Leukaemia and nuclear installations

International Nuclear Information System (INIS)

Beral, V.

1991-01-01

The editorial comments on the paper by Gardner et al (BMJ 17 Feb 1990) which suggests a link between leukaemia and the occupational exposure of father to radiation and draws attention to the very small numbers involved and the only other relevant data available from the children of A-bomb survivors which do not show evidence of increased risk of leukaemia in the offspring. (author). 10 refs

In vitro validation of bioluminescent monitoring of disease progression and therapeutic response in leukaemia model animals

International Nuclear Information System (INIS)

Inoue, Yusuke; Okubo, Toshiyuki; Tojo, Arinobu; Sekine, Rieko; Soda, Yasushi; Kobayashi, Seiichiro; Nomura, Akiko; Izawa, Kiyoko; Kitamura, Toshio; Ohtomo, Kuni

2006-01-01

The application of in vivo bioluminescence imaging to non-invasive, quantitative monitoring of tumour models relies on a positive correlation between the intensity of bioluminescence and the tumour burden. We conducted cell culture studies to investigate the relationship between bioluminescent signal intensity and viable cell numbers in murine leukaemia model cells. Interleukin-3 (IL-3)-dependent murine pro-B cell line Ba/F3 was transduced with firefly luciferase to generate cells expressing luciferase stably under the control of a retroviral long terminal repeat. The luciferase-expressing cells were transduced with p190 BCR-ABL to give factor-independent proliferation. The cells were cultured under various conditions, and bioluminescent signal intensity was compared with viable cell numbers and the cell cycle stage. The Ba/F3 cells showed autonomous growth as well as stable luciferase expression following transduction with both luciferase and p190 BCR-ABL, and in vivo bioluminescence imaging permitted external detection of these cells implanted into mice. The bioluminescence intensities tended to reflect cell proliferation and responses to imatinib in cell culture studies. However, the luminescence per viable cell was influenced by the IL-3 concentration in factor-dependent cells and by the stage of proliferation and imatinib concentration in factor-independent cells, thereby impairing the proportionality between viable cell number and bioluminescent signal intensity. Luminescence per cell tended to vary in association with the fraction of proliferating cells. Although in vivo bioluminescence imaging would allow non-invasive monitoring of leukaemia model animals, environmental factors and therapeutic interventions may cause some discrepancies between tumour burden and bioluminescence intensity. (orig.)

Causes of childhood leukaemia and lymphoma

International Nuclear Information System (INIS)

Lightfoot, Tracy J.; Roman, Eve

2004-01-01

Childhood cancer is rare comprising less than 1% of all malignancies diagnosed each year in developed countries. Leukaemia is the commonest form of cancer in children accounting for around a third of all childhood cancer, with acute lymphoblastic leukaemia (ALL) being the most prevalent. Biologically specific subtypes of ALL and acute myeloblastic leukaemia (AML), the other major morphological type of childhood leukaemia, are characterised by chromosomal changes. Whilst over 200 genes have been associated with chromosomal translocations, to date, only MLL, TEL, and AML1 have been linked with childhood leukaemia. Interestingly, there is increasing evidence to support the theory that gene rearrangements such as these may originate in utero. As with many other human diseases, both genetic and environmental factors have been implicated in the aetiology of the disease. Although much has been documented with regard to diet, smoking, alcohol consumption and recreational and prescription drug use during pregnancy, there is no consistent evidence to support a link with any of these factors and childhood leukaemia. However, findings from studies investigating prenatal and early life exposures are often based on small numbers of cases as both the type of cancer and exposure are rare. Furthermore, accurate information relating to past exposures can be difficult to obtain and is often reliant on self-reporting. To further our understanding of the aetiology of childhood leukaemia and lymphoma, there are areas which clearly warrant investigation. These include collection of parental dietary folate data combined with genetic analysis of the folate related genes, in utero exposure to DNA topoisomerase II inhibitors, and the possible effects of assisted reproduction technology on disease susceptibility

Leukaemia in East Suffolk

International Nuclear Information System (INIS)

Bush, M.F.H.

1983-09-01

An investigation was conducted by the East Suffolk Health Authority to determine whether there were any geographical variations in the incidence of leukaemia over the last fifteen years in East Suffolk suggesting an environmental hazard, e.g. Sizewell Power Station. No areas were found to have a statistically significant increased incidence of leukaemia cases although there did appear to be a cluster of cases in the Leiston area. (U.K.)

Clinical presentation of acute myeloid leukaemia - A decade-long institutional follow-up.

Science.gov (United States)

Kulsoom, Bibi; Shamsi, Tahir Sultan; Ahmed, Nikhat; Hasnain, Syed Nazrul

2017-12-01

To analyse a decade-long pattern of clinical presentation of acute myeloid leukaemia patients and compare it with contemporary data. The retrospective cohort study was conducted at the National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, and comprised of medical record of acute myeloid leukaemia patients from March 2006 to October 2016. Data noted age at presentation, gender, medical history, physical examination, blood and bone marrow investigations such as, haemoglobin levels, blood cell count myeloperoxidase activity, periodic acid-Schiff and reticulin staining as well as final diagnosis. Comparison, where possible, was done with contemporary literature. SPSS 19 was used for data analysis. Of the 626 subjects, 248(39.6%) were females and 378(60.4%) males. The overall mean age was 35.3±17.1 years. The most common age group was 15-40 years with 354(56.5%) patients. The most common subtype was acute myeloid leukaemia with maturation 183(33.6%). Myeloperoxidase activity was positive for the majority of the acute myeloid leukaemia patients. Periodic acid-Schiff test, done on only selected patients, was mostly negative. Reticulin staining was positive for 113(65.3%) patients. The most common presenting complaints were fever 266(71.9%) and weakness 168(45.4%). Mean haemoglobin and red blood cell count were 8.3 ± 2.4 g/dL and 2.9 ± 1.2 1012/L, respectively. Acute myeloid leukaemia was found to be a highly variable disease that presented with non-specific signs and symptoms.

Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction sites, with a comparison with Sellafield nuclear site

International Nuclear Information System (INIS)

Kinlen, L.J.; Dickson, M.; Stiller, C.A.

1995-01-01

The objective was to determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin's lymphoma. A study was undertaken of the incidence of leukaemia and non-Hodgkin's lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. A 37% excess of leukaemia and non-Hodgkin's lymphoma at 0-14 years of age was recorded during construction and the following calendar year. The excesses were greater at times when construction workers and operating staff overlapped (72%), particularly in areas of relatively high social class. For several sites the excesses were similar to or greater than that near the nuclear site of Sellafield (67%), which is distinctive in its large workforce with many construction workers. Seascale, near Sellafield, with a ninefold increase had an unusually high proportion of residents in social class I. The findings support the infection hypothesis and reinforce the view that the excess of childhood leukaemia and non-Hodgkin's lymphoma near Sellafield has a similar explanation. (author)

Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy.

Science.gov (United States)

Sandri, Sara; De Sanctis, Francesco; Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T; Nishimura, Michael I; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

2017-10-20

Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment.

Cranial irradiation of leukaemia in childhood

International Nuclear Information System (INIS)

Gyenes, Gy.; Sator, G.; Varjas, G.

1979-01-01

The fundamental combined cytostatic treatment, initiated immediatly after the diagnosis, of the acute lymphoid leukaemia in the childhood is the method of choice. The haematologic remission, however, does not signify recovery, the starting-place of the relapse is mostly in the central nervous system. Telecobalt irradiation of the neurocranium using the known ray-physical and ray-biological advantages regularly distroys the leukaemia cells hidden in this region. In the paper the experiences gained with the irradiation of 151 children are reported. Further ulterior informations could be obtained by the authors only from 66 patients, out of them meningeosis leukaemia developed in 12%. (author)

Acute leukaemia: making sense of a complex blood cancer.

LENUS (Irish Health Repository)

Meenaghan, Teresa

2012-01-01

Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.

Large granular lymphocytic leukaemia pathogenesis and management.

Science.gov (United States)

Dearden, Claire

2011-02-01

The WHO classification recognises three distinct disorders of large granular lymphocytes: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and agressive NK-cell leukaemia. Despite the different cell of origin, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK-cell leukaemia and the rare CD56(+) aggressive T-LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease. © 2010 Blackwell Publishing Ltd.

Neurological Complications Of Chronic Myeloid Leukaemia: Any ...

African Journals Online (AJOL)

, of the neurological deficits complicating chronic myeloid leukaemia. Method: Using patients\\' case folders and haematological malignancy register all cases of chronic myeloid leukaemia seen in Jos University Teaching Hospital between July ...

Cytogenetics of Post-Irradiation Mouse Leukaemia

Energy Technology Data Exchange (ETDEWEB)

Wald, N.; Pan, S.; Upton, A.; Brown, R. [Graduate School of Public Health, University of Pittsburgh, PA (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States)

1969-11-15

The interrelationship between radiation, cytogenetic abnormalities, and viruses in leukaemogenesis has been studied in the RF/Un mouse which develops a high incidence of granulocytic leukaemia on radiation exposure. A virus-like agent has been demonstrated in such leukaemic animals and the disease has been transmitted by passage of apparently acellular materials from irradiated primary animals to normal recipients. Pilot cytogenetic studies revealed consistent abnormal chromosome markers and modal shifts in both irradiated leukaemic animals and in non-irradiated animals developing leukaemia after passage injection. To define better the relationship between consistent bone-marrow chromosome aberrations and postirradiation primary and passaged leukaemia, 100 RF/Un mice were studied which were irradiated with 300 R of 250-kVp X-rays at 100 weeks of age and subsequently developed leukaemia. Eighty-seven had granulocytic leukaemia and in 72 of these, bone-marrow cytogenetic abnormalities were found. The distribution of-numerical and structural chromosome aberrations in 3225 cells studied are reviewed in derail. The correlation of specific aberrations to clinical and histopathologic findings has been attempted: Sequential passages of apparently cell-free material from the post-irradiation leukaemic mice into unirradiated RE/Un recipients and subsequent passages from leukaemic recipients were performed to observe the evolution of any initial chromosome markers and shifts in modal chromosome number in the passage generations. Two-hundred-thirty-six mice were inoculated with the material obtained either from primary post-irradiation leukaemic mice or from serially-passaged leukaemia cases. In the most extensive passaged line, 22 transfer generations containing 129 leukaemic mice were examined by clinical, histopathologic, -haematologic and cytogenetic procedures. Evolution of abnormal chromosome modes from 41 in the early passages to 39 chromosomes consistently after the 4

Leukaemia: some unsolved problems

International Nuclear Information System (INIS)

Doll, Richard; Darby, Sarah

1991-01-01

The objectives of this session of the Human Radiation Research workshop were to review knowledge of radiation-induced leukaemia and identify major uncertainties and areas for future research. It is concluded that some of the most outstanding problems are to determine the risk of childhood leukaemia produced by parental gonad exposure, the relative risks produced by exposure of the embryo and fetus at different stages of intra-uterine life, how long the effect of intra-uterine radiation persists, and the leukaemogenic effects of radon. (UK)

An investigation into childhood leukaemia in Northamptonshire

International Nuclear Information System (INIS)

1996-01-01

This report has been written specifically for the families of children who have had leukaemia in Northamptonshire. It gives the Health Authority's answers to the questions and worries that they raised at a meeting we had on 22nd September 1995. The report will also be circulated to other people who have been concerned by this problem and will, therefore, include some background information as well. The report thus has several different purposes: to give a brief summary of what is known about leukaemia and its causes; to explain the implications of having five cases of childhood leukaemia in a small area over a number of years; to let people know what Northamptonshire Health Authority has done in response to their concerns; to explain why a local epidemiological study of these cases could not tell us what caused leukaemia in the affected children; to reassure residents in the Pembroke Road area that we have found no reason to be concerned that their children are at an increased risk of developing leukaemia; to give information to the families about the current scientific evidence on the relationship between several potential environmental hazards they have identified and childhood leukaemia; to let people know that the important questions about what causes leukaemia in children are being addressed in several important and well-designed scientific studies. We hope that this report can be understood by people who are not familiar with medical jargon. Sometimes it has been necessary to use medical and technical terms, so at the back of this report there is a glossary which gives the meaning of any medical terms used

Aetiology of childhood acute leukaemias: Current status of knowledge

International Nuclear Information System (INIS)

Rossig, C.; Juergens, H.

2008-01-01

Acute leukaemia is a consequence of malignant transformation of a haematopoietic progenitor cell. Molecular studies have revealed a prenatal origin of many childhood leukaemias. According to current models, a pre-leukaemic stem cell clone is generated by a first mutation in utero which, in a minority of children, progresses to leukaemia after receiving further postnatal genetic hits. The nature of pre- and postnatal events involved in leukemogenesis in children is not well understood. Although genetic predisposition and specific environmental exposures may account for individual cases, the bulk of childhood leukaemia cannot be explained by any of these factors. The higher incidence of the most common leukaemia subtype in affluent societies, as well as the age peak between 2-5 y, suggest a contributory role of socioeconomic factors. An abnormal immune response during delayed exposure to common infections provides a plausible mechanism for malignant progression of pre-leukaemic clones in a subgroup of children. As highlighted in this review, a common cause for all types and subtypes of childhood leukaemia is highly unlikely. Deeper insights into the pathogenesis of childhood leukaemia will rely on large-scale and combined epidemiological and bio-molecular studies. (authors)

Fallout, radiation doses near Dounreay, and childhood leukaemia

International Nuclear Information System (INIS)

Darby, S.C.; Doll, Richard

1987-01-01

Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by underestimate of the relative biological efficiency of high compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease and exposure to other, unidentified environmental agents. These findings weigh against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated. (author)

immunophenotyping of acute leukaemias by flow cytometry

African Journals Online (AJOL)

2009-12-01

Dec 1, 2009 ... acute leukaemias and selection of monoclonal antibodies. Data sources: The literature review ... step towards diagnosis of leukaemia. It should be ... antibodies, (B-cell, T-cell, myeloid, monocytic, plasma cells) which is based ...

Supplementary oxygen and risk of childhood lymphatic leukaemia.

Science.gov (United States)

Naumburg, E; Bellocco, R; Cnattingius, S; Jonzon, A; Ekbom, A

2002-01-01

Childhood leukaemia has been linked to several factors, such as asphyxia and birthweight, which in turn are related to newborn resuscitation. Based on the findings from a previous study a population-based case-control study was performed to investigate the association between childhood leukaemia and exposure to supplementary oxygen and other birth-related factors. Children born in Sweden and diagnosed with lymphatic leukaemia between 1973 and 1989 (578 cases) were individually matched by gender and date of birth to a randomly selected control. Children with Down's syndrome were excluded. Exposure data were blindly gathered from antenatal, obstetric and other standardized medical records. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression. Resuscitation with 100% oxygen with a facemask and bag immediately postpartum was significantly associated with an increased risk of childhood lymphatic leukaemia (OR = 2.57, 95% Cl 1.21-6.82). The oxygen-related risk further increased if the manual ventilation lasted for 3 min or more (OR = 3.54, 95% CI 1.16-10.80). Low Apgar scores at 1 and 5 min were associated with a non-significantly increased risk of lymphatic leukaemia. There were no associations between lymphatic leukaemia and supplementary oxygen later in the neonatal period or other birth-related factors. Resuscitation with 100% oxygen immediately postpartum is associated with childhood lymphatic leukaemia, but further studies are warranted to confirm the findings.

Comprehensive Analysis of MILE Gene Expression Data Set Advances Discovery of Leukaemia Type and Subtype Biomarkers.

Science.gov (United States)

Labaj, Wojciech; Papiez, Anna; Polanski, Andrzej; Polanska, Joanna

2017-03-01

Large collections of data in studies on cancer such as leukaemia provoke the necessity of applying tailored analysis algorithms to ensure supreme information extraction. In this work, a custom-fit pipeline is demonstrated for thorough investigation of the voluminous MILE gene expression data set. Three analyses are accomplished, each for gaining a deeper understanding of the processes underlying leukaemia types and subtypes. First, the main disease groups are tested for differential expression against the healthy control as in a standard case-control study. Here, the basic knowledge on molecular mechanisms is confirmed quantitatively and by literature references. Second, pairwise comparison testing is performed for juxtaposing the main leukaemia types among each other. In this case by means of the Dice coefficient similarity measure the general relations are pointed out. Moreover, lists of candidate main leukaemia group biomarkers are proposed. Finally, with this approach being successful, the third analysis provides insight into all of the studied subtypes, followed by the emergence of four leukaemia subtype biomarkers. In addition, the class enhanced DEG signature obtained on the basis of novel pipeline processing leads to significantly better classification power of multi-class data classifiers. The developed methodology consisting of batch effect adjustment, adaptive noise and feature filtration coupled with adequate statistical testing and biomarker definition proves to be an effective approach towards knowledge discovery in high-throughput molecular biology experiments.

Pneumocystis carinii Pneumonia in Acute Lymphatic Leukaemia ...

African Journals Online (AJOL)

A case report of a patient who developed fatal pneumocystis pneumonia while in remission from acute lymphatic leukaemia is presented. Clinical and aetiological aspects of this rare infection are discussed. Attention is drawn to diagnostic pitfalls encountered in leukaemia.

Childhood leukaemia around Canadian nuclear facilities. Phase 1

International Nuclear Information System (INIS)

Clarke, E.A.; McLaughlin, J.; Anderson, T.W.

1989-05-01

A ninefold excess risk of leukaemia, as observed in vicinity of the Sellafield facility, was not observed amongst children born to mothers residing in the areas around nuclear research facilities and uranium mining, milling and refining facilities in Ontario. In the vicinity of nuclear research facilities, the rate of leukaemia was, in fact, less than expected. In the areas around the uranium mining, milling and refining facilities; leukaemia occurred slightly more frequently than expected; however, due to small frequencies these results may have risen by chance. A slightly greater than expected occurrence of leukaemia was also detected, which may well have been due to chance, in an exploratory study of the areas around nuclear power generating stations in Ontario

Genital ulcers as diagnostic clue for acute myeloid leukaemia.

Science.gov (United States)

Schröder, Sina D; Krause, Stefan W; Erfurt-Berge, Cornelia

2018-04-23

Acute myeloid leukaemia is a myeloid neoplasm with an extremely varying clinical appearance. Skin lesions are common for specific subtypes of acute myeloid leukaemia but are often misinterpreted. Here, we present a case of acute myeloid leukaemia in a young woman exhibiting genital ulcerations and gingival erosions. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Analysis of images of acute human and animal leukaemia

International Nuclear Information System (INIS)

Feinermann, Emmanuel

1981-01-01

This research thesis first proposes a review of the development of stereology: historical backgrounds, basic principles. It discusses the choices regarding instrumentation: Coulter counter (principle and theory), quantitative analysis of particles, image analyser (optical microscope, epidiascope, scanners, detection, electronic pencil, computers, programming and data processing system), and stereo-logical parameters. The author then reports the stereo-logical study of acute human leukaemia: definition, classification, determination of spherical particle size distribution, lympho-blast size distributions. He reports the comparative study of rat L 5222 leukaemia and Brown Norway rat acute myelocytic leukaemia, and discusses their relationship with acute human leukaemia

Clinicopathological features of transient myeloproliferative syndrome and congenital leukaemia

International Nuclear Information System (INIS)

Sajid, N.; Ahmed, N.; Mahmood, S.

2010-01-01

The objectives of the study were to determine the spectrum of the clinical and pathological findings, the management and prognosis of patients of transient myeloproliferative syndrome (TMS) and congenital leukaemia. Study Design: Case series. Place and Duration of Study: The study was conducted over a period of 8 years, from January 2000 to December 2007, at the Children's Hospital and the Institute of Child Health, Lahore. Methodology: Suspected patients presenting with fever, pallor, bruises and hepatosplenomegaly and diagnosed as either transient myeloproliferative disorder or congenital leukaemia were studied. The complete blood count, reticulocyte count, leukocyte alkaline phosphatase score, liver function tests, karyotyping studies and bone marrow aspiration biopsy were performed in all of those patients. Management and out come was noted. Results were described as frequency percentages. Results: Out of 10,000 patients presenting during this period, 24 patients were diagnosed as either of transient myeloproliferative syndrome or congenital leukaemia. Fifteen of these were diagnosed as patients of TMS and 9 as patients of congenital leukaemia. Down syndrome (DS) was diagnosed in 75% of these patients. TMS patients were put on supportive treatment and recovered spontaneously. One DS patient with congenital leukaemia went into spontaneous remission and 2 of DS patients with congenital leukaemia responded to chemotherapy while rest of them either died or lost to follow-up. Conclusion: TMS and congenital leukaemia were not very uncommon in the studied population. Majority had Down syndrome. It is important to differentiate their clinical and pathological presentations for proper management. TMS may resolve with supportive treatment while congenital leukaemia is a fatal condition requiring chemotherapy. (author)

Childhood leukaemia and socioeconomic status: What is the evidence?

International Nuclear Information System (INIS)

Adam, M.; Rebholz, C. E.; Egger, M.; Zwahlen, M.; Kuehni, C. E.

2008-01-01

The objectives of this systematic review are to summarise the current literature on socioeconomic status (SES) and the risk of childhood leukaemia, to highlight methodological problems and formulate recommendations for future research. Starting from the systematic review of Poole et al. (Socioeconomic status and childhood leukaemia: a review. Int. J. Epidemiol. 2006;35(2):370-384.), an electronic literature search was performed covering August 2002-April 2008. It showed that (1) the results are heterogeneous, with no clear evidence to support a relation between SES and childhood leukaemia; (2) a number of factors, most importantly selection bias, might explain inconsistencies between studies; (3) there is some support for an association between SES at birth (rather than later in childhood) and childhood leukaemia and (4) if there are any associations, these are weak, limited to the most extreme SES groups (the 10-20% most or least deprived). This makes it unlikely that they would act as strong confounders in research addressing associations between other exposures and childhood leukaemia. Future research should minimise case and control selection bias, distinguish between different SES measures and leukaemia subtypes and consider timing of exposures and cancer outcomes. (authors)

Childhood leukaemia, fallout and radiation doses near Dounreay

International Nuclear Information System (INIS)

Darby, S.C.; Doll, Richard

1987-01-01

The possible explanations of the recently reported increase in the incidence of childhood leukaemia around Dounreay are examined in the light of the changes in national leukaemia incidence that occurred during the period of exposure to fallout from international atmospheric testing of nuclear weapons. It is concluded that the increase cannot be due to underestimation of the risk of leukaemia per unit dose of radiation, nor to an underestimate of the relative biological efficiency of high as compared with low LET radiation. Possible explanations of the increase include an underestimate of the red bone marrow doses due to the Dounreay discharges relative to those from fallout, a misconception of the site of origin of childhood leukaemia, epidemics of infectious disease and exposure to some other unidentified environmental agent. (author)

Leukaemia risks and exposure to ionizing radiations. ASN seminar, Tuesday, June 9, 2015, report

International Nuclear Information System (INIS)

Niel, Jean-Christophe; Samain, Jean-Paul; Colonna, Marc; Maynadie, Marc; Richardson, David; Bey, Pierre; Leuraud, Klervi; Laurier, Dominique; Hemon, Denis; Spycher, Ben; Kosti, Ourania; Bouville, Andre; Grosche, Bernd; Ziegelberger, Gunde; Kesminiene, Ausrele; Clavel, Jacqueline; Smeesters, Patrick; Murith, Christophe

2015-08-01

This seminar aims at proposing a review of present knowledge on leukaemia risks for children and adults associated with ionizing radiations, and at sharing knowledge between experts. After an introduction which outlined the interest of the ASN in research issues, and the importance awarded by the ASN to the variety of points of view, a first session addressed leukaemia and exposures to ionizing radiations. The contributions addressed some general aspects (an overview of leukaemia in France, the different types of adult and child leukaemia), leukaemia and acute exposures to ionizing radiations (ionizing radiation and leukaemia among Japanese bomb survivors, risks of leukaemia after radiotherapy), leukaemia and chronic exposures to ionizing radiations (assessment of epidemiological studies for adult chronic exposures). The second session addressed childhood leukaemia and ionizing radiations. The contributions of this second session more particularly addressed the following topics: childhood leukaemia and natural radioactivity (French studies, synthesis of international studies and a new Swiss study), childhood leukaemia and proximity of nuclear base installations (assessment of national and international studies, analysis of cancer risks in populations near nuclear facilities in the US, calculation of dose at the medulla as example of dosimetry of ionizing radiations and leukaemia, conclusions of the 2012 MELODI workshop), childhood leukaemia and scanner (recent results and perspectives), childhood leukaemia and other risk factors (etiology of childhood leukaemia - presentation of French studies initiated by the INSERM, and presentation of studies initiated by BfS)

Childhood leukaemia around Canadian nuclear facilities. Phase 2

International Nuclear Information System (INIS)

Clarke, E.A.; McLaughlin, J.; Anderson, T.W.

1991-06-01

Prompted by findings of increased occurrence of childhood leukaemia in the vicinity of some nuclear facilities in the United Kingdom, this study aimed to investigate whether the frequency of leukaemia among children born to mothers living near nuclear facilities in Ontario differed from the provincial average. The Ontario Cancer Registry was used to identify 1894 children aged 0 to 14 years who died from leukaemia between 1950 and 1987, and 1814 children who were diagnosed with leukaemia between 1964 and 1986. Residence at birth and death was obtained from birth and death certificates. Analyses were performed separately for nuclear research and development facilities; uranium mining, milling and refining facilities; and, nuclear generating stations; and for areas within the same county as the facility and 'nearby' - within a 25-km radius of the facility. Risk estimates were calculated as the ratio of the observed (O) number of events over the expected (E) number. In the vicinity of nuclear research and development facilities the rate of leukaemia was less than expected and within the bound of chance variation. In the areas around the uranium mining, milling and refining facilities and nuclear power plants leukaemia occurred slightly more frequently than expected, but due to small frequencies these differences may have arisen due to chance. Large differences between observed and expected rates were not detected around any of the Ontario facilities. This study was large enough to detect excess risks of the magnitude reported in the United Kingdom, but it was not large enough to discriminate between the observed relative risks and a chance finding. Levels of leukaemia detected near nuclear generating stations indicate the need for further investigation. (20 tabs., 15 figs., 32 refs.)

Proximity to overhead power lines and childhood leukaemia

DEFF Research Database (Denmark)

Amoon, Aryana T; Crespi, Catherine M; Ahlbom, Anders

2018-01-01

BACKGROUND: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with d...

New leukaemia link

International Nuclear Information System (INIS)

Roche, P.

1993-01-01

A new study around the Aldermaston and Burghfield nuclear weapons establishments published in the British Medical Journal has found a similar association between the risk of childhood leukaemia and employment in the nuclear industry to that found by Professor Gardner in 1990 at Sellafield. It suggests that occupational exposure to radiation prior to conception increases the risk of a subsequent child developing leukaemia by 9 times. It is clear that working at Aldermaston or Burghfield does not explain the entire excess of cancers -there must be another factor at work. The one factor that Aldermaston, Burghfield, Sellafield and Dounreay where a similar pattern is found, have in common is plutonium. Whilst further studies are important to determine the role played by plutonium, it should be declared 'guilty until proven innocent'. The production and use of plutonium should cease immediately. (author)

Attentional ability among survivors of leukaemia.

Science.gov (United States)

Rodgers, J; Horrocks, J; Britton, P G; Kernahan, J

1999-04-01

Attentional ability in 19 survivors of acute lymphoblastic leukaemia and 19 sibling controls was assessed using a neuropsychological model of attention. Analysis revealed that children who had received treatment for leukaemia exhibited significantly poorer performance on measures of the "focus encode" and "focus execute" elements of attention and on measures of the ability to respond to external cues and feedback. No significant differences in performance were found for measures of sustained attention and the ability to shift attention. These results indicate that children who have received treatment for leukaemia may experience highly specific attentional deficits that could have an impact on academic performance, particularly mathematical and reading skills. It is suggested that this underlying attentional deficit might be the source of the neuropsychological sequelae associated with the disease. Future attempts at remediation should incorporate activities specifically designed to ameliorate focusing difficulties.

Child leukaemia and low frequency electromagnetic fields

International Nuclear Information System (INIS)

Clavel, J.

2009-01-01

The author discusses the possible causes of child leukaemia: exposure to natural ionizing radiation (notably radon), to pesticides, and to hydrocarbons emitted by road traffic. Some studies suggested that an inadequate reaction of the immune system to an ordinary infection could result in leukaemia. Other factors are suspected, notably extremely low frequency electromagnetic fields, the influence of which is then discussed by the author. She evokes and discusses results of different investigations on this topic which have been published since the end of the 1970's. It appears that a distance less than 50 meters from high voltage lines or the vicinity of transformation stations may double the risk of child leukaemia

Low dose irradiation and risk of leukaemia: A case-control study

International Nuclear Information System (INIS)

Chobanova, N.; Bayrakova, A.

1997-01-01

The effect of low dose irradiation (medical X-ray diagnostic) on the developing of leukaemias in adults is investigated. The influence of non-radiation agents (occupational exposure to chemical carcinogens, past viral infections, family aggregations) to leukaemias are considered also. During this retrospective study 228 patients have been examined with the following diagnosis: acute myeloid leukaemia, chronic myelogenous leukaemias, myelodisplastic syndrome and non-Hodgkin lymphoma (diagnosed between 1991-1993). Each case has been matched with two controls. Statistically significant increase has been found in the risk of developing leukaemias after X-ray diagnostic irradiation (OR = 1.98, 95% CI = 1.14 ./. 3.46). Exposure to chemical agents is also associated with significant increase in the risk (OR = 1.98, 95% CI = 1.25 ./. 2.86). (author)

Acute lymphocytic leukaemia in children in the Netherlands

International Nuclear Information System (INIS)

Does-van den Berg, A. van der.

1980-01-01

Some features, present at diagnosis in children with acute lymphocytic leukaemia, investigated during the period 1973-1975, and the results of treatment according to protocol AL II of the Dutch Childhood Leukaemia Study Group (SNWLK), are described. This report concerns the results of induction treatment, elective treatment of the central nervous system, and also of the prospective comparative study on the influence of the addition of cyclophosphamide to maintenance treatment with 6-mercaptopurine and methotrextate. In the context of the investigation of long-term side effects of disease and treatment, the immunocompetence of children with acute lymphocytic leukaemia in continuous remission after cessation of therapy was studied. (Auth.)

Pattern of Leukaemia Patients Admitted in Ayub Teaching Hospital Abbottabad

International Nuclear Information System (INIS)

Khan, T. M.

2016-01-01

Background: Any tissue of the body can give rise to cancer. However, those tissues which multiply rapidly are at high risk of developing cancer and haematopoietic system is one of them. Neoplasms of this system are known as leukaemia and lymphoma, according to the types of white cells involved.Study of cancer patterns in different societies, however can contribute a substantial knowledge about the aetiology of cancer. The present Study was designed and aimed to estimate the frequency of different types of leukaemia in patients admitted in Ayub Teaching hospital Abbottabad. Methods: Data from the patients admitted at oncology Department of Ayub Teaching Hospital Abbottabad from 2010 to 2015 was collected and analysed to calculate cumulative and year-wise frequency of leukaemia and its major types. Frequency distribution with reference to gender and age was also calculated. Results: In our analysis about 16 percent patients had acute myelocytic leukaemia and 32 percent patients had acute lymphocytic leukaemia; while chronic myeloid leukaemia outnumbered chronic lymphocytic leukaemia (11 percent and 3 percent); Hodgkin lymphoma was seen in 18 percent cases while Non Hodgkin lymphoma (NHL) was present in 20 percent cases. Out of the total, 150 cases (75 percent) belonged to mountainous areas of Hazara, i.e., 40 cases belonged to Kohistan, another 40 cases were residents of Battagram, 45 cases belonged to hilly areas of Mansehra and 25 cases to Kaghan valley, while only 50 (25 percent) cases were from the plain areas of Abbottabad and Haripur districts, i.e., 20 and 30 cases respectively. Conclusion: Leukaemia is more common in hilly areas of Hazara, since majority of the cases belonged to well-known mountainous regions of Kohistan, Battagram, Kaghan or Mansehra and only few cases belonged to the plain areas of Abbottabad and Haripur districts. (author)

Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain

International Nuclear Information System (INIS)

Kinlen, L.

1988-01-01

Increases of leukaemia in young people that cannot be explained in terms of radiation have been recorded near both of Britain's nuclear reprocessing plants at Dounreay and Sellafield. These were built in unusually isolated places where herd immunity to a postulated widespread virus infection (to which leukaemia is a rare response) would tend to be lower than average. The large influxes of people in the 1950s to those areas might have been conducive to epidemics. The hypothesis has been tested in Scotland in an area identified at the outset as the only other rural area that received a large influx at the same time, when it was much more cut off from the nearest conurbation than at present - the New Town of Glenrothes. A significant increase of leukaemia below age 25 was found (10 observed, expected 3.6), with a greater excess below age 5 (7 observed, expected 1.5). (author)

Some implications of current therapy in leukaemia | Jacobs | South ...

African Journals Online (AJOL)

Improved survival in acute leukaemia follows aggressive combination chemotherapy based on a proper understanding of tumour cell kinetics and principles of modern pharmacology. Such cytoreduction ... Logically, patients with acute leukaemia should have the benefit of management in these units. S. Afr. Med. J., 48 ...

Childhood leukaemia around nuclear facilities

International Nuclear Information System (INIS)

Wojcik, Andrzej; Feychting, Maria

2010-06-01

In December 2007 the German Federal Office for Radiation Protection (BfS) published a report on the incidence of childhood cancers among children living in the vicinity of 16 German nuclear power plants. The results show a significantly enhanced risk of leukaemia in children aged below 5 years, who live within 5 km from a nuclear power plant. The study is known as KiKK (Epidemiologische Studie zu Kinderkrebs in der Umgebung von Kernkraftwerken) and stirred considerable concern about the safety of nuclear installations. In this review we summarise the present state-of-the art regarding childhood leukaemia in the vicinity of nuclear installations and present the main results of the KiKK study with a critical evaluation

Childhood leukaemia around nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Wojcik, Andrzej (Centre for Radiation Protection Research, GMT Dept., Stockholm Univ., Stockholm (Sweden)); Feychting, Maria (Inst. of Environmental Medicine, Karolinska Inst., Stockholm (Sweden))

2010-06-15

In December 2007 the German Federal Office for Radiation Protection (BfS) published a report on the incidence of childhood cancers among children living in the vicinity of 16 German nuclear power plants. The results show a significantly enhanced risk of leukaemia in children aged below 5 years, who live within 5 km from a nuclear power plant. The study is known as KiKK (Epidemiologische Studie zu Kinderkrebs in der Umgebung von Kernkraftwerken) and stirred considerable concern about the safety of nuclear installations. In this review we summarise the present state-of-the art regarding childhood leukaemia in the vicinity of nuclear installations and present the main results of the KiKK study with a critical evaluation

Late effects of treatment in survivors of childhood acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Roux, P.

1987-01-01

The overall aim of this study was a comprehensive assessment of the nature and severity of the late effects of treatment in a group of children surviving acute lymphoblastic leukaemia. In the absence of damage preceding treatment, late effects could be ascribed to treatment. Cranial irradiation, methotrexate, L-asparaginase and cytosine arabinoside are therapeutic modalities most likely to cause injury to the central nervous system. Survivors of childhood leukaemia also showed an increase in weight-for-height during and after therapy which appeared to be the consequence of a loss in statural growth as well as increasing weight-for-age. Assessment of endocrine function in leukaemia survivors indicated abnormalities in the regulation of growth hormone and thyroid stimulating hormone in some patients. Survivors of childhood leukaemia were shown to have an intellectual deficit compared with their siblings and a high incidence of visual-perceptual defects. The intellectual effects of lower doses of cranial irradiation are as yet unknown. A variety of minor neurological abnormalities were detected among leukaemia survivors and thought to be related to preceding central nervous system 'prophylactic' chemotherapy and irradiation. A new instrument, the functional deficit score, was derived to reflect overall outcome in survivors of childhood leukaemia. With few exceptions, leukaemia survivors in this study had received 2400 rads of deep x-ray therapy as cranial irradiation. This dosage has since been reduced world-wide. Current cranial irradiation 'prophylaxis' consists of 1800 rad of megavoltage radiotherapy

Late effects of treatment in survivors of childhood acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Roux, P

1987-01-01

The overall aim of this study was a comprehensive assessment of the nature and severity of the late effects of treatment in a group of children surviving acute lymphoblastic leukaemia. In the absence of damage preceding treatment, late effects could be ascribed to treatment. Cranial irradiation, methotrexate, L-asparaginase and cytosine arabinoside are therapeutic modalities most likely to cause injury to the central nervous system. Survivors of childhood leukaemia also showed an increase in weight-for-height during and after therapy which appeared to be the consequence of a loss in statural growth as well as increasing weight-for-age. Assessment of endocrine function in leukaemia survivors indicated abnormalities in the regulation of growth hormone and thyroid stimulating hormone in some patients. Survivors of childhood leukaemia were shown to have an intellectual deficit compared with their siblings and a high incidence of visual-perceptual defects. The intellectual effects of lower doses of cranial irradiation are as yet unknown. A variety of minor neurological abnormalities were detected among leukaemia survivors and thought to be related to preceding central nervous system 'prophylactic' chemotherapy and irradiation. A new instrument, the functional deficit score, was derived to reflect overall outcome in survivors of childhood leukaemia. With few exceptions, leukaemia survivors in this study had received 2400 rads of deep x-ray therapy as cranial irradiation. This dosage has since been reduced world-wide. Current cranial irradiation 'prophylaxis' consists of 1800 rad of megavoltage radiotherapy.

Childhood leukaemia and low-level radiation - are we underestimating the risk?

International Nuclear Information System (INIS)

Wakeford, R.

1996-01-01

The Seascale childhood leukaemia 'cluster' can be interpreted as indicating that the risk of childhood leukaemia arising from low-level exposure to ionising radiation has been underestimated. Indeed, several variants of such an interpretation have been advanced. These include exposure to particular radionuclides, an underestimation of the radiation risk coefficient for childhood leukaemia, and the existence of a previously unrecognized risk of childhood leukaemia from the preconceptional irradiation of fathers. However, the scientific assessment of epidemiological associations is a complex matter, and such associations must be interpreted with caution. It would now seem most likely that the Seascale 'cluster' does not represent an unanticipated effect of the exposure to ionising radiation, but rather the effect of unusual population mixing generated by the Sellafield site which has produced an increase in the infection-based risk of childhood leukaemia. This episode in the history of epidemiological research provides a timely reminder of the need for great care in the interpretation-of novel statistical associations. (author)

Changes of Tc-99m sestamibi uptake in P-glycoprotein expressing leukaemia cells treated in vivo with antisense oligodeoxynucleotide complementary to mdr1 mRNA

International Nuclear Information System (INIS)

Kinuya, S.; Yokoyama, K; Fukuoka, M.; Michigishi, T.; Tonami, N.; Shiba, K.; Mori, H.; Watanabe, N.; Shuke, N.

2006-01-01

We examined the feasibility of Tc-99m sestamibi to monitor changes of mRNA expression of MDRl/P-glycoprotein (Pgp) following antisense oligodeoxynucleotide (AS-ODN) treatment in vivo. Three days after the intraperitoneal inoculation of murine leukaemia P388/R cells expressing MDR1/P-gp in CDFI mice, 15-mer phosphorothioate ASODN to the initiation codon of mouse mdr1 mRNA was administered intraperitoneally at 10 mg/kg daily for 3 or 4 days. Cells collected from ascites were suspended in medium for Tc-99m sestamibi uptake studies. To know the duration of antisense effects, cells were harvested 2 days later after the 3-day treatment. AS-ODN treatment increased Tc-99m sestamibi uptake. Effects of 3-day treatment and 4-day treatment were the same. Treatment effects were not detected when uptake was observed 2 days after 3-day treatment. Based on the results it was concluded that in vivo treatment with AS-ODN specific to the coding portion of mdr1 mRNA increased Tc-99m sestamibi uptake in leukaemia cells possessing MDR function. (author)

Leukaemia and lymphoma among Czech uranium miners

International Nuclear Information System (INIS)

Tomasek, L.; Malatova, I.

2006-01-01

Leukaemia is one of the most sensitive cancers in relation to ionizing radiation. It is surprising that in studies of uranium miners, no risk of leukaemia in relation to cumulated radon exposure was observed (Darby et al, 1995). However, when the risk among Czech uranium miners was analyzed in dependence on duration of exposure, the trend was significant. These results were based on 10 cases (Tomasek, 1993). Since then the original cohort of 4320 miners has been extended by another cohort, now including nearly 10 000 uranium miners and the follow-up is longer by 10 years. The present report aims to analyze the risk of haemopoietic cancers in the Czech cohort accounting for both external and internal doses, similarly as reported by Jacobi and Roth (1995), and using available data on metal content and airborne particulates for dose estimates.The present results of follow-up show that increased risk of leukaemia among uranium miners is significantly associated with cumulated equivalent red bone marrow doses which is dominated by exposures to long lived alpha radionuclides in airborne particulates. The increased mortality is mainly observed decades after exposure and is consistent with estimated internal dose to red bone marrow. The estimated risk coefficient for leukaemia is consistent with results from other studies, however, further studies are needed to reduce uncertainty in the risk estimates. (N.C.)

Leukaemia and lymphoma among Czech uranium miners

Energy Technology Data Exchange (ETDEWEB)

Tomasek, L.; Malatova, I. [National Radiation Protection Institute, Prague (Czech Republic)

2006-07-01

Leukaemia is one of the most sensitive cancers in relation to ionizing radiation. It is surprising that in studies of uranium miners, no risk of leukaemia in relation to cumulated radon exposure was observed (Darby et al, 1995). However, when the risk among Czech uranium miners was analyzed in dependence on duration of exposure, the trend was significant. These results were based on 10 cases (Tomasek, 1993). Since then the original cohort of 4320 miners has been extended by another cohort, now including nearly 10 000 uranium miners and the follow-up is longer by 10 years. The present report aims to analyze the risk of haemopoietic cancers in the Czech cohort accounting for both external and internal doses, similarly as reported by Jacobi and Roth (1995), and using available data on metal content and airborne particulates for dose estimates.The present results of follow-up show that increased risk of leukaemia among uranium miners is significantly associated with cumulated equivalent red bone marrow doses which is dominated by exposures to long lived alpha radionuclides in airborne particulates. The increased mortality is mainly observed decades after exposure and is consistent with estimated internal dose to red bone marrow. The estimated risk coefficient for leukaemia is consistent with results from other studies, however, further studies are needed to reduce uncertainty in the risk estimates. (N.C.)

Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

2017-01-01

BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re......-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. METHODS: Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute...... lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal...

The risks of leukaemia and non-cancer mortality in the offspring of the Japanese bomb survivors and a comparison of leukaemia risks with those in the offspring of the Sellafield workforce

International Nuclear Information System (INIS)

Little, M.P.

1992-01-01

The incidence of leukaemia and mortality from various causes other than cancer observed in offspring of the Japanese bomb survivors are analysed using linear and exponential forms of a relative risk model. Relative risk coefficients for leukaemia as a function of total pre-conception dose in the offspring of the Japanese and those for children of the Sellafield workforce are compared, and statistically significant differences are found. The statistical significance of these differences is no less marked if attention is restricted to those born before the end of 1950 in the Japanese cohort; therefore it is unlikely that the differences between the preconception irradiation leukamia risks in the Japanese and Sellafield datasets are a result of different distributions of parental ages at exposure in the two groups, or of different lengths of time between exposures of spermatogonia and conception. (Author)

The risks of leukaemia and non-cancer mortality in the offspring of the Japanese bomb survivors and a comparison of leukaemia risks with those in the offspring of the Sellafield workforce

Energy Technology Data Exchange (ETDEWEB)

Little, M.P. (National Radiological Protection Board, Chilton (United Kingdom))

1992-12-01

The incidence of leukaemia and mortality from various causes other than cancer observed in offspring of the Japanese bomb survivors are analysed using linear and exponential forms of a relative risk model. Relative risk coefficients for leukaemia as a function of total pre-conception dose in the offspring of the Japanese and those for children of the Sellafield workforce are compared, and statistically significant differences are found. The statistical significance of these differences is no less marked if attention is restricted to those born before the end of 1950 in the Japanese cohort; therefore it is unlikely that the differences between the preconception irradiation leukamia risks in the Japanese and Sellafield datasets are a result of different distributions of parental ages at exposure in the two groups, or of different lengths of time between exposures of spermatogonia and conception. (Author).

Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System.

Science.gov (United States)

Banjar, Haneen; Adelson, David; Brown, Fred; Chaudhri, Naeem

2017-01-01

The use of intelligent techniques in medicine has brought a ray of hope in terms of treating leukaemia patients. Personalized treatment uses patient's genetic profile to select a mode of treatment. This process makes use of molecular technology and machine learning, to determine the most suitable approach to treating a leukaemia patient. Until now, no reviews have been published from a computational perspective concerning the development of personalized medicine intelligent techniques for leukaemia patients using molecular data analysis. This review studies the published empirical research on personalized medicine in leukaemia and synthesizes findings across studies related to intelligence techniques in leukaemia, with specific attention to particular categories of these studies to help identify opportunities for further research into personalized medicine support systems in chronic myeloid leukaemia. A systematic search was carried out to identify studies using intelligence techniques in leukaemia and to categorize these studies based on leukaemia type and also the task, data source, and purpose of the studies. Most studies used molecular data analysis for personalized medicine, but future advancement for leukaemia patients requires molecular models that use advanced machine-learning methods to automate decision-making in treatment management to deliver supportive medical information to the patient in clinical practice.

Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.

Science.gov (United States)

Hattori, Ayuna; Tsunoda, Makoto; Konuma, Takaaki; Kobayashi, Masayuki; Nagy, Tamas; Glushka, John; Tayyari, Fariba; McSkimming, Daniel; Kannan, Natarajan; Tojo, Arinobu; Edison, Arthur S; Ito, Takahiro

2017-05-25

Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids. Blocking BCAT1 gene expression or enzymatic activity induces cellular differentiation and impairs the propagation of blast crisis CML both in vitro and in vivo. Stable-isotope tracer experiments combined with nuclear magnetic resonance-based metabolic analysis demonstrate the intracellular production of BCAAs by BCAT1. Direct supplementation with BCAAs ameliorates the defects caused by BCAT1 knockdown, indicating that BCAT1 exerts its oncogenic function through BCAA production in blast crisis CML cells. Importantly, BCAT1 expression not only is activated in human blast crisis CML and de novo acute myeloid leukaemia, but also predicts disease outcome in patients. As an upstream regulator of BCAT1 expression, we identified Musashi2 (MSI2), an oncogenic RNA binding protein that is required for blast crisis CML. MSI2 is physically associated with the BCAT1 transcript and positively regulates its protein expression in leukaemia. Taken together, this work reveals that altered BCAA metabolism activated through the MSI2-BCAT1 axis drives cancer progression in myeloid leukaemia.

Exposure to electromagnetic fields and the risk of childhood leukaemia: A review

International Nuclear Information System (INIS)

Schuez, J.; Ahlbom, A.

2008-01-01

Extremely low-frequency magnetic fields have been classified as possibly carcinogenic to humans, mainly based on epidemiological studies consistently showing an association between long-term average exposures to magnetic fields above 0.3/0.4 μT and the risk of childhood leukaemia. No mechanism to explain this finding has been established and no support for a causal link emerged from experimental studies. Chance or bias cannot be ruled out with reasonable confidence as an explanation for the observed association. If the association is causal, it explains only a small fraction of childhood leukaemia cases. There were some reports of childhood leukaemia clusters in the vicinity of high-power radio and television broadcast transmitters in studies in Australia and Italy. However, recent large-scale systematic studies in Korea and Germany show no association between exposure to radio frequency electromagnetic fields emitted from broadcast towers and childhood leukaemia risk. Studies on mobile phone use and leukaemia risk in adolescents and young adults may be indicated. (authors)

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.

Science.gov (United States)

Karimpoor, Mahroo; Yebra-Fernandez, Eva; Parhizkar, Maryam; Orlu, Mine; Craig, Duncan; Khorashad, Jamshid S; Edirisinghe, Mohan

2018-04-01

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells. © 2018 The Author(s).

The risk of childhood leukaemia near nuclear establishments

International Nuclear Information System (INIS)

Stather, J.W.; Clarke, R.H.; Duncan, K.P.

1988-01-01

Childhood leukaemia has been reported to be increased in communities living near a number of nuclear sites in the United Kingdom. The National Radiological Protection Board has, over the last three and a half years, published the results of a series of studies giving radiation doses and risks calculated for some of these populations. The studies have all indicated that it is most unlikely that radiation doses arising from releases of radioactive materials into the environment could have contributed to any increase in the leukaemia incidence in local communities. In the absence of any other obvious causative agent, however, there remains some concern that the radiation doses and risks of leukaemia have been underestimated. This report, therefore, summarises the methods used in the analyses by the Board, examines possible sources of uncertainty in the calculations, and considers the extent to which more information is required. (author)

Are maternal fertility problems related to childhood leukaemia

International Nuclear Information System (INIS)

Steensel-Moll, H.A. van; Valkenburg, H.A.; Vandenbroucke, J.P.; Zanen, G.E. van

1985-01-01

A study was conducted in the Netherlands, from a nationwide register of childhood leukaemia (1973-1980). Controls were matched with cases for year of birth, sex and place of residence. Information about exposures of the mother to potential risk factors in the year before and during pregnancy was collected via mailed questionnaires. Analyses concerned data on 519 patients with acute lymphocytic leukaemia and 507 controls. An association between maternal subfertility and childhood leukaemia might be suggested by several findings. A history of two or more miscarriages (OR 1.6; 95% Cl 1.0-2.7) and fertility problems (OR 6.0; 95% Cl 0.9-38.2) were more frequently reported among mothers of cases. Use of oral contraceptives (OC) was significantly higher (OR 1.3; 95% Cl 1.0-1.8) and the duration between discontinuation of OC and the relevant pregnancy was significantly longer. The OR for threatened abortion during the relevant pregnancy was 1.6 (95% Cl 1.0-2.6) and the related use of 'drugs to maintain pregnancy' was 1.9; 95% Cl 1.0-3.5. Among known risk factors, an increased OR for diagnostic irradiation was confirmed (OR 2.2; 95% Cl 1.2-3.8). No association between childhood leukaemia and prenatal viral infections, smoking and alcohol was found. (author)

Canada refutes Gardner. [Study of effect of parental exposure on childhood leukaemia

Energy Technology Data Exchange (ETDEWEB)

Anon.

1993-02-01

An epidemiological study of childhood leukaemia in relation to the preconception occupational exposure of fathers to ionizing radiation has been carried out by an academic team for the Canadian Atomic Energy Control Board. The study had twice as many cases of childhood leukaemia as the study around Sellafield by Gardner et al and had ample statistical power to check the Gardner result. However, the Canadian study found no evidence of any significant effect of parental radiation exposure on childhood leukaemia. (Author).

The therapeutic power of play: examining the play of young children with leukaemia.

Science.gov (United States)

Gariépy, N; Howe, N

2003-11-01

The therapeutic function of play has been investigated in relation to recognized stressors such as hospitalization, illness and medical treatments for ill children. While medical treatments in the past 30 years have improved survival rates, children's psychological experiences and quality of life during and after their illness have received limited attention. The present study investigated the therapeutic effects of play on 3- to 5-year-old children with leukaemia compared with a control group of healthy children. The participants with leukaemia (n = 11) were from the external oncology clinic of an urban children's hospital; control children (n = 11) attended a day care centre. Measures included children's experience of stress, social and cognitive play behaviours, and daily mood. A series of manova revealed that the children with leukaemia, compared with the control children, engaged in (a) significantly fewer total play behaviours, and in particular less (b) parallel, (c) group and (d) dramatic play. Pearson correlations revealed significant relationships between reports of 'being happy' and play only for children with leukaemia. Quantitative and qualitative analyses revealed a pattern of repetitive play activities week after week for children with leukaemia, but not controls. Findings are discussed in light of the theoretical and practical implications for children undergoing treatment for leukaemia.

The experience of acute leukaemia in adult patients: a qualitative thematic synthesis.

Science.gov (United States)

Papadopoulou, Constantina; Johnston, Bridget; Themessl-Huber, Markus

2013-10-01

The aim of this review was to systematically identify and synthesise all qualitative evidence on how adult patients diagnosed with acute leukaemia experience living with their illness. A systematic search strategy was developed comprising of two search strings: i) acute leukaemia and ii) qualitative methodology. The search strategy was run in seven electronic databases (Medline, CINAHL, PsychINFO, EMBASE, BNI & Archive, SSCI and ASSIA). Nine qualitative studies in adult patients with acute leukaemia, published in peer reviewed journals between 01/1990 and 01/2013 were included in the final sample. The qualitative thematic synthesis resulted in the development of a conceptual model describing a person's path to build a renewed self. Following the initial blow of diagnosis with the range of initial reactions, patients with acute leukaemia are living in a contracting world; they have to deal with the life in hospital, the several losses and the impact of their illness on their emotions and interpersonal relationships. Several factors take up a buffering role at that stage: coping, support, information and hope. Finally, patients accommodate acute leukaemia in their lives through re-evaluating personal values and assigning new meaning to their experience. Results from this thematic synthesis are indicative of the impact of acute leukaemia on patients' lives and the processes they use to make sense and accommodate the illness in their life. Increasing our understanding of these processes is warranted to improve patient care. Copyright © 2013. Published by Elsevier Ltd.

A comparison between the risks of childhood leukaemia from parental exposure to radiation in the Sellafield workforce and those displayed among the Japanese bomb survivors

International Nuclear Information System (INIS)

Little, M.P.

1990-01-01

The cases of childhood leukaemia found near the Sellafield plant and those observed in the offspring of the Japanese bomb survivors are analysed using a relative risk model. The leukaemia relative risk coefficients for total paternal (whole-body) pre-conception exposure for the Sellafield children are found to be about 50 to 80 times higher than the (gonadal) coefficients applying to the offspring of the bomb survivors. This difference is statistically significant, and in particular the risk coefficients for the Sellafield cohort are significantly positive, unlike those for the Japanese. If the assumption is made that the excess relative risk estimated from the Sellafield data lasts for the whole of the life of the offspring, the apparent population leukaemia risk to the first-generation offspring (for an England and Wales population) would be between 4% Sv -1 and 5% Sv -1 . (author)

Leukaemia litigation

Energy Technology Data Exchange (ETDEWEB)

Stather, John (National Radiological Protection Board, Chilton (United Kingdom))

1993-11-01

One case of acute lymphatic leukaemia and another of non-Hodgkin's lymphoma that occurred in the Seascale area have been the subject of recent litigation in the High Court in England. The main feature of the trial was the argument by the plaintiffs' solicitors that the diseases were primarily the result of paternal preconception irradiation resulting from exposure of the fathers at the nuclear fuel reprocessing plant operated by the defendants British Nuclear Fuels plc. Judgment in favour of the defendants was given by Mr Justice French on Friday 8 October 1993. (author).

Dipeptide species regulate p38MAPK–Smad3 signalling to maintain chronic myelogenous leukaemia stem cells

Science.gov (United States)

Naka, Kazuhito; Jomen, Yoshie; Ishihara, Kaori; Kim, Junil; Ishimoto, Takahiro; Bae, Eun-Jin; Mohney, Robert P.; Stirdivant, Steven M.; Oshima, Hiroko; Oshima, Masanobu; Kim, Dong-Wook; Nakauchi, Hiromitsu; Takihara, Yoshihiro; Kato, Yukio; Ooshima, Akira; Kim, Seong-Jin

2015-01-01

Understanding the specific survival of the rare chronic myelogenous leukaemia (CML) stem cell population could provide a target for therapeutics aimed at eradicating these cells. However, little is known about how survival signalling is regulated in CML stem cells. In this study, we survey global metabolic differences between murine normal haematopoietic stem cells (HSCs) and CML stem cells using metabolomics techniques. Strikingly, we show that CML stem cells accumulate significantly higher levels of certain dipeptide species than normal HSCs. Once internalized, these dipeptide species activate amino-acid signalling via a pathway involving p38MAPK and the stemness transcription factor Smad3, which promotes CML stem cell maintenance. Importantly, pharmacological inhibition of dipeptide uptake inhibits CML stem cell activity in vivo. Our results demonstrate that dipeptide species support CML stem cell maintenance by activating p38MAPK–Smad3 signalling in vivo, and thus point towards a potential therapeutic target for CML treatment. PMID:26289811

High-flow priapism in acute lymphatic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

2004-07-01

Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

High-flow priapism in acute lymphatic leukaemia

International Nuclear Information System (INIS)

Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A.; Kentouche, Karim; Doerfel, Claus; Zintl, Felix

2004-01-01

Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

Control of feline leukaemia virus.

NARCIS (Netherlands)

K. Weijer (Kees); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

1989-01-01

textabstractFeline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS

Myeloid leukaemia/osteosarcoma ratio in CBA/H mice given radium 224

International Nuclear Information System (INIS)

Humphreys, E.R.; Stones, V.A.

1989-01-01

Four groups of 400 12-week-old CBA/H mice were injected intraperitoneally with mean amounts of 69, 139, 280 and 550 Bq/g -1 radium 224. A further group of 400 mice were injected intraperitoneally with diluting solution only. The mice were allowed unrestricted access to food and water until they died or were killed. To date (September 1988) about 40% of the mice are dead, and 28 cases of myeloid leukaemia and four cases of osteosarcoma have been diagnosed in the animals given radium 224. The relationship between the yield of myeloid leukaemia and the amount of radium 224 injected was found to be curvilinear. The determined value of the myeloid leukaemia:osteosarcoma ratio is discussed. (author)

Childhood leukaemia incidence below the age of 5 years near French nuclear power plants

International Nuclear Information System (INIS)

Laurier, D; Hemon, D; Clavel, J

2008-01-01

A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants. (note)

Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

International Nuclear Information System (INIS)

Pierpaoli, W.

1985-01-01

Haemopoietic radiation chimeras across the H-2 barrier (BALB/c → C57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c → C57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c → C57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

Environmental exposure to ionizing radiation and childhood leukaemia incidence

International Nuclear Information System (INIS)

Evrard, Anne-Sophie

2006-01-01

This thesis aimed at providing an epidemiological approach of the hypothesis of the existence of an association between environmental exposure to ionizing radiation and childhood leukaemia incidence. From 1990 to 2001, 5,330 cases of acute leukaemia were registered by the French National Registry of Childhood Leukemia and Lymphoma in children under 15 years of age and living in mainland France at the time of diagnosis. Indoor radon concentration was estimated using 13,240 measurements carried out by the Institute for Radiation Protection and Nuclear Safety (IRSN), and covering the whole country. Exposure to terrestrial gamma radiation was based on continuous measurements, using thermoluminescent dosimeters, at about 1,000 sites covering the whole of France, in order to monitor the level of environmental radioactivity in France. Analyses were conducted using Poisson regressions, including ecological co-variates, at the level of the 'Departments' (95 administrative geographical units in France). A significant positive ecological association between indoor radon concentration and the incidence of acute myeloid leukaemia was evidenced (SIR=1.19 per 100 Bq/m 3 - 95% confidence interval=[1.03-1.38]) and remained significant in multivariate regression analyses including exposure to terrestrial gamma radiation and/or some ecological co-variates. Conversely, there was no evidence of an ecological association between exposure to terrestrial gamma radiation and childhood leukaemia incidence. The epidemiological studies of the incidence of childhood leukaemia around nuclear sites analyzed incidence with respect to the distance from the plants, without considering any information on the levels or geographic distribution of the radiation dose due to discharges from the plants. The present study investigated for the first time the incidence of childhood leukaemia around French nuclear installations using a geographic zoning based on estimated doses due to gaseous

A Ten Year Descriptive Study of Adult Leukaemia at Al-Jomhori Teaching Hospital in Sana'a, Yemen

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Jameel Al-Ghazaly

2014-12-01

Full Text Available Background: There is scarcity of data of the epidemiology of leukaemia in Arab countries including Yemen. Understanding patterns of leukaemia underpins epidemiology and can provide insight into disease etiology. The aim of this research is to determine the epidemiologic pattern of adult leukaemia in Yemen. Methods: The research is a descriptive cross-sectional study. We analyzed the data of 702 adult patients with leukaemia, who were newly diagnosed over a ten-year period between October 1999 and October 2009 at the referral haematology centre in Sana’a at Al-Jomhori Teaching Hospital, according to type of leukaemia, age, sex, geographic distribution and time of diagnosis. Results: Acute Myeloid Leukaemia (AML was found to be the most common (45.1% followed by Chronic Myeloid Leukaemia (CML (26.5%, Acute Lymphoid Leukaemia (ALL (17.7% and Chronic Lymphoid Leukaemia (CLL (10.7%, respectively. There was an almost equal prevalence of AML and CML for males and females but males had significantly more cases of ALL and CLL (p =0.008. A significant variation in geographic pattern showed that the highest number of cases is seen the Central mountainous region and the least number of cases in the South-eastern region which is coastal and lowland (p<0.001. The seasonal variation showed that higher number of ALL cases was seen in the summer months (33% compared with other seasons (21% in the spring, 24.2% in autumn and 21.8% in winter. Conclusions: The pattern of adult leukaemia in Yemen is different from that seen in western countries which could be attributed to different environmental exposure. The geographic pattern indicates a possible role of certain environmental factors which warrant further investigations. The pattern of seasonal variation needs further studies for evaluating the seasonality.

Myeloid sarcoma in a child with acute myeloblastic leukaemia

International Nuclear Information System (INIS)

Ahmad, J.; Zafar, L.; Hussain, G.

2011-01-01

We report a rare occurrence of myeloid sarcoma in a 7 years old child with acute myeloblastic leukaemia (AML - FAB type M2). He presented with fever, generalized weakness, bilateral proptosis and left parotid swelling. CT scan revealed a mass in paranasal sinuses extending into brain and retro-orbital region. Diagnosis of AML M2 was made on bone marrow aspiration and special stains. Induction therapy for AML was given according to standard protocol. The extramedullary lesion as well as the acute leukaemia went into complete remission. (author)

Leukaemia incidence among workers in the shoe and boot manufacturing industry: a case-control study

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Forand Steven P

2004-08-01

Full Text Available Abstract Background Previous reports have indicated an excess of leukaemia in Broome County, New York, particularly in the Town of Union. Surveillance of cancer incidence data indicates that a large proportion of these cases occurred among males ages 65 and older. Shoe and boot manufacturing has been the largest single industry in this area throughout much of the past century. Occupational studies from Europe suggest a link between leukaemia and employment in the shoe and boot manufacturing industry. However, researchers have not found a positive association between leukaemia and employment in the shoe industry among workers in the United States. Methods A matched case-control study was conducted to investigate the association between leukaemia incidence among males 65 and older and employment in the shoe and boot manufacturing industry. Thirty-six cases of leukaemia occurring between 1981–1990; among males age 65 and older; residing in the town of Union met the study case criteria. Death certificates were obtained for each of the cases. These were matched to death certificates of 144 controls on date of death and date of birth +/- 1 year. Death certificates were then examined to determine the employer and occupation of each study subject. Conditional logistic regression was used to determine the risk of leukaemia among those working in the industry. Results The risk of both leukaemia (OR = 1.47; 95% CI 0.70, 3.09 and acute myeloid leukaemia (OR = 1.19; 95% CI 0.33, 4.28 were elevated among those employed in the shoe and boot manufacturing industry, however neither was statistically significant. Conclusion The results, though suggestive of an association between leukaemia and employment in the shoe and boot manufacturing industry, were not statistically conclusive due mainly to limited study power. Several additional limitations may also have prevented the observance of more conclusive findings. Better exposure assessment, information on

A case-control study of risk of leukaemia in relation to mobile phone use.

Science.gov (United States)

Cooke, R; Laing, S; Swerdlow, A J

2010-11-23

Mobile phone use is now ubiquitous, and scientific reviews have recommended research into its relation to leukaemia risk, but no large studies have been conducted. In a case-control study in South East England to investigate the relation of acute and non-lymphocytic leukaemia risk to mobile phone use, 806 cases with leukaemia incident 2003-2009 at ages 18-59 years (50% of those identified as eligible) and 585 non-blood relatives as controls (provided by 392 cases) were interviewed about mobile phone use and other potentially aetiological variables. No association was found between regular mobile phone use and risk of leukaemia (odds ratio (OR)=1.06, 95% confidence interval (CI)=0.76, 1.46). Analyses of risk in relation to years since first use, lifetime years of use, cumulative number of calls and cumulative hours of use produced no significantly raised risks, and there was no evidence of any trends. A non-significantly raised risk was found in people who first used a phone 15 or more years ago (OR=1.87, 95% CI=0.96, 3.63). Separate analyses of analogue and digital phone use and leukaemia subtype produced similar results to those overall. This study suggests that use of mobile phones does not increase leukaemia risk, although the possibility of an effect after long-term use, while biologically unlikely, remains open.

IMMUNOPHENOTYPING IN ACUTE LEUKAEMIA- AN INSTITUTIONAL STUDY

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Aparajita Das

2018-02-01

Full Text Available BACKGROUND Leukaemias are biologically a diverse group of disorders with differences in their morphology, antigen expression, chromosomal and molecular abnormalities, response to treatment, and prognosis. The main objective of the study was to compare morphological and flowcytometric diagnosis in patients diagnosed with acute leukaemia. MATERIALS AND METHODS The prospective study was carried out at S.C.B. Medical College and hospital, Cuttack, in department of Pathology and Clinical haematology, for the period of November 2015- November 2017. The findings were based on 100 patients who underwent both flow cytometry and peripheral smear/bone marrow morphology tests for diagnosis of acute leukaemia. RESULTS Using the peripheral smear/bone marrow morphology, 27% patients had ALL-L1, 38% had ALL-L2, 05% had AML-M1, 21% had AML-M2, 06% had AML-M3, 02% had AML-M4, and 01% had AML-M5. Immunophenotyping by flow cytometry confirms 50% patients to be B-ALL, 07% to be T-ALL, 32% AML, 08% APML/AML-M3, and 03% to be MPAL. There was a concordance between the morphological and flowcytometry of 88% in ALL, 91% in AML, 75% in APML, but, no concordance at all for MPAL. CONCLUSION Hence, flowcytometry is mandatory in all cases of acute leukemia, to confirm a definite diagnosis, as treatment nowadays is target oriented.

Residential exposures to pesticides and childhood leukaemia

International Nuclear Information System (INIS)

Metayer, C.; Buffler, P. A.

2008-01-01

Like many chemicals, carcinogenicity of pesticides is poorly characterised in humans, especially in children, so that the present knowledge about childhood leukaemia risk derives primarily from epidemiological studies. Overall, case-control studies published in the last decade have reported positive associations with home use of insecticides, mostly before the child's birth, while findings for herbicides are mixed. Previous studies relied solely on self-reports, therefore lacking information on active ingredients and effects of potential recall bias. Few series to date have examined the influence of children's genetic susceptibility related to transport and metabolism of pesticides. To overcome these limitations, investigators of the Northern California Childhood Leukaemia Study (NCCLS) have undertaken, in collaboration with a multidisciplinary team, a comprehensive assessment of residential pesticide exposure, including: (1) quality control of self-reports; (2) home pesticide inventory and linkage to the Environmental Protection Agency to obtain data on active ingredients; (3) collection and laboratory analyses of ∼600 home dust samples for over 60 pesticides and (4) geographic information studies using California environmental databases to assess exposure to agricultural pesticides. The NCCLS is also conducting large-scale geno-typing to evaluate the role of genes in xenobiotic pathways relevant to the transport and metabolism of pesticides. A better quantification of children's exposures to pesticides at home is critical to the evaluation of childhood leukaemia risk, especially for future gene-environment interaction studies. (authors)

Observations on transition of polycythaemia vera into acute or chronic granulocytic leukaemia during treatment with radioactive phosphorus 32P

International Nuclear Information System (INIS)

Krasnik, W.

1975-01-01

In a group of 172 cases of polycythaemia vera treated with radioactive phosphorus 32 P acute granulocytic leukaemia developed in 3 cases and chronic granulocytic leukaemia in 6 cases. Development of acute granulocytic leukaemia during treatment with radioactive phosphorus for polycythaemia vera may be considered with some probability as a result of leukaemia-inducing action of ionizing radiation. Transition of polycythaemia vera into chronic granulocytic leukaemia seems to a natural outcome of this complex myeloproliferative syndrome in patients with survival prolonged by treatment with 32 P. (author)

Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

International Nuclear Information System (INIS)

Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

2003-01-01

Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

Impact on learning of an e-learning module on leukaemia: a randomised controlled trial.

Science.gov (United States)

Morgulis, Yuri; Kumar, Rakesh K; Lindeman, Robert; Velan, Gary M

2012-05-28

e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group's evaluation of the module was overwhelmingly positive. A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

Risk of childhood leukaemia in the vicinity of nuclear installations: Findings and recent controversies

International Nuclear Information System (INIS)

Dominique Laurier; Bernd Grosche; Hall, Per

2002-01-01

The identification of a local excess of cancer cases, possibly associated with ionizing radiation, always receives substantial media coverage and communication about clusters is difficult. We reviewed studies that examined the risk of leukaemia among young people near nuclear installations. An excess of leukaemia exists near some nuclear installations, at least for the reprocessing plants at Sellafield and Dounreay and the nuclear power plant Kruemmel. Nonetheless, the results of multi-site studies invalidate the hypothesis of an increased risk of leukaemia related to nuclear discharge. Up until now, analytic studies have not found an explanation for the leukaemia clusters observed near certain nuclear installations. The hypothesis of an infectious aetiology associated with population mixing has been proposed, but needs to be investigated further. The review illustrates two recent examples in France (La Hague reprocessing plant) and in Germany (Kruemmel power plant), where controversies developed after reports of increased leukaemia risks. These examples show the importance of recalling the current epidemiological knowledge and of using systematic recording of cases to replace the alleged excesses in a more general framework. Some elements should also be suggested from the recent French and German experiences to reinforce credibility in the results

The leukaemogenic effect of whole-body irradiation of the mouse: Experimental work at the Radiobiological Research Unit, Harwell

International Nuclear Information System (INIS)

Mole, R.H.

1960-01-01

Mouse 'leukaemia' is a generic term which might well be replaced by the clumsier, but more accurate, 'malignant disease of reticular tissue'. There are a variety of cytologically definable types (reticulosarcoma, 'histiocytoma' or monocytic leukaemia, lymphosarcoma and lymphoid leukaemia, myeloid leukosis) and a variety of morbid anatomical patterns, but there is only an approximate correlation between morbid anatomy and cytological type. True leukaemia where the white blood cell count is raised and morphologically abnormal white cells are found in the blood) occurs but is relatively uncommon; leukaemoid blood pictures are also found. Normally the murine thymus persists for much of the reproductive life-span, atrophying only in middle age, instead of in early childhood as in man. This may be the reason why the anatomical region of the thymus is more often involved in leukaemia in younger than in older animals, and why 'thymic leukaemia' is a characteristically murine disease and does not seem to occur in man. A great deal of the experimental work on mouse leukaemia reported in the literature is concerned with 'thymic leukaemia,' and this is often considered to be synonymous with thymic lymphoma or lymphosarcoma. However, the anatomy of tumour masses in the superior mediastinum. not infrequently suggests that they are not truly thymic in origin and their cell type is often not lymphoid

The leukaemogenic effect of whole-body irradiation of the mouse: Experimental work at the Radiobiological Research Unit, Harwell

Energy Technology Data Exchange (ETDEWEB)

Mole, R H

1960-12-01

Mouse 'leukaemia' is a generic term which might well be replaced by the clumsier, but more accurate, 'malignant disease of reticular tissue'. There are a variety of cytologically definable types (reticulosarcoma, 'histiocytoma' or monocytic leukaemia, lymphosarcoma and lymphoid leukaemia, myeloid leukosis) and a variety of morbid anatomical patterns, but there is only an approximate correlation between morbid anatomy and cytological type. True leukaemia where the white blood cell count is raised and morphologically abnormal white cells are found in the blood) occurs but is relatively uncommon; leukaemoid blood pictures are also found. Normally the murine thymus persists for much of the reproductive life-span, atrophying only in middle age, instead of in early childhood as in man. This may be the reason why the anatomical region of the thymus is more often involved in leukaemia in younger than in older animals, and why 'thymic leukaemia' is a characteristically murine disease and does not seem to occur in man. A great deal of the experimental work on mouse leukaemia reported in the literature is concerned with 'thymic leukaemia,' and this is often considered to be synonymous with thymic lymphoma or lymphosarcoma. However, the anatomy of tumour masses in the superior mediastinum. not infrequently suggests that they are not truly thymic in origin and their cell type is often not lymphoid.

Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia

NARCIS (Netherlands)

J.E. Park (Julie E.); H.F. Yuen (Hiu Fung); J.B. Zhou (Jian Biao); A.Q.O. Al-aidaroos (Abdul Qader); K. Guo (Ke); P.J.M. Valk (Peter); S.D. Zhang (Shu Dong); W.J. Chng (Wee); C.W. Hong (Cheng William); K. Mills (Ken); Q. Zeng (Qi)

2013-01-01

textabstractFLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD

Granulocytic sarcoma in a patient with chronic myeloid leukaemia in complete haematological, cytogenetic and molecular remission.

Science.gov (United States)

Kittai, Adam; Yu, Eun-Mi; Tabbara, Imad

2014-12-23

Granulocytic sarcoma, also known as myeloid sarcoma, is an extramedullary tumour composed of immature myeloid cells. Granulocytic sarcoma is typically found in patients with acute myeloid leukaemia, accelerated phase or blast crisis of chronic myeloid leukaemia, myelodysplastic syndrome, or as an isolated event without bone marrow involvement. We present a case of granulocytic sarcoma in a patient with chronic myeloid leukaemia in the setting of complete haematological, molecular and cytogenetic remission. Our patient was first treated with imatinib for chronic-phase chronic myeloid leukaemia. After maintaining remission for 42 months, he developed a granulocytic sarcoma in his spine. In this case report, we describe our case, along with the three other cases reported in the literature. In addition to being a rare diagnosis, this case demonstrates the importance of being vigilant in diagnosing the cause of back pain and atypical symptoms in patients with a history of leukaemia. 2014 BMJ Publishing Group Ltd.

Childhood leukaemia and lymphoma: African experience supports a role for environmental factors in leukaemogenesis

Science.gov (United States)

Williams, Christopher KO; Foroni, Letizia; Luzzatto, Lucio; Saliu, Idris; Levine, Arthur; Greaves, Mel F

2014-01-01

Major differences exist in the nature of leukaemia and lymphoma in low-income African children compared to those in the high-income countries. These include the absence of the peak incidence of acute lymphoblastic leukaemia (ALL) in under-five-year olds that characterizes the disease in high-income countries. Conversely, chloroma association with acute myelogenous leukaemia (CA-AML/AMML) and Burkitt’s lymphoma (BL) are rare in the high-income countries. This report describes clinical and laboratory as well as epidemiological features of childhood leukaemia and lymphoma reported betwen 1982 and 1984 in the city of Ibadan, Nigeria. The observed pattern of distribution of childhood haematological malignancies in the city is more consistent with the observations of Ludwik Gross’s experiments on environmental influences, such as malnutrition and infections, animal leukaemogenesis, and mirroring the consequences of the primordial pressures that have shaped human genetics and pathophysiology. PMID:25435906

Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

Directory of Open Access Journals (Sweden)

Morgulis Yuri

2012-05-01

Full Text Available Abstract Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

Science.gov (United States)

2012-01-01

Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines. PMID:22640463

Splenic irradiation for hairy cell leukaemia

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Al-Moundhri, A.; Graham, P.H. [St George Hospital, Kogarah, NSW, (Australia). Department of Radiation Oncology

1997-11-01

Splenic irradiation in the management of hairy cell leukaemia is previously unreported. A case is presented here to illustrate that splenic irradiation may be a useful addition to systemic therapies. It achieved local splenic and blood picture response and remission similar to splenectomy without any significant toxicity. (authors). 7 refs., 2 figs.

Chromosomal mechanisms in murine radiation acute myeloid leukemogenesis

International Nuclear Information System (INIS)

Bouffler, S.D.; Breckon, G.; Cox, R.

1996-01-01

Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-radiation events in bone marrow cells in vivo and karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2; 11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal tranlocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis. (Author)

Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study.

Science.gov (United States)

Lin, Jiun-Nong; Lin, Cheng-Li; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Yang, Chih-Hui; Sung, Fung-Chang; Kao, Chia-Hung

2015-10-01

The association between enterovirus infections in children and risk of leukaemia is unclear. We aimed to assess the risk of leukaemia after enterovirus infection in children. We did a nationwide retrospective cohort study by analysing data from the National Health Insurance Research Database (NHIRD) in Taiwan. Children with enterovirus infections aged younger than 18 years were identified. With use of computer-generated random numbers, children not infected with enterovirus were randomly selected and frequency matched (1:1) with children infected with enterovirus by sex, age, urbanisation level, parental occupation, and index year of enterovirus infection. We only included children with complete baseline data for age and sex and who had at least three clinic visits with the diagnosis of enterovirus infection. The diagnosis date of the first clinic visit for the enterovirus infection was defined as the index date for initiation of follow-up person-year measurement and participants. All study patients were followed up until they developed leukaemia, were lost to follow-up, withdrew from the NHI programme, or until the end of the study without leukaemia (censored). Our primary endpoint was a diagnosis of leukaemia during follow-up. Insurance claims data for 3 054 336 children younger than 18 years were randomly selected from all insured children in the NHIRD. We identified 282 360 children infected with enterovirus and 282 355 children not infected with enterovirus between Jan 1, 2000, and Dec 31, 2007. The incidence density rates of leukaemia were 3·26 per 100 000 person-years for the enterovirus-infected and 5·84 per 100 000 person-years for the non-enterovirus-infected cohorts. The risk of leukaemia was significantly lower in the enterovirus-infected cohort than in the non-enterovirus-infected cohort (adjusted subhazard ratio [SHR] 0·44, 95% CI 0·31-0·60; penterovirus have a reduced risk of both lymphocytic leukaemia (adjusted SHR 0·44, 0·30-0�

Discrimination between leukaemia and non-leukaemia-related chromosomal abnormalities in the patient's lymphocytes

International Nuclear Information System (INIS)

Lucas, J.N.; Hill, F.; Burk, C.; Straume, T.; Swansbury, G.; Clutterbuck, R.

1994-01-01

The inability to measure precancer-related genetic damage accurately in blood cells of patients with leukaemia or lymphoma has prevented the use in such patients of available biodosimetric methods to determine prior exposure to clastogenic agents. This is because a substantial amount of disease-related genetic damage appears in the blood cells of these patients, thus masking genetic damage that may have been caused prior to the disease. We describe a new approach that may be used to measure pre-cancer-related chromosomal aberrations in such patients by totally separating the affected T lymphocytes from the malignant B lymphocytes. The approach employs stable chromosome translocations and will detect prior exposures above the detection limit of ∼ 0.05-0.1 Gy. The utility of this approach is illustrated by using blood lymphocytes from a nuclear dockyard worker who claims his B cell leukaemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements were made of the frequency of chromosomal abnormalities in PHA-stimulated lymphocytes without prior separation of T and B cells and in T lymphocytes after complete separation from B cells using a rosetting technique. Results show that the separation of T cells prior to PHA stimulation eliminates the cancer-related chromosomal damage and thus appears to facilitate biodosimetry of pre-cancer in such patients. (Author)

Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

African Journals Online (AJOL)

Background: Acute Lymphoblastic Leukaemia in children commonly presents with osteo articular manifestations that may mimic Juvenile Idiopathic Arthritis. This may create considerable diagnostic difficulty and lead to delay in commencing appropriate treatment. Case: An eight year old boy who presented with multiple ...

Radon: possible links with leukaemia and other non-lung cancers

International Nuclear Information System (INIS)

Henshaw, D.L.; Eatough, J.P.

1993-01-01

The evidence for possible links between domestic radon exposure and incidence of leukaemia and other non-lung cancers is reviewed. Recent calculations of the radon derived dose to red bone marrow suggests that if background radiation is linked to leukaemia in the general population then radon exposure may be a causative factor. Accordingly, statistically significant geographical correlations between domestic radon exposure and incidence of leukaemia have been observed in several data sets. In a preliminary study the level of hprt mutation in peripheral blood of individuals has been found to correlate with radon concentration in their homes. Geographical associations have also been observed between domestic radon exposure and certain other cancers. A model has been developed which predicts the possible carcinogenic effect of simultaneous exposure to alpha particles and gamma radiation and to radon and cigarette smoke, reflecting the nature of natural exposures. The model is used to suggest a mechanism for an antagonistic effect of radon and smoking at domestic levels but a synergistic effect at higher dose rates such as in uranium miners. (orig.)

IRSN-ANCCLI partnership. Information day: Childhood leukaemia around French nuclear power plants - April 2012

International Nuclear Information System (INIS)

Clavel, Jacqueline; Laurier, Dominique; Sommelet, Daniele; Chantal Bardelay

2012-04-01

As an epidemiological study performed by the INSERM highlighted an excess of childhood leukaemia within 5 km around nuclear power plants during the 2002-2007 period, this meeting has been organised to discuss this issue. After a presentation of these results, a contribution discusses the context and research perspectives on the relationship between childhood leukaemia and nuclear sites. After the reported debate, a contribution presents the conclusion of a work-group on childhood leukaemia and ASN works, and a last one presents the activities of a work-group gathering the ANCCLI, IRSN and InVS on the health impact of nuclear installations. A debate on these issues is reported

Imaging findings of upper abdominal involvement by acute megakaryoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Amemiya, Shiori; Akahane, Masaaki; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan); Takita, Junko; Igarashi, Takashi [University of Tokyo, Department of Paediatrics, Graduate School of Medicine, Tokyo (Japan)

2008-04-15

Acute megakaryoblastic leukaemia (AMKL), a relatively rare type of acute myeloid leukaemia, is characterized by frequent involvement of the liver, spleen and lymph nodes in addition to myelofibrosis in children. Diagnosis is difficult both clinically and pathologically, and the hepatic or lymph node involvement is not uncommonly misinterpreted as solid tumour. We report the imaging findings of upper abdominal involvement by AMKL in an infant. The hepatic lesion, initially suspected to be hepatoblastoma, showed a distinctive appearance on MRI suggesting its infiltrative nature. With the association of splenic lesion and lymphadenopathy, the imaging findings were considered indicative of a haematological disorder. (orig.)

The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods

International Nuclear Information System (INIS)

Linka, Y; Ginzel, S; Krüger, M; Novosel, A; Gombert, M; Kremmer, E; Harbott, J; Thiele, R; Borkhardt, A; Landgraf, P

2013-01-01

The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation

Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia

OpenAIRE

Núñez-Enríquez, J C; Fajardo-Gutiérrez, A; Buchán-Durán, E P; Bernáldez-Ríos, R; Medina-Sansón, A; Jiménez-Hernández, E; Amador-Sanchez, R; Peñaloza-Gonzalez, J G; Paredes-Aguilera, R; Alvarez-Rodriguez, F J; Bolea-Murga, V; de Diego Flores-Chapa, J; Flores-Lujano, J; Bekker-Mendez, V C; Rivera-Luna, R

2013-01-01

Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. O...

Joint scientific publication by the INSERM and IRSN concerning child leukaemia about French nuclear power stations on the Internet site of the 'International Journal of Cancer' the 4 January 2012

International Nuclear Information System (INIS)

2012-01-01

This document describes the cooperation between the INSERM and IRSN in the field of child leukaemia about nuclear power stations, and presents the published study: context and objectives, methodology (epidemiological data, geographical data), and obtained results (risks and comparison with a German study)

Childhood leukaemia in Great Britain and fallout from nuclear weapons testing

International Nuclear Information System (INIS)

Haynes, R.; Bentham, G.

1995-01-01

The possible effects of radiation from fallout on childhood leukaemia mortality from 1950 to 1987 and registrations from 1963 to 1987 were assessed using a division of Great Britain into regions with higher rainfall and a consequently higher fallout radiation dose in the 1960s and regions with lower rainfall and a lower radiation dose. Childhood leukaemia mortality rates declined and registration rates increased throughout the period. For ages 0-14 years, the differences between rates in wet regions and dry regions were small and appeared unrelated to periods of low, medium and high radiation exposure based on dose equivalent to the red bone marrow after birth. For the 0-4 years age group the highest ratios of leukaemia death rates and registration rates in the wet compared with the dry part of Great Britain occurred in the period of highest radiation exposure after birth. The death rate ratio was significantly raised in the period of high exposure compared with the surrounding medium exposure periods, but the difference in registration rate ratios between the high exposure period and the medium exposure period following was not statistically significant. The results might be explained by survival and registration changes, or chance in the case of registrations, but do not exclude the possibility that low doses of radiation from fallout were responsible for an increased risk of leukaemia in young children in Great Britain. (author)

Childhood leukaemia following medical diagnostic exposure to ionizing radiation in utero or after birth

International Nuclear Information System (INIS)

Wakeford, R.

2008-01-01

A statistical association between childhood leukaemia and an abdominal X-ray examination of the pregnant mother was first reported in 1956 from a case-control study of childhood cancer mortality conducted in Great Britain. This study, later called the Oxford Survey of Childhood Cancers (OSCC), was continued and eventually showed a highly statistically significant ∼50% proportional increase in the risk of childhood leukaemia associated with antenatal diagnostic radiography. The association has been confirmed by many case-control studies carried out around the world, the appropriately combined results of which show a highly statistically significant increase in risk that is compatible with the OSCC finding. There is no doubt about the reality of the statistical association, but a causal interpretation has been questioned. On balance, however, the evidence points to low-level irradiation of the fetus increasing the risk of leukaemia in childhood, with an excess relative risk coefficient of around 50 Gy -1 (equivalent to an excess absolute risk coefficient of about 3% Gy -1 ), although the uncertainty associated with these coefficients is considerable and they are likely to be overestimates. In contrast to exposure in utero, the evidence from case-control studies for an association between childhood leukaemia and postnatal exposure to medical diagnostic irradiation is equivocal and sometimes conflicting. Since standard radiation risk models predict that low-level exposure in the early years of life should produce an increased risk of childhood leukaemia that is roughly similar to that arising from fetal exposure, this absence of persuasive evidence is likely to be due to various problems with the studies. This is unfortunate given the rise in relatively high dose diagnostic procedures (e.g. paediatric CT scans) that would be predicted to materially increase the relative risk of childhood leukaemia. (authors)

Use of DNA from milk tank for diagnosis and typing of bovine leukaemia virus

International Nuclear Information System (INIS)

Felmer, R.; Zuniga, J.; Recabal, M.; Floody, H.

2005-01-01

With the aim of achieving a better understanding of the epidemiology of Bovine leukaemia virus (BLV) infection, we investigated the suitability of milk tank samples for effecting molecular epidemiology studies of BLV in a southern area of Chile. As part of a serological survey for BLV antibodies carried out in 280 herds, we selected 33 strong positive samples, from which DNA was isolated to perform a BLV-specific nested PCR. Using RFLP analysis, all 33 PCR products could be assigned to the known Australian or the Belgium subgroups. A phylogenetic tree resulting from the comparison of these sequences demonstrates the relations and differences among and within the subgroups. (author)

Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Henriksen, Louise Tram; Nersting, Jacob; Raja, Raheel A

2014-01-01

L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The o...... in CSF asparagine corresponded to serum enzyme activities above 50 iu/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000 iu/m(2) i.m. every second week effectively reduced CSF asparagine levels.......L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy....... The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m(2) i.m. every second week, and to correlate CSF asparagine concentration with serum L-asparaginase enzyme activity. Danish children (1-17 years) with ALL, treated according...

MPLW515L mutation in acute megakaryoblastic leukaemia.

Science.gov (United States)

Hussein, K; Bock, O; Theophile, K; Schulz-Bischof, K; Porwit, A; Schlue, J; Jonigk, D; Kreipe, H

2009-05-01

The thrombopoietin receptor gene (MPL) is expressed in megakaryocytes and exhibits the gain of function point mutation W515K/L in approximately 5% of patients with primary myelofibrosis/idiopathic myelofibrosis (PMF) representing one subtype of the chronic myeloproliferative disorders (myeloproliferative neoplasm). A series of primary and secondary acute myeloid leukaemias (AML) with megakaryoblastic phenotype and myelofibrosis unrelated to PMF (n=12) was analysed for the MPL(W515K/L) mutation by pyrosequencing. In three cases (25%), MPL(W515L) was found and in two of these a combination with trisomy 21 or the Philadelphia chromosome occurred. None of the secondary AML cases evolving from pre-existing PMF showed MPL(W515K/L) (n=4). We conclude that MPL(W515L) occurs in a considerable proportion of acute megakaryoblastic leukaemias with myelofibrosis unrelated to PMF.

Transgenerational induction of leukaemia following parental irradiation. Genomic instability and the bystander in vivo

Energy Technology Data Exchange (ETDEWEB)

Lord, B.I. [Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester (United Kingdom)

2003-07-01

Internal radiation from small amounts of bone-incorporated plutonium-239 has been shown to result in long-term perturbation to haemopoiesis - in particular to the pluripotent bone marrow stem and progenitor cells - in mice. Associated with these changes is a small but finite induction of myeloid leukaemia. Preliminary experiments showed some instabilities in haemopoiesis following preconception, paternal irradiation (PPI) with {sup 239}Pu and these studies were extended to consider whether similar sensitivity to leukaemia induction might also arise in these offspring. Male mice were injected with 0, 128 or 256 Bq/g bodyweight with plutonium-239 citrate, 12 weeks before mating with normal untreated females. Bone marrow assays were conducted on their male offspring at 6-18 weeks after birth. Female offspring were injected with 50 mg/kg methyl nitrosourea (MNU), or irradiated with 3.3 Gy {gamma}-rays, at 10 weeks of age and observed continuously for onset of dysfunction when they were immediately sacrificed. In a parallel study set up by Stones and Humphreys (personal communication) incorporating significant numbers of offspring from PPI only, no case of leukaemia was observed. However, in this study, offspring of fathers treated with {sup 239}Pu showed significantly greater sensitivity than normal mice to treatment with known inducers of lympho-myeloid leukaemia such as MNU (or irradiation). Although a somewhat greater frequency of chromosomal abnormalities was seen in bone marrow of PPI offspring, the estimated mutation rates were insufficient to account for the degree of leukaemia induction and suggested an indirect mechanism. Detailed study of the bone marrow in individual offspring showed subtle changes in their stem cell content and in their haemopoietic inductive microenvironment, a component seen to be damaged also in the earlier radiation studies. It will be argued that low-dose radiation is rarely a direct cause of leukaemia (in mice). Rather that damage

Cases of leukaemia in the Sellafield area: the ''Sir Douglas Black'' report

International Nuclear Information System (INIS)

Dousset, M.; Jammet, H.

1984-01-01

The report of this Advisory Group was published in the summer of 1984. Its conclusions can be summarised as follows: 1. Epidemiological surveys, although still incomplete, show that the incidence of cases of leukaemia and deaths caused by leukaemia in persons under 25 years of age is ''unusual'' in the village of Seascale and the Millom rural district. However, they are not unique and the same phenomenon can be found in comparable population groups located far away from any nuclear plants. 2. Taking all children born Seascale since 1950 who lived in the village up until 1980, their equivalent dose in the red marrow of the bone caused by Sellafield nuclear waste and the Windscale reactor fire of 1957 is only 13% of the equivalent dose due to background radiation. 3. The excessive leukaemia mortality rate at Seascale cannot be explained by radioactive waste. For this, a factor of 40 to 400 would be necessary. However, since doubts remain with respect to Sellafield nuclear waste, it must be temporarily concluded that the hypothesis of a connexion between the proximity of the nuclear plant and the excessive leukaemia rate cannot be fully eliminated. But neither can it be easily proven. The advisory Group recommendations are relating to: the surveys to be carried on; the inspection to be improved around the Sellafield plant; the incumbent regulations to be taken into consideration [fr

Chronic lymphocytic leukaemia manifestating as exfoliative dermatitis

Directory of Open Access Journals (Sweden)

Dhir R

1995-01-01

Full Text Available A 60-year-old patient reported with a history of redness and peeling of the skin, and sensations of chills and tightness of the skin of three months duration. Clinical examination revealed exfoliative dermatitis, generalised lymphadenopathy and hepatosplenomegely. A peripheral smear showed features of chronic lymphocytic leukaemia.

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

Energy Technology Data Exchange (ETDEWEB)

James, N D; Apperley, J F; Kam, K C; Mackinnon, S; Goldman, J M; Goolden, A W.G.; Sikora, K [Royal Postgraduate Medical School, London (UK)

1989-03-01

Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author).

Total lymphoid irradiation preceding bone marrow transplantation for chronic myeloid leukaemia

International Nuclear Information System (INIS)

James, N.D.; Apperley, J.F.; Kam, K.C.; Mackinnon, S.; Goldman, J.M.; Goolden, A.W.G.; Sikora, K.

1989-01-01

Between August 1985 and October 1987 35 patients with chronic myeloid leukaemia (CML) were treated by high dose chemotherapy, total body irradiation (TBI) (1000 or 1200 cGy, n=31) and total lymphoid irradiation (TLI) (800 or 600 cGy, n=35) preceding allogeneic bone marrow transplantation (BMT). Both TBI and TLI were given at 200 cGy/fraction. Twenty-three patients had HLA-identical sibling donors, nine patients had HLA-matched but unrelated donors, and three partially HLA-mismatched donors. Twenty-two patients received T-cell depleted marrow. TLI did not add greatly to the toxicity. Four patients had recurrent leukaemia before engraftment was evaluable. The other 31 patients engrafted and no graft failed. Twenty-two patients survive at a median time from transplant of 305 days (range 81-586 days). Fourteen have no evidence of disease; eight have or had only cytogenetic evidence of leukaemia. It is concluded that addition of TLI to pretransplant immunosuppression increases the probability of reliable engraftment in patients receiving T-cell depleted marrow. This is not associated with significantly increased toxicity. (author)

Chronic lymphocytic leukaemia: An immunobiology approach

Directory of Open Access Journals (Sweden)

Kostareli Efterpi

2008-01-01

Full Text Available B cell chronic lymphocytic leukaemia (CLL is the most common adult leukaemia that follows an extremely variable clinical course. Several important prognostic parameters defining pathogenic and clinical subgroups of CLL have been identified and validated recently. The biological significance of immunoglobulin (Ig heavy chain variable region gene (IgHV mutational status and associated ZAP-70 over-expression, CD38 and chromosomal aberrations have enabled to identify patients at high risk for early disease progression and inferior survival. Moreover, studies of the B cell antigen receptor (BCR structure and receptor signaling have been most helpful in revealing some new aspects of the biology of this disease. In particular, the analysis of IG genes has revealed that the expressed IgHV/IgKV/IgLV gene repertoires of CLL cells differ from those of normal B cells. A further unique feature of the CLL IG repertoire is the existence of subsets of cases with "stereotyped" BCRs. Accumulating molecular and phenotypic data support the notion that CLL development and evolution is not a simple scholastic event and strongly indicates a role for antigen in driving the cell of origin for at least some subsets of CLL cases.

Epidemiological studies of leukaemia in children and young adults around nuclear facilities: a critical review

International Nuclear Information System (INIS)

2008-01-01

An epidemiological study published in late 2007 described an increased risk of leukaemia in children under 5 living within 5 kilometres of German nuclear power plants. A great deal of research has been carried out on this subject since the early 1980's. The aim of this report was to provide a synthesis and critical analysis of results related to the risk of leukaemia in children and young adults aged under 25 living close to nuclear facilities. The report is structured in three sections: - a reminder of the main characteristics of childhood leukaemia and a description of the methods used to conduct epidemiological studies; - the most exhaustive review possible of epidemiological studies published in the international literature describing the frequency of leukaemia close to nuclear facilities in different countries around the world. A critical analysis is made of the published results. Some results from studies not focused on nuclear facilities are also presented. The methodological limitations associated with descriptive studies are explained and discussed; - the last section discusses the possible causes of childhood leukaemia and the main hypotheses explored to explain certain clusters of cases observed locally close to some nuclear sites. Appendices at the end of the document provide additional explanations of the concepts and methods used in epidemiology and statistics, and of the classification of malignant hemopathies. (authors)

Childhood Leukaemia Incidence in Hungary, 1973-2002. Interpolation Model for Analysing the Possible Effects of the Chernobyl Accident

International Nuclear Information System (INIS)

Toeroek, Szabolcs; Borgulya, Gabor; Lobmayer, Peter; Jakab, Zsuzsanna; Schuler, Dezsoe; Fekete, Gyoergy

2005-01-01

The incidence of childhood leukaemia in Hungary has yet to be reported, although data are available since the early 70s. The Hungarian data therefore cover the time before and after the Chernobyl nuclear accident (1986). The aim of this study was to assess the effects of the Chernobyl accident on childhood leukaemia incidence in Hungary. A population-based study was carried out using data of the National Paediatric Cancer Registry of Hungary from 1973 to 2002. The total number of cases was 2204. To test the effect of the Chernobyl accident the authors applied a new approach called 'Hypothesized Impact Period Interpolation'-model, which takes into account the increasing trend of childhood leukaemia incidence and the hypothesized exposure and latency times. The incidence of leukaemia in the age group 0-14 varied between 33.2 and 39.4 per million person-years along the observed 30 year period, and the incidence of childhood leukaemia showed a moderate increase of 0.71% annually (p=0.0105). In the period of the hypothesized impact of the Chernobyl accident the incidence rate was elevated by 2.5% (95% CI: -8.1%; +14.3%), but this change was not statistically significant (p=0.663). The age standardised incidence, the age distribution, the gender ratio, and the magnitude of increasing trend of childhood leukaemia incidence in Hungary were similar to other European countries. Applying the presented interpolation method the authors did not find a statistically significant increase in the leukaemia incidence in the period of the hypothesized impact of the Chernobyl accident

Childhood leukaemia and nuclear power

International Nuclear Information System (INIS)

Berry, R.J.; Wakeford, R.

1992-01-01

There has been considerable scientific and media interest in the question of whether the risk of childhood leukemia is raised near nuclear facilities, and, if so, the reasons why. Serious consideration of this issue was initiated by a media report of an unusually large number of cases around the Sellafield installation in England, and reports of excess cases in the vicinity of other facilities in Britain have followed. Detailed radiological assessments have demonstrated that radioactive discharges are most unlikely to have been the cause of these reported excess cases, seemingly contradicting the epidemiological evidence. However, epidemiology is an observational (non-experimental) science, and the results of such studies must be interpreted with considerable care. The influence of prior knowledge of data upon the structure of a study has been a particular inferential problem. Furthermore, there are indications that non-radiological factors may be important in communities near nuclear facilities. Recently, a study has shown an association between childhood leukaemia cases near Sellafield and the recorded occupational radiation doses received by fathers before the conception of these children; but this novel finding has received little independent scientific support. At present, the British childhood leukaemia findings have not been replicated in studies based in other countries, and the reasons for the reported case excesses around British nuclear facilities remain unclear

Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research

International Nuclear Information System (INIS)

Laurier, D; Jacob, S; Grosche, B; Dehos, A; Hornhardt, S; Ziegelberger, G

2014-01-01

Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out. (review)

[An immunological approach to acute myeloid leukaemia].

Science.gov (United States)

González, B; Bueno, D; Rubio, P M; San Román, S; Plaza, D; Sastre, A; García-Miguel, P; Fernández, L; Valentín, J; Martínez, I; Pérez-Martínez, A

2016-04-01

Acute myeloid leukaemia (AML) is the second haematological malignancy in the paediatric population, and one of the leading causes of childhood cancer mortality. Survival is currently around 60%, with no improvement in last decades, suggesting that new therapeutic approaches are needed. The anti-leukaemia effect mediated by the lymphocytes and natural killer (NK) cells of the immune system has been established in haematopoietic stem cell transplantation, and also as adoptive immunotherapy after consolidation chemotherapy schemes. A retrospective study was conducted on the clinical characteristics of patients diagnosed and treated for AML in our centre during 1996-2014. The mean fluorescence intensities of HLA-I, MICA/B and ULBP1-4, ligands for NK cell receptors, were also analysed in ten new diagnosed leukaemia cases, five myeloid and five lymphoid. A total of 67 patients were used in this analysis. With a median follow up of 25 months, the event-free survival was 62% (95% CI: 55-67). Secondary AML, non-M3 phenotype, and the absence of favourable cytogenetic markers had a lower survival. The probability of relapse was 38% (95% CI: 31-45). The expression of HLA-I and ULBP-4 was significantly lower in myeloid than in lymphoid blast cells. Our clinical results are similar to those described in the literature. Survival did not significantly change in recent decades, and the likelihood of relapse remains high. Myeloid blasts might be more susceptible to the cytotoxicity of NK cells through their lower expression of HLA-I. NK therapy strategies in minimal disease situation could be effective, as reported by other groups. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Membrane and Soluble Apo-1 as a Marker of Apoptosis in Patients with Acute Leukaemia

International Nuclear Information System (INIS)

Abu Taleb, F.M.; El-Nemr, D.M.; Shawky, N.M.; Esh, S.S.

2002-01-01

comparison with normal control. After initial induction chemotherapy, the level of soluble CD95 was found to be significantly decreased in both ALL and AML patients in comparison to its level before therapy ((ρ < 0.001 and < 0.01, respectively). By following up patients who were resistant to chemotherapy, it was observed that patients who did not achieve complete remission after induction chemotherapy had relatively higher levels of sAPO- 1. Conclusion: From these results we can conclude that, since there is a significant relationship between surface CD95 expression in both ALL and AML patients and response to chemotherapy, the expression of surface CD95 could serve as a new prognostic marker as it is helpful in predicting the outcome of therapy. In addition, because soluble APO- 1 was found to be relatively high in patients resistant to anti-leukaemic therapy, so measurement of sAPO- 1 in sera of acute leukaemia patients could serve as a putative marker for an active persisting leukaemia

ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

Science.gov (United States)

Goossens, Steven; Radaelli, Enrico; Blanchet, Odile; Durinck, Kaat; Van der Meulen, Joni; Peirs, Sofie; Taghon, Tom; Tremblay, Cedric S.; Costa, Magdaline; Ghahremani, Morvarid Farhang; De Medts, Jelle; Bartunkova, Sonia; Haigh, Katharina; Schwab, Claire; Farla, Natalie; Pieters, Tim; Matthijssens, Filip; Van Roy, Nadine; Best, J. Adam; Deswarte, Kim; Bogaert, Pieter; Carmichael, Catherine; Rickard, Adam; Suryani, Santi; Bracken, Lauryn S.; Alserihi, Raed; Canté-Barrett, Kirsten; Haenebalcke, Lieven; Clappier, Emmanuelle; Rondou, Pieter; Slowicka, Karolina; Huylebroeck, Danny; Goldrath, Ananda W.; Janzen, Viktor; McCormack, Matthew P.; Lock, Richard B.; Curtis, David J.; Harrison, Christine; Berx, Geert; Speleman, Frank; Meijerink, Jules P. P.; Soulier, Jean; Van Vlierberghe, Pieter; Haigh, Jody J.

2015-01-01

Early T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression initiates T-cell leukaemia. Moreover, Zeb2-driven mouse leukaemia exhibit some features of the human immature/ETP-ALL gene expression signature, as well as an enhanced leukaemia-initiation potential and activated Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signalling through transcriptional activation of IL7R. This study reveals ZEB2 as an oncogene in the biology of immature/ETP-ALL and paves the way towards pre-clinical studies of novel compounds for the treatment of this aggressive subtype of human T-ALL using our Zeb2-driven mouse model. PMID:25565005

Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

Directory of Open Access Journals (Sweden)

Mao-Qiang Man

2012-01-01

Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.

Leukaemia mortality and morbidity in Bavaria

International Nuclear Information System (INIS)

Grosche, B.; Hinz, G.; Tsavachidis, C.

1987-01-01

Two studies dealing with leukaemia in Bavaria/FRG are presented: a mortality study (1972-1978) and a morbidity study (1976-1981). Both were conducted as ecological studies, i.e. under inclusion of environmental factors. Major point of view is first the amount of natural background radiation and second the sites of nuclear reactors, which are six. Mortality and incidence is described. Calculations were made on the influence of migration on patterns of regional distribution. (author)

Chemotherapy in a transplantable myeloid leukaemia in brown Norway rats : studies on BNML as a model for human acute myeloid leukaemia

NARCIS (Netherlands)

L.P. Colly

1980-01-01

textabstractLeukaemia accounts for less than 5% of the total number of malignant diseases in the USA {McCredie et al., 1976),· while about 9% of all neeplasros in the Netherlands originate in the lymphatic and blood forming organs. Because of the relatively easy accessibility of the turnoor cells in

Depleted uranium and radiation - induced lung cancer and leukaemia

International Nuclear Information System (INIS)

Mould, R.F.

2002-01-01

Reports of leukaemias and other cancers among servicemen who took part in the 1991 Gulf war or in the more recent operations in the Balkans are of continuing interest, as is the possibility, however slight, that depleted uranium (DU) is one of the causative factors. This commentary includes the results of a UK epidemiological study on the mortality of Gulf war veterans and , although not containing information on DU exposure, gives data on overall levels of mortality and therefore carries more weight than anecdotal reports. Also included are brief summaries on radiation-induced lung cancer in uranium workers as well as radiation-induced leukaemia in Japanese atomic bomb survivors and patients ankylosing spondylitis treated using x-rays. This commentary concludes with a critique of Iraqi cancer statistics as well as giving information on environmental contamination in Kosovo and the use of DU ammunition. (author)

Has fallout from the Chernobyl accident caused childhood leukaemia in Europe? An update on epidemiologic evidence

International Nuclear Information System (INIS)

Hoffmann, W.

2001-01-01

Background: According to radiation risk estimates uniformly adopted by various official organizations, exposure to Chernobyl fallout is unlikely to have caused any measurable health risk in central Europe. Methods and Results: A reevaluation of ECLIS (European Childhood Leukaemia and Lymphoma Incidence Study), a large IARC-coordinated project revealed a slightly higher leukaemia incidence in the most contaminated European regions, and an increasing trend with estimated cumulative excess radiation dose. The excess corresponds to 20 cases of childhood leukaemia in the study area until 1991. Recent evidence from Greece and Germany indicate significantly higher risks in the cohort of children in utero at the time of the initial fallout. In Greece, a positive trend was observed over three regions of increasing average fallout contamination (p=0.005). Conclusion: Chernobyl fallout could well have caused a small, but significant excess of childhood leukaemia cases in Europe. The etiologic mechanism might include an induction of chromosome aberrations in early pregnancy. Increased risks in the birth cohort exposed in utero correspond to 11 excess cases in Greece and another 11.4 excess cases in Germany alone. Exposure misclassification and underascertainment of incident cases render post-Chernobyl risk estimates probably too low. If indeed Chernobyl fallout has caused childhood leukaemia cases in Europe, we would also expect an increased incidence for other childhood cancers and excess malignancies in adults as well as non-malignant diseases of all ages. Neither of these endpoints have as yet been systematically studied. (orig.)

Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions.

Science.gov (United States)

Upadhyay, Vivek A; Fathi, Amir T

2018-03-01

This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations. Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody drug conjugates and liposomal formulations have demonstrated significant potential as modifications to traditional induction chemotherapy.

Herpesvirus in the oral cavity of children with leukaemia and its impact on the oral bacterial community profile.

Science.gov (United States)

Bezerra, Tacíria M; Ferreira, Dennis C; Carmo, Flávia L; Pinheiro, Raquel; Leite, Deborah C A; Cavalcante, Fernanda S; Belinho, Raquel A; Peixoto, Raquel S; Rosado, Alexandre S; dos Santos, Kátia R N; Castro, Gloria F B A

2015-03-01

This cross-sectional study investigated the association between eight herpesviruses and the bacterial community profiles from the oral cavity of children with and without leukaemia. Sixty participants (aged 3-13), divided into the leukaemia group (LG) and healthy group (HG), were evaluated. Collection of medical data, intraoral examination and collection of clinical specimens were carried out. Single PCR and nested-PCR techniques were used to identify the viral types; denaturing gradient gel electrophoresis (DGGE) and real-time PCR techniques were used to evaluate the profile and abundance of bacterial communities. All the children with leukaemia were positive for at least one type of herpesvirus, compared with healthy participants (33.3%; pherpesvirus-7 (HHV-7; 20%) and HHV-8 (77.3%) were in higher prevalence in the LG (p ≤ 0.01). Children with leukaemia had positive associations with the presence of HCMV, HHV-7 and HHV-8 in the oral cavity when under chemotherapy (pherpesviruses and the qualitative bacterial profiles was higher in children with leukaemia and HCMV, HHV-7 and HHV-8 were related to the use of chemotherapy. Moreover, HHV-6 was correlated with an increased bacterial community profile in patients with leukaemia (p<0.05). More attention should be paid to the oral health of these individuals, mainly those under chemotherapy, in order to prevent infections by opportunistic pathogens. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Updated estimates of the proportion of childhood leukaemia incidence in Great Britain that may be caused by natural background ionising radiation

International Nuclear Information System (INIS)

Little, Mark P; Wakeford, Richard; Kendall, Gerald M

2009-01-01

The aetiology of childhood leukaemia remains generally unknown, although exposure to moderate and high levels of ionising radiation, such as was experienced during the atomic bombings of Japan or from radiotherapy, is an established cause. Risk models based primarily upon studies of the Japanese A-bomb survivors imply that low-level exposure to ionising radiation, including to ubiquitous natural background radiation, also raises the risk of childhood leukaemia. In a recent paper (Wakeford et al 2009 Leukaemia 23 770-6) we estimated the proportion of childhood leukaemia incidence in Great Britain attributable to natural background radiation to be about 20%. In this paper we employ the two sets of published leukaemia risk models used previously, but use recently published revised estimates of natural background radiation doses received by the red bone marrow of British children to update the previous results. Using the newer dosimetry we calculate that the best estimate of the proportion of cases of childhood leukaemia in Great Britain predicted to be attributable to this source of exposure is 15-20%, although the uncertainty associated with certain stages in the calculation (e.g. the nature of the transfer of risk between populations and the pertinent dose received from naturally occurring alpha-particle-emitting radionuclides) is significant. The slightly lower attributable proportions compared with those previously derived by Wakeford et al (Leukaemia 2009 23 770-6) are largely due to the lower doses (and in particular lower high LET doses) for the first year of life.

Therapy related Acute Myeloid Leukaemia 8 Years after Treatment ...

African Journals Online (AJOL)

Hodgkin's Disease (HD) is a curable malignancy even in Nigeria, our limitations in health care delivery notwithstanding. However, secondary malignancies especially Acute Myeloid Leukaemia (AML) may occur as late complications following alkylating cytotoxic drugs therapy, with or without radiotherapy. This is a case ...

Radiation-associated chronic myelogenous leukaemia in younger people

International Nuclear Information System (INIS)

Shimaoka, K.; Sokal, J.E.

1978-01-01

Chronic myelogenous leukaemia (CML) is known to be induced by exposure to ionizing radiation, as is acute leukaemia. However, CML has been recorded only rarely as a complication of radiation exposure early in life. During the period from 1973 to 1976, 75 patients with CML were admitted to Roswell Park Memorial Institute (RPMI). In addition, 64 patients admitted to RPMI previously were also available for study in 1973. Among 79 patients who were born after 1925, information regarding radiation exposure was obtained in 89%; 49 were interviewed and 21 responded to a mailed questionnaire. Consultation with parents was achieved in 52 of the 70 responding cases (74%). Replies were obtained from 15 of the 18 patients below the age of 25, and were confirmed by parents or siblings in all instances. Replies to the mailed questionnaire were obtained from 45 age- and sex-matched controls. In addition to two patients already known to have radiation exposure for treatment of malignant neoplasms, these inquiries yielded a total of nine patients with histories of radiation exposure for benign conditions. Three had therapeutic irradiation, two for thymic enlargement and one for eczema. Three had exposure in utero by pelvimetry. Two had diagnostic exposure during the perinatal period and one had occupational exposure as a nurse. Four of these patients were below the age of 25. All nine patients had the Ph' chromosome. The course of CML in these patients was not different from that of other patients with Ph' chromosome-positive CML without a history of radiation exposure. A history of radiation exposure was elicited in one-fourth of the younger patients (<25) in this study, compared with one of 45 age- and sex-matched controls without leukaemia (p<0.02)

Recent work on local leukaemia incidence and mortality

International Nuclear Information System (INIS)

Cook-Mozaffari, P.J.

1987-01-01

Two approaches have been used recently, based on study of local variation in leukaemia occurrence to examine whether there is evidence of a general elevation of risk at different ages in the vicinity of nuclear installations in England and Wales. Both studies give some information also on risk in the vicinity of individual installations. (author)

Exposure to infections through day-care attendance and risk of childhood leukaemia

International Nuclear Information System (INIS)

Urayama, K. Y.; Ma, X.; Buffler, P. A.

2008-01-01

There is growing evidence supporting a role for infections in the aetiology of childhood leukaemia. Hypotheses proposed by both Greaves and Kinlen describe childhood leukaemia to be a rare response to one or more common infections acquired through personal contacts. Previous epidemiological studies have used day-care attendance as an indicator of the increased likelihood of early and frequent exposure to infections. It is well-documented that in developed countries, exposures to common infections occur more frequently in this type of setting. Within the Northern California Childhood Leukaemia Study, the role of social contact has been assessed and a unique 'child-hours' summary measure incorporating information on the number of months attending a day-care, mean hours per week at this day-care and the number of children in the day-care setting was constructed. In this review, the previously reported day-care results have been described, showing that in non-Hispanic White children, children in the highest category of total child-hours of exposure had a reduced risk of acute lymphoblastic leukaemia (ALL), particularly common B-cell precursor ALL (c-ALL), compared with children without such exposures, with evidence of a dose-response effect. In addition, a literature review of relevant studies has been conducted, examining the relationship between day-care attendance and risk of childhood ALL. Overall, the 14 studies identified provided consistent support for this hypothesis, with the majority of studies reporting some evidence of a reduced risk. A meta-analysis is currently underway, which will provide a quantitative evaluation of the overall consistency and strength of the association between day-care attendance or social contact and risk of childhood ALL. (authors)

Breaking bad news--parents' experience of learning that their child has leukaemia.

LENUS (Irish Health Repository)

Oshea, J

2012-02-03

This study aimed to seek parents\\' experiences of how they learned their child had leukaemia and therefore identify ways of improving this process. To achieve this task a questionnaire was designed to ask parents about specific elements of the initial interview and give them opportunity to add their thoughts and feelings on the subject. All children with a diagnosis of leukaemia over an eighteen-year period were identified and parents of those children still alive were invited to partake in the study. 49 out of 50 families agreed to participate of which 35 (72%) returned completed questionnaires. The majority 29 (83%) expressed overall satisfaction. Their replies confirmed some findings of previous studies, and also offered some new insights. Examples of new findings or expansion on previous findings include observations on the presence of young children at the initial interview; the importance of the language used in conveying the diagnosis and prognostic information, and a preference for actuarial terms when discussing prognosis. Telling parents their child has leukaemia is a challenging and important task. The experience of parents gives us valuable insights into our own communication skills and highlights areas of possible improvement in this difficult area.

Hypermethylation of the FANCC and FANCL Promoter Regions in Sporadic Acute Leukaemia

Directory of Open Access Journals (Sweden)

C. J. Hess

2008-01-01

Full Text Available Objective: Inactivation of the FA-BRCA pathway results in chromosomal instability. Fanconi anaemia (FA patients have an inherited defect in this pathway and are strongly predisposed to the development of acute myeloid leukaemia (AML. Studies in sporadic cancers have shown promoter methylation of the FANCF gene in a significant proportion of various solid tumours. However, only a single leukaemic case with methylation of one of the FA-BRCA genes has been described to date, i.e. methylation of FANCF in cell line CHRF-288. We investigated the presence of aberrant methylation in 11 FA-BRCA genes in sporadic cases of leukaemia.

Evidence from population mixing in British New Towns 1946-85 of an infective basis for childhood leukaemia

Energy Technology Data Exchange (ETDEWEB)

Kinlen, L.J.; Clarke, K. (Edinburgh Univ. (UK). CRC Cancer Epidemiology Unit); Hudson, C. (Oxford Univ. (UK). CRC Cancer Epidemiology Research Group)

1990-09-08

Mortality from leukaemia under age 25 was studied in British New Towns to test the hypothesis that leukaemia represents a rare response to a much commoner (unrecognised) infection, the transmission of which is facilitated when large numbers of people come together. The density of children was higher in the rural, but lower in the overspill, New Towns than in areas from which their incomers originated. Residents of the rural New Towns had greater diversity of origin than those of overspill towns of London and Glasgow. These two factors would encourage a greater rise in the postulated underlying infection in the rural towns, and in these a significant excess of leukaemia at ages 0-4 was found in 1946-65. In both sets there was a significant deficit in other age groups consistent with immunising effects of the relevant infection. There are parallels with feline leukaemia virus infection, in which contrasting leukaemogenic and immunising effects occur in different social settings owing mainly to differences in intensity of viral exposure. (author).

Evidence from population mixing in British New Towns 1946-85 of an infective basis for childhood leukaemia

International Nuclear Information System (INIS)

Kinlen, L.J.; Clarke, K.; Hudson, C.

1990-01-01

Mortality from leukaemia under age 25 was studied in British New Towns to test the hypothesis that leukaemia represents a rare response to a much commoner (unrecognised) infection, the transmission of which is facilitated when large numbers of people come together. The density of children was higher in the rural, but lower in the overspill, New Towns than in areas from which their incomers originated. Residents of the rural New Towns had greater diversity of origin than those of overspill towns of London and Glasgow. These two factors would encourage a greater rise in the postulated underlying infection in the rural towns, and in these a significant excess of leukaemia at ages 0-4 was found in 1946-65. In both sets there was a significant deficit in other age groups consistent with immunising effects of the relevant infection. There are parallels with feline leukaemia virus infection, in which contrasting leukaemogenic and immunising effects occur in different social settings owing mainly to differences in intensity of viral exposure. (author)

The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias

Directory of Open Access Journals (Sweden)

Maher Eamonn R

2009-07-01

Full Text Available Abstract Background The Ras-assocation family (RASSF of tumour suppressor genes (TSGs contains 10 members that encode proteins containing Ras-assocation (RA domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL and normal blood and bone marrow samples. Results COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51 B-ALL and 41% (12/29 T-ALL, whilst RASSF10 was methylated in 16% (8/51 B-ALL and 88% (23/26 T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC. Conclusion This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.

The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

Energy Technology Data Exchange (ETDEWEB)

Janowski, M [Centre d' Etude de l' Energie Nucleaire, Mol (Belgium); Cox, R [Medical Research Council, Harwell (UK). Radiobiological Research Unit; Strauss, P G [GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie

1990-04-01

In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

Risk analysis of leukaemia incidence among people living along the Techa River: a nested case-control study

International Nuclear Information System (INIS)

Ostroumova, E; Gagniere, B; Laurier, D; Gudkova, N; Krestinina, L; Verger, P; Hubert, P; Bard, D; Akleyev, A; Tirmarche, M; Kossenko, M

2006-01-01

Large quantities of radioactive materials released over time from the Mayak nuclear weapons facility caused significant internal and external exposure for people living along the banks of the Techa River (Southern Urals, Russia). We conducted a nested case-control study in the Extended Techa River Cohort to determine whether the risk of leukaemia incidence increased with protracted exposure to ionising radiation or with other non-radiation risk factors. The study included 83 cases identified over 47 years of follow-up and 415 controls matched for sex, age at diagnosis, age (within a 5 year age group), and date of initial residence in the riverside area. External and internal doses have been calculated using the Techa River Dosimetry System 1996 (TRDS96). Conditional logistic regression was used to calculate odds ratios per Gray (OR/Gy) and 95% confidence intervals (95% CI). After excluding cases of chronic lymphoid leukaemia, the OR/Gy of total, external, and internal doses were 4.6 (95% CI: 1.7-12.3), 7.2 (95%CI: 1.7-30.0) and 5.4 (95%CI: 1.1-27.2), respectively. A history of solid tumour, either malignant or benign, before the leukaemia diagnosis was associated with a 2.5-fold increase in the leukaemia risk (95% CI: 1.1-5.9). Even though the analysis of confounders was less useful than expected because of missing data, multivariate analyses that took the exposure dose into account confirmed the association between leukaemia incidence and tumour history

Leukaemia and occupation: a New Zealand Cancer Registry-based case-control Study.

Science.gov (United States)

McLean, David; Mannetje, Andrea 't; Dryson, Evan; Walls, Chris; McKenzie, Fiona; Maule, Milena; Cheng, Soo; Cunningham, Chris; Kromhout, Hans; Boffetta, Paolo; Blair, Aaron; Pearce, Neil

2009-04-01

To examine the association between occupation and leukaemia. We interviewed 225 cases (aged 20-75 years) notified to the New Zealand Cancer Registry during 2003-04, and 471 controls randomly selected from the Electoral Roll collecting demographic details, information on potential confounders and a comprehensive employment history. Associations between occupation and leukaemia were analysed using logistic regression adjusted for gender, age, ethnicity and smoking. Elevated odds ratios (ORs) were observed in agricultural sectors including horticulture/fruit growing (OR: 2.62, 95% confidence interval (CI): 1.51, 4.55), plant nurseries (OR: 7.51, 95% CI: 1.85, 30.38) and vegetable growing (OR: 3.14, 95% CI: 1.18, 8.40); and appeared greater in women (ORs: 4.71, 7.75 and 7.98, respectively). Elevated ORs were also observed in market farmers/crop growers (OR: 1.84, 95% CI: 1.12, 3.02), field crop/vegetable growers (OR: 3.98, 95% CI: 1.46, 10.85), market gardeners (OR: 5.50, 95% CI: 1.59, 19.02), and nursery growers/workers (OR: 4.23, 95% CI: 1.34, 13.35); also greater in women (ORs: 3.48, 7.62, 15.74 and 11.70, respectively). These elevated ORs were predominantly for chronic lymphocytic leukaemia (CLL). Several associations persisted after semi-Bayes adjustment. Elevated ORs were observed in rubber/plastics products machine operators (OR: 3.76, 95% CI: 1.08, 13.08), predominantly in plastic product manufacturing. CLL was also elevated in tailors and dressmakers (OR: 7.01, 95% CI: 1.78, 27.68), cleaners (OR: 2.04, 95% CI: 1.00, 4.14) and builder's labourers (OR: 4.03, 95% CI: 1.30, 12.53). These findings suggest increased leukaemia risks associated with certain agricultural, manufacturing, construction and service occupations in New Zealand.

Living with the Diagnosis and Treatment of Leukaemia in a Child with Down's Syndrome: A Mother's Reflection

Science.gov (United States)

Self, Donna

2008-01-01

In this article I will discuss the impact of my 2-year-old son's diagnosis and treatment of leukaemia. I will outline the background to being told he had leukaemia before describing the family dynamics that emerged during this time for me, my husband and our other child. My story will focus on managing the practicalities of a long stay in hospital…

Splenic Trapping of Heat-Treated Erythrocytes in Leukaemia and Allied Conditions

Energy Technology Data Exchange (ETDEWEB)

Badrawi, H. S.; Razzak, M. A.; Guirgis, B. [Department of Medicine and Division of Nuclear Medicine, Faculty of Medicine, Cairo University, Cairo, United Arab Republic (Egypt)

1971-02-15

In a trial to find whether or not the enlarged spleen plays a role in the production of the form of anaemia commonly encountered in leukaemias and allied conditions, 44 patients suffering from these disease states were studied using {sup 51}Cr-labelled erythrocytes heated at 50 Degree-Sign C for 60 min. Cells altered in this manner have been shown by various workers to be selectively sequestered by the spleen. As a control, the test was performed on 24 normal subjects. In these normals, the disappearance half-time of radioactivity from the circulation (T{sub Vulgar-Fraction-One-Half} amounted to 172 {+-} 69 min (mean {+-} 1 S.D.), the lowest limit being 74 min. Accordingly, patients with less than 74 min were considered to have an abnormally rapid disappearance of heat-treated erythrocytes from the circulation and consequently exaggerated splenic sequestration of these altered cells. Splenic trapping of heat-treated erythrocytes was most marked in acute leukaemia (four out of six patients). However, three had associated normoblastic hypoplasia of the sternal marrow. Corticosteroids induced a remission with reversion of both processes responsible for the anaemia in two out of the four patients. In chronic myeloid leukaemia, exaggerated splenic sequestration of altered cells was seen in four of the 15 cases examined. This condition was of extra-erythrocytic origin, since repetition of the test using normal donor heat-treated erythrocytes did not significantly alter the disappearance half-time. However, there was no correlation between the size of the spleen and its avidity for trapping the altered cells. Follow-up studies showed that therapy caused prolongation of the half-time of heat-treated erythrocytes, the effect being more apparent after corticosteroids than with X-rays or Endoxan, In Hodgkin's disease, increased red cell trapping was observed in two out of the seven patients studied. In contrast, five cases of chronic lymphatic leukaemia, six lymphosarcoma and

Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission.

Science.gov (United States)

Saldaña Garrido, J D; Martínez Rubio, M; Carrión Campo, R; Moya Moya, M A; Rico Sergado, L

2017-03-01

A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples.

Science.gov (United States)

Szulzewsky, Frank; Arora, Sonali; de Witte, Lot; Ulas, Thomas; Markovic, Darko; Schultze, Joachim L; Holland, Eric C; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut

2016-08-01

Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) to CD11b(+) microglia isolated from non-tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs. In comparison to human control microglia hGAMs upregulated genes associated with mitotic cell cycle, cell migration, cell adhesion, and extracellular matrix organization. We validated the expression of several genes associated with extracellular matrix organization in samples of human control microglia, hGAMs, and the hGAMs-depleted fraction via qPCR. The comparison to murine GAMs (mGAMs) showed that both cell populations share a significant fraction of upregulated transcripts compared with their respective controls. These genes were mostly related to mitotic cell cycle. However, in contrast to murine cells, human GAMs did not upregulate genes associated to immune activation. Comparison of human and murine GAMs expression data to several data sets of in vitro-activated human macrophages and murine microglia showed that, in contrast to mGAMs, hGAMs share a smaller overlap to these data sets in general and in particular to cells activated by proinflammatory stimulation with LPS + INFγ or TNFα. Our findings provide new insights into the biology of human glioblastoma-associated microglia/monocytes and give detailed information about the validity of murine experimental models. GLIA 2016 GLIA 2016;64:1416-1436. © 2016 Wiley Periodicals, Inc.

Occupational exposure of fathers to ionizing radiation and the risk of leukaemia in offspring

International Nuclear Information System (INIS)

McLaughlin, J.R.; Clarke, E.A.; Anderson, T.W.; King, W.

1992-08-01

An epidemiologic study was performed to determine whether there was an association between childhood leukaemia and the occupational exposure of fathers in the nuclear industry to ionizing radiation prior to the child's conception. The study employed a case-control design. Children with cancer ('cases') and children who did not develop cancer ('controls') were compared with respect to their exposure history. The cases, which occurred from 1950 to 1988, consisted of children aged 0 to 14 years who died from or were diagnosed with leukaemia and were born to mothers who lived near an operating nuclear facility in Ontario. Eight controls were matched to each case according to date of birth and mother's residence. There were 112 cases and 890 controls (six controls died before the development of the associated case's leukaemia). Data on the occupational exposure of the 1002 fathers were obtained from the Canadian National Dose Registry (NDR) and examination of employer records. Links to the NDR were found for 95 fathers. For each father doses were obtained regarding whole body external dose, tritium dose, and (for uranium miners) internal exposures to the lungs due to radon and radon daughters. Radiation exposures were estimated (a) over the father's lifetime before the child's conception; (b) during the six months prior to the child's conception; (c) during the three months prior to the child's conception; and (d) over the father's lifetime, ending in the month of the child's diagnosis. There was no evidence of an elevated leukaemia risk in relation to any exposure period or exposure type, and there was no apparent gradient of effect with increasing radiation dose. It is concluded that there was no association between childhood leukaemia and the occupational exposure of fathers to ionizing radiation prior to conception or diagnosis. Odds ratios were close to 1.0 for all radiation dose categories and occupations except for uranium mining, which had a larger but not

Cell-targeted sup 114 In sup m and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia. [Bischloroethylnitrosourea

Energy Technology Data Exchange (ETDEWEB)

Jackson, N.C.; Jackson, H.; Bock, M.; Sharma, H.L. (Manchester Univ. (United Kingdom). Dept. of Medical Biophysics); Ramsden, C. (Manchester Univ. (United Kingdom). Dept. of Immunology)

1992-08-01

A proportion of syngeneic female rats inoculated intramuscularly with a lethal T-cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine)(10 mg kg{sup -1}) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide {sup 114}In{sup m}, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells. (author).

Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

OpenAIRE

Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

1985-01-01

We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in...

Negative trends for in utero Chernobyl exposure and early childhood leukaemia in Western Germany

International Nuclear Information System (INIS)

Burkart, W.; Steiner, M.; Grosche, B.; Kaletsch, U.; Michaelis, J.

1997-01-01

A recent report in Nature linked increased incidence of early infant leukaemia in Greece with 137 Cs fallout density, attributing the effect to an increased in utero exposure to ionizing radiation from the Chernobyl accident. As a validation exercise in a similarly affected region, we performed an analysis based on the data of the Childhood Cancer Registry for Western Germany. Using the same definitions as Petridou et al. we also observed an increased incidence of infant leukaemia in a cohort of children who were born after the Chernobyl accident. More detailed analyses of embryonic/foetal doses regarding areas of different contamination levels and dose rate gradients with time since the accident showed non-significant negative trends with exposure. Therefore, we conclude that the observed effect was not caused by exposure to ionizing radiation due to the Chernobyl accident. Dosimetric considerations per se, based on careful assessment of in utero doses in three different exposure categories, show doses much too small relative to natural radiation exposures to account for a significant effect on leukaemia rates. (author)

Residential mobility of populations near UK power lines and implications for childhood leukaemia

International Nuclear Information System (INIS)

Swanson, John

2013-01-01

Epidemiological studies suggest associations between childhood leukaemia and living near high-voltage power lines, but the most obvious potential causative agent, the magnetic fields produced by the power lines, is not supported by laboratory studies or a known mechanism. An alternative hypothesised explanation is if there is greater population mobility near power lines, linking to the findings of Kinlen that population mixing increases leukaemia rates. We used the names recorded in electoral registers to see whether people near power lines move house more often than the population as a whole. We did find variations, but only small ones, and not such as to support the hypothesis. (note)

MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick; Deville, Anne; Kurzenne, Jean-Yves

2008-01-01

Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment. (orig.)

MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick [Regional Hospital Centre and University of Nice, Medical Imaging Service, Archet 2 Hospital, 151 route de Saint Antoine de Ginestiere, B.P. 3079, Nice Cedex 3 (France); Deville, Anne [Regional Hospital Centre and University of Nice, Paediatric Service, Archet 2 Hospital, Nice (France); Kurzenne, Jean-Yves [Regional Hospital Centre and University of Nice, Paediatric Surgery Service, Archet 2 Hospital, Nice (France)

2008-03-15

Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment. (orig.)

Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia

NARCIS (Netherlands)

Avvisati, G.; ten Cate, J. W.; Büller, H. R.; Mandelli, F.

1989-01-01

In a double-blind study, 12 consecutive patients with acute promyelocytic leukaemia were randomised either to tranexamic acid (TA group) or to placebo (control group) for 6 days to see whether inhibition of fibrinolysis would reduce haemorrhage and transfusion requirements. The total study period

Complications of lumbar puncture in a child treated for leukaemia

International Nuclear Information System (INIS)

Staebler, Melanie; Delpierre, Isabelle; Damry, Nash; Christophe, Catherine; Azzi, Nadira; Sekhara, Tayeb

2005-01-01

Lumbar puncture may lead to neurological complications. These include intracranial hypotension, cervical epidural haematomas, and cranial and lumbar subdural haematomas. MRI is the modality of choice to diagnose these complications. This report documents MRI findings of such complications in a child treated for leukaemia. (orig.)

A review of the automated detection and classification of acute leukaemia: Coherent taxonomy, datasets, validation and performance measurements, motivation, open challenges and recommendations.

Science.gov (United States)

Alsalem, M A; Zaidan, A A; Zaidan, B B; Hashim, M; Madhloom, H T; Azeez, N D; Alsyisuf, S

2018-05-01

Acute leukaemia diagnosis is a field requiring automated solutions, tools and methods and the ability to facilitate early detection and even prediction. Many studies have focused on the automatic detection and classification of acute leukaemia and their subtypes to promote enable highly accurate diagnosis. This study aimed to review and analyse literature related to the detection and classification of acute leukaemia. The factors that were considered to improve understanding on the field's various contextual aspects in published studies and characteristics were motivation, open challenges that confronted researchers and recommendations presented to researchers to enhance this vital research area. We systematically searched all articles about the classification and detection of acute leukaemia, as well as their evaluation and benchmarking, in three main databases: ScienceDirect, Web of Science and IEEE Xplore from 2007 to 2017. These indices were considered to be sufficiently extensive to encompass our field of literature. Based on our inclusion and exclusion criteria, 89 articles were selected. Most studies (58/89) focused on the methods or algorithms of acute leukaemia classification, a number of papers (22/89) covered the developed systems for the detection or diagnosis of acute leukaemia and few papers (5/89) presented evaluation and comparative studies. The smallest portion (4/89) of articles comprised reviews and surveys. Acute leukaemia diagnosis, which is a field requiring automated solutions, tools and methods, entails the ability to facilitate early detection or even prediction. Many studies have been performed on the automatic detection and classification of acute leukaemia and their subtypes to promote accurate diagnosis. Research areas on medical-image classification vary, but they are all equally vital. We expect this systematic review to help emphasise current research opportunities and thus extend and create additional research fields. Copyright �

A comparison of the risks of childhood leukaemia from parental pre-conception exposure to radiation in the Sellafield and Dounreay workforces and the Japanese bomb survivors

International Nuclear Information System (INIS)

Little, M.P.

1991-01-01

The cases of childhood leukemia found among children of the Sellafield (West Cumbria) and Dounreay (Caithness) workforces and those observed in the offspring of the Japanese bomb survivors are analysed using exponential and linear forms of a relative risk model and employing dose estimates both for the period 6 months pre-conception and also for total pre-conception doses. The leukemia relative risk coefficients for paternal (whole-body) exposure in these pre-conception periods for children in Caithness are found to be statistically compatible with those of the children of Sellafield workers but also with the (gonadal dose) coefficients applying to the offspring of the bomb survivors. There remains the need to explain adequately the absence of a discernibly raised risk of childhood leukaemia in the offspring of the Japanese bomb survivors if the statistical association between paternal pre-conception radiation and the raised incidence of childhood leukaemia found in the West Cumbria study represents a causal relationship. (author)

Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.

Science.gov (United States)

Rushworth, Stuart A; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J; MacEwan, David J; Bowles, Kristian M

2015-05-01

Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. We obtained acute myeloid leukaemia blast cells from unselected patients attending our UK hospital between Feb 19, 2010, and Jan 20, 2014. We isolated primary acute myeloid leukaemia blast cells from heparinised blood and human peripheral blood mononuclear cells to establish the activity of BTK in response to CD117 activation. Furthermore, we investigated the effects of ibrutinib on CD117-induced BTK activation, downstream signalling, adhesion to primary bone-marrow mesenchymal stromal cells, and proliferation of primary acute myeloid leukaemia blast cells. We used the Mann-Whitney U test to compare results between groups. We obtained acute myeloid leukaemia blast cells from 29 patients. Ibrutinib significantly inhibited CD117-mediated proliferation of primary acute myeloid leukaemia blast cells (p=0·028). CD117 activation increased BTK activity by inducing phosphorylated BTK in patients with CD117-positive acute myeloid leukaemia. Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more. CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0·028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond. Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib

Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview.

Science.gov (United States)

Manola, Kalliopi N

2013-10-01

Acute leukaemia of ambiguous lineage (ALAL) is a rare complex entity with heterogeneous clinical, immunophenotypic, cytogenetic and molecular genetic features and adverse outcome. According to World Health Organization 2008 classification, ALAL encompasses those leukaemias that show no clear evidence of differentiation along a single lineage. The rarity of ALAL and the lack of uniform diagnostic criteria have made it difficult to establish its cytogenetic features, although cytogenetic analysis reveals clonal chromosomal abnormalities in 59-91% of patients. This article focuses on the significance of cytogenetic analysis in ALAL supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow up and treatment selection of ALAL. It reviews in detail the types of chromosomal aberrations, their molecular background, their correlation with immunophenotype and age distribution and their prognostic relevance. It also summarizes some novel chromosome aberrations that have been observed only once. Furthermore, it highlights the ongoing and future research on ALAL in the field of cytogenetics. © 2013 John Wiley & Sons Ltd.

Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes

DEFF Research Database (Denmark)

Schmiegelow, K.

2016-01-01

Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all...... patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring...... childhood ALL cases are due to such germline mutations, but the figure may be higher. Most of these syndromes are primarily characterized by their non-malignant phenotype, whereas ALL may be the dominating or even only striking manifestation of the syndrome in some families. Identification of such ALL...

Spatial variation of natural radiation and childhood leukaemia incidence in Great Britain

International Nuclear Information System (INIS)

Richardson, Sylvia; Monfort, Christine; Green, Martyn; Muirhead, Colin; Draper, Gerald

1995-01-01

This paper describes an analysis of the geographical variation of childhood leukaemia incidence in Great Britain over a 15 year period in relation to natural radiation (gamma and radon). Data at the level of the 459 district level local authorities in England, Wales and regional districts in Scotland are analysed in two complementary ways: first, by Poisson regressions with the inclusion of environmental covariates and a smooth spatial structure; secondly, by a hierarchical Bayesian model in which extra-Poisson variability is modelled explicitly in terms of spatial and non-spatial components. From this analysis, we deduce a strong indication that a main part of the variability is accounted for by a local neighbourhood 'clustering' structure. This structure is furthermore relatively stable over the 15 year period for the lymphocytic leukaemias which make up the majority of observed cases. We found no evidence of a positive association of childhood leukaemia incidence with outdoor or indoor gamma radiation levels. There is no consistent evidence of any association with radon levels. Indeed, in the Poisson regressions, a significant positive association was only observed for one 5-year period, a result which is not compatible with a stable environmental effect. Moreover, this positive association became clearly non-significant when over-dispersion relative to the Poisson distribution was taken into account. (author)

Child leukaemia and low frequency electromagnetic fields; Les leucemies de l'enfant et les champs electromagnetiques basse frequence

Energy Technology Data Exchange (ETDEWEB)

Clavel, J.

2009-07-01

The author discusses the possible causes of child leukaemia: exposure to natural ionizing radiation (notably radon), to pesticides, and to hydrocarbons emitted by road traffic. Some studies suggested that an inadequate reaction of the immune system to an ordinary infection could result in leukaemia. Other factors are suspected, notably extremely low frequency electromagnetic fields, the influence of which is then discussed by the author. She evokes and discusses results of different investigations on this topic which have been published since the end of the 1970's. It appears that a distance less than 50 meters from high voltage lines or the vicinity of transformation stations may double the risk of child leukaemia

The UK Childhood Cancer Study: Maternal occupational exposures and childhood leukaemia and lymphoma

International Nuclear Information System (INIS)

McKinney, P. A.; Raji, O. Y.; Van Tongeren, M.; Feltbower, R. G.

2008-01-01

Risks of childhood leukaemia and lymphoma were investigated for specific work-related exposures of mothers in the UK Childhood Cancer Study. Interviews with parents of 1881 leukaemia and lymphoma cases (0-14 years) and 3742 controls collected job histories recording exposure to eight specific agents. Exposure was (1) self-reported and (2) reviewed, based mainly on exposure probability and exposure level. Completeness, consistency and sufficiency evaluated data quality. Of all job exposures which were self-reported as exposed, 33% cases and 34% controls remained classified as exposed after review, with the remainder designated as partially exposed or unexposed. No review of underreporting of exposure was made. Data quality was 'good' for 26% of cases and 24% of controls. For self-reported exposure, significant risks of acute lymphoblastic leukaemia (ALL) were observed for solvents and petrol in all time windows. For reviewed exposure, solvents remained significant for ALL during pregnancy and post-natality. Restricting analyses to good-quality information removed all significant results. Refinement of exposure assessment revealed misclassification of self-reported exposures and data quality influenced risk assessment. Maternal exposure to solvents should further be investigated. These findings must invoke caution in the interpretation of risks reliant on self-reported occupational data. (authors)

Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

Science.gov (United States)

Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

1985-06-01

We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.

Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

DEFF Research Database (Denmark)

Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

2016-01-01

SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we...... prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD......57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia. These T cell populations were clonal in 20/20 patients and stably present...

The relevance of population mixing to the aetiology of childhood leukaemia

International Nuclear Information System (INIS)

Kinlen, L.J.

1989-01-01

It is postulated that childhood leukaemia represents a rare response to some unidentified common infection(s), epidemics of which would be encouraged by mixing of populations with plausibly different previous experiences of infective agents. This has been tested in two studies, the first in the only rural local authority district of Scotland moderately separated from a conurbation that received a large influx of people in the 1950s; the second concerned those new towns in Britain designated by 1950 situated away from the major conurbations of London and Glasgow. In both, highly significant excesses of leukaemia at ages 0-4 were observed, suggesting that it originates in some form of infective process and in one that is favoured by certain types of population mixing. Strong reasons would be required for supposing that this effect did not operate near nuclear reprocessing sites, so unusual is the population mixing associated with them. (author)

Comparison of Health and Safety Executive and Cumbrian birth cohort studies of risk of leukaemia/non-Hodgkin's lymphoma in relation to paternal preconceptional irradiation

International Nuclear Information System (INIS)

Dickinson, H O; Hodgson, J T; Parker, L

2003-01-01

In 1993, a case-control study by the Health and Safety Executive (HSE) assessed the risk of leukaemia and non-Hodgkin's lymphoma (LNHL) among children of fathers employed at the Sellafield nuclear installation in relation to paternal preconceptional irradiation (PPI). It concluded that the statistical association between risk of LNHL and PPI was confined to children born in the village of Seascale, where the dose-response was extremely high and very significant. In contrast, in 2002, a Cumbrian birth cohort study, investigating largely the same cases, concluded that this statistical association was not significantly different among children born inside and outside Seascale and estimated the dose-response inside Seascale to be much lower. This review makes a detailed comparison of the two studies, considering their design, data and analyses. The differences between their findings are due to: (i) differences in the distribution of offspring-years which are differential with respect to dose category and Seascale birth status, (ii) a non-Seascale high-dose case included in the Cumbrian but not the HSE study, (iii) differences between analyses using categorical and continuous PPI dose and (iv) the presence of Seascale controls with PPI over 200 mSv in the Cumbrian but not the HSE study

Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

Science.gov (United States)

Iland, Harry J; Collins, Marnie; Bradstock, Ken; Supple, Shane G; Catalano, Alberto; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Campbell, Lynda J; Hugman, Amanda; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Seymour, John F

2015-09-01

patients were enrolled between Nov 10, 2004, and Sept 23, 2009, with data cutoff of March 15, 2012. Four (3%) patients died early. After a median follow-up of 4·2 years (IQR, 3·2-5·2), the 5 year freedom from relapse was 95% (95% CI 89-98), disease-free survival was 95% (89-98), event-free survival was 90% (83-94), and overall survival was 94% (89-97). The comparison with APML3 data showed that hazard ratios were 0·23 (95% CI 0·08-0·64, p=0·002) for freedom from relapse, 0·21 (0·07-0·59, p=0·001) for disease-free survival, 0·34 (0·16-0·69, p=0·002) for event-free survival, and 0·35 (0·14-0·91, p=0·02) for overall survival. Incorporation of arsenic trioxide in initial therapy induction and consolidation for acute promyelocytic leukaemia reduced the risk of relapse when compared with historical controls. This improvement, together with a non-significant reduction in early deaths and absence of deaths in remission, translated into better event-free and overall survival. Phebra. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced detection and study of murine norovirus-1 using a more efficient microglial cell line

Directory of Open Access Journals (Sweden)

Lu Yuanan

2009-11-01

Full Text Available Abstract Background Human Noroviruses are the predominant cause of non-bacterial gastroenteritis worldwide. To facilitate prevention and control, a norovirus isolated from mice can provide a model to understand human noroviruses. To establish optimal viral infectivity conditions for murine noroviruses, several cell lines of hematopoietic lineage, including murine BV-2, RAW 264.7, and TIB, as well as human CHME-5, were tested comparatively for their sensitivity to murine norovirus-1. Results Except for CHME-5, all three murine-derived cell lines were susceptible to MNV infection. Viral infection of these cells was confirmed by RT-PCR. Using both viral plaque and replication assays, BV-2 and RAW 264.7 cells were determined to have comparable sensitivities to MNV-1 infection. Comparisons of cell growth characteristics, general laboratory handling and potential in-field applications suggest the use of BV-2 to be more advantageous. Conclusion Results obtained from these studies demonstrate that an immortalized microglial cell line can support MNV-1 replication and provides a more efficient method to detect and study murine noroviruses, facilitating future investigations using MNV-1 as a model to study, detect, and control Human Norovirus.

SWI/SNF Subunits SMARCA4, SMARCD2 and DPF2 Collaborate in MLL-Rearranged Leukaemia Maintenance

DEFF Research Database (Denmark)

Cruickshank, V Adam; Sroczynska, Patrycja; Sankar, Aditya

2015-01-01

the selective requirement for these proteins for leukaemic cell expansion and self-renewal in-vitro as well as in leukaemia. Gene expression profiling in human cells of each of these three factors suggests that they have overlapping functions in leukaemia. The gene expression changes induced by loss...... of the three proteins demonstrate that they are required for the expression of haematopoietic stem cell associated genes but in contrast to previous results obtained in mouse cells, the three proteins are not required for the expression of c-MYC regulated genes....

Infective basis in childhood leukaemia

International Nuclear Information System (INIS)

Kinlen, Leo

1995-01-01

Leukaemia in children has often been suspected of having an infective basis (as specifically identified in certain animal species) but, until recently, formal studies had gone no further than to show that it does not markedly cluster in time and space. Many infective illnesses, however, are uncommon responses to infections that are mainly spread by the majority of infected individuals who are not ill. These include, for example, glandular fever and certain types of meningitis. Such illnesses are not contagious and do not normally cluster. The possibilities that childhood leukamia might belong to this class of infective illnesses and be subject to increases in incidence as a result of epidemics of an underlying infection were suggested by the well-known excesses near Sellafield and Dounreay. (author)

Host, family and community proxies for infections potentially associated with leukaemia

International Nuclear Information System (INIS)

Law, G. R.

2008-01-01

Three hypotheses have proposed the involvement of infections in the aetiology of childhood leukaemia, suggesting either a specific leukemogenic infection or a series of common infections that lead to a dys-regulation of the immune system. Much of the evidence for the link with infections has been based on epidemiological observations, often using proxy measures of infection. Proxy measures include population mixing, parental occupation, age distribution of incidence, spatial and space-time clustering of cases, birth order and day care during infancy. This paper discusses the proxies used and examines to what extent a commonly used proxy measure, birth order, is a fair representation of either specific infections or general infectious load. It is clear that although leukaemia, and other diseases, may be linked with infections, one needs to (1) measure specific and general infections with more accuracy and (2) understand how proxy measures relate to real infections in the population. (authors)

Childhood leukaemia in the West Berkshire and Basingstoke and North Hampshire District Health Authorities in relation to nuclear establishments in the vicinity

International Nuclear Information System (INIS)

Roman, Eve; Beral, Valerie; Carpenter, Lucy; Watson, Ann; Barton, Carol; Ryder, Hilary; Aston, D.L.

1987-01-01

These data indicate that in the two district health authorities studied there was an excess incidence of childhood leukaemia during 1972-85 in the vicinity of the nuclear establishments. In the West Berkshire and Basingstoke and North Hampshire District Health Authorities an average of 60 000 children aged 0-14 lived within a 10 km radius of a nuclear establishment each year. The normal expectation of leukaemia in these children was two cases a year, whereas the recorded incidence was three cases per year, representing one extra case of leukaemia each year among these 60 000 children. (author)

Leukaemia and non-Hodgkin lymphoma risk among Chernobyl liquidators

International Nuclear Information System (INIS)

Kesminiene, Ausrele; Evrard, Anne-Sophie; Tenet, Vanessa; Elisabeth, Cardis; Ivanov, Viktor K.; Chekin, Sergei; Khait, Svetlana E.; Maksyoutov, Marat; Shchukina, Natalia; Malakhova, Irina V.; Polyakov, Semion; Tserakhovich, Tatyana I.; Kurtinaitis, Juozas; Stengrevics, Aivars; Tekkel, Mare; Anspaugh, Lynn R.; Chumak, Vadim V.; Gapanovich, Vladimir; Golovanov, Ivan; Krjuchkov, Viktor P.; Tukov, Aleksandr R.; Hubert, Phillip; Illichev, Sergei V.; Maceika, Evaldas; Mirkhaidarov, Anatoly K.; Tsykalo, Aleksandr

2008-01-01

Full text: Chernobyl liquidators were workers involved in the clean-up of contaminated areas around the Chernobyl power plant following the accident on 26 April 1986. These workers form a potentially important population for evaluation of the effects of protracted low doses of ionizing radiation. A collaborative case-control study of leukaemia and non-Hodgkin lymphoma (NHL) was set-up, nested within cohorts of Belarus, Russian and Baltic countries liquidators. The objective was to evaluate the radiation-induced risk of these diseases in this population and to study the effect of exposure protraction and radiation type on the risk of radiogenic cancer in the low to medium (0-500 mSv) radiation dose range. The study population consisted of approximately 66,000 Belarus, 65,000 Russian and 15,000 Baltic countries liquidators who took part in the clean-up activities between 26 April 1986 and 31 December 1987. In Belarus and Russia, liquidators are followed through the Chernobyl Registries and must undergo regular health check-ups, while in the Baltic countries their migration, vital and cancer status are assessed through population, death and cancer registries. The case ascertainment period ranged from 1990 to 2000 with minor differences among the countries. Information on study subjects was obtained through a face-to-face interview with the study subject and/or a proxy (a relative or a colleague), using a standardized questionnaire on demographic factors, time, place and conditions of work as a liquidator and on potential risk and confounding factors for leukaemia. A method of analytical dose reconstruction, entitled RADRUE (Realistic Analytical Dose Reconstruction with Uncertainty Estimation), was developed within the study, validated and applied to estimate individual dose to the bone marrow and related uncertainties for each subject. 117 cases (69 leukaemia, 34 NHL and 14 other malignancies of lymphoid and haematopoietic tissue) and 481 matched controls were

Chronic myelocytic leukaemia with unusual (27 years) complete remission terminating in acute undifferentiated leukaemia: a clinical and karyotypic study.

Science.gov (United States)

Najean, Y; Miclea, M; Tanzer, J; Lessard, M; Sigaux, F

1991-07-01

A case of clinically typical CML (300 x 10(6)/l leukocytes, 400 x 10(6)/l platelets, splenomegaly) is presented. After complete remission induced by busulphan, no clinical or haematological abnormalities were observed for 27 years until the development of acute leukaemia (type M1), which was rapidly fatal after a brief chemotherapy-induced remission. The cytogenetic findings were also original: no chromosome Ph1 (during remission 3 years after the onset of the disease), no translocation (banding study 5 years later), and no bcr/abl rearrangement (during the terminal phase).

Ecotropic murine leukemia virus-induced fusion of murine cells

International Nuclear Information System (INIS)

Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

1986-01-01

Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with [ 3 H]thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells

Leukaemia and thyroid cancer in emergency workers of the Chernobyl accident:. Estimation of radiation risks (1986-1995)

International Nuclear Information System (INIS)

Ivanov, V.K.; Tsyb, A.F.; Gorsky, A.I.; Maksyutov, M.A.; Rastopchin, E.M.; Konogorov, A.P.; Korelo, A.M.; Biryukov, A.P.; Matyash, V.A.

1997-01-01

This work focuses on the direct epidemiological assessment of the risks of radiation-induced leukaemia and thyroid cancer in emergency workers (EW) after the Chernobyl accident. The Russian National Medical Dosimetric Registry (RNMDR) contains data for 168 000 EW as of January 1, 1996. The analysis relates to 48 leukaemias and 47 thyroid cancers, diagnosed and verified. Radiation risks are estimated by comparing the EW data with national data for a male population of the same age distribution. For leukaemia, an excess relative risk per Gy (ERR/Gy) of 4.30 (95% CI: 0.83, 7.75) is obtained, while the excess absolute risk per 10 4 person-years (PY) Gy (EAR/10 4 PY Gy) is found to be 1.31 (95% CI: 0.23, 2.39); for thyroid cancer an ERR/Gy of 5.31 (95% CI: 0.04, 10.58) is obtained, and an EAR/10 4 PY Gy of 1.15 (95% CI: 0.08, 2.22). (orig.). With 9 figs., 10 tabs

Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study

DEFF Research Database (Denmark)

Villumsen, Marie; Sørup, Signe; Jess, Tine

2009-01-01

Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines...... cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.......31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas....

An analysis of leukaemia, lymphoma and other malignancies together with certain categories of non-cancer mortality in the first generation offspring (F1) of the Japanese bomb survivors

International Nuclear Information System (INIS)

Little, M.P.; Wakeford, R.; Charles, M.W.

1994-01-01

The absence of any significant excess of childhood leukaemia in the offspring of the Japanese bomb survivors has provided strong evidence against a causal interpretation of the association between paternal preconception radiation dose and the incidence of childhood leukaemia in the offspring of employees at the Sellafield nuclear installation, West Cumbria. The use of the Japanese data has, however, been questioned on the basis that leukaemia cases may have been under-recorded in the years immediately following the bombings. In order to investigate possible misdiagnoses of leukaemia cases in the first generation offspring (F 1 ) of the Japanese bomb survivors, analyses have been undertaken of cases of leukaemia, non-Hodgkin's lymphoma (NHL), and all other malignancies, together with deaths due to blood diseases, deaths due to infectious diseases and deaths from unknown causes. (author)

Quercus Suber L. Cork Extracts Induce Apoptosis in Human Myeloid Leukaemia HL-60 Cells.

Science.gov (United States)

Bejarano, Ignacio; Godoy-Cancho, Belén; Franco, Lourdes; Martínez-Cañas, Manuel A; Tormo, María A

2015-08-01

Quercus suber L. cork contains a diversity of phenolic compounds, mostly low molecular weight phenols. A rising number of reports support with convergent findings that polyphenols evoke pro-apoptotic events in cancerous cells. However, the literature related to the anti-cancer bioactivity of Q. suber L. cork extractives (QSE) is still limited. Herein, we aim to describe the antitumor potential displayed by cork extractives obtained by different extraction methods in the human promyelocytic leukaemia cells. In order to quantify the effects of QSE on cancer cells viability, phosphatidylserine exposure, caspase-3 activity, mitochondrial membrane potential and cell cycle were evaluated. The results indicated that the QSE present a time-dependent and dose-dependent cytotoxicity in the human promyelocytic leukaemia cells. Such a noxious effect leads these leukaemia cells to their death through apoptotic processes by altering the mitochondrial outer membrane potential, activating caspase-3 and externalizing phosphatidylserine. However, cells cycle progression was not affected by the treatments. This study contributes to open a new way to use this natural resource by exploiting its anti-cancer properties. Moreover, it opens new possibilities of application of cork by-products, being more efficient in the sector of cork-based agriculture. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy.

Science.gov (United States)

Tan, S Y; Poh, B K; Nadrah, M H; Jannah, N A; Rahman, J; Ismail, M N

2013-07-01

The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia. This cross-sectional study included 53 paediatric patients aged 3-12 years old, who were diagnosed with either acute lymphoblastic leukaemia or acute myelogenous leukaemia and were undergoing chemotherapy treatments (induction or consolidation phase). Patients were matched for sex, age (±6 months) and ethnicity with healthy children as controls. Weight, height, body mass index, waist circumference, mid-upper arm circumference, triceps skinfold thickness, mid-upper arm muscle area and fat area were determined. Dietary intake was assessed using 3-day food records. Anthropometric variables were generally higher among patients compared to controls, although the differences were not statistically significant (P > 0.05). The prevalence of overnutrition among patients according to body mass index-for-age, waist circumference-for-age, mid-upper arm circumference-for-age and triceps skinfold-for-age were 24.5%, 29.1%, 17.0% and 30.2%, respectively. Mean energy [5732 ± 1958 kJ (1370 ± 468 kcal) versus 6945 ± 1970 kJ (1660 ± 471 kcal), P children with acute leukaemia was higher despite lower energy intake compared to controls. Studies assessing physical activity, the complex interaction and the effects of treatment drugs are warranted to better manage malnutrition among paediatric patients. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Using multistage models to describe radiation-induced leukaemia

International Nuclear Information System (INIS)

Little, M.P.; Muirhead, C.R.; Boice, J.D. Jr.; Kleinerman, R.A.

1995-01-01

The Armitage-Doll model of carcinogenesis is fitted to data on leukaemia mortality among the Japanese atomic bomb survivors with the DS86 dosimetry and on leukaemia incidence in the International Radiation Study of Cervical Cancer patients. Two different forms of model are fitted: the first postulates up to two radiation-affected stages and the second additionally allows for the presence at birth of a non-trivial population of cells which have already accumulated the first of the mutations leading to malignancy. Among models of the first form, a model with two adjacent radiation-affected stages appears to fit the data better than other models of the first form, including both models with two affected stages in any order and models with only one affected stage. The best fitting model predicts a linear-quadratic dose-response and reductions of relative risk with increasing time after exposure and age at exposure, in agreement with what has previously been observed in the Japanese and cervical cancer data. However, on the whole it does not provide an adequate fit to either dataset. The second form of model appears to provide a rather better fit, but the optimal models have biologically implausible parameters (the number of initiated cells at birth is negative) so that this model must also be regarded as providing an unsatisfactory description of the data. (author)

Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

International Nuclear Information System (INIS)

Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

1990-01-01

Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

Leukaemia and occupation: a New Zealand Cancer Registry-based case-control Study.

NARCIS (Netherlands)

McLean, D.; 't Mannetje, A.; Dryson, E.; Walls, C.; McKenzie, F.; Maule, M.; Cheng, S.; Cunningham, C.; Kromhout, H.; Boffetta, P.; Blair, A.; Pearce, N.

2009-01-01

BACKGROUND: To examine the association between occupation and leukaemia. METHODS: We interviewed 225 cases (aged 20-75 years) notified to the New Zealand Cancer Registry during 2003-04, and 471 controls randomly selected from the Electoral Roll collecting demographic details, information on

A comparison of the apparent risks of childhood leukaemia from parental exposure to radiation in the six months prior to conception in the Sellafield workforce and the Japanese bomb survivors

International Nuclear Information System (INIS)

Little, M.P.

1991-01-01

The cases of childhood leukaemia found among children of the Sellafield workforce and those observed in the offspring of the Japanese bomb survivors are analysed using both exponential and linear forms of a relative risk model and employing dose estimates for the period 6 months pre-conception. The leukaemia relative risk coefficients for paternal (whole-body) exposure in this pre-conception period for children of Sellafield workers are found to be statistically incompatible with the (gonadal dose) coefficients applying to the offspring of the bomb survivors born in the period May 1946 to December 1946, i.e. born 9 to 16 months after the bombings. The incompatibility does not depend on whether the risks in the Japanese children are assumed to be a function simply of paternal gonadal dose or of combined paternal and maternal gonadal dose. (author)

Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

LENUS (Irish Health Repository)

Kelly, Kevin

2008-12-01

Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

Gross and fine motor skills in children treated for acute lymphoblastic leukaemia.

Science.gov (United States)

De Luca, Cinzia R; McCarthy, Maria; Galvin, Jane; Green, Jessica L; Murphy, Alexandra; Knight, Sarah; Williams, Jacqueline

2013-06-01

Chemotherapy treatment for acute lymphoblastic leukaemia (ALL) may disrupt motor development, with suggestions that gross and fine motor deficits are different depending on time since treatment. Thirty-seven participants aged between 2.5 to 5 years at the time of diagnosis were assessed using the Movement Assessment Battery for Children, 2nd Edition (MABC-2) and the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition, Short Form (BOT-2 SF), and divided into groups (i.e., months-off-treatment): (1) 0-12, (2) 13-24, and (3) 25-60 for comparison. MABC-2 and BOT-2 SF mean total scores fell within the average range. Twenty-six percent of the sample performed in the impaired range on the MABC-2. Group 2 had significantly lower Manual Dexterity scores than the normative population and lower BOT-2 SF scores than Group 1. Most children treated for ALL display appropriate motor skills, yet around a quarter experience general motor difficulties. Time-off-treatment did not affect the prevalence of motor impairments on any measure.

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia.

Science.gov (United States)

Deeks, Emma D

2017-02-01

Ibrutinib (Imbruvica ® ) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE). Likewise, a combination of ibrutinib, bendamustine and rituximab was more effective in previously-treated adults than bendamustine plus rituximab in a phase III placebo-controlled study (HELIOS). These ibrutinib regimens were associated with significantly better progression-free survival, overall response rates, and overall survival than the comparators (in protocol-specified or planned analyses), with ibrutinib therapy providing benefit regardless of adverse prognostic factors, such as del(17p)/TP53 mutation and del(11q). Ibrutinib has an acceptable tolerability profile, although certain adverse events (e.g. bleeding and atrial fibrillation) require consideration. Redistribution lymphocytosis can occur, but is not indicative of disease progression. Although longer-term data would be beneficial, ibrutinib is a welcome treatment option for patients with CLL, including those who have higher-risk disease or are less physically fit. Indeed, current EU and US guidelines recommend/prefer the drug for the first- and/or subsequent-line treatment of certain patients, including those with del(17p)/TP53 mutation.

DNA apoptosis and stability in B-cell chronic lymphoid leukaemia: implication of the DNA double-strand breaks repair system by non homologous recombination

International Nuclear Information System (INIS)

Deriano, L.

2005-01-01

After an introduction presenting the diagnosis and treatment of chronic lymphoid leukaemia, its molecular and genetic characteristics, and its cellular origin and clonal evolution, this research thesis describes the apoptosis (definition and characteristics, cancer and chemotherapy, apoptotic ways induced by gamma irradiation), the genotoxic stresses, the different repair mechanisms for different damages, and the DNA repair processes. It reports how human chronic lymphocytic leukaemia B cells can escape DNA damage-induced apoptosis through the non-homologous end-joining DNA repair pathway, and presents non-homologous end-joining DNA repair as a potent mutagenic process in human chronic lymphocytic leukaemia B cells

Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Salomons, G. S.; Buitenhuis, C. K.; Martínez Muñoz, C.; Verwijs-Jassen, M.; Behrendt, H.; Zsiros, J.; Smets, L. A.

1998-01-01

In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies.

Leukaemia risks and radon

International Nuclear Information System (INIS)

Wolff, S.P.

1991-01-01

A correlation has been established between domestic radon exposure and mutation in peripheral T lymphocytes. Some caution must be exercised, however, in interpreting this result as evidence that levels of domestically encountered radon are sufficient to cause leukaemogenic chromosomal alterations. Radon may simply be acting as a surrogate for some other mutagenic factor. Correlations with Local Authority statistics collected in the United Kingdom 1981 Census appear to show that lower domestic radon levels reflect relatively greater socioeconomic deprivation whereas higher levels reflect greater prosperity. The relative risk of lymphoproliferative disease correlates with the same factors that determine domestic radon levels at the county level. Putative relationships between domestic radon exposure and cancer thus need to be controlled for socioeconomic status and associated factors, at least at the county level. (The correlations may not apply to smaller areas.) Similarly, the causative factors underlying the relationships between higher regional socioeconomic status and leukaemia require closer examination. (author)

Estimation of the risk of radiation-induced leukaemia among young people in the vicinity of the La Hague reprocessing plant. Results from the nord-cotentin radioecological study

International Nuclear Information System (INIS)

Rommens, C.; Laurier, D.; Merle-Szeremeta, A.; Sugier, A.; Drombry-Ringeard, C.

2000-01-01

A radioecological study has been performed around the La-Hague nuclear reprocessing plant (Nord-Cotentin, France). The Working Group included nuclear operators, authorities, international experts and members of environmental organisations and was supported by IPSN. The study aimed to reconstruct radiation doses received by members of the public aged 0 to 24 years and living in the area, with a view to estimate the associated risk of leukaemia between 1978 and 1996. The assessment involved three steps: 1. reconstruction of a cohort of people aged 0 to 24 years, using local birth rates for the years 1954 to 1996 and taking into account the additional migrations of young people in the area. 2. estimation of doses to the red bone marrow received from all source of radiation (natural, medical, local nuclear industries and Chernobyl and weapons testing). Concentrations of radionuclides in the environment were estimated with a combination of two approaches: the modelling of the transfer of the releases in the environment and the use of environmental measurements. The dose computation takes into account the life style of the local population. ICRP dose coefficients to the red bone marrow were used. 3. derivation of leukaemia risk from a dose response model recommended by the UNSCEAR committee. The reconstructed population includes 6656 people born between 1954 and 1996, who inhabited the study area for at least one year between 1978 and 1996 before the age of 25. The number of person-years between 1978 and 1996 is 69308. The total collective dose to the red bone marrow due to local nuclear installations is 0.5 man.Sv. For the sake of comparison, the collective dose due to all sources of exposure is 241 man.Sv: The estimated number of leukaemia due to all exposure sources is 0.835. 74% are due to natural exposures, 24% to medical ones and 2% to the Chemobyl accident and nuclear arm testing. Nuclear facilities of Nord-Cotentin contribute only for 0.1% (between 0.0009 and 0

Lactobacillus reuteri 100-23 modulates urea hydrolysis in the murine stomach.

Science.gov (United States)

Wilson, Charlotte M; Loach, Diane; Lawley, Blair; Bell, Tracey; Sims, Ian M; O'Toole, Paul W; Zomer, Aldert; Tannock, Gerald W

2014-10-01

Comparisons of in vivo (mouse stomach) and in vitro (laboratory culture) transcriptomes of Lactobacillus reuteri strain 100-23 were made by microarray analysis. These comparisons revealed the upregulation of genes associated with acid tolerance, including urease production, in the mouse stomach. Inactivation of the ureC gene reduced the acid tolerance of strain 100-23 in vitro, and the mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice. Urine analysis showed that stable isotope-labeled urea, administered by gavage, was metabolized to a greater extent in Lactobacillus-free mice than animals colonized by strain 100-23. This surprising observation was associated with higher levels of urease activity and fecal-type bacteria in the stomach digesta of Lactobacillus-free mice. Despite the modulation of urea hydrolysis in the stomach, recycling of urea nitrogen in the murine host was not affected since the essential amino acid isoleucine, labeled with a stable isotope, was detected in the livers of both Lactobacillus-free and 100-23-colonized animals. Therefore, our experiments reveal a new and unexpected impact of Lactobacillus colonization on urea hydrolysis in the murine gut. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The investigation of leukaemia incidence around sites of special interest

International Nuclear Information System (INIS)

Urquhart, J.

1991-01-01

The study of the incidence of leukaemia and non-Hodgkin's lymphoma around sites of special interest has created many methodological and philosophical problems. Not least of these is the construction of boundaries of space and time to delineate areas of study around a point source of interest. Studies such as those of the incidence of childhood leukaemia around Dounreay have made use of arbitrarily selected fixed geographic boundaries. The Poisson maximum method proposed by Stone and Bithell provides an alternative approach in which no prior selection of geographic boundaries is required. The application of an adaptation of this method to each of the Scottish nuclear sites confirmed the results found for Dounreay by other methods. No excess incidence was observed around the Hunterston Nuclear Installation and an observed excess incidence around Chapelcross was not statistically significant. The further development of statistical techniques which do not require the arbitrary selection of boundaries will facilitate the monitoring of the incidence of disease around sites of special interest and perhaps permit it to be carried out in a less combative climate than has hitherto been the case. (author)

Myeloid leukaemia frequency after protracted exposure to ionizing radiation: experimental confirmation of the flat dose-response found in ankylosing spondylitis after a single treatment course with x-rays

Energy Technology Data Exchange (ETDEWEB)

Mole, R H; Major, I R [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1983-01-01

The dose-response for leukaemia induction by exposure to ionizing radiation protracted over several weeks was largely independent of dose not only in X-rayed patients with ankylosing spondylitis but also in experimentally ..gamma..-rayed CBA/H mice. In the experiment the induced leukaemia frequency of acute myeloid leukaemia was independent of a several thousand-fold variation in physical dose rate. Any difference in leukaemia induction between brief and protracted exposures must therefore depend on specifically biological consequences of protracted exposures. Experimental analysis is required to provide the guides for inference about risks of low level exposure from observations on relatively heavily irradiated populations.

An analysis of leukaemia, lymphoma and other malignancies together with certain categories of non-cancer mortality in the first generation offspring (F[sub 1]) of the Japanese bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Little, M.P. (National Radiological Protection Board, Chilton (United Kingdom)); Wakeford, R. (British Nuclear Fuels plc, Risley (United Kingdom)); Charles, M.W. (Nuclear Electric plc, Berkeley (United Kingdom). Berkeley Technology Centre)

1994-09-01

The absence of any significant excess of childhood leukaemia in the offspring of the Japanese bomb survivors has provided strong evidence against a causal interpretation of the association between paternal preconception radiation dose and the incidence of childhood leukaemia in the offspring of employees at the Sellafield nuclear installation, West Cumbria. The use of the Japanese data has, however, been questioned on the basis that leukaemia cases may have been under-recorded in the years immediately following the bombings. In order to investigate possible misdiagnoses of leukaemia cases in the first generation offspring (F[sub 1]) of the Japanese bomb survivors, analyses have been undertaken of cases of leukaemia, non-Hodgkin's lymphoma (NHL), and all other malignancies, together with deaths due to blood diseases, deaths due to infectious diseases and deaths from unknown causes. (author).

Recruitment of childhood leukaemia patients to clinical trials in Great Britain during 1980-2007: variation by birth weight, congenital malformation, socioeconomic status and ethnicity.

Science.gov (United States)

Shah, Anjali; Diggens, Nicole; Stiller, Charles; Richards, Sue; Stevens, Michael C G; Murphy, Michael F G

2014-05-01

To assess recruitment of children to national clinical trials for acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in Great Britain during 1980-2007 and describe variation by some factors that might influence trial entry. Records of leukaemia patients aged 0-14 years at diagnosis were identified in the National Registry of Childhood Tumours and linked to birth registrations, Children's Cancer and Leukaemia Group records, Hospital Episode Statistics and Medical Research Council clinical trial registers. Trial entry rates were compared between categories of birth weight, congenital malformation, socioeconomic status and ethnicity. 9147 ALL and 1466 AML patients were eligible for national clinical trials during 1980-2007. Overall recruitment rates were 81% and 60% respectively. For ALL, rates varied significantly with congenital malformation (Down syndrome 61%, other malformations 80%, none 82%; p4000 g 67%; p=0.001) and congenital malformation (Down syndrome 28%, other malformations 56%, none 63%; pcongenital malformations.

Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

2011-01-01

BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving

Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival.

Science.gov (United States)

January

2016-04-01

codynamic interactions are also likely in view of its adverse effect profile. There is no consensus on the treatment of patients with refractory or relapsed mantle cell lymphoma, or for patients with relapsed or possibly refractory chronic lymphocytic leukaemia. Ibrutinib inhibits an enzyme involved in regulating B lymphocyte activity. It has been authorised in the European Union for these conditions. Clinical evaluation of ibrutinib in mantle cell lymphoma is based on a single non-comparative trial in 111 patients, in which the median overall survival time was 22.5 months. Clinical evaluation of ibrutinib in chronic lymphocytic leukaemia is based on two randomised trials. One unblinded trial compared ibrutinib versus ofatumumab and involved 391 patients, most of whom were sufficiently fit to receive anticancer combination therapy. Ibrutinib was more effective than ofatumumab, but the choice of this comparator might not have been appropriate for most of the patients who received it. The other double-blind, placebo-controlled trial involved 578 patients with relapsed or refractory chronic lymphocytic leukaemia. Ibrutinib was added to the bendamustine + rituximab combination. No significant difference in mortality was observed between the two groups. The main adverse effects of ibrutinib were: gastrointestinal disorders such as diarrhoea; life-threatening infections and bleeding disorders; and cardiac disorders, including atrial fibrillation. Ibrutinib carries a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely in view of its adverse effect profile.

The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia.

Science.gov (United States)

Furness, Caroline L; Mansur, Marcela B; Weston, Victoria J; Ermini, Luca; van Delft, Frederik W; Jenkinson, Sarah; Gale, Rosemary; Harrison, Christine J; Pombo-de-Oliveira, Maria S; Sanchez-Martin, Marta; Ferrando, Adolfo A; Kearns, Pamela; Titley, Ian; Ford, Anthony M; Potter, Nicola E; Greaves, Mel

2018-03-20

Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones. Xenografting confirmed that self-renewing or propagating cells were genetically diverse. These data suggest that the STIL-TAL1 fusion is a likely founder or truncal event. Therapies targeting the TAL1 auto-regulatory complex are worthy of further investigation in T-ALL.

A case of hypotriploid chromosome in a patient with acute lymphoblastic leukaemia.

Science.gov (United States)

Khan, Bilal Ahmed; Ali Baig, Mirza Faris; Siddiqui, Nadir

2017-11-01

TA 58-61, XXXX, hypotriploid chromosome was detected in the cytogenetics report of a 28 years old female patient, known case of B-cell Acute Lymphoblastic Leukaemia. On admission, the patient had normal physical examination findings and mental status, except history of fever spikes and generalized bone pains. The patient was admitted for induction of chemotherapy. Bone Marrow/Trephine biopsy report showed diffuse infiltration with blast cells with overall cellularity around 80-85% and suppressed normal haematopoiesis. Hypotriploid chromosome number in patients with B-cell Acute Lymphoblastic Leukaemia is a unique finding which, according to WHO classification of ALL, is an important prognostic factor itself and these cases have a favourable prognosis. There are only a few medical reports published about cases with similar presentations in Pakistan. Therefore, this case is very unique and further work should be done for better understanding of similar presentations and to find out more about its epidemiology.

Leukaemia following childhood radiation exposure in the Japanese atomic bomb survivors and in medically exposed groups

International Nuclear Information System (INIS)

Little, M. P.

2008-01-01

Incidence and mortality risks of radiation-associated leukaemia are surveyed in the Japanese atomic bomb (A-bomb) survivors exposed in early childhood and in utero. Leukaemia incidence and mortality risks are also surveyed in 16 other studies of persons who received appreciable doses of ionizing radiation in the course of treatment in childhood and for whom there is adequate dosimetry and cancer incidence or mortality follow-up. Relative risks tend to be lower in the medical series than in the Japanese A-bomb survivors. The relative risks in the medical studies tend to diminish with increasing average therapy dose. After taking account of cell sterilisation and dose fractionation, the apparent differences between the relative risks for leukaemia in the Japanese A-bomb survivors and in the medical series largely disappear. This suggests that cell sterilisation largely accounts for the discrepancy between the relative risks in the Japanese data and the medical studies. Excess absolute risk has also been assessed in four studies, and there is found to be more variability in this measure than in excess relative risk. In particular, there is a substantial difference between the absolute risk in the Japanese atomic bomb survivor data and those in three other (European) populations. In summary, the relative risks of leukaemia in studies of persons exposed to appreciable doses of ionizing radiation in the course of treatment for a variety of malignant and non-malignant conditions in childhood are generally less than those in the Japanese A-bomb survivor data. The effects of cell sterilisation can largely explain the discrepancy between the Japanese and the medical series. (authors)

Experience and nursing needs of school-age children undergoing lumbar puncture during the treatment of acute lymphoblastic leukaemia: a descriptive and qualitative study.

Science.gov (United States)

Xie, Anwei; Shan, Yuying; Niu, Mei E; Chen, Yi; Wang, Xiya

2017-11-01

To describe experiences and nursing needs of school-age Chinese children undergoing lumbar puncture for the treatment of acute lymphoblastic leukaemia. Lumbar puncture is an invasive procedure, causing psychological changes and physical discomfort in patients. In a previous study, it was proved that distraction intervention, such as music therapy, relieves pain and anxiety. There is limited evidence regarding the experience and needs of school-age children during lumbar puncture after being diagnosed with acute lymphoblastic leukaemia. To minimise their anxiety and pain during the procedure, it is important to collect information directly from these children. A descriptive qualitative research. Twenty-one school-age children with acute lymphoblastic leukaemia participated in semi-structured interviews at a Children's Hospital in China. Data were collected by an experienced and trained interviewer. Qualitative content analysis was chosen to describe experiences of children undergoing lumbar puncture. While undergoing lumbar puncture for the treatment of acute lymphoblastic leukaemia, school-age Chinese children experienced complex psychological feelings (fear, tension, helplessness, sadness and anxiety). They also experienced physical discomfort. They had multipolar needs, such as information, communication, respect, self-actualisation, environment and equipment. This study identified important areas that must be closely monitored by healthcare staff, performing lumbar puncture on acute lymphoblastic leukaemia children. Thus, a successful and smooth procedure can be performed on these patients, and their quality of life can be improved. The experiences described in this study contribute to a better understanding of the needs of acute lymphoblastic leukaemia children undergoing lumbar puncture. They also provide valuable information to professional medical care staff that develops future nursing assessments. © 2016 John Wiley & Sons Ltd.

A review of epidemiological studies concerning leukaemia and lymphoma among young people and the genetic effects of ionizing radiation

International Nuclear Information System (INIS)

Rose, K.S.B.

1994-01-01

The review seeks to identify consistent patterns of results between 30 epidemiological studies of low dose parental exposure to radiation and leukaemia etc. in their offspring. Eight of the studies show significant increases in leukaemia but most are unreliable because they have flawed methodologies and several analyse the same basic data. Two studies free from major criticism do show an association with parental irradiation but both contain data from Seascale and are not independent. Two well conducted studies based on other areas (Canada and Scotland) are claimed by their authors to have sufficient statistical power to test the Seascale findings and do not confirm an association with paternal irradiation. It is concluded that there is little reliable evidence from epidemiological studies for a causal association between pre-conception, paternal or maternal, irradiation and an increase in the frequency of leukaemia or malignancies among offspring. (author)

Irradiation Design for an Experimental Murine Model

International Nuclear Information System (INIS)

Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

2010-01-01

In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA.

Science.gov (United States)

Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L

1988-06-01

Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way.

Comparison of Health and Safety Executive and Cumbrian birth cohort studies of risk of leukaemia/non-Hodgkin's lymphoma in relation to paternal preconceptional irradiation

Energy Technology Data Exchange (ETDEWEB)

Dickinson, H O [North of England Children' s Cancer Research Unit, Paediatric and Lifecourse Epidemiology Research Group, Sir James Spence Institute of Child Health, University of Newcastle, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP (United Kingdom); Hodgson, J T [Epidemiology and Medical Statistics Unit, Health and Safety Executive, Magdalen House (room 241), Stanley Precinct, Bootle L20 3QZ (United Kingdom); Parker, L [North of England Children' s Cancer Research Unit, Paediatric and Lifecourse Epidemiology Research Group, Sir James Spence Institute of Child Health, University of Newcastle, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP (United Kingdom)

2003-12-01

In 1993, a case-control study by the Health and Safety Executive (HSE) assessed the risk of leukaemia and non-Hodgkin's lymphoma (LNHL) among children of fathers employed at the Sellafield nuclear installation in relation to paternal preconceptional irradiation (PPI). It concluded that the statistical association between risk of LNHL and PPI was confined to children born in the village of Seascale, where the dose-response was extremely high and very significant. In contrast, in 2002, a Cumbrian birth cohort study, investigating largely the same cases, concluded that this statistical association was not significantly different among children born inside and outside Seascale and estimated the dose-response inside Seascale to be much lower. This review makes a detailed comparison of the two studies, considering their design, data and analyses. The differences between their findings are due to: (i) differences in the distribution of offspring-years which are differential with respect to dose category and Seascale birth status, (ii) a non-Seascale high-dose case included in the Cumbrian but not the HSE study, (iii) differences between analyses using categorical and continuous PPI dose and (iv) the presence of Seascale controls with PPI over 200 mSv in the Cumbrian but not the HSE study.

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

DEFF Research Database (Denmark)

Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

2016-01-01

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi ...

Changes in the national mortality from leukaemia

Energy Technology Data Exchange (ETDEWEB)

Court Brown, W M; Doll, R

1960-12-01

In the last 30 years the number of deaths ascribed to leukaemia has increased steadily in all, countries for which adequate statistics are available. Death rates for England and Wales are given show that during this period the rate of mortality has increased threefold-a rate of increase which has been exceeded among the major causes of death only by cancer of the lung and coronary thrombosis. Clearly it is important to discover the reason for this change; more so, perhaps, because ionizing radiations are known to be capable of causing the disease and it is possible that some of the increase may have been due to their more extensive use.

Induction-related cost of patients with acute myeloid leukaemia in France.

Science.gov (United States)

Nerich, Virginie; Lioure, Bruno; Rave, Maryline; Recher, Christian; Pigneux, Arnaud; Witz, Brigitte; Escoffre-Barbe, Martine; Moles, Marie-Pierre; Jourdan, Eric; Cahn, Jean Yves; Woronoff-Lemsi, Marie-Christine

2011-04-01

The economic profile of acute myeloid leukaemia (AML) is badly known. The few studies published on this disease are now relatively old and include small numbers of patients. The purpose of this retrospective study was to evaluate the induction-related cost of 500 patients included in the AML 2001 trial, and to determine the explanatory factors of cost. "Induction" patient's hospital stay from admission for "induction" to discharge after induction. The study was performed from the French Public Health insurance perspective, restrictive to hospital institution costs. The average management of a hospital stay for "induction" was evaluated according to the analytical accounting of Besançon University Teaching Hospital and the French public Diagnosis-Related Group database. Multiple linear regression was used to search for explanatory factors. Only direct medical costs were included: treatment and hospitalisation. Mean induction-related direct medical cost was estimated at €41,852 ± 6,037, with a mean length of hospital stay estimated at 36.2 ± 10.7 days. After adjustment for age, sex and performance status, only two explanatory factors were found: an additional induction course and salvage course increased induction-related cost by 38% (± 4) and 15% (± 1) respectively, in comparison to one induction. These explanatory factors were associated with a significant increase in the mean length of hospital stay: 45.8 ± 11.6 days for 2 inductions and 38.5 ± 15.5 if the patient had a salvage course, in comparison to 32.9 ± 7.7 for one induction (P cost for patients with AML.

Case report: Concomitant Chronic Lymphocytic Leukaemia and Cytogenetically Normal de novo Acute Leukaemia in a Patient.

Science.gov (United States)

Kajtár, Béla; Rajnics, Péter; Egyed, Miklós; Alizadeh, Hussain

2015-01-01

The simultaneous occurrence of acute myeloid leukaemia with untreated chronic lymphocytic leukemia is extremely rare. We report a case of a 74-year-old man who was evaluated for macrocytic anaemia. Based on the morphology and immunophenotyping analysis of peripheral blood, a diagnosis of chronic lymphocytic leukemia was established. Subsequently, the bone marrow examination revealed the presence of two distinct, coexisting CLL and AML clones. Cytogenetic and molecular genetic analysis detected deletion 13q14.3 and unmutated immunoglobulin variable heavy-chain in the CLL clone, only. The AML and CLL clones did not share clonality, and the AML did not involve the peripheral blood. A diagnosis of cytogenetically normal de novo AML occurring concurrently with untreated CLL has not been reported previously in English literature. © 2015 by the Association of Clinical Scientists, Inc.

Self-Esteem and Academic Difficulties in Preadolescents and Adolescents Healed from Paediatric Leukaemia.

Science.gov (United States)

Tremolada, Marta; Taverna, Livia; Bonichini, Sabrina; Basso, Giuseppe; Pillon, Marta

2017-05-24

Adolescents with cancer may demonstrate problems in their self-esteem and schooling. This study aims to screen the preadolescents and adolescents more at risk in their self-esteem perception and schooling difficulties post-five years from the end of therapy. Twenty-five paediatric ex-patients healed from leukaemia were recruited at the Haematology-Oncologic Clinic (University of Padua). The mean age of the children was 13.64 years (Standard Deviation (SD)) = 3.08, range = 10-19 years), most were treated for acute lymphoblastic leukaemia (ALL) (84%) and relatively equally distributed by gender. They filled in the Multidimensional Self-Esteem Test, while parents completed a questionnaire on their child's schooling. Global self-esteem was mostly below the 50 percentile (58.5%), especially regarding interpersonal relationships (75%). An independent sample t -test showed significant mean differences on the emotionality scale ( t = 2.23; degree of freedom (df) = 24; p = 0.03) and in the bodily experience scale ( t = 3.02; df = 24; p = 0.006) with survivors of Acute Myeloid Leukaemia (AML) having lower scores. An Analysis of Variance (ANOVA ) showed significant mean differences in the bodily experience scale ( F = 12.31; df = 2, p = 0.0001) depending on the survivors' assigned risk band. The parent reports showed that 43.5% of children had difficulties at school. Childhood AML survivors with a high-risk treatment were more at risk in their self-esteem perceptions. Preventive interventions focusing on self-esteem and scholastic wellbeing are suggested in order to help their return to their normal schedules.

Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases.

Science.gov (United States)

Zhang, Shaoyan; Fortenberry, James A; Cohen, Noam A; Sorscher, Eric J; Woodworth, Bradford A

2009-01-01

The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. The change in forskolin-stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/- 1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

Studies on the role of RNA tumour viruses in human leukaemia

International Nuclear Information System (INIS)

Nooter, K.

1979-01-01

A search has been made for an etiological role of retroviruses in human leukemia and cocultivation studies have led to the isolation of a presumed human type C virus which appeared to be oncogenic for experimental animals. The experimental procedures and results are fully discussed. The parallels between irradiation induced lymphomas in mice and leukaemias in man are explored. (C.F.)

Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia.

Science.gov (United States)

Hansson, Lotta; Asklid, Anna; Diels, Joris; Eketorp-Sylvan, Sandra; Repits, Johanna; Søltoft, Frans; Jäger, Ulrich; Österborg, Anders

2017-10-01

This study explored the relative efficacy of ibrutinib versus previous standard-of-care treatments in relapsed/refractory patients with chronic lymphocytic leukaemia (CLL), using multivariate regression modelling to adjust for baseline prognostic factors. Individual patient data were collected from an observational Stockholm cohort of consecutive patients (n = 144) diagnosed with CLL between 2002 and 2013 who had received at least second-line treatment. Data were compared with results of the RESONATE clinical trial. A multivariate Cox proportional hazards regression model was used which estimated the hazard ratio (HR) of ibrutinib versus previous standard of care. The adjusted HR of ibrutinib versus the previous standard-of-care cohort was 0.15 (p ibrutinib in the RESONATE study were significantly longer than with previous standard-of-care regimens used in second or later lines in routine healthcare. The approach used, which must be interpreted with caution, compares patient-level data from a clinical trial with outcomes observed in a daily clinical practice and may complement results from randomised trials or provide preliminary wider comparative information until phase 3 data exist.

Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg.

Science.gov (United States)

van de Vrugt, Henri J; Koomen, Mireille; Berns, Mariska A D; de Vries, Yne; Rooimans, Martin A; van der Weel, Laura; Blom, Eric; de Groot, Jan; Schepers, Rik J; Stone, Stacie; Hoatlin, Maureen E; Cheng, Ngan Ching; Joenje, Hans; Arwert, Fré

2002-03-01

Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder. Six distinct FA disease genes have been identified, the products of which function in an integrated pathway that is thought to support a nuclear caretaker function. Comparison of FA gene characteristics in different species may help to unravel the molecular function of the FA pathway. We have cloned the murine homologue of the Fanconi anaemia complementation group G gene, FANCG/XRCC9. The murine Fancg protein shows an 83% similarity to the human protein sequence, and has a predicted molecular weight of 68.5 kDa. Expression of mouse Fancg in human FA-G lymphoblasts fully corrects their cross-linker hypersensitivity. At mRNA and protein levels we detected the co-expression of Fancg and Fanca in murine tissues. In addition, mouse Fancg and Fanca proteins co-purify by immunoprecipitation. Upon transfection into Fanca-deficient mouse embryonic fibroblasts EGFP-Fancg chimeric protein was detectable in the nucleus. We identified a murine cDNA, Fancg, which cross-complements the cellular defect of human FA-G cells and thus represents a true homologue of human FANCG. Spleen, thymus and testis showed the highest Fancg expression levels. Although Fancg and Fanca are able to form a complex, this interaction is not required for Fancg to accumulate in the nuclear compartment.

Analysis of the Fanconi anaemia complementation group A gene in acute myeloid leukaemia.

Science.gov (United States)

Condie, Alison; Powles, Raymond L; Hudson, Chantelle D; Shepherd, Valerie; Bevan, Stephen; Yuille, Martin R; Houlston, Richard S

2002-09-01

Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults. Around 10-15% of individuals with recessively inherited Fanconi anaemia (FA) develop AML. FA is one of a group of recessive syndromes characterized by excessive spontaneous chromosomal breakage in which heterozygote carriers appear to display an increased risk of cancer and there is some indirect evidence that FA carriers may also be at increased risk of AML. This suggests that FA genes may play a role in the development of AML in the wider context. To examine this proposition, further, we have screened samples from 79 AML patients for mutations in the major FA gene, FANCA. No truncating FANCA mutations were detected. One missense mutation previously designated as pathogenic and five novel missense mutations causing non-conservative amino acid substitutions were detected. The data suggests that while FANCA mutations are rare, FANCA mutations may contribute to the development of the disease in a subset of AML.

Incidence, time trends and regional variation of childhood leukaemia in Germany and Europe

International Nuclear Information System (INIS)

Kaatsch, P.; Mergenthaler, A.

2008-01-01

This paper presents data on the German and Europe-wide incidence, time trends and regional variations of childhood leukaemia. Data were provided by the German Childhood Cancer Registry (GCCR), a population-based cancer registry recording all cases of malignant diseases in children under 15 y of age residing in Germany and by the Automated Childhood Cancer Information System (ACCIS) co-ordinated at International Agency for Research on Cancer, Lyon, that combines and evaluates data from several European population-based cancer registries. The incidence of leukaemia (44.0 per million) has increased in Europe as well as in Germany in the last decades (0.6% annually on average). Germany shows no systematic aggregation of regions with low or high cancer incidence in terms of regional clustering. Incidence rates differ between European regions with the highest rates in Northern Europe (48.0 per million) and the lowest rates in Eastern Europe (39.1). Altogether, the results from ACCIS and the GCCR show good agreement. (authors)

Intravitreal Bevacizumab and Triamcinolone for Treatment of Cystoid Macular Oedema Associated with Chronic Myeloid Leukaemia and Imatinib Therapy

Directory of Open Access Journals (Sweden)

Eric K. Newcott

2015-01-01

Full Text Available Purpose. To evaluate the efficacy of intravitreal bevacizumab and triamcinolone in the treatment of cystoid macular oedema in a case with chronic myeloid leukaemia on imatinib treatment. Methods. We treated a 78-year-old man with bilateral cystoid macular oedema with intravitreal triamcinolone and subsequent bevacizumab in one eye and intravitreal bevacizumab, alone, in the fellow eye. Results. Serial intravitreal bevacizumab with and without triamcinolone treated cystoid macular oedema in both eyes and improved the vision. Conclusion. Intravitreal bevacizumab and triamcinolone could be viable options to treat cystoid macular oedema due to chronic myeloid leukaemia and imatinib therapy.

Interferon in chronic myeloid leukaemia: past and future.

Science.gov (United States)

Guilhot, François; Roy, Lydia; Saulnier, Pierre-Jean; Guilhot, Joëlle

2009-09-01

Imatinib has revolutionized the therapy of chronic myeloid leukaemia. However the complete eradication of leukaemic stem cells is still a matter of discussion. Interferon (IFN) has been used in the past with success. However the proportion of patients who achieved sustained complete cytogenetic response was small. Recently, in addition to its direct antineoplastic effect and immunomodulatory activity, IFN has been shown to stimulate the quiescent leukaemic stem cells. Thus there is now a rational for combining Imatinib and IFN. Large prospective phase III trials are in good progress to demonstrate in humans the usefullness of a combination therapy using Imatinib and IFN.

[Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

2008-01-01

Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

The eye in acute leukaemia. 2

International Nuclear Information System (INIS)

Harnett, A.N.; Plowman, P.N.

1987-01-01

Solitary relapse of acute lymphoblastic leukaemia (ALL) was diagnosed in the anterior chamber of the eye in five children. In all these cases, pathological confirmation of the diagnosis was obtained and there was no other evidence of relapse including cerebrospinal fluid (CSF) and bone marrow examinations. Each child had one adverse prognostic sign at the initial presentation. Relapse always occurred soon after completion of maintenance chemotherapy (between 1 and 4 months), supporting the hypothesis that the eye is a pharmacological sanctuary to cytotoxic chemotherapeutic drugs. Radiotherapy to the involved orbit was given with an immediate response in all patients. The details of this treatment are discussed. Four of the five patients later relapsed, one locally and three in bone marrow; the prognosis of solitary ocular relapse therefore appears grave. 19 refs.; 1 table

Major differences between human atopic dermatitis and murine models as determined by global transcriptomic profiling

DEFF Research Database (Denmark)

Ewald, David Adrian; Noda, Shinji; Oliva, Margeaux

2017-01-01

, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin. Transcriptomic profiling was performed using microarrays and qRT-PCR on biopsies from NC/Nga, flaky...

Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

DEFF Research Database (Denmark)

Mortensen, B T; Jensen, P O; Helledie, N

1998-01-01

The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....

Dose-response for X-ray induction of myeloid leukaemia in male CBA/H mice

Energy Technology Data Exchange (ETDEWEB)

Mole, R H; Papworth, D G; Corp, M J [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1983-02-01

The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD/sup 2/esup(-..gamma..D) (D = dose) in agreement with induction at the cellular level in proportion to D/sup 2/ over the whole dose range 0.25-6.0 Gy. The factor esup(-..gamma..D) accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.

Bi-allelic silencing of the Fanconi anaemia gene FANCF in acute myeloid leukaemia.

NARCIS (Netherlands)

Tischkowitz, M; Ameziane, N.; Waisfisz, Q.; Winter, de J.P.; Harris, R; Taniguchi, T; Andrea, d' A; Hodgson, SV; Mathew, C.G.; Joenje, H.

2003-01-01

Fanconi anaemia (FA) is a chromosomal instability disorder associated with a high risk of acute myeloid leukaemia (AML). Previous work has shown that the AML cell line CHRF-288, derived from a sporadic AML-M7 patient, does not express FANCF protein and exhibits a cellular FA phenotype. We show that

Rural population mixing and childhood leukaemia: effects of the North Sea oil industry in Scotland, including the area near Dounreay nuclear site

International Nuclear Information System (INIS)

Kinlen, L.J.; O'Brien, F.; Clarke, K.; Balkwill, A.; Matthews, F.

1993-01-01

The objective of this study was to determine if any excess of childhood leukaemia and non-Hodgkin's lymphoma was associated with certain striking examples of population mixing in rural Scotland produced by the North Sea oil industry. Details were traced for over 30 000 workers (25 yrs old) involved in the construction of the large oil terminals in the Shetland and Orkney islands in northern Scotland or employed offshore. Home addresses of the 17160 Scottish residents were postcoded, integrated with census data, and then classified as urban or rural. Rural postcode sectors, ranked by proportion of oil workers, were grouped into three categories with similar numbers of children but contrasting densities of oil workers. The incidence of leukaemia and non-Hodgkin's lymphoma was examined in these rural (and also in urban) categories in the periods 1974-8, 1979-83 and 1984-8. A significant excess of leukaemia and non-Hodgkin's lymphoma was found in 1979-83 in the group of rural home areas with the largest proportion of oil workers, following closely on large increases in the workforce. The area near the Dounreay nuclear installation, where an excess of leukaemia is already well known, was within the rural high oil category. (Author)

Host genome variations and risk of infections during induction treatment for childhood acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Lund, Bendik; Wesolowska-Andersen, Agata; Lausen, Birgitte

2014-01-01

Objectives: To investigate association of host genomic variation and risk of infections during treatment for childhood acute lymphoblastic leukaemia (ALL). Methods: We explored association of 34 000 singlenucleotide polymorphisms (SNPs) related primarily to pharmacogenomics and immune function...

Effectiveness of environmental control measures to decrease the risk of invasive aspergillosis in acute leukaemia patients during hospital building work.

Science.gov (United States)

Combariza, J F; Toro, L F; Orozco, J J

2017-08-01

Invasive aspergillosis (IA) is a significant problem in acute leukaemia patients. Construction work near hospital wards caring for immunocompromised patients is one of the main risk factors for developing invasive pulmonary aspergillosis (IPA). To assess the impact of environmental control measures used during hospital construction for the prevention of IA in acute leukaemia patients. A retrospective cohort study was developed to evaluate the IA incidence in acute leukaemia patients with different environmental control measures employed during hospital construction. We used European Organisation for the Research and Treatment of Cancer (EORTC) criterial diagnosis parameters for definition of IA. A total of 175 episodes of inpatient care were evaluated, 62 of which did not have any environmental control measures (when an outbreak occurred), and 113 that were subject to environmental control measures directed to preventing IA. The study showed an IA incidence of 25.8% for the group without environmental control measures vs 12.4% for those who did receive environmental control measures (P=0.024). The relative risk for IA was 0.595 (95% confidence interval: 0.394-0.897) for the group with environmental control measures. The current study suggests that the implementation of environmental control measures during a hospital construction has a positive impact for prevention of IA in patients hospitalized with acute leukaemia. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

Science.gov (United States)

Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

2016-10-04

To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia.

Science.gov (United States)

Blanco, Teresa Mortera; Mantalaris, Athanasios; Bismarck, Alexander; Panoskaltsis, Nicki

2010-03-01

Acute myeloid leukaemia (AML) is a cancer of haematopoietic cells that develops in three-dimensional (3-D) bone marrow niches in vivo. The study of AML has been hampered by lack of appropriate ex vivo models that mimic this microenvironment. We hypothesised that fabrication and optimisation of suitable biomimetic scaffolds for culturing leukaemic cells ex vivo might facilitate the study of AML in its native 3-D niche. We evaluated the growth of three leukaemia subtype-specific cell lines, K-562, HL60 and Kasumi-6, on highly porous scaffolds fabricated from biodegradable and non-biodegradable polymeric materials, such as poly (L-lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly (methyl-methacrylate), poly (D, L-lactade), poly (caprolactone), and polystyrene. Our results show that PLGA and PU supported the best seeding efficiency and leukaemic growth. Furthermore, the PLGA and PU scaffolds were coated with extracellular matrix (ECM) proteins, collagen type I (62.5 or 125 microg/ml) and fibronectin (25 or 50 microg/ml) to provide biorecognition signals. The 3 leukaemia subtype-specific lines grew best on PU scaffolds coated with 62.5 microg/ml collagen type I over 6 weeks in the absence of exogenous growth factors. In conclusion, PU-collagen scaffolds may provide a practical model to study the biology and treatment of primary AML in an ex vivo mimicry. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

Directory of Open Access Journals (Sweden)

Denise Niewerth

2016-09-01

Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

Neutrophil Gelatinase-Associated Lipocalin (NGAL, Pro-Matrix Metalloproteinase-9 (pro-MMP-9 and Their Complex Pro-MMP-9/NGAL in Leukaemias

Directory of Open Access Journals (Sweden)

Sandrine Bouchet

2014-04-01

Full Text Available Matrix metalloproteinase (MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9 also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro-MMP-9 (active and latent forms and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

Energy Technology Data Exchange (ETDEWEB)

Bouchet, Sandrine; Bauvois, Brigitte, E-mail: brigitte.bauvois@crc.jussieu.fr [INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris 75006 (France)

2014-04-04

Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

Measuring the impact of a restrictive transfusion guideline in patients with acute myeloid leukaemia

DEFF Research Database (Denmark)

Hoeg, R T; Leinoe, E B; Andersen, P

2013-01-01

practice, but has not been used to evaluate behavioral interventions. We examined the effect of a Danish National Board of Health December 2007 transfusion guideline on the behavior of clinicians treating acute myeloid leukaemia (AML). We compared the effect of the guideline on pre-transfusion haemoglobin...

Childhood leukaemia near British nuclear installations: Methodological issues and recent results

International Nuclear Information System (INIS)

Bithell, J. F.; Keegan, T. J.; Kroll, M. E.; Murphy, M. F. G.; Vincent, T. J.

2008-01-01

In 2008, the German Childhood Cancer Registry published the results of the Kinderkrebs in der Umgebung von Kernkraftwerken (KiKK) study of childhood cancer and leukaemia around German nuclear power stations. The positive findings appeared to conflict with the results of a recent British analysis carried out by the Committee on Medical Aspects of Radiation in the Environment (COMARE), published in 2005. The present paper first describes the COMARE study, which was based on data from the National Registry of Children's Tumours (NRCT); in particular, the methodology used in this study is described. Although the results of the COMARE study were negative for childhood leukaemia, this apparent discrepancy could be accounted for by a number of differences in approach, especially those relating to the distances from the power stations and the ages of the children studied. The present study was designed to match the KiKK study as far as possible. The incidence observed (18 cases within 5 km against 14.58 expected, p = 0.21) was not significantly raised. The risk estimate for proximity in the regression fitted was actually negative, though the confidence intervals involved are so wide that the difference from that reported in the KiKK study is only marginally statistically significant (p = 0.063). (authors)

Methods and basic data of case-control study of leukaemia and lymphona among young people near Sellafield nuclear plant in West Cumbria

International Nuclear Information System (INIS)

Gardner, M.J.; Hall, A.J.; Snee, M.P.; Downes, S.; Powell, C.A.

1990-01-01

The methods and basic data of a case-control study of leukaemia and lymphoma among young people near Sellafield are examined for reliability. Fifty-two cases of leukaemia, 22 of non-Hodgkin's lymphoma and 23 of Hodgkins disease occurring in people born in the area and diagnosed there in 1950-85 under the age of 25, and 1001 controls matched for sex and date of birth taken from the same birth registers were used in the study. (author)

Effects of stem cell factor on hypoxia-inducible factor 1 alpha accumulation in human acute myeloid leukaemia and LAD2 mast cells.

Directory of Open Access Journals (Sweden)

Bernhard F Gibbs

Full Text Available Stem cell factor (SCF is a hematopoietic growth factor that exerts its activity by signalling through the tyrosine kinase receptor known as Kit or CD117. SCF-Kit signalling is crucial for the survival, proliferation and differentiation of hematopoietic cells of myeloid lineage. Furthermore, since myeloid leukaemia cells express the Kit receptor, SCF may play an important role in myeloid leukaemia progression too. However, the mechanisms of this pathophysiological effect remain unclear. Recent evidence shows that SCF triggers accumulation of the inducible alpha subunit of hypoxia-inducible factor 1 (HIF-1 in hematopoietic cells--a transcription complex that plays a pivotal role in cellular adaptation to low oxygen availability. However, it is unknown how SCF impacts on HIF-1α accumulation in human myeloid leukaemia and mast cells. Here we show that SCF induces HIF-1α accumulation in THP-1 human myeloid leukaemia cells but not in LAD2 mast cells. We demonstrated that LAD2 cells have a more robust glutathione (GSH-dependent antioxidative system compared to THP-1 cells and are therefore protected against the actions of ROS generated in an SCF-dependent manner. BSO-induced GSH depletion led to a significant decrease in HIF-1α prolyl hydroxylase (PHD activity in THP-1 cells and to near attenuation of it in LAD2 cells. In THP-1 cells, SCF-induced HIF-1α accumulation is controlled via ERK, PI3 kinase/PKC-δ/mTOR-dependent and to a certain extent by redox-dependent mechanisms. These results demonstrate for the first time an important cross-talk of signalling pathways associated with HIF-1 activation--an important stage of the myeloid leukaemia cell life cycle.

T cells in chronic lymphocytic leukaemia display an exhausted phenotype and impaired functionality that can be restored by chemotherapy

International Nuclear Information System (INIS)

Gassner, F.

2012-01-01

In chronic lymphocytic leukaemia (CLL), beside a massive accumulation of neoplastic B cells, tumour-induced deficiencies in autologous T cells have been reported that impede efficient tumour control and might even support survival of the malignant clone. Here, we investigated our hypothesis that T cells in CLL, due to the persistent availability of tumour antigen, are exhausted, and that reduction of tumour load by chemotherapy might restore T cell functions. We could show that T cells in CLL patients and in a CLL mouse model display an exhausted phenotype, with high expression of the inhibitory surface receptor PD-1, that is clearly induced by the presence of tumour cells. Although the PD-1 ligand PD-L1 is not expressed on peripheral CLL cells, abundant expression could be shown in lymph node sections. Intriguingly, blocking the PD-1/PD-L1 pathway increased short term tumour lysis in a murine in vivo cytotoxicity assay. Furthermore, we present data that after cytoreduction by fludarabine, a standard chemotherapy agent for CLL, the surviving T cell pool consists mainly of fully functional memory T cells with high proliferative potential and increased secretion of pro-inflammatory Th1 cytokines. Taken together, we conclude that the impaired tumour surveillance observed in CLL might be rooted in the exhaustion of tumour-specific effector T cells. A combination of cytodepletion by chemotherapy and blockade of PD-1 might hence represent a novel therapeutic approach for CLL. (author) [de

Exposure assessment and other challenges in non-ionizing radiation studies of childhood leukaemia

International Nuclear Information System (INIS)

Kheifets, L.; Oksuzyan, S.

2008-01-01

Studies of electromagnetic fields (EMF) and the development of childhood leukaemia face unique difficulties. EMF are imperceptible, ubiquitous, have multiple sources, and can vary greatly over time and distances. Childhood leukaemia and high average exposures to magnetic fields are both quite rare. Thus, a major challenge in EMF epidemiology is the small number of highly exposed cases and the necessity for retrospective assessment of exposure. Only studies designed to minimize bias while maximizing our ability to detect an association, should one exist, would have a potential to contribute to our understanding. New approaches are needed; the most promising in the extremely low-frequency range involves a study of a highly exposed cohort of children who have lived in apartments next to built-in transformers or electrical equipment rooms. Another promising avenue is an investigation of possible joint effects of environmental exposures and genetic co-factors. An exposure assessment methodology for residential radiofrequency fields is still in its infancy. Rapid changes in technology and exponential increases in its use make exposure assessment more difficult and urgent. (authors)

The risks of leukaemia and other cancers in Seascale from radiation exposure

International Nuclear Information System (INIS)

Stather, J.W.; Dionian, J.; Brown, J.; Fell, T.P.; Muirhead, C.R.

1986-04-01

Including new data in the radiation dose calculations for the Seascale study population of 1225 children and young persons, followed to 20 years of age or 1980, has, with modifications to dosimetric models, increased the predicted number of radiation-induced leukaemia resulting from Sallafield discharges from 0.01 to 0.016. Risk to the average child in the study, from the discharges, is now calculated as about 1 in 75,000 with a maximum risk of about 1 in 30,000 for children born in the mid-1950s. For the four fatal leukemias to be attributed to the Sellafield operations, the calculated average risk for all the children would have to be increased about 250 times. Estimate of the overall risk of radiation-induced leukaemia in the study population, from combined sources, has increased by less than 10% of the previous estimate and the total number of cases is still rounded to 0.1, as in R171. Risk to the average child is now calculated as about 1 in 12,250, about two thirds from natural background, 16% from Sellafield discharges, and 9% each from weapons fallout and medical exposure. (U.K.)

Atypical chronic myeloid leukaemia: A case of an orphan disease-A multicenter report by the Polish Adult Leukemia Group.

Science.gov (United States)

Drozd-Sokołowska, Joanna; Mądry, Krzysztof; Waszczuk-Gajda, Anna; Biecek, Przemysław; Szwedyk, Paweł; Budziszewska, Katarzyna; Raźny, Magdalena; Dutka, Magdalena; Obara, Agata; Wasilewska, Ewa; Lewandowski, Krzysztof; Piekarska, Agnieszka; Bober, Grażyna; Krzemień, Helena; Stella-Hołowiecka, Beata; Kapelko-Słowik, Katarzyna; Sawicki, Waldemar; Paszkowska-Kowalewska, Małgorzata; Machowicz, Rafał; Dwilewicz-Trojaczek, Jadwiga

2018-03-07

Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses. Thirteen patients were male, median age 64.6 years (range 40.4-80.9). The median parameters at diagnosis were as follows: white blood cell count 97 × 10 9 /L (23.8-342) with immature progenitors amounting at 27.5% (12-72), haemoglobin 8.6 g/dL (3.9-14.9), and platelet count 66 × 10 9 /L (34-833). Cytoreductive treatment was used in all patients, and 2 patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival was 14.1 months (95% CI, 7.2), with median acute myeloid leukaemia-free survival of 13.3 months (95% CI, 3.6-22.6). Cumulative incidence of acute myeloid leukaemia transformation after 1 year in aCML group was 12.5% (95% CI, 0%-29.6%). To conclude, aCML harbours a poor prognosis. Treatment options are limited, with allogeneic hematopoietic stem cell transplantation being the only curative method at present, although only a minority of patients are transplant eligible. Educational measures are needed to improve the quality of diagnoses. Copyright © 2018 John Wiley & Sons, Ltd.

Avascular necrosis of the femoral head in patients treated for leukaemia. Assessment of the need for a diagnostic protocol.

Science.gov (United States)

Alguacil Pinel, J; Vila Vives, P; Salom Taverner, M

To evaluate the incidence of avascular necrosis of the hip in leukaemia patients treated in our hospital with high doses of corticosteroids in order to evaluate the necessity for an early detection protocol. Observational-descriptive and retrospective study from 2005 to 2016 of 253 patients diagnosed with paediatric leukaemia. Patients with musculoskeletal pathology were identified and patients with avascular necrosis were analysed. A total of 26 patients (10%) had musculoskeletal symptoms. Three patients with avascular necrosis (1.2%) were analysed. One girl, 7 years old, was treated conservatively with traction - suspension and discharge. Two boys, an 11 and a 15.4 year-old,who developed graft-versus-host disease secondary to bone marrow transplantation, and whose treatment included high doses of corticosteroids, developed avascular necrosis of the hip. One was treated with bisphosphonates and forage and the other ended up with a total hip arthroplasty. The occurrence of musculoskeletal symptoms during the treatment of leukaemia is different according to the bibliographic series (0.43 -12.6%). Some authors observe an increased risk in female patients between the ages of 10 and 17. A retrospective study reveals that there is a delay of 3.9 months in the diagnosis of CAP since the onset of pain. Other authors relate NAV to loading joints, age and high doses of corticosteroids. Based on the low incidence of avascular necrosis of the hip in our 14-year-old population treated for leukaemia, the creation of diagnostic protocols seems not to be necessary. However, close monitoring of patients with potential risk factors recognized in the literature, is advisable. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of radiation in the treatment of acute myelogenous leukaemia

Energy Technology Data Exchange (ETDEWEB)

Honeyman, L D; Morgan, D E [Groote Schuur Hospital, Cape Town (South Africa). Dept. of Radiotherapy

1982-06-01

The article deals with the radiation treatment of acute myelogenous leukaemia. The contribution of radiotherapy can be considered in three parts: a) irradiation of blood packs for patient support; b) irradiation of laboratory animals in order to improve existing knowledge and techniques; c) total body irradiation of the patient on the day of the transplant using a dose large enough to destroy the bone marrow and the immune system. The radiation effects, post graft immunosuppression and the supporting of the patient after transplantation are also discussed.

A comparison of the risks of leukaemia in the offspring of the Sellafield workforce born in Seascale and those born elsewhere in West Cumbria with the risks in the offspring of the Ontario and Scottish workforces and the Japanese bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Little, M.P. (National Radiological Protection Board, Chilton (United Kingdom)); Wakeford, R. (British Nuclear Fuels plc, Risley (United Kingdom)); Charles, M.W. (Nuclear Electric plc, Berkeley (United Kingdom). Berkeley Technology Centre)

1994-09-01

The cases of childhood leukaemia found among children of the Sellafield (West Cumbria), Ontario and Scottish radiation workers and in the offspring of the Japanese bomb survivors are analysed using linear and exponential forms of a relative risk model with total preconception external radiation dose estimates. In particular, the risks among children of the Sellafield workforce born in Seascale and among those born elsewhere in West Cumbria are compared with the risks derived from the other datasets. There is a highly significant inconsistency between the raised paternal preconception exposure excess relative risk coefficients for leukaemia in those children of the Sellafield workforce born in Seascale and the coefficients for children born elsewhere in West Cumbria, those for the offspring of the Ontario or Scottish workforces as well as those for the offspring of the Japanese bomb survivors. These incompatabilities are independent of the models used. In contrast to this, the leukaemia excess relative risk coefficients for paternal preconception exposure of those children of the Sellafield workforce born elsewhere in West Cumbria are not significantly elevated and do not differ significantly from those observed in the Japanese, Ontario and Scottish datasets. (author).

A comparison of the risks of leukaemia in the offspring of the Sellafield workforce born in Seascale and those born elsewhere in West Cumbria with the risks in the offspring of the Ontario and Scottish workforces and the Japanese bomb survivors

International Nuclear Information System (INIS)

Little, M.P.; Wakeford, R.; Charles, M.W.

1994-01-01

The cases of childhood leukaemia found among children of the Sellafield (West Cumbria), Ontario and Scottish radiation workers and in the offspring of the Japanese bomb survivors are analysed using linear and exponential forms of a relative risk model with total preconception external radiation dose estimates. In particular, the risks among children of the Sellafield workforce born in Seascale and among those born elsewhere in West Cumbria are compared with the risks derived from the other datasets. There is a highly significant inconsistency between the raised paternal preconception exposure excess relative risk coefficients for leukaemia in those children of the Sellafield workforce born in Seascale and the coefficients for children born elsewhere in West Cumbria, those for the offspring of the Ontario or Scottish workforces as well as those for the offspring of the Japanese bomb survivors. These incompatabilities are independent of the models used. In contrast to this, the leukaemia excess relative risk coefficients for paternal preconception exposure of those children of the Sellafield workforce born elsewhere in West Cumbria are not significantly elevated and do not differ significantly from those observed in the Japanese, Ontario and Scottish datasets. (author)

A novel inherited mutation of the transcription factor RUNX1 causes thrombocytopenia and may predispose to acute myeloid leukaemia.

Science.gov (United States)

Walker, Logan C; Stevens, Jane; Campbell, Hamish; Corbett, Rob; Spearing, Ruth; Heaton, David; Macdonald, Donald H; Morris, Christine M; Ganly, Peter

2002-06-01

The RUNX1 (AML1, CBFA2) gene is a member of the runt transcription factor family, responsible for DNA binding and heterodimerization of other non-DNA binding transcription factors. RUNX1 plays an important part in regulating haematopoiesis and it is frequently disrupted by illegitimate somatic recombination in both acute myeloid and lymphoblastic leukaemia. Germline mutations of RUNX1 have also recently been described and are dominantly associated with inherited leukaemic conditions. We have identified a unique point mutation of the RUNX1 gene (A107P) in members of a family with autosomal dominant inheritance of thrombocytopenia. One member has developed acute myeloid leukaemia (AML).

Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12)

DEFF Research Database (Denmark)

Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels

2007-01-01

Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1(...... in leukaemias; however, it encodes a protein that specifically interacts with SET, fused to NUP214 in a case of acute undifferentiated leukaemia.......Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1...

Case-control study of leukaemia and non-Hodgkin's lymphoma in children in Caithness near the Dounreay nuclear installation

International Nuclear Information System (INIS)

Urquhart, J.D.; Black, R.J.; Muirhead, M.J.; Sharp, Linda; Maxwell, Margaret; Jones, D.A.; Eden, O.B.

1991-01-01

A case-control study was performed to examine whether the observed excess of childhood leukaemia and non-Hodgkin's lymphoma in the area around the Dounreay nuclear installation is associated with established risk factors, or with factors related to the plant, or with parental occupation in the nuclear industry. No raised relative risks were found for prenatal exposure to X-rays, social class of parents, employment at Dounreay before conception or diagnosis, father's dose of ionising radiation before conception, or child's residence within 50 m of the path of microwave transmission beams. Results also proved negative for all lifestyle factors except an apparent association with use of beaches within 25 km of Dounreay. However, this result was based on small numbers, arose in the context of multiple hypothesis testing, and is certainly vulnerable to possible systematic bias. It was concluded that the raised incidence of childhood leukaemia and non-Hodgkin's lymphoma around Dounreay cannot be explained by paternal occupation at Dounreay or by paternal exposure to external ionising radiation before conception. The observation of an apparent association between the use of beaches around Dounreay and the development of childhood leukaemia and non-Hodgkin's lymphoma might be an artefact of multiple testing and influenced by recall bias. (author)

N-methylnicotinamide as a possible prognostic indicator of recovery from leukaemia in patients treated with total-body irradiation and bone marrow transplants

Energy Technology Data Exchange (ETDEWEB)

Tamulevicius, P; Streffer, C

1984-04-01

N-methylnicotinamide was determined in urine from patients with acute myelocytic leukaemia following total-body X-irradiation with 8.6 Gy and bone marrow transplantation. Patients that are alive and in excellent condition i.e. with acute leukaemia in full remission showed a distinct enhanced excretion of this metabolite about 20 days p.r. which returned to normal levels at about day 40 p.r. Patients that have died intercurrently of early leukaemic recurrences showed considerable fluctuations in N-methylnicotinamide excretion over the entire period and no ''normalization'' of levels in these patients was seen. In those cases where late leukaemic recurrence or infections were the cause of death, usually after discharge from the clinic, excretion patterns typical of those seen in disease-free patients were observed. We thus conclude that this metabolite appears to be a suitable tentative prognostic indicator for the overall state of recovery from leukaemia in the patients.

Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

NARCIS (Netherlands)

Jethwa, Alexander; Hüllein, Jennifer; Stolz, Tatjana; Blume, Carolin; Sellner, Leopold; Jauch, Anna; Sill, Martin; Kater, Arnon P.; te Raa, G. Doreen; Geisler, Christian; van Oers, Marinus; Dietrich, Sascha; Dreger, Peter; Ho, Anthony D.; Paruzynski, Anna; Schmidt, Manfred; von Kalle, Christof; Glimm, Hanno; Zenz, Thorsten

2013-01-01

Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were

Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

DEFF Research Database (Denmark)

Jethwa, Alexander; Hüllein, Jennifer; Stolz, Tatjana

2013-01-01

Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were...

Imported rickettsioses : think of murine typhus

NARCIS (Netherlands)

van der Kleij, FGH; Gansevoort, RT; Kreeftenberg, HG

Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur,

Joint scientific publication by the INSERM and IRSN concerning child leukaemia about French nuclear power stations on the Internet site of the 'International Journal of Cancer' the 4 January 2012; Publication scientifique conjointe Inserm et IRSN concernant les leucemies chez l'enfant autour des centrales nucleaires francaises sur le site internet de la revue 'International Journal of Cancer' le 4 Janvier 2012

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-01-12

This document describes the cooperation between the INSERM and IRSN in the field of child leukaemia about nuclear power stations, and presents the published study: context and objectives, methodology (epidemiological data, geographical data), and obtained results (risks and comparison with a German study)

Successful treatment of acute promyelocytic leukaemia without chemotherapy and blood transfusion

DEFF Research Database (Denmark)

Tøstesen, Michael; Østgård, Lene S G; Kjeldsen, Eigil

2018-01-01

Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year......-old female patient, who due to religious conviction refused supportive therapy with blood products. A treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was successful without the use of blood transfusions....

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

Science.gov (United States)

Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

2012-01-01

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

Leukaemia inhibitory factor--an exercise-induced myokine

DEFF Research Database (Denmark)

Broholm, Christa; Pedersen, Bente Klarlund

2010-01-01

During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... to oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due...

The effect of game-based exercise on infant acute lymphocytic leukaemia patients

OpenAIRE

Cortés-Reyes, Édgar; Escobar-Zabala, Paola; González-García, Laura

2013-01-01

Objective. To establish the effect of a game-based exercise programme on Physical Deconditioning Syndrome (PDS) in 5 to 12 year-old children suffering Acute Lymphocytic Leukaemia (ALL). Materials and methods. This was a quasi-experimental study involving seven children being treated for ALL at the National Cancer Institute (NCI) in Bogotá, Colombia. Fitness determinants (aerobic capacity, muscle strength, flexibility, motor skills and proprioception) were initially assessed to establish their...

Hypercalcaemia associated with chronic lymphocytic leukaemia in a Giant Schnauzer.

Science.gov (United States)

Kleiter, M; Hirt, R; Kirtz, G; Day, M J

2001-05-01

A 7-year-old male Giant Schnauzer was referred with a history of severe vomiting, lethargy, weight loss, polydipsia and polyuria. Detailed investigations revealed leucocytosis with a marked lymphocytosis, mild non-regenerative anaemia, thrombocytopenia, hypercalcaemia and azotaemia. Circulating lymphocytes were small and well-differentiated, and the same lymphoid population was present in bone marrow. Chronic lymphocyctic leukaemia with associated paraneoplastic hypercalcaemia was diagnosed. Immunohistochemical staining of a bone marrow biopsy revealed a neoplastic B-cell line expressing CD79. The dog responded to therapy with prednisolone and chlorambucil for a period of 8 months.

Tumour genesis syndrome: severe hypophosphatemia and hypokalemia may be ominous presenting findings in childhood acute myeloid leukaemia.

Science.gov (United States)

Chan, Winnie Ky; Chang, Kai On; Lau, Wing Hung

2017-08-01

We report a 16-year-old girl who was diagnosed with acute leukaemia and a marked leucocytosis >200 × 10 9 /L. She presented with marked hypophosphatemia, hypokalemia, acute renal failure and acute respiratory failure. These electrolytes disturbances may indicate rapid tumour genesis. These ominous findings required urgent treatment to halt the crises of rapid leukemic cell proliferation. Mark hypophosphatemia and hypokalemia may be presenting electrolyte abnormalities in a patient with acute leukaemia, and these may be indicators of aggressive tumour genesis. What is known: • Mild electrolyte disturbances are common in oncology patients • Tumour lysis syndrome is well recognized by paediatriaticians What is new: • Life-threatening hypophosphatemia is an uncommon presentation • These electrolytes disorders may indicate an aggressive tumour genesis process even at presentation and require urgent treatment.

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2012-01-01

Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2015-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2017-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

The incidence and survival of acute de novo leukaemias in Estonia and in a well-defined region of western Sweden during 1982-1996: a survey of patients aged > or =65 years.

Science.gov (United States)

Luik, E; Palk, K; Everaus, H; Varik, M; Aareleid, T; Wennström, L; Juntikka, E-L; Safai-Kutti, S; Stockelberg, D; Holmberg, E; Kutti, J

2004-07-01

To compare the incidence and survival of acute de novo leukaemias with particular reference to political/socio-economic and environmental factors in two neighbouring countries over the three 5-year periods (1982-1996). The present report covers only patients diagnosed when aged > or =65 years. A well-defined area of Sweden, the so-called Western Swedish Health Care Region and Estonia. Population-wise, the western Swedish Region and Estonia are very similar; area-wise they are also well comparable. The number of acute de novo leukaemias was quite dissimilar in the two countries (Estonia, n = 137, Sweden, n = 354). The age standardized incidence rates regarding the total number of acute de novo leukaemias was 5.31 per 100,000 inhabitants/year for Estonia and 7.99 for Sweden, this difference being statistically significant. However, the difference was merely attributable to incidence rates as regards acute myeloblastic leukaemias (AML); on the contrary, differences as regards acute lymphoblastic leukaemias (ALL) and non-classifiable, undifferentiated or biphenotypic acute leukaemias (uAL) were negligible. The relative survival for the total material of patients was significantly higher for Swedish when compared with Estonian patients (P or =65 years in Estonia at 1 year was 8.5% and at 3 years 3.5% respectively. The corresponding figures for the Swedish patients were considerably higher, 22.7 and 7.7% respectively. This difference, however, applied only for patients with AML (P acute leukemia patients in two neighbouring countries.

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies.

Science.gov (United States)

Teh, Benjamin W; Tam, Constantine S; Handunnetti, Sasanka; Worth, Leon J; Slavin, Monica A

2018-04-23

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunological and molecular biological identification of a true case of T-hairy cell leukaemia

DEFF Research Database (Denmark)

Demeter, J; Pálóczi, K; Földi, J

1990-01-01

A hairy cell leukaemia (HCL) patient is presented in whom the peripheral blood mononuclear cells (PBMCs) carried suppressor T-cell markers (CD3+, CD2+, CD8+/CD4-, CD38+). Analysis of genomic DNA of PBMNC showed the presence of a monoclonal population of T cells, the T-cell receptor (TCR) beta-cha...

Effect of central nervous system radiotherapy in children with acute lymphoblastic leukaemia on lymphocyte subpopulations and indicators of leucocyte migration inhibition in the peripheral blood

International Nuclear Information System (INIS)

Cesarz-Kruz, E.; Lukas, A; Sroczynska, M.; Lukas, W; Sonta-Jakimczyk, D.

1981-01-01

The reported investigations of changes in lymphocyte subpopulations and indicators of leycocyte migration inhibition in the peripheral blood were carried out in 17 children with acute lymphoblastic leukaemia subjected to prophylactic irradiation of the central nervous system. It was found that the depressive effect of radioprophylaxis affected mostly lymphocytes B. The usefulness of immunomodulation application in children with this leukaemia immediately after completion of radiotherapy is considered. (author)

Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

International Nuclear Information System (INIS)

Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M.; Matsuoka, M.; Yamamoto, T.; Jhono, M.; Eto, K.

2002-01-01

Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

Central nervous system lesions in adult T-cell leukaemia: MRI and pathology

Energy Technology Data Exchange (ETDEWEB)

Kitajima, M.; Korogi, Y.; Shigematsu, Y.; Liang, L.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Matsuoka, M. [Second Division of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Yamamoto, T. [Department of Pathology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Jhono, M. [Department of Dermatology, Kumamoto University School of Medicine, Honjo, Kumamoto (Japan); Eto, K. [The National Institute for Minamata Disease, Minamata (Japan)

2002-07-01

Adult T-cell leukaemia (ATL) is a T-cell lymphoid neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Radiological findings in central nervous system (CNS) involvement have not been well characterised. We reviewed the MRI of 18 patients with ATL who developed new neurological symptoms or signs, and pathology specimens from a 53-year-old woman who died of ATL. MRI findings were divided into three categories: definite, probable, and other abnormal. Definite and probable findings were defined as ATL-related. The characteristic findings were multiple parenchymal masses with or without contrast enhancement adjacent to cerebrospinal fluid (CSF) spaced and the deep grey matter of both cerebral hemispheres, plus leptomeningeal lesion. One patient had both cerebral and spinal cord lesions. Other abnormal findings in eight patients included one case of leukoencephalopathy caused by methotrexate. The histology findings consisted of clusters of tumour cells along perivascular spaces, and scattered infiltration of the parenchyma, with nests of tumour cells. Leptomeningeal infiltration by tumour spread into the parenchyma and secondary degeneration of the neuronal tracts was observed. MRI was useful for detecting CNS invasion by ATL and differentiating it from other abnormalities. The MRI findings seemed to correlate well with the histological changes. (orig.)

Feasibility of a school reintegration programme for children with acute lymphoblastic leukaemia.

Science.gov (United States)

Annett, R D; Erickson, S J

2009-07-01

Despite children with acute lymphoblastic leukaemia missing a significant amount of school, little empirical literature guides the optimal content, setting and timing of a school reintegration programme. We examined the feasibility of a 4-month school reintegration intervention by: (1) developing collaboration with a community-based advocacy organisation; (2) developing intervention modules and observable end points; and (3) determining how the study achieved recruitment expectations. Eight families with children aged 6-12 years diagnosed with acute lymphoblastic leukaemia and parents were enrolled in the study. An experienced advocate implemented a series of eight modules over a 4-month period (twice per month) with the families. Participants completed pre-post measures. Successful collaboration with the advocacy organisation and the development of an intervention module series were achieved. Recruitment aims proved more difficult: enrolment was extended when recruitment for the original 1- to 6-month post-diagnosis window proved difficult. The advocate was able to complete between three and seven of the modules (mean = 5.2, standard deviation = 1.5). Families preferred clinic-based intervention. Challenges faced and lessons learned include: (1) advocacy organisations may be useful resources for school reintegration interventions; (2) school reintegration interventions must be flexibly applied; and (3) measurement end points constructed to gauge programme effectiveness.

Structural biology contributions to the discovery of drugs to treat chronic myelogenous leukaemia

International Nuclear Information System (INIS)

Cowan-Jacob, Sandra W.; Fendrich, Gabriele; Floersheimer, Andreas; Furet, Pascal; Liebetanz, Janis; Rummel, Gabriele; Rheinberger, Paul; Centeleghe, Mario; Fabbro, Doriano; Manley, Paul W.

2006-01-01

A case study showing how the determination of multiple cocrystal structures of the protein tyrosine kinase c-Abl was used to support drug discovery, resulting in a compound effective in the treatment of chronic myelogenous leukaemia. Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery

Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia

Directory of Open Access Journals (Sweden)

Philipp Koehler

2012-01-01

Full Text Available B-cell chronic lymphocytic leukaemia (B-CLL remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells.

Preconception paternal occupational radiation exposure and the risk of childhood leukaemia: a paradox within an enigma

Energy Technology Data Exchange (ETDEWEB)

Berry, R.J. [Westlakes Research Institute, Cumbria (United Kingdom)

1995-02-01

A brief review is given of the evidence leading to the theory that preconception paternal occupational radiation exposure is a factor involved in the incidence of childhood leukaemia near nuclear facilities. Evidence is also presented which casts doubt on this theory (UK).

T cell receptor-transgenic primary T cells as a tool for discovery of leukaemia-associated antigens

NARCIS (Netherlands)

Ivanov, R.; Hol, S.; Aarts, T. I.; Hagenbeek, A.; Ebeling, S. B.

2006-01-01

Identification of a broad array of leukaemia-associated antigens is a crucial step towards immunotherapy of haematological malignancies. However, it is frequently hampered by the decrease of proliferative potential and functional activity of T cell clones used for screening procedures. Transfer of

Fatal veno-occlusive disease of the liver after chemotherapy, whole-body irradiation and bone marrow transplantation for refractory acute leukaemia

International Nuclear Information System (INIS)

Jacobs, P.; Miller, J.L.; Uys, C.J.; Dietrich, B.E.

1979-01-01

Rapid onset of liver failure with fatal outcome occured in a young woman after successful bone marrow transplantation undertaken for refractory acute leukaemia. Centrilobular necrosis was demonstrated at autopsy and was attributed to prior cytotoxic chemotherapy, possibly potentiated by the total-body irradiation that was used in preparation for the transplant. This association between liver damage and prolonged drug therapy, coupled with the short median survival currently achieved within these chemotherapy regimens, has initiated an evaluation of bone marrow transplantation in patients with leukaemia during the first complete remission, rather than at a later stage when cumulative drug toxicity to the liver may have taken place

Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

DEFF Research Database (Denmark)

Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

2010-01-01

This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

Total body irradiation and marrow transplantation for acute leukaemia. The Royal Marsden Hospital experience

Energy Technology Data Exchange (ETDEWEB)

Barrett, A; Barrett, A J; Powles, R L [Institute of Cancer Research, Sutton (UK). Surrey Branch; Royal Marsden Hospital, London (UK))

1979-06-01

The experience with total body irradiation at the Royal Marsden Hospital is described for an elective program of transplantation in patients with acute myeloid leukaemia (AML) in first remission. Dose rate appears to be a critical factor in the reduction of radiation-associated damage and careful monitoring of the actual dose distribution and dose received is mandatory.

Caffeine-hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells

Czech Academy of Sciences Publication Activity Database

Kaplánek, R.; Jakubek, M.; Rak, J.; Kejik, Z.; Havlík, M.; Dolenský, B.; Frydrych, I.; Hajduch, M.; Kolář, M.; Bogdanová, K.; Králová, Jarmila; Dzubak, P.; Král, V.

2015-01-01

Roč. 60, Jun (2015), s. 19-29 ISSN 0045-2068 Grant - others:GA MŠk(CZ) EE2.3.30.0060; GA MŠk CZ.1.07/2.3.00/30.0041; GA MŠk(CZ) LO1304 Program:EE; LD Institutional support: RVO:68378050 Keywords : Anticancer agents * Cancer treatment * Caffeine -hydrazones * Leukaemia * Selectivity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.252, year: 2015

A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study

NARCIS (Netherlands)

M.L. den Boer (Monique); M.A. van Slegtenhorst (Marjon); R.X. de Menezes (Renee); M.H. Cheok (Meyling); J.G.C.A.M. Buijs-Gladdines (Jessica); S.T.C.J.M. Arentsen-Peters (Susan); L.J.C.M. van Zutven (Laura); H.B. Beverloo (Berna); P.J. van der Spek (Peter); G. Escherich (Gabriele); M.A. Horstmann (Martin); G.E. Janka-Schaub (Gritta); W.A. Kamps (Willem); W.E. Evans (William); R. Pieters (Rob)

2009-01-01

textabstractBackground: Genetic subtypes of acute lymphoblastic leukaemia (ALL) are used to determine risk and treatment in children. 25% of precursor B-ALL cases are genetically unclassified and have intermediate prognosis. We aimed to use a genome-wide study to improve prognostic classification of

Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

LENUS (Irish Health Repository)

Monk, Ian R

2010-12-13

Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

Directory of Open Access Journals (Sweden)

Hill Colin

2010-12-01

Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

Comparison of loop-mediated isothermal amplification (LAMP) and nested-PCR assay targeting the RE and B1 gene for detection of Toxoplasma gondii in blood samples of children with leukaemia.

Science.gov (United States)

Fallahi, Shirzad; Seyyed Tabaei, Seyyed Javad; Pournia, Yadollah; Zebardast, Nozhat; Kazemi, Bahram

2014-07-01

Toxoplasmosis diagnosis constitutes an important measure for disease prevention and control. In this paper, a newly described DNA amplification technique, loop-mediated isothermal amplification (LAMP), and nested-PCR targeting the repeated element (RE) and B1 gene, were compared to each other for the detection of Toxoplasma gondii DNA in blood samples of children with leukaemia. One hundred ten blood samples from these patients were analyzed by LAMP and nested-PCR. Out of 50 seropositive samples (IgM+, IgG+), positive results were obtained with 92% and 86% on RE, B1-LAMP and 82% and 68% on RE, B1-nested PCR analyses, respectively. Of the 50 seronegative samples, three, two and one samples were detected positive by RE-LAMP, B1-LAMP and RE-nested PCR assays, respectively, while none were detected positive by B1-nested PCR. None of the 10 IgM-, IgG+ samples was detected positive after testing LAMP and nested-PCR assays in duplicate. This is the first report of a study in which the LAMP method was applied with high sensitivity and efficacy for the diagnosis of T. gonii in blood samples of children with leukaemia. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Waal, R.I.F. van der; Waal, I. van der [Univ. Hospital Vrije Univ., Dept. of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam (Netherlands); Veerman, A.J.P. [Univ. Hospital Vrije Univ., Dept. of Paediatric Oncology, Amsterdam (Netherlands); Snow, G.B. [Univ. Hospital Vrije Univ., Dept. of Otorhinolaryngology, Amsterdam (Netherlands)

1997-02-01

With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs.

Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Waal, R.I.F. van der; Waal, I. van der; Veerman, A.J.P.; Snow, G.B.

1997-01-01

With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs

The relation of illness perceptions to stress, depression, and fatigue in patients with chronic lymphocytic leukaemia.

Science.gov (United States)

Westbrook, Travis D; Maddocks, Kami; Andersen, Barbara L

2016-07-01

Chronic lymphocytic leukaemia (CLL) is the most prevalent adult leukaemia and is incurable. The course and treatment of CLL is unique and characterised by repeated cycles of treatment, stable disease and relapse. Utilising a Self-Regulatory Model framework, we examined the relationship between patients' illness perceptions and cancer-specific stress, depressive symptoms and fatigue. Our aim was to test illness perceptions as predictors of these outcomes when variance due to disease and treatment variables was controlled. Data were collected on 147 patients with relapsed/refractory CLL as they entered a phase II clinical trial of an investigational medication at a university affiliated, National Cancer Institute designated comprehensive cancer center. Cancer-specific stress, depressive symptoms and fatigue interference. . Hierarchical multiple regression was used. Consequences and emotional representation were related to all outcomes (ps stress (p fatigue interference (p stress, depressive symptoms and fatigue interference in relapsed/refractory CLL. Interventions targeted at restructuring maladaptive illness perceptions may have clinical benefit in this population.

Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

W. Y. Lim

2015-01-01

Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature.

Science.gov (United States)

Lim, W Y; Care, R; Lau, M; Chiruka, S; Dawes, P J D

2015-01-01

Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL) representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia) with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

Childhood leukaemia in Europe after Chernobyl: Five year follow-up of cancer registry populations

Energy Technology Data Exchange (ETDEWEB)

Parkin, D M; Black, R J; Kramarova, E [International Agency for Research on Cancer, Lyon (France); Clayton, D [University of Cambridge, Cambridge (United Kingdom)

1997-09-01

The European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) aims to monitor trends in the incidence of these diseases in European populations in relation to estimated exposures to radioactive material released at the time of the Chernobyl accident. Thirty-six cancer registries in 23 countries are collaborating in ECLIS, coordinated by the International Agency for Research on Cancer (IARC). 3 figs, 3 tabs.

Childhood leukaemia in Europe after Chernobyl: Five year follow-up of cancer registry populations

International Nuclear Information System (INIS)

Parkin, D.M.; Black, R.J.; Kramarova, E.; Clayton, D.

1997-01-01

The European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) aims to monitor trends in the incidence of these diseases in European populations in relation to estimated exposures to radioactive material released at the time of the Chernobyl accident. Thirty-six cancer registries in 23 countries are collaborating in ECLIS, coordinated by the International Agency for Research on Cancer (IARC). 3 figs, 3 tabs

Human parvovirus B19 in childhood acute lymphoblastic leukaemia in Basrah.

Science.gov (United States)

Ibrahem, Wijdan Nazar; Hasony, Hassan Jaber; Hassan, Jenan Ghulam

2014-01-01

To investigate the association of human parvovirus B19 infection with the onset of acute lymphoblastic leukaemia and its effect on TEL-AML-1 fusion gene and the presence of mutant P53. The case-control study was conducted at Basrah Hospital for Paediatrics and Gynaecology, Basrah, Iraq, from May 2009 to April 2010. A total of 100 blood samples were collected from 40 newly diagnosed cases and 60 healthy children to serve as control matched by age and gender. Human parvovirus B19-IgG and anti-P53 antibody were detected by enzyme-linked immunosorbent assay and TEL-AML-1 fusion gene was detected by reverse transcriptase-polymerase chain reaction on extracted ribonucleic acid from fresh blood samples using specified primers. SPSS 15 was used for statistical analysis. A higher proportion of human parvovirus B19-positive cases was found in leukaemic patients (n=19; 47.5%) compared to 12 (20%) in the control group (pparvovirus-B19 infection as 10 (71.4%) of TEL-AML-1 translocation-positive cases had human parvovirus-B19 IgG. On the other hand, there was no association between such infections and P53 gene mutation in the patients. Human parvovirus-B19 infection is common in the population, with higher prevalence among leukaemic patients with significant association between human parvovirus-B19 and TEL-AML-1 fusion gene in patients of acute lymphoblastic leukaemia.

Effects of epigenetic-based anti-cancer drugs in leukaemia and multiple myeloma cells

Czech Academy of Sciences Publication Activity Database

Jugová, Alžbeta; Galiová-Šustáčková, Gabriela; Legartová, Soňa; Stixová, Lenka; Kozubek, Stanislav; Bártová, Eva

2011-01-01

Roč. 35, č. 12 (2011), 1195-1203 ISSN 1065-6995 R&D Projects: GA MŠk(CZ) LC06027; GA MŠk(CZ) ME 919; GA ČR(CZ) GAP302/10/1022; GA MŠk(CZ) LD11020 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : epigenetics * histone code * leukaemia cells Subject RIV: BO - Biophysics Impact factor: 1.482, year: 2011

Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal

Directory of Open Access Journals (Sweden)

Ward Sean M

2003-06-01

Full Text Available Abstract Background The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. Method The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Results Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. Conclusions These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.

Birth characteristics and the risk of childhood leukaemias and lymphomas in New Zealand: a case-control study

Directory of Open Access Journals (Sweden)

Dockerty John D

2006-09-01

Full Text Available Abstract Background Some studies have found that lower parity and higher or lower social class (depending on the study are associated with increased risks of childhood acute lymphoblastic leukaemia (ALL. Such findings have led to suggestions that infection could play a role in the causation of this disease. An earlier New Zealand study found a protective effect of parental marriage on the risk of childhood ALL, and studies elsewhere have reported increased risks in relation to older parental ages. This study aimed to assess whether lower parity, lower social class, unmarried status and older parental ages increase the risk of childhood ALL (primarily. These variables were also assessed in relation to the risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin's lymphomas and Hodgkin's disease. Methods A case control study was conducted. The cases were 585 children diagnosed with leukaemias or lymphomas throughout New Zealand over a 12 year period. The 585 age and sex matched controls were selected at random from birth records. Birth records from cases (via cancer registration record linkage and from controls provided accurate data on maternal parity, social class derived from paternal occupation, maternal marital status, ages of both parents, and urban status based on the address on the birth certificate. Analysis was by conditional logistic regression. Results There were no statistically significant associations overall between childhood ALL and parity of the mother, social class, unmarried maternal status, increasing parental ages (continuous analysis, or urban status. We also found no statistically significant associations between the risks of childhood acute non-lymphoblastic leukaemia, non-Hodgkin lymphomas, or Hodgkin's disease and the variables studied. Conclusion This study showed no positive results though of reasonable size, and its record linkage design minimised bias. Descriptive studies (eg of time trends of ALL show that

Simultaneous determination of polyamines, N-acetylated polyamines and the polyamine analogues BE-3-3-3 and BE-4-4-4-4 by capillary gas chromatography with nitrogen-phosphorus detection

NARCIS (Netherlands)

Dorhout, B; Kingma, AW; deHoog, E; Muskiet, FAJ

1997-01-01

We describe a method for the profiling of polyamines, N-acetylated polyamines and the polyamine analogues N-1,N-11 bis(ethyl)norspermine (BE-3-3-3) and 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) in L1210 murine leukaemia cells by capillary gas chromatography with nitrogen-phosphorus

High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.

Science.gov (United States)

Takahashi, Hiroyuki; Watanabe, Tomoyuki; Kinoshita, Akitoshi; Yuza, Yuki; Moritake, Hiroshi; Terui, Kiminori; Iwamoto, Shotaro; Nakayama, Hideki; Shimada, Akira; Kudo, Kazuko; Taki, Tomohiko; Yabe, Miharu; Matsushita, Hiromichi; Yamashita, Yuka; Koike, Kazutoshi; Ogawa, Atsushi; Kosaka, Yoshiyuki; Tomizawa, Daisuke; Taga, Takashi; Saito, Akiko M; Horibe, Keizo; Nakahata, Tatsutoshi; Miyachi, Hayato; Tawa, Akio; Adachi, Souichi

2016-08-01

We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered. © 2016 John Wiley & Sons Ltd.

Endoplasmic reticulum calcium transport ATPase expression during differentiation of colon cancer and leukaemia cells

International Nuclear Information System (INIS)

Papp, Bela; Brouland, Jean-Philippe; Gelebart, Pascal; Kovacs, Tuende; Chomienne, Christine

2004-01-01

The calcium homeostasis of the endoplasmic reticulum (ER) is connected to a multitude of cell functions involved in intracellular signal transduction, control of proliferation, programmed cell death, or the synthesis of mature proteins. Calcium is accumulated in the ER by various biochemically distinct sarco/endoplasmic reticulum calcium transport ATPase isoenzymes (SERCA isoforms). Experimental data indicate that the SERCA composition of some carcinoma and leukaemia cell types undergoes significant changes during differentiation, and that this is accompanied by modifications of SERCA-dependent calcium accumulation in the ER. Because ER calcium homeostasis can also influence cell differentiation, we propose that the modulation of the expression of various SERCA isoforms, and in particular, the induction of the expression of SERCA3-type proteins, is an integral part of the differentiation program of some cancer and leukaemia cell types. The SERCA content of the ER may constitute a new parameter by which the calcium homeostatic characteristics of the organelle are adjusted. The cross-talk between ER calcium homeostasis and cell differentiation may have some implications for the better understanding of the signalling defects involved in the acquisition and maintenance of the malignant phenotype

Disease burden of chronic lymphocytic leukaemia within the European Union.

Science.gov (United States)

Watson, Louise; Wyld, Peter; Catovsky, Daniel

2008-10-01

Whilst Chronic lymphocytic leukaemia (CLL) is considered a rare disease, to our knowledge, the current prevalence of CLL within the European Union (EU) member states is not published. Understanding the number of individuals with CLL is vital to assess disease burden within the wider population. Using 2002 data from the International Agency for Research on Cancer, we estimated the number of individuals with CLL (ICD-10 C91.1) from those reported for all leukaemias (C91-95) and extrapolated the figures by the population increase within the EU between 2002 and 2006, the last year with fully updated community population estimates. One- and 5-yr partial prevalence estimates are reported (i.e. the number of individuals still living 1-5 yr post-diagnosis). We then applied proportional estimates from the literature to assess those requiring immediate treatment, those under observation and their likely progression rates. We found that within the 27 EU states plus Iceland, Norway and Lichtenstein, 1- and 5-yr CLL partial prevalence estimates totalled approximately 13,952 and 46,633 individuals respectively in 2006. By applying Binet staging to the 1-yr estimate, 40% of patients will be stage B/C and require immediate treatment. Thus, 5581 individuals may be treated within the first year of diagnosis. Of the 60% (8371) under observation, by 5 yr up to 33% (2763) may have more advanced disease with increased risk of mortality. Whilst CLL is a rare disease, the number of individuals burdened by the disease within the EU is considerable and thousands of patients require treatment and physician care, which has cost implications for member states.

The pharmacokinetics and metabolism of lumiracoxib in chimeric humanized and murinized FRG mice.

Science.gov (United States)

Dickie, A P; Wilson, C E; Schreiter, K; Wehr, R; Wilson, E M; Bial, J; Scheer, N; Wilson, I D; Riley, R J

2017-07-01

The pharmacokinetics and metabolism of lumiracoxib were studied, after administration of single 10mg/kg oral doses to chimeric liver-humanized and murinized FRG mice. In the chimeric humanized mice, lumiracoxib reached peak observed concentrations in the blood of 1.10±0.08μg/mL at 0.25-0.5h post-dose with an AUC inf of 1.74±0.52μgh/mL and an effective half-life for the drug of 1.42±0.72h (n=3). In the case of the murinized animals peak observed concentrations in the blood were determined as 1.15±0.08μg/mL at 0.25h post-dose with an AUC inf of 1.94±0.22μgh/mL and an effective half-life of 1.28±0.02h (n=3). Analysis of blood indicated only the presence of unchanged lumiracoxib. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles obtained in humanized mice were different compared to murinized animals with e.g., a higher proportion of the dose detected in the form of acyl glucuronide metabolites and much reduced amounts of taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57bl/6J mice and humans, revealed a greater though not complete match between chimeric humanized mice and humans, such that the liver-humanized FRG model may represent a useful approach to assessing the biotransformation of such compounds in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Minimal residual disease in chronic lymphocytic leukaemia.

Science.gov (United States)

García Vela, José Antonio; García Marco, José Antonio

2018-02-23

Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy. In this review, we discuss the different MRD methods of analysis, which source of tumour samples must be analysed, the future role of the detection of circulating tumour DNA, and the potential role of MRD negativity in clinical practice in the modern era of CLL therapy. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Human Parvovirus B19 in childhood acute lymphoblastic leukaemia in basrah

International Nuclear Information System (INIS)

Ibrahem, W.N.; Hasony, H.J.; Hassan, J.G.

2014-01-01

Objective: To investigate the association of human parvovirus B19 infection with the onset of acute lymphoblastic leukaemia and its effect on TEL-AML-1 fusion gene and the presence of mutant P53. Methods: The case-control study was conducted at Basrah Hospital for Paediatrics and Gynaecology, Basrah, Iraq, from May 2009 to April 2010. A total of 100 blood samples were collected from 40 newly diagnosed cases and 60 healthy children to serve as control matched by age and gender. Human parvovirus B19-IgG and anti-P53 antibody were detected by enzyme-linked immunosorbent assay and TEL-AML-1 fusion gene was detected by reverse transcriptase-polymerase chain reaction on extracted ribonucleic acid from fresh blood samples using specified primers. SPSS 15 was used for statistical analysis. Results: A higher proportion of human parvovirus B19-positive cases was found in leukaemic patients (n=19; 47.5%) compared to 12 (20%) in the control group (p<0.05). There was significant association between Tel-Amyl-1 translocation and human parvovirus-B19 infection as 10 (71.4%) of TEL-AML-1 translocation-positive cases had human parvovirus-B19 IgG. On the other hand, there was no association between such infections and P53 gene mutation in the patients. Conclusion: Human parvovirus-B19 infection is common in the population, with higher prevalence among leukaemic patients with significant association between human parvovirus-B19 and TEL-AML-1 fusion gene in patients of acute lymphoblastic leukaemia. (author)

Breastfeeding and early infection in the aetiology of childhood leukaemia in Down syndrome

OpenAIRE

Flores-Lujano, J; Perez-Saldivar, M L; Fuentes-Panan?, E M; Gorodezky, C; Bernaldez-Rios, R; Del Campo-Martinez, M A; Martinez-Avalos, A; Medina-Sanson, A; Paredes-Aguilera, R; De Diego-Flores Chapa, J; Bolea-Murga, V; Rodriguez-Zepeda, M C; Rivera-Luna, R; Palomo-Colli, M A; Romero-Guzman, L

2009-01-01

Background: For a child to develop acute leukaemia (AL), environmental exposure may not be sufficient: interaction with a susceptibility factor to the disease, such as Down syndrome (DS), may also be necessary. We assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. Methods: Children with DS in Mexico City, and either with or without AL, were the cases (N=57) and controls (N=218), respectively. Population was divided in childre...

Variation in survival of European children with acute lymphoblastic leukaemia, diagnosed in 1978-1992 : the EUROCARE study

NARCIS (Netherlands)

Coebergh, JW; Pastore, G; Gatta, G; Corazziari, [No Value; Kamps, W

The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13 344 newly diagnosed children (0-14 years) with ALL were included in the EUROCARE study

Acute myeloid leukaemia presenting as bilateral proptosis in a young child

Directory of Open Access Journals (Sweden)

Charudutt Kalamkar

2016-06-01

Full Text Available Myeloid sarcoma is an extramedullary manifestation of acute myeloid leukaemia (AML. Aims We are reporting a paediatric case presenting with bilateral proptosis, which we were able to diagnose with peripheral blood smear (PBS examination. Methods Case Report Results This case highlights the utility of simple routinely available PBS test in diagnosing this rare disease. Conclusion Our case highlights the importance of haemogram and peripheral blood smear in the initial evaluation of proptosis. Correct diagnosis of this rare entity is vital especially in cases where (myeloid sarcoma MS is the presenting feature of AML.

DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma

DEFF Research Database (Denmark)

Hedeland, Rikke L; Hvidt, Kristian; Nersting, Jacob

2010-01-01

To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN...

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).

Science.gov (United States)

Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire; Clavel, Jacqueline; Petridou, Eleni Th; Schüz, Joachim; Ezzat, Sameera; Dockerty, John D; Metayer, Catherine; Magnani, Corrado; Scheurer, Michael E; Mueller, Beth A; Mora, Ana M; Wesseling, Catharina; Skalkidou, Alkistis; Rashed, Wafaa M; Francis, Stephen S; Ajrouche, Roula; Erdmann, Friederike; Orsi, Laurent; Spector, Logan G

2016-04-01

Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). Our results suggest an increased risk of

Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.

Science.gov (United States)

Gorden, D Lee; Ivanova, Pavlina T; Myers, David S; McIntyre, J Oliver; VanSaun, Michael N; Wright, J Kelly; Matrisian, Lynn M; Brown, H Alex

2011-01-01

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD. Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts. Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts. Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.

Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer

DEFF Research Database (Denmark)

Søgaard, Kirstine Kobberøe; Farkas, Dóra Körmendiné; Sørensen, Henrik Toft

2017-01-01

of pneumonia was a clinical marker of the three most common childhood cancers. DESIGN: Population-based cohort study. SETTING: Denmark, hospital diagnoses, 1994-2013. METHODS: Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children...... with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk. RESULTS: The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid...

DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008)

DEFF Research Database (Denmark)

Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

2017-01-01

BACKGROUND: Adjustment of mercaptopurine and methotrexate maintenance therapy of acute lymphoblastic leukaemia by leucocyte count is confounded by natural variations. Cytotoxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to establish w...

Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study.

Science.gov (United States)

O'Brien, Susan; Jones, Jeffrey A; Coutre, Steven E; Mato, Anthony R; Hillmen, Peter; Tam, Constantine; Österborg, Anders; Siddiqi, Tanya; Thirman, Michael J; Furman, Richard R; Ilhan, Osman; Keating, Michael J; Call, Timothy G; Brown, Jennifer R; Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F; Chu, Alvina D; Hallek, Michael; Stilgenbauer, Stephan

2016-10-01

The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall

Nuclear power plant and childhood leukaemia - Report by the pluralist working group

International Nuclear Information System (INIS)

Sommelet, Daniele; Barbey, Pierre; Baruchel, Andre; Bey, Pierre; Catelinois, Olivier; Vacquier, Blandine; Chartier, Michel; Chenal, Christian; Clavel, Jacqueline; De Vathaire, Florent; Grosche, Bernd; Faure, Claire; Jacob, Sophie; Laurier, Dominique; Marignac, Yves; Unwin, Philippe; Vernez, David; Gagniere, Bertrand; Perel, Yves

2011-04-01

nuclear power plant and the risk of leukaemia in children? There is no official answer to this question, barring that exposure to high doses or to high dose rates increases the risk. Many other genetic and environmental causes must also be taken into consideration, in order to prevent any misunderstanding. The molecular heterogeneity of leukaemia must also be taken into account when interpreting the data. Despite this complexity, the general public needs objective, comprehensible information. Scientists are under the obligation to meet the legitimate expectations of a society that is not only fully aware of its 'right to know', but is also eager for greater humanity and trust. For the reasons listed above, an independent, pluralist, technical working group composed of French and foreign experts with complementary skills and interests was created with the following mandate: - Issue an opinion on the available epidemiological knowledge of the effects of nuclear power plant (NPP), focusing in particular on the risk of childhood leukaemia; - Define the research needed to improve the existing data; - Help to deliver clear, transparent and regular information to the general public.; - Draw up guidelines for improving the existing knowledge on the link between childhood leukaemia and nuclear power plant (especially the impact of very low doses of ionising radiations). These guidelines will be made public. - Present the progress of this work to a national committee tasked with planning and monitoring the measures needed to improve the available knowledge of the effects of discharge from the nuclear industry on the health of people living nearby

Granulocytic sarcoma presenting with necrotic cervical lymph nodes as an initial manifestation of childhood leukaemia: imaging features

Energy Technology Data Exchange (ETDEWEB)

An, Sang Bu; Cheon, Jung-Eun; Kim, In-One; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea); Ahn, Hyo Seop; Shin, Hee Young; Kang, Hyoung Jin; Yeon, Kyung Mo [Seoul National University College of Medicine, Department of Pediatrics, Cancer Research Institute, Seoul (Korea)

2008-06-15

We present two cases of granulocytic sarcoma of the cervical lymph nodes with central necrosis as an initial manifestation of childhood leukaemia, focusing on the imaging features. Recognition of the CT and MR imaging findings of granulocytic sarcoma involving the cervical lymph nodes assists the differential diagnosis of noninfective lymphadenopathy in children. (orig.)

Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

Directory of Open Access Journals (Sweden)

Perry A. Soriano

2011-01-01

Full Text Available Introduction. We examined the murine hepatectomy model of liver regeneration (LR in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP injections of a control, oxaliplatin (15 mg/kg, or irinotecan (100 mg/Kg or 250 mg/Kg solution. Hepatectomy (70% was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. -tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, =0.048 with no difference on D7 (=0.21. Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3. Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis.

Oxaliplatin but Not Irinotecan Impairs Posthepatectomy Liver Regeneration in a Murine Model

Science.gov (United States)

Soriano, Perry A.; Liu, Nian; Castillo, Erick; Foster, Brock; Artinyan, Avo; Kim, Joseph; Huang, Wendong; Wagman, Lawrence D.

2011-01-01

Introduction. We examined the murine hepatectomy model of liver regeneration (LR) in the setting of neoadjuvant chemotherapy. Methods. C57BL/6 mice were randomized to receive neoadjuvant intraperitoneal (IP) injections of a control, oxaliplatin (15 mg/kg), or irinotecan (100 mg/Kg or 250 mg/Kg) solution. Hepatectomy (70%) was performed 14 days after the final IP treatment. Animals were sacrificed at postoperative day (D) 0, 1, 2, 3, and 7. Liver remnants and serum were collected for analysis. T-tests for independent samples were used for statistical comparisons. Results. For oxaliplatin, percent LR did not differ at D1 or D2 but was significantly less at D3 (89.0% versus 70.0%, P = 0.048) with no difference on D7 (P = 0.21). Irinotecan-treated mice at both dose levels (100 mg/Kg and 250 mg/Kg) showed no significant differences in LR. BrdU incorporation was significantly decreased in oxaliplatin-treated animals (D1,2,3). Conclusions. Neoadjuvant oxaliplatin but not irinotecan impairs early LR in a posthepatectomy murine model which correlates with decreased DNA synthesis. PMID:22164336

Anatomy and Histology of the Human and Murine Prostate.

Science.gov (United States)

Ittmann, Michael

2018-05-01

The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas

2015-01-01

High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

In vitro experimental (211)At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin.

Science.gov (United States)

Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Frömke, Cornelia; Meyer, Geerd J; Knapp, Wolfram H

2010-05-01

Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter (211)At and compared survival of leukaemic HL-60 and K-562 cells treated with the (211)At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free (211)At. The mean labelling ratio of (211)At-labelled antibodies was 1:1,090 +/- 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of (211)At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. (211)At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after (211)At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that (211)At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase (211)At-anti-CD33 therapeutic effects.

Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Lund, Bendik; Åsberg, Ann; Heyman, Mats

2011-01-01

-cell disease (HR: 1.9, 95% CI: 1.01-3.7), Down syndrome (HR: 7.3, 95% CI: 3.6-14.9) and haematopoietic stem cell transplantation in CR1 (HR: 8.0, 95% CI: 3.3-19.5) were identified as independent risk factors for TRD. CONCLUSION: Several TRDs were potentially preventable and future efforts should be directed......BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92...

CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

Science.gov (United States)

Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor

2011-07-01

Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with ~ 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of ~ 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in ~ 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of ~ 12 nm retained bright fluorescence over an extended duration of ~ a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of ~ 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of ~ 8.2% in human peripheral blood cells (PBMCs) which are CD33low. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

International Nuclear Information System (INIS)

Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor

2011-01-01

Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with ∼ 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of ∼ 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in ∼ 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of ∼ 12 nm retained bright fluorescence over an extended duration of ∼ a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of ∼ 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of ∼ 8.2% in human peripheral blood cells (PBMCs) which are CD33 low . The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

Energy Technology Data Exchange (ETDEWEB)

Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor, E-mail: manzoork@aims.amrita.edu, E-mail: ullasmony@aims.amrita.edu [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin 682 041 (India)

2011-07-15

Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with {approx} 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of {approx} 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in {approx} 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of {approx} 12 nm retained bright fluorescence over an extended duration of {approx} a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of {approx} 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of {approx} 8.2% in human peripheral blood cells (PBMCs) which are CD33{sup low}. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

Validation of diffuse correlation spectroscopy sensitivity to nicotinamide-induced blood flow elevation in the murine hindlimb using the fluorescent microsphere technique

Science.gov (United States)

Proctor, Ashley R.; Ramirez, Gabriel A.; Han, Songfeng; Liu, Ziping; Bubel, Tracy M.; Choe, Regine

2018-03-01

Nicotinamide has been shown to affect blood flow in both tumor and normal tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was used as a simple intervention to test the sensitivity of noninvasive diffuse correlation spectroscopy (DCS) to changes in blood flow in the murine left quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard fluorescent microsphere (FM) technique for validation. The nicotinamide dose-response experiment showed that relative blood flow measured by DCS increased following treatment with 500- and 1000-mg / kg nicotinamide. The DCS and FM technique comparison showed that blood flow index measured by DCS was correlated with FM counts quantified by image analysis. The results of this study show that DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left quadriceps femoris. Additionally, the results of the comparison were consistent with similar studies in higher-order animal models, suggesting that mouse models can be effectively employed to investigate the utility of DCS for various blood flow measurement applications.

Stem cell targets and dosimetry for radiation-induced leukaemia and bone cancer

International Nuclear Information System (INIS)

Richardson, R.B.

2007-01-01

The ICRP are proposing changes to the assumed targets for the induction of bone cancer and leukaemias as described by Harrison et al in an accompanying article. This study of radiation targets in the skeleton finds that the endosteum of the long bone medullary cavities is not an important target, especially in the adult, as it supports a very low stem cell population associated with high adiposity, whereas the periosteum has a strong mesenchymal stem cell population throughout lifetime. Quiescent stem cells are found to be preferentially located close to the trabecular bone surface in the osteoblastic niche, whereas progenitors of stem cells prefer to reside in perivascular niches. Evidence is given in support of the suggestion that the absence of excess bone-cancer in atomic bomb survivors may be related to the extremely low prevalence of Paget's disease in Japan. The hypoxic conditions of the endosteum adjacent to quiescent bone surfaces provide a radioprotective stem cell microenvironment by a factor of 2-3 fold, whereas greater radiosensitivity is prevalent in the young and individuals with benign diseases of bone. Increasing the volume of the bone cancer target from a 10 μm thick endosteum to a 50 μm peripheral marrow layer will result in an approximately three-fold decline in the mean dose from alpha-emitters in bone. These new observations are shown to go some way in explaining the low incidences for leukaemia and especially bone cancer in radium dial painters, Thorotrast patients and Mayak nuclear workers. (author)

Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

Science.gov (United States)

Rushton, L; Schnatter, A R; Tang, G; Glass, D C

2014-01-01

Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case–control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone. PMID:24357793

Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia.

Science.gov (United States)

Tesio, M; Trinquand, A; Ballerini, P; Hypolite, G; Lhermitte, L; Petit, A; Ifrah, N; Baruchel, A; Dombret, H; Macintyre, E; Asnafi, V

2017-12-01

The tumour suppressor gene PTEN is commonly altered in T-cell acute lymphoblastic leukaemia but its prognostic impact is still debated. We screened a cohort of 573 fully characterised adult and paediatric T-cell acute lymphoblastic leukaemia (T-ALL) patients for genomic PTEN abnormalities. PTEN-inactivating mutations and/or deletions were identified in 91 cases (16%), including 18% of paediatric (49/277) and 14% of adult cases (42/296). Thirty-four patients harboured only mutations, 12 cases demonstrated only large deletions and 9 only microdeletions. About 36 patients had combined alterations. Different mechanisms of PTEN inactivation predicted differences in the clinical outcome for both adult and paediatric patients treated according to the GRAALL03/05 and FRALLE2000 protocols. Whereas large deletions predicted lower 5-year overall survival (P=0.0053 in adults, P=0.001 in children) and disease-free survival (P=0.0009 in adults, P=0.0002 in children), mutations were not associated with a worse prognosis. The prognostic impact of PTEN loss is therefore linked to the underlying type of genomic abnormality, both in adult and paediatric T-ALLs, demonstrating that detailed analysis of the type of abnormality type would be useful to refine risk stratification.

In vitro experimental {sup 211}At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin

Energy Technology Data Exchange (ETDEWEB)

Petrich, Thorsten; Korkmaz, Zekiye; Krull, Doris; Meyer, Geerd J.; Knapp, Wolfram H. [Hanover University School of Medicine, Department of Nuclear Medicine, Hanover (Germany); Froemke, Cornelia [Hanover University School of Medicine, Department of Biometry, Hanover (Germany)

2010-05-15

Monoclonal anti-CD33 antibodies conjugated with toxic calicheamicin derivative (gemtuzumab ozogamicin, GO) are a novel therapy option for acute myeloid leukaemia (AML). Key prognostic factors for patients with AML are high CD33 expression on the leukaemic cells and the ability to overcome mechanisms of resistance to cytotoxic chemotherapies, including drug efflux or other mechanisms decreasing apoptosis. Alpha particle-emitting radionuclides overwhelm such anti-apoptotic mechanisms by producing numerous DNA double-stranded breaks (DSBs) accompanied by decreased DNA repair. We labelled anti-CD33 antibodies with the alpha-emitter {sup 211}At and compared survival of leukaemic HL-60 and K-562 cells treated with the {sup 211}At-labelled antibodies, GO or unlabelled antibodies as controls. We also measured caspase-3/7 activity, DNA fragmentation and necrosis in HL-60 cells after treatment with the different antibodies or with free {sup 211}At. The mean labelling ratio of {sup 211}At-labelled antibodies was 1:1,090 {+-} 364 (range: 1:738-1:1,722) in comparison to 2-3:1 for GO. Tumour cell binding of {sup 211}At-anti-CD33 was high in the presence of abundant CD33 expression and could be specifically blocked by unlabelled anti-CD33. {sup 211}At-anti-CD33 decreased survival significantly more than did GO at comparable dilution (1:1,000). No significant differences in induction of apoptosis or necrosis or DNA DSB or in decreased survival were observed after {sup 211}At-anti-CD33 (1:1,090) versus GO (1:1) treatment. Our results suggest that {sup 211}At is a promising, highly cytotoxic radioimmunotherapy in CD33-positive leukaemia and kills tumour cells more efficiently than does calicheamicin-conjugated antibody. Labelling techniques leading to higher chemical yield and specific activities must be developed to increase {sup 211}At-anti-CD33 therapeutic effects. (orig.)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

2005-01-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

2005-03-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

International Nuclear Information System (INIS)

Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A.; Martin, H.; Bergmann, L.

2001-01-01

Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ( 188 Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2±2.1 (range 6.9-15.8) GBq 188 Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4±5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188 Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia; an open-label study

NARCIS (Netherlands)

Huisman, J.; Aukema, E.J.; Deijen, J.B.; van den Coeverden, S.C.C.M.; Kaspers, G.J.L.; van der Pal, H.J.H.; Delemarre-van de Waal, H.A.

2008-01-01

Background: To reduce the risk of brain damage children with acute lymphoblastic leukaemia (ALL) are nowadays mainly treated with intrathecal chemotherapy (ITC) instead of central nervous system (CNS) radiation therapy (CRT) to prevent CNS relapse. However, chemotherapy may also lead to cognitive

Intracellular metabolites of mercaptopurine in children with lymphoblastic leukaemia: a possible indicator of non-compliance?

OpenAIRE

Lennard, L.; Welch, J.; Lilleyman, J. S.

1995-01-01

As part of a programme assessing the pharmacokinetics of oral thiopurines given for lymphoblastic leukaemia, we assayed intracellular metabolites of mercaptopurine in children from all over the United Kingdom who were given a standard dose of the drug. The metabolites we measured, thioguanine nucleotides and methylmercaptopurines, are products of two competing metabolic pathways and would be expected to show an inverse correlation. A total of 327 children from 17 centres in the UK were studie...

(/sup 3/H)ouabain binding to leukaemic cells and intralymphocytic sodium content in chronic lymphocytic leukaemia; no evidence for alterations of the Na/sup +//K/sup +/-pump

Energy Technology Data Exchange (ETDEWEB)

Berntorp, E; Berntorp, K

1987-01-01

The number of specific (/sup 3/H)ouabain binding sites and dissociation constants (K/sub d/) were determined by Scatchard analysis of values for leucocytes from patients with B-cell chronic lymphocytic leukaemia (CCL), chronic myeloid leukaemia (CML), acute blastic leukaemia (AL) and healthy subjects. CCL lymphocytes and normal B-cells bound significantly less (/sup 3/H)ouabain than did normal T-lymphocytes. CML granulocytes showed the same binding characteristics as normal granulocytes, while blast cells from AL patients bound significantly more (/sup 3/H)ouabain than did normal granulocytes or B-cells. The increased binding capacity in blast cells might, at least partly, reflect their larger cell size. A decrease in K/sub d/ values was only found in CLL lymphocytes, as compared with normal B-cells. Intralymphocytic sodium content in CLL lymphocytes was significantly increased, as sompared with that in T-cell-enriched normal lymphocytes. (/sup 3/H)ouabain binding did not show any relationship to different prognostic variables in CLL. The present data mainly argue against altered Na/sup +//K/sup +/-ATPase enzyme activity as an indicator of malignancy.

T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments.

Science.gov (United States)

Hawkins, Edwin D; Duarte, Delfim; Akinduro, Olufolake; Khorshed, Reema A; Passaro, Diana; Nowicka, Malgorzata; Straszkowski, Lenny; Scott, Mark K; Rothery, Steve; Ruivo, Nicola; Foster, Katie; Waibel, Michaela; Johnstone, Ricky W; Harrison, Simon J; Westerman, David A; Quach, Hang; Gribben, John; Robinson, Mark D; Purton, Louise E; Bonnet, Dominique; Lo Celso, Cristina

2016-10-27

It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment

Chronic Subdural Hematoma development in Accelerated phase of Chronic Myeloid Leukaemia presenting with seizure and rapid progression course with fatal outcome

Directory of Open Access Journals (Sweden)

Raheja Amol

2015-06-01

Full Text Available Occurrence of chronic subdural hematoma (CSDH in leukemia is rare, and most reported cases occurred in relation with acute myeloid leukaemia; however, occurrence is extremely rare in accelerated phase of chronic myelogenous leukaemia (CML. Seizure as presentation of SDH development in CML cases is not reported in literature. Authors report an elderly male, who was diagnosed as CML, accelerated phase of developing SDH. Initially presented to local physician with seizure; urgent CT scan head was advised, but ignored and sensorium rapidly worsened over next day and reported to our emergency department in deeply comatose state, where imaging revealed chronic subdural hematoma with hypoxic brain injury with fatal outcome. Seizure, progressive worsening of headache, vomiting and papilloedema are harbinger of intracranial space occupying lesion and requires CT head in emergency medical department for exclusion, who are receiving treatment of haematological malignancy

Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands

NARCIS (Netherlands)

van den Hoek, J. A.; Al, E. J.; Huisman, J. G.; Goudsmit, J.; Coutinho, R. A.

1991-01-01

The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV-I enzyme immunoassays (EIA). Infection in these three

Reactivity of some mammalian sera with the bovine leukaemia virus env gene polypeptide expressed in Escherichia coli

International Nuclear Information System (INIS)

Slavikova, K.; Zajac, V.

1989-01-01

Sera from bovine leukaemia virus (BLV)-infected cattle and sheep were tested by radioimmunoassay and Western blot for their reactivity with 60,000 protein coded by the env gene of BLV and expressed in Escherichia coli. This protein, antigenically similar to BLV protein, reacted with antibodies against BLV antigens in the sera tested. (author). 3 figs., 1 tab., 13 refs

Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

DEFF Research Database (Denmark)

Nysom, K; Holm, K; Hesse, B

1996-01-01

Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

Murine Models of Gastric Corpus PreneoplasiaSummary

Directory of Open Access Journals (Sweden)

Christine P. Petersen

2017-01-01

Full Text Available Intestinal-type gastric adenocarcinoma evolves in a field of pre-existing metaplasia. Over the past 20 years, a number of murine models have been developed to address aspects of the physiology and pathophysiology of metaplasia induction. Although none of these models has achieved true recapitulation of the induction of adenocarcinoma, they have led to important insights into the factors that influence the induction and progression of metaplasia. Here, we review the pathologic definitions relevant to alterations in gastric corpus lineages and classification of metaplasia by specific lineage markers. In addition, we review present murine models of the induction and progression of spasmolytic polypeptide (TFF2–expressing metaplasia, the predominant metaplastic lineage observed in murine models. These models provide a basis for the development of a broader understanding of the physiological and pathophysiological roles of metaplasia in the stomach. Keywords: SPEM, Intestinal Metaplasia, Gastric Cancer, TFF2, Chief Cell, Hyperplasia

Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

Directory of Open Access Journals (Sweden)

Gurjot Basra

2012-01-01

Full Text Available Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient’s acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.

Gene expression in IFN-g-activated murine macrophages

Directory of Open Access Journals (Sweden)

Pereira C.A.

2004-01-01

Full Text Available Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up- or down-regulated by IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated or BALB/c (297 and 58 genes, respectively, up- and down-regulated mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated macrophages of resistant mice.

Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS)

Energy Technology Data Exchange (ETDEWEB)

Lorenz, Bernd

2015-07-01

Since July 2015 the study ''ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS) - an international cohort study'' is available. INWORKS comprised data from 300.000 occupational exposed and dosimetric monitored persons from France, USA and UK. The contribution is a critical discussion of this study with respect to the conclusion of a strong evidence of positive associations between protracted low-dose irradiation exposure and leukemia.

Lipid peroxidation in microsomes of murine bone marrow after low-dose γ-irradiation

International Nuclear Information System (INIS)

Schwenke, K.; Coslar, S.; Muehlensiepen, H.; Altman, K.I.; Feinendegen, L.E.

1994-01-01

The principal aim of the study was to investigate the effect of low-dose γ-irradiation on lipid peroxidation (LPO) in murine bone marrow. To this end, the degree of LPO in suspensions of microsomes of murine bone marrow cells (BMC) was determined in terms of malondialdehyde (MDA) formation after whole-body or in vitro exposure to various doses of γ-radiation. These effects were compared to some extent with similar effects in liver and spleen preparations. As to the effect of γ-irradiation on LPO in BMC, the response depends on the dose level and on whether whole-body or in vitro exposures are involved. Whole-body irradiation did not result in an increase in LPO in BMC microsomes, even at such high doses as 15 Gy, although hepatic microsomes showed a marked increase. In contrast, in vitro irradiation of BMC microsomes with 0.1, 10 and 50 Gy brought about an increase in LPO. This increase was already significant (P < 0.05) at 0.1 Gy following a post-irradiation incubation and substantial at 50 Gy, even without subsequent incubation. The results show that low doses of γ-irradiation are able to induce an elevation of LPO in murine BMC microsomes, but only after in vitro irradiation. In the case of whole-body irradiation cellular radical scavengers and other metabolic reactions may prevent a measurable increase in LPO. This is partly illustrated by the case of vitamin-E deficiency, where a substantial increase in LPO in BMC microsomes is observed even without γ-irradiation in comparison with euvitaminotic mice because normally occurring radicals are not scavenged sufficiently. (orig.)

Improved outcome after relapse in children with acute myeloid leukaemia

DEFF Research Database (Denmark)

Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran

2007-01-01

investigated. The study included all 146 children in the Nordic countries diagnosed with AML between 1988 and 2003, who relapsed. Data on disease characteristics and relapse treatment were related to outcome. Sixty-six percentage achieved remission with survival after relapse (5 years) 34 +/- 4%. Of 122......In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...... patients who received re-induction therapy, 77% entered remission with 40 +/- 5% survival. Remission rates were similar for different re-induction regimens but fludarabine, cytarabine, granulocyte colony-stimulating factor-based therapy had low treatment-related mortality. Prognostic factors for survival...

Constitutional sequence variation in the Fanconi anaemia group C (FANCC) gene in childhood acute myeloid leukaemia.

Science.gov (United States)

Barber, Lisa M; McGrath, Helen E N; Meyer, Stefan; Will, Andrew M; Birch, Jillian M; Eden, Osborn B; Taylor, G Malcolm

2003-04-01

The extent to which genetic susceptibility contributes to the causation of childhood acute myeloid leukaemia (AML) is not known. The inherited bone marrow failure disorder Fanconi anaemia (FA) carries a substantially increased risk of AML, raising the possibility that constitutional variation in the FA (FANC) genes is involved in the aetiology of childhood AML. We have screened genomic DNA extracted from remission blood samples of 97 children with sporadic AML and 91 children with sporadic acute lymphoblastic leukaemia (ALL), together with 104 cord blood DNA samples from newborn children, for variations in the Fanconi anaemia group C (FANCC) gene. We found no evidence of known FANCC pathogenic mutations in children with AML, ALL or in the cord blood samples. However, we detected 12 different FANCC sequence variants, of which five were novel to this study. Among six FANCC variants leading to amino-acid substitutions, one (S26F) was present at a fourfold greater frequency in children with AML than in the cord blood samples (odds ratio: 4.09, P = 0.047; 95% confidence interval 1.08-15.54). Our results thus do not exclude the possibility that this polymorphic variant contributes to the risk of a small proportion of childhood AML.

Promyelocytic leukaemia zinc finger maintains self-renewal of male germline stem cells (mGSCs) and its expression pattern in dairy goat testis.

Science.gov (United States)

Song, W; Zhu, H; Li, M; Li, N; Wu, J; Mu, H; Yao, X; Han, W; Liu, W; Hua, J

2013-08-01

Previous studies have shown that promyelocytic leukaemia zinc finger (PLZF) is a spermatogonia-specific transcription factor in the testis, required to regulate self-renewal and maintenance of the spermatogonia stem cell. Up to now, expression and function of PLZF in the goat testis has not been known. The objectives of this study were to investigate PLZF expression pattern in the dairy goat and its effect on male goat germline stem cell (mGSC) self-renewal and differentiation. Testis development and expression patterns of PLZF in the dairy goat were analysed by haematoxylin and eosin staining, immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, effects of PLZF overexpression on mGSC self-renewal and differentiation were evaluated by quantitative RT-PCR (QRT-PCR), immunofluorescence and BrdU incorporation assay. Promyelocytic leukaemia zinc finger was essential for dairy goat testis development and expression of several proliferation and pluripotency-associated proteins including OCT4, C-MYC were upregulated by PLZF overexpression. The study demonstrated that PLZF played a key role in maintaining self-renewal of mGSCs and its overexpression enhanced expression of proliferation-associated genes. Promyelocytic leukaemia zinc finger could function in the dairy goat as well as in other species in maintaining self-renewal of germline stem cells and this study provides a model to study the mechanism on self-renewal and differentiation of mGSCs in livestock. © 2013 John Wiley & Sons Ltd.

Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

Energy Technology Data Exchange (ETDEWEB)

Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

1995-06-15

To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

International Nuclear Information System (INIS)

Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won; Park, Choong Ki

1995-01-01

To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly (ρ < 0.01) and azygos engorgement (ρ < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality

Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

Energy Technology Data Exchange (ETDEWEB)

Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

1995-06-15

To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

Analysis of cardiomyocyte movement in the developing murine heart

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

2015-09-04

The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

Comparison of Adipose-Derived and Bone Marrow Mesenchymal Stromal Cells in a Murine Model of Crohn's Disease.

Science.gov (United States)

Xie, Minghao; Qin, Huabo; Luo, Qianxin; He, Xiaosheng; He, Xiaowen; Lan, Ping; Lian, Lei

2017-01-01

Mesenchymal stromal cells (MSCs) have been used in the treatment of Crohn's disease (CD) because of the immunomodulatory ability. The aim of this study was to investigate the therapeutic effect of adipose-derived MSCs (AD-MSCs) and to compare the therapeutic effect of AD-MSCs with that of bone marrow MSCs (BM-MSCs) in a murine model of CD. Murine colitis model of CD was created by trinitrobenzene sulfonic acid (TNBS). Twelve hours after treatment with TNBS, the mouse model was injected with MSCs intraperitoneally. Real-time polymerase chain reaction and immunohistochemistry staining were used to measure the expression levels of inflammatory cytokines in colonic tissues to investigate the therapeutic effect of AD-MSCs. The ten-day survival was recorded after infusion of MSCs. Intraperitoneal injection of MSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and improved the survival of the TNBS-induced mouse model of CD. AD-MSCs could effectively increase the expression of interleukin-10 and reduce the secretion of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor. The mucosal injury was repaired by AD-MSCs. These effects were comparable between AD-MSCs and BM-MSCs. The therapeutic effect appears similar between AD-MSCs and BM-MSCs in treating CD. AD-MSCs may be a potential alternative of cell-based therapy for CD.

DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

L-asparaginase induced hyperlipidaemia in acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Nesheli, H. M.; Tamaddoni, A.; Hosseinzadeh, F.; Moghaddam, T. G.

2013-01-01

Objective: To evaluate hyperlipidaemia in patients with acute lymphoblastic leukaemia (ALL) receiving L-asparaginase. Methods: A case-control study carried out between October 2007 and October 2010 with 77 patients undergoing chemotherapy at a teaching children hospital in Babol, Iran. Patients were treated with anti-leukaemic agents according to the protocols for standard-risk and high-risk ALL. Those patients who received asparaginase represented the cases and those who did not receive it were the controls. Biochemical markers were checked during the induction phase chemotherapy. Lipid profile of patients was recorded. Data was analysed using SPSS 16. Results: Of the 77 patients, 37 (48.05%) received asparaginase therapy and 40 (51.94%) patients did not. The mean peak triglyceride and cholesterol levels during asparaginase therapy in the first group were significantly higher than the levels in the second group. Conclusion: Severe hyperlipidaemia may be the cause of some morbidity in children receiving asparaginase. Asparaginase-induced hyperlipidaemia should be monitored in ALL patients during the induction phase of treatment. (author)

Structural studies on leukaemia inhibitory factor

Energy Technology Data Exchange (ETDEWEB)

Norton, R.S.; Maurer, T.; Smith, D.K. [Biomolecular Research Institute, Parville (Australia); Nicola, N.A. [Institute of Medical Research, Melbourne (Australia)

1994-12-01

Leukaemia Inhibitory Factor (LIF) is a pleiotropic cytokine that acts on a wide range of target cells, including mega-karyocytes, osteoblasts, hepatocytes, adipocytes, neurons, embryonic stem cells, and primordial germ cells. Many of its activities are shared with other cytokines, particularly interleukin-6, oncostatin-M, ciliary neurotrophic factor, and granulocyte colony-stimulating factor (G-CSF). Although secreted in vivo as a glycoprotein, nonglycosylated recombinant protein expressed in E. coli is fully active and has been used in our nuclear magnetic resonance (NMR) studies of the three-dimensional structure and structure-function relationships of LIF. With 180 amino acids and a molecular mass of about 20 kDa, OF is too large for direct structure determination by two-dimensional and three-dimensional {sup 1}HNMR. It is necessary to label the protein with the stable isotopes {sup 15}N and {sup 13}C and employ heteronuclear three-dimensional NMR in order to resolve and interpret the spectral information required for three-dimensional structure determination. This work has been undertaken with both human LIF and a mouse-human chimaera that binds to the human LIF receptor with the same affinity as the human protein and yet expresses in E. coli at much higher levels. Sequence-specific resonance assignments and secondary structure elements for these proteins will be presented and progress towards determination of their three-dimensional structures described.

Childhood vaccinations and risk of acute lymphoblastic leukaemia in children

DEFF Research Database (Denmark)

Søegaard, Signe Holst; Rostgaard, Klaus; Schmiegelow, Kjeld

2017-01-01

information on ALL subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing vaccinated with unvaccinated children.Results: Childhood ALL was diagnosed in 490 children during 10 829 194 person-years of follow-up. Neither the total number of vaccine doses received nor exposure to each......Background: It has been proposed that childhood vaccinations protect against acute lymphoblastic leukaemia (ALL) in children by modulation of future responses to common infections in childhood. However, the available studies provide inconsistent findings, and population-based cohort studies...... with longitudinal information on vaccinations are lacking.Methods: In a register-based cohort of all children born in Denmark from 1 January 1990 to 31 December 2008, followed up until age 15 years or 31 December 2009 (n=1 225 404), we evaluated exposure to childhood vaccination and risk of childhood ALL, including...

Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

DEFF Research Database (Denmark)

Borst, Louise; Wesolowska, Agata; Joshi, Tejal

2012-01-01

The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism...... childhood ALL, which may be important for understanding poor responses among this otherwise highly curable subset of ALL and lead to novel targeted treatment strategies....

The risk of leukaemia in young children from exposure to tritium and carbon-14 in the discharges of German nuclear power stations and in the fallout from atmospheric nuclear weapons testing.

Science.gov (United States)

Wakeford, Richard

2014-05-01

Towards the end of 2007, the results were published from a case-control study (the "KiKK Study") of cancer in young children, diagnosed study found a tendency for cases of leukaemia to live closer to the nearest nuclear power station than their matched controls, producing an odds ratio that was raised to a statistically significant extent for residence within 5 km of a nuclear power station. The findings of the study received much publicity, but a detailed radiological risk assessment demonstrated that the radiation doses received by young children from discharges of radioactive material from the nuclear reactors were much lower than those received from natural background radiation and far too small to be responsible for the statistical association reported in the KiKK Study. This has led to speculation that conventional radiological risk assessments have grossly underestimated the risk of leukaemia in young children posed by exposure to man-made radionuclides, and particular attention has been drawn to the possible role of tritium and carbon-14 discharges in this supposedly severe underestimation of risk. Both (3)H and (14)C are generated naturally in the upper atmosphere, and substantial increases in these radionuclides in the environment occurred as a result of their production by atmospheric testing of nuclear weapons during the late 1950s and early 1960s. If the leukaemogenic effect of these radionuclides has been seriously underestimated to the degree necessary to explain the KiKK Study findings, then a pronounced increase in the worldwide incidence of leukaemia among young children should have followed the notably elevated exposure to (3)H and (14)C from nuclear weapons testing fallout. To investigate this hypothesis, the time series of incidence rates of leukaemia among young children risk of leukaemia in young children following the peak of above-ground nuclear weapons testing, or that incidence rates are related to level of exposure to fallout, is

Murine macrophage heparanase: inhibition and comparison with metastatic tumor cells

International Nuclear Information System (INIS)

Savion, N.; Disatnik, M.H.; Nevo, Z.

1987-01-01

Circulating macrophages and metastatic tumor cells can penetrate the vascular endothelium and migrate from the circulatory system to extravascular compartments. Both activated murine macrophages and different metastatic tumor cells attach, invade, and penetrate confluent vascular endothelial cell monolayer in vitro, by degrading heparan sulfate proteoglycans in the subendothelial extracellular matrix. The sensitivity of the enzymes from the various sources degrading the heparan sulfate proteoglycan was challenged and compared by a series of inhibitors. Activated macrophages demonstrate a heparanase with an endoglycosidase activity that cleaves from the [ 35 S]O 4 - -labeled heparan sulfate proteoglycans of the extracellular matrix 10 kDa glycosaminoglycan fragments. The degradation of [ 35 S]O 4 - -labeled extracellular matrix proteoglycans by the macrophages' heparanase is significantly inhibited in the presence of heparan sulfate (10μg/ml), arteparon (10μg/ml), and heparin at a concentration of 3 μg/ml. Degradation of this heparan sulfate proteoglycan is a two-step sequential process involving protease activity followed by heparanase activity. B16-BL6 metastatic melanoma cell heparanase, which is also a cell-associated enzyme, was inhibited by heparin to the same extent as the macrophage haparanase. On the other hand, heparanase of the highly metastatic variant (ESb) of a methylcholanthrene-induced T lymphoma, which is an extracellular enzyme released by the cells to the incubation medium, was more sensitive to heparin and arteparon than the macrophages' heparanase. These results may indicate the potential use of heparin or other glycosaminoglycans as specific and differential inhibitors for the formation in certain cases of blood-borne tumor metastasis

RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia.

Science.gov (United States)

Zuber, Johannes; Shi, Junwei; Wang, Eric; Rappaport, Amy R; Herrmann, Harald; Sison, Edward A; Magoon, Daniel; Qi, Jun; Blatt, Katharina; Wunderlich, Mark; Taylor, Meredith J; Johns, Christopher; Chicas, Agustin; Mulloy, James C; Kogan, Scott C; Brown, Patrick; Valent, Peter; Bradner, James E; Lowe, Scott W; Vakoc, Christopher R

2011-08-03

Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.

Naja nigricollis CMS-9 enhances the mitochondria-mediated death pathway in adaphostin-treated human leukaemia U937 cells.

Science.gov (United States)

Chen, Ying-Jung; Wang, Jeh-Jeng; Chang, Long-Sen

2011-11-01

1. The aim of the present study was to explore the effect of the Naja nigricollis phospholipase A(2) CMS-9 on adaphostin-induced death of human leukaemia U937 cells. 2. Leukaemia U937 cells (Bcr/Abl-negative cells) were treated with adaphostin (0-10 μmol/L) and CMS-9 (0-1 μmol/L). The effects of CMS-9, adaphostin and their combination on cell viability, the generation reactive oxygen species (ROS), [Ca(2+) ](i) , p38 mitogen-activated protein kinase (MAPK) activation, Akt and extracellular signal-regulated kinase (ERK) inactivation, mitochondrial membrane potential (ΔΨ(m) ) and Bcl-2 family proteins were analysed. 3. Both adaphostin and CMS-9 induced U937 cell apoptosis, characterized by dissipation of ΔΨ(m) and ROS generation. Combined treatment further increased ΔΨ(m) loss and reduced the viability of adaphostin-treated cells. Unlike in CMS-9-treated cells, in adaphostin-treated cells ROS-induced increases in [Ca(2+) ](i) were observed. CMS-9-induced ROS generation resulted in p38 MAPK activation, whereas adaphostin treatment elicited ROS/Ca(2+) -mediated inactivation of Akt and ERK. Moreover, Akt was found to be involved in ERK phosphorylation. Suppression of p38 MAPK activation blocked CMS-9-induced ΔΨ(m) loss and Bcl-xL downregulation. Overexpression of constitutively active Akt and mitogen-activated protein kinase kinase (MEK) 1 rescued adaphostin-induced ΔΨ(m) loss and Bcl-2 downregulation. Similarly, CMS-9 augmented adaphostin toxicity in human leukaemia K562 cells via increased mitochondrial alterations. 4. The results suggest that two distinct pathways mediate adaphostin- and CMS-9-induced mitochondrial damage (i.e. the ROS-Ca(2+) -Akt-ERK and ROS-p38 MAPK pathways, respectively). These distinct pathway explain the augmentation by CMS-9 of ΔΨ(m) loss and apoptosis in adaphostin-treated U937 cells. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology

DEFF Research Database (Denmark)

Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne

2014-01-01

We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO...

Antibody responses to vaccination and immune function in patients with haematological malignancies - studies in patients with chronic lymphocytic leukaemia autologous stem cell recipients

NARCIS (Netherlands)

Velden, A.M.T. van der

2007-01-01

This thesis concerns the antibody responses to vaccination and immune function of patients with several forms of haematological diseases. Antibody responses in patients with chronic lymphocytic leukaemia (CLL) and in autologous stem cell transplant recipients were studied. In the autologous stem

Child leukaemia around Sellafield: what Seascale said about the Black Report

Energy Technology Data Exchange (ETDEWEB)

Macgill, S M

1986-07-01

The paper investigates reaction to the Black Report by the inhabitants of Seascale, the community whose situation - in terms of leukaemia incidence and proximity to Sellafield - was the focus of interest of that Report. The paper draws on an original interview-based social survey among the inhabitants of Seascale. As well as routine examination of response frequencies, a new methodological tool for reconstructing aggregate patterns of a large number of multiple character responses (from the Galois connections between response categories) is used as primary basis for interpretative analysis. It is found that the Black Report was received in Seascale with a mixture of confusion, satisfaction, deferred judgement and sharp criticism, and implications of this finding for the risk perception research field, as well as for policy makers, are brought out.

Child leukaemia around Sellafield: what Seascale said about the Black Report

International Nuclear Information System (INIS)

Macgill, S.M.

1986-07-01

The paper investigates reaction to the Black Report by the inhabitants of Seascale, the community whose situation - in terms of leukaemia incidence and proximity to Sellafield - was the focus of interest of that Report. The paper draws on an original interview-based social survey among the inhabitants of Seascale. As well as routine examination of response frequencies, a new methodological tool for reconstructing aggregate patterns of a large number of multiple character responses (from the Galois connections between response categories) is used as primary basis for interpretative analysis. It is found that the Black Report was received in Seascale with a mixture of confusion, satisfaction, deferred judgement and sharp criticism, and implications of this finding for the risk perception research field, as well as for policy makers, are brought out. (author)

Case report: hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?

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Alexopoulos Evangelos C

2006-07-01

Full Text Available Abstract Background Exposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML. Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells. Case presentation Two white females (A and B hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5. The patient did not respond to therapy and died threeweeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3. Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987–1993 and 1997–2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently

Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

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Amelia Kellar

2015-01-01

Full Text Available Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.

COMARE incidence of cancer and childhood leukaemia in the vicinity of the former Greenham Common Airbase, Newbury, Berkshire

International Nuclear Information System (INIS)

Hamlet, R.

1998-01-01

On 26 March 1998 the Committee on Medical Aspects of Radiation in the Environment (COMARE), under the Chairmanship of Professor Bryn Bridges, published its Fifth Report entitled 'Incidence of cancer and leukaemia in the area around the former Greenham Common Airbase. An investigation of a possible association with measured environmental radiation levels' (1998). The proceedings leading up to this report and its main conclusions are given in this short news item

Cloning and Characterization of the Genes Encoding the Murine Homologues of the Human Melanoma Antigens MART1 and gp100

Science.gov (United States)

Zhai, Yifan; Yang, James C.; Spiess, Paul; Nishimura, Michael I.; Overwijk, Willem W.; Roberts, Bruce; Restifo, Nicholas P.; Rosenberg, Steven A.

2008-01-01

The recent identification of genes encoding melanoma-associated antigens has opened new possibilities for the development of cancer vaccines designed to cause the rejection of established tumors. To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp 100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library. The open reading frames of murine MART1 and gp 100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins. Comparison of the DNA sequences of the murine MART1 genes, derived from normal melanocytes, the immortalized nontumorgenic melanocyte line Melan-a and the B16 melanoma, showed all to be identical. Northern and Western blot analyses confirmed that both genes encoded products that were melanocyte lineage proteins. Mice immunized with murine MART1 or gp 100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma. In contrast, immunization of mice with human gp 100 using recombinant adenoviruses elicited T cells specific for hgp100, but these T cells also cross reacted with B16 tumor in vitro and induced significant but weak protection against B16 challenge. Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hep100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma. These results may suggest that immunization with heterologous tumor antigen, rather than self, may be more effective as an immunotherapeutic reagent in designing antigen-specific cancer vaccines. PMID:9101410

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial.

Science.gov (United States)

O'Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

2014-01-01

Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one

Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

Science.gov (United States)

Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

2016-01-01

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

Intellectual abilities among survivors of childhood leukaemia as a function of CNS irradiation

International Nuclear Information System (INIS)

Eiser, C.

1978-01-01

Twenty-eight children in remission at least 2 years after completing chemotherapy for acute lymphoblastic leukaemia were assessed on standardised psychological tests. It was found that 7 who never had central nervous system (CNS) irradiation and 9 having prophylactic CNS irradiation at least 6 months after diagnosis tended to perform at average or above levels, while those 10 each having prophylactic CNS irradiation (within 2 months of diagnosis) were generally at lower ability. Within the latter group 3 children showed serious intellectual impairments, while the group as a whole functioned especially poorly on quantitative tasks and those involving speeded performance with abstract material. General language ability was not affected. Practical and theoretical implications are discussed. (author)

Co-trimoxazole alone for prevention of bacterial infection in patients with acute leukaemia.

Science.gov (United States)

Starke, I D; Donnelly, P; Catovsky, D; Darrell, J; Johnson, S A; Goldman, J M; Galton, D A

1982-01-02

43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Epidemiological and immunological characteristics of childhood leukaemia in the Netherlands: population-based data from a nationwide co-operative group of paediatricians

International Nuclear Information System (INIS)

Coebergh, J.W.W.; Steensel-Moll, A. van; Veer, M.B. van't

1985-01-01

Results are reviewed from several population-based epidemiological and immunological studies of children with leukaemia in The Netherlands, who were diagnosed between 1973 and 1982 through a nationwide co-operative group of paediatricians. From 1973 till 1980 annual incidence rates appeared to be 3.1 per 10 5 person-yr. No significant trend was observed in this period. However a preliminary analysis of patients in the 1980-1982 period showed an increase. Mortality rates are decreasing since 1973, as expected. Incidence rates and proportions of different morphological and immunological subtypes reflect the pattern of occurrence in populations with a high standard of living. A relatively high incidence rate of acute lymphocytic leukaemia (ALL) is observed with a peak at the age of 3-5. The proportion of patients with T-cell phenotype among ALL-patients, immunologically typed between 1979 and 1982, appeared to increase with age, while the proportion of common ALL decreased. Statistical analysis of the data of patients with ALL in the Western part of the country including areas with nuclear plants, gave no indication for the presence of clustering. (author)

A shared promoter region suggests a common ancestor for the human VCX/Y, SPANX, and CSAG gene families and the murine CYPT family

DEFF Research Database (Denmark)

Hansen, Martin A; Nielsen, John E; Retelska, Dorota

2008-01-01

, sequences corresponding to the shared promoter region of the CYPT family were identified at 39 loci. Most loci were located immediately upstream of genes belonging to the VCX/Y, SPANX, or CSAG gene families. Sequence comparison of the loci revealed a conserved CYPT promoter-like (CPL) element featuring TATA...... cell types. The genomic regions harboring the gene families were rich in direct and inverted segmental duplications (SD), which may facilitate gene conversion and rapid evolution. The conserved CPL and the common expression profiles suggest that the human VCX/Y, SPANX, and CSAG2 gene families together......Many testis-specific genes from the sex chromosomes are subject to rapid evolution, which can make it difficult to identify murine genes in the human genome. The murine CYPT gene family includes 15 members, but orthologs were undetectable in the human genome. However, using refined homology search...

Paternal occupational contact level and childhood leukaemia in rural Scotland: a case-control study.

Science.gov (United States)

Kinlen, L J; Bramald, S

2001-04-06

In a national Scottish study of 809 cases of leukaemia and non-Hodgkins lymphoma diagnosed in 1950-89 among children aged 0-4 years who were born in Scotland, together with 2363 matched population controls, we investigated one aspect of the infective hypothesis. This concerns whether in rural areas (where the prevalence of susceptible individuals is likely to be higher) the risk is greater among the young children of men whose work involves contacts with many different people, particularly children, as noted in certain childhood infections. A positive trend was found in rural areas across 3 levels of increasing paternal occupational contact (as recorded at birth) by each of 2 previously defined classifications; no such effect was found in urban areas. The rural trend was more marked in that part of the study period with greater population mixing, but the difference from the period with less mixing was not itself significant, leaving open whether these rural findings reflect the extreme isolation of much of rural Scotland, or the effects in such areas of a degree of population mixing. In marked contrast, among the 850 cases and 2492 controls aged 5-14, those in rural areas in the higher population mixing period showed a significantly decreasing trend with increasing paternal occupational contact level. This would be consistent with immunity produced either by earlier infection at ages 0-4 years, or directly by low doses of the infective agent that were largely immunizing at these older ages. The findings overall provide further support for infection underlying childhood leukaemia and for the role of adults. Copyright 2001 Cancer Research Campaign http://www.bjcancer.com.

Violacein induces death of resistant leukaemia cells via kinome reprogramming, endoplasmic reticulum stress and Golgi apparatus collapse.

Directory of Open Access Journals (Sweden)

Karla C S Queiroz

Full Text Available It is now generally recognised that different modes of programmed cell death (PCD are intimately linked to the cancerous process. However, the mechanism of PCD involved in cancer chemoprevention is much less clear and may be different between types of chemopreventive agents and tumour cell types involved. Therefore, from a pharmacological view, it is crucial during the earlier steps of drug development to define the cellular specificity of the candidate as well as its capacity to bypass dysfunctional tumoral signalling pathways providing insensitivity to death stimuli. Studying the cytotoxic effects of violacein, an antibiotic dihydro-indolone synthesised by an Amazon river Chromobacterium, we observed that death induced in CD34(+/c-Kit(+/P-glycoprotein(+/MRP1(+ TF1 leukaemia progenitor cells is not mediated by apoptosis and/or autophagy, since biomarkers of both types of cell death were not significantly affected by this compound. To clarify the working mechanism of violacein, we performed kinome profiling using peptide arrays to yield comprehensive descriptions of cellular kinase activities. Pro-death activity of violacein is actually carried out by inhibition of calpain and DAPK1 and activation of PKA, AKT and PDK, followed by structural changes caused by endoplasmic reticulum stress and Golgi apparatus collapse, leading to cellular demise. Our results demonstrate that violacein induces kinome reprogramming, overcoming death signaling dysfunctions of intrinsically resistant human leukaemia cells.

Serial passaging of Candida albicans in systemic murine infection suggests that the wild type strain SC5314 is well adapted to the murine kidney.

Directory of Open Access Journals (Sweden)

Anja Lüttich

Full Text Available The opportunistic fungal pathogen Candida albicans has a remarkable ability to adapt to unfavorable environments by different mechanisms, including microevolution. For example, a previous study has shown that passaging through the murine spleen can cause new phenotypic characteristics. Since the murine kidney is the main target organ in murine Candida sepsis and infection of the spleen differs from the kidney in several aspects, we tested whether C. albicans SC5314 could evolve to further adapt to infection and persistence within the kidney. Therefore, we performed a long-term serial passage experiment through the murine kidney of using a low infectious dose. We found that the overall virulence of the commonly used wild type strain SC5314 did not change after eight passages and that the isolated pools showed only very moderate changes of phenotypic traits on the population level. Nevertheless, the last passage showed a higher phenotypic variability and a few individual strains exhibited phenotypic alterations suggesting that microevolution has occurred. However, the majority of the tested single strains were phenotypically indistinguishable from SC5314. Thus, our findings indicate that characteristics of SC5314 which are important to establish and maintain kidney infection over a prolonged time are already well developed.

miRNA analysis in B-cell chronic lymphocytic leukaemia : proliferation centres characterized by low miR-150 and high BIC/milk-155 expression

NARCIS (Netherlands)

Wang, M.; Tan, L. P.; Dijkstra, M. K.; van Lom, K.; Robertus, J-L; Harms, G.; Blokzijl, T.; Kooistra, K.; van t'Veer, M. B.; Rosati, S.; Visser, L.; Jongen-Lavrencic, M.; Kluin, P. M.; van den Berg, Anke

Several miRNAs have been reported to be associated with immunoglobulin heavy chain (IgH) mutation and ZAP-70 expression status in blood samples of B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma (B-CLL/SLL). In the bone marrow and lymphoid tissues, proliferation centres (PCs)

COMARE incidence of cancer and childhood leukaemia in the vicinity of the former Greenham Common Airbase, Newbury, Berkshire

Energy Technology Data Exchange (ETDEWEB)

Hamlet, R

1998-06-01

On 26 March 1998 the Committee on Medical Aspects of Radiation in the Environment (COMARE), under the Chairmanship of Professor Bryn Bridges, published its Fifth Report entitled 'Incidence of cancer and leukaemia in the area around the former Greenham Common Airbase. An investigation of a possible association with measured environmental radiation levels' (1998). The proceedings leading up to this report and its main conclusions are given in this short news item.

Parental communication and children's behaviour following diagnosis of childhood leukaemia.

Science.gov (United States)

Clarke, Sally-Ann; Davies, Helena; Jenney, Meriel; Glaser, Adam; Eiser, Christine

2005-04-01

Many parents find decisions about what to tell their child with cancer difficult. Open communication is generally considered the best policy and most health care professionals encourage parents to talk openly and honestly about the illness. However, parents differ in their views about what to tell the child. In this study 55 parents of children (36 boys and 19 girls, mean age = 7.33 years) newly diagnosed with acute lymphoblastic leukaemia (ALL) were interviewed about (i) the child's reactions and behaviour following diagnosis, (ii) their views about what to tell their child and (iii) factors influencing parents' communication with the child. Interviews were analysed using thematic analysis. Most children showed behavioural and mood difficulties after diagnosis. Older children were given more information. In addition, parents' perceptions of childhood cancer affect the way they communicate with their child. These findings may be used to inform training packages in order to facilitate improved communication amongst health professionals. Copyright 2004 John Wiley & Sons, Ltd.

Childhood leukaemia in relation to radiofrequency electromagnetic fields emitted from television and radio broadcast transmitters: epidemiological aspects of a case-control study in Germany; Leukaemie bei Kindern in der Umgebung von Sendestationen des Rundfunks. Anforderungen an das Studiendesign

Energy Technology Data Exchange (ETDEWEB)

Merzenich, H.; Bennack, S.; Blettner, M. [Mainz Univ. (DE). Inst. fuer Medizinische Biometrie, Epidemiologie und Informatik (IMBEI); Schmiedel, S.; Schuez, J. [Mainz Univ. (DE). Inst. fuer Medizinische Biometrie, Epidemiologie und Informatik (IMBEI); Danish Cancer Society, Copenhagen (Denmark). Inst. of Cancer Epidemiology; Brueggemeyer, H. [Niedersaechsischer Landesbetrieb fuer Wasserwirtschaft, Kuesten- und Naturschutz, AB35 - Strahlenschutz in Niedersachsen, Hannover (Germany); Philipp, J. [Suedwestrundfunk, Stuttgart (Germany). Abt. Frequenz- und Versorgungsplanung; Spix, C. [Mainz Univ. (Germany). Deutsches Kinderkrebsregister

2007-07-01

Leukaemia is the most common type of cancer in children accounting for about a third of all cancers in children under the age of 15 years. Environmental factors such as non-ionising radiation exposure might play a role in the aetiology of childhood leukaemia. However, data to support such hypotheses are inconsistent. A case control study has been set up in West Germany (University of Mainz) in order to determine whether there is an increased risk of childhood leukaemia in populations exposed to radiofrequency electromagnetic fields from TV and/or Radio towers. Cases are children aged 0 to 14 years with a primary leukaemia diagnosed between 1984 and 2003 who lived in the vicinity of these TV- and/ or Radio towers. Cases have been identified through the German Childhood Cancer Registry. Three controls per case have been individually matched by age at diagnosis, sex, time of diagnosis and study area. The study focuses on an individual retrospective exposure assessment using data from transmitter network operators. The study has started in March 2005 with a pilot investigation in order to specify the study design and the methods for exposure assessment. A total of 2009 eligible cases have been identified. The study will be finished end of 2007. (orig.)

Changes in the expression of FGFR3 in patients with chronic myeloid leukaemia receiving transplants of allogeneic peripheral blood stem cells

Czech Academy of Sciences Publication Activity Database

Dvořáková, D.; Krejčí, P.; Mayer, J.; Fajkus, Jiří; Hampl, Aleš; Dvořák, Petr

2001-01-01

Roč. 113, č. 3 (2001), s. 832-835 ISSN 0007-1048 R&D Projects: GA ČR GA312/97/0393; GA MŠk ME 198 Institutional research plan: CEZ:AV0Z5045916 Keywords : fibroblast growth factor receptor 3 * chronic myeloid leukaemia * stem cell transplantation Subject RIV: BO - Biophysics Impact factor: 2.815, year: 2001

Primary osteopathy of vertebrae in a neurofibromatosis type 1 murine model.

Science.gov (United States)

Zhang, Wei; Rhodes, Steven D; Zhao, Liming; He, Yongzheng; Zhang, Yingze; Shen, Yong; Yang, Dalong; Wu, Xiaohua; Li, Xiaohong; Yang, Xianlin; Park, Su-Jung; Chen, Shi; Turner, Charles; Yang, Feng-Chun

2011-06-01

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder caused by mutation of the NF1 tumor suppressor gene. Spinal deformities are common skeletal manifestations in patients with NF1. To date, the mechanism of vertebral abnormalities remains unclear because of the lack of appropriate animal models for the skeletal manifestations of NF1. In the present study, we report a novel murine NF1 model, Nf1(flox/-);Col2.3Cre(+) mice. These mice display short vertebral segments. In addition, a significant reduction in cortical and trabecular bone mass of the vertebrae was observed in Nf1(flox/-);Col2.3Cre(+) mice as measured by dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT). Peak stress and peak load were also significantly reduced in Nf1(flox/-);Col2.3Cre(+) mice as compared to controls. Furthermore, the lumbar vertebrae showed enlargement of the inter-vertebral canal, a characteristic feature of lumbar vertebrae in NF1 patients. Finally, histologic analysis demonstrated increased numbers of osteoclasts and decreased numbers of osteoblasts in the vertebrae of Nf1(flox/-);Col2.3Cre(+) mice in comparison to controls. In summary, Nf1(flox/-);Col2.3Cre(+) mice demonstrate multiple structural and functional abnormalities in the lumbar vertebrae which recapitulate the dystrophic vertebral changes in NF1 patients. This novel murine model provides a platform to understand the cellular and molecular mechanisms underlying the pathogenesis of spinal deficits in NF1 patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Murine Models of Sepsis and Trauma: Can We Bridge the Gap?

Science.gov (United States)

Stortz, Julie A; Raymond, Steven L; Mira, Juan C; Moldawer, Lyle L; Mohr, Alicia M; Efron, Philip A

2017-07-01

Sepsis and trauma are both leading causes of death in the United States and represent major public health challenges. Murine models have largely been used in sepsis and trauma research to better understand the pathophysiological changes that occur after an insult and to develop potential life-saving therapeutic agents. Mice are favorable subjects for this type of research given the variety of readily available strains including inbred, outbred, and transgenic strains. In addition, they are relatively easy to maintain and have a high fecundity. However, pharmacological therapies demonstrating promise in preclinical mouse models of sepsis and trauma often fail to demonstrate similar efficacy in human clinical trials, prompting considerable criticism surrounding the capacity of murine models to recapitulate complex human diseases like sepsis and traumatic injury. Fundamental differences between the two species include, but are not limited to, the divergence of the transcriptomic response, the mismatch of temporal response patterns, differences in both innate and adaptive immunity, and heterogeneity within the human population in comparison to the homogeneity of highly inbred mouse strains. Given the ongoing controversy, this narrative review aims to not only highlight the historical importance of the mouse as an animal research model but also highlight the current benefits and limitations of the model as it pertains to sepsis and trauma. Lastly, this review will propose future directions that may promote further use of the model. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Characterization of the binding of radioiodinated hybrid recombinant IFN-alpha A/D to murine and human lymphoid cell lines

International Nuclear Information System (INIS)

Faltynek, C.R.; Princler, G.L.; Schwabe, M.; Shata, M.T.; Lewis, G.K.; Kamin-Lewis, R.M.

1990-01-01

The hybrid recombinant human interferon (IFN) rIFN-alpha A/D was radioiodinated. Specific binding of [125I]rIFN-alpha A/D was observed with both human and murine cell lines. The binding of [125I]rIFN-alpha A/D to human Daudi cells had similar characteristics to the previously described binding of [125I]rIFN-alpha A or -alpha 2. The following lines of evidence demonstrated that [125I]rIFN-alpha A/D bound with high affinity to the same receptor on murine cells as murine IFN-alpha and -beta: (i) the binding of [125I]rIFN-alpha A/D to murine LBRM cells was inhibited to a similar extent by natural murine IFN-alpha, natural murine IFN-beta, and rIFN-A/D; (ii) the Kd (approximately 2 X 10(-10) M) obtained from both competition experiments and saturation binding experiments with [125I]rIFN-alpha A/D was comparable to the previously reported Kd for the binding of natural murine IFN-alpha and -beta to other murine cell lines; (iii) the size of the cross-linked [125I]rIFN-alpha A/D receptor complex formed on murine LBRM cells was similar to the previously reported cross-linked complex formed after binding radioiodinated natural murine IFN-beta to other murine cell lines. Due to the current lack of readily available recombinant murine IFN-alpha or -beta for radiolabeling and the previously demonstrated biological activity of rIFN-alpha A/D on murine cells, [125I]rIFN-alpha A/D should prove to be a useful reagent for further studies of murine IFN receptors

Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

Directory of Open Access Journals (Sweden)

Anne Sophie Weingertner

2009-01-01

Full Text Available The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

Transplantation of autologous bone marrow in three patients with acute myelogenous leukaemia during the first remission

Energy Technology Data Exchange (ETDEWEB)

Loewenberg, B; Sizoo, W; Sintnicolaas, K; Hendriks, W D.H.; Poel, J van der [Rotterdams Radio Therapeutisch Inst. (Netherlands); Abels, J; Dzoljic, G [Akademisch Ziekenhuis Rotterdam-Dijkzigt (Netherlands); Bekkum, D.W. van; Wagemaker, G [Gezondheidsorganisatie TNO, Rijswijk (Netherlands). Radiobiologisch Inst. TNO

1983-07-23

A report is presented on the first results of transplantation of autologous bone marrow in 3 adult patients with acute myelogenous leukaemia. The treatment consisted of intensive chemotherapy and whole-body irradiation and was followed by transplantation of a limited number of non-purified bone-marrow cells that had previously been collected from the patient. In all three patients, transplantation was followed by a stable remission. One patient had a fatal recurrence after a total period of 21 months of remission. In 2 patients, the remissions continue. The clinical significance of these findings is discussed.

Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria

International Nuclear Information System (INIS)

Gardner, M.J.; Snee, M.P.; Hall, A.J.; Powell, C.A.; Downes, S.

1990-01-01

The raised incidence of leukaemia, particularly, and non-Hodgkin's lymphoma among children near Sellafield was associated with paternal employment and recorded external dose of whole body penetrating radiation during work at the plant before conception. The association can explain statistically the observed geographical excess. This result suggests an effect of ionising radiation on fathers that may be leukaemogenic in their offspring, though other, less likely, explanations are possible. (author)

Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor

International Nuclear Information System (INIS)

Gough, N.M.; Gearing, D.P.; King, J.A.; Willson, T.A.; Hilton, D.J.; Nicola, N.A.; Metcalf, D.

1988-01-01

A human homologue of the recently cloned murine leukemia-inhibitory factor (LIF) gene was isolated from a genomic library by using the marine cDNA as a hybridization probe. The nucleotide sequence of the human gene indicated that human LIF has 78% amino acid sequence identity with murine LIF, with no insertions or deletions, and that the region of the human gene encoding the mature protein has one intervening sequence. After oligonucleotide-mediated mutagenesis, the mature protein-coding region of the LIF gene was introduced into the yeast expression vector YEpsec1. Yeast cells transformed with the resulting recombinant could be induced with galactose to produce high levels of a factor that induced the differentiation of murine M1 leukemic cells in a manner analogous to murine LIF. This factor competed with 125 I-labeled native murine LIF for binding to specific cellular receptors on murine cells, compatible with a high degree of structural similarity between the murine and human factors

Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

Science.gov (United States)

Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

1992-05-15

A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

Dendritic cells in chronic myelomonocytic leukaemia.

Science.gov (United States)

Vuckovic, S; Fearnley, D B; Gunningham, S; Spearing, R L; Patton, W N; Hart, D N

1999-06-01

Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.

TREATMENT OF PRIMARY PLASMA CELL LEUKAEMIA

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Peter Černelč

2003-04-01

Full Text Available Background. The author describes long-term survival in 3 patients with primary plasma cell leukaemia (PL after different therapeutic regimen and maintenance treatment with interferon alpha (INF.Patients and treatment. In a 52-year-old male patient, a partial remission of PL was achieved after 6 months of treatment with melphalan and prednisone. The patient did not consent to stem cell transplantation (SCT. An 86-year-old female patient with PL achieved a complete remission after 6 months of treatment with vincristine, doxorubicin and dexamethasone. A 31-year-old male patient experienced a complete remission of PL after 6 months of treatment with cyclophosphamide, vincristine, doxorubicin, methilprednisone, followed by autologous SCT. All three patients were placed on maintenance therapy with INF-2b (Intron A 3 × 106 IU given subcutaneously on two days per week. In the 52-year-old man, the remission lasted 9 months and in the woman 23 months, whereupon they developed a relapse with signs of disseminated plasmacytoma. In both patients the former chemotherapy was applied again, resulting in a slight improvement. The man died 37 months and the woman 43 months after the diagnosis of PL, while the youngest patient has been in complete remission for 82 months.Conclusions. Long remission achieved in our patients confirmed the favourable effect of INF in terms of prolongation of the remission duration in this patients. The effect of maintenance treatment with INF is usually directly dependent on the degree of remission induced by different therapeutic regimen.

The murine Cd48 gene: allelic polymorphism in the IgV-like region.

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Cabrero, J G; Freeman, G J; Reiser, H

1998-12-01

The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activation of T lymphocytes. prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV-like domain of murine CD48.

Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.

Science.gov (United States)

Chang, Ko; Lee, Nan-Yao; Ko, Wen-Chien; Lin, Wei-Ru; Chen, Yen-Hsu; Tsai, Jih-Jin; Chen, Tun-Chieh; Lin, Chun-Yu; Chang, Ya-Ting; Lu, Po-Liang

2017-06-22

The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Copyright © 2017. Published by Elsevier B.V.

In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA).

Science.gov (United States)

Larsson, R; Fridborg, H; Kristensen, J; Sundström, C; Nygren, P

1993-05-01

The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the interactions ranging from antagonistic to synergistic in terms of the multiplicative concept for drug interactions. However, an 'additive' model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) for several common antileukaemic drug combinations. When the two interaction models were related to treatment outcome 38% of the non-responders showed preference for the additive model whereas the corresponding figure for responders was 80%. Overall, in 248 of 290 (85%) tests performed with drug combinations, there was an agreement between the effect of the combination and that of the most active single component. Direct comparison of Dmax and the combination for correlation with clinical outcome demonstrated only minor differences in the ability to predict drug resistance. The results show that FMCA appear to report drug interactions in samples from patients with AML in accordance with clinical experience. Furthermore, testing single agents as a substitute for drug combinations may be adequate for detection of clinical drug resistance to combination therapy in AML.

Various distinctive cytogenetic abnormalities in patients with acute myeloid leukaemia aged 60 years and older express adverse prognostic value : results from a prospective clinical trial

NARCIS (Netherlands)

van der Holt, Bronno; Breems, Dimitri A.; Beverloo, H. Berna; van den Berg, Eva; Burnett, Alan K.; Sonneveld, Pieter; Lowenberg, Bob

Diagnostic cytogenetic abnormalities are considered important prognostic factors in patients with acute myeloid leukaemia (AML). However, the prognostic assessments have mainly been derived from patients with AML aged <60 years. Two recent studies of AML patients of 60 years and older proposed

Leukaemia inhibitory factor (LIF) gene mutations in women diagnosed with unexplained infertility and endometriosis have a negative impact on the IVF outcome a pilot study

Czech Academy of Sciences Publication Activity Database

Novotný, Z.; Křižan, Jiří; Šíma, R.; Šíma, Petr; Uher, P.; Zech, N.; Huttelová, R.; Baborová, P.; Ulčová-Gallová, Z.; Šubrt, I.; Ulmanová, E.; Houdek, Z.; Rokyta, Z.; Babuška, V.; Králíčková, M.

2009-01-01

Roč. 55, č. 3 (2009), s. 92-97 ISSN 0015-5500 R&D Projects: GA MZd NR9135 Institutional research plan: CEZ:AV0Z50200510 Keywords : leukaemia inhibitory factor * infertility * mutation Subject RIV: EC - Immunology Impact factor: 0.924, year: 2009

Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukaemia

NARCIS (Netherlands)

Uyl-de Groot, CA; Lowenberg, B; Vellenga, E; Suciu, S; Willemze, R; Rutten, FFH

We conducted a prospective, randomized, multicentre clinical trial comparing the effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia (AML). The patients were randomized to either daunomycin-cytosine arabinoside (control arm: rr = 161)

Expression of leukaemia inhibitory factor at the conceptus-maternal interface during preimplantation development and in the endometrium during the oestrous cycle in the mare

NARCIS (Netherlands)

De Ruijter-Villani, M.; Deelen, C.; Stout, T. A E

2016-01-01

Leukaemia inhibitory factor (LIF) plays a critical role in blastocyst development and implantation in several species. The present study investigated mRNA and protein expression for LIF, as well as the low-affinity LIF receptor (LIFR) and interleukin-6 signal transducer (IL6ST), in equine

The risk of leukaemia in young children from exposure to tritium and carbon-14 in the discharges of German nuclear power stations and in the fallout from atmospheric nuclear weapons testing

Energy Technology Data Exchange (ETDEWEB)

Wakeford, Richard [The University of Manchester, Centre for Occupational and Environmental Health, Institute of Population Health, Manchester (United Kingdom)

2014-05-15

Towards the end of 2007, the results were published from a case-control study (the ''KiKK Study'') of cancer in young children, diagnosed <5 years of age during 1980-2003 while resident near nuclear power stations in western Germany. The study found a tendency for cases of leukaemia to live closer to the nearest nuclear power station than their matched controls, producing an odds ratio that was raised to a statistically significant extent for residence within 5 km of a nuclear power station. The findings of the study received much publicity, but a detailed radiological risk assessment demonstrated that the radiation doses received by young children from discharges of radioactive material from the nuclear reactors were much lower than those received from natural background radiation and far too small to be responsible for the statistical association reported in the KiKK Study. This has led to speculation that conventional radiological risk assessments have grossly underestimated the risk of leukaemia in young children posed by exposure to man-made radionuclides, and particular attention has been drawn to the possible role of tritium and carbon-14 discharges in this supposedly severe underestimation of risk. Both {sup 3}H and {sup 14}C are generated naturally in the upper atmosphere, and substantial increases in these radionuclides in the environment occurred as a result of their production by atmospheric testing of nuclear weapons during the late 1950s and early 1960s. If the leukaemogenic effect of these radionuclides has been seriously underestimated to the degree necessary to explain the KiKK Study findings, then a pronounced increase in the worldwide incidence of leukaemia among young children should have followed the notably elevated exposure to {sup 3}H and {sup 14}C from nuclear weapons testing fallout. To investigate this hypothesis, the time series of incidence rates of leukaemia among young children <5 years of age at diagnosis has been

Comparison of postoperative corneal changes between dry eye and non-dry eye in a murine cataract surgery model.

Science.gov (United States)

Kwon, Jin Woo; Chung, Yeon Woong; Choi, Jin A; La, Tae Yoon; Jee, Dong Hyun; Cho, Yang Kyung

2016-01-01

To compare the effects of the surgical insult of cataract surgery on corneal inflammatory infiltration, neovascularization (NV) and lymphangiogenesis (LY) between the dry eye and non-dry eye in murine cataract surgery models. We established two groups of animals, one with normal eyes (non-dry eye) and the second with induced dry eyes. In both groups, we used surgical insults to mimic human cataract surgery, which consisted of lens extraction, corneal incision and suture. After harvesting of corneas on the 9(th) postoperative day and immunohistochemical staining, we compared NV, LY and CD11b+ cell infiltration in the corneas. Dry eye group had significantly more inflammatory infiltration (21.75%±7.17% vs 3.65%±1.49%; P=0.049). The dry eye group showed significantly more NV (48.21%±4.02% vs 26.24%±6.01%; P=0.016) and greater levels of LY (9.27%±0.48% vs 4.84%±1.15%; P=0.007). In corneas on which no surgery was performed, there was no induction of NV in both the dry and non-dry group, but dry eye group demonstrated more CD11b+ cells infiltration than the non-dry eye group (0.360%±0.160% vs 0.023%±0.006%; P=0.068). Dry eye group showed more NV than non-dry eye group in both topical PBS application and subconjunctival PBS injection (P=0.020 and 0.000, respectively). In a murine cataract surgery model, preexisting dry eye can induce more postoperative NV, LY, and inflammation in corneal tissue.

Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

Science.gov (United States)

Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

2011-10-15

Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

Intracellular metabolites of mercaptopurine in children with lymphoblastic leukaemia: a possible indicator of non-compliance?

Science.gov (United States)

Lennard, L; Welch, J; Lilleyman, J S

1995-10-01

As part of a programme assessing the pharmacokinetics of oral thiopurines given for lymphoblastic leukaemia, we assayed intracellular metabolites of mercaptopurine in children from all over the United Kingdom who were given a standard dose of the drug. The metabolites we measured, thioguanine nucleotides and methylmercaptopurines, are products of two competing metabolic pathways and would be expected to show an inverse correlation. A total of 327 children from 17 centres in the UK were studied. All were on the same therapeutic schedule of mercaptopurine. All had been on an unattenuated full protocol-directed dose (at least 75 mg m-2) for a minimum of 7 days before assay. There was a very wide variation in the concentration of the two metabolites measured; the thioguanine nucleotides ranged from 0 to 1255 pmol per 8 x 10(8) red cells (median 289, lower quartile 210, upper quartile 377) and the methylmercaptopurine metabolites ranged from 0 to 46.3 nmol per 8 x 10(8) red cells (median 5.18, lower quartile 2.31, upper quartile 11.59). The anticipated negative correlation was not apparent, but the ratio between the two was not randomly distributed. No child had both metabolite concentrations in the upper quartiles, but in 32 (10%) children the concentration of both metabolites was in the lower quartile. Of the 32, only one metabolite was detected in four and none at all in six. The most likely explanation for these findings is that a minority of children with lymphoblastic leukaemia fail to take oral mercaptopurine either totally or intermittently. The extent of the problem is unknown, but we suspect it may be clinically important in at least 10% of patients.

RUNX3 is involved in caspase-3-dependent apoptosis induced by a combination of 5-aza-CdR and TSA in leukaemia cell lines.

Science.gov (United States)

Zhai, Feng-Xian; Liu, Xiang-Fu; Fan, Rui-Fang; Long, Zi-Jie; Fang, Zhi-Gang; Lu, Ying; Zheng, Yong-Jiang; Lin, Dong-Jun

2012-03-01

Epigenetic therapy has had a significant impact on the management of haematologic malignancies. The aim of this study was to assess whether 5-aza-CdR and TSA inhibit the growth of leukaemia cells and induce caspase-3-dependent apoptosis by upregulating RUNX3 expression. K562 and Reh cells were treated with 5-aza-CdR, TSA or both compounds. RT-PCR and Western blot analyses were used to examine the expression of RUNX3 at the mRNA and protein levels, respectively. Immunofluorescence microscopy was used to detect the cellular location of RUNX3. Additionally, after K562 cells were transfected with RUNX3, apoptosis and proliferation were studied using Annexin V staining and MTT assays. The expression of RUNX3 in leukaemia cell lines was markedly less than that in the controls. Demethylating drug 5-aza-CdR could induce RUNX3 expression, but the combination of TSA and 5-aza-CdR had a greater effect than did treatment with a single compound. The combination of 5-aza-CdR and TSA induced the translocation of RUNX3 from the cytoplasm into the nucleus. TSA enhanced apoptosis induced by 5-aza-CdR, and Annexin V and Hoechst 33258 staining showed that the combination induced apoptosis but not necrosis. Furthermore, apoptosis was dependent on the caspase-3 pathway. RUNX3 overexpression in K562 cells led to growth inhibition and apoptosis and potentiated the effects of 5-aza-CdR induction. RUNX3 plays an important role in leukaemia cellular functions, and the induction of RUNX3-mediated effects may contribute to the therapeutic value of combination TSA and 5-aza-CdR treatment.

Acute Febrile Illness and Complications Due to Murine Typhus, Texas, USA1,2.

Science.gov (United States)

Afzal, Zeeshan; Kallumadanda, Sunand; Wang, Feng; Hemmige, Vagish; Musher, Daniel

2017-08-01

Murine typhus occurs relatively commonly in southern Texas, as well as in California. We reviewed records of 90 adults and children in whom murine typhus was diagnosed during a 3-year period in 2 hospitals in southern Texas, USA. Most patients lacked notable comorbidities; all were immunocompetent. Initial signs and symptoms included fever (99%), malaise (82%), headache (77%), fatigue (70%), myalgias (68%), and rash (39%). Complications, often severe, in 28% of patients included bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis; the last 3 are previously unreported in murine typhus. Low serum albumin and elevated procalcitonin, consistent with bacterial sepsis, were observed in >70% of cases. Rash was more common in children; thrombocytopenia, hyponatremia, elevated hepatic transaminases, and complications were more frequent in adults. Murine typhus should be considered as a diagnostic possibility in cases of acute febrile illness in southern and even in more northern US states.

Mapping of murine radiation-induced acute myeloid leukaemia susceptibility loci

International Nuclear Information System (INIS)

Darakhshan, F.

2001-01-01

Studies on radiation-induced AML have shown characteristic phenotypic variation in susceptibility amongst inbred mouse strains, suggesting the involvement of genetic factors in determining the development of AML post-irradiation exposure. The main objective of the present study therefore was to identify and map markers in linkage disequilibrium with gene variants associated with influencing susceptibility to radiation induced AML in mice. Given Chr 2 abnormalities are characteristic of AML in mice, this feature was exploited in an effort to overcome the long latency for AML development. Analysis of Chr 2 aberrations at 24 and 48 h following irradiation established a positive correlation between Chr 2 radiosensitivity and radiation-AML susceptibility thus validating the choice of substitute assay. The analysis also resulted in the identification of a further trait, additional to Chr 2 radiosensitivity, termed overall chromosome radiosensitivity. Genetic mapping of Chr 2 radiosensitivity using public domain microsatellite database information resulted in the definition of cluster regions on 7 different chromosomes. Further genotyping reduced the candidate regions to 3 specific regions of interest. A test of allelic association could not ascertain a conclusive link between markers at these regions and the Chr 2 radiosensitivity/radiation-AML susceptibility phenotype. However, a region on Chr 4 around D4Mit221 appears to be most strongly associated. Similar studies identified three chromosomal regions of interest (on Chrs 4, 8 and 16) associated with overall chromosome radiosensitivity trait. An independent mapping strategy using F3 RCS confirmed the likely involvement of two of the candidate Chr 2 radiosensitivity regions identified by the inbred analysis including that on Chr 4 and also highlighted phenotypic heterogeneity amongst resistant RC strains, suggesting the influence of multiple alleles in specific phenotypes. RFLP analysis of candidate genes, localised on physical maps of the chromosomal regions, did not show a positive correlation with Chr 2 radiosensitivity, although it is anticipated that with the assembly of denser maps new prospective genes will warrant close analysis. (author)

A murine model of targeted infusion for intracranial tumors.

Science.gov (United States)

Kim, Minhyung; Barone, Tara A; Fedtsova, Natalia; Gleiberman, Anatoli; Wilfong, Chandler D; Alosi, Julie A; Plunkett, Robert J; Gudkov, Andrei; Skitzki, Joseph J

2016-01-01

Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.

The cribriform plate: a sanctuary site for meningeal leukaemia

International Nuclear Information System (INIS)

Williams, M.V.

1987-01-01

Cranial irradiation is an effective prophylactic treatment for subclinical meningeal infiltration in lymphoblastic leukaemia, but, central nervous system (CNS) relapse still occurs in 6-10% of cases overall and as many as 30% of cases with a poor prognosis in some series. These recurrences may be due in part to inadvertent underdosage of the cribriform plate, centrally situated between the orbits and projected over their upper third in a lateral view. The dose to the adjacent meninges may thus be reduced by shielding of the radiosensitive lenses. This problem is exacerbated if conventional lateral fields centred on the mid-skull are used, because the eyes will not then project over one another. If the field centre is moved to the edge of the orbit, this problem of beam divergence can be overcome. Central axis beam blocking of both lenses is possible, in some patients the cribriform plate can be adequately irradiated. In most children the geometry of the orbit is such that it is necessary to add an anterior electron beam to ensure homogeneous dosage. These refinements in technique might prevent meningeal relapse with a lower whole-brain dose and, hence, fewer neurophyschological sequelae. (author)

Reemergence of Murine Typhus in the US

Centers for Disease Control (CDC) Podcasts

2015-04-21

Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions

Directory of Open Access Journals (Sweden)

Z.K. Tuong

2018-06-01

Full Text Available Currently available vaccines prevent HPV infection and development of HPV-associated malignancies, but do not cure existing HPV infections and dysplastic lesions. Persistence of infection(s in immunocompetent patients may reflect induction of local immunosuppressive mechanisms by HPV, providing a target for therapeutic intervention. We have proposed that a mouse, expressing HPV16 E7 oncoprotein under a Keratin 14 promoter (K14E7 mice, and which develops epithelial hyperplasia, may assist with understanding local immune suppression mechanisms that support persistence of HPV oncogene-induced epithelial hyperplasia. K14E7 skin grafts recruit immune cells from immunocompetent hosts, but consistently fail to be rejected. Here, we review the literature on HPV-associated local immunoregulation, and compare the findings with published observations on the K14E7 transgenic murine model, including comparison of the transcriptome of human HPV-infected pre-malignancies with that of murine K14E7 transgenic skin. We argue from the similarity of i the literature findings and ii the transcriptome profiles that murine K14E7 transgenic skin recapitulates the cellular and secreted protein profiles of high-grade HPV-associated lesions in human subjects. We propose that the K14E7 mouse may be an appropriate model to further study the immunoregulatory effects of HPV E7 expression, and can facilitate development and testing of therapeutic vaccines.

Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study.

Directory of Open Access Journals (Sweden)

Teresa Fiebig

Full Text Available Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.

Transplantation of autologous bone marrow in three patients with acute myelogenous leukaemia during the first remission

International Nuclear Information System (INIS)

Loewenberg, B.; Sizoo, W.; Sintnicolaas, K.; Hendriks, W.D.H.; Poel, J. van der; Abels, J.; Dzoljic, G.; Bekkum, D.W. van; Wagemaker, G.

1983-01-01

A report is presented on the first results of transplantation of autologous bone marrow in 3 adult patients with acute myelogenous leukaemia. The treatment consisted of intensive chemotherapy and whole-body irradiation and was followed by transplantation of a limited number of non-purified bone-marrow cells that had previously been collected from the patient. In all three patients, transplantation was followed by a stable remission. One patient had a fatal recurrence after a total period of 21 months of remission. In 2 patients, the remissions continue. The clinical significance of these findings is discussed. (Auth.)

Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

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Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

1997-01-01

Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with ...

DNA instability, paternal irradiation and leukaemia in children around Sellafield

International Nuclear Information System (INIS)

Baverstock, K.F.

1991-01-01

The chemical instability of DNA under physiological conditions requires that cells have highly developed processes for repairing stochastic single-strand damage. It is proposed here that provided ionising-radiation-induced single-strand damage does not occur at a rate sufficient to perturb the dynamic steady state between degradation and repair, it can be regarded as 'irrelevant' to biological effect, leaving double-strand damage and DNA-protein crosslinks as 'relevant' damage to biological effect. At dose rates of ∼ 0.05 Gy/min low-LET radiation the rate of induced single-strand damage equals that of the spontaneous damage, and in this region a transition, with increasing dose-rate, from constant effect to increasing effect, will be expected. This is observed in studies of specific locus mutation by radiation in the male mouse. The application of this biophysical principle governing the influence of radiation dose-rate, to the association observed between paternal preconceptional dose to Sellafield workers and childhood leukaemia in their offspring, shows that the likelihood of a casual relationship is extremely remote. (author)

Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models

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Rosthøj, Susanne; Keiding, Niels; Schmiegelow, Kjeld

2012-01-01

Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is t...... of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy....

Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

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Virijevic Marijana

2016-12-01

Full Text Available Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2 genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK. The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up.

Comparison of postoperative corneal changes between dry eye and non-dry eye in a murine cataract surgery model

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Kwon, Jin Woo; Chung, Yeon Woong; Choi, Jin A; La, Tae Yoon; Jee, Dong Hyun; Cho, Yang Kyung

2016-01-01

AIM To compare the effects of the surgical insult of cataract surgery on corneal inflammatory infiltration, neovascularization (NV) and lymphangiogenesis (LY) between the dry eye and non-dry eye in murine cataract surgery models. METHODS We established two groups of animals, one with normal eyes (non-dry eye) and the second with induced dry eyes. In both groups, we used surgical insults to mimic human cataract surgery, which consisted of lens extraction, corneal incision and suture. After harvesting of corneas on the 9th postoperative day and immunohistochemical staining, we compared NV, LY and CD11b+ cell infiltration in the corneas. RESULTS Dry eye group had significantly more inflammatory infiltration (21.75%±7.17% vs 3.65%±1.49%; P=0.049). The dry eye group showed significantly more NV (48.21%±4.02% vs 26.24%±6.01%; P=0.016) and greater levels of LY (9.27%±0.48% vs 4.84%±1.15%; P=0.007). In corneas on which no surgery was performed, there was no induction of NV in both the dry and non-dry group, but dry eye group demonstrated more CD11b+ cells infiltration than the non-dry eye group (0.360%±0.160% vs 0.023%±0.006%; P=0.068). Dry eye group showed more NV than non-dry eye group in both topical PBS application and subconjunctival PBS injection (P=0.020 and 0.000, respectively). CONCLUSION In a murine cataract surgery model, preexisting dry eye can induce more postoperative NV, LY, and inflammation in corneal tissue. PMID:26949638

Expression of biologically active murine interleukin-18 in Lactococcus lactis.

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Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

2016-11-01

The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL -1 and 0.6-0.7 ng mL -1 , respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Murine typhus in two travelers returning from Bali, Indonesia: an underdiagnosed disease.

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Takeshita, Nozomi; Imoto, Kazuya; Ando, Shuji; Yanagisawa, Kunio; Ohji, Goh; Kato, Yasuyuki; Sakata, Akiko; Hosokawa, Naoto; Kishimoto, Toshio

2010-01-01

Two Japanese travelers from Bali were diagnosed with murine typhus in Japan during the same period. Although one had only mild illness, the other experienced liver and kidney dysfunction. Murine typhus may be missed not only in endemic areas around the world, but also in travelers, especially those returning from marine resorts in these areas. © 2010 International Society of Travel Medicine.

Association between SLC19A1 gene polymorphism and high dose methotrexate toxicity in childhood acute lymphoblastic leukaemia and non Hodgkin malignant lymphoma: introducing a haplotype based approach

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Kotnik Barbara Faganel

2017-09-01

Full Text Available We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL and non Hodgkin malignant lymphoma (NHML.

Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

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Mayumi Oakland

2013-01-01

Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

Molecular techniques for the personalised management of patients with chronic myeloid leukaemia.

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Alikian, Mary; Gale, Robert Peter; Apperley, Jane F; Foroni, Letizia

2017-03-01

Chronic myeloid leukemia (CML) is the paradigm for targeted cancer therapy. RT-qPCR is the gold standard for monitoring response to tyrosine kinase-inhibitor (TKI) therapy based on the reduction of blood or bone marrow BCR-ABL1 . Some patients with CML and very low or undetectable levels of BCR-ABL1 transcripts can stop TKI-therapy without CML recurrence. However, about 60 percent of patients discontinuing TKI-therapy have rapid leukaemia recurrence. This has increased the need for more sensitive and specific techniques to measure residual CML cells. The clinical challenge is to determine when it is safe to stop TKI-therapy. In this review we describe and critically evaluate the current state of CML clinical management, different technologies used to monitor measurable residual disease (MRD) focus on comparingRT-qPCR and new methods entering clinical practice. We discuss advantages and disadvantages of new methods.

Wernicke's encephalopathy induced by total parenteral nutrition in patient with acute leukaemia: unusual involvement of caudate nuclei and cerebral cortex on MRI

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D' Aprile, P.; Tarantino, A.; Carella, A. [Division of Neuroradiology, Policlinico, Univ. of Bari (Italy); Santoro, N. [Inst. of Paediatric Clinic I, Policlinico, University of Bari, Bari (Italy)

2000-10-01

We report a 13-year-old girl with leukaemia and Wernicke's encephalopathy induced by total parenteral nutrition. MRI showed unusual bilateral lesions of the caudate nuclei and cerebral cortex, as well as typical lesions surrounding the third ventricle and aqueduct. After intravenous thiamine, the patient improved, and the abnormalities on MRI disappeared. (orig.)

The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

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Marcell Cserhalmi

2017-09-01

Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

DMPD: Toll-like receptor 9 in murine lupus: more friend than foe! [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18241699 Toll-like receptor 9 in murine lupus: more friend than foe! Yu P, Musette ...us: more friend than foe! PubmedID 18241699 Title Toll-like receptor 9 in murine lupus...P, Peng SL. Immunobiology. 2008;213(2):151-7. Epub 2007 Sep 21. (.png) (.svg) (.html) (.csml) Show Toll-like receptor 9 in murine lup

An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

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Bowden, Steven D; Ramachandran, Vinoy K; Knudsen, Gitte M; Hinton, Jay C D; Thompson, Arthur

2010-11-08

In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice. We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence. Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous.

Bivalent promoter marks and a latent enhancer may prime the leukaemia oncogene LMO1 for ectopic expression in T-cell leukaemia.

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Oram, S H; Thoms, J; Sive, J I; Calero-Nieto, F J; Kinston, S J; Schütte, J; Knezevic, K; Lock, R B; Pimanda, J E; Göttgens, B

2013-06-01

LMO1 is a transcriptional regulator and a T-acute lymphoblastic leukaemia (T-ALL) oncogene. Although first identified in association with a chromosomal translocation in T-ALL, the ectopic expression of LMO1 occurs far more frequently in the absence of any known mutation involving its locus. Given that LMO1 is barely expressed in any haematopoietic lineage, and activation of transcriptional drivers in leukaemic cells is not well described, we investigated the regulation of this gene in normal haematopoietic and leukaemic cells. We show that LMO1 has two promoters that drive reporter gene expression in transgenic mice to neural tissues known to express endogenous LMO1. The LMO1 promoters display bivalent histone marks in multiple blood lineages including T-cells, and a 3' flanking region at LMO1 +57 contains a transcriptional enhancer that is active in developing blood cells in transgenic mouse embryos. The LMO1 promoters become activated in T-ALL together with the 3' enhancer, which is bound in primary T-ALL cells by SCL/TAL1 and GATA3. Taken together, our results show that LMO1 is poised for expression in normal progenitors, where activation of SCL/TAL1 together with a breakdown of epigenetic repression of LMO1 regulatory elements induces ectopic LMO1 expression that contributes to the development and maintenance of T-ALL.

Escape from R-peptide deletion in a γ-retrovirus

International Nuclear Information System (INIS)

Schneider, Irene C.; Eckhardt, Manon; Brynza, Julia; Collins, Mary K.; Cichutek, Klaus; Buchholz, Christian J.

2011-01-01

The R peptide in the cytoplasmic tail (C-tail) of γ-retroviral envelope proteins (Env) prevents membrane fusion before budding. To analyse its role in the formation of replication competent, infectious particles, we developed chimeric murine leukaemia viruses (MLV) with unmodified or R-peptide deleted Env proteins of the gibbon ape leukaemia virus (GaLV). While titres of these viruses were unaffected, R-peptide deficiency led to strongly impaired spreading. Most remarkably, we isolated an escape mutant which had restored an open reading frame for a C-terminal extension of the truncated C-tail. A reconstituted virus encoding this escape C-tail replicated in cell culture. In contrast to R-peptide deficient Env, particle incorporation of the escape Env was effective due to an enhanced protein expression and restored intracellular co-localisation with Gag proteins. Our data demonstrate that the R peptide not only regulates membrane fusion but also mediates efficient Env protein particle incorporation in γ-retrovirus infected cells.

Induction of myeloid leukaemia by whole-body single exposure of CBA male mice to X-rays

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Major, I R [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1979-12-01

A curvilinear dose response of myeloid leukaemia induction in CBA male mouse was obtained after single whole-body X-irradiation at about 3 months of age. This strain has a very low spontaneous incidence of the disease and no cases were found in the unirradiated controls. The incidence was independent of dose rate over the range used (4.2-552 rad/min). Diagnosis required histopathological examination of various body tissues, the gross anatomical changes being easily confused with other haemopoietic disorders, but a few cases were recognized in life from blood samples. Curve-fitting to various models based on theories of radiocarcinogenic mechanism is described.

A case of all-trans retinoic acid-induced myositis in the treatment of acute promyelocytic leukaemia.

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Chan, K H; Yuen, S L S; Joshua, D

2005-12-01

The use of all-trans retinoic acid (ATRA) is now standard therapy for the treatment of acute promyelocytic leukaemia (APML). There have been increasing reports of ATRA-induced myositis, with its frequent association with retinoic acid syndrome and Sweet's syndrome. We report a case of a young man with APML who developed ATRA-induced myositis characterized by unexplained fevers, bilateral leg swelling and a non-painful purpuric, petechial rash, with prompt resolution of symptoms and signs with high-dose steroids and cessation of ATRA. Rapid recognition of this adverse reaction and prompt institution of steroids is of prime importance given its potentially fatal course.

Pharmacokinetics and pharmacokinetic/pharmacodynamic associations of ofatumumab, a human monoclonal CD20 antibody, in patients with relapsed or refractory chronic lymphocytic leukaemia: a phase 1-2 study

DEFF Research Database (Denmark)

Coiffier, Bertrand; Losic, Nedjad; Rønn, Birgitte Biilmann

2010-01-01

The purpose of this phase 1-2 study was to investigate the association between the pharmacokinetic properties of ofatumumab, a human monoclonal CD20 antibody, and outcomes in 33 patients with relapsed/refractory chronic lymphocytic leukaemia receiving 4 weekly infusions of ofatumumab. The ofatumu...

Radiation-induced acute myeloid leukaemia in mice

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Bouffler, S.D.; Silver, A.R.J.; Cox, R. [National Radiological Protection Board, Chilton (United Kingdom)

2000-07-01

Ample epidemiological studies of human populations implicate ionizing radiation as a carcinogen and these quantitative studies provide the foundation for the core estimates of radiation cancer risk. The majority of the epidemiological data originate from situations of radiation exposure at high dose and high dose rate. The relevance of risk estimates based on such exposures to the more commonly encountered low dose and dose rate situation has been questioned frequently. Thus, there is a need to investigate and quantitate low dose and dose rate effects. A number of approaches may be considered, for example, very large scale epidemiology, very large scale animal experimentation; however, both of these present problems of a practical and/or ethical nature. A further possible approach is that of mechanistic modelling. This requires a fairly detailed understanding of neoplastic disease and how it develops post-irradiation. Many factors and variables have to be taken into consideration in mechanistic modelling approaches. Testing of mechanistic modelling schemes is best carried out using animal model systems. Acute myeloid leukaemia (AML) is a radiogenic cancer of significance in man and several good mouse models of the disease are available. Here, recent studies conducted at NRPB with the aim of elucidating the post-irradiation development of AML will be discussed. In particular three areas critical for developing a sound mechanistic model will be covered, definition of the initiating event; study of disease progression, this addresses the question of the frequency of conversion of initiated cells into the neoplastic state and the influence of genetic background on leukaemogenesis. (author)

Biomechanical Properties of Murine Meniscus Surface via AFM-based Nanoindentation

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Li, Qing; Doyran, Basak; Gamer, Laura W.; Lu, X. Lucas; Qin, Ling; Ortiz, Christine; Grodzinsky, Alan J.; Rosen, Vicki; Han, Lin

2015-01-01

This study aimed to quantify the biomechanical properties of murine meniscus surface. Atomic force microscopy (AFM)-based nanoindentation was performed on the central region, proximal side of menisci from 6- to 24-week old male C57BL/6 mice using microspherical tips (Rtip ≈ 5 μm) in PBS. A unique, linear correlation between indentation depth, D, and response force, F, was found on menisci from all age groups. This non-Hertzian behavior is likely due to the dominance of tensile resistance by the collagen fibril bundles on meniscus surface that are mostly aligned along the circumferential direction observed on 12-week old menisci. The indentation resistance was calculated as both the effective stiffness, Sind = dF/dD, and the effective modulus, Eind, via the isotropic Hertz model. Values of Sind and Eind were found to depend on indentation rate, suggesting the existence of poro-viscoelasticity. These values do not significantly vary with anatomical sites, lateral versus medial compartments, or mouse age. In addition, Eind of meniscus surface (e.g., 6.1 ± 0.8 MPa for 12 weeks of age, mean ± SEM, n = 13) was found to be significantly higher than those of meniscus surfaces in other species, and of murine articular cartilage surface (1.4 ± 0.1 MPa, n = 6). In summary, these results provided the first direct mechanical knowledge of murine knee meniscus tissues. We expect this understanding to serve as a mechanics-based benchmark for further probing the developmental biology and osteoarthritis symptoms of meniscus in various murine models. PMID:25817332

Increased Cerebral Tff1 Expression in Two Murine Models of Neuroinflammation

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Eva B Znalesniak

2016-11-01

Full Text Available Background/Aims: The trefoil factor family (TFF peptide TFF1 is a typical secretory product of the gastric mucosa and a very low level of expression occurs in nearly all regions of the murine brain. TFF1 possesses a lectin activity and binding to a plethora of transmembrane glycoproteins could explain the diverse biological effects of TFF1 (e.g., anti-apoptotic effect. It was the aim to test whether TFF expression is changed during neuroinflammation. Methods: Expression profiling was performed using semi-quantitative RT-PCR analyses in two murine models of neuroinflammation, i.e. Toxoplasma gondii-induced encephalitis and experimental autoimmune encephalomyelitis (EAE, the latter being the most common animal model of multiple sclerosis. Tff1 expression was also localized using RNA in situ hybridization histochemistry. Results: We report for the first time on a significant transcriptional induction in cerebral Tff1 expression in both T. gondii-induced encephalitis and EAE. In contrast, Tff2 and Tff3 expression were not altered. Tff1 transcripts were predominantly localized in the internal granular layer of the cerebellum indicating neuronal expression. Furthermore, also glial cells are expected to express Tff1. Characterization of both experimental models by expression profiling (e.g., inflammasome sensors, inflammatory cytokines, microglial marker Iba1, ependymin related protein 1 revealed differences concerning the expression of the inflammasome sensor Nlrp1 and interleukin 17a. Conclusion: The up-regulated expression of Tff1 is probably the result of a complex inflammatory process as its expression is induced by tumor necrosis factor α as well as interleukins 1β and 17. However on the transcript level, Tff1KO mice did not show any significant signs of an altered immune response after infection with T. gondii in comparison with the wild type animals.

Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

International Nuclear Information System (INIS)

Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M.; Dallapiccola, B.

1982-01-01

2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease. (author)

Current approach to the treatment of chronic myeloid leukaemia.

Science.gov (United States)

Pasic, Ivan; Lipton, Jeffrey H

2017-04-01

Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP). Copyright © 2017 Elsevier Ltd. All rights reserved.

[Virulence of Sporothrix globosa in murine models].

Science.gov (United States)

Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Three-dimensional alginate spheroid culture system of murine osteosarcoma.

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Akeda, Koji; Nishimura, Akinobu; Satonaka, Haruhiko; Shintani, Ken; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Kasai, Yuichi; Masuda, Koichi; Uchida, Atsumasa

2009-11-01

Osteosarcoma (OS) is the most common primary malignant tumor of the bone and often forms pulmonary metastases, which are the most important prognostic factor. For further elucidation of the mechanism underlying the progression and metastasis of human OS, a culture system mimicking the microenvironment of the tumor in vivo is needed. We report a novel three-dimensional (3D) alginate spheroid culture system of murine osteosarcoma. Two different metastatic clones, the parental Dunn and its derivative line LM8, which has a higher metastatic potential to the lungs, were encapsulated in alginate beads to develop the 3D culture system. The beads containing murine OS cells were also transplanted into mice to determine their metastatic potential in vivo. In this culture system, murine OS cells encapsulated in alginate beads were able to grow in a 3D structure with cells detaching from the alginate environment. The number of detaching cells was higher in the LM8 cell line than the Dunn cell line. In the in vivo alginate bead transplantation model, the rate of pulmonary metastasis was higher with LM8 cells compared with that of Dunn cells. The cell characteristics and kinetics in this culture system closely reflect the original malignant potential of the cells in vivo.

Dose-effect relationship of apoptosis induced by fission-neutron in murine thymocytes

International Nuclear Information System (INIS)

Yuan Bin; Li Liang; Xue Wencheng; Sun Jianmin; Wang Baoqin

2000-01-01

Objective: To investigate the effectiveness of high LET fission-neutron to induce apoptosis in murine thymocytes and to compare it with that of low LET 60 Co γ-ray. Methods: Apoptosis induction was studied qualitatively by light and transmission electron microscopy and DNA gel electrophoresis,also quantitatively by flow cytometry(FCM) and diphenylamine (DPA)methods. Results: DNA ladders of murine thymocytes were detectable, the typical apoptosis of thymocytes could be observed morphologically by means of light and electron microscopy at 6 h after fission-neutron irradiation with doses ranging from 0.5 to 5.0 Gy, meanwhile the percentages of apoptosis increased with increasing doses. After exposure to γ-rays with doses ranging from 1.0 to 30 Gy, the experimental results were similar to those from neutron radiation. The incidence of apoptosis peaked at about 20 Gy, the percentages did not increase further when doses increased. Conclusion: Apoptosis of murine thymocytes can be induced when mice are exposed to either fission-neutron (0.5-5.0 Gy) or to γ-ray (1-30 Gy). Although the relationship between apoptosis and radiation doses is similar, the percentage of apoptosis induced by neutron irradiation is higher than that induced by γ-irradiation. The RBE values of fission-neutron for inducing apoptosis murine thymocytes are 2.09 (by FCM method) and 2.37 (by DPA method), respectively. These results also suggest that fission-neutron-induced murine immune tissue is more severe than that induced by γ-rays at several hours post-irradiation and this might be the basis for heavy damage to immune tissues induced by fission-neutron-irradiation in later period

Azithromycin prophylaxis and treatment of murine toxoplasmosis.

Science.gov (United States)

Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

2005-03-01

To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

Whole-exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia.

Science.gov (United States)

Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Okuno, Yusuke; Yamato, Genki; Hara, Yusuke; Nagata, Yasunobu; Chiba, Kenichi; Tanaka, Hiroko; Terui, Kiminori; Kato, Motohiro; Park, Myoung-Ja; Ohki, Kentaro; Shimada, Akira; Takita, Junko; Tomizawa, Daisuke; Kudo, Kazuko; Arakawa, Hirokazu; Adachi, Souichi; Taga, Takashi; Tawa, Akio; Ito, Etsuro; Horibe, Keizo; Sanada, Masashi; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

2016-11-01

Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole-exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations. We also revealed intratumoural heterogeneities in many patients, implicating multiple clonal evolution events in the development of AML. Furthermore, targeted deep sequencing in 182 paediatric AML patients identified three major categories of recurrently mutated genes: cohesion complex genes [STAG2, RAD21 and SMC3 in 17 patients (8·3%)], epigenetic regulators [ASXL1/ASXL2 in 17 patients (8·3%), BCOR/BCORL1 in 7 patients (3·4%)] and signalling molecules. We also performed WES in four patients with relapsed AML. Relapsed AML evolved from one of the subclones at the initial phase and was accompanied by many additional mutations, including common driver mutations that were absent or existed only with lower allele frequency in the diagnostic samples, indicating a multistep process causing leukaemia recurrence. © 2016 John Wiley & Sons Ltd.

lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis

DEFF Research Database (Denmark)

Brünner, N; Thompson, E W; Spang-Thomsen, M

1992-01-01

in the animals by usual histological procedures would require extensive sectioning of the whole animal. To overcome this problem, we transduced human breast cancer cells with a replication-defective Moloney murine leukaemia retroviral vector (M-MuLV) containing both neoR (neomycin resistance) and lacZ genes...... but not the surrounding mouse tissue on either whole tissue blocks or histological sections. The staining procedure was highly sensitive, allowing detection of microfoci of human cancer cells, and quantitative estimation of the metastatic capacity of the cells. These results indicate that lacZ transduction of human...

Chimeric anti-tenascin antibody 81C6: Increased tumor localization compared with its murine parent

International Nuclear Information System (INIS)

Zalutsky, Michael R.; Archer, Gary E.; Garg, Pradeep K.; Batra, Surinder K.; Bigner, Darell D.

1996-01-01

When labeled using the Iodogen method, a chimeric antibody composed of the human IgG 2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current study, three paired-label experiments were performed in athymic mice with subcutaneous D-54 MG human glioma xenografts to evaluate further the properties of radioiodinated chimeric 81C6. These studies demonstrated that (a) the enhanced tumor uptake of chimeric 81C6 is specific; (b) when labeling was performed using N-succinimidyl 3-iodobenzoate, chimeric 81C6 again showed preferential accumulation in tumor compared with murine 81C6; and (c) the tumor uptake advantage observed previously with murine 81C6 for N-succinimidyl 3-iodobenzoate compared with Iodogen labeling did not occur with chimeric 81C6

Splenic artery pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase

DEFF Research Database (Denmark)

Larsen, Cæcilie Crawley; Laursen, Christian B; Dalby, Kasper

2014-01-01

Acute pancreatitis is a rare phenomenon in children but its incidence seems to be increasing. In children, it is generally caused due to systemic illness, biliary disease, trauma, idiopathy and side effects of medicines like L-aspariginase. Acute pancreatitis is difficult to diagnose in children ...... pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase. He presented with fever, irritability and pain in his left groin region....

Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.

Science.gov (United States)

Wang, Gang G; Song, Jikui; Wang, Zhanxin; Dormann, Holger L; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J; Allis, C David

2009-06-11

Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

New Complex Chromosomal Translocation in Chronic Myeloid Leukaemia: t(9;18;22(q34;p11;q11

Directory of Open Access Journals (Sweden)

Abdeljabar El Andaloussi

2007-01-01

Full Text Available A Chronic myeloid leukaemia (CML case with a new complex t(9;18;22(q34;p11;q11 of a 29-year-old man is being reported. For the first time, this translocation has been characterized by karyotype complemented with fluorescence in situ hybridization (FISH. In CML, the complex and standard translocations have the same prognosis. The patient was treated with standard initial therapy based on hydroxyurea before he died due to heart failure four months later. Our finding indicates the importance of combined cytogenetic analysis for diagnosis and guidance of treatment in clinical diagnosis of CML.

Novel Application of Micro-Computerized Tomography for Morphologic Characterization of the Murine Penis.

Science.gov (United States)

O'Neill, Marisol; Huang, Gene O; Lamb, Dolores J

2017-12-01

The murine penis model has enriched our understanding of anomalous penile development. The morphologic characterization of the murine penis using conventional serial sectioning methods is labor intensive and prone to errors. To develop a novel application of micro-computerized tomography (micro-CT) with iodine staining for rapid, non-destructive morphologic study of murine penis structure. Penises were dissected from 10 adult wild-type mice and imaged using micro-CT with iodine staining. Images were acquired at 5-μm spatial resolution on a Bruker SkyScan 1272 micro-CT system. After images were acquired, the specimens were washed of any remaining iodine and embedded in paraffin for conventional histologic examination. Histologic and micro-CT measurements for all specimens were made by 2 independent observers. Measurements of penile structures were made on virtual micro-CT sections and histologic slides. The Lin concordance correlation coefficient demonstrated almost perfect strength of agreement for interobserver variability for histologic section (0.9995, 95% CI = 0.9990-0.9997) and micro-CT section (0.9982, 95% CI = 0.9963-0.9991) measurements. Bland-Altman analysis for agreement between the 2 modalities of measurement demonstrated mean differences of -0.029, 0.022, and -0.068 mm for male urogenital mating protuberance, baculum, and penile glans length, respectively. There did not appear to be a bias for overestimation or underestimation of measured lengths and limits of agreement were narrow. The enhanced ability offered by micro-CT to phenotype the murine penis has the potential to improve translational studies examining the molecular pathways contributing to anomalous penile development. The present study describes the first reported use of micro-CT with iodine staining for imaging the murine penis. Producing repeated histologic sections of identical orientation was limited by inherent imperfections in mounting and tissue sectioning, but this was

Leukaemia and non-Hodgkin's lymphoma: incidence in children and young adults resident in the Dounreay area of Caithness, Scotland in 1968-91

International Nuclear Information System (INIS)

Black, R.J.; Sharp, L.; Harkness, E.F.; McKinney, P.A.; Leeds Univ.

1994-01-01

The study objective was to review the incidence of leukaemia and non-Hodgkin's lymphoma in children and young adults in the area less than 25 km from the Dounreay nuclear installation and the remainder of the Kirkwall postcode area in the full time period for which data are now available (1968-91), and to determine whether the excess incidence reported in the period up to 1984 has continued in subsequent years. (author)

Preclinical targeted alpha therapy for melanoma, leukaemia, breast, prostate and colorectal cancers

International Nuclear Information System (INIS)

Allen, B.J.; Rizvi, S.; Li, Y.; Tian, Z.; University of Wollongong, NSW; Ranson, M.

2000-01-01

Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micro-metastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 are produced by accelerator and generator respectively and are chelated to a cancer specific monoclonal antibody, peptide or protein to form the alpha-conjugates (AC) against melanoma, leukaemia, breast, prostate and colorectal cancers. These ACs are tested for stability, specificity and cytotoxicity in vitro and in vivo using several nude mouse models. The Australian TAT program began some 7 years at ANSTO but was still-born. Later, TAT had a second wind at St George Hospital, where collaborative research led to the investigation of Tb-149 as a new alpha emitting radionuclide. Subsequently, increased emphasis was placed on the Ac-225 generator to produce Bi-213. Although in-house funding was terminated in 1998, the project received its third wind with local fund raising in the Shire and a US grant in 1999, and continues to break new ground in the control of the above cancers. Stable alpha-ACs are produced which are highly specific and cytotoxic in vitro against melanoma, leukaemia, colorectal, breast and prostate cancers. Subcutaneous inoculation of 11.5 million cells into the flanks of nude mice causes tumours to grow in all mice. The tumour growth is compared with untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of melanoma xenografts and gives almost complete control of breast cancer tumour growth in the primary site and metastatic invasion of the lymph nodes. These results point to the application of local

Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis ...

African Journals Online (AJOL)

NO Al-Harbi, SA Bahashwan, MS Aboonq, MA Ramadan, AA Bahashwan. Abstract. Purpose: To evaluate the safety, pharmacological effect and mechanism of action of an antifibrotic compound, safironil (SAF)/praziquantel (PZQ) combination on reversal of liver fibrogenesis in chronic murine Schistosomiasis mansoni.

Assignment of the murine protein kinase gene DLK to chromosome 15 in the vicinity of the bt/Koa locus by genetic linkage analysis

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Toshio; Yanagisawa, Masahiro; Matsubara, Nobumichi [Tokyo Univ. (Japan)] [and others

1997-03-01

We have cloned protein kinase genes from murine primordial germ cell-derived EG cells by a PCR-based strategy using degenerate primers corresponding to the conserved sequences in the catalytic domain of protein kinases. One of these clones, designated Gek2 (germ cell kinase 2), was used as a probe for screening of a mouse brain cDNA library and obtained clones contained an entire coding sequence. Comparison of the sequence of Gek2 with those in databases revealed that it was identical to a previously reported protein kinase gene, DLK. 8 refs., 1 fig.

A novel murine model for evaluating bovine papillomavirus prophylactics/therapeutics for equine sarcoid-like tumours.

Science.gov (United States)

Bogaert, Lies; Woodham, Andrew W; Da Silva, Diane M; Martens, Ann; Meyer, Evelyne; Kast, W Martin

2015-09-01

Equine sarcoids are highly recurrent bovine papillomavirus (BPV)-induced fibroblastic neoplasms that are the most common skin tumours in horses. In order to facilitate the study of potential equine sarcoid prophylactics or therapeutics, which can be a slow and costly process in equines, a murine model for BPV-1 protein-expressing equine sarcoid-like tumours was developed in mice through stable transfection of BPV-1 E5 and E6 in a murine fibroblast tumour cell line (K-BALB). Like equine sarcoids, these murine tumour cells (BPV-KB) were of fibroblast origin, were tumorigenic and expressed BPV-1 proteins. As an initial investigation of the preclinical potential of this tumour model for equine sarcoids prophylactics, mice were immunized with BPV-1 E5E6 Venezuelan equine encephalitis virus replicon particles, prior to BPV-KB challenge, which resulted in an increased tumour-free period compared with controls, indicating that the BPV-KB murine model may be a valuable preclinical alternative to equine clinical trials.

Ponatinib versus imatinib for newly diagnosed chronic myeloid leukaemia: an international, randomised, open-label, phase 3 trial.

Science.gov (United States)

Lipton, Jeffrey H; Chuah, Charles; Guerci-Bresler, Agnès; Rosti, Gianantonio; Simpson, David; Assouline, Sarit; Etienne, Gabriel; Nicolini, Franck E; le Coutre, Philipp; Clark, Richard E; Stenke, Leif; Andorsky, David; Oehler, Vivian; Lustgarten, Stephanie; Rivera, Victor M; Clackson, Timothy; Haluska, Frank G; Baccarani, Michele; Cortes, Jorge E; Guilhot, François; Hochhaus, Andreas; Hughes, Timothy; Kantarjian, Hagop M; Shah, Neil P; Talpaz, Moshe; Deininger, Michael W

2016-05-01

Ponatinib has shown potent activity against chronic myeloid leukaemia that is resistant to available treatment, although it is associated with arterial occlusion. We investigated whether this activity and safety profile would result in superior outcomes compared with imatinib in previously untreated patients with chronic myeloid leukaemia. The Evaluation of Ponatinib versus Imatinib in Chronic Myeloid Leukemia (EPIC) study was a randomised, open-label, phase 3 trial designed to assess the efficacy and safety of ponatinib, compared with imatinib, in newly diagnosed patients with chronic-phase chronic myeloid leukaemia. Patients from 106 centres in 21 countries were randomly assigned (1:1, with stratification by Sokal score at diagnosis) using an interactive voice and web response system to receive oral ponatinib (45 mg) or imatinib (400 mg) once daily until progression, unacceptable toxicity, or other criteria for withdrawal were met. Eligible patients were at least 18 years of age, within 6 months of diagnosis, and Philadelphia chromosome-positive by cytogenetic assessment, with Eastern Cooperative Oncology Group performance status of 0-2, and had not previously been treated with tyrosine kinase inhibitors. The primary endpoint was major molecular response at 12 months. Patients who remained on study and had molecular assessments at specified timepoints were studied at those timepoints. Safety analyses included all treated patients, as per study protocol. This trial is registered with ClinicalTrials.gov, number NCT01650805. Between Aug 14, 2012, and Oct 9, 2013, 307 patients were randomly assigned to receive ponatinib (n=155) or imatinib (n=152). The trial was terminated early, on Oct 17, 2013, following concerns about vascular adverse events observed in patients given ponatinib in other trials. Trial termination limited assessment of the primary endpoint of major molecular response at 12 months, as only 13 patients in the imatinib group and ten patients in the

A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

Science.gov (United States)

Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

2017-07-01

To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

International Nuclear Information System (INIS)

Chattopadhyay, Kausik; Ramagopal, Udupi A.; Nathenson, Stanley G.; Almo, Steven C.

2009-01-01

1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL

1.8 Å structure of murine GITR ligand dimer expressed in Drosophila melanogaster S2 cells

Energy Technology Data Exchange (ETDEWEB)

Chattopadhyay, Kausik [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Ramagopal, Udupi A. [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Nathenson, Stanley G., E-mail: nathenso@aecom.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Almo, Steven C., E-mail: nathenso@aecom.yu.edu [Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

2009-05-01

1.8 Å X-ray crystal structure of mouse GITRL expressed in D. melanogaster S2 cells shows an identical ‘strand-exchanged’ dimeric assembly similar to that observed previously for the E. coli-expressed protein. Glucocorticoid-induced TNF receptor ligand (GITRL), a prominent member of the TNF superfamily, activates its receptor on both effector and regulatory T cells to generate critical costimulatory signals that have been implicated in a wide range of T-cell immune functions. The crystal structures of murine and human orthologs of GITRL recombinantly expressed in Escherichia coli have previously been determined. In contrast to all classical TNF structures, including the human GITRL structure, murine GITRL demonstrated a unique ‘strand-exchanged’ dimeric organization. Such a novel assembly behavior indicated a dramatic impact on receptor activation as well as on the signaling mechanism associated with the murine GITRL costimulatory system. In this present work, the 1.8 Å resolution crystal structure of murine GITRL expressed in Drosophila melanogaster S2 cells is reported. The eukaryotic protein-expression system allows transport of the recombinant protein into the extracellular culture medium, thus maximizing the possibility of obtaining correctly folded material devoid of any folding/assembly artifacts that are often suspected with E. coli-expressed proteins. The S2 cell-expressed murine GITRL adopts an identical ‘strand-exchanged’ dimeric structure to that observed for the E. coli-expressed protein, thus conclusively demonstrating the novel quaternary structure assembly behavior of murine GITRL.

Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

International Nuclear Information System (INIS)

Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

1986-01-01

The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

Protective effects of astaxanthin from Paracoccus carotinifaciens on murine gastric ulcer models.

Science.gov (United States)

Murata, Kenta; Oyagi, Atsushi; Takahira, Dai; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Ishibashi, Takashi; Hara, Hideaki

2012-08-01

The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol- and acidified aspirin-induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1-diphenyl-2-picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models. Copyright © 2011 John Wiley & Sons, Ltd.

Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

DEFF Research Database (Denmark)

Lundorf, Mikkel D.; Pedersen, Finn Skou; O'Hara, Bryan

1998-01-01

Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch...

PERCENTAGE OF CIPROFLOXACIN-RESISTANT STRAINS OF CITROBACTER FREUNDII IN ACUTE LEUKAEMIA PATIENTS WITH CIPROFLOXACIN PROPHYLAXIS

Directory of Open Access Journals (Sweden)

Rika Strauch

2004-12-01

Full Text Available Background. Authors tried to determine an efficiency of ciprofloxacin as infection prophylaxis in patients with acute leukaemia treated at the Department of Haematology in Clinical Center of Ljubljana. Due to cytotoxic chemotherapy, aplasia of bone marrow is inevitable. Therefore, these patients are at high risk for bacterial and fungal infection. The authors have noticed a rise in the number of ciprofloxacin-resistant strains of Citrobacter freundii and decided to find out if ciprofloxacin is still usable in this setting.Patients and methods. 45 patients with acute leukaemia were admitted to the Department of Haematology in the Clinical Center of Ljubljana during the year 2001 and 2002. All the patients received ciprofloxacin 2 × 500 mg on a daily basis. Citrobacter freundii was isolated in 11 patients, to whom we determined the proportion of ciprofloxacin-resistant strains of Citrobacter freundii and other Enterobacteriaceae. Susceptibility testing was done by the NCCCLS standards by the disc diffusion method and minimal inhibitory concentration.Results. C. freundii was isolated in 11 patients with AL. Extended-spectrum beta-lactamases (ESBL C. freundii was isolated in 6 patients (54.5%. Ciprofloxacin-resistant C. freundii was isolated in 6 patients (54.5%. Six patients (54.5% had ciprofloxacin-resistant C. freundii which was ESBL positive at the same time. In AL patients with C. freundii (n = 11 almost half of isolated bacteria were Gram negative bacilli (45.2%, n = 292, mostly from the family of Enterobacteriaceae. More than half of enterobacteria were ciprofloxacin-resistant, one third of them were also ESBL positive. Out of 131 enterobacteria, C. freundii was isolated 37 times. (28.2%.Conclusions. C. freundii was isolated in one fourth of AL patients. Half of the isolates were ciprofloxacin-resistant. The same was true for isolated enterobacteria. Almost all of ciprofloxacin-resistant bacteria were ESBL positive. There is a question

Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

International Nuclear Information System (INIS)

Schwab, Felix; Schleede, Simone; Hahn, Dieter

2013-01-01

Purpose: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and Methods: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. Results: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p = 0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p = 0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p = 0.03). Conclusion: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI. (orig.)

Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

International Nuclear Information System (INIS)

Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok

2000-01-01

The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21 WAF1/CIP1 . Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 WAF1/CIP1 . Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21 WAF1/CIP1

Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

Energy Technology Data Exchange (ETDEWEB)

Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

2000-12-01

The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21{sup WAF1/CIP1}. Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 {sup WAF1/CIP1}. Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21{sup WAF1/CIP1}.

Murine mammary tumor virus pol-related sequences in human DNA: characterization and sequence comparison with the complete murine mammary tumor virus pol gene

International Nuclear Information System (INIS)

Deen, K.C.; Sweet, R.W.

1986-01-01

Sequences in the human genome with homology to the murine mammary tumor virus (MMTV) pol gene were isolated from a human phage library. Ten clones with extensive pol homology were shown to define five separate loci. These loci share common sequences immediately adjacent to the pol-like segments and, in addition, contain a related repeat element which bounds this region. This organization is suggestive of a proviral structure. The authors estimate that the human genome contains 30 to 40 copies of these pol-related sequences. The pol region of one of the cloned segments (HM16) and the complete MMTV pol gene were sequenced and compared. The nucleotide homology between these pol sequences is 52% and is concentrated in the terminal regions. The MMTV pol gene contains a single long open reading frame encoding 899 amino acids and is demarcated from the partially overlapping putative gag gene by termination codons and a shift in translational reading frame. The pol sequence of HM16 is multiply terminated but does contain open reading frames which encode 370, 105, and 112 amino acids residues in separate reading frames. The authors deduced a composite pol protein sequence for HM16 by aligning it to the MMTV pol gene and then compared these sequences with other retroviral pol protein sequences. Conserved sequences occur in both the amino and carboxyl regions which lie within the polymerase and endonuclease domains of pol, respectively

Potentiation of electrochemotherapy by intramuscular IL-12 gene electrotransfer in murine sarcoma and carcinoma with different immunogenicity

International Nuclear Information System (INIS)

Sedlar, Ales; Dolinsek, Tanja; Markelc, Bostjan; Prosen, Lara; Kranjc, Simona; Bosnjak, Masa; Blagus, Tanja; Cemazar, Maja; Sersa, Gregor

2012-01-01

Electrochemotherapy provides good local tumor control but requires adjuvant treatment for increased local response and action on distant metastasis. In relation to this, intramuscular interleukin-12 (IL-12) gene electro-transfer, which provides systemic shedding of IL-12, was combined with local electrochemotherapy with cisplatin. Furthermore, the dependence on tumor immunogenicity and immunocompetence of the host on combined treatment response was evaluated. Sensitivity of SA-1 sarcoma and TS/A carcinoma cells to electrochemotherapy with cisplatin was tested in vitro. In vivo, intratumoral electrochemotherapy with cisplatin (day 1) was combined with a single (day 0) or multiple (days 0, 2, 4) intramuscular murine IL-12 (mIL-12) gene electrotransfer. The antitumor effectiveness of combined treatment was evaluated on immunogenic murine SA-1 sarcoma in A/J mice and moderately immunogenic murine TS/A carcinoma, in immunocompetent BALB/c and immunodeficient SCID mice. Electrochemotherapy in vitro resulted in a similar IC 50 values for both sarcoma and carcinoma cell lines. However, in vivo electrochemotherapy was more effective in the treatment of sarcoma, the more immunogenic of the tumors, resulting in a higher log cell kill, longer specific tumor growth delay, and also 17% tumor cures compared to carcinoma where no tumor cures were observed. Adjuvant intramuscular mIL-12 gene electrotransfer increased the log cell kill in both tumor models, potentiating the specific tumor growth delay by a factor of 1.8-2 and increasing tumor cure rate by approximately 20%. In sarcoma tumors, the potentiation of the response by intramuscular mIL-12 gene electrotransfer was dose-dependent and also resulted in a faster onset of tumor cures. Comparison of the carcinoma response to the combined treatment modality in immunocompetent and immunodeficient mice demonstrated that the immune system is needed both for increased cell kill and for attaining tumor cures. Based on the comparison of

Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

DEFF Research Database (Denmark)

Raja, Raheel A; Schmiegelow, Kjeld; Albertsen, BK

2014-01-01

L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis...... within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO...... ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m(2) /dose at 2-6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed...

Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

Directory of Open Access Journals (Sweden)

K. Brandt

2010-10-01

Full Text Available Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun, E-mail: xuejunshao@hotmail.com

2015-04-03

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

Science.gov (United States)

Park, Myoung-Ja; Taki, Tomohiko; Oda, Megumi; Watanabe, Tomoyuki; Yumura-Yagi, Keiko; Kobayashi, Ryoji; Suzuki, Nobuhiro; Hara, Junichi; Horibe, Keizo; Hayashi, Yasuhide

2009-04-01

Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).

Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.

Science.gov (United States)

Ziegler, Kathryn M; Considine, Robert V; True, Eben; Swartz-Basile, Deborah A; Pitt, Henry A; Zyromski, Nicholas J

2016-04-01

Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p TGP-47 cells. These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Antigen-specific murine T cell clones produce soluble interleukin 2 receptor on stimulation with specific antigens

International Nuclear Information System (INIS)

Wagner, D.K.; York-Jolley, J.; Malek, T.R.; Berzofsky, J.A.; Nelson, D.L.

1986-01-01

In this study, monoclonal antibodies were used to the murine IL 2 receptor (IL 2R) termed 3C7 and 7D4, which bind to different epitopes on the murine IL 2R, to develop an ELISA to measure soluble murine IL 2R. Surprisingly, stimulated murine spleen cells not only expressed cell-associated IL 2R, but also produced a considerable level of cellfree IL 2R in the culture supernatant fluid. To assess the fine specificity of this response, myoglobin-immune murine T cell clones were stimulated with appropriate or inappropriate antigen and syngeneic or allogeneic presenting cells. Proliferation, measured by [ 3 H] thymidine incorporation, and levels of soluble IL 2R were determined at day 4. The production of soluble IL2R displayed the same epitope fine specificity, genetic restriction, and antigen dose-response as the proliferative response. Indeed, in some cases there was sharper discrimination of epitope specificity and genetic restriction with the soluble IL 2R levels. There was also reproducible clone-to-clone variation in the amount of soluble receptor produced in response to antigen among 12 T cell clones and lines tested. In time course experiments, proliferation was greatest at day 3, whereas soluble IL 2R levels continued to rise in subsequent days. To the authors' knowledge, this is the first demonstration of release of secretion of soluble IL 2R by murine T cells, and the first demonstration of the fine specificity and genetic restriction of the induction of soluble IL 2R by specific antigen

Clofarabine in the treatment of poor risk acute myeloid leukaemia.

LENUS (Irish Health Repository)

Krawczyk, Janusz

2010-09-01

Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

Directory of Open Access Journals (Sweden)

Ryan W Carroll

Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

The Role of the MHV Receptor and Related Glycoproteins in Murine Hepatitis Virus Infection of Murine Cell Lines

Science.gov (United States)

1995-04-13

vaccinia virus-T7 RNA polymerase s y stem for e xpression of target genes . Mol . Cell . BioI . 7 : 2538-2544 . Gagneten , S ., Gout , 0 ., Dubois-Dalcq...glycoprotein. These results showed f or the first time that two murine CEA- related genes can be co-expressed in some cell lines from inbred mice...49 Southern Hybridization ................ . ............ 50 Subcloning of PCR Products and Gene Cloning ........ 51 Growth

Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

LENUS (Irish Health Repository)

Monk, Ian R

2010-01-01

Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

The TEL-AML1 real-time quantitative polymerase chain reaction (PCR) might replace the antigen receptor-based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia

NARCIS (Netherlands)

de Haas, V.; Breunis, W. B.; dee, R.; Verhagen, O. J. H. M.; Kroes, W.; van Wering, E. R.; van Dongen, J. J. M.; van den Berg, H.; van der Schoot, C. E.

2002-01-01

Prospective studies in children with B-precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene rearrangements as targets can be used to identify patients

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

International Nuclear Information System (INIS)

Buchmann, I.; Helisch, A.; Bartenstein, P.; Meyer, R.G.; Herr, W.

2005-01-01

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

An effective modestly intensive re-induction regimen with bortezomib in relapsed or refractory paediatric acute lymphoblastic leukaemia.

Science.gov (United States)

Kaspers, Gertjan J L; Niewerth, Denise; Wilhelm, Bram A J; Scholte-van Houtem, Peggy; Lopez-Yurda, Marta; Berkhof, Johannes; Cloos, Jacqueline; de Haas, Valerie; Mathôt, Ron A; Attarbaschi, Andishe; Baruchel, André; de Bont, Eveline S; Fagioli, Franca; Rössig, Claudia; Klingebiel, Thomas; De Moerloose, Barbara; Nelken, Brigitte; Palumbo, Giuseppe; Reinhardt, Dirk; Rohrlich, Pierre-Simon; Simon, Pauline; von Stackelberg, Arend; Zwaan, Christian Michel

2018-05-01

This trial explored the efficacy of re-induction chemotherapy including bortezomib in paediatric relapsed/refractory acute lymphoblastic leukaemia. Patients were randomized 1:1 to bortezomib (1.3 mg/m 2 /dose) administered early or late to a dexamethasone and vincristine backbone. Both groups did not differ regarding peripheral blast count on day 8, the primary endpoint. After cycle 1, 8 of 25 (32%) patients achieved complete remission with incomplete blood count recovery, 7 (28%) a partial remission and 10 had treatment failure. Most common grade 3-4 toxicities were febrile neutropenia (31%) and pain (17%). Bortezomib was safely combined with vincristine. Bortezomib rarely penetrated the cerebrospinal fluid. © 2018 John Wiley & Sons Ltd.

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10)

DEFF Research Database (Denmark)

Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin

2016-01-01

BACKGROUND: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less....... The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. FINDINGS: 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included...

Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

Energy Technology Data Exchange (ETDEWEB)

Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

1990-05-01

The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

Pathogenetical Characterization of MHV-76: a Spontaneous 9.5-Kilobase-Deletion Mutant of Murine Lymphotropic Gammaherpesvirus 68

Directory of Open Access Journals (Sweden)

A. Chalupková

2008-01-01

Full Text Available Murid gammaherpesvirus 4 (MuHV-4 provides a small animal model for the study of animal gammaherpesviruses. MHV-76 is a spontaneous deletion mutant as compared to the prototype strain of MuHV-4 (MHV-68. The MHV-76 genome lacks at least 12 ORFs at the 5'-end including the M1, M2, M3 and M4 genes and the eight viral t-RNA-like genes. During 27 months of experimental infection of BALB/c mice we followed their pathogenesis, immunology and oncogenic properties. After intranasal infection with MHV-76, the infectious virus was detected in the blood, thymus, lungs, heart, liver, spleen, bone marrow, peritoneal macrophages, lymph nodes, kidneys, mammary glands, brain and small intestine. The acute phase of infection was attenuated, but the chronic phase of infection was accompanied with long persistence of virus not only in the lymphatic, but in the neural and glandular tissue, as well. In comparison with the prototype strain, splenomegaly and lymphocytosis was very low. Surprisingly, during 27 months the BALB/c mice infected with MHV-76 did not develop lymphoproliferative disorders like infectious mononucleosis, leukaemia or lymphomas. We hypothesize that the M4 gene, present in all oncogenic MHV isolates, might be related (directly or indirectly to their transforming properties.

Murine alpha1-adrenoceptor subtypes. I. Radioligand binding studies

NARCIS (Netherlands)

Yang, M.; Reese, J.; Cotecchia, S.; Michel, M. C.

1998-01-01

Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with

Signaling pathways regulating murine pancreatic development

DEFF Research Database (Denmark)

Serup, Palle

2012-01-01

The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

The time factor in dose-effect relationships

International Nuclear Information System (INIS)

Jones, H.B.; Grendon, A.; White, M.R.; California Univ., Berkeley

1976-01-01

The assumption that carcinogenic risk is proportional to dose fails to consider that probable time of actual cancer incidence. The time lag between exposure and carcinogenic effect for radiation and chemical agents varies as Dosesup(-1/n), with napproximately3. A model is offered explaining that concentration of initially altered cells depends on dose, whereas their chance for development into tumours on their proximity, which varies as Dsup(-1/3). Because of biological variability, n has a range of values. The model implies that tumours resulting from a single exposure should be closely distributed in time, producing a pulse of cases and subsequently being essentially without effect. Testing of the Dsup(-1/3) rule was extended and its model, by further refinement of methods, applied to radiogenic leukaemia risk and to the effect of urethan in inducing lung tumours in mice with and without radiation exposure as a possible cocarcinogen. Radiation did not affect the tumour yield from urethan in mice. Radiogenic leukaemia and lung tumours induced by urethan both occur in proportion to exposure, but the time of their occurrence is limited to a short interval in relation to life span. Similarly, in murine or in human radiogenic leukaemia, leukaemia risk occurs in proportion to exposure, but the time of occurrences is limited to a short interval in relation to life span. In both sets of observations, as well as in other test systems of carcinogenesis, the peak of occurrence or the mean latent period is roughly inversely related to Dsup(-1/3). Applied to lung tumours and leukaemia, the spread of cases about the peak incidence was found to be typically less than a fifth of the life span. Exposure risks do not continue to act over life span. Neoplastic disease risk from carcinogens levels too low to be tested experimentally, theoretically usually lies beyond the life span. The social and economic consequences of a theoretically calculated number of deaths due to those

Temporal Regulation of fim Genes in Uropathogenic Escherichia coli during Infection of the Murine Urinary Tract

Directory of Open Access Journals (Sweden)

William R. Schwan

2017-01-01

Full Text Available Uropathogenic Escherichia coli (UPEC adhere to cells in the human urinary tract via type 1 pili that undergo phase variation where a 314-bp fimS DNA element flips between Phase-ON and Phase-OFF orientations through two site-specific recombinases, FimB and FimE. Three fim-lux operon transcriptional fusions were created and moved into the clinical UPEC isolate NU149 to determine their temporal regulation in UPEC growing in the urinary tract. Within murine urinary tracts, the UPEC strains demonstrated elevated transcription of fimA and fimB early in the infection, but lower transcription by the fifth day in murine kidneys. In contrast, fimE transcription was much lower than either fimA or fimB early, increased markedly at 24 h after inoculation, and then dropped five days after inoculation. Positioning of fimS was primarily in the Phase-ON position over the time span in UPEC infected bladders, whereas in UPEC infected murine kidneys the Phase-OFF orientation was favored by the fifth day after inoculation. Hemagglutination titers with guinea pig erythrocytes remained constant in UPEC growing in infected murine bladders but fell substantially in UPEC infected kidneys over time. Our results show temporal in vivo regulation of fim gene expression in different environmental niches when UPEC infects the murine urinary tract.

Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations

DEFF Research Database (Denmark)

Farooqui, Mohammed Z H; Valdez, Janet; Martyr, Sabrina

2015-01-01

BACKGROUND: Patients with chronic lymphocytic leukaemia (CLL) with TP53 aberrations respond poorly to first-line chemoimmunotherapy, resulting in early relapse and short survival. We investigated the safety and activity of ibrutinib in previously untreated and relapsed or refractory CLL with TP53...... aberrations. METHODS: In this investigator-initiated, single-arm phase 2 study, we enrolled eligible adult patients with active CLL with TP53 aberrations at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Patients received 28-day cycles of ibrutinib 420 mg orally once daily until...... in one (2%) patient. INTERPRETATION: The activity and safety profile of single-agent ibrutinib in CLL with TP53 aberrations is encouraging and supports its consideration as a novel treatment option for patients with this high-risk disease in both first-line and second-line settings. FUNDING: Intramural...

HSE investigation of leukaemia and other cancers in the children of male workers at Sellafield

International Nuclear Information System (INIS)

1994-01-01

This report presents two findings of the U.K. Health and Safety Executive study group responsible for examining the conclusions of the Gardner Report that ''the raised incidence of leukaemia particularly, and non-Hodgkin's lymphoma, among children near Sellafield was associated with paternal employment and recorded external dose of whole body penetrating radiation during work at the plant before conception''. The HSE report is divided into three:- the Case-only study and the Radiation Dose study, concerned with the 11 case fathers who had worked at Sellafield. The third part, the Case-control study, is an epidemiological study which seeks to identify all cancer cases diagnosed before the age of 25, where the children concerned had been born in West Cumbria to fathers who were Sellafield employees. The search included the whole country from January 1980 to September 1989. (UK)

Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

DEFF Research Database (Denmark)

Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

2010-01-01

antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

Efficacy of DSP30-IL2/TPA for detection of cytogenetic abnormalities in chronic lymphocytic leukaemia/small lymphocytic lymphoma.

Science.gov (United States)

Holmes, P J; Peiper, S C; Uppal, G K; Gong, J Z; Wang, Z-X; Bajaj, R

2016-10-01

Chronic lymphocytic leukaemia (CLL) is the most prevalent leukaemia in the Western Hemisphere. Cytogenetic abnormalities in CLL are used for diagnosis, prognosis and treatment. However, detecting these is difficult because mature B cells do not readily divide in culture. Here, we present data on two mitogen cocktails: CpG-oligonucleotide DSP30/Interleukin-2 (IL-2) and DSP30/IL-2 in combination with 12-O-tetradecanoylphorbol-13-acetate (TPA). We analysed 165 cases of CLL with FISH and cytogenetics from January 2011 to June 2013. In 2011, three cultures were set-up: unstimulated, DSP30/IL-2-stimulated and TPA-stimulated. In 2012-2013, two cultures were set-up: unstimulated and stimulated with TPA/DSP30/IL-2. In 2011, FISH had a detection rate of 91% and cytogenetics using DSP30/IL2 had a detection rate of 91% (n = 22). In 2012-2013, FISH had a detection rate of 79% and cytogenetics using TPA/DSP30/IL-2 had a detection rate of 98% (n = 40). The percentage of cases with normal FISH but abnormal cytogenetics increased from 9% in 2011 to 21% in 2012-2013. The TPA/DSP30/IL-2 cultures in 2012-2013 detected more novel abnormalities (n = 5) as compared to DSP30/IL-2 alone (n = 3). TPA/DSP30/IL2 was as good as or better than DSP30/IL2 alone. TPA/DSP30/IL-2 offers a high detection rate for CLL abnormalities with a single stimulated culture and may increase detection of clinically significant abnormalities. © 2016 John Wiley & Sons Ltd.

Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.

Science.gov (United States)

Suehiro, Youko; Hasegawa, Atsuhiko; Iino, Tadafumi; Sasada, Amane; Watanabe, Nobukazu; Matsuoka, Masao; Takamori, Ayako; Tanosaki, Ryuji; Utsunomiya, Atae; Choi, Ilseung; Fukuda, Tetsuya; Miura, Osamu; Takaishi, Shigeo; Teshima, Takanori; Akashi, Koichi; Kannagi, Mari; Uike, Naokuni; Okamura, Jun

2015-05-01

Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate- to high-risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax-specific CTL responses were observed with peaks at 16-20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL. © 2015 John Wiley & Sons Ltd.

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

Science.gov (United States)

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.