patients with primary brain lymphoma. Early accurate diagnosis is crucial to avoid the unnecessary operation and shift patients from extensive surgery to chemoradiotherapy.

  18. Growth

    Science.gov (United States)

    John R. Jones; George A. Schier

    1985-01-01

    This chapter considers aspen growth as a process, and discusses some characteristics of the growth and development of trees and stands. For the most part, factors affecting growth are discussed elsewhere, particularly in the GENETICS AND VARIATION chapter and in chapters in PART 11. ECOLOGY. Aspen growth as it relates to wood production is examined in the WOOD RESOURCE...

  19. Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis

    International Nuclear Information System (INIS)

    Grant, Nicola J.; Coates, Philip J.; Woods, Yvonne L.; Bray, Susan E.; Morrice, Nicholas A.; Hastie, C. James; Lamont, Douglas J.; Carey, Francis A.; Sutherland, Calum

    2015-01-01

    Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

  20. Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis.

    Science.gov (United States)

    Grant, Nicola J; Coates, Philip J; Woods, Yvonne L; Bray, Susan E; Morrice, Nicholas A; Hastie, C James; Lamont, Douglas J; Carey, Francis A; Sutherland, Calum

    2015-11-10

    Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

  1. Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

    LENUS (Irish Health Repository)

    Tan, B

    2012-02-03

    BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

  2. Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hertel, Christina B; Zhou, Xiao-ge; Hamilton-Dutoit, Stephen J

    2002-01-01

    In classical Hodgkin lymphoma the malignant Hodgkin/Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS ce...

  3. Cystic tumours of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Itai, Y. [Dept. of Radiology, Inst. of Clinical Medicine, Tsukuba Univ. (Japan); Ohtomo, K. [Univ. of Tokyo Hospital, Tokyo (Japan)

    1996-12-01

    In this pictorial essay we present the typical appearances of cystic pancreatic tumours, the wide spectrum of their features, and differential features among cystic pancreatic masses with an emphasis on CT. Pseudocysts are the most common cystic lesion in the pancreas and can be induced by pancreatitis, trauma or surgery. Pseudocysts appear as a round cystic mass with a definite wall. However, they can mimic cystic tumours associated with internal septation and/or necrotic mass of various shapes. Conversely, cystic tumours can appear as a simple cyst lacking any thickening of wall, septation or mural nodule. Pancreatic carcinoma not infrequently induces secondary cysts upstream of the obstructed pancreatic duct. The cysts are pseudocysts or retention cysts in nature. When cysts are formed in the pancreatic parenchyma or adjacent to pancreatic carcinoma they may mimic cystic tumour. (orig./VHE)

  4. Cystic tumours of the pancreas

    International Nuclear Information System (INIS)

    Itai, Y.; Ohtomo, K.

    1996-01-01

    In this pictorial essay we present the typical appearances of cystic pancreatic tumours, the wide spectrum of their features, and differential features among cystic pancreatic masses with an emphasis on CT. Pseudocysts are the most common cystic lesion in the pancreas and can be induced by pancreatitis, trauma or surgery. Pseudocysts appear as a round cystic mass with a definite wall. However, they can mimic cystic tumours associated with internal septation and/or necrotic mass of various shapes. Conversely, cystic tumours can appear as a simple cyst lacking any thickening of wall, septation or mural nodule. Pancreatic carcinoma not infrequently induces secondary cysts upstream of the obstructed pancreatic duct. The cysts are pseudocysts or retention cysts in nature. When cysts are formed in the pancreatic parenchyma or adjacent to pancreatic carcinoma they may mimic cystic tumour. (orig./VHE)

  5. Imaging oxygenation of human tumours

    International Nuclear Information System (INIS)

    Padhani, Anwar R.; Krohn, Kenneth A.; Lewis, Jason S.; Alber, Markus

    2007-01-01

    Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. 18 F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy. (orig.)

  6. How I treat double-hit lymphoma.

    Science.gov (United States)

    Friedberg, Jonathan W

    2017-08-03

    The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

  7. Tumour markers in urology

    International Nuclear Information System (INIS)

    Schmid, L.; Fornara, P.; Fabricius, P.G.

    1988-01-01

    The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.) [de

  8. Reproductive tract tumours: the scourge of woman reproduction ails Indian rhinoceroses.

    Directory of Open Access Journals (Sweden)

    Robert Hermes

    Full Text Available In Indian rhinoceros, extensive leiomyoma, a benign smooth muscle tumour, was sporadically diagnosed post mortem and commonly thought of as contributing factor for reduced fecundity of this species in captivity. However, to date, the prevalence of reproductive tract tumours and their relevance for fecundity are unknown. Our analysis of the international studbook now reveals that females cease reproducing at the age of 18.1±1.2 years; equivalent to a reproductive lifespan of just 9.5±1.3 years. This short reproductive life is in sharp contrast to their longevity in captivity of over 40 years. Here we show, after examining 42% of the captive female population, that age-related genital tract tumours are highly prevalent in this endangered species. Growth and development of these tumours was found to be age-related, starting from the age of 10 years. All females older than 12 years had developed genital tumours, just 7-9 years past maturity. Tumour sizes ranged from 1.5-10 cm. With age, tumours became more numerous, sometimes merging into one large diffuse tumour mass. These tumours, primarily vaginal and cervical, presumably cause widespread young-age infertility by the age of 18 years. In few cases, tumour necrosis suggested possible malignancy of tumours. Possible consequences of such genital tract tumour infestation are hindered intromission, pain during mating, hampered sperm passage, risk of ascending infection during pregnancy, dystocia, or chronic vaginal bleeding. In humans, leiomyoma affect up to 80% of pre-menopause women. While a leading cause for infertility, pregnancy is known to reduce the risk of tumour development. However, different from human, surgical intervention is not a viable treatment option in rhinoceroses. Thus, in analogy to humans, we suggest early onset and seamless consecutive pregnancies to help reduce prevalence of this disease, better maintain a self-sustained captive population and improve animal welfare.

  9. Follicular non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Hayashi, D.; Lee, J.C.; Devenney-Cakir, B.; Zaim, S.; Ounadjela, S.; Solal-Celigny, P.; Juweid, M.; Guermazi, A.

    2010-01-01

    Follicular non-Hodgkin's lymphoma (NHL) is a unique subtype of NHL, which is indolent, incurable with a high prevalence of residual mass after treatment, and may transform to more aggressive NHL. The aim of this review is to (1) describe the histological and flow cytometry characteristics of follicular NHL; (2) introduce the Follicular Lymphoma International Prognostic Index 2 (FLIPI-2), which allows better treatment selection and patient stratification for clinical trials; (3) illustrate the classic and atypical ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET)/CT appearance of follicular NHL; and (4) characterize the appearance of nodal and extranodal follicular NHL with pathological correlation. Imaging is essential in every step of the management of patients with follicular lymphoma. Overall survival is improved with better predictive tools and new targeted biological therapies. Radiologists should be aware of possible active residual mass, indolent recurrence, transformation, and association with other primary cancers in patients treated for follicular lymphoma.

  10. Primary lymphoma of the breast involving both axillae with bilateral breast carcinoma

    Directory of Open Access Journals (Sweden)

    Rubin Gary

    2008-05-01

    Full Text Available Abstract Background Primary Non-Hodgkin's Lymphoma (PHNL of the breast is a rare entity, while secondary involvement of the breast with diffuse disease of Non-Hodgkin's lymphoma (NHL is more common. However, PNHL is the most frequent haematopoietic tumour of the breast. Diagnostic criteria for PNHL of the breast are presence of technically adequate pathologic specimens, close association of mammary tissue and lymphomatous infiltrate, no prior diagnosis of an extarammamary lymphoma, and no evidence of concurrent widespread disease, except for ipsilateral axillary lymph nodes if concomitant with the primary lesion. Case presentation A 57-year-old woman was recalled because her screening mammograms revealed three separate lesions in her right breast and one in the left. Histology of the lesions confirmed lymphoma in one breast with ductal carcinoma in the other. Conclusion Most of reported cases in literature have been involving the right breast, and almost all the patients were females. NHLs of the breast typically present as unilateral mass; the frequency of bilateral disease at first presentation ranges from 5–25%. Our objective is to report a case of primary lymphoma of the breast involving both axillae with concomitant bilateral primary breast cancer which has not been reported yet to our best of knowledge in literature.

  11. Doubling time of thymic epithelial tumours on CT: correlation with histological subtype

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Jooae; Lee, Sang Min; Kim, Namkug; Do, Kyung-Hyun; Seo, Joon Beom [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Songpa-gu, Seoul (Korea, Republic of); Lim, Soyeoun [Ulsan University Hospital, Department of Radiology, University of Ulsan College of Medicine, Ulsan (Korea, Republic of); Choi, Se Hoon [University of Ulsan College of Medicine, Department of Thoracic and Cardiovascular Surgery, Seoul (Korea, Republic of)

    2017-10-15

    We retrospectively evaluated the doubling time (DT) of thymic epithelial tumours (TET) according to the histological subtype on CT. From January 2005 to June 2016, we enrolled 53 patients who had pathologically confirmed TET and at least two CT scans. Tumour size was measured using a two-dimensional method, and the DT was calculated. DTs were compared among histological subtypes, and factors associated with rapid tumour growth (DT <180 days) were assessed. In 42 of the 53 patients (79.2%) the tumours showed interval growth (>2 mm) during follow-up. The median DT for all tumours was 400 days (range 48-1,964 days). There were no significant differences in DT in relation to histological subtype (p = 0.177). When TETs were recategorized into three groups, i.e. low-risk thymomas (types A, AB, B1), high-risk thymomas (types B2, B3), and thymic carcinoma, DT was significantly different among the groups (median DT 436, 381 and 189 days, respectively; p = 0.031). Histological subtype (type B3 and thymic carcinoma) was the single independent predictor of rapid tumour growth. The majority of TETs grew during follow-up with variable and relatively slow growth rates. Histological features of aggressive behaviour significantly correlated with a decreased DT and rapid growth. circle The majority of thymic epithelial tumours grew during follow-up (79.2%, 42/53). (orig.)

  12. FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Woetmann, A; Odum, Niels

    2007-01-01

    FOXP3 is a unique marker for CD4+CD25+ regulatory T cells (Tregs). In solid tumours, high numbers of Tregs are associated with a poor prognosis. Knowledge about the implications of Tregs for the behaviour of haematological malignancies is limited. In this study, skin biopsies from 86 patients...... with mycosis fungoides (MF) and cutaneous T-cell lymphoma (CTCL) unspecified were analysed for the expression of FOXP3 on tumour cells and tumour-infiltrating Tregs. Labelling of above 10% of the neoplastic cells was seen in one case classified as an aggressive epidermotropic CD8+ cytotoxic CTCL....... In the remaining 85 cases, the atypical neoplastic infiltrate was either FOXP3 negative (n=80) or contained only very occasional weakly positive cells (n=5). By contrast, all biopsies showed varying numbers of strongly FOXP3+ tumour-infiltrating Tregs. MF with early or infiltrated plaques had significantly higher...

  13. Renal angiomyoadenomatous tumour: Imaging features

    Science.gov (United States)

    Sahni, V. Anik; Hirsch, Michelle S.; Silverman, Stuart G.

    2012-01-01

    Renal angiomyoadenomatous tumour is a rare, recently described neoplasm with a distinctive histological appearance. Although reported in the pathology literature, to our knowledge, no prior reports have described its imaging appearance. We describe the computed tomography and magnetic resonance imaging features of an incidentally detected renal angiomyoadenomatous tumour that appeared as a well-marginated, solid T2-hypointense enhancing mass, in a 50-year-old woman. It is indistinguishable from a variety of benign and malignant renal neoplasms. PMID:23093565

  14. Lymphoma in pregnancy

    International Nuclear Information System (INIS)

    Ballova, V.

    2016-01-01

    The diagnosis of malignant lymphoma during pregnancy is always a challenging situation, as for the patient a her family as well as for the whole medical team. Medical and communication skills are crucial in this situation. Interdisciplinary approach and a close cooperation between oncologist, obstetrician and neonatologist are equally important. The diagnosis of malignant potentially lethal disease and the need of treatment during pregnancy raise concerns about the life of mother if treatment was delayed and at the same time concerns about adverse fetal outcomes. This gives raise dilemmas at the therapeutical, ethical, moral and social levels. The patient must be included in the decisional process and the cultural as well as the religious aspects must be taken into account. (author)

  15. Localized folicular lymphomas

    International Nuclear Information System (INIS)

    Soubeyran, P.; Eghbali, H.; Bonichon, F.; Coindre, J.M.; Richaud, P.; Hoerni, B.

    1988-01-01

    From 1966 to 1985, 103 patients with a localized follicular lymphoma were treated at the Fondation Bergonie. Clinical staging was performed using, after physical examination, chest X-rays, bipedal lymphangiography and unilateral bone marrow biopsy (BMB). The patients were then treated by radiotherapy with or without chemotherapy. Overall survival (OS) at 5 and 10 years is 69 and 56.3%, respectively. Relapse-free survival (RFS) is 53.7 and 49%. Unifactorial analysis shows three prognostic parameters to be independently significant in terms of OS: age, stage and B symptons. In terms of RFS, only 2 factors are significant: age and B symptons. Multivariate analysis (Cox model) shows that age is a more important prognostic factor than stage. 40 refs.; 3 figs.; 3 tabs

  16. Tumour metastasis as an adaptation of tumour cells to fulfil their phosphorus requirements.

    Science.gov (United States)

    de Carvalho, Carla C C R; Caramujo, Maria José

    2012-05-01

    Inorganic phosphate (Pi) is a vital component of nucleotides, membrane phospholipids, and phosphorylated intermediates in cellular signalling. The Growth Rate Hypothesis (GRH) states that fast growing organisms should be richer in phosphorus (relatively low C:P and N:P cell content) than slow developing organisms as a result of high ribosome biogenesis. Cells that proliferate rapidly, such as cancer cells, require a high amount of ribosomes and other P-rich RNA components that are necessary to manufacture proteins. The GRH hypothesis may be applied to cancer predicting that tumour cells are richer in phosphorus than the surrounding tissue, and that they resort to metastasis in order to meet their nutrient demands. Considering that the cells most P-deprived should be located in the inner parts of the tumour we propose that changes in the membrane of these cells favour the detachment of the more peripheral cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  18. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1

    International Nuclear Information System (INIS)

    Williams, Kaye J.; Telfer, Brian A.; Xenaki, Dia; Sheridan, Mary R.; Desbaillets, Isabelle; Peters, Hans J.W.; Honess, Davina; Harris, Adrian L.; Dachs, Gabi U.; Kogel, Albert van der; Stratford, Ian J.

    2005-01-01

    Background and purpose: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. Patients and methods: Tumours comprising mouse hepatoma cells lacking HIF-1β (and thereby HIF-1 function) were grown in nude mice and radiation-induced growth delay compared with that seen for wild-type tumours and tumours derived from HIF-1β negative cells where HIF-1 function had been restored. Results: The xenografts that lack HIF-1 activity take longer to establish their growth and are more radioresponsive than both parental xenografts and those with restored HIF-1 function. Pre-treatment of the HIF-1 deficient xenografts with the hypoxic radiosensitizer misonidazole, had little effect on radioresponse. In contrast this treatment radiosensitized the parental xenografts. In spite of this, no difference in oxygenation status was found between the tumour types as measured by Eppendorf O 2 -electrodes and by binding of the hypoxic cell marker NITP. Admixing wild type and HIF-1 deficient cells in the same tumour at ratios of 1 in 10 and 1 in 100 restores the growth of the mixed tumours to that of a 100% HIF-1 proficient cell population. However, when comparing the effects of radiation on the mixed tumours, radioresponsiveness is maintained in those tumours containing the high proportion of HIF-1 deficient cells. Conclusions: The differences in radioresponse do not correlate with tumour oxygenation, suggesting that the hypoxic cells within the HIF-1 deficient tumours do not contribute to the outcome of radiotherapy. Thus, hypoxia impacts on tumour radioresponsiveness not simply because of the physio-chemical mechanism of oxygen with radiation-induced radicals causing damage 'fixation', but also because hypoxia/HIF-1 promotes expression of genes that allow tumour cells to survive under these adverse conditions. Further, the results from the cell mixing experiments uncouple the growth

  19. Surgical approach to pineal tumours.

    Science.gov (United States)

    Pluchino, F; Broggi, G; Fornari, M; Franzini, A; Solero, C L; Allegranza, A

    1989-01-01

    During a period of 10 years (1977-1986) 40 cases of tumour of the pineal region have been treated at the Istituto Neurologico "C. Besta"-of Milan. Out of these 40 cases, 27 (67.5%) were in the paediatric (10-15 years) or juvenile (15-20 years) age at the time of operation. Since 1983 a specific diagnostic and therapeutic protocol has been adopted and thereafter direct surgical removal of the tumour was performed only when the neuroradiological investigations were highly suggestive of a benign extrinsic lesion. Sixteen cases in this series underwent direct surgical removal; in the remaining 24 cases stereotactic biopsy of the tumour was performed in the first instance. On the basis of the histological diagnosis obtained by this procedure surgical excision of the tumour (9 cases) or radiotherapy (15 cases) was then performed. 25 cases underwent surgical removal of the lesion. In all the cases the infratentorial supracerebellar approach as introduced by Krause and then modified by Stein was adopted. On analysis of the data of this series it was observed that in 25% of the cases completely benign resectable tumours were found; in 25% of the cases astrocytoma (grade I-II) which could be treated at least by partial removal were present; in 30% of the cases radiosensitive lesions were encountered. In the remaining 20% of the cases highly malignant tumours were found which should be treated only by radiotherapy and/or chemotherapy.

  20. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  1. Treatment results of localized gastric lymphoma

    International Nuclear Information System (INIS)

    Abe, Tatsuyuki; Gomi, Hiromichi; Sakaino, Shinjiro; Nakajima, Yasuo

    2008-01-01

    Between 2000 and 2007, 17 patients with localized gastric lymphoma (10 mucosa-associated lymphoid tissue lymphomas and 7 diffuse large B-cell lymphomas) were treated with radiotherapy alone or doxorubicin-based chemotherapy followed by radiotherapy. Radiation dose of mucosa-associated lymphoid tissue (MALT) lymphoma was 30 Gy with a daily fraction size of 1.5 Gy. Sixteen patients achieved complete remission and the 5-year overall survival of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) were 100% and 87%, respectively. No gastric perforation and hemorrhage were noticed. Using AP/LR 2-port radiotherapy markedly decreased the liver dose. (author)

  2. Plasma cytokine profiles at diagnosis in pediatric patients with non-hodgkin lymphoma

    DEFF Research Database (Denmark)

    Mellgren, Karin; Hedegaard, Chris Juul; Schmiegelow, Kjeld

    2012-01-01

    Non-Hodgkin lymphoma (NHL) has been associated with elevated levels of inflammatory and immune-regulating cytokines, and polymorphisms in the genes encoding interleukin (IL)-10 and tumor necrosis factor (TNF)-α have been associated with increased incidence of certain subtypes of NHL. The aim......, between 1995 and 2008. Cytokines and growth factors were measured in serum using the Luminex platform by application of a 30-plex kit. Levels of IL-6, IL-2R, IL-10, TNF-RI, and macrophage inflammatory protein-1α were significantly higher in patients with anaplastic large-cell lymphoma compared...... with patients diagnosed with B-cell lymphomas and lymphoblastic lymphomas. High levels of IL-4, IL-13, TNF-RI, and epidermal growth factor were associated with a poorer general condition at diagnosis. The present study suggests that NHL subgrouping and the general condition of pediatric patients at diagnosis...

  3. Osteopenia in children surviving brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Whitton, A.C.; Eves, M. [Children' s Hospital at Chedoke-McMaster, Room 3N27B, Health Sciences Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario (Canada); Hay, J. [Brock University, St. Catharines, Ontario (Canada); Gill, G.J.; Webber, C.E. [Faculty of Health Sciences, McMaster University (Canada); Simpson, T. [Hamilton Regional Cancer Centre, Hamilton, Ontario (Canada); Barr, R.D. [Children' s Hospital at Chedoke-McMaster, Room 3N27B, Health Sciences Centre, McMaster University, 1200 Main Street West, Hamilton, Ontario (Canada)

    1998-05-01

    Osteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a crucial role in this disorder. To explore that possibility, survivors of brain tumours in childhood, all of whom had received radiotherapy, were examined for evidence of bone mineral loss. 19 children were assessed, on average at 7 years after treatment. Measurements of growth velocities, plain radiography of the skeleton, bone densitometry, health-related quality of life and physical activity were undertaken. Growth hormone (GH) deficiency had been detected in 6 children and 5 had received GH replacement, for a minimum of more than 3 years. 9 children were radiographically osteopenic (including the 5 who had received GH). Z scores for bone mineral density (BMD) were negative in the majority of children. Health-related quality of life was less and pain more frequent in those with low BMD scores. Pain was correlated negatively with both free-time activity and seasonal activity (P<0.01). Osteopenia is a common sequel of therapy in children with brain tumours. Those with osteopenia have more pain and more compromised, health-related quality of life than those who are not osteopenic, and pain significantly limits physical activity. The pathogenesis of osteopenia in these children is still uncertain, but is likely to be multifactorial. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  4. A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

    Directory of Open Access Journals (Sweden)

    Daisuke Usuda

    2017-11-01

    Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

  5. Malignant spinal cord compression in cancer patients may be mimicked by a primary spinal cord tumour.

    Science.gov (United States)

    Mohammadianpanah, M; Vasei, M; Mosalaei, A; Omidvari, S; Ahmadloo, N

    2006-12-01

    Although it is quite rare, second primary neoplasms in cancer patients may present with the signs and symptoms of malignant spinal cord compression. Primary spinal cord tumours in the cancer patients may be deceptive and considered as the recurrent first cancer. Therefore, it should be precisely differentiated and appropriately managed. We report such a case of intramedullary ependymoma of the cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord compression. A 50-year-old man developed intramedullary ependymoma of the cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring lymphoma. He presented with a 2-month history of neck pain, progressive upper- and lower-extremity numbness and weakness, and bowel and bladder dysfunction. Magnetic resonance imaging revealed an intramedullary expansive lesion extending from C4 to C6 levels of the cervical spinal cord. The clinical and radiological findings were suggestive of malignant process. A comprehensive investigation failed to detect another site of disease. He underwent operation, and the tumour was subtotally resected. The patient's neurological deficits improved subsequently. The development of the intramedullary ependymoma following treating lymphoma has not been reported. We describe the clinical, radiological and pathological findings of this case and review the literature.

  6. Palliative embolisation of renal tumours with iodine-marked Ethibloc

    International Nuclear Information System (INIS)

    Weber, J.; Kaufmann, J.; Kult, K.; Allgemeines Krankenhaus Altona, Hamburg

    1984-01-01

    In 59 patients having non-operable malignant renal tumours, palliative trans-catheter embolization was performed. In 42 of them follow-up observations were realized over 18 months. The average survival rate was then 43% of cases. Local tumour growth was documented in 9 patients (23%) due to recanalization of the embolized arteries (13%) and to non-occluded collateral vessels (10%). The choice of suitable embolizing materials mainly influences the therapeutic result: Oily contrast labeled amino-acid Ethibloc is considered to be the material of choice for safe application and reliable vascular distribution causing persisting occlusion of the renal arteries. (orig.) [de

  7. Efficient gene transfer into lymphoma cells using adenoviral vectors combined with lipofection.

    Science.gov (United States)

    Buttgereit, P; Weineck, S; Röpke, G; Märten, A; Brand, K; Heinicke, T; Caselmann, W H; Huhn, D; Schmidt-Wolf, I G

    2000-08-01

    Tumor cells, such as lymphoma cells, are possible targets for gene therapy. In general, gene therapeutic approaches require efficient gene transfer to host cells and sufficient transgene expression. However, lymphoma cells previously have been demonstrated to be resistant to most of the currently available gene transfer methods. The aim of this study was to analyze various methods for transfection of lymphoma cells and to improve the efficiency of gene delivery. In accordance with previously published reports, lymphoma cells were demonstrated to be resistant to lipofection and electroporation. In contrast, we present an improved adenoviral protocol leading to highly efficient gene transfer to lymphoma cell lines derived from B cells as well as primary lymphoma cells being achieved with an adenoviral vector system encoding the beta-galactosidase protein. At a multiplicity of infection of 200, up to 100% of Daudi cells and Raji cells and 70% of OCI-Ly8-LAM53 cells could be transfected. Even at high adenoviral concentrations, no marked toxicity was observed, and the growth characteristics of the lymphoma cell lines were not impaired. The transfection rates in primary cells derived from six patients with non-Hodgkin's lymphoma were 30-65%, respectively. Transfection efficiency could be further increased by addition of cationic liposomes to adenoviral gene transfer. Furthermore, we examined the expression of the Coxsackie-adenoviral receptor (CAR) and the integrin receptors on the lymphoma cell surface. Flow cytometric analysis showed that 88% of Daudi cells, 69% of Raji cells, and 6% of OCI-Ly8-LAM53 cells expressed CAR on the cell surface. According to our data, adenoviral infection of lymphoma cells seems to be mediated by CAR. In contrast, integrin receptors are unlikely to play a major role, because lymphoma cells were negative for alphavbeta3-integrins and negative for alphavbeta5-integrins. In conclusion, this study demonstrates that B-lymphoma cell lines and

  8. The Askin tumour. Neuroactodermic tumour of the thoracic wall

    International Nuclear Information System (INIS)

    Velazquez, P.; Nicolas, A. I.; Vivas, I.; Damaso Aquerreta, J.; Martinez-Cuesta, A.

    1999-01-01

    The Askin tumours is an extremely rare and malignant process in the thoracic pulmonary region during infancy and youth. The differential diagnosis has to be considered with other thoracic wall tumours that are more common in pediatrics like the undifferentiated neuroblastoma, the embionic rabdomiosarcoma, the Ewing sarcoma and the linfoma. A retrospective examination was carried out on 473 thoracic wall tumours from 1994 to 1997 at our centre, resulting in 4 patients with an anatomopathologically tested Askin tumour (ages from 13-21). All the cases were studied using simple radiography and CT. In two cases MRI was also used. The most common clinical manifestation was a palpable painful mass in the thoracic wall. In the simple radiograph the main finding was a large mass of extrapleural soft material, with costal destruction ( n=3) and a pleural effusion (n=2). In the CT study the mass was heterogeneous, with internal calcifications in one case. CT and MRI showed invasion in the mediastinum (n=1), medular channel (n=1) and phrenic and sulphrenic extension (n=1). The Askin tumour should be included in the differential diagnosis of thoracic wall masses in infant-youth ages. There are no specific morphological characteristics. Both CT and MRI are useful for the diagnosis, staging and follow up. (Author) 11 refs

  9. Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats

    International Nuclear Information System (INIS)

    Oliveira, André G.; Gomes-Marcondes, Maria Cristina C.

    2016-01-01

    Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition. Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour-bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays. Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste. Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats

  10. Carfilzomib With or Without Rituximab in the Treatment of Waldenstrom Macroglobulinemia or Marginal Zone Lymphoma

    Science.gov (United States)

    2018-02-05

    Marginal Zone Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory Marginal Zone Lymphoma; Refractory Waldenstrom Macroglobulinemia; Waldenstrom Macroglobulinemia

  11. Metastatic tumours to hypophysis: a report of three cases and review of literature

    Directory of Open Access Journals (Sweden)

    Tomaž Šmigoc

    2016-10-01

    Full Text Available Background. Metastatic tumours to pituitary are rare. The most frequent are metastases from breast and lung.Methods. In this paper, three cases of metastatic tumours to the pituitary are presented with panhypopituitarism as a common symptom: I a 60-year-old gentleman with metastasis of diffuse large B cell lymphoma, who presented with diabetes insipidus, II a 54-year-old lady with metastatic renal clear cell carcinoma and consequent disturbances in visual acuity, brain nerve paresis and III a 57-year-old lady with breast cancer metastasis, visual impairment and brain nerve paresis.Results. A transnasal endoscopic resection of the tumours was performed in all cases, followed by oncological treatment. All patients improved after the treatment.Conclusions. Despite the rarity of the disease, a metastatic tumour to the pituitary gland must be included in the differential diagnosis when symptoms such as diabetes insipidus, ophthalmoplegy due to brain nerve palsies, rapid course of the disease and headache are observed. In 20% to 30%, pituitary metastases are the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival and prognosis are generally poor.

  12. Childhood Adrenocortical Tumours: a Review

    Directory of Open Access Journals (Sweden)

    Marques-Pereira Rosana

    2006-05-01

    Full Text Available Abstract Childhood adrenocortical tumour (ACT is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6% or mixed with Cushing's syndrome (42.0% was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.

  13. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

    Directory of Open Access Journals (Sweden)

    Refaeli Yosef

    2008-05-01

    Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

  14. Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

    Science.gov (United States)

    Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

    2017-01-01

    We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

  15. The role of radiology in head and neck tumours in children

    Science.gov (United States)

    McHugh, Kieran

    2010-01-01

    Abstract Head and neck malignancy is rare in children. However, distinguishing malignant tumours from the more common and numerous benign causes of neck masses in childhood is crucial as many malignant conditions have an excellent prognosis with appropriate oncological management. Ultrasound, computed tomography and magnetic resonance imaging all have crucial roles in the diagnosis of head and neck malignancy in children and there is an emerging role for positron emission tomography, particularly in the management and follow-up of lymphoma. We describe the imaging appearances of the common malignant tumours arising in the extracranial head and neck in children, focusing on lymphoma, rhabdomyosarcoma and nasopharyngeal carcinoma. The clinical presentation and radiological appearances of benign tumours in the head and neck in children may overlap with those seen in malignant disease. We describe the imaging appearances of juvenile angiofibroma, vascular abnormalities involving the extracranial head and neck and cervical teratomas. Advances in both imaging techniques and cancer staging systems, many of the latter aimed at avoiding over-treatment and treatment-related complications, will lead to an increasingly central role for imaging in childhood head and neck cancer. PMID:20199940

  16. Increasing the radiosensitivity of tumours in an hypoxic environment using inhibitors of the pentose phosphate pathway

    International Nuclear Information System (INIS)

    Sahasrabudhe, M.B.; Bhonsle, S.R.; Krishnamurti, K.; Tilak, B.D.

    1977-01-01

    Rapidly growing tumours contain few blood vessels in the tumour mass. Cells in such tumours obtain nutrients and oxygen from the periphery by diffusion, resulting in a diminishing oxygen and nutrient gradient from the periphery to centre of the tumour mass. In normal tissues, oxygen is utilized via a tricarboxylic acid (TCA) cycle; in tumour cells oxygen is utilized via a hexose monophosphate (HMP) pathway and through the TCA cycle at a 30% reduced level. Interference with the HMP pathway selectively inhibits the utilization of oxygen by tumour cells, thus increasing the availability of oxygen to hypoxic cells situated deeper in the tumour mass. This effect has been exploited for increasing the radiosensitivity of tumour cells situated in an hypoxic environment. The influence of sixteen potential antimetabolites on the HMP pathway has been studied. Of these, six compounds, namely, (1) 2-carboxy 5-hydroxymethyl thiophene, (2) the sodium salt of 2:5 dicarbethoxy 3:4 dihydroxy thiophene, (3) the dihydrazide of 2:5 dicarboxy thiophene, (4) the dihydrazide of 3:4 dimethoxy 2:5 dicarboxy thiophene, (5) trithiocyanuric acid, and (6) cyanuric trithioglycollic acid showed an inhibiting effect on the HMP pathway without any influence on the TCA cycle. Influence of administration of compounds (1), (2) and (4) prior to radiation on the growth of transplanted fibrosarcomas in mice has been studied and is reported here. These three compounds showed marked potentiation of radiosensitivity of tumours. (author)

  17. Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

    NARCIS (Netherlands)

    Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

    Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

  18. Treatment Options for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... lymphoma may come back as indolent lymphoma. Treatment Option Overview Key Points There are different types of ...

  19. General Information about Adult Hodgkin Lymphoma

    Science.gov (United States)

    ... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

  20. Parotid lymphomas - clinical and computed tomogrphic imaging ...

    African Journals Online (AJOL)

    Parotid lymphomas - clinical and computed tomogrphic imaging features. ... South African Journal of Surgery ... Lymphoma has a clinical presentation similar ... CT scanning is a useful adjunctive investigation to determine the site and extent of ...

  1. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  2. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers.

    Science.gov (United States)

    Cleary, Allison S; Leonard, Travis L; Gestl, Shelley A; Gunther, Edward J

    2014-04-03

    Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.

  3. Imaging in unilateral Wilms tumour

    International Nuclear Information System (INIS)

    Brisse, Herve J.; Smets, Anne M.; Kaste, Sue C.; Owens, Catherine M.

    2008-01-01

    Wilms tumour is one of the most common malignancies in children, with an excellent prognosis after therapy. There is a very diverse approach to treatment according to geographical location. This variation in therapeutic attitude toward Wilms tumour, particularly between the United States and Europe, has consequences for the choice of imaging modality at diagnosis. In Europe, the International Society of Paediatric Oncology (SIOP) treatment protocol is based on chemotherapy followed by surgery. Imaging (US, CT and MRI), clinical history and examination will help predict whether the findings are consistent with Wilms tumour. Furthermore, in the UK preoperative image-guided biopsy is advised to help identify the small group of patients who, despite typical imaging features of Wilms tumour, have other types of neoplasia that require alternative management. In the United States, the National Wilms Tumor Study (NWTS) advises surgery prior to chemo- and radiotherapy. Hence imaging must provide detailed anatomical information for surgical planning. This article discusses the role of imaging at diagnosis and the relative strengths and weaknesses of the available radiological techniques. We also focus on imaging the lung for metastatic disease and the consequences (to the patient's ultimate outcome) of CT-diagnosed small pulmonary nodules and discuss the radiological diagnosis and consequences of tumour rupture present at diagnosis. (orig.)

  4. Effect of aspirin on tumour cell colony formation and evolution.

    Science.gov (United States)

    Wodarz, Dominik; Goel, Ajay; Boland, C Richard; Komarova, Natalia L

    2017-09-01

    Aspirin is known to reduce the risk of colorectal cancer (CRC) incidence, but the underlying mechanisms are not fully understood. In a previous study, we quantified the in vitro growth kinetics of different CRC tumour cell lines treated with varying doses of aspirin, measuring the rate of cell division and cell death. Here, we use these measured parameters to calculate the chances of successful clonal expansion and to determine the evolutionary potential of the tumour cell lines in the presence and absence of aspirin. The calculations indicate that aspirin increases the probability that a single tumour cell fails to clonally expand. Further, calculations suggest that aspirin increases the evolutionary potential of an expanding tumour cell colony. An aspirin-treated tumour cell population is predicted to result in the accumulation of more mutations (and is thus more virulent and more difficult to treat) than a cell population of the same size that grew without aspirin. This indicates a potential trade-off between delaying the onset of cancer and increasing its evolutionary potential through chemoprevention. Further work needs to investigate to what extent these findings apply to in vivo settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection. © 2017 The Author(s).

  5. Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

    International Nuclear Information System (INIS)

    Hendry, Jolyon H.

    2001-01-01

    Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

  6. Identification of differentially expressed proteins in spontaneous thymic lymphomas from knockout mice with deletion of p53

    DEFF Research Database (Denmark)

    Honoré, Bent; Buus, Søren; Claësson, Mogens H

    2008-01-01

    ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two-dimensiona......ABSTRACT: BACKGROUND: Knockout mice with a deletion of p53 spontaneously develop thymic lymphomas. Two cell lines (SM5 and SM7), established from two independent tumours, exhibited about fifty to seventy two-fold differentially expressed proteins compared to wild type thymocytes by two...... alpha type 3, transforming acidic coiled-coil containing protein 3, mitochondrial ornithine aminotransferase and epidermal fatty acid binding protein and down-regulation of adenylosuccinate synthetase, tubulin beta-3 chain, a 25 kDa actin fragment, proteasome subunit beta type 9, cofilin-1 and glia...

  7. Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

    Science.gov (United States)

    2017-08-28

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

  8. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  9. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  10. Pitfalls in colour photography of choroidal tumours

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  11. Pitfalls in colour photography of choroidal tumours.

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  12. Cure of incurable lymphoma

    International Nuclear Information System (INIS)

    De Nardo, Gerald L.; Sysko, Vladimir V.; De Nardo, Sally J.

    2006-01-01

    The most potent method for augmenting the cytocidal power of monoclonal antibody (MAb) treatment is to conjugate radionuclides to the MAb to deliver systemic radiotherapy (radioimmunotherapy; RIT). The antigen, MAb, and its epitope can make a difference in the performance of the drug. Additionally, the radionuclide, radiochemistry, chelator for radiometals and the linker between the MAb and chelator can have a major influence on the performance of drugs (radiopharmaceuticals) for RIT. Smaller radionuclide carriers, such as antibody fragments and mimics, and those used for pretargeting strategies, have been described and evaluated. All of these changes in the drugs and strategies for RIT have documented potential for improved performance and patient outcomes. RIT is a promising new therapy that should be incorporated into the management of patients with B-cell non-Hodgkin's lymphoma (NHL) soon after these patients have proven incurable. Predictable improvements using better drugs, strategies, and combinations with other drugs seem certain to make RIT integral to the management of patients with NHL, and likely lead to cure of currently incurable NHL

  13. Leucine-rich diet alters the 1H-NMR based metabolomic profile without changing the Walker-256 tumour mass in rats.

    Science.gov (United States)

    Viana, Laís Rosa; Canevarolo, Rafael; Luiz, Anna Caroline Perina; Soares, Raquel Frias; Lubaczeuski, Camila; Zeri, Ana Carolina de Mattos; Gomes-Marcondes, Maria Cristina Cintra

    2016-10-03

    Cachexia is one of the most important causes of cancer-related death. Supplementation with branched-chain amino acids, particularly leucine, has been used to minimise loss of muscle tissue, although few studies have examined the effect of this type of nutritional supplementation on the metabolism of the tumour-bearing host. Therefore, the present study evaluated whether a leucine-rich diet affects metabolomic derangements in serum and tumour tissues in tumour-bearing Walker-256 rats (providing an experimental model of cachexia). After 21 days feeding Wistar female rats a leucine-rich diet, distributed in L-leucine and LW-leucine Walker-256 tumour-bearing groups, we examined the metabolomic profile of serum and tumour tissue samples and compared them with samples from tumour-bearing rats fed a normal protein diet (C - control; W - tumour-bearing groups). We utilised 1 H-NMR as a means to study the serum and tumour metabolomic profile, tumour proliferation and tumour protein synthesis pathway. Among the 58 serum metabolites examined, we found that 12 were altered in the tumour-bearing group, reflecting an increase in activity of some metabolic pathways related to energy production, which diverted many nutrients toward tumour growth. Despite displaying increased tumour cell activity (i.e., higher Ki-67 and mTOR expression), there were no differences in tumour mass associated with changes in 23 metabolites (resulting from valine, leucine and isoleucine synthesis and degradation, and from the synthesis and degradation of ketone bodies) in the leucine-tumour group. This result sugge