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Sample records for durable tumour responses

  1. Improving tumour response

    International Nuclear Information System (INIS)

    Bentzen, S.

    2003-01-01

    Radiation oncology is in the middle of the most exciting developments in its 100-year history. Progress in treatment planning and delivery, in medical imaging and in basic cancer and normal tissue biology is likely to change the indication for radiotherapy as well as the way it is prescribed and delivered. Technological and conceptual advances, in particular the development of the multi-leaf collimator and the concept of inverse treatment planning, have led to the introduction of intensity modulated radiation therapy (IMRT) with its capability to plan and deliver non-uniform dose distributions in the clinic. This has forced us to re-think radiation oncology: refining the indication for radiotherapy, optimizing the prescription of dose distributions and considering how, based on clinical evidence, radiation can best be combined with other treatment modalities, surgery, cytotoxic chemotherapy and biologically targeted therapies. The attraction of radiation therapy as an element of multi-modality cancer therapy is that it induces DNA damage that can be modulated in space and time. Progress in basic cancer biology, genomics and proteomics, as well as biological imaging provides novel avenues for individualization of cancer therapy and for biological optimization of radiotherapy. In improving cancer care, it is the therapeutic ratio, rather than tumour control per se, that must be optimised. Interestingly, the two main avenues for improving the effectiveness of radiotherapy currently being actively pursued in the clinic generally aim at different sides of the therapeutic ratio: 3D conformal radiotherapy and IMRT predominantly aim to reduce normal-tissue side effects - and by doing this, open the way for dose escalation that may lead to increased tumour control rates - whereas combined radio-chemotherapy aims to improve tumour response - while keeping the fingers crossed that this will not increase normal-tissue complications to the same extent. In parallel with these

  2. Radiation response of tumours

    International Nuclear Information System (INIS)

    Twentyman, P.R.

    1988-01-01

    In this chapter knowledge regarding cellular radiation response and the factors which modify it is related to the volume changes and probability of control of irradiated solid tumors. After a discussion of the different cell populations present within solid tumors the cell population kinetics of the neoplastic cells are considered in more detail. The influence of factors related to the three-dimensional geometry of the tumor, particularly hypoxia, are considered, and also the role of the tumor vasculature in radiation response. Repair of sublethal damage (SLD) and potentially lethal damage (PLD) is dealt with and finally the relationship between the various end-points of tumor radioresponsiveness is discussed

  3. Comparison of tumour age response to radiation for cells derived from tissue culture or solid tumours

    International Nuclear Information System (INIS)

    Keng, P.C.; Siemann, D.W.; Rochester Univ., NY; Rochester Univ., NY; Wheeler, K.T.

    1984-01-01

    Direct comparison of the cell age response of 9L and KHT tumour cells derived either from tissue culture or solid tumours was achieved. Cells from dissociated KHT and 9L tumours (the latter implanted either subcutaneously or intracerebrally) and cells from tissue culture were separated into homogenous sized populations by centrifugal elutriation. In both tumour models these homogeneous sized populations correspond to populations enriched at different stages of the cell cycle. The survival of these elutriated cell populations was measured after a single dose of Cs-137 gamma rays. For cells isolated from 9L solid tumours, there was little variation in radiosensitivity throughout the cell cycle; however, a very small but significant increase in resistance was found in late G 1 cells. This lack of a large variation in radiosensitivity through the cell cycle for 9L cells from solid tumours also was seen in 9L cells growing in monolayer tissue culture. When similar experiments were performed using the KHT sarcoma tumour model, the results showed that KHT cells in vitro exhibited a fairly conventional increase in radioresistance in both mid G 1 and late S. However, the cell age response of KHT cells from solid tumours was different; particularly in the late S and G 2 + M phases. (author)

  4. Relationship between tumour size and response to neoadjuvant ...

    African Journals Online (AJOL)

    2018-03-16

    Mar 16, 2018 ... Introduction. Efforts to improve response of breast tumours to chemotherapy and maximize the benefit-to-adverse events ratio of chemotherapy include molecular subtyping to classify tumours, combined and cyclical use of chemotherapy and surgical de-bulking to stimulate proliferation. Molecular ...

  5. Tumour response and morphological changes of acoustic neurinomas after radiosurgery

    International Nuclear Information System (INIS)

    Valentino, V.; Raimondi, A.J.

    1995-01-01

    Twenty-seven of the 1560 patients treated by radiosurgery during the period 1984-1993 had acoustic neurinomas. Four cases were excluded from this study because they had a follow-up of less than 2 years. There were 24 neurinomas treated in 23 patients as one patient had a bilateral tumour. Seven patients underwent radiosurgery for a recurrent tumour (already operated on once or twice), while it was the first treatment for 16 patients. The tumour volume ranged from 1.99 cm 3 to 18.30 cm 3 , and the patient follow-up was from 2 to 8 years. To determine the target on CT/NMR for linear accelerator stereotactic irradiation, the Greitz-Bergstroem non-invasive head fixation device was used. It was again adopted for subsequent serial imaging, and for repeat radiosurgery when necessary. The total peripheral tumour dose ranged from 12 to 45 Gy. In 9 patients there was a reduction in tumour volume varying from 39 to 100% , while 14 of the neurinomas appeared stable after an average follow-up of 3 years. In one patient there was an increase in size of the tumour. Variable morphological changes were present in 66% of the neurinomas treated. Radiosurgery is indicated as an alternative to microsurgery for inoperab1e patients and for those who refuse surgery, for recurrent tumours, and as a post-operative complementary treatment for partially removed tumours. A gradual approach to radiosurgery, depending on tumour response, allows a greater efficacy with minimal risk. In the present series no complications were observed. Hearing was preserved at almost the same level as that prior to radiosurgery in all patients. (author)

  6. Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

    International Nuclear Information System (INIS)

    Hendry, Jolyon H.

    2001-01-01

    Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

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

    Science.gov (United States)

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

    2015-04-29

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

  8. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  9. Measurement of human normal tissue and tumour responses

    International Nuclear Information System (INIS)

    Ross, G.; Yarnold, J.R.

    1988-01-01

    The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  11. Is cell survival a determinant of the in situ response of 9L tumours

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Wallen, C.A.

    1980-01-01

    The influence of growth rate, location, size and potential lethal damage (PLD) recovery on the cellular radiosensitivity and the tumour response was studied in 9L/Ro and 9L/SF rat tumours. The median day of death of rats bearing the intracerebral (i.c.) 9L/Ro tumours was 16-18 days; for i.c. 9L/SF tumours it was 23-25 days. The doubling time of 9L/Ro cells was slightly faster than for 9L/SF cells both in culture and in the brain. The cellular radiosensitivity of both i.c. tumour cell sublines was identical. However, subcutaneous (s.c.) 9L/Ro tumour cells were more resistant. There was no evidence of a substantial hypoxic fraction in either site. When i.c. 9L/Ro and 9L/SF tumours of similar size were treated with fractionated doses of BCNU, X-rays or combinations of the two, the responses of the two tumours were essentially identical. The rate of recovery from radiation-induced PLD was identical in the two sublines and the two sites. Increase in life-span of rats bearing i.c. 9L/Ro tumours appeared to be correlated with the tumour cell kill measured after completion of PLD recovery rather than with the tumour cell kill determined immediately after irradiation. (author)

  12. The influence of the oestrous cycle on the radiation response of solid tumours

    Science.gov (United States)

    Swann, Patricia R.

    Oestrogen increases the transcription of nitric oxide synthase, thus increasing nitric oxide production, which can result in vasodilation of blood vessels. Fluctuating levels of oestrogen throughout the menstrual cycle has the potential to affect tumour blood flow. Variations of blood supply to a solid tumour can influence tumour oxygenation and subsequently the percentage of hypoxic cells. As hypoxic cells are more resistant to radiation than well-oxygenated cells, this could potentially affect the radiation response of the tumour. This project evaluated the impact of the oestrous stage on the radiation response of BCHT, RIF-1 and SCCvii tumours in syngeneic C3H mice. The oestrous cycle consists of the following stages, pro-oestrus, oestrus, metoestrus and dioestrus and each stage can be determined by the cellular composition of vaginal smears. The peak of oestrogen occurs in the ovulatory phase and a second smaller peak occurs in dioestrus. Subcutaneous tumour were treated at a volume of 200 - 250 mm3 with local irradiation of 10 Gy ionising radiation at different stages of the oestrous cycle. Tumours were excised either immediately or 24 hours after irradiation and disaggregated into a single cell suspension. Tumour cell survival was assessed by clonogenic assay of the excised tumour relative to untreated tumours excised at the corresponding oestrous stage. Tumours irradiated in oestrus consistently produced the lowest surviving fraction after immediate and delayed excision. Tumours irradiated in pro-oestrus and excised immediately after irradiation, showed a two-fold increase in surviving fraction compared to tumours irradiated in oestrus. The surviving fractions of tumours excised 24 hours after irradiation were less than for tumours excised immediately after irradiation. Surviving fractions of irradiated, clamped KHT tumours were independent of oestrous stage. To confirm that these oestrous stage dependent changes were due to changes in tumour perfusion, the

  13. Dose-response models for the radiation-induction of skin tumours in mice

    International Nuclear Information System (INIS)

    Papworth, D.G.; Hulse, E.V.

    1983-01-01

    Extensive data on radiation-induced skin tumours in mice were examined using 8 models, all based on the concept that incidences of radiation-induced tumours depend on a combination of two radiation effects: a tumour induction process and the loss of reproductive integrity by the potential tumour cells. Models with and without a threshold were used, in spite of theoretical objections to threshold models. No model fitted well both the epidermal and the dermal tumour data and models which proved to be statistically satisfactory for some of the data were rejected for biological reasons. It is concluded that, for skin tumours, dose-response curves depending on a combination of cancer induction and loss of cellular reproductive integrity are distorted by some special, relatively radio-resistant, factor which we have previously postulated as being involved in radiation skin carcinogenesis. (author)

  14. Significance of manipulating tumour hypoxia and radiation dose rate in terms of local tumour response and lung metastatic potential, referring to the response of quiescent cell populations

    Science.gov (United States)

    Masunaga, S; Matsumoto, Y; Kashino, G; Hirayama, R; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kinashi, Y; Maruhashi, A; Ono, K

    2010-01-01

    The purpose of this study was to evaluate the influence of manipulating intratumour oxygenation status and radiation dose rate on local tumour response and lung metastases following radiotherapy, referring to the response of quiescent cell populations within irradiated tumours. B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation at high dose rate (HDR) or reduced dose rate (RDR) following treatment with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the quiescent (Q) and total (proliferating + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Following HDR irradiation, nicotinamide and MTH enhanced the sensitivity of the total and Q-cell populations, respectively. The decrease in sensitivity at RDR irradiation compared with HDR irradiation was slightly inhibited by MTH, especially in Q cells. Without γ-ray irradiation, nicotinamide treatment tended to reduce the number of lung metastases. With γ-rays, in combination with nicotinamide or MTH, especially the former, HDR irradiation decreased the number of metastases more remarkably than RDR irradiation. Manipulating both tumour hypoxia and irradiation dose rate have the potential to influence lung metastasis. The combination with the acute hypoxia-releasing agent nicotinamide may be more promising in HDR than RDR irradiation in terms of reducing the number of lung metastases. PMID:20739345

  15. The candidate TB vaccine, MVA85A, induces highly durable Th1 responses.

    Directory of Open Access Journals (Sweden)

    Michele Tameris

    Full Text Available Vaccination against tuberculosis (TB should provide long-term protective immunity against Mycobacterium tuberculosis (M.tb. The current TB vaccine, Bacille Calmette-Guerin (BCG, protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone.We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011.Of 252 potential participants, 183 (72.6% consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA-CCR7+ central memory or CD45RA-CCR7- effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination.MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not

  16. Preclinical studies for increasing radiation response of malignant brain tumours

    International Nuclear Information System (INIS)

    Kalia, Vijay K.; Kumari, Kalyani; Sai Shyam; George, Jennifer; Shobha, A.G.; Chandrasekhar Sagar, B.K.; Lal, Jagath

    2013-01-01

    Malignant gliomas are the most common among the CNS cancers. Standard treatment for these tumours - comprises of surgery, followed by Radiotherapy (RT). Combination of Temozolomide (TMZ) increases survival, but hematological toxicities are also increased as compared to RT alone. The median survival depends on grade and location of tumour, as well as the age of the patient. Grade IV gliomas (GSMs) are third leading cause of cancer induced death in the age group of 15 to 34 years. Therefore, it is important to carry out further preclinical studies to develop more effective treatment of malignant gliomas. The present studies were carried out on different established malignant glioma cell lines. (U373MG) as well as primary monolayer cultures derived from biopsies obtained from patients with malignant gliomas. Exponentially growing cells were exposed to TMZ, Lonidamine (LND) (in 0.1% DMSO), or 2-Deoxy-D-Glucose (2-DG, aqueous solution) - with or without 60 Co-Gamma-rays (1- 2 Gy). The drugs were removed 4 hours after irradiation and the cultures were processed further for different assays of damage. Short term (4 h) treatments with TMZ 20 μM, LND 100 μM or their combination; did not induce micronuclei formation in the unirradiated cultures of U373MG cells. However, radiation (2 Gy) induced micronuclei was significantly increased by drug treatments. In primary cultures from different tumours, TMZ (≤ 10 μM) or 2-DG (1 mM), or gamma-irradiation (1-2 Gy) induced micronuclei and/ or apoptosis. The effects, however, varied in different tumours. These data show that clinically achievable, very low concentrations of these drugs could induce cellular damage and death; and increase radiosensitivity of malignant gliomas. Therefore, adjuvants like Lonidamine and 2-DG, with non-overlapping toxicities, could optimize treatment of malignant gliomas, by reducing the side effects of radio-chemotherapy. (author)

  17. The adaptive response of mouse tumours to anaemia and retransfusion

    International Nuclear Information System (INIS)

    Hirst, D.G.; Wood, P.J.

    1987-01-01

    Exchange transfusion methods have been developed to alter the haematocrit of tumour-bearing mice. The effects of anaemia and its correction by blood transfusion on the radiosensitivity of two mouse tumours (SCCVII/St and RIF-1) were studied using excision, in vivo/in vitro assay. Acute reduction in haematocrit caused a high degree of radioresistance equivalent to an increase in the hypoxic fractions by factors of 10 (SCCVII/St) and 30 (RIF-1). As the duration of anaemia was prolonged, radioresistance was lost until within about 6 h normal radiosensitivity was observed even though the anaemia persisted. The restoration of the normal haematocrit by red blood cell transfusion after 24 h of anaemia caused increased radiosensitivity equivalent to a reduction in the hypoxic fraction by factors of 5 (SCCVII/St) and 10 (RIF-1), but again the effect was transient and normal radiosensitivity re-established within 24-48 h of retransfusion. Measurements of 14 C misonidazole (MISO) binding to RIF-1 tumours after these procedures indicated changes in the number of hypoxic cells which were qualitatively almost identical to those using the cell survival endpoint, leading to the belief that changes in oxygenation were reponsible for the altered radiosensitivity. (author)

  18. Assessment of the response of tumours to radiation: clinical and experimental studies

    International Nuclear Information System (INIS)

    Suit, H.D.; Walker, A.M.

    1980-01-01

    There is an important and active research programme at the laboratory and clinical level to develop indicators of the ultimate local response of tumours to radiation. In order to be of great value clinically indicators should yield a high true positivity and a low false positivity so that revisions of therapeutic strategy will be made only when there is a real need for such a change. The available data in the literature from the clinical studies, when analysed in terms of the true and false positive rates, indicate that the extent of regression at the completion of external beam therapy is not a useful prognostic indicator. This pertains to populations of tumour of a specific histopathological type, tumour size and anatomic site. Studies of laboratory animal tumour models have shown that regression patterns may be useful prognostic indicators for a tumour which is characterized by moderate immunogenicity and where there is close correlation between complete regression and permanent control. In contrast for tumours which are weakly or nonimmunogenic and which regress completely even at low tumour control probabilities, the pattern of regression has not been demonstrated to be of prognostic value. (author)

  19. Relational Benefit on Satisfaction and Durability in Strategic Corporate Social Responsibility

    Directory of Open Access Journals (Sweden)

    Minseok Kim

    2018-04-01

    Full Text Available These days, companies are moving from Corporate Social Responsibility (CSR activities for short-term profit generation to the ones for achieving economic and social long-term goals. This phenomenon results from the idea that CSR is not a mere cost but can be used as a source of opportunity, innovation and competitive advantage. Deemed as a great business strategy, strategic CSR activities are being emphasized by various stakeholders in the global market. The purpose of this study is to present specific implications and to empirically research the relations among relational benefits, commitment, and authenticity. It identifies the main factors of relationship management in expanding the stakeholder pool and forming relationships for strategic CSR activities. To this end, we conducted a questionnaire survey of 113 CSR practitioners in Korea and analyzed how social, psychological, and economic benefits affect the satisfaction and durability of strategic CSR activities through relational commitment and authenticity. Consequently, social, psychological, and economic benefits have an impact on relationships and, by extension, have a positive effect on relational satisfaction and durability. However, economic benefits affect relational authenticity, but social and psychological benefits do not. As a result, relational benefits cannot affect satisfaction through relationships. Therefore, relational benefits and commitment are more important variables for the satisfaction and durability of strategic CSR activities.

  20. Background parenchymal enhancement in breast MRI before and after neoadjuvant chemotherapy: correlation with tumour response

    Energy Technology Data Exchange (ETDEWEB)

    Preibsch, H.; Wanner, L.; Bahrs, S.D.; Wietek, B.M.; Nikolaou, K.; Wiesinger, B. [University Hospital Tuebingen, Diagnostic and Interventional Radiology, Tuebingen (Germany); Siegmann-Luz, K.C. [Diagnostic Center for Breast Cancer and Screening Mammography Brandenburg Ost, Koenigs Wusterhausen (Germany); Oberlecher, E.; Hahn, M. [University Hospital Tuebingen, Department of Gynecology and Obstetrics, Tuebingen (Germany); Staebler, A. [University Hospital Tuebingen, Institute of Pathology and Neuropathology, Tuebingen (Germany)

    2016-06-15

    To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC). One hundred and forty-six MRI examinations of 73 patients with 80 biopsy-proven breast cancers who underwent breast MRI before and after NAC were retrospectively analysed. All images were reviewed by two blinded readers, who classified BPE into categories (BEC; 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) before and after NAC. Histopathological and morphological tumour responses were analysed and compared. The distribution of BEC 1/2/3/4 was 25/46/18/11 % before and 78/20/2/0 % after NAC. On average, BPE decreased by 0.87 BEC. Cohen's kappa showed substantial agreement (k = 0.73-0.77) before and moderate agreement (k = 0.43-0.60) after NAC and moderate agreement (k = 0.62-0.60) concerning the change in BEC. Correlating the change in BPE with tumour response, the average decrease in BEC was 1.3 in cases of complete remission, 0.83 in cases with partial response, 0.85 in cases with stable disease and 0.40 in cases with progressive disease. Correlation analysis showed a significant correlation between the decrease in BEC and tumour response (r = -0.24, p = 0.03). BPE decreased by, on average, 0.87 BEC following NAC for breast cancer. The degree of BPE reduction seemed to correlate with tumour response. (orig.)

  1. The role of polyamine catabolism in anti-tumour drug response.

    Science.gov (United States)

    Casero, R A; Wang, Y; Stewart, T M; Devereux, W; Hacker, A; Wang, Y; Smith, R; Woster, P M

    2003-04-01

    Interest in polyamine catabolism has increased since it has been directly associated with the cytotoxic response of multiple tumour types to exposure to specific anti-tumour polyamine analogues. Human polyamine catabolism was considered to be a two-step pathway regulated by the rate-limiting enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) that provides substrate for an acetylpolyamine oxidase (APAO). Further, the super-induction of SSAT by several anti-tumour polyamine analogues has been implicated in the cytotoxic response of specific solid-tumour phenotypes to these agents. This high induction of SSAT has been correlated with cellular response to the anti-tumour polyamine analogues in several systems and considerable progress has been made in understanding the molecular mechanisms that regulate the analogue-induced expression of SSAT. A polyamine response element has been identified and the transacting transcription factors that bind and stimulate transcription of SSAT have been cloned and characterized. The link between SSAT activity and cellular toxicity is thought to be based on the production of H(2)O(2) by the activity of the constitutive APAO that uses the SSAT-produced acetylated polyamines. The high induction of SSAT and the subsequent activity of APAO are linked to the cytotoxic response of some tumour cell types to specific polyamine analogues. However, we have recently cloned a variably spliced human polyamine oxidase (PAOh1) that is inducible by specific polyamine analogues, efficiently uses unacetylated spermine as a substrate, and also produces toxic H(2)O(2) as a product. The results of studies with PAOh1 suggest that it is an additional enzyme in polyamine catabolism that has the potential to significantly contribute to polyamine homoeostasis and drug response. Most importantly, PAOh1 is induced by specific polyamine analogues in a tumour-phenotype-specific manner in cell lines representative of the major forms of solid tumours, including

  2. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

    Directory of Open Access Journals (Sweden)

    Karen A.O. Martins

    2016-01-01

    Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

  3. Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

    Science.gov (United States)

    Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

    2016-01-01

    Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

  4. Can cell kinetic parameters predict the response of tumours to radiotherapy?

    Science.gov (United States)

    McNally, N J

    1989-11-01

    Three potential predictive assays of the repopulation component in tumour response to therapy are considered. (1) The DNA index can easily be measured. It is of prognostic value for cancers of certain sites, aneuploidy being a bad prognostic indicator. It is not strictly an indicator of cell proliferation. (2) The in vitro labelling index is of predictive value in early stage operable breast cancer and in head and neck cancer. In the former a high pretreatment labelling index can identify patients who could benefit from adjuvant chemotherapy. (3) The tumour potential doubling time (Tpot) can be measured rapidly following in vivo labelling with bromodeoxyuridine or iododeoxyuridine. We have measured Tpot in over 100 solid tumours with a success rate of about 75 per cent. Nearly 50 per cent of the tumours have a pre-treatment potential doubling time of 5 days or less. These would be suitable candidates for accelerated fractionation.

  5. Can cell kinetic parameters predict the response of tumours to radiotherapy?

    International Nuclear Information System (INIS)

    McNally, N.J.

    1989-01-01

    Three potential predictive assays of the repopulation component in tumour response to therapy are considered. (1) The DNA index can easily be measured. It is of prognostic value for cancers of certain sites, aneuploidy being a bad prognostic indicator. It is not strictly an indicator of cell proliferation. (2) The in vitro labelling index is of predictive value in early stage operable breast cancer and in head and neck cancer. In the former a high pretreatment labelling index can identify patients who could benefit from adjuvant chemotherapy. (3) The tumour potential doubling time can be measured rapidly following in vivo labelling with bromodeoxyuridine or iododeoxyuridine. The authors measured T pot in over 100 solid tumours with a success rate of about 75%. Nearly 50% of the tumours have a pre-treatment potential doubling time of 5 days or less. These would be suitable candidates for accelerated fractionation. (author)

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  7. Tumour T1 changes in vivo are highly predictive of response to chemotherapy and reflect the number of viable tumour cells – a preclinical MR study in mice

    International Nuclear Information System (INIS)

    Weidensteiner, Claudia; Allegrini, Peter R; Sticker-Jantscheff, Melanie; Romanet, Vincent; Ferretti, Stephane; McSheehy, Paul MJ

    2014-01-01

    measure of cell density but reflects the decreased number of remaining viable and proliferating tumour cells due to perhaps cell and tissue destruction releasing proteins and/or metals that cause T 1 relaxation. ΔT 1 is a highly sensitive and specific predictor of response. This MRI method provides the opportunity to stratify a patient population during tumour therapy in the clinic

  8. The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation

    Science.gov (United States)

    Toma-Dasu, Iuliana; Dasu, Alexandru; Karlsson, Mikael

    2004-10-01

    The polarographic oxygen sensor is one of the most used devices for in vivo measurements of oxygen and many other measurement techniques for measuring tumour hypoxia are correlated with electrode measurements. Little is known however about the relationship between electrode measurements and the real tissue oxygenation. This paper investigates the influence of the temporal change of the hypoxic pattern on the electrode measurements and the tumour response. Electrode measurements and tumour response were simulated using a computer program that allows both the calculation of the tissue oxygenation with respect to the two types of hypoxia that might arise in tumours and the virtual insertion of the electrode into the tissue. It was therefore possible to control the amount of each type of hypoxia in order to investigate their influence on the measurement results. Tissues with several vascular architectures ranging from well oxygenated to poorly oxygenated were taken into consideration as might be seen in practice. The influence of the electrode measurements on the treatment outcome was estimated by calculating the tumour control probability for the tumours characterized either by the real or by the measured tumour oxygenation. We have simulated electrode oxygen measurements in different types of tissues, covering a wide range of tumour oxygenations. The results of the simulations showed that the measured distribution depends on the details of the vascular network and not on the type of hypoxia. We have also simulated the effects of the temporal change of the acute hypoxic pattern due to the opening and the closure of different blood vessels during a full fractionated treatment. The results of this simulation suggested that the temporal variation of the hypoxic pattern does not lead to significantly different results for the electrode measurements or the predicted tumour control probabilities. In conclusion, it was found that the averaging effect of the electrode leads

  9. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

    Science.gov (United States)

    Kanamala, Manju; Wilson, William R; Yang, Mimi; Palmer, Brian D; Wu, Zimei

    2016-04-01

    As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Effects of methylglyoxal bis(guanylhydrazone) on tumour and skin responses to hyperthermia in mice

    International Nuclear Information System (INIS)

    Miyakoshi, J.; Oda, W.; Inagaki, C.; Hiraoka, M.; Takahashi, M.; Abe, M.

    1984-01-01

    Effects of methylglyoxal bis(guanylhydrazone) (MGBG) on tumour and skin responses to hyperthermia (42degC) were examined in C3H mice. MGBG (50 mg/kg) was administered intraperitoneally to mice 4 hours before hyperthermic treatment. The tumour (FM3A) growth time was elongated by an amount dependent on the exposure time of treatment at 42degC (60, 90 and 120 min). Pre-treatment of mice with MGBG (50 mg/kg, i.p.) apparently further lengthened the tumour growth time after treatment at 42degC. No significant damage of foot skin was caused by 42degC hyperthermia. Pre-treatment with MGBG did not make the foot skin susceptible to the heating. From these findings, it can be considered that MGBG or related less-toxic compounds may have a clinical advantage for the mild (42degC) hyperthermic treatment in cancer therapy. (author)

  11. Effects of methylglyoxal bis(guanylhydrazone) on tumour and skin responses to hyperthermia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Miyakoshi, J.; Oda, W.; Inagaki, C. (Kyoto Coll. of Pharmacy (Japan)); Hiraoka, M.; Takahashi, M.; Abe, M. (Kyoto Univ. (Japan). Faculty of Medicine)

    1984-09-01

    Effects of methylglyoxal bis(guanylhydrazone) (MGBG) on tumour and skin responses to hyperthermia (42degC) were examined in C3H mice. MGBG (50 mg/kg) was administered intraperitoneally to mice 4 hours before hyperthermic treatment. The tumour (FM3A) growth time was elongated by an amount dependent on the exposure time of treatment at 42degC (60, 90 and 120 min). Pre-treatment of mice with MGBG (50 mg/kg, i.p.) apparently further lengthened the tumour growth time after treatment at 42degC. No significant damage of foot skin was caused by 42degC hyperthermia. Pre-treatment with MGBG did not make the foot skin susceptible to the heating. From these findings, it can be considered that MGBG or related less-toxic compounds may have a clinical advantage for the mild (42degC) hyperthermic treatment in cancer therapy.

  12. Building a durable response to HIV/AIDS: implications for health systems.

    Science.gov (United States)

    Atun, Rifat; Bataringaya, Jacqueline

    2011-08-01

    The remarkable rise in investments for HIV control programs in 2003-2010 enabled an unprecedented expansion of access to HIV services in low-income and middle-income countries. By the end of 2010, more than 5.2 million people were receiving antiretroviral therapy (ART), which transformed HIV infection, once a death sentence, into a long-term illness. The rapid expansion in the number of persons receiving ART means that health systems must continue to provide acute life-saving care for those with advanced HIV/AIDS although also providing chronic care services to expanding cohorts of more stable patients who are doing well on ART. This expansion also means a transition from an emergency response to the epidemic, characterized by a public health approach, to a more integrated and durable approach to HIV prevention, care, and treatment services that fosters individualized care for those requiring long-term antiretroviral treatment. Yet most low-income and middle-income countries, which have weak health systems, are poorly prepared to make this transition. In this article, we highlight the challenges health systems face in developing a sustained and durable response to HIV/AIDS. The article analyses the readiness of health systems to combine rapid expansion of ART access with long-term treatment and continuity of care for a growing cohort of patients. We argue that effective management of a transition from an emergency AIDS response to long-term programatic strategies will require a paradigm shift that enables leveraging investments in HIV to build sustainable health systems for managing large cohorts of patients receiving ART although meeting the immediate needs of those who remain without access to HIV treatment and care.

  13. Endogenous and exogenously-induced immunomodulation of tumour-host responsiveness

    Directory of Open Access Journals (Sweden)

    Richard J. Ablin

    1987-01-01

    Full Text Available In spite of the availability of multiple effector mechanisms of the immune system to combat tumour growth and metastases, their impairment frequently accompanies the appearance of cancer. Factors contributing to this impairment may be related to properties of the host and/or the tumour itself and may be with respect to their origin -endogenous or exogenour. Based on the unique biological behavior of prostate cancer (PCa, and its apparent escape from immune surveillance in the presence of tumour immuno genicity, continuing investigation of endogenous and exogenous factors thought to be relevant to its pathogenesis have been made. For this purpose further studies of the suggested role of human seminal plasma (SePl and the synthetic oestrogen, diethylstiboestrol (DES, as representative endogenous and exogenous immunomodulatory factors (IMF of tumour-host responsiveness, together with evaluation of human prostatic tissue extracts and leuprolide (the luteinizing-hormone-releasing-hormone proposed as an alternate to DES therapy have been made by evaluating their effect on the lytic activity of natural killer (NK cells. SePl and prostate extracts significantly suppressed NK cell lysis. Physicochemical studies suggest SePl and prostate IMF to be associated with high and low molecular weight macromolecules; and implicate the participation of transglutaminase and prostaglandins. Comparative study of therapeutic levels of DES vs. leuprolide on NK cell lysis demonstrated significant suppression by DES vs. a negligible effect of leuprolide. Metastases are highly prevalent in PCa, and contribute significantly to its morbidity and mortality. Further knowledge of the range of effects of endogenous and exogenous IMF on effector mechanisms of tumour-host responsiveness, to include suppression of NK cells, and elucidation of their nature, may contribute toward our understanding of the unique biological behavior of tumours of the prostate, in addition to

  14. In vivo tissue response and durability of five novel synthetic polymers in a rabbit model.

    Science.gov (United States)

    Sahin, E; Cingi, C; Eskiizmir, G; Altintoprak, N; Calli, A; Calli, C; Yilgör, I; Yilgör, E

    2016-04-01

    Alloplastic materials are frequently used in facial plastic surgeries such as rhinoplasty and nasal reconstruction. Unfortunately, the ideal alloplastic material has not been found. This experimental study evaluates the tissue response and durability of five novel polymers developed as an alloplastic material. In this experimental study involving a tertiary university hospital, six subcuticular pockets were formed at the back of 10 rabbits for the implantation of each polymer and sham group. Each pocket was excised with its adjacent tissue after three months, and collected for histopathological examination. Semi-quantitative examination including neovascularisation, inflammation, fibrosis, abscess formation, multinucleated foreign body giant cells was performed, and integrity of polymer was evaluated. A statistical comparison was performed. No statically significant difference was detected in neovascularisation, inflammation, fibrosis, abscess formation and multinucleated foreign body giant cells when a paired comparison between sham and polymer II, III and IV groups was performed individually. Nevertheless, the degree of fibrosis was less than sham group in polymer I (p = .027) and V (p = .018), although the other variables were almost similar. The integrity of polymers III (9 intact, 1 fragmented) and IV (8 intact, 2 absent) was better than the other polymers. These novel synthetic polymers could be considered as good candidates for clinical applicability. All polymers provided satisfactory results in terms of tissue response; however, fibrovascular integration was higher in polymers II, III and IV. In addition, the durability of polymer III and IV was better than the others. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.

  15. Circulating Tumour DNA for Monitoring Treatment Response to Anti-PD-1 Immunotherapy in Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Atsuko Ashida

    2017-08-01

    Full Text Available Anti-programmed cell death-1 (anti-PD-1 antibody shows high therapeutic efficacy in patients with advanced melanoma. However, assessment of its therapeutic activity can be challenging because of tumour enlargement associated with intratumoural inflammation. Because circulating tumour DNA (ctDNA correlates with tumour burden, we assessed the value of ctDNA levels as an indicator of tumour changes. Quantification of ctDNA (BRAFmutant or NRASmutant levels by droplet digital PCR in 5 patients with BRAF or NRAS mutant melanoma during the treatment course showed dynamic changes corresponding to radiological and clinical alterations. In 3 cases in which the anti-PD-1 antibody was effective, ctDNA levels decreased within 2–4 weeks after treatment initiation. In 2 cases in which the anti-PD-1 antibody was ineffective, ctDNA levels did not decrease after treatment initiation. ctDNA could be a useful biomarker to predict early response to treatment in patients with advanced melanoma treated with anti-PD-1 immunotherapy.

  16. Modelling the interplay between hypoxia and proliferation in radiotherapy tumour response

    International Nuclear Information System (INIS)

    Jeong, J; Deasy, J O; Shoghi, K I

    2013-01-01

    A tumour control probability computational model for fractionated radiotherapy was developed, with the goal of incorporating the fundamental interplay between hypoxia and proliferation, including reoxygenation over a course of radiotherapy. The fundamental idea is that the local delivery of oxygen and glucose limits the amount of proliferation and metabolically-supported cell survival a tumour sub-volume can support. The model has three compartments: a proliferating compartment of cells receiving oxygen and glucose; an intermediate, metabolically-active compartment receiving glucose; and a highly hypoxic compartment of starving cells. Following the post-mitotic cell death of proliferating cells, intermediate cells move into the proliferative compartment and hypoxic cells move into the intermediate compartment. A key advantage of the proposed model is that the initial compartmental cell distribution is uniquely determined from the assumed local growth fraction (GF) and volume doubling time (T D ) values. Varying initial cell state distributions, based on the local (voxel) GF and T D , were simulated. Tumour response was simulated for head and neck squamous cell carcinoma using relevant parameter values based on published sources. The tumour dose required to achieve a 50% local control rate (TCD 50 ) was found for various GFs and T D ’s, and the effect of fraction size on TCD 50 was also evaluated. Due to the advantage of reoxygenation over a course of radiotherapy, conventional fraction sizes (2–2.4 Gy fx −1 ) were predicted to result in smaller TCD 50 's than larger fraction sizes (4–5 Gy fx –1 ) for a 10 cc tumour with GFs of around 0.15. The time to eliminate hypoxic cells (the reoxygenation time) was estimated for a given GF and decreased as GF increased. The extra dose required to overcome accelerated stem cell accumulation in longer treatment schedules was estimated to be 0.68 Gy/day (in EQD2 6.6 ), similar to published values derived from clinical

  17. Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response

    Energy Technology Data Exchange (ETDEWEB)

    Hebbar, S.A.; Mitra, A.K.; George, K.C.; Verma, N.C. [Radiation Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)]. E-mail: ncverma@apsara.barc.ernet.in

    2002-03-01

    Intramuscular administration of caffeine at a dose of 80 mg kg{sup -1} body weight to the gastrocnemius muscles of Swiss mice 5 min prior to local irradiation (35 Gy) of the leg delayed the progression of radiation-induced skin reactions in such animals. While 90% epilation with reddening of the skin was noted in animals treated with radiation alone, animals pretreated with caffeine suffered only partial hair loss with slight reddening of the skin on the 16th and 20th days post-irradiation. Beyond the 28th day, damage scores in irradiated feet for both the groups were similar (score 3) and remained unchanged until the 32nd day and then decreased and disappeared completely in both treatment groups by the 40th day after irradiation. In addition, the effect of caffeine on the radiation response of a mouse fibrosarcoma was investigated. Results showed that intratumoral administration of caffeine at a dose of 80 mg kg{sup -1} body weight 5 min prior to local exposure of tumours to 10 Gy of {sup 60}Co {gamma}-rays did not influence the response of tumours to radiation. The present study thus showed that although caffeine ameliorated radiation-induced skin reactions in the mouse leg, it did not affect the tumour radiation response, indicating its potential application in cancer radiotherapy. (author)

  18. Genomancy: predicting tumour response to cancer therapy based on the oracle of genetics.

    Science.gov (United States)

    Williams, P D; Lee, J K; Theodorescu, D

    2009-01-01

    Cells are complex systems that regulate a multitude of biologic pathways involving a diverse array of molecules. Cancer can develop when these pathways become deregulated as a result of mutations in the genes coding for these proteins or of epigenetic changes that affect gene expression, or both1,2. The diversity and interconnectedness of these pathways and their molecular components implies that a variety of mutations may lead to tumorigenic cellular deregulation3-6. This variety, combined with the requirement to overcome multiple anticancer defence mechanisms7, contributes to the heterogeneous nature of cancer. Consequently, tumours with similar histology may vary in their underlying molecular circuitry8-10, with resultant differences in biologic behaviour, manifested in proliferation rate, invasiveness, metastatic potential, and unfortunately, response to cytotoxic therapy. Thus, cancer can be thought of as a family of related tumour subtypes, highlighting the need for individualized prediction both of disease progression and of treatment response, based on the molecular characteristics of the tumour.

  19. Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib.

    Science.gov (United States)

    Shinagare, Atul B; Jagannathan, Jyothi P; Kurra, Vikram; Urban, Trinity; Manola, Judith; Choy, Edwin; Demetri, George D; George, Suzanne; Ramaiya, Nikhil H

    2014-03-01

    To compare performance of various tumour response criteria (TRCs) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour (GIST) with prior failure of imatinib and sunitinib. Twenty participants in a phase II trial received oral regorafenib (median duration 47 weeks; interquartile range (IQR) 24-88) with computed tomography (CT) imaging at baseline and every two months thereafter. Tumour response was prospectively determined on using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and retrospectively reassessed for comparison per RECIST 1.0, World Health Organization (WHO) and Choi criteria, using the same target lesions. Clinical benefit rate [CBR; complete or partial response (CR or PR) or stable disease (SD)≥16 weeks] and progression-free survival (PFS) were compared between various TRCs using kappa statistics. Performance of TRCs in predicting overall survival (OS) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics. PR was more frequent by Choi (90%) than RECIST 1.1, RECIST 1.0 and WHO (20% each), however, CBR was similar between various TRCs (overall CBR 85-90%, 95-100% agreement between all TRC pairs). PFS per RECIST 1.0 was similar to RECIST 1.1 (median 44 weeks versus 58 weeks), and shorter for WHO (median 34 weeks) and Choi (median 24 weeks). With RECIST 1.1, RECIST 1.0 and WHO, there was moderate concordance between PFS and OS (c-statistics 0.596-0.679). Choi criteria had less favourable concordance (c-statistic 0.506). RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

    Science.gov (United States)

    Andtbacka, Robert H I; Kaufman, Howard L; Collichio, Frances; Amatruda, Thomas; Senzer, Neil; Chesney, Jason; Delman, Keith A; Spitler, Lynn E; Puzanov, Igor; Agarwala, Sanjiv S; Milhem, Mohammed; Cranmer, Lee; Curti, Brendan; Lewis, Karl; Ross, Merrick; Guthrie, Troy; Linette, Gerald P; Daniels, Gregory A; Harrington, Kevin; Middleton, Mark R; Miller, Wilson H; Zager, Jonathan S; Ye, Yining; Yao, Bin; Li, Ai; Doleman, Susan; VanderWalde, Ari; Gansert, Jennifer; Coffin, Robert S

    2015-09-01

    Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma. © 2015 by

  1. RECIST response and variation of circulating tumour cells in phase 1 trials: A prospective multicentric study.

    Science.gov (United States)

    Massard, Christophe; Borget, Isabelle; Farace, Françoise; Aspeslagh, Sandrine; Le Deley, Marie-Cécile; Le Tourneau, Christophe; Bidard, François-Clement; Pierga, Jean-Yves; Dieras, Veronique; Hofman, Paul; Spano, Jean-Philippe; Ferte, Charles; Lacroix, Ludovic; Soria, Jean-Charles

    2017-09-01

    Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials. Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation. Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively. An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Membrane fatty acid composition and radiation response of Bp8 sarcoma ascites tumour cells

    International Nuclear Information System (INIS)

    Harms-Ringdahl, M.

    1987-01-01

    Radiation responses of Bp8 sarcoma ascites tumour cells with differences in membrane fatty acid composition was studied. The cells were grown i.p. in NMRI mice and their membrane composition was changed in response to different dietary regimes provided to the hosts. Cell survival, varied insignificantly between the four dietary groups, while repair capacity differed significantly. Increased repair capacity was observed for ascites cells grown in animals on diets enriched in sunflower seed oil and coconut oil, compared with cells from mice fed the hydrogenated lard diet or from cells from the control animals. The membrane fatty acid composition of the cells from the two dietary groups with increased levels of repair capacity differed extensively, and in general there was no correlation between radiation response and the membrane fatty acid composition of the four groups. For coconut oil and control groups with marked differences in membrane fatty acid composition, the effects of irradiation on ascites tumour growth rate and cell cycle distribution were followed in vivo. For none of the parameters was an effect on membrane fatty acid composition on radiation response observed. (author)

  3. Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice.

    Directory of Open Access Journals (Sweden)

    Tracy S P Heng

    Full Text Available Recent evidence suggests that the decline in resistance to viral infections with age occurs predominantly as a result of a gradual loss of naïve antigen-specific T cells. As such, restoration of the naïve T cell repertoire to levels seen in young healthy adults may improve defence against infection in the aged. We have previously shown that sex steroid ablation (SSA rejuvenates the ageing thymus and increases thymic export of naïve T cells, but it remains unclear whether T cell responses are improved. Using mouse models of clinically relevant diseases, we now demonstrate that SSA increases the number of naïve T cells able to respond to antigen, thereby enhancing effector responses in aged mice. Specifically, aged mice exhibit a delay in clearing influenza A virus, which correlates with diminished specific cytotoxic activity. This is due to a decreased magnitude of response and not an intrinsic defect in effector T cell function. Upon SSA, aged mice exhibit increased T cell responsiveness that restores efficient viral clearance. We further demonstrate that SSA decreases the incidence of an inducible tumour in aged mice and can potentially increase their responsiveness to a low-dose human papillomavirus vaccine in clearing pre-formed tumours. As thymectomy abrogates the increase in T cell numbers and responsiveness following SSA, we propose that the T cell effects of SSA are dependent on thymic reactivation and subsequent replenishment of the peripheral T cell pool with newly emigrated naïve T cells. These findings have important implications for strategies to improve protection from infection and responsiveness to vaccination in the aged.

  4. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1.

    NARCIS (Netherlands)

    Williams, K.J.; Telfer, B.A.; Xenaki, D.; Sheridan, M.R.; Desbaillets, I.; Peters, H.J.; Honess, D.; Harris, A.L.; Dachs, G.U.; Kogel, A.J. van der; Stratford, I.J.

    2005-01-01

    BACKGROUND AND PURPOSE: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. PATIENTS AND METHODS: Tumours comprising mouse hepatoma cells lacking HIF-1beta (and thereby HIF-1 function) were grown

  5. Immunity to tumour antigens.

    Science.gov (United States)

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

    2005-01-01

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

  6. The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.

    Science.gov (United States)

    Hong, Sung Pil; Min, Byung So; Kim, Tae Il; Cheon, Jae Hee; Kim, Nam Kyu; Kim, Hoguen; Kim, Won Ho

    2012-05-01

    Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Modification of nucleotide metabolism in relationship with differentiation and in response to irradiation in human tumour cells

    International Nuclear Information System (INIS)

    Wei, Shuang

    1998-01-01

    This research thesis reports the study of the metabolism of nucleotides in human tumour cells. The first part addresses the modifications of nucleotide (more specifically purine) metabolism in relationship with human melanoma cell proliferation and differentiation. The second part addresses the modifications of this metabolism in response to an irradiation in human colon tumour cells. For each part, the author proposes a bibliographic synthesis, and a presentation of studied cells and of methods used to grow cells, and respectively to proliferate and differentiate them or to irradiate them, and then discusses the obtained results [fr

  8. MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer

    Science.gov (United States)

    Seierstad, T; Hole, K H; Grøholt, K K; Dueland, S; Ree, A H; Flatmark, K

    2015-01-01

    Objective: To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods: Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T2 weighted MR images obtained pre-treatment (VPRE), after NACT (VNACT) and after the full course of NACT followed by CRT (VCRT). VPRE, VNACT and tumour volume changes relative to VPRE, ΔVNACT and ΔVCRT were calculated and correlated to histological tumour regression grade (TRG). Results: 61% of good histological responders (TRG 1–2) to NACT followed by CRT were correctly predicted by combining VPRE  −78.2% and VNACT volumetry may be a tool for early identification of good and poor responders to NACT followed by CRT and surgery in LARC in order to aid more individualized, multimodal treatment. PMID:25899892

  9. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1

    International Nuclear Information System (INIS)

    Williams, Kaye J.; Telfer, Brian A.; Xenaki, Dia; Sheridan, Mary R.; Desbaillets, Isabelle; Peters, Hans J.W.; Honess, Davina; Harris, Adrian L.; Dachs, Gabi U.; Kogel, Albert van der; Stratford, Ian J.

    2005-01-01

    Background and purpose: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. Patients and methods: Tumours comprising mouse hepatoma cells lacking HIF-1β (and thereby HIF-1 function) were grown in nude mice and radiation-induced growth delay compared with that seen for wild-type tumours and tumours derived from HIF-1β negative cells where HIF-1 function had been restored. Results: The xenografts that lack HIF-1 activity take longer to establish their growth and are more radioresponsive than both parental xenografts and those with restored HIF-1 function. Pre-treatment of the HIF-1 deficient xenografts with the hypoxic radiosensitizer misonidazole, had little effect on radioresponse. In contrast this treatment radiosensitized the parental xenografts. In spite of this, no difference in oxygenation status was found between the tumour types as measured by Eppendorf O 2 -electrodes and by binding of the hypoxic cell marker NITP. Admixing wild type and HIF-1 deficient cells in the same tumour at ratios of 1 in 10 and 1 in 100 restores the growth of the mixed tumours to that of a 100% HIF-1 proficient cell population. However, when comparing the effects of radiation on the mixed tumours, radioresponsiveness is maintained in those tumours containing the high proportion of HIF-1 deficient cells. Conclusions: The differences in radioresponse do not correlate with tumour oxygenation, suggesting that the hypoxic cells within the HIF-1 deficient tumours do not contribute to the outcome of radiotherapy. Thus, hypoxia impacts on tumour radioresponsiveness not simply because of the physio-chemical mechanism of oxygen with radiation-induced radicals causing damage 'fixation', but also because hypoxia/HIF-1 promotes expression of genes that allow tumour cells to survive under these adverse conditions. Further, the results from the cell mixing experiments uncouple the growth

  10. Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential

    Science.gov (United States)

    Masunaga, S; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kondo, N; Maruhashi, A; Ono, K

    2011-01-01

    Objectives The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results 3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. Conclusion Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide. PMID:21586505

  11. Tumour microenvironment and radiation response in sarcomas originating from tumourigenic human mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Safwat, Akmal Ahmed; Burns, Jorge S.

    2012-01-01

    : Immune deficient female mice were implanted on the backs with cells from one of the clones. The subsequent tumours were subjected to either radiation treatment or had the tumour microenvironment assayed, when they reached 400mm3. Radiation was given as a single fraction of 0 to 15 Gy and the degree...

  12. Positron emission tomography response criteria in solid tumours criteria for quantitative analysis of [18F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography for treatment response assessment in metastasised solid tumours: All that glitters is not gold.

    Science.gov (United States)

    Willemsen, Annelieke E C A B; Vlenterie, Myrella; van Herpen, Carla M L; van Erp, Nielka P; van der Graaf, Winette T A; de Geus-Oei, Lioe-Fee; Oyen, Wim J G

    2016-03-01

    For solid tumours, quantitative analysis of [(18)F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography potentially can have significant value in early response assessment and thereby discrimination between responders and non-responders at an early stage of treatment. Standardised strategies for this analysis have been proposed, and the positron emission tomography response criteria in solid tumours (PERCIST) criteria can be regarded as the current standard to perform quantitative analysis in a research setting, yet is not implemented in daily practice. However, several exceptions and limitations limit the feasibility of PERCIST criteria. In this article, we point out dilemmas that arise when applying proposed criteria like PERCIST on an expansive set of patients with metastasised solid tumours. Clinicians and scientists should be aware of these limitations to prevent that methodological issues impede successful introduction of research data into clinical practice. Therefore, to deliver on the high potential of quantitative imaging, consensus should be reached on a standardised, feasible and clinically useful analysis methodology. This methodology should be applicable in the majority of patients, tumour types and treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin

    International Nuclear Information System (INIS)

    Biaglow, J.E.; Durand, R.E.

    1978-01-01

    Any inhibition of oxygen consumption by respiring cells should result in indirect radiosensitization of the more centrally located hypoxic cells of a tumour. Amygdalin (D-mandelonitrile-β-D-glucosido-6-β-D-glucoside) when hydrolysed by the enzyme β-D-glucoside glycohydrolase (β-glucosidase) releases the respiratory inhibitor cyanide. A study has been made of the conditions for enhancing the gamma radiation response of multi-cell spheroids of V79 cells by cyanide or by cyanide released by enzymatic hydrolysis of amygdalin. Amygdalin hydrolysis was monitored by the increase in absorbancy at 250nm (production of benzaldehyde). Oxygen utilization was recorded by an oxygen electrode. The respiratory effects produced by the additon of amygdalin to cell suspensions containing β-glucosidase were immediate and essentially the same as those obtained by adding the equivalent amounts of KCN to the cell suspensions. The radio-resistant 'tail' of the survival curve of multi-cell spheroids was reduced in the presence of cyanide (added directly or secondarily released). The radiation response of the spheroids in the presence of cyanide was slightly greater than that for reoxygenation alone. (U.K.)

  14. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

    Energy Technology Data Exchange (ETDEWEB)

    Campana, Davide; Nori, Francesca; Cacciari, Giulia; Tomassetti, Paola [University of Bologna, Department of Medical and Surgical Sciences, Bologna (Italy); Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco [University of Rome, Digestive and Liver Disease Unit, Rome (Italy); Partelli, Stefano [Sacro Cuore Don Calabria Hospital, Department of Surgery, Negrar (Italy); University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy); Tamburrino, Domenico; Falconi, Massimo [University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy)

    2013-08-15

    Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with {sup 90}Y or {sup 177}Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided. (orig.)

  15. Concrete durability

    OpenAIRE

    Gaspar Tébar, Demetrio

    1991-01-01

    The evidence that the concrete is not a material for ever was noticed from the beginning of its industrial use. In the present work, the author describes the studies carried out during the last century and the early ages of the present one, mainly devoted to the study of the durability in sea water. At the present days, and in spite of the numerous papers published from then, the study of the concrete durability continues focusing the research priorities and economical resources of rese...

  16. Parametric response mapping of contrast-enhanced biphasic CT for evaluating tumour viability of hepatocellular carcinoma after TACE

    Energy Technology Data Exchange (ETDEWEB)

    Hinrichs, Jan B.; Shin, Hoen-Oh; Kaercher, Daniel; Hasdemir, Davut; Kaireit, Till; Lutat, Carolin; Meyer, Bernhard C.; Wacker, Frank K.; Rodt, Thomas [Hannover Medical School, Department of Diagnostic and Interventional Radiology, Hannover (Germany); Murray, Tim [Beaumont Hospital, Department of Diagnostic and Interventional Radiology, Dublin (Ireland); Vogel, Arndt [Hannover Medical School, Gastroenterology, Hepatology and Endocrinology, Hannover (Germany)

    2016-10-15

    To determine the feasibility and role of parametric response mapping (PRM) for quantitative assessment of regional contrast-enhancement patterns in hepatocellular carcinoma (HCC). Biphasic CT of 19 patients receiving repetitive conventional transarterial chemoembolisation (cTACE) for intermediate stage HCC were retrospectively analysed at baseline and follow-up at 3, 6, and 9 months. Voxel-based registration of arterial and porto-venous phases, with segmentation of the largest target lesion was performed. Frequency distribution plots of density-pairs of segmented voxels were generated. To differentiate necrotic, hypervascular and non-hypervascular tumour, and lipiodol/calcification, thresholds of 30, 100, and 300 HU were applied. Changes in density frequency plots over time were analysed and compared to response and assessment criteria (WHO, RECIST, EASL, mRECIST) and survival. PRM was feasible in all cases. Tumour volumes and hypervascular/non-hypervascular volume ratio showed significant longitudinal decrease (p < 0.05). Hypervascular volume at baseline was inversely correlated to survival (R = -0.57, p = 0.005). The only predictive parameter following cTACE to show significant survival difference was the change of the viable/non-viable ratio (p = 0.044), whereas common response assessment criteria showed no significant difference in survival. PRM allows a quantitative and more precise assessment of regional tumour vascularisation patterns and may be helpful for TACE treatment planning and response assessment. (orig.)

  17. Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Maisonobe, Jacques-Antoine; Necib, Hatem; Buvat, Irene [IMNC UMR 8165 CNRS - Paris 7 and Paris 11 Universities, Orsay Cedex (France); Garcia, Camilo A.; Vanderlinden, Bruno; Flamen, Patrick [Universite Libre de Bruxelles, Department of Nuclear Medicine, Institut Jules Bordet, Brussels (Belgium); Hendlisz, Alain [Universite Libre de Bruxelles, Department of Gastroenterology, Institut Jules Bordet, Brussels (Belgium)

    2013-02-15

    To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total lesion glycolysis (TLG). The relative change in each index between the two scans was calculated for each lesion. Lesions were also classified as responding and nonresponding lesions using the Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6-8 weeks after starting therapy. Bland-Altman analyses were performed to compare the various indices. Based on the RECIST classification, ROC analyses were used to determine how accurately the indices predicted lesion response to therapy later seen with RECIST. RECIST showed 27 responding and 74 nonresponding lesions. Bland-Altman analyses showed that the four SUV indices uncorrected for PVE could not be used interchangeably, nor could the two SUV corrected for PVE. The areas under the ROC curves (AUC) were not significantly different between the SUV indices not corrected for PVE. The mean SUV change in a lesion better predicted lesion response without than with PVE correction. The AUC was significantly higher for SUV uncorrected for PVE than for the MV, but change in MV provided some information regarding the lesion response to therapy (AUC >0.5). In these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour response on day 14 after starting therapy as assessed 4 to 6 weeks later (i.e. 6 to 8 weeks after therapy initiation) using the RECIST criteria. Neither correcting SUV for PVE nor measuring TLG improved the assessment of tumour

  18. FDG-PET for prediction of tumour aggressiveness and response to intra-arterial chemotherapy and radiotherapy in head and neck cancer

    International Nuclear Information System (INIS)

    Kitagawa, Yoshimasa; Sano, Kazuo; Nakamura, Mikiko; Ogasawara, Toshiyuki; Nishizawa, Sadahiko; Sadato, Norihiro; Yonekura, Yoshiharu

    2003-01-01

    The aim of this study was to evaluate the possible usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting tumour aggressiveness and response to intra-arterial chemotherapy (THP-ADM + 5-FU + carboplatin) and radiotherapy in head and neck carcinomas. Twenty patients with squamous cell carcinoma (SCC) of the head and neck were included in the study. All patients completed the treatment regimen, and each patient underwent two FDG-PET studies, one prior to and one at 4 weeks after the chemoradiotherapy. For the quantitative evaluation of regional FDG uptake in the tumour, standardised uptake values (SUVs) with an uptake period of 50 min were used. The pre-treatment SUV (pre-SUV) and post-treatment SUV (post-SUV) were compared with immunohistologically evaluated tumour proliferative potential (MIB-1 and PCNA), tumour cellularity and other parameters including histological grade, tumour size and stage, clinical response and histological evaluation after therapy. All neoplastic lesions showed high SUVs (mean, 9.75 mg/ml) prior to the treatment, which decreased significantly after the therapy (3.41 mg/ml, P 7 mg/ml) showed residual tumour cells after treatment in 4 out of 15 patients, whereas patients whose lesions showed a low pre-SUV (<7 mg/ml, five patients) were successfully treated. Four out of six tumours with a post-SUV higher than 4 mg/ml had viable tumour cells, whereas all tumours (14/14) with a post-SUV lower than 4 mg/ml showed no viable tumour cells. Computational multivariate analysis using multiple regression revealed four factors (MIB-1 labelling index, cellularity, the number of MIB-1 labelled tumour cells and tumour size grade) contributing to pre-SUV and pre-post SUV (difference between pre-treatment SUV and post-treatment SUV in each patient) with statistical significance. FDG uptake in the tumour might reflect tumour aggressiveness, which is closely related to the proliferative activity and cellularity. Pre

  19. A spatio-temporal simulation model of the response of solid tumours to radiotherapy in vivo: parametric validation concerning oxygen enhancement ratio and cell cycle duration

    International Nuclear Information System (INIS)

    Antipas, Vassilis P; Stamatakos, Georgios S; Uzunoglu, Nikolaos K; Dionysiou, Dimitra D; Dale, Roger G

    2004-01-01

    Advanced bio-simulation methods are expected to substantially improve radiotherapy treatment planning. To this end a novel spatio-temporal patient-specific simulation model of the in vivo response of malignant tumours to radiotherapy schemes has been recently developed by our group. This paper discusses recent improvements to the model: an optimized algorithm leading to conformal shrinkage of the tumour as a response to radiotherapy, the introduction of the oxygen enhancement ratio (OER), a realistic initial cell phase distribution and finally an advanced imaging-based algorithm simulating the neovascularization field. A parametric study of the influence of the cell cycle duration T c , OER, OER β for the beta LQ parameter on tumour growth, shrinkage and response to irradiation under two different fractionation schemes has been made. The model has been applied to two glioblastoma multiforme (GBM) cases, one with wild type (wt) and another one with mutated (mt) p53 gene. Furthermore, the model has been applied to a hypothetical GBM tumour with α and β values corresponding to those of generic radiosensitive tumours. According to the model predictions, a whole tumour with shorter T c tends to repopulate faster, as is to be expected. Furthermore, a higher OER value for the dormant cells leads to a more radioresistant whole tumour. A small variation of the OER β value does not seem to play a major role in the tumour response. Accelerated fractionation proved to be superior to the standard scheme for the whole range of the OER values considered. Finally, the tumour with mt p53 was shown to be more radioresistant compared to the tumour with wt p53. Although all simulation predictions agree at least qualitatively with the clinical experience and literature, a long-term clinical adaptation and quantitative validation procedure is in progress

  20. Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document.

    Science.gov (United States)

    Nguyen, S M; Thamm, D H; Vail, D M; London, C A

    2015-09-01

    In veterinary medical oncology, there is currently no standardized protocol for assessing response to therapy in solid tumours. The lack of such a formalized guideline makes it challenging to critically compare outcome measures across various treatment protocols. The Veterinary Cooperative Oncology Group (VCOG) membership consensus document presented here is based on the recommendations of a subcommittee of American College of Veterinary Internal Medicine (ACVIM) board-certified veterinary oncologists. This consensus paper has used the human response evaluation criteria in solid tumours (RECIST v1.1) as a framework to establish standard procedures for response assessment in canine solid tumours that is meant to be easy to use, repeatable and applicable across a variety of clinical trial structures in veterinary oncology. It is hoped that this new canine RECIST (cRECIST v1.0) will be adopted within the veterinary oncology community and thereby facilitate the comparison of current and future treatment protocols used for companion animals with cancer. © 2013 Blackwell Publishing Ltd.

  1. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    LENUS (Irish Health Repository)

    Whelan, M C

    2012-01-31

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.

  2. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab.

    Science.gov (United States)

    McDermott, David F; Drake, Charles G; Sznol, Mario; Choueiri, Toni K; Powderly, John D; Smith, David C; Brahmer, Julie R; Carvajal, Richard D; Hammers, Hans J; Puzanov, Igor; Hodi, F Stephen; Kluger, Harriet M; Topalian, Suzanne L; Pardoll, Drew M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; McDonald, Dan; Sankar, Vindira; Sosman, Jeffrey A; Atkins, Michael B

    2015-06-20

    Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC. © 2015 by American Society of Clinical Oncology.

  3. Durability of response to vaccination against viral hepatitis A in HIV-infected patients: a 5-year observation.

    Science.gov (United States)

    Jabłonowska, E; Kuydowicz, J

    2014-09-01

    The aim of this study was to estimate the prevalence of total antibodies to hepatitis A virus (anti-HAV-T) in the group of HIV-positive adults in Lodz region of Poland, and to evaluate the response and long-term immunity after vaccination against hepatitis A virus. In the group of 234 HIV-infected patients, 72 persons (30.8%) were anti-HAV-T positive (>20 IU/L). In multivariate analysis, two independent factors associated with the presence of anti-HAV-T were identified: the age of patients (OR = 1.07) and the presence of antibodies to hepatitis C virus (OR = 2.87). Vaccination was completed in 83 patients. Good response (anti-HAV-T >20 IU/L one month after the booster dose) was obtained in 79.5% of patients. In patients with CD4 >200 cells/µL in multivariate analysis only presence of antibodies to hepatitis C virus was a prognostic factor for the response to vaccination (OR = 0.13). Among responders available for the follow-up, 82% (50 out of 61) had detectable anti-HAV-T at 1 year and 75.5% (37 out of 49) at 5 years. Our results demonstrate that most of the studied HIV-positive patients were susceptible to hepatitis A virus infection. Most HIV-infected adults with high CD4 counts had a durable response even up to 5 years after vaccination. Patients with a HIV/hepatitis C virus coinfection displayed a worse response to vaccination. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  4. Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, Bart de; Hoekstra, Anne; Rijk, Peter P. van; Klerk, John M.H. de [Department of Nuclear Medicine, Room E02.222, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands); Brans, Boudewijn; Dierckx, Rudi A. [Department of Nuclear Medicine, Ghent University Hospital, Ghent (Belgium); Zelissen, Pierre M.J.; Koppeschaar, Hans P.F.; Lips, Cees J.M. [Department of Endocrinology, University Medical Center Utrecht (Netherlands)

    2003-03-01

    The development of recombinant human thyrotropin (rhTSH) has given clinicians new options for diagnostic follow-up and treatment of patients with differentiated thyroid cancer (DTC). This paper evaluates the tumour dosimetry and response following -iodine-131 treatment of metastatic thyroid cancer patients after rhTSH stimulation instead of classical hormone withdrawal-induced hypothyroidism. Nineteen consecutive {sup 131}I treatments in 16 patients were performed after rhTSH stimulation. All patients had undergone a near-total thyroidectomy followed by an ablative dosage of {sup 131}I. They all suffered from metastatic or recurrent disease showing tumoral {sup 131}I uptake on previous post-treatment scintigraphy. Dosimetric calculations were performed using {sup 131}I tumour uptake measurements from post-treatment {sup 131}I scintigrams and tumour volume estimations from radiological images. Response was assessed by comparing pre-treatment serum thyroglobulin (Tg) level with the Tg level 3 months post treatment. In 18 out of 19 treatments, uptake of {sup 131}I in metastatic or recurrent lesions was seen. The median tumour radiation dose was 26.3 Gy (range 1.3-368 Gy), and the median effective half-life was 2.7 days (range 0.5-6.5 days). Eleven of 19 treatments (10/16 patients) were evaluable for response after 3 months. {sup 131}I therapy with rhTSH resulted in a biochemical partial response in 3/11 or 27% of treatments (two patients), biochemical stable disease in 2/11 or 18% of treatments and biochemical progressive disease in 6/11 or 55% of treatments. Our study showed that although tumour doses in DTC patients treated with {sup 131}I after rhTSH were highly variable, 45% of treatments led to disease stabilisation or partial remission when using rhTSH in conjunction with {sup 131}I therapy, without serious side-effects and with minimal impact on quality of life. RhTSH is therefore adequately satisfactory as an adjuvant tool in therapeutic settings and is

  5. Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

    Science.gov (United States)

    Stephens, T. C.; Peacock, J. H.

    1977-01-01

    The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY. PMID:921888

  6. Durable remission of leptomeningeal metastases from hormone-responsive prostate cancer.

    Science.gov (United States)

    Zhang, Meng; Mahta, Ali; Kim, Ryan Y; Akar, Serra; Kesari, Santosh

    2012-06-01

    Prostate cancer is rarely associated with leptomeningeal metastasis. An 87-year-old man with a history of prostate cancer presented with leptomeningeal metastasis. He received hormonal therapy with leuprolide. Subsequently, he achieved an impressive response, indicated by a constant fall in his PSA levels and by the stabilization of leptomeningeal disease and clinical improvement. Hormonal therapy may be effective in inducing remission in hormone-sensitive prostate cancer with leptomeningeal metastasis.

  7. Efficacy and toxicity management of CAR-T-cell immunotherapy: a matter of responsiveness control or tumour-specificity?

    Science.gov (United States)

    Alonso-Camino, Vanesa; Harwood, Seandean Lykke; Álvarez-Méndez, Ana; Alvarez-Vallina, Luis

    2016-04-15

    Chimaeric antigen receptor (CAR)-expressing T-cells have demonstrated potent clinical efficacy in patients with haematological malignancies. However, the use of CAR-T-cells targeting solid tumour-associated antigens (TAAs) has been limited by organ toxicities related to activation of T-cell effector functions through the CAR. Most existing CARs recognize TAAs, which are also found in normal tissues. CAR-T-cell-mediated destruction of normal tissues constitutes a major roadblock to CAR-T-cell therapy, and must be avoided or mitigated. There is a broad range of strategies for modulating antigen responsiveness of CAR-T-cells, with varying degrees of complexity. Some of them might ameliorate the acute and chronic toxicities associated with current CAR constructs. However, further embellishments to CAR therapy may complicate clinical implementation and possibly create new immunogenicity issues. In contrast, the development of CARs targeting truly tumour-specific antigens might circumvent on-target/off-tumour toxicities without adding additional complexity to CAR-T-cell therapies, but these antigens have been elusive and may require novel selection strategies for their discovery. © 2016 Authors; published by Portland Press Limited.

  8. A metastatic colon adenocarcinoma harboring BRAF V600E has a durable major response to dabrafenib/trametinib and chemotherapy

    Directory of Open Access Journals (Sweden)

    Williams CB

    2015-12-01

    Full Text Available Casey B Williams,1,* Caitlin McMahon,2,* Siraj M Ali,2 Mark Abramovitz,1 Kirstin A Williams,1 Jessica Klein,1 Heidi McKean,1 Roman Yelensky,2 Thomas J George Jr,3 Julia A Elvin,2 Salil Soman,4 Doron Lipson,2 Juliann Chmielecki,2 Deborah Morosini,2 Vincent A Miller,2 Philip J Stephens,2 Jeffrey S Ross,2,5 Brian Leyland-Jones1 1Avera Cancer Institute, Sioux Falls, SD, USA; 2Foundation Medicine, Inc., Cambridge, MA, USA; 3University of Florida College of Medicine, Gainesville, FL, USA; 4Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Albany Medical College, Albany, NY, USA *These authors contributed equally to this work Abstract: The subset of metastatic colorectal adenocarcinomas that harbor BRAF V600E mutations are aggressive tumors with significantly shortened survival and limited treatment options. Here we present a colorectal cancer patient whose disease progressed through standard chemotherapy and who developed liver metastasis. Comprehensive genomic profiling (FoundationOne® identified a BRAF V600E mutation in the liver lesion, as well as other genomic alterations consistent with colorectal cancers. Combination therapy of dabrafenib and trametinib with standard cytotoxic chemotherapy resulted in a durable major ongoing response for the patient. This report illustrates the utility of comprehensive genomic profiling with personalized targeted therapy for aggressive metastatic colorectal adenocarcinomas. Keywords: oxaliplatin, colorectal adenocarcinoma, combination targeted therapy, BRAF mutations

  9. Acid phosphates response in murine rhabdomyosarcoma for various tumour volumes and after different doses of neutron irradiation, alone or combined with exogenous ATP

    International Nuclear Information System (INIS)

    Szeinfeld, D.; De Villiers, N.

    1991-01-01

    Acid phosphatase activity measured in a methylocholanthrene-induced murine rhabdomyosarcoma showed a monotonically increasing relation between enzyme activity and tumour volume. This could be related to the lytic activity of the enzyme in large tumours which become more hypoxic and necrotic, and hence enhance degradation and turnover of damaged tumour cells. The tumours were also subjected to irradiation using doses of 2.0, 3.8 and 6.0 Gy from a neutron therapy facility p(66 MeV)/Be. The correlation between different doses and response of acid phosphatase activity could reflect the relation of magnitude of damage from metabolic disturbances, with dose. Furthermore exogenous ATP was shown to provide radioprotective action against neutron irradiation in two different experiments. The ATP reduced the activity of this lytic enzyme in irradiated tumours and also decreased tumour growth delay. This radioprotective role of exogenous ATP in a murine tumour could be related to physiological regulatory processes during defence mechanisms to maintain self-organisation in response to the radiation damage. (orig.) [de

  10. TUMOUR VACCINE

    NARCIS (Netherlands)

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

    1999-01-01

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

  11. Quantitative MRI assessment of VX2 tumour oxygenation changes in response to hyperoxia and hypercapnia

    Energy Technology Data Exchange (ETDEWEB)

    Winter, Jeff D; Cheng, Hai-Ling Margaret [Research Institute and Diagnostic Imaging, Hospital for Sick Children, Toronto M5G 1X8 (Canada); Akens, Margarete K, E-mail: Hai-Ling.Cheng@sickkids.ca [Division of Orthopaedic Surgery, Orthopaedic Biomechanics Laboratory, Sunnybrook Health Science, Toronto M4N 3M5 (Canada)

    2011-03-07

    Magnetic resonance imaging (MRI) relaxation times provide indirect estimates of tissue O{sub 2} for monitoring tumour oxygenation. This study provides insight into mechanisms underlying longitudinal (R{sub 1} = 1/T{sub 1}) and transverse effective (R{sub 2}* = 1/T{sub 2}*) relaxation rate changes during inhalation of 100% O{sub 2} and 3%, 6% and 9% CO{sub 2} (balanced O{sub 2}) in a rabbit tumour model. Quantitative R{sub 1}, R{sub 2}*, and dynamic contrast-enhanced (DCE) imaging was performed in six rabbits 12-23 days following implantation of VX2 carcinoma cells in the quadricep muscle. Invasive measurements of tissue partial pressure of O{sub 2} (pO{sub 2}) and perfusion were also performed, which revealed elevated pO{sub 2} levels in all tumour regions for all hyperoxic gases compared to baseline (air) and reduced perfusion for carbogen. During 100% O{sub 2} breathing, an R{sub 1} increase and R{sub 2}* decrease consistent with elevated pO{sub 2} were observed within tumours. DCE-derived blood flow was weakly correlated with R{sub 1} changes from air to 100% O{sub 2}. Further addition of CO{sub 2} (carbogen) did not introduce considerable changes in MR relaxation rates, but a trend towards higher R{sub 1} relative to breathing 100% O{sub 2} was observed, while R{sub 2}* changes were inconsistent. This observation supports the predominance of dissolved O{sub 2} on R{sub 1} sensitivity and demonstrates the value of R{sub 1} over R{sub 2}* for tissue oxygenation measures.

  12. Emerging roles of extracellular vesicles in the adaptive response of tumour cells to microenvironmental stress

    Directory of Open Access Journals (Sweden)

    Paulina Kucharzewska

    2013-03-01

    Full Text Available Cells are constantly subjected to various types of endogenous and exogenous stressful stimuli, which can cause serious and even permanent damage. The ability of a cell to sense and adapt to environmental alterations is thus vital to maintain tissue homeostasis during development and adult life. Here, we review some of the major phenotypic characteristics of the hostile tumour microenvironment and the emerging roles of extracellular vesicles in these events.

  13. Specific Cytotoxicity Against Autologous Tumour and Proliferative Responses of Human Lymphocytes Grown in Interleukin 2

    Science.gov (United States)

    1981-08-11

    reactivity against tumour cells. These cellular reagents will be useful in defining the antigenicity of human neoplasms and possibly in therapy . S, N 0) 02...Stjernswird. of human neoplasms and possibly in therapy . 1979; Vose et al., 1978; Vinky et al., 1979). Purifica- The derivation of cultured T cells...mononuclear cells were sepa- had increased 100- to 200-fold. Cells were cultured in rated by floatation on Ficoll-Hypaque (LSM, Litton- medium without IL-2 for

  14. Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033

    International Nuclear Information System (INIS)

    Dorow, Donna S.; Cullinane, Carleen; Conus, Nelly; Roselt, Peter; Binns, David; McCarthy, Timothy J.; McArthur, Grant A.; Hicks, Rodney J.

    2006-01-01

    This study was designed as ''proof of concept'' for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy. Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6-8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [ 18 F]fluorodeoxyglucose, [ 18 F]fluoro-L-thymidine, [ 18 F]fluoro-azoazomycinarabinoside or [ 18 F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia. During the study period, mean uptake of all PET tracers generally increased for control tumours compared to baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20-60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle markers was unchanged or increased in control tumours and generally decreased with CI-1033 treatment, compared to baseline. Thymidine kinase activity was reduced in all tumours compared to baseline at day 3 but was sevenfold higher in control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the hypoxia marker pimonidazole was stable in control tumours but was severely reduced following 7 days of CI-1033 treatment. CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET. The PET findings correlated well with ex vivo biomarkers for each of the cellular processes studied. These results confirm the utility of small animal PET for evaluation of the effectiveness of molecularly targeted therapies and simultaneously definition of specific cellular processes involved in the therapeutic response. (orig.)

  15. CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology.

    Science.gov (United States)

    Shaw, Richard J; Hall, Gillian L; Lowe, Derek; Bowers, Naomi L; Liloglou, Triantafillos; Field, John K; Woolgar, Julia A; Risk, Janet M

    2007-10-01

    Studies in several tumour sites highlight the significance of the CpG island methylation phenotype (CIMP), with distinct features of histology, biological aggression and outcome. We utilise pyrosequencing techniques of quantitative methylation analysis to investigate the presence of CIMP in oral squamous cell carcinoma (OSCC) for the first time, and evaluate its correlation with allelic imbalance, pathology and clinical behaviour. Tumour tissue, control tissue and PBLs were obtained from 74 patients with oral squamous cell carcinoma. Pyrosequencing was used to analyse methylation patterns in 75-200 bp regions of the CpG rich gene promoters of 10 genes with a broad range of cellular functions. Allelic imbalance was investigated using a multiplexed panel of 11 microsatellite markers. Corresponding variables, histopathological staging and grading were correlated with these genetic and epigenetic aberrations. A cluster of tumours with a greater degree of promoter methylation than would be predicted by chance alone (P=0.001) were designated CIMP+ve. This group had less aggressive tumour biology in terms of tumour thickness (p=0.015) and nodal metastasis (P=0.012), this being apparently independent of tumour diameter. Further, it seems that these CIMP+ve tumours excited a greater host inflammatory response (P=0.019). The exact mechanisms underlying CIMP remain obscure but the association with a greater inflammatory host response supports existing theories relating these features in other tumour sites. As CIMP has significant associations with other well documented prognostic indicators, it may prove beneficial to include methylation analyses in molecular risk modelling of tumours.

  16. Durability of treatment response to zolpidem with three different maintenance regimens: a preliminary study.

    Science.gov (United States)

    Perlis, Michael; Grandner, Michael; Zee, Jarcy; Bremer, Erin; Whinnery, Julia; Barilla, Holly; Andalia, Priscilla; Gehrman, Phil; Morales, Knashawn; Thase, Michael; Bootzin, Richard; Ader, Robert

    2015-09-01

    At present, there is no consensus regarding how to medically manage chronic insomnia in the long term. The unstated standard of practice is for patients to use hypnotics intermittently. The present study aimed to compare a partial reinforcement strategy with nightly and intermittent dosing strategies for its potential as a maintenance therapy. A mixed model was used in the study. One between-subjects factor: group (n = 4). One repeated-measures factor: time (12 weekly assessments). A total of 74 subjects with chronic Insomnia were treated with 10 mg zolpidem for 4 weeks. Treatment respondents were randomized to nightly dosing with 10 mg or 5 mg (QHS-10 and QHS-5), intermittent dosing with 10 mg (IDS-10 [3-5 days weekly]), or partial reinforcement dosing with 10 mg (PRS-10 [nightly pill use with 50% active medication and 50% placebos]) for 12 weeks. It was found, in compliant subjects (n = 55), that all four strategies evaluated maintained treatment response over time (ie, prevented or delayed relapse). For the subjects that remained in remission, the subjects in the intermittent dosing group (IDS-10) group exhibited poorer sleep continuity. While best considered a preliminary study, the present findings suggest that the partial reinforcement strategy may be a viable means toward maintaining treatment gains over time with less active medication. Copyright © 2015. Published by Elsevier B.V.

  17. Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

    Science.gov (United States)

    Link, C S; Teipel, R; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Reinhardt, J; Oelschlägel, U; von Bonin, M; Middeke, J M; Muetherig, A; Trautmann-Grill, K; Platzbecker, U; Bornhäuser, M; Schetelig, J

    2016-06-01

    Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

  18. Long Rest Interval Promotes Durable Testosterone Responses in High-Intensity Bench Press.

    Science.gov (United States)

    Scudese, Estevão; Simão, Roberto; Senna, Gilmar; Vingren, Jakob L; Willardson, Jeffrey M; Baffi, Matheus; Miranda, Humberto

    2016-05-01

    The purpose of this study was to examine the influence of rest period duration (1 vs. 3 minute between sets) on acute hormone responses to a high-intensity and equal volume bench press workout. Ten resistance-trained men (25.2 ± 5.6 years; 78.2 ± 5.7 kg; 176.7 ± 5.4 cm; bench press relative strength: 1.3 ± 0.1 kg per kilogram of body mass) performed 2 bench press workouts separated by 1 week. Each workout consisted of 5 sets of 3 repetitions performed at 85% of 1 repetition maximum, with either 1- or 3-minute rest between sets. Circulating concentrations of total testosterone (TT), free testosterone (FT), cortisol (C), testosterone/cortisol ratio (TT/C), and growth hormone (GH) were measured at preworkout (PRE), and immediately (T0), 15 minutes (T15), and 30 minutes (T30) postworkout. Rating of perceived exertion was recorded before and after each set. For TT, both rest lengths enhanced all postexercise verifications (T0, T15, and T30) compared with PRE, with 1 minute showing decreases on T15 and T30 compared with T0. For FT, both 1- and 3-minute rest protocols triggered augmentations on distinct postexercise moments (T0 and T15 for 1 minute; T15 and T30 for 3-minute) compared with PRE. The C values did not change throughout any postexercise verification for either rests. The TT/C ratio was significantly elevated for both rests in all postexercise moments compared with PRE. Finally, GH values did not change for both rest lengths. In conclusion, although both short and long rest periods enhanced acute testosterone values, the longer rest promoted a long-lasting elevation for both TT and FT.

  19. Concrete durability

    Directory of Open Access Journals (Sweden)

    Gaspar Tébar, Demetrio

    1991-03-01

    Full Text Available The evidence that the concrete is not a material for ever was noticed from the beginning of its industrial use. In the present work, the author describes the studies carried out during the last century and the early ages of the present one, mainly devoted to the study of the durability in sea water. At the present days, and in spite of the numerous papers published from then, the study of the concrete durability continues focusing the research priorities and economical resources of researchers and industries related with this material. Moreover, the new laboratory techniques are allowing to understand old problems and even to open again the discussion on reaction mechanisms which were believed to be completely understood. The article finalizes with a brief description of the numerous studies carried out at the Institute Eduardo Torroja on concrete durability, mainly those related with the resistance against gypsum attack (so abundant in our country land and against sea water attack.

    La realidad de que el hormigón no es un material eterno y es susceptible de sufrir ataques por agentes químicos, fue constatada desde el comienzo mismo de su uso industrial. En el presente trabajo el autor enumera los estudios realizados el siglo pasado y a comienzos del presente sobre la durabilidad del hormigón en agua de mar. En la actualidad y a pesar de los numerosos trabajos desarrollados desde entonces, el estudio de la durabilidad del hormigón sigue centrando la atención prioritaria y los recursos económicos de los investigadores e industrias relacionadas con este material. Además las nuevas técnicas de estudio están permitiendo comprender antiguos problemas e incluso reabrir la discusión sobre mecanismos de reacción que se creían completamente explicados. Finaliza el artículo con una descripción somera de los múltiples trabajos realizados en el Instituto Eduardo Torreja sobre la materia, en especial los estudios realizados sobre

  20. Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial.

    Science.gov (United States)

    Hale, Matthew D; Nankivell, Matthew; Hutchins, Gordon G; Stenning, Sally P; Langley, Ruth E; Mueller, Wolfram; West, Nicholas P; Wright, Alexander I; Treanor, Darren; Hewitt, Lindsay C; Allum, William H; Cunningham, David; Hayden, Jeremy D; Grabsch, Heike I

    2016-11-22

    Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402. This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification.Proportion of tumour is a novel biomarker which can be measured in the pre-treatment diagnostic biopsy and which may enable the identification of chemotherapy responders and non-responders among patients with oesophageal carcinoma. Proportion of tumour could easily become part of the routine reporting of oesophageal cancer biopsies and may aid in managing patients with borderline resectable cancer.

  1. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg

    2014-01-01

    . Time from ILP to recurrence was a median of seven months (range 1-37 months) for patients with CR or PR. Survival was longer for patients with CR or PR than for patients showing NC or progression. Several patients had mild or moderate local toxicity reactions, two patients developed severe local...... toxicity. CONCLUSION: ILP induces tumour regression in the vast majority of patients. One patient, i.e. 1% of the group, died from surgical complications. Otherwise, ILP treatment had an acceptable morbidity in this group of very sick patients. We are convinced that the treatment should be offered...

  2. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a

  3. Anti-tumour activity in RAS-driven tumours by blocking AKT and MEK

    Science.gov (United States)

    Tolcher, Anthony W.; Khan, Khurum; Ong, Michael; Banerji, Udai; Papadimitrakopoulou, Vassiliki; Gandara, David R.; Patnaik, Amita; Baird, Richard D.; Olmos, David; Garrett, Christopher R.; Skolnik, Jeffrey M.; Rubin, Eric H.; Smith, Paul D.; Huang, Pearl; Learoyd, Maria; Shannon, Keith A.; Morosky, Anne; Tetteh, Ernestina; Jou, Ying-Ming; Papadopoulos, Kyriakos P.; Moreno, Victor; Kaiser, Brianne; Yap, Timothy A.; Yan, Li; de Bono, Johann S.

    2014-01-01

    Purpose KRAS is the most commonly mutated oncogene in human tumours. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. Experimental Design We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumours. Recommended dosing schedules were defined as MK-2206 135 mg weekly and selumetinib 100 mg once-daily. Results Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhoea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical anti-tumour activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. Conclusion Responses in KRAS-mutant cancers were generally durable. Clinical co-targeting of MEK and AKT signalling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748). PMID:25516890

  4. Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations.

    Directory of Open Access Journals (Sweden)

    Nori Yoshioka

    Full Text Available Health care workers (HCWs are frequently exposed to hepatitis B virus (HBV infection. The efficacy and safety of immunization with the hepatitis B (HB vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years, and long responders (those who retained positive anti-HBs levels for 3 years and more. We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229, 54.5% after two doses (n = 11, and 4.2% after a single dose (n = 24. Of 213 primary responders, the anti-HBs levels of 95 participants (44.6% fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective

  5. Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy

    International Nuclear Information System (INIS)

    Matthews, Q; Jirasek, A; Lum, J J; Brolo, A G

    2011-01-01

    This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF 2 > 0.6) and the R3 cell lines are radiosensitive (SF 2 < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1) the

  6. HPV 16-associated tumours: IL-12 can repair the absence of cytotoxic and proliferative responses of tumour infiltrating cells after chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Bieblová, Jana; Rossowska, J.; Kuropka, P.; Pajtasz-Piasecka, E.; Bubeník, Jan; Reiniš, Milan

    2009-01-01

    Roč. 34, č. 1 (2009), s. 173-180 ISSN 1019-6439 R&D Projects: GA ČR GA301/06/0774 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Polish Ministry of Science and Higher Education(PL) N401 235334 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * vaccines * tumour-infiltrating cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.447, year: 2009

  7. Use of positron emission tomography for staging, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour

    International Nuclear Information System (INIS)

    Misch, Daniel; Steffen, Ingo G.; Furth, Christian; Stoever, Brigitte; Amthauer, Holger; Denecke, Timm; Schoenberger, Stefan; Voelker, Thomas; Henze, Guenter; Hautzel, Hubertus

    2008-01-01

    To evaluate FDG-PET for staging, grading, preoperative response assessment and posttherapeutic evaluation in children with Wilms tumour (WT). In this study, 23 FDG-PET examinations in 12 paediatric patients (female, n=5; male, n=7; age, 1-19 years) with WT (primary, n=9; relapsed, n=3) were analysed. All patients were examined with conventional imaging methods (CIM) according to the SIOP2001/GPOH trial protocol. Additionally, FDG-PET/PET-CT was performed for staging (n = 12), preoperative response assessment (n=6) and posttherapeutic evaluation (n=5). Imaging results of FDG-PET and CIM were analysed regarding the accuracy in tumour visualisation, impact on therapeutic management and preoperative response assessment, with clinical follow-up and histopathology as the standard of reference. FDG-PET and CIM showed concordant results for staging of primary WT, whereas FDG-PET was superior in 1/3 cases with recurrent WT. Concerning histological differentiation, one case with anaplastic WT had an standard uptake value (SUV) of 12.3, which was remarkably higher than the average SUV in the eight cases with intermediate risk histology. No parameter analysed for PET or CIM was reliably predictive for histological regression or clinical outcome. After completion of therapy, FDG-PET was superior to CIM in 2/5 cases in detecting residual disease with therapeutic relevance. FDG-PET does not provide additional information to the traditional imaging work-up for staging WT patients, preoperative response assessment and clinical outcome. FDG-PET was advantageous in ruling out residual disease after completion of first line treatment and in pretherapeutic staging of relapse patients. Furthermore, there seems to be a good correlation of initial SUV and histological differentiation. (orig.)

  8. Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

    Science.gov (United States)

    Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

    2012-01-01

    Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

  9. Predictive factors for the response of pulmonary tumours treated by robotic stereotactic radiotherapy; Facteurs predictifs pour la reponse des tumeurs pulmonaires traitees par radiotherapie stereotaxique robotisee

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, J.; Benezery, K.; Thariat, J.; Angellier, G.; Poudenx, M.; Bondiau, P.Y. [Centre Antoine-Lacassagne, 06 - Nice (France); Beckendorf, V. [Centre Alexis-Vautrin, 54 - Nancy (France); Venissac, N. [Centre hospitalo-universitaire Pasteur, 06 - Nice (France)

    2010-10-15

    The authors report a study which aimed at identifying factors influencing the response to radiotherapy performed in robotic stereotactic conditions with CyberKnife within the frame of treatment of primitive or secondary pulmonary tumours. Thirty eight stage I cancers, 22 metastases including 17 epidermoid carcinomas, and 43 adenocarcinomas have been treated this way. The analysis of data and results reveals that feminine gender, a biological dose greater than 140 Gy, and an age greater than 65 year old are associated with a better tumour response. Short communication

  10. Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model

    International Nuclear Information System (INIS)

    Lo Dico, A.; Martelli, C.; Valtorta, S.; Belloli, S.; Raccagni, I.; Moresco, R.M.; Diceglie, C.; Gianelli, U.; Bosari, S.; Vaira, V.; Politi, L.S.; Lucignani, G.; Ottobrini, L.

    2015-01-01

    Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures. (orig.)

  11. Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model

    Energy Technology Data Exchange (ETDEWEB)

    Lo Dico, A.; Martelli, C. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); Valtorta, S.; Belloli, S. [National Researches Council (CNR), Institute of Molecular Bioimaging and Physiology (IBFM), Segrate, MI (Italy); IRCCS San Raffaele Scientific Institute, Experimental Imaging Center, Milan (Italy); Raccagni, I.; Moresco, R.M. [IRCCS San Raffaele Scientific Institute, Experimental Imaging Center, Milan (Italy); University of Milano-Bicocca, Department of Health Sciences, Monza (Italy); Diceglie, C. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Doctorate School of Molecular Medicine, Milan (Italy); Gianelli, U.; Bosari, S. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Division of Pathology, Milan (Italy); Vaira, V. [Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Division of Pathology, Milan (Italy); Istituto Nazionale Genetica Molecolare ' ' Romeo ed Enrica Invernizzi' ' (INGM), Milan (Italy); Politi, L.S. [IRCCS San Raffaele Scientific Institute, Neuroradiology Department and Neuroradiology Research Group, Milan (Italy); Lucignani, G. [University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); University of Milan, Department of Health Sciences, Milan (Italy); San Paolo Hospital, Department of Diagnostic Services, Unit of Nuclear Medicine, Milan (Italy); Ottobrini, L. [University of Milan, Department of Pathophysiology and Transplantation, Milan (Italy); University of Milan, Centre of Molecular and Cellular Imaging-IMAGO, Milan (Italy); National Researches Council (CNR), Institute of Molecular Bioimaging and Physiology (IBFM), Segrate, MI (Italy)

    2015-03-27

    Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model. U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging. This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action. The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures. (orig.)

  12. Expression patterns of endogenous avian retrovirus ALVE1 and its response to infection with exogenous avian tumour viruses.

    Science.gov (United States)

    Hu, Xuming; Zhu, Wenqi; Chen, Shihao; Liu, Yangyang; Sun, Zhen; Geng, Tuoyu; Song, Chengyi; Gao, Bo; Wang, Xiaoyan; Qin, Aijian; Cui, Hengmi

    2017-01-01

    Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates and have been implicated in a variety of human diseases, including cancer. However, the characteristic expression patterns of ERVs, particularly in virus-induced tumours, is not fully clear. DNA methylation was analysed by bisulfite pyrosequencing, and gene expression was analysed by RT-qPCR. In this study, we first found that the endogenous avian retrovirus ALVE1 was highly expressed in some chicken tissues (including the heart, bursa, thymus, and spleen) at 2 days of age, but its expression was markedly decreased at 35 days of age. In contrast, the CpG methylation level of ALVE1 was significantly lower in heart and bursa at 2 days than at 35 days of age. Moreover, we found that the expression of ALVE1 was significantly inhibited in chicken embryo fibroblast cells (CEFs) and MSB1 cells infected with avian leukosis virus subgroup J (ALVJ) and reticuloendotheliosis virus (REV) at the early stages of infection. In contrast, the expression of the ALVE1 env gene was significantly induced in CEFs and MSB1 cells infected with Marek's disease virus (MDV). However, the methylation and expression levels of the ALVE1 long terminal repeat (LTR) did not show obvious alterations in response to viral infection. The present study revealed the expression patterns of ALVE1 in a variety of chicken organs and tissues and in chicken cells in response to avian tumour virus infection. These findings may be of significance for understanding the role and function of ERVs that are present in the host genome.

  13. Mouse Model of Devil Facial Tumour Disease establishes that an effective immune response can be generated against the cancer cells

    Directory of Open Access Journals (Sweden)

    Terry L Pinfold

    2014-05-01

    Full Text Available The largest carnivorous marsupial in Australia, the Tasmanian devil (Sarcophilus harrisii is facing extinction in the wild due to a transmissible cancer known as Devil Facial Tumour Disease (DFTD. DFTD is a clonal cell line transmitted from host to host with 100% mortality and no known immunity. While it was first considered that low genetic diversity of the population of devils enabled the allograft transmission of DFTD recent evidence reveals that genetically diverse animals succumb to the disease. The lack of an immune response against the DFTD tumor cells may be due to a lack of immunogenicity of the tumor cells. This could facilitate transmission between devils. To test immunogenicity, mice were injected with viable DFTD cells and anti-DFTD immune responses analyzed. A range of antibody isotypes against DFTD cells was detected, indicating that as DFTD cells can induce an immune response they are immunogenic. This was supported by cytokine production, when splenocytes from mice injected with DFTD cells were cultured in vitro with DFTD cells and the supernatant analyzed. There was a significant production of IFN-γ and TNF-α following the first injection with DFTD cells and a significant production of IL-6 and IL-10 following the second injection. Splenocytes from naïve or immunized mice killed DFTD cells in in vitro cytotoxicity assays. Thus they are also targets for immunological destruction. We conclude that as an immune response can be generated against DFTD cells they would be suitable targets for a vaccine.

  14. Response of clonogenic cells of mice solid tumour NKLy/LL to N-methyl-N-nitrosourea

    International Nuclear Information System (INIS)

    Chan Tik Kan; Afanas'ev, G.G.; Pelevina, I.I.

    1979-01-01

    By cloning in vitro the cells of NKLy/LL solid tumour of mice it has been shown that the curve of clonogenic cell survival versus N-methyl-N-nitrosourea (MNU) dose in the 12.5-200.0 mg/kg interval is exponential and characterized by Dsub(o)=29.15 mg/kg dose value. Large size tumours (15.0-17.0 g) are characterized by higher death rate of clonogenic cells (survivor fraction approximately 0.5%) than in 1.0-7.0 g tumours (survivor fraction 2-4%). That is, evidently, related to higher sensitivity of the resting tumour cells to MNU

  15. Associations between the uptake of {sup 111}In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts

    Energy Technology Data Exchange (ETDEWEB)

    McLarty, Kristin; Cornelissen, Bart; Scollard, Deborah A. [University of Toronto, Department of Pharmaceutical Sciences, Toronto, ON (Canada); Done, Susan J. [University of Toronto, Department of Medical Biophysics, Toronto, ON (Canada)]|[University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, ON (Canada)]|[University Health Network, Department of Pathology, Toronto, ON (Canada); Chun, Kathy [North York General Hospital, Genetics Program, Toronto, ON (Canada); Reilly, Raymond M. [University of Toronto, Department of Pharmaceutical Sciences, Toronto, ON (Canada)]|[University of Toronto, Department of Medical Imaging, Toronto, ON (Canada)]|[University Health Network, Toronto General Research Institute, Toronto, ON (Canada)]|[University of Toronto, Leslie Dan Faculty of Pharmacy, Toronto, ON (Canada)

    2009-01-15

    The purpose of the study was to investigate the associations between uptake of {sup 111}In-DTPA-trastuzumab, tumour HER2 density and response to trastuzumab (Herceptin) of human breast cancer (BC) xenografts in athymic mice. The tumour uptake of {sup 111}In-DTPA-trastuzumab in athymic mice bearing BC xenografts with increasing HER2 density (0 to 3+) was evaluated. Specific uptake ratios were established in biodistribution (SUR) and imaging studies (ROI-SUR) using {sup 111}In-labeled mouse IgG ({sup 111}In-DTPA-mIgG). Further corrections were made for circulating radioactivity using tumour-to-blood ratios defined as a localization index (LI) and region-of-interest localization index (ROI-LI), respectively. Mice were treated with trastuzumab (Herceptin). A tumour growth inhibition index (TGI) was calculated and relative TGIs calculated by dividing the TGI of control by that of trastuzumab-treated mice. Strong, nonlinear associations with HER2 density were obtained if the uptake of {sup 111}In-DTPA-trastuzumab was corrected for nonspecific IgG localization (i.e., SUR; r{sup 2}=0.99) and circulating radioactivity (i.e., LI; r{sup 2} =0.87), but without these corrections, the association between HER2 density and tumour uptake was poor (r{sup 2}=0.22). There was a strong association between ROI-SUR and ROI-LI values and HER2 expression (r{sup 2}=0.90 and r{sup 2}=0.95), respectively. All tumours were imaged. Relative TGI values were associated with increasing uncorrected tumour uptake of {sup 111}In-DTPA-trastuzumab but not always with HER2 density (i.e., MCF-HER2-18 cells with trastuzumab-resistance). HER2 expression (0 to 3+) can be differentiated using {sup 111}In-DTPA-trastuzumab, but requires correction of tumour uptake for nonspecific IgG localization and circulating radioactivity. The uncorrected uptake of {sup 111}In-DTPA-trastuzumab was associated with tumour response to trastuzumab. (orig.)

  16. DNA damage response mediators MDC1 and 53BP1: constitutive activation and aberrant loss in breast and lung cancer, but not in testicular germ cell tumours

    Czech Academy of Sciences Publication Activity Database

    Bartkova, J.; Hořejší, Zuzana; Sehested, M.; Nesland, J.M.; Rajpert-De Meyts, E.; Skakkebaek, N.E.; Stucki, M.; Jackson, S.; Lukas, J.; Bartek, Jiří

    2007-01-01

    Roč. 26, č. 53 (2007), s. 7414-7422 ISSN 0950-9232 Institutional research plan: CEZ:AV0Z50520514 Keywords : DNA damage response * cancer * MDC1 and 53BP1 defects * tumour suppressors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.440, year: 2007

  17. Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.

    Science.gov (United States)

    Wyluda, Edward J; Cheng, Jihua; Schell, Todd D; Haley, Jeremy S; Mallon, Carol; Neves, Rogerio I; Robertson, Gavin; Sivik, Jeffrey; Mackley, Heath; Talamo, Giampaolo; Drabick, Joseph J

    2015-01-01

    We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on

  18. Concrete aggregate durability study.

    Science.gov (United States)

    2009-06-01

    There are many factors that affect the durability of Portland cement concrete (PCC), including the mix design and the : materials used, the quality of construction, and the environment. Durability is not an intrinsic property of the concrete, but : i...

  19. Texture analysis of {sup 18}F-FDG PET/CT to predict tumour response and prognosis of patients with esophageal cancer treated by chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nakajo, Masatoyo; Jinguji, Megumi; Nakabeppu, Yoshiaki; Higashi, Ryutarou; Fukukura, Yoshihiko; Yoshiura, Takashi [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Nakajo, Masayuki [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Sasaki, Ken; Uchikado, Yasuto; Natsugoe, Shoji [Kagoshima University, Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

    2017-02-15

    This retrospective study was done to examine whether the heterogeneity in primary tumour F-18-fluorodeoxyglucose ({sup 18}F-FDG) distribution can predict tumour response and prognosis of patients with esophageal cancer treated by chemoradiotherapy (CRT). The enrolled 52 patients with esophageal cancer underwent {sup 18}F-FDG-PET/CT studies before CRT. SUVmax, SUVmean, metabolic tumour volume (MTV, SUV ≥ 2.5), total lesion glycolysis (TLG) and six heterogeneity parameters assessed by texture analysis were obtained. Patients were classified as responders or non-responders according to Response Evaluation Criteria in Solid Tumors. Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Prognostic significance was assessed by Cox proportional hazards analysis. Thirty four non-responders showed significantly higher MTV (p = 0.006), TLG (p = 0.007), intensity variability (IV; p = 0.003) and size-zone variability (SZV; p = 0.004) than 18 responders. The positive and negative predictive values for non-responders were 77 % and 69 % in MTV, 76 % and 100 % in TLG, 78 % and 67 % in IV and 78 % and 82 % in SZV, respectively. Although PFS and OS were significantly shorter in patients with high MTV (PFS, p = 0.018; OS, p = 0.014), TLG (PFS, p = 0.009; OS, p = 0.025), IV (PFS, p = 0.013; OS, p = 0.007) and SZV (PFS, p = 0.010; OS, p = 0.007) at univariate analysis, none of them was an independent factor, while lymph node status, stage and tumour response status were independent factors at multivariate analysis. Texture features IV and SZV, and volumetric parameters MTV and TLG can predict tumour response, but all of them have limited value in prediction of prognosis of patients with esophageal cancer treated by CRT. (orig.)

  20. Tumour-Derived Interleukin-1 Beta Induces Pro-inflammatory Response in Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Alajez, Nehad M; Al-toub, Mashael; Almusa, Abdulaziz

    ’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. Background Over the past several years, significant amount of research has emerged......, the goal of this study was to assess the cellular and molecular changes in MSCs in response to secreted factors present in conditioned media (CM) from a panel of human tumor cell lines covering a spectrum of human cancers (Breast, Prostate, Lung, colon, and head and neck). Research Morphological changes...... with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (~80-99%, and 55...

  1. The influence of obesity on response to tumour necrosis factor-α inhibitors in psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Glintborg, Bente; Kristensen, Lars Erik

    2016-01-01

    OBJECTIVES: To investigate the impact of obesity on response to the first TNF-α inhibitor (TNFI) treatment course in patients with PsA followed in routine care. METHODS: We performed an observational cohort study based on the Danish and Icelandic biologics registries. Kaplan-Meier plots, Cox and ...

  2. Association between tobacco smoking and response to tumour necrosis factor α inhibitor treatment in psoriatic arthritis

    DEFF Research Database (Denmark)

    Højgaard, Pil; Glintborg, Bente; Hetland, Merete Lund

    2015-01-01

    study based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, logistic and Cox regression analyses by smoking status (current/previous/never smoker) were calculated for treatment adherence, ACR20/50/70-responses and EULAR-good-response. Additional stratified analyses were performed according...... to gender and TNFi-subtype (adalimumab/etanercept/infliximab). RESULTS: Among 1388 PsA patients included in the study, 1148 (83%) had known smoking status (33% current, 41% never and 26% previous smokers). Median follow-up time was 1.22 years (IQR 0.44-2.96). At baseline, current smokers had lower Body Mass...... Assessment Questionnaire (HAQ) score (1.1 (0.7 to 1.5)/1.0 (0.5 to 1.5)) than never smokers (all psmokers had shorter treatment adherence than never smokers (1.56 years (0.97 to 2.15)/2.43 years (1.88 to 2.97), (median (95% CI)), log rank p=0.02) and poorer 6 months' EULAR-good-response rates...

  3. O6-Methylguanine-DNA methyltransferase status in neuroendocrine tumours: prognostic relevance and association with response to alkylating agents.

    Science.gov (United States)

    Walter, T; van Brakel, B; Vercherat, C; Hervieu, V; Forestier, J; Chayvialle, J-A; Molin, Y; Lombard-Bohas, C; Joly, M-O; Scoazec, J-Y

    2015-02-03

    O(6)-Methylguanine-DNA methyltransferase (MGMT) loss of expression has been suggested to be predictive of response to temozolomide in neuroendocrine tumours (NETs), but so far, only limited data are available. We evaluated the prognostic and predictive value of MGMT status, assessed by two molecular methods and immunohistochemistry, in a large series of NETs of different origins. A total of 107 patients, including 53 treated by alkylants (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation of promoter methylation and immunohistochemistry for evaluation of protein status. MGMT promoter methylation was detected in 12 out of 99 (12%) interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O(6)-Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of 89 (33%) interpretable cases. Status of MGMT was not correlated with overall survival (OS) from diagnosis. Progression-free survival and OS from first alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, Palkylant-based chemotherapy in NETs.

  4. Tumour gene expression predicts response to cetuximab in patients with KRAS wild-type metastatic colorectal cancer.

    Science.gov (United States)

    Baker, J B; Dutta, D; Watson, D; Maddala, T; Munneke, B M; Shak, S; Rowinsky, E K; Xu, L-A; Harbison, C T; Clark, E A; Mauro, D J; Khambata-Ford, S

    2011-02-01

    Although it is accepted that metastatic colorectal cancers (mCRCs) that carry activating mutations in KRAS are unresponsive to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, a significant fraction of KRAS wild-type (wt) mCRCs are also unresponsive to anti-EGFR therapy. Genes encoding EGFR ligands amphiregulin (AREG) and epiregulin (EREG) are promising gene expression-based markers but have not been incorporated into a test to dichotomise KRAS wt mCRC patients with respect to sensitivity to anti-EGFR treatment. We used RT-PCR to test 110 candidate gene expression markers in primary tumours from 144 KRAS wt mCRC patients who received monotherapy with the anti-EGFR antibody cetuximab. Results were correlated with multiple clinical endpoints: disease control, objective response, and progression-free survival (PFS). Expression of many of the tested candidate genes, including EREG and AREG, strongly associate with all clinical endpoints. Using multivariate analysis with two-layer five-fold cross-validation, we constructed a four-gene predictive classifier. Strikingly, patients below the classifier cutpoint had PFS and disease control rates similar to those of patients with KRAS mutant mCRC. Gene expression appears to identify KRAS wt mCRC patients who receive little benefit from cetuximab. It will be important to test this model in an independent validation study.

  5. Intraprocedural blood volume measurement using C-arm CT as a predictor for treatment response of malignant liver tumours undergoing repetitive transarterial chemoembolization (TACE)

    International Nuclear Information System (INIS)

    Vogl, Thomas J.; Schaefer, Patrik; Lehnert, Thomas; Mbalisike, Emmanuel; Hammerstingl, Renate; Eichler, Katrin; Zangos, Stephan; Nour-Eldin, Nour-Eldin A.; Ackermann, Hanns; Naguib, Nagy N.N.

    2016-01-01

    To evaluate feasibility of measuring parenchymal blood volume (PBV) of malignant hepatic tumours using C-arm CT, test the changes in PBV following repeated transarterial chemoembolization (TACE) and correlate these changes with the change in tumour size in MRI. 111 patients with liver malignancy were included. Patients underwent MRI and TACE in a 4- to 6-week interval. During intervention C-arm CT was performed. Images were post-processed to generate PBV maps. Blood volume data in C-arm CT and change in size in MRI were evaluated. The correlation between PBV and size was tested using Spearman rank test. Pre-interventional PBV maps showed a mean blood volume of 84.5 ml/1000 ml ± 62.0, follow-up PBV maps after multiple TACE demonstrated 61.1 ml/1000 ml ± 57.5. The change in PBV was statistically significant (p = 0.02). Patients with initial tumour blood volume >100 ml/1000 ml dropped 7.1 % in size and 47.2 % in blood volume; 50-100 ml/1000 ml dropped 4.6 % in size and 25.7 % in blood volume; and <50 ml/1000 ml decreased 2.8 % in size and increased 82.2 % in blood volume. PBV measurement of malignant liver tumours using C-arm CT is feasible. Following TACE PBV decreased significantly. Patients with low initial PBV show low local response rates and further increase in blood volume, whereas high initial tumour PBV showed better response to TACE. (orig.)

  6. Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

    Science.gov (United States)

    Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

    2006-09-15

    Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained protection against re-challenge.

  7. Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome

    Energy Technology Data Exchange (ETDEWEB)

    Vandecasteele, K.; Eijkeren, M. van; Meerleer, G. de [Ghent University Hospital (Belgium). Dept. of Radiotherapy; Makar, A.; Broecke, R. van den; Tummers, P. [Ghent University Hospital (Belgium). Dept. of Gynecology; Delrue, L. [Ghent University Hospital (Belgium). Dept. of Radiology; Denys, H. [Ghent University Hospital (Belgium). Dept. of Medical Oncology; Lambein, K. [Ghent University Hospital (Belgium). Dept. of Pathology; Lambert, B. [Ghent University Hospital (Belgium). Dept. of Nuclear Medicine

    2012-07-15

    Purpose: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy {+-} cisplatin (IMAT {+-} C) followed by hysterectomy for locally advanced cervical cancer. Patients and methods: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT {+-} C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. Results: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. Conclusion: Surgery after IMAT {+-} C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising. (orig.)

  8. Effects of sensitizers on cell respiration. 3. The effects of hypoxic cell radiosensitizers on oxidative metabolism and the radiation response of an in vitro tumour model

    Energy Technology Data Exchange (ETDEWEB)

    Durand, R E [Wisconsin Clinical Cancer Center, Madison (USA). Dept. of Human Oncology; Biaglow, J E; Greenstock, C L

    1978-06-01

    Physiological factors are important when considering the effects of radiosensitizers on the radiation response of complex systems such as multi-cellular spheroids. In this system, under conditions of unlimited nutrient supply, cells are rendered hypoxic by metabolism. Thus, using the spheroid system as an in vitro model of the tumour-cell microenvironment, we have determined the relative contribution of radiosensitization and respiratory effects of a number of electron-affinic sensitizers having potential clinical use. These studies are indicative of physiological responses at the cellular level, and suggest optimal drug administration schemes for obtaining maximal radiation response in vivo with hypoxic cell sensitizers.

  9. Immunohistochemical characterisation of the local immune response in azoxymethane-induced colon tumours in the BDIX inbred rat strain

    DEFF Research Database (Denmark)

    Kobæk Larsen, Morten; Diederichsen, Axel Cosmus Pyndt; Agger, Ralf

    2004-01-01

    by four weekly subcutaneous azoxymethane injections in inbred rats of the BDIX/OrlIco strain in two separate studies. Azoxymethane-induced tumours show many similarities to spontaneously occurring human colon carcinomas with respect to histopathological appearance. In our studies, the overall inflammatory...

  10. Hyper-IL-15 suppresses metastatic and autochthonous liver cancer by promoting tumour-specific CD8+ T cell responses.

    Science.gov (United States)

    Cheng, Liang; Du, Xuexiang; Wang, Zheng; Ju, Jianqi; Jia, Mingming; Huang, Qibin; Xing, Qiao; Xu, Meng; Tan, Yi; Liu, Mingyue; Du, Peishuang; Su, Lishan; Wang, Shengdian

    2014-12-01

    Liver cancer has a very dismal prognosis due to lack of effective therapy. Here, we studied the therapeutic effects of hyper-interleukin15 (hyper-IL-15), which is composed of IL-15 and the sushi domain of the IL-15 receptor α chain, on metastatic and autochthonous liver cancers. Liver metastatic tumour models were established by intraportally injecting syngeneic mice with murine CT26 colon carcinoma cells or B16-OVA melanoma cells. Primary hepatocellular carcinoma (HCC) was induced by diethylnitrosamine (DEN). A hydrodynamics-based gene delivery method was used to achieve sustained hyper-IL-15 expression in the liver. Liver gene delivery of hyper-IL-15 robustly expanded CD8(+) T and NK cells, leading to a long-term (more than 40 days) accumulation of CD8(+) T cells in vivo, especially in the liver. Hyper-IL-15 treatment exerted remarkable therapeutic effects on well-established liver metastatic tumours and even on DEN-induced autochthonous HCC, and these effects were abolished by depletion of CD8(+) T cells but not NK cells. Hyper-IL-15 triggered IL-12 and interferon-γ production and reduced the expression of co-inhibitory molecules on dendritic cells in the liver. Adoptive transfer of T cell receptor (TCR) transgenic OT-1 cells showed that hyper-IL-15 preferentially expanded tumour-specific CD8(+) T cells and promoted their interferon-γ synthesis and cytotoxicity. Liver delivery of hyper-IL-15 provides an effective therapy against well-established metastatic and autochthonous liver cancers in mouse models by preferentially expanding tumour-specific CD8(+) T cells and promoting their anti-tumour effects. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  11. Gastric Calcifying Fibrous Tumour

    Directory of Open Access Journals (Sweden)

    Tan Attila

    2006-01-01

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

  12. A heterologous prime-boost Ebola virus vaccine regimen induces durable neutralizing antibody response and prevents Ebola virus-like particle entry in mice.

    Science.gov (United States)

    Chen, Tan; Li, Dapeng; Song, Yufeng; Yang, Xi; Liu, Qingwei; Jin, Xia; Zhou, Dongming; Huang, Zhong

    2017-09-01

    Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Monetary Policy with Sectoral Linkages and Durable Goods

    DEFF Research Database (Denmark)

    Petrella, Ivan; Rossi, Raffaele; Santoro, Emiliano

    We study the normative implications of a New Keynesian model featuring intersectoral trade of intermediate goods between two sectors that produce durables and non-durables. The interplay between durability and sectoral production linkages fundamentally alters the intersectoral stabilization trade....... Aggregating durable and non-durable inflation depending on the relative degrees of sectoral price stickiness may induce a severe bias. Input materials attenuate the response of sectoral inflations to movements in the real marginal costs, so that the effective slopes of the sectoral supply schedules...

  14. Ribosomal protein S6 phosphorylation and morphological changes in response to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate in primary human tumour cells, established and transformed cell lines

    DEFF Research Database (Denmark)

    Rance, A J; Thönnes, M; Issinger, O G

    1985-01-01

    lifespan (fibroblasts, primary human tumour cells) can be mimicked by unknown steps also associated with immortalization (establishment function) and the transformed state of the tumour cells. Another interesting observation were morphological changes of the established and SV40-transformed cells which...

  15. The use of biological isodoses ''IsobioGy 2'' for evaluation of tumour and normal tissues response for fractionated irradiation

    International Nuclear Information System (INIS)

    Maciejewski, B.; Skolyszewski, J.; Majewski, S.; Lobodziec, W.; Jedynak, T.; Slosarek, K.

    1988-01-01

    Divergences between physical and biological dose distributions were analysed using linear quadratic model. It was found that small variations in physical dose distribution and differences in normal tissue sensitivity for change in dose per fraction, expressed by a α/β value, can cause a high difference between physical and biological doses. This difference significantly increases when one field instead of two fields is daily treated. If there is no enough separation between treated fields, the biological dose may dramatically increase. The use of biological ''isobioGy 2'' isodoses, instead of physical isodoses, can provide an important information on biological effect in tumour or normal tissue and may diminish the risk of giving too high dose to normal tissue and too low dose to the tumour. 6 figs., 13 refs. (author)

  16. Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF.

    Science.gov (United States)

    Ahmad, Murrium; Rees, Robert C; McArdle, Stephanie E; Li, Geng; Mian, Shahid; Entwisle, Claire; Loudon, Peter; Ali, Selman A

    2005-07-20

    Direct intratumour injection of the disabled infectious single-cycle-herpes simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete tumour rejection in up to 70% of treated animals (regressors), while the remaining mice developed progressive tumours (progressors). This murine Balb/c model was used to dissect the cellular mechanisms involved in tumour regression or progression following immunotherapy. CTLs were generated by coculturing lymphocytes and parenchymal cells from the same spleens of individual regressor or progressor animals in the presence of the relevant AH-1 peptide derived from the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma) production. Conversely, progressor splenocytes exhibited weak to no CTL activity and poor IFN-gamma production, concomitant with the presence of a suppressor cell population in the progressor splenic parenchymal cell fraction. Further fractionation of this parenchymal subpopulation demonstrated that cells inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with peptide, were present in the nonadherent parenchymal fraction. In vitro depletion of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells) and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes present in the parenchymal fraction regulated the CTL response to AH-1. We examined the cellular responses associated with tumour rejection and progression, identifying regulatory pathways associated with failure to respond to immunotherapy. Copyright 2005 Wiley-Liss, Inc.

  17. Cone-beam computed tomography for lung cancer - validation with CT and monitoring tumour response during chemo-radiation therapy.

    Science.gov (United States)

    Michienzi, Alissa; Kron, Tomas; Callahan, Jason; Plumridge, Nikki; Ball, David; Everitt, Sarah

    2017-04-01

    Cone-beam computed tomography (CBCT) is a valuable image-guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non-small cell lung cancer (NSCLC) tumour volumes compared to the anatomical 'gold standard', CT. Tumour regression or progression on CBCT was also analysed. Patients with Stage I-III NSCLC, prescribed 60 Gy in 30 fractions RT with concurrent platinum-based chemotherapy, routine CBCT and enrolled in a prospective study of serial PET/CT (baseline, weeks two and four) were eligible. Time-matched CBCT and CT gross tumour volumes (GTVs) were manually delineated by a single observer on MIM software, and were analysed descriptively and using Pearson's correlation coefficient (r) and linear regression (R 2 ). Of 94 CT/CBCT pairs, 30 patients were eligible for inclusion. The mean (± SD) CT GTV vs CBCT GTV on the four time-matched pairs were 95 (±182) vs 98.8 (±160.3), 73.6 (±132.4) vs 70.7 (±96.6), 54.7 (±92.9) vs 61.0 (±98.8) and 61.3 (±53.3) vs 62.1 (±47.9) respectively. Pearson's correlation coefficient (r) was 0.98 (95% CI 0.97-0.99, ρ < 0.001). The mean (±SD) CT/CBCT Dice's similarity coefficient was 0.66 (±0.16). Of 289 CBCT scans, tumours in 27 (90%) patients regressed by a mean (±SD) rate of 1.5% (±0.75) per fraction. The mean (±SD) GTV regression was 43.1% (±23.1) from the first to final CBCT. Primary lung tumour volumes observed on CBCT and time-matched CT are highly correlated (although not identical), thereby validating observations of GTV regression on CBCT in NSCLC. © 2016 The Royal Australian and New Zealand College of Radiologists.

  18. Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis

    International Nuclear Information System (INIS)

    Grant, Nicola J.; Coates, Philip J.; Woods, Yvonne L.; Bray, Susan E.; Morrice, Nicholas A.; Hastie, C. James; Lamont, Douglas J.; Carey, Francis A.; Sutherland, Calum

    2015-01-01

    Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

  19. Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis.

    Science.gov (United States)

    Grant, Nicola J; Coates, Philip J; Woods, Yvonne L; Bray, Susan E; Morrice, Nicholas A; Hastie, C James; Lamont, Douglas J; Carey, Francis A; Sutherland, Calum

    2015-11-10

    Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

  20. Skull base tumours

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil, Servico de Radiologia, Rua Professor Lima Basto, 1093 Lisboa Codex (Portugal)], E-mail: borgesalexandra@clix.pt

    2008-06-15

    With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base.

  1. Skull base tumours

    International Nuclear Information System (INIS)

    Borges, Alexandra

    2008-01-01

    With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base

  2. Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

    Science.gov (United States)

    Díaz-Expósito, R; Martí-Bonmatí, L; Burgués, O; Casáns-Tormo, I; Bermejo-de Las Heras, B; Julve-Parreño, A; Caballero-Garate, A

    Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, pcancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  3. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer

    Science.gov (United States)

    Koski, Gary K.; Koldovsky, Ursula; Xu, Shuwen; Mick, Rosemarie; Sharma, Anupama; Fitzpatrick, Elizabeth; Weinstein, Susan; Nisenbaum, Harvey; Levine, Bruce L; Fox, Kevin; Zhang, Paul; Czerniecki, Brian J

    2011-01-01

    Twenty-seven subjects with HER-2/neu over-expressing ductal carcinoma in situ of the breast were enrolled in a neoadjuvant immunization trial for safety and immunogenicity of DC1-polarized dendritic cells (DC1) pulsed with six HER-2/neu promiscuous MHC class II-binding peptides, plus two additional HLA-A2.1 class I-binding peptides. DC1 were generated with IFN-γ plus a special clinical-grade bacterial endotoxin (LPS) and administered directly into groin lymph nodes four times at weekly intervals prior to scheduled surgical resection of DCIS. Subjects were monitored for the induction of new or enhanced anti-peptide reactivity by IFN-γ ELIspot and ELISA assays performed on Th cells obtained from peripheral blood or excised sentinel lymph nodes. Responses by CTL against HLA-A2.1-binding peptides were measured using peptide-pulsed T2 target cells or HER-2/neu-expressing or non-expressing tumor cell lines. DC1 showed surface phenotype indistinct from “gold standard” inflammatory cocktail-activated DC, but displayed a number of distinguishing functional characteristics including the secretion of soluble factors and enhanced “killer DC” capacity against tumor cells in vitro. Post-immunization, we observed sensitization of Th cells to at least 1 class II peptide in 22 of 25 (88%, 95% exact CI 68.8 – 97.5%) evaluable subjects, while eleven of 13 (84.6%, 95% exact CI 64 – 99.8%) HLA-A2.1 subjects were successfully sensitized to class I peptides. Perhaps most importantly, anti-HER-2/neu peptide responses were observed up to 52 months post-immunization. These data show even in the presence of early breast cancer such DC1 are potent inducers of durable type I-polarized immunity, suggesting potential clinical value for development of cancer immunotherapy. PMID:22130160

  4. Azacytidine in combination with tyrosine kinase inhibitors induced durable responses in patients with advanced phase chronic myelogenous leukemia.

    Science.gov (United States)

    Ruggiu, Mathilde; Oberkampf, Florence; Ghez, David; Cony-Makhoul, Pascale; Beckeriche, Florence; Cano, Isabelle; Taksin, Anne L; Benbrahim, Omar; Ghez, Stéphanie; Farhat, Hassan; Rigaudeau, Sophie; de Gunzburg, Noémie; Lara, Diane; Terre, Christine; Raggueneau, Victoria; Garcia, Isabel; Spentchian, Marc; De Botton, Stéphane; Rousselot, Philippe

    2017-11-28

    Although the tyrosine kinase inhibitor (TKI) era has brought great improvement in outcome in chronic myelogenous leukemia (CML), prognosis of accelerated phase or myeloid blast crisis patients or of de novo Philadelphia chromosome-positive acute myeloid leukemia remains poor. We conducted a retrospective study on patients with advanced phase disease treated with a TKI and azacytidine. Sixteen patients were eligible. Median age was 64.9 years, the median number of previous therapies was 2.5 lines, and median follow-up was 23.1 months. Hematologic response (HR) rate was 81.3%. Median overall survival (OS), event free survival and relapse-free survival (RFS) were 31.5, 23.3, and 32.2 months, respectively. All except one patient were treated as out-patients after the first cycle. Five patients were bridged to allogenic hematopoietic stem cells transplant. The combination of a TKI and azacytidine is a safe and efficient regiment for patients with CML patients in advanced phases.

  5. Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of the mediastinum: A favourable response to treatment and review of the literature.

    Science.gov (United States)

    Ghandi, Narges; Ghanadan, Alireza; Azizian, Mohammad-Reza; Hejazi, Pardis; Aghazadeh, Nessa; Tavousi, Parvin; Daneshpazhooh, Maryam

    2015-05-01

    Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder that occurs in association with an underlying neoplasm. Inflammatory myofibroblastic tumour (IMT) is a rare low-grade sarcoma of fibroblasts and myofibroblasts associated with inflammatory cells, most commonly occurring in the lung. In this study, a case of PNP associated with IMT of the mediastinum is reported. The patient had a favourable outcome following surgical resection and treatment with a systemic steroid, azathioprine, and i.v. immunoglobulin. The occurrence of PNP with sarcomas, specifically IMT, is noteworthy although it is not well studied in the existing literature. © 2014 The Australasian College of Dermatologists.

  6. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  7. Tumour cell lysate-loaded dendritic cell vaccine induces biochemical and memory immune response in castration-resistant prostate cancer patients.

    Science.gov (United States)

    Reyes, D; Salazar, L; Espinoza, E; Pereda, C; Castellón, E; Valdevenito, R; Huidobro, C; Inés Becker, M; Lladser, A; López, M N; Salazar-Onfray, F

    2013-09-17

    Recently, we produced a tumour antigen-presenting cells (TAPCells) vaccine using a melanoma cell lysate, called TRIMEL, as an antigen source and an activation factor. Tumour antigen-presenting cells induced immunological responses and increased melanoma patient survival. Herein, we investigated the effect of TAPCells loaded with prostate cancer cell lysates (PCCL) as an antigen source, and TRIMEL as a dendritic cell (DC) activation factor; which were co-injected with the Concholepas concholepas haemocyanin (CCH) as an adjuvant on castration-resistant prostate cancer (CRPC) patients. The lysate mix capacity, for inducing T-cell activation, was analysed by flow cytometry and Elispot. Delayed-type hypersensitivity (DTH) reaction against PCCL, frequency of CD8(+) memory T cells (Tm) in blood and prostate-specific antigen (PSA) levels in serum were measured in treated patients. The lysate mix induced functional mature DCs that were capable of activating PCCL-specific T cells. No relevant adverse reactions were observed. Six out of 14 patients showed a significant decrease in levels of PSA. DTH(+) patients showed a prolonged PSA doubling-time after treatment. Expansion of functional central and effector CD8(+) Tm were detected. Treatment of CRPC patients with lysate-loaded TAPCells and CCH as an adjuvant is safe: generating biochemical and memory immune responses. However, the limited number of cases requires confirmation in a phase II clinical trial.

  8. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    International Nuclear Information System (INIS)

    Chapiro, Julius; Savic, Lynn Jeanette; Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois; Lin, MingDe; Lesage, David

    2015-01-01

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  9. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  10. Tumour sleuths

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  11. Imaging brain tumour microstructure.

    Science.gov (United States)

    Nilsson, Markus; Englund, Elisabet; Szczepankiewicz, Filip; van Westen, Danielle; Sundgren, Pia C

    2018-05-08

    Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging. Copyright © 2018. Published by Elsevier Inc.

  12. Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zschaeck, Sebastian [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Hofheinz, Frank [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). PET Center, Inst. of Radiopharmaceutical Cancer Research; Zoephel, Klaus; Kotzerke, Joerg [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Carl Gustav Carus, Dresden (Germany). Dept. of Nuclear Medicine; National Center for Tumor Diseases (NCT), Dresden (Germany); Buetof, Rebecca; Schmollack, Julia [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Jentsch, Christina [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Loeck, Steffen; Baumann, Michael; Krause, Mechthild [University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); University Hospital Carl Gustav Carus Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; National Center for Tumor Diseases (NCT), Dresden (Germany); Baretton, Gustavo [German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Pathology; Weitz, Juergen [German Cancer Consortium (DKTK), Dresden (DE); German Cancer Research Center (DKFZ), Heidelberg (DE); National Center for Tumor Diseases (NCT), Dresden (DE); University Hospital Carl Gustav Carus Technische Univ. Dresden (DE). Dept. of Visceral, Thoracic and Vascular Surgery

    2017-10-15

    Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis. This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUV{sub max}, SUV{sub mean}) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis. Increased FDG uptake, measured in terms of SUV{sub mean} in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUV{sub max} and SUV{sub mean} in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUV{sub max} and SUV{sub mean} in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011). FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization. (orig.)

  13. Adnexal Tumours Of Skin

    Directory of Open Access Journals (Sweden)

    Parate Sanjay N

    1998-01-01

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

  14. The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperative radiochemotherapy in patients with rectal cancer

    International Nuclear Information System (INIS)

    Oblak, Irena; Velenik, Vaneja; Anderluh, Franc; Mozina, Barbara; Ocvirk, Janja

    2013-01-01

    The aim of this study was to analyse whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients. Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I– III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA). Median follow-up time was 68 months (range: 3–93 months) while in survivors it was 80 months (range: 68–93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22–523 ng/mL) and the mean level (±standard deviation) was 192 (±87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2–3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage. Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative

  15. Computed tomography in malignant primary bone tumours

    International Nuclear Information System (INIS)

    Kersjes, W.; Harder, T.; Haeffner, P.

    1990-01-01

    The importance of computed tomography is examined in malignant primary bone tumours using a strongly defined examination group of 13 Patients (six Ewing's-sarcomas, five osteosarcomas, one chondrosarcoma and one spindle-shaped cell sarcoma). Computed tomography is judged superior compared to plain radiographs in recognition of bone marrow infiltration and presentation of parosteal tumour parts as well as in analysis of tissue components of tumours, CT is especially suitable for therapy planning and evaluating response to therapy. CT does not provide sufficient diagnostic information to determine dignity and exact diagnosis of bone tumours. (orig.) [de

  16. Malignant tumours of the kidney: imaging strategy

    International Nuclear Information System (INIS)

    Smets, Anne M.; Kraker, Jan de

    2010-01-01

    Primitive malignant renal tumours comprise 6% of all childhood cancers. Wilms tumour (WT) or nephroblastoma is the most frequent type accounting for more than 90%. Imaging alone cannot differentiate between these tumours with certainty but it plays an important role in screening, diagnostic workup, assessment of therapy response, preoperative evaluation and follow-up. The outcome of WT after therapy is excellent with an overall survival around 90%. In tumours such as those where the outcome is extremely good, focus can be shifted to a risk-based stratification to maintain excellent outcome in children with low risk tumours while improving quality of life and decreasing toxicity and costs. This review will discuss the imaging issues for WT from the European perspective and briefly discuss the characteristics of other malignant renal tumours occurring in children and new imaging techniques with potential in this matter. (orig.)

  17. Molecular response assessed by {sup 68}Ga-DOTANOC and survival after {sup 90}Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Luca; Salvatori, Rita; Bagni, Oreste [Santa Maria Goretti Hospital, Department of Nuclear Medicine, Latina (Italy); Scopinaro, Francesco [Sant' Andrea Hospital, Department of Nuclear Medicine, Rome (Italy); Pelle, Giuseppe; Cianni, Roberto [Santa Maria Goretti Hospital, Department of Interventional Radiology, Latina (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy)

    2016-03-15

    We investigated the prognostic role of {sup 68}Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing {sup 90}Y radioembolization ({sup 90}Y-RE). A group of 15 consecutive patients with unresectable NET liver metastases underwent {sup 68}Ga-DOTANOC PET at baseline and 6 weeks after {sup 90}Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following {sup 90}Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). A decrease in T/S ratio was seen in all patients on {sup 68}Ga-DOTANOC PET scans performed after {sup 90}Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. Molecular response assessed with {sup 68}Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with {sup 90}Y-RE. (orig.)

  18. Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours: informed scheduling of the bioreductive drug AQ4N improves treatment response.

    Science.gov (United States)

    Ming, Louise; Byrne, Niall M; Camac, Sarah Nicole; Mitchell, Christopher A; Ward, Claire; Waugh, David J; McKeown, Stephanie R; Worthington, Jenny

    2013-03-15

    Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment, hypoxia is known to drive malignant progression. Our study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold (DSF) chambers were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide-treated and vehicle-only-treated tumours were re-established in vitro, and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2 mg/kg/day) decreased tumour oxygenation by 45% within 24 hr, reaching a nadir of 0.09% oxygen (0.67 ± 0.06 mmHg) by Day 7; this persisted until Day 14 when it increased up to Day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at Days 7 and 14 with revascularisation occurring by Day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50 mg/kg, single dose) caused greater tumour growth delay than bicalutamide alone. Our study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit. Copyright © 2012 UICC.

  19. Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients.

    Science.gov (United States)

    Massi, Daniela; Romano, Emanuela; Rulli, Eliana; Merelli, Barbara; Nassini, Romina; De Logu, Francesco; Bieche, Ivan; Baroni, Gianna; Cattaneo, Laura; Xue, Gongda; Mandalà, Mario

    2017-06-01

    The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome. Quantitative assessment of mRNA transcripts associated with Wnt/β-catenin pathway and immune response was performed in 51 patients. We found an inverse correlation between tumoural β-catenin expression and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio, OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly associated with a higher probability of response to MAPKi monotherapy. Responding patients showed a significantly increased expression of mRNA transcripts associated with adaptive immunity and antigen presentation. By multivariate analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10-0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006) were longer in patients with high density of CD8+ T cells and β-catenin <10% than those without CD8+ T cells infiltration and β-catenin ≥10%. Our findings provide evidence that in the context of MAPKi monotherapy, immune subsets in the (TME) and

  20. Revisiting the relationship between tumour volume and diameter in advanced NSCLC patients: An exercise to maximize the utility of each measure to assess response to therapy

    International Nuclear Information System (INIS)

    Nishino, M.; Jackman, D.M.; DiPiro, P.J.; Hatabu, H.; Jänne, P.A.; Johnson, B.E.

    2014-01-01

    Aim: To revisit the presumed relationship between tumour diameter and volume in advanced non-small-cell lung cancer (NSCLC) patients, and determine whether the measured volume using volume-analysis software and its proportional changes during therapy matches with the calculated volume obtained from the presumed relationship and results in concordant response assessment. Materials and methods: Twenty-three patients with stage IIIB/IV NSCLC with a total of 53 measurable lung lesions, treated in a phase II trial of erlotinib, were studied with institutional review board approval. Tumour volume and diameter were measured at baseline and at the first follow-up computed tomography (CT) examination using volume-analysis software. Using the measured diameter (2r) and the equation, calculated volume was obtained as (4/3)πr 3 at baseline and at the follow-up. Percent volume change was obtained by comparing to baseline for measured and calculated volumes, and response assessment was assigned. Results: The measured volume was significantly smaller than the calculated volume at baseline (median 11,488.9 mm 3 versus 17,148.6 mm 3 ; p < 0.0001), with a concordance correlation coefficient (CCC) of 0.7022. At follow-up, the measured volume was once again significantly smaller than the calculated volume (median 6573.5 mm 3 versus 9198.1 mm 3 ; p = 0.0022), with a CCC of 0.7408. Response assessment by calculated versus measured volume changes had only moderate agreement (weighted κ = 0.545), with discordant assessment results in 20% (8/40) of lesions. Conclusion: Calculated volume based on the presumed relationship significantly differed from the measured volume in advanced NSCLC patients, with only moderate concordance in response assessment, indicating the limitations of presumed relationship. - Highlights: • Response assessment by measured vs calculated values has only moderate agreement. • It is important to obtain the actual measured values for tumor response

  1. Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

    Energy Technology Data Exchange (ETDEWEB)

    Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

    2016-07-15

    The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

  2. Introduction of Hypermatrix and Operator Notation into a Discrete Mathematics Simulation Model of Malignant Tumour Response to Therapeutic Schemes In Vivo. Some Operator Properties

    Directory of Open Access Journals (Sweden)

    Georgios S. Stamatakos

    2009-10-01

    Full Text Available The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code. However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators’ commutativity and outline the “summarize and jump” strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83–02, thus strengthening the reliability of the model developed.

  3. Introduction of hypermatrix and operator notation into a discrete mathematics simulation model of malignant tumour response to therapeutic schemes in vivo. Some operator properties.

    Science.gov (United States)

    Stamatakos, Georgios S; Dionysiou, Dimitra D

    2009-10-21

    The tremendous rate of accumulation of experimental and clinical knowledge pertaining to cancer dictates the development of a theoretical framework for the meaningful integration of such knowledge at all levels of biocomplexity. In this context our research group has developed and partly validated a number of spatiotemporal simulation models of in vivo tumour growth and in particular tumour response to several therapeutic schemes. Most of the modeling modules have been based on discrete mathematics and therefore have been formulated in terms of rather complex algorithms (e.g. in pseudocode and actual computer code). However, such lengthy algorithmic descriptions, although sufficient from the mathematical point of view, may render it difficult for an interested reader to readily identify the sequence of the very basic simulation operations that lie at the heart of the entire model. In order to both alleviate this problem and at the same time provide a bridge to symbolic mathematics, we propose the introduction of the notion of hypermatrix in conjunction with that of a discrete operator into the already developed models. Using a radiotherapy response simulation example we demonstrate how the entire model can be considered as the sequential application of a number of discrete operators to a hypermatrix corresponding to the dynamics of the anatomic area of interest. Subsequently, we investigate the operators' commutativity and outline the "summarize and jump" strategy aiming at efficiently and realistically address multilevel biological problems such as cancer. In order to clarify the actual effect of the composite discrete operator we present further simulation results which are in agreement with the outcome of the clinical study RTOG 83-02, thus strengthening the reliability of the model developed.

  4. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

    International Nuclear Information System (INIS)

    Krause, Mechthild; Prager, Jenny; Zhou Xuanjing; Yaromina, Ala; Doerfler, Annegret; Eicheler, Wolfgang; Baumann, Michael

    2007-01-01

    Background and purpose: Waiting times before radiotherapy may reduce tumour control probability due to proliferation of tumour cells. The aim of the experiment was to test whether the growth inhibiting effect of epidermal growth factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results in a lower tumour mass at time of irradiation and can thereby improve local tumour control. Materials and methods: The EGFR-tyrosine kinase inhibitor BIBX1382BS was applied over 14 days starting from microscopically non-in-sano-resection of FaDu tumours or from tumour transplantation, followed by irradiation (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas, pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability in vitro were tested in control tumours and after BIBX1382BS treatment (starting from transplantation). Results: The tumour volume at start of irradiation was significantly lower in the BIBX1382BS treated tumours as compared to the control groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting). However, the reduced volume did not translate into improved local control after irradiation. The TCD 50 values after surgery were 25.4 Gy [95% CI 18; 33 Gy] in the control group and 30.5 Gy [24; 37] in the BIBX1382BS group (p = 0.25). Treatment after transplantation resulted in TCD 50 values of 41.1 Gy [35; 47] in the control group and 41.1 Gy [33; 49] in the BIBX1382BS group (p = 1). While the proportion of S-phase cells decreased after BIBX1382BS treatment, no differences were observed between the pimonidazole hypoxic fractions and in vitro colony forming ability. Conclusions: EGFR-TK inhibition with BIBX1382BS over 14 days between macroscopically complete tumour resection or tumour transplantation and start of radiotherapy significantly reduced tumour volume but did not improve local tumour control. One possible explanation is that the EGFR-TK inhibitor has a higher activity in

  5. CBF and CMRo2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

    International Nuclear Information System (INIS)

    Madsen, J.B.; Cold, G.E.; Eriksen, H.O.; Eskesen, V.; Blatt-Lyon, B.

    1986-01-01

    In 14 patients with supratentorial cerebral tumours with midline shift ≤ 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRo 2 ) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety and Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In group 1 (n=7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRo 2 measured about 70 min after induction averaged 30.1 ml 100 g -1 min -1 and 1.98 ml O 2 100 g -1 min -1 , respectively. During the second CBF study 1 h later, CBF and CMRo 2 were unchanged (P>0.05). In group 2 (n=7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRo 2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRo 2 and suppression in the EEG activity, whereas CBF was unchanged (author)

  6. of brain tumours

    African Journals Online (AJOL)

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

  7. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with

  8. Induction of the early response protein EGR-1 in human tumour cells after ionizing radiation is correlated with a reduction of repair of lethal lesions and an increase of repair of sublethal lesions

    NARCIS (Netherlands)

    Franken, Nicolaas A. P.; ten Cate, Rosemarie; van Bree, Chris; Haveman, Jaap

    2004-01-01

    The role of EGR-1 in potentially lethal damage repair (PLDR) was studied. Induction of the early response protein EGR-1 and survival after ionizing radiation of two human tumour cell lines after culturing for 48 h in serum-deprived medium was investigated. The glioblastoma cell line (Gli-6) and a

  9. MHC class II molecules and tumour immunotherapy

    International Nuclear Information System (INIS)

    Oven, I.

    2005-01-01

    Background. Tumour immunotherapy attempts to use the specificity and capability of the immune system to kill malignant cells with a minimum damage to normal tissue. Increasing knowledge of the identity of tumour antigens should help us design more effective therapeutic vaccines. Increasing evidence has demonstrated that MHC class II molecules and CD4+ T cells play important roles in generating and maintaining antitumour immune responses in animal models. These data suggest that it may be necessary to involve both CD4+ and CD8+ T cells for more effective antitumour therapy. Novel strategies have been developed for enhancing T cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells, by the inclusion of MHC class II-restricted tumour antigens and by genetically modifying tumour cells to present antigen to T lymphocytes directly. Conclusions. Vaccines against cancers aim to induce tumour-specific effector T cells that can reduce tumour mass and induce development of tumour-specific T cell memory, that can control tumour relapse. (author)

  10. Decoration and durability

    DEFF Research Database (Denmark)

    Riisberg, Vibeke; Munch, Anders V.

    2015-01-01

    Throughout the scales of design there has been an exploding interest in the ornament that seems to be fuelled by different kinds of digital technology and media from CAD to digital printing in both 2D and 3D. In architecture and industrial design, it is discussed as a “return of ornament” because...... from fashion and tableware to archi- tecture and link ornamentation to the aesthetics of durability....

  11. Durability of critical infrastructures

    OpenAIRE

    Raluca Pascu; Ramiro Sofronie

    2011-01-01

    The paper deals with those infrastructures by which world society, under the pressure ofdemographic explosion, self-survives. The main threatening comes not from terrorist attacks, but fromthe great natural catastrophes and global climate change. It’s not for the first time in history when suchmeasures of self-protection are built up. First objective of this paper is to present the background fordurability analysis. Then, with the aid of these mathematical tools the absolute durability of thr...

  12. Decoration and Durability

    DEFF Research Database (Denmark)

    Riisberg, Vibeke; Munch, Anders V.

    2015-01-01

    Throughout the scales of design there has been an exploding interest in the ornament that seems to be fuelled by different kinds of digital technology and media from CAD to digital printing in both 2D and 3D. In architecture and industrial design it is discussed as a Return of ornament, because...... appropriate or not. This leads us to suggest an array of parameters that points out different situations and meanings of ornamentation: Product categories, Durability of materials, Styles, Aesthetic experience, Emotional attachment and Historical references. We discuss these parameters in cases from fashion...

  13. Imaging of sacral tumours

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  14. Imaging of sacral tumours

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-04-15

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

  15. Response of tumour necrosis factor alpha (TNF ) in blood and spleen mice that vaccinated with P.berghei radiation

    International Nuclear Information System (INIS)

    Darlina; Tur R; Teja K

    2015-01-01

    Tumor necrosis factor is a glycoprotein derived from helper T lymphocytes that play an important role in the body's response against malaria infection. However, TNF-α has double play that is on appropriate levels will provide protection and healing, while at excessive levels which may be a response to hyperparasitemia. Thus investigated the expression of TNF alpha secreted blood lymphocytes and spleen cells the mice that's infected with 1 x 10 7 P.berghei infectious or inactivated by radiation. Levels of TNF alpha serum and spleen cell culture medium was monitored on days 2, 7, 14 post infection. Monitoring of parasite growth every two days for 60 days. Determination of TNF alpha levels were measure using ELISA. The results showed parasitaemia mice infected with 175 Gy irradiated parasites have pre patent period of 16 days longer than the control (non-irradiated parasites) with low parasitaemia. TNF alpha concentration that secreted spleen cells of mice vaccinated higher than control mice. Concentration of TNF alpha that secreted blood lymphocyte of mice vaccinated lower than control mice. It was concluded that the secretion of TNF alpha by blood lymphocytes caused more pathogenic factors of the parasite, while the secretion of TNF alpha in spleen due to an immune response against the parasite. (author)

  16. Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG)

    International Nuclear Information System (INIS)

    Siddiqui, M.R.S.; Gormly, K.L.; Bhoday, J.; Balyansikova, S.; Battersby, N.J.; Chand, M.; Rao, S.; Tekkis, P.; Abulafi, A.M.; Brown, G.

    2016-01-01

    Aim: To investigate whether the magnetic resonance imaging (MRI) tumour regression grading (mrTRG) scale can be taught effectively resulting in a clinically reasonable interobserver agreement (>0.4; moderate to near perfect agreement). Materials and methods: This study examines the interobserver agreement of mrTRG, between 35 radiologists and a central reviewer. Two workshops were organised for radiologists to assess regression of rectal cancers on MRI staging scans. A range of mrTRGs on 12 patient scans were used for assessment. Results: Kappa agreement ranged from 0.14–0.82 with a median value of 0.57 (95% CI: 0.37–0.77) indicating good overall agreement. Eight (26%) radiologists had very good/near perfect agreement (κ>0.8). Six (19%) radiologists had good agreement (0.8≥κ>0.6) and a further 12 (39%) had moderate agreement (0.6≥κ>0.4). Five (16%) radiologists had a fair agreement (0.4≥κ>0.2) and two had poor agreement (0.2>κ). There was a tendency towards good agreement (skewness: 0.92). In 65.9% and 90% of cases the radiologists were able to correctly highlight good and poor responders, respectively. Conclusions: The assessment of the response of rectal cancers to chemoradiation therapy may be performed effectively using mrTRG. Radiologists can be taught the mrTRG scale. Even with minimal training, good agreement with the central reviewer along with effective differentiation between good and intermediate/poor responders can be achieved. Focus should be on facilitating the identification of good responders. It is predicted that with more intensive interactive case-based learning a κ>0.8 is likely to be achieved. Testing and retesting is recommended. - Highlights: • Inter-observer agreement of radiologists was assessed using MRI rectal tumour regression scale. • Kappa agreement had a median value of 0.57 (95% CI: 0.37–0.77) indicating an overall good agreement. • In 65.9% and 90% of cases the radiologists were able to correctly highlight

  17. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT)

    Energy Technology Data Exchange (ETDEWEB)

    Kong, G.; Thompson, M.; Johnston, V.; Eu, P. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); Collins, M.; Herschtal, A. [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne, VIC (Australia); Hofman, M.S.; Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Michael, M. [The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia)

    2014-10-15

    To review the response and outcomes of {sup 177}Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was

  18. Wilms' tumour (nephroblastoma)

    African Journals Online (AJOL)

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

  19. Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

    Science.gov (United States)

    Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

    2015-03-01

    Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. © 2015 The authors.

  20. High clinical and morphologic response using 90Y-DOTA-octreotate sequenced with 177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

    Science.gov (United States)

    Kong, Grace; Callahan, Jason; Hofman, Michael S; Pattison, David A; Akhurst, Tim; Michael, Michael; Eu, Peter; Hicks, Rodney J

    2017-03-01

    Bulky disease is an adverse prognostic factor for 177 Lu-DOTA-octreotate ( 177 Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). 90 Y-DOTA-octreotate ( 90 Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than 177 Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of 90 Y-DOTATATE followed by 2-3 cycles of 177 Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq 90 Y-DOTATATE, and 21 GBq 177 Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with 90 Y -DOTATATE followed by 177 Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved

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

    International Nuclear Information System (INIS)

    Sassolas, G.

    1996-01-01

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

  2. The hypoxic tumour cell in radiation therapy

    International Nuclear Information System (INIS)

    Trott, K.R.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Neuherberg/Muenchen

    1976-01-01

    In most tumours there is a disproportion between the tumour cells and vascular connective tissue. A lack of oxygen depending on extent and duration, leads to changes of the metabolism and of the proliferative properties of the cells, to an increase of radiation resistance and to a reduction of the ability to recover from radiation injuries. Finally with longer duration, hypoxy leads to cell killing. As a result of irradiation, a reoxygenation of a part of the previous hypoxic tumour cell occurs more or less quickly. The time and topographic changes of these factors are involved in a complex manner in the radiotherapy of malignant tumours and essentially share the responsibility regarding the curative success of radiotherapy. (orig./LH) [de

  3. Electrochemotherapy of tumours

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  4. Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness two years after treatment with Ombitasvir/Paritaprevir/Ritonavir ±Dasabuvir ±Ribavirin in the AMBER, real-world experience study.

    Science.gov (United States)

    Flisiak, Robert; Janczewska, Ewa; Łucejko, Mariusz; Karpińska, Ewa; Zarębska-Michaluk, Dorota; Nazzal, Khalil; Bolewska, Beata; Białkowska, Jolanta; Berak, Hanna; Fleischer-Stępniewska, Katarzyna; Tomasiewicz, Krzysztof; Karwowska, Kornelia; Simon, Krzysztof; Piekarska, Anna; Tronina, Olga; Tuchendler, Ewelina; Garlicki, Aleksander

    2018-06-11

    We followed for 2 years patients treated with Direct Acting Agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction of liver stiffness (LS), and risk of hepatocellular carcinoma (HCC).The study included patients from 16 hepatologic centers involved in the AMBER, investigators initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. A total of 204 patients among 209 from the primary study were enrolled; 200 with available testing at 2 years follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 non-responders retreated). During 2yFU 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses was lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, two-years follow-up confirmed durability of virologic response after treatment of HCV infection with Ombitasvir/Paritaprevir/ritonavir±Dasabuvir±Ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics, that support the need for longer than 2-year monitoring for possible disease progression. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Modelling of tumour repopulation after chemotherapy

    International Nuclear Information System (INIS)

    Marcu, Loredana; Bezak, Eva

    2010-01-01

    Full text: While repopulation is a clinically observed phe nomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radio therapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed vit1ual head and neck tumour and to study the effect of cisplatin on tumour regres sion and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occu ring, is a highly potent phenomenon, similar to drug resis tance, therefore it should not be neglected during treatment.

  6. Tumour-induced osteomalacia.

    Science.gov (United States)

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

    2017-07-13

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

  7. Malignant thyroid tumours

    International Nuclear Information System (INIS)

    Boerner, W.; Reiners, C.

    1987-01-01

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

  8. Acetyltransferases and tumour suppression

    International Nuclear Information System (INIS)

    Phillips, A C; Vousden, Karen H

    2000-01-01

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

  9. Durable terrestrial bedrock predicts submarine canyon formation

    Science.gov (United States)

    Smith, Elliot; Finnegan, Noah J.; Mueller, Erich R.; Best, Rebecca J.

    2017-01-01

    Though submarine canyons are first-order topographic features of Earth, the processes responsible for their occurrence remain poorly understood. Potentially analogous studies of terrestrial rivers show that the flux and caliber of transported bedload are significant controls on bedrock incision. Here we hypothesize that coarse sediment load could exert a similar role in the formation of submarine canyons. We conducted a comprehensive empirical analysis of canyon occurrence along the West Coast of the contiguous United States which indicates that submarine canyon occurrence is best predicted by the occurrence of durable crystalline bedrock in adjacent terrestrial catchments. Canyon occurrence is also predicted by the flux of bed sediment to shore from terrestrial streams. Surprisingly, no significant correlation was observed between canyon occurrence and the slope or width of the continental shelf. These findings suggest that canyon incision is promoted by greater yields of durable terrestrial clasts to the shore.

  10. Fatty degeneration in a Wilms' tumour after chemotherapy

    International Nuclear Information System (INIS)

    Jeanes, A.C.; Beese, R.C.; McHugh, K.; Ramsay, A.D.

    2002-01-01

    We report a case of extensive fatty change in a Wilms' tumour after chemotherapy demonstrated on CT associated with an increase in tumour volume, in a 10-month-old girl with Beckwith-Wiedemann syndrome. Changes in tumour characteristics after chemotherapy on imaging usually reflect necrosis, haemorrhage and calcification. Assessment of response to therapy is dependent on a documented reduction in tumour volume. In this case, CT showed an increase in tumour size with development of an extensive fatty component following treatment. Subsequent histological examination on the nephrectomy specimen confirmed an extensive fatty component with no evidence of residual blastema. The development of such an extensive fatty component is very unusual. In this case such fatty change was an indicator of tumour sensitivity and response to treatment. (orig.)

  11. Radiopharmaceutical therapy of brain tumours

    International Nuclear Information System (INIS)

    Riva, P.; Franceschi, G.; Frattarelli, M.; Casi, M.; Santimaria, M.; Cremonini, A.M.; Guiducci, G.; Riva, N.

    1999-01-01

    Full text: The loco-regional radioimmunotherapy (RIT) of high-grade malignant glioma may represent a further favourable therapeutic approach, able to ameliorate the ominous prognosis of these diseases. The anti-tenascin monoclonal antibodies (MAbs) are directly injected in the tumoral bed after the operation. In the first pilot study, 81 glioblastoma patients received the MAbs (BC2 and BC4) labelled with 131 I (mean dose 2035 MBq). The toxicity was absent. The median survival was prolonged up to 25 months and the response rate (PR + CR + NED: no evidence of disease in cases with minimal lesions after customary treatments) was 44%. More recently, 90 Y instead of 131 I was employed. The benzyl-DTPA chelator was utilized for 90 Y conjugation. A phase I study was performed in 20 glioblastoma patients, who previously received all conventional regimens, but with progressive tumour. They were intralesionally given escalating 90 Y doses (185, 370, 555, 740, 925 MBq), 4 cases were included in each incremental level. No change in haematology, liver and renal parameters were encountered. The brain MTD was 925 MBq. The radiopharmaceutical remained in high amount only in the neoplastic area and did not diffuse in normal brain region nor in normal organs. The radiation dose to the tumour was, on average, 0.54 Gy per MBq of 90 Y administered (about 4 times higher in comparison to 131 I). Now a phase II study has been initiated. 30 evaluable patients (23 glioblastoma and 7 anaplastic astrocytoma; 8 newly diagnosed and 22 recurrent tumours) who have been already treated with surgery and radiotherapy, underwent loco-regional RIT, by administering a mean 90 Y dose of 740 MBq; in many cases multiple cycles were given. The median survival of patients who had the antibody infusion when their tumour burden was reduced was 28 months. The objective response consisted of 8 PD, 5 SD, 11 PR, 1 CR and 4 NED. The global response rate (PR + CR + NED) was 53.3% (47.8% in glioblastoma and 75.7% in

  12. Durability Evaluation of Superconducting Magnets

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Akihiko; Ogata, Masafumi; Nakauchi, Masahiko; Asahara, Tetsuo; Herai, Toshiki; Nishikawa, Yoichi

    2006-06-01

    It is one of the most essential things to verify the durability of devices and components of JR-Maglev system to realize the system into the future inauguration. Since the load requirements were insufficient in terms of the durability under vibrations under mere running tests carried out on Yamanashi Maglev Test Line hereinafter referred to YMTL, we have developed supplemental method with bench tests. Superconducting magnets hereinafter referred to SCM as used in the experimental running for the last seven years on the YMTL were brought to Kunitachi Technical Research Institute; we conducted tests to evaluate the durability of SCM up to a period of the service life in commercial use. The test results have indicated that no irregularity in each part of SCM proving that SCM are sufficiently durable for the practical application.

  13. Durability Evaluation of Superconducting Magnets

    International Nuclear Information System (INIS)

    Inoue, Akihiko; Ogata, Masafumi; Nakauchi, Masahiko; Asahara, Tetsuo; Herai, Toshiki; Nishikawa, Yoichi

    2006-01-01

    It is one of the most essential things to verify the durability of devices and components of JR-Maglev system to realize the system into the future inauguration. Since the load requirements were insufficient in terms of the durability under vibrations under mere running tests carried out on Yamanashi Maglev Test Line hereinafter referred to YMTL, we have developed supplemental method with bench tests. Superconducting magnets hereinafter referred to SCM as used in the experimental running for the last seven years on the YMTL were brought to Kunitachi Technical Research Institute; we conducted tests to evaluate the durability of SCM up to a period of the service life in commercial use. The test results have indicated that no irregularity in each part of SCM proving that SCM are sufficiently durable for the practical application

  14. Targeting radiation to tumours

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  15. [Gastric mesenchymal tumours (GIST)].

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-05-01

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

  17. Analysis of clonogenic human brain tumour cells: preliminary results of tumour sensitivity testing with BCNU

    Energy Technology Data Exchange (ETDEWEB)

    Rosenblum, M L; Dougherty, D A; Deen, D F; Hoshino, T; Wilson, C B [California Univ., San Francisco (USA). Dept. of Neurology

    1980-04-01

    Biopsies from 6 patients with glioblastoma multiforme were disaggregated and single cells were treated in vitro with various concentrations of 1,3-bis(2-chloroethyl)-1-nitroso urea (BCNU) and plated for cell survival. One patient's cells were sensitive to BCNU in vitro; after a single dose of BCNU her brain scan reverted to normal and she was clinically well. Five tumours demonstrated resistance in vitro. Three of these tumours progressed during the first course of chemotherapy with a nitrosourea and the patients died at 21/2, 4 and 81/2 months after operation. Two patients who showed dramatic responses to radiation therapy were considered unchanged after the first course of nitrosourea therapy (although one demonstrated tumour enlargement on brain scan). The correlation of in vitro testing of tumour cell sensitivity with actual patient response is encouraging enough to warrant further work to determine whether such tests should weigh in decisions on patient therapy.

  18. Differences in radiosensitivity among cells in culture and in experimental tumours: Significance for the effectiveness of human cancer therapy

    International Nuclear Information System (INIS)

    Barendsen, G.W.; Amsterdam Univ.

    1987-01-01

    Problems in the application of radiobiological data on various types of models, cell in vitro, experimental tumours, and clinical models, to the prediction of tumour radiocurability are discussed. On the basis of observations on cells in culture and experimental tumours it is suggested that heterogeneity in responsiveness of tumours in patients is caused in a large part by differences in intrinsic cellular radiosensitivity. Methods and developments are reviewed, which may yield better assays for the prediction of tumour responsiveness to treatments. (Auth.)

  19. Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

    Science.gov (United States)

    Joachim, Agricola; Munseri, Patricia J; Nilsson, Charlotta; Bakari, Muhammad; Aboud, Said; Lyamuya, Eligius F; Tecleab, Teghesti; Liakina, Valentina; Scarlatti, Gabriella; Robb, Merlin L; Earl, Patricia L; Moss, Bernard; Wahren, Britta; Mhalu, Fred; Ferrari, Guido; Sandstrom, Eric; Biberfeld, Gunnel

    2017-08-01

    We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.

  20. Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

    Science.gov (United States)

    Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

    2012-01-01

    Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

  1. IL-12 immunotherapy of minimal residual disease in murine models of HPV16-associated tumours: induction of immune responses, cytokine production and kinetics of immune cell subsets

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Bieblová, Jana; Bubeník, Jan; Reiniš, Milan

    2008-01-01

    Roč. 32, č. 2 (2008), s. 499-507 ISSN 1019-6439 R&D Projects: GA ČR GA301/06/0774 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * MHC class I-positive and -deficient tumours * immature myeloid cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.234, year: 2008

  2. Experimental tumour treatment

    International Nuclear Information System (INIS)

    1985-08-01

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

  3. Impact of F DOPA-PET on therapeutic decision in endocrine tumours: digestive tumours, medullary thyroid cancer or pheochromocytoma

    International Nuclear Information System (INIS)

    Montravers, F.; Grahek, D.; Kerrou, K.; Gutman, F.; Beco, V. de; Nataf, V.; Balard, M.; Talbot, J.N.

    2006-01-01

    FDOPA-PET has been proposed for a decade in oncology, in particular in endocrine tumours. To the best of our knowledge, only one impact rate has been reported: 31% in 17 patients with digestive carcinoid tumours. We did a questionnaire survey to evaluate this impact reported by the referring clinician in 87 patients who had FDOPA PET due to digestive carcinoid tumour or another type of digestive endocrine tumour or a medullary thyroid cancer or a pheochromocytoma. The response rate to the survey was 87%. The overall impact of FDOPA PET on patient's management was 36%. Its value was greater for digestive carcinoid tumour and for medullary thyroid cancer; the number of patients with pheochromocytoma is still limited. In the other digestive endocrine tumours, a change in patient management was less frequent and FDOPA PET should be performed when the other examinations are inconclusive. (author)

  4. Cone-beam computed tomography for lung cancer – validation with CT and monitoring tumour response during chemo-radiation therapy

    International Nuclear Information System (INIS)

    Michienzi, Alissa; Kron, Tomas; Callahan, Jason; Plumridge, Nikki; Ball, David; Everitt, Sarah

    2017-01-01

    Cone-beam computed tomography (CBCT) is a valuable image-guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non-small cell lung cancer (NSCLC) tumour volumes compared to the anatomical ‘gold standard’, CT. Tumour regression or progression on CBCT was also analysed. Patients with Stage I-III NSCLC, prescribed 60 Gy in 30 fractions RT with concurrent platinum-based chemotherapy, routine CBCT and enrolled in a prospective study of serial PET/CT (baseline, weeks two and four) were eligible. Time-matched CBCT and CT gross tumour volumes (GTVs) were manually delineated by a single observer on MIM software, and were analysed descriptively and using Pearson's correlation coefficient (r) and linear regression (R 2 ). Of 94 CT/CBCT pairs, 30 patients were eligible for inclusion. The mean (± SD) CT GTV vs CBCT GTV on the four time-matched pairs were 95 (±182) vs 98.8 (±160.3), 73.6 (±132.4) vs 70.7 (±96.6), 54.7 (±92.9) vs 61.0 (±98.8) and 61.3 (±53.3) vs 62.1 (±47.9) respectively. Pearson's correlation coefficient (r) was 0.98 (95% CI 0.97–0.99, ρ < 0.001). The mean (±SD) CT/CBCT Dice's similarity coefficient was 0.66 (±0.16). Of 289 CBCT scans, tumours in 27 (90%) patients regressed by a mean (±SD) rate of 1.5% (±0.75) per fraction. The mean (±SD) GTV regression was 43.1% (±23.1) from the first to final CBCT. Primary lung tumour volumes observed on CBCT and time-matched CT are highly correlated (although not identical), thereby validating observations of GTV regression on CBCT in NSCLC.

  5. Durability of air lime mortar

    DEFF Research Database (Denmark)

    Nielsen, Anders

    2016-01-01

    This contribution deals with the physical and chemical reasons why pure air lime mortars used in masonry of burned bricks exposed to outdoor climate have shown to be durable from the Middle Ages to our days. This sounds strange in modern times where pure air lime mortars are regarded as weak...... materials, which are omitted from standards for new masonry buildings, where use of hydraulic binders is prescribed. The reasons for the durability seam to be two: 1. The old mortars have high lime contents. 2. The carbonation process creates a pore structure with a fine pored outer layer and coarser pores...

  6. Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

    Science.gov (United States)

    Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

    2006-05-01

    The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

  7. Multiple familial trichoepithelioma: a rare cutaneous tumour

    International Nuclear Information System (INIS)

    Arfan-ul-Bari; Simeen-ber-Rehman

    2004-01-01

    Multiple familial trichoepithelioma (MFT) is a rare autosomal dominant skin disease that presents as many small tumours predominantly on the face. We report a case of multiple familial trichoepithelioma occurring in three members of a family. They were diagnosed simultaneously. Only one was treated with medium depth chemical peeling with partial response. (author)

  8. Excellent and durable response to radiotherapy in a rare case of spinal cord compression due to extra-medullary hematopoiesis in β-thalassemia intermedia: case report and clinicoradiological correlation.

    Science.gov (United States)

    Yathiraj, Prahlad H; Singh, Anshul; Vidyasagar, Sudha; Varma, Muralidhar; Mamidipudi, Vidyasagar

    2017-04-01

    Spinal cord compression (SCC) is an unusual sequale of extra-medullary hematopoiesis (EMH). We report a patient diagnosed with β-thalassemia intermedia at the age of 7 years presenting as a 24-year-old with symptoms suggestive of paraparesis. MR imaging revealed long masses of EMH opposite T5-T11 and L5-S2 vertebrae with cord compression at T6 vertebrae. Patient was treated with external beam radiotherapy (EBRT) to a low dose of 20 Gy in 10 fractions over 2 weeks. The patient had symptomatic relief of paraparesis by the 5th fraction and nearly regained full power in bilateral lower limbs by EBRT conclusion. Patient was begun on hydroxyurea post EBRT and was symptom free at 2-month follow up. With a follow-up of 18 months so far, he remains asymptomatic and free of recurrence. MRI correlation of pre-EBRT, post-EBRT and at first follow-up showed a significant reduction in the size of EMH, increase in diameter of spinal canal post EBRT but a persistent edema which had no clinical manifestation. Though there was a 58% drop in leukocyte count by the end of EBRT, there was no leukocytopenia. We suggest that EBRT should be treatment of choice for SCC due to EMH as it produces as rapid and durable response with minimal acute hematological side-effects.

  9. Genetically modified tumour vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2005-01-01

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

  10. Putting tumours in context.

    Science.gov (United States)

    Bissell, M J; Radisky, D

    2001-10-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

  12. Spatio-temporal tumour model for analysis and mechanism of action ...

    Indian Academy of Sciences (India)

    We have developed a one-dimensional tumour simulator to describe the biodistribution of chemotherapeutic drugs to a tumoral lesion and the tumour cell's response to therapy. A three-compartment model is used for drug dynamics within the tumour. The first compartment represents the extracellular space in which cells ...

  13. Durability of building joint sealants

    Science.gov (United States)

    Christopher C. White; Kar Tean Tan; Donald L. Hunston; R. Sam Williams

    2009-01-01

    Predicting the service life of building joint sealants exposed to service environments in less than real time has been a need of the sealant community for many decades. Despite extensive research efforts to design laboratory accelerated tests to duplicate the failure modes occurring in field exposures, little success has been achieved using conventional durability...

  14. Analysis of the transient response and durability characteristics of a proton exchange membrane fuel cell with different micro-porous layer penetration thicknesses

    International Nuclear Information System (INIS)

    Cho, Junhyun; Park, Jaeman; Oh, Hwanyeong; Min, Kyoungdoug; Lee, Eunsook; Jyoung, Jy-Young

    2013-01-01

    Highlights: • The GDL which has a large MPL penetration showed a better transient response. • The transient response of the PEMFC was affected by the water balance of the GDL. • A large MPL penetration balanced the capillary pressure gradient through the GDL. • The carbon corrosion induced loss of the MPL penetration region. - Abstract: The optimal design of the gas diffusion layer (GDL) of proton exchange membrane fuel cells is crucial because it directly determines the mass transport mechanism of the reactants and products. In this study, the micro-porous layer (MPL) penetration thickness, which affects the pore size profile through the GDL, is varied as the design parameter of the GDL. The cell performance is investigated under various humidity conditions, and the water permeability characteristics are studied. In addition, the accelerated carbon corrosion stress test is conducted to determine the effect of MPL penetration on GDL degradation. GDLs with large MPL penetration thickness show better performance in the high-current–density region due to the enhanced management of water resulting from a balanced capillary pressure gradient. However, the loss of penetrated MPL parts is observed due to the low binding force between the MPL and the GDL substrate

  15. Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Han Ah Lee

    2016-09-01

    Full Text Available Background/Aims Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV off-treatment response. Methods This study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10 IU/mL treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal. Results After stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031. When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5, while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log10 IU/mL (n=11 and >3 log10 IU/mL (n=28, respectively. Conclusion The off-treatment HBsAg level is closely related to clinical relapse after treatment

  16. Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

    Science.gov (United States)

    Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

    2013-08-01

    Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.

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

    Science.gov (United States)

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

    2014-02-01

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

  18. Nuclear medicine in childhood tumours

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    2004-01-01

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

  19. Compositional threshold for Nuclear Waste Glass Durability

    International Nuclear Information System (INIS)

    Kruger, Albert A.; Farooqi, Rahmatullah; Hrma, Pavel R.

    2013-01-01

    Within the composition space of glasses, a distinct threshold appears to exist that separates 'good' glasses, i.e., those which are sufficiently durable, from 'bad' glasses of a low durability. The objective of our research is to clarify the origin of this threshold by exploring the relationship between glass composition, glass structure and chemical durability around the threshold region

  20. Durability of fibre reinforced concrete structures

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan De Place; Hansen, Kurt Kielsgaard

    1996-01-01

    The planned research will indicate, whether fibre reinforced concrete has better or worse durability than normal concrete. Durability specimens will be measured on cracked as well as uncracked specimens. Also the pore structure in the concrete will be characterized.Keywords: Fibre reinforced...... concrete, durability, pore structure, mechanical load...

  1. DURABILITY TESTING OF FLUIDIZED BED STEAM REFORMER (FBSR) WASTE FORMS

    International Nuclear Information System (INIS)

    Jantzen, C

    2006-01-01

    Fluidized Bed Steam Reforming (FBSR) is being considered as a potential technology for the immobilization of a wide variety of high sodium aqueous radioactive wastes. The addition of clay and a catalyst as co-reactants converts high sodium aqueous low activity wastes (LAW) such as those existing at the Hanford and Idaho DOE sites to a granular ''mineralized'' waste form that may be made into a monolith form if necessary. Simulant Hanford and Idaho high sodium wastes were processed in a pilot scale FBSR at Science Applications International Corporation (SAIC) Science and Technology Applications Research (STAR) facility in Idaho Falls, ID. Granular mineral waste forms were made from (1) a basic Hanford Envelope A low-activity waste (LAW) simulant and (2) an acidic INL simulant commonly referred to as sodium-bearing waste (SBW). The FBSR waste forms were characterized and the durability tested via ASTM C1285 (Product Consistency Test), the Environmental Protection Agency (EPA) Toxic Characteristic Leaching Procedure (TCLP), and the Single Pass Flow Through (SPFT) test. The durability of the FBSR waste form products was tested in order to compare the measured durability to previous FBSR waste form testing on Hanford Envelope C waste forms that were made by THOR Treatment Technologies (TTT) and to compare the FBSR durability to vitreous LAW waste forms, specifically the Hanford low activity waste (LAW) glass known as the Low-activity Reference Material (LRM). The durability of the FBSR waste form is comparable to that of the LRM glass for the test responses studied

  2. Haemorrhagic pituitary tumours

    International Nuclear Information System (INIS)

    Lazaro, C.M.; Philippine General Hospital, Manila; Guo, W.Y.; Sami, M.; Hindmarsch, T.; Ericson, K.; Hulting, A.L.; Wersaell, J.

    1994-01-01

    In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI. (orig.)

  3. Tumours following retinoblastoma radiotherapy

    International Nuclear Information System (INIS)

    Mollot, J.-P.

    1978-01-01

    Radioinduced tumours in young patients irradiated in childhood for retinoblastoma take on a particularly deadly aspect. The onset of this true clinical entity characterized by a long post-irradiation latency period induced by a dose above 6000 rads is a real tragedy. The vast majority of patients then enter into a long martyrdom ending in death. The only cure is surgical, but seldom possible. Treatment is limited to palliative radiotherapy, effective for a while, and chemiotherapy as a last resort but often difficult to prescribe. Prevention alone is the answer. The quality and reliability of the radiotherapeutic treatment depend not only on the personal talent of the radiotherapist but above all on the standard of the equipment. A strong reduction in the doses employed as well as recent technological progress improving the material, its precision and reproducibility appear already to have lowered the frequency curve of these fatal radioinduced tumours [fr

  4. Malignant salivary gland tumours

    International Nuclear Information System (INIS)

    Thompson, S.H.

    1982-01-01

    The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy

  5. Malignant salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, S.H. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Oral Pathology)

    1982-08-01

    The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy.

  6. Durability of building materials and components

    CERN Document Server

    Delgado, JMPQ

    2013-01-01

    Durability of Building Materials and Components provides a collection of recent research works to contribute to the systematization and dissemination of knowledge related to the long-term performance and durability of construction and, simultaneously, to show the most recent advances in this domain. It includes a set of new developments in the field of durability, service life prediction methodologies, the durability approach for historical and old buildings, asset and maintenance management and on the durability of materials, systems and components. The book is divided in several chapters that intend to be a resume of the current state of knowledge for benefit of professional colleagues.

  7. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Alice; Stenholm, Anna Catharina Olsen; Kronborg, O

    1998-01-01

    Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...... the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80...

  8. [Adrenal tumours in childhood].

    Science.gov (United States)

    Martos-Moreno, G A; Pozo-Román, J; Argente, J

    2013-09-01

    This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  9. Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue

    International Nuclear Information System (INIS)

    Kubota, Kazuo; Tada, Masao; Yamada, Susumu; Hori, Katsuyoshi; Saito, Sachiko; Sato, Kazunori; Fukuda, Hiroshi; Iwata, Ren; Ido, Tatsuo

    1999-01-01

    To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14 C-2-deoxyglucose (2DG) and 14 C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P<0.05), while both 2DG and Met uptake by the control tumours was higher than uptake by hypoxic tumours. When individual tumours were examined, the uptake of FMISO was inversely correlated with that of Met (r = -0.507, P<0.02), while 2DG showed almost uniform uptake with no significant correlation to FMISO. In conclusion, hypoxic and radioresistant tumours could be identified by increased FMISO uptake in our model, consistent with findings reported by others. We found a large overlap in the distribution of FMISO and 2DG within the tumour, but only a small overlap in the distribution of FMISO and Met. A combination of FMISO and other tracers in positron emission tomography or single-photon emission tomography studies might be more helpful than single-tracer studies in predicting the response of tumour tissues to radiotherapy. (orig.)

  10. Chemical durability of silicoborate glasses

    International Nuclear Information System (INIS)

    Nieto, M.I.; Rodriguez, M.A.; Rubio, J.; Fernandez, A.; Oteo, J.L.

    1987-01-01

    A general view of the durability in silicoborate glasses is presented with more emphasis on the etching factors (chemical composition, lattice structure, pH...) the techniques used for this study and the experimental results. Likewise, the research presently developed in this area at the Instituto de Ceramica y Vidrio, CSIC, is related to the applications. Future research in this field is also mentioned. (author) 15 figs

  11. Vaginal haemangioendothelioma: an unusual tumour.

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

    Vaginal tumours are uncommon and this is a particularly rare case of a vaginal haemangioendothelioma in a 38-year-old woman. Initial presentation consisted of symptoms similar to uterovaginal prolapse with "something coming down". Examination under anaesthesia demonstrated a necrotic anterior vaginal wall tumour. Histology of the lesion revealed a haemangioendothelioma which had some features of haemangiopericytoma. While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma. Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our "knowledge bank" to guide management of these unusual tumours.

  12. Primary bone tumours in infants

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Beluffi, G.; Cohen, D.H.; Padovani, J.; Tamaela, L.; Azouz, M.; Bale, P.; Martin, H.C.; Nayanar, V.V.; Arico, M.

    1985-09-01

    Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomastosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the auhtors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

  13. Radiological diagnosis of liver tumours

    International Nuclear Information System (INIS)

    Lundstedt, C.

    1987-01-01

    Sixty patients treated with an intra-arterial cytostatic drug for metastases from colo-rectal carcinoma were evaluated with angiography to determine prognostic parameters. The extent of tumour in the liver and an unchanged or diminished tumour volume following treatment, as demonstrated with angiography, were associated with significant prolongation of survival. Patients who developed occlusion of the hepatic artery or of branches of the portal vein, also survived longer. 189 patients examined with angiography, 161 with computed tomography (CT), 95 with computed tomographic arteriography (CTA) and 71 with ultrasound (US) were subjected to liver evaluation at laparotomy consisting of inspection and palpation. The result of this surgical liver evaluation was for the purpose of the study regarded as completely accurate and was used to assess the accuracy of the different radiological methods. The location of tumour in the liver lobes or segments was analysed, with a separate evaluation of the right and left liver lobes. The rate of detection of individual tumour nodules was also determined. Angiography detected 55% of liver areas affected by tumour and 47% of individual tumour nodules. CT detected 83% of liver lobes or segments containing tumour, and 70% of the tumour nodules. US detected 69% of the portions of liver holding tumour, and also 69% of the tumour nodules. CTA detected 85% of tumours areas and 74% of separate tumour nodules. Some lesions detected with CT were not seen with CTA and vice versa. More false-positive results were recorded with CTA than with CT using intravenous contrast enhancement. (orig.)

  14. Review article: Pathogenesis and management of gastric carcinoid tumours.

    Science.gov (United States)

    Burkitt, M D; Pritchard, D M

    2006-11-01

    Gastric carcinoid tumours are rare, but are increasing in incidence. To discuss tumour pathogenesis and outline current approaches to patient management. Review of published articles following a Pubmed search. Although interest in gastric carcinoids has increased since it was recognized that they are associated with achlorhydria, to date there is no definite evidence that humans taking long-term acid suppressing medication are at increased risk. Type I tumours are associated with autoimmune atrophic gastritis and hypergastrinaemia, type II are associated with Zollinger-Ellison syndrome, multiple endocrine neoplasia-1 and hypergastrinaemia and sporadic type III carcinoids are gastrin-independent and carry the worst prognosis. Careful investigation of these patients is required, particularly to identify the tumour type, the source of hypergastrinaemia and the presence of metastases. Treatment can be directed at the source of hypergastrinaemia if type I or II tumours are still gastrin responsive and not growing autonomously. Type III tumours should be treated surgically. Advances in our understanding of the pathogenesis of gastric carcinoids have led to recent improvements in investigation and management. Challenges remain in identifying the genetic and environmental factors, in addition to hypergastrinaemia, that are responsible for tumour development in susceptible patients.

  15. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-01

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

  16. Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours

    International Nuclear Information System (INIS)

    Barrande, G.; Kujas, M.; Gancel, A.; Turpin, G.; Bruckert, E.; Kuhn, J.M.; Luton, J.P.

    1995-01-01

    Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab

  17. Management of parapharyngeal space tumours

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  18. Askin Tumour: Case Report

    International Nuclear Information System (INIS)

    Gomez, Carolina; Ramirez, Sandra Milena; Quesada, Diana Constanza; Unigarro Luz Adriana

    2011-01-01

    In this article we report a case of a 19 year-old woman with a final diagnosis of an extra skeletal Primitive Neuroectodermal Tumor/Ewing sarcoma of the chest, also known as Askin tumour. The histologic features and the immunohistochemical profile were consistent with this aggressive malignancy of the chest wall that affects young people. Because the low incidence of this entity, as well as the clear radiological findings, we considered it interesting to describe this documented case and undertake a review of the literature.

  19. Eukaryotic translation initiation factor 5A induces apoptosis in colon cancer cells and associates with the nucleus in response to tumour necrosis factor α signalling

    International Nuclear Information System (INIS)

    Taylor, Catherine A.; Sun Zhong; Cliche, Dominic O.; Ming, Hong; Eshaque, Bithi; Jin Songmu; Hopkins, Marianne T.; Thai, Boun; Thompson, John E.

    2007-01-01

    Eukaryotic translation initiation factor 5A (eIF5A) is thought to function as a nucleocytoplasmic shuttle protein. There are reports of its involvement in cell proliferation, and more recently it has also been implicated in the regulation of apoptosis. In the present study, we examined the effects of eIF5A over-expression on apoptosis and of siRNA-mediated suppression of eIF5A on expression of the tumour suppressor protein, p53. Over-expression of either eIF5A or a mutant of eIF5A incapable of being hypusinated was found to induce apoptosis in colon carcinoma cells. Our results also indicate that eIF5A is required for expression of p53 following the induction of apoptosis by treatment with Actinomycin D. Depiction of eIF5A localization by indirect immunofluorescence has indicated, for the first time, that the protein is rapidly translocated from the cytoplasm to the nucleus by death receptor activation or following treatment with Actinomycin D. These findings collectively indicate that unhypusinated eIF5A may have pro-apoptotic functions and that eIF5A is rapidly translocated to the nucleus following the induction of apoptotic cell death

  20. Evaluating the agreement between tumour volumetry and the estimated volumes of tumour lesions using an algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Laubender, Ruediger P. [German Cancer Consortium (DKTK), Heidelberg (Germany); University Hospital Munich - Campus Grosshadern, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Lynghjem, Julia; D' Anastasi, Melvin; Graser, Anno [University Hospital Munich - Campus Grosshadern, Institute for Clinical Radiology, Munich (Germany); Heinemann, Volker; Modest, Dominik P. [University Hospital Munich - Campus Grosshadern, Department of Medical Oncology, Munich (Germany); Mansmann, Ulrich R. [University Hospital Munich - Campus Grosshadern, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); Sartorius, Ute; Schlichting, Michael [Merck KGaA, Darmstadt (Germany)

    2014-07-15

    To evaluate the agreement between tumour volume derived from semiautomated volumetry (SaV) and tumor volume defined by spherical volume using longest lesion diameter (LD) according to Response Evaluation Criteria In Solid Tumors (RECIST) or ellipsoid volume using LD and longest orthogonal diameter (LOD) according to World Health Organization (WHO) criteria. Twenty patients with metastatic colorectal cancer from the CIOX trial were included. A total of 151 target lesions were defined by baseline computed tomography and followed until disease progression. All assessments were performed by a single reader. A variance component model was used to compare the three volume versions. There was a significant difference between the SaV and RECIST-based tumour volumes. The same model showed no significant difference between the SaV and WHO-based volumes. Scatter plots showed that the RECIST-based volumes overestimate lesion volume. The agreement between the SaV and WHO-based relative changes in tumour volume, evaluated by intraclass correlation, showed nearly perfect agreement. Estimating the volume of metastatic lesions using both the LD and LOD (WHO) is more accurate than those based on LD only (RECIST), which overestimates lesion volume. The good agreement between the SaV and WHO-based relative changes in tumour volume enables a reasonable approximation of three-dimensional tumour burden. (orig.)

  1. Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

    Science.gov (United States)

    Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

    2004-09-09

    OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.

  2. Cement replacement materials. Properties, durability, sustainability

    International Nuclear Information System (INIS)

    Ramezanianpour, Ali Akbar

    2014-01-01

    The aim of this book is to present the latest findings in the properties and application of Supplementary Cementing Materials and blended cements currently used in the world in concrete. Sustainability is an important issue all over the world. Carbon dioxide emission has been a serious problem in the world due to the greenhouse effect. Today many countries agreed to reduce the emission of CO2. Many phases of cement and concrete technology can affect sustainability. Cement and concrete industry is responsible for the production of 7% carbon dioxide of the total world CO2 emission. The use of supplementary cementing materials (SCM), design of concrete mixtures with optimum content of cement and enhancement of concrete durability are the main issues towards sustainability in concrete industry.

  3. ICP experiments more durable pavements

    International Nuclear Information System (INIS)

    Carta Petrolera

    1994-01-01

    A new asphalts technology that will make more durable the pavement in the highways and roads of the cities of Colombia investigates the Colombian Institute of the Petroleum ICP. The project that will have important incidence in the solution of one of the main problems in the roads of cities like Bogota, is only one of the 35 investigation programs and application of new technologies that with relationship to the sector of the hydrocarbons and its influence branches the ICP advances. The investigation looks for to elevate the current average of useful life of the pavements, with that it would be reached a standard that has the developed countries in this field

  4. Estimating Durability of Reinforced Concrete

    Science.gov (United States)

    Varlamov, A. A.; Shapovalov, E. L.; Gavrilov, V. B.

    2017-11-01

    In this article we propose to use the methods of fracture mechanics to evaluate concrete durability. To evaluate concrete crack resistance characteristics of concrete directly in the structure in order to implement the methods of fracture mechanics, we have developed special methods. Various experimental studies have been carried out to determine the crack resistance characteristics and the concrete modulus of elasticity during its operating. A comparison was carried out for the results obtained with the use of the proposed methods and those obtained with the standard methods for determining the concrete crack resistance characteristics.

  5. Gastric neuroendocrine tumours.

    Science.gov (United States)

    Crosby, David A; Donohoe, Claire L; Fitzgerald, Louise; Muldoon, Cian; Hayes, Brian; O'Toole, Dermot; Reynolds, John V

    2012-01-01

    Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment. Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs. Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted. Copyright © 2012 S. Karger AG, Basel.

  6. Radiotherapy in ocular tumours

    International Nuclear Information System (INIS)

    Pinto, J.M.

    1982-01-01

    Ocular tumours at the Tata Memorial Hospital, Bombay, form about 0.14% of all the proved cancer cases. In case of unilateral retinoblastoma with the other eye being not non-seeing for any reason, enucleation is advised, as the diagnosis may sometimes be in doubt. If after enucleation, optic nerve and/or peribulbar tissues are found to be involved, post-operative irradiation is given to the whole orbit. In bilateral retinoblastoma the more affected eye is enucleated and an attempt is made to preserve vision in the other eye. A tumour dose of 3500 to 4000 rad in about 4 weeks is given with a cobalt beam using a direct anterior field. A cataract that may develop has to be taken care of. Lateral and/or medial fields are used with deep X-rays. In certain cases, an implant of cobalt-60 or gold-198 grain is done. For carcinoma of conjuctiva, small lesions or early lesions are excised and a beta radiation dose of 2000 rad weekly for about 4 to 5 weeks is given; larger lesions require enucleation or exenteration followed by irradiation with super-voltage radiation. Post-irradiation sarcomas may develop many years later. Irradiation is repeated for recurrences. (M.G.B.)

  7. Durability Improvements Through Degradation Mechanism Studies

    Energy Technology Data Exchange (ETDEWEB)

    Borup, Rodney L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mukundan, Rangachary [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Spernjak, Dusan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Baker, Andrew M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lujan, Roger W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Langlois, David Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ahluwalia, Rajesh [Argonne National Lab. (ANL), Argonne, IL (United States); Papadia, D. D. [Argonne National Lab. (ANL), Argonne, IL (United States); Weber, Adam Z. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kusoglu, Ahmet [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Shi, Shouwnen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); More, K. L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Grot, Steve [Ion Power, New Castle, DE (United States)

    2015-08-03

    The durability of polymer electrolyte membrane (PEM) fuel cells is a major barrier to the commercialization of these systems for stationary and transportation power applications. By investigating cell component degradation modes and defining the fundamental degradation mechanisms of components and component interactions, new materials can be designed to improve durability. To achieve a deeper understanding of PEM fuel cell durability and component degradation mechanisms, we utilize a multi-institutional and multi-disciplinary team with significant experience investigating these phenomena.

  8. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab.

    Science.gov (United States)

    Pierga, J-Y; Bidard, F-C; Autret, A; Petit, T; Andre, F; Dalenc, F; Levy, C; Ferrero, J-M; Romieu, G; Bonneterre, J; Lerebours, F; Bachelot, T; Kerbrat, P; Campone, M; Eymard, J-C; Mouret-Reynier, M-A; Gligorov, J; Hardy-Bessard, A-C; Lortholary, A; Soulie, P; Boher, J-M; Proudhon, C; Charafe-Jaufret, E; Lemonnier, J; Bertucci, F; Viens, P

    2017-01-01

    We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials. © The Author 2016

  9. Hygrothermal Behavior, Building Pathology and Durability

    CERN Document Server

    Delgado, JMPQ

    2013-01-01

    The main purpose of this book, Hygrothermal, Building Pathology and Durability, is to provide a collection of recent research works to contribute to the systematization and dissemination of knowledge related to construction pathology, hygrothermal behaviour of buildings, durability and diagnostic techniques and, simultaneously, to show the most recent advances in this domain. It includes a set of new developments in the field of building physics and hygrothermal behaviour, durability approach for historical and old buildings and building pathology vs. durability. The book is divided in several chapters that are a resume of the current state of knowledge for benefit of professional colleagues, scientists, students, practitioners, lecturers and other interested parties to network.

  10. Carcinoid Tumour of the Ovary

    African Journals Online (AJOL)

    Abstract. A case of bilateral carcinoid tumour of the ovary, with benign cystic teratoma in one ovary, in a 38 year old woman is presented. She had total abdominal hysterectomy, bilateral salpingoophorectomy, infracolic omentectomy and appendectomy. There was no macroscopic tumour in the vermiform appendix and the ...

  11. Experimental Study on Durability Improvement of Fly Ash Concrete with Durability Improving Admixture

    OpenAIRE

    Quan, Hong-zhu; Kasami, Hideo

    2014-01-01

    In order to improve the durability of fly ash concrete, a series of experimental studies are carried out, where durability improving admixture is used to reduce drying shrinkage and improve freezing-thawing resistance. The effects of durability improving admixture, air content, water-binder ratio, and fly ash replacement ratio on the performance of fly ash concrete are discussed in this paper. The results show that by using durability improving admixture in nonair-entraining fly ash concrete,...

  12. Durability of Self Compacting Concrete

    International Nuclear Information System (INIS)

    Benmarce, A.; Boudjehem, H.; Bendjhaiche, R.

    2011-01-01

    Self compacting concrete (SCC) seem to be a very promising materials for construction thanks to their properties in a fresh state. Studying of the influence of the parameters of specific designed mixes to their mechanical, physical and chemical characteristics in a state hardened is an important stage so that it can be useful for new-to-the-field researchers and designers (worldwide) beginning studies and work involving self compacting concrete. The objective of this research is to study the durability of self compacting concrete. The durability of concrete depends very much on the porosity; the latter determines the intensity of interactions with aggressive agents. The pores inside of concrete facilitate the process of damage, which began generally on the surface. We are interested to measure the porosity of concrete on five SCC with different compositions (w/c, additives) and vibrated concrete to highlight the influence of the latter on the porosity, thereafter on the compressive strength and the transfer properties (oxygen permeability, chloride ion diffusion, capillary absorption). (author)

  13. Residential Radon and Brain Tumour Incidence in a Danish Cohort

    DEFF Research Database (Denmark)

    Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus Erik

    2013-01-01

    Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect of expo...... significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.......Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect...... of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods: During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced...

  14. [Neonatal tumours and congenital malformations].

    Science.gov (United States)

    Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

    2008-06-01

    The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

  15. Adapting radiotherapy to hypoxic tumours

    Science.gov (United States)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  16. Adapting radiotherapy to hypoxic tumours

    International Nuclear Information System (INIS)

    Malinen, Eirik; Soevik, Aste; Hristov, Dimitre; Bruland, Oeyvind S; Olsen, Dag Rune

    2006-01-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO 2 -related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO 2 -related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO 2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO 2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure

  17. 31P NMR spectroscopy of tumors in the evaluation of response to therapy

    International Nuclear Information System (INIS)

    Sijens, P.E.

    1988-01-01

    In this thesis the effects of different kinds of therapy on tumour metabolism were investigated by in vivo 31P NMR spectroscopy. From the first five chapters (laboratory-animal studies) it turns out that after radiotherapy as well as after hyperthermy or chemoterapy changes can be observed in the 31P NMR spectra of tumours. In a number of cases a durable decline occurred in the ratio of the high-energetic adenosinephosphate (ATP) and the low-energeic anorganic phosphate, cuased by the mortification of tumourcells. On the other hand, tumour regression after effective chemotherapy resulted in a growth of the ATP/Pi ratio. In one case a temporary drop occurred which could be related to a temporary decrease in tumour perfusion. In anoter case a temporary drop of the ATP/Pi ratio correlated with resistence against treatment with cis-diaminodichoroplatina. In contrast with the changes in ATP/Pi ratio, the changes, after (chemo)therapy, in tumour pH do not seem to be related with the respons of the tumour. The results of the laboratory-animal experiments indicate that in vivo 31P NMR spectroscopy could be applied in the clinic in order to establish betime the response of tumours on therapy. In ch. 6 initial experiences with clinical NMR spectroscopy of human breast cancer are described. The results indicate that by 31P NMR spectroscopy malignant breast tissues can be discerned from normal breast tissues, following radiotherapy and subsequent tumour regression, in the spectrum of the tumorous region an intense PCr signal developed which appeared to reflect a metabolic change in the tumous itself. 177 refs.; 27 figs.; 6 tabs

  18. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

    KAUST Repository

    Perlman, Elizabeth J.

    2015-12-04

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.

  19. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

    KAUST Repository

    Perlman, Elizabeth J.; Gadd, Samantha; Arold, Stefan T.; Radhakrishnan, Anand; Gerhard, Daniela S.; Jennings, Lawrence; Huff, Vicki; Guidry Auvil, Jaime M.; Davidsen, Tanja M.; Dome, Jeffrey S.; Meerzaman, Daoud; Hsu, Chih Hao; Nguyen, Cu; Anderson, James; Ma, Yussanne; Mungall, Andrew J; Moore, Richard A.; Marra, Marco A.; Mullighan, Charles G; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Gastier-Foster, Julie M.; Ross, Nicole; Smith, Malcolm A.

    2015-01-01

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.

  20. Cancer and tumour markers

    International Nuclear Information System (INIS)

    Osifo, B.

    1999-02-01

    Cancer has been a major cause of death world wide and in Nigeria there are six commonest forms of manifestation of cancer known. Of these prostrate cancer is the highest with 16% occurrence of all known cancers according to a study by the Histopathology Department of the UCH. Many factors, amongst them dietary, environmental, lifestyle, age and sedentary work are possible causes. With the global rise in incidents, the IAEA initiated the Tumour Marker Project as a means of screening cancers in 15 African countries including Nigeria. In Nigeria, 4 groups of the commonest cancers have been chosen for screening. These are prostrate cancer, primary liver cancer, cancer of the GI tract and trophoblastic cancer

  1. Single-hit mechanism of tumour cell killing by radiation.

    Science.gov (United States)

    Chapman, J D

    2003-02-01

    To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells

  2. Effect of glass composition on waste form durability: A critical review

    International Nuclear Information System (INIS)

    Ellison, A.J.G.; Mazer, J.J.; Ebert, W.L.

    1994-11-01

    This report reviews literature concerning the relationship between the composition and durability of silicate glasses, particularly glasses proposed for immobilization of radioactive waste. Standard procedures used to perform durability tests are reviewed. It is shown that tests in which a low-surface area sample is brought into contact with a very large volume of solution provide the most accurate measure of the intrinsic durability of a glass composition, whereas high-surface area/low-solution volume tests are a better measure of the response of a glass to changes in solution chemistry induced by a buildup of glass corrosion products. The structural chemistry of silicate and borosilicate glasses is reviewed to identify those components with the strongest cation-anion bonds. A number of examples are discussed in which two or more cations engage in mutual bonding interactions that result in minima or maxima in the rheologic and thermodynamic properties of the glasses at or near particular optimal compositions. It is shown that in simple glass-forming systems such interactions generally enhance the durability of glasses. Moreover, it is shown that experimental results obtained for simple systems can be used to account for durability rankings of much more complex waste glass compositions. Models that purport to predict the rate of corrosion of glasses in short-term durability tests are evaluated using a database of short-term durability test results for a large set of glass compositions. The predictions of these models correlate with the measured durabilities of the glasses when considered in large groupings, but no model evaluated in this review provides accurate estimates of durability for individual glass compositions. Use of these models in long-term durability models is discussed. 230 refs

  3. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  4. Durability as integral characteristic of concrete

    Science.gov (United States)

    Suleymanova, L. A.; Pogorelova, I. A.; Suleymanov, K. A.; Kirilenko, S. V.; Marushko, M. V.

    2018-03-01

    The carried-out research provides insight into the internal bonds energy in material as the basis of its durability, deformability, integrity and resistance to different factors (combined effects of external loadings and (or) environment), into the limits of technical possibilities, durability and physical reality of the process of concrete deterioration, which allows designing reliable and cost-effective ferroconcrete constructions for different purposes.

  5. Reliability and durability in solar energy systems

    Energy Technology Data Exchange (ETDEWEB)

    Godolphin, D.

    1982-10-01

    The reliability and durability in solar energy systems for residential buildings is discussed. It is concluded that although strides have been made in design and manufacturing over the past years, the reliability and durability of the equipment depends on the proper installation. (MJF)

  6. Bone marrow oedema associated with benign and malignant bone tumours

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)], E-mail: steven.james@roh.nhs.uk; Panicek, D.M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)

    2008-07-15

    Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed.

  7. VIP secreting tumours in infancy

    International Nuclear Information System (INIS)

    Davies, R.P.; Slavotinek, J.P.; Dorney, S.F.A.

    1990-01-01

    Vasoactive intestinal polypeptide (VIP) secreting neural crest tumours are an uncommon but important treatable cause of intractable childhood diarrhoea. The radiological appearances of two cases are presented with a review of radiological findings in childhood VIP secreting neural crest tumours. Twenty eight cases of childhood VIP secreting neural crest tumours were reviewed. Nineteen (68%) were ganglioneuroblastomas and nine (32%) were ganglioneuromas. The majority of tumours (66%) were in a paravertebral location in the abdomen indicating that a search for such a tumour should be initiated at this site. Eighteen of the twenty eight cases reviewed discussed relevant radiological investigations. Calcification was detected in 50% of abdominal radiographs. Gut dilatation was often a prominent feature. A mass was detected in 5 of 5 cases where ultrasound findings were reported, and seven of seven cases with CT findings reported. Prior to the availability of CT and ultrasound the most useful investigation was IVU which demonstrated evidence of a mass in 5 of 9 cases. The presence of paravertebral calcification and gut dilatation on the plain radiograph of a child with intractable diarrhoea suggests the presence of a VIP secreting neural crest tumour. If an abdominal tumour is not found in the appropriate clinical setting and VIP levels are elevated, a widespread search of the paravertebral region is indicated. (orig.)

  8. Ceramics: Durability and radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, R.C.; Lutze, W. [Univ. of New Mexico, Albuquerque, NM (United States); Weber, W.J. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-05-01

    At present, there are three seriously considered options for the disposition of excess weapons plutonium: (1) incorporation, partial burn-up and direct disposal of MOX-fuel; (2) vitrification with defense waste and disposal as glass {open_quotes}logs{close_quotes}; (3) deep borehole disposal. The first two options provide a safeguard due to the high activity of fission products in the irradiated fuel and the defense waste. The latter option has only been examined in a preliminary manner, and the exact form of the plutonium has not been identified. In this paper, we review the potential for the immobilization of plutonium in highly durable crystalline ceramics apatite, pyrochlore, zirconolite, monazite and zircon. Based on available data, we propose zircon as the preferred crystalline ceramic for the permanent disposition of excess weapons plutonium.

  9. Durability of aircraft composite materials

    Science.gov (United States)

    Dextern, H. B.

    1982-01-01

    Confidence in the long term durability of advanced composites is developed through a series of flight service programs. Service experience is obtained by installing secondary and primary composite components on commercial and military transport aircraft and helicopters. Included are spoilers, rudders, elevators, ailerons, fairings and wing boxes on transport aircraft and doors, fairings, tail rotors, vertical fins, and horizontal stabilizers on helicopters. Materials included in the evaluation are boron/epoxy, Kevlar/epoxy, graphite/epoxy and boron/aluminum. Inspection, maintenance, and repair results for the components in service are reported. The effects of long term exposure to laboratory, flight, and outdoor environmental conditions are reported for various composite materials. Included are effects of moisture absorption, ultraviolet radiation, and aircraft fuels and fluids.

  10. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    International Nuclear Information System (INIS)

    Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

    2008-01-01

    High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically

  11. Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, J; Moudry, P; Hodny, Z

    2011-01-01

    activation in CIS; and enhanced HP1α in teratoma structures with epithelial and neuronal differentiation. Differential expression of the three heterochromatin markers suggests their partly non-overlapping roles, and separation of heterochromatinization from DDR activation highlights distinct responses...

  12. Primary vertebral tumours in children

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-03-01

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

  13. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

    International Nuclear Information System (INIS)

    Aboagye, Eric O.; Kenny, Laura M.; Myers, Melvyn; Gilbert, Fiona J.; Fleming, Ian N.; Beer, Ambros J.; Cunningham, Vincent J.; Marsden, Paul K.; Visvikis, Dimitris; Gee, Antony D.; Groves, Ashley M.; Cook, Gary J.; Kinahan, Paul E.; Clarke, Larry

    2012-01-01

    The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [ 15 O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics. (orig.)

  14. An experimental study of tumour size and radiosensitivity

    International Nuclear Information System (INIS)

    Hill, S.A.; Denekamp, J.

    1989-01-01

    When designing experimental studies of tumours, it is considered important to control all variables that might alter the radiosensitivity and hence influence the variability of the data. One such variable is tumour size. We have studied the regrowth delay of a mammary carcinoma treated at 2-10 mm mean diameter (a 125-fold change of volume) with X-rays alone or X-rays plus misonidazole (MISO). The data were analysed to give dose-response curves, using four endpoints. Regrowth to a fixed size (4.5 mm larger than treatment size), or by a fixed increment (4 times the original volume) was expressed either as absolute delay, or as specific growth delay to allow for the changes in volume doubling time as the tumour grows. The method of analysis made no difference to the measured sensitizer enhancement ratio (SER) for MISO. The SER was dose-dependent, being higher doses, but was not different in tumours of 2 or 10 mm diameter. However, when comparing response to X-rays alone, the method of analysis made a very big difference to the conclusions. Regrowth to R + 4.5 mm showed no change in radiosensitivity with tumour size, but regrowth to 4 times the original volume (the most logical endpoint) indicated that large tumours were more sensitive than small. We conclude that regrowth delay may be an inappropriate method for comparing absolute sensitivities of tumours of different sizes. However, for studying the effectiveness of a radiomodifier the constraints of tumour size at irradiation seem to be less severe than previously believed. (author). 8 refs.; 8 figs

  15. The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Klausen, Camilla; Caye-Thomasen, Per

    2015-01-01

    -34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported...... been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg...

  16. Cystic tumours of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Itai, Y. [Dept. of Radiology, Inst. of Clinical Medicine, Tsukuba Univ. (Japan); Ohtomo, K. [Univ. of Tokyo Hospital, Tokyo (Japan)

    1996-12-01

    In this pictorial essay we present the typical appearances of cystic pancreatic tumours, the wide spectrum of their features, and differential features among cystic pancreatic masses with an emphasis on CT. Pseudocysts are the most common cystic lesion in the pancreas and can be induced by pancreatitis, trauma or surgery. Pseudocysts appear as a round cystic mass with a definite wall. However, they can mimic cystic tumours associated with internal septation and/or necrotic mass of various shapes. Conversely, cystic tumours can appear as a simple cyst lacking any thickening of wall, septation or mural nodule. Pancreatic carcinoma not infrequently induces secondary cysts upstream of the obstructed pancreatic duct. The cysts are pseudocysts or retention cysts in nature. When cysts are formed in the pancreatic parenchyma or adjacent to pancreatic carcinoma they may mimic cystic tumour. (orig./VHE)

  17. Cystic tumours of the pancreas

    International Nuclear Information System (INIS)

    Itai, Y.; Ohtomo, K.

    1996-01-01

    In this pictorial essay we present the typical appearances of cystic pancreatic tumours, the wide spectrum of their features, and differential features among cystic pancreatic masses with an emphasis on CT. Pseudocysts are the most common cystic lesion in the pancreas and can be induced by pancreatitis, trauma or surgery. Pseudocysts appear as a round cystic mass with a definite wall. However, they can mimic cystic tumours associated with internal septation and/or necrotic mass of various shapes. Conversely, cystic tumours can appear as a simple cyst lacking any thickening of wall, septation or mural nodule. Pancreatic carcinoma not infrequently induces secondary cysts upstream of the obstructed pancreatic duct. The cysts are pseudocysts or retention cysts in nature. When cysts are formed in the pancreatic parenchyma or adjacent to pancreatic carcinoma they may mimic cystic tumour. (orig./VHE)

  18. Imaging oxygenation of human tumours

    International Nuclear Information System (INIS)

    Padhani, Anwar R.; Krohn, Kenneth A.; Lewis, Jason S.; Alber, Markus

    2007-01-01

    Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. 18 F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy. (orig.)

  19. Highly Sensitive, Transparent, and Durable Pressure Sensors Based on Sea-Urchin Shaped Metal Nanoparticles.

    Science.gov (United States)

    Lee, Donghwa; Lee, Hyungjin; Jeong, Youngjun; Ahn, Yumi; Nam, Geonik; Lee, Youngu

    2016-11-01

    Highly sensitive, transparent, and durable pressure sensors are fabricated using sea-urchin-shaped metal nanoparticles and insulating polyurethane elastomer. The pressure sensors exhibit outstanding sensitivity (2.46 kPa -1 ), superior optical transmittance (84.8% at 550 nm), fast response/relaxation time (30 ms), and excellent operational durability. In addition, the pressure sensors successfully detect minute movements of human muscles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Tumour markers in urology

    International Nuclear Information System (INIS)

    Schmid, L.; Fornara, P.; Fabricius, P.G.

    1988-01-01

    The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.) [de

  1. Integrated durability process in product development

    International Nuclear Information System (INIS)

    Pompetzki, M.; Saadetian, H.

    2002-01-01

    This presentation describes the integrated durability process in product development. Each of the major components of the integrated process are described along with a number of examples of how integrated durability assessment has been used in the ground vehicle industry. The durability process starts with the acquisition of loading information, either physically through loads measurement or virtually through multibody dynamics. The loading information is then processed and characterized for further analysis. Durability assessment was historically test based and completed through field or laboratory evaluation. Today, it is common that both the test and CAE environments are used together in durability assessment. Test based durability assessment is used for final design sign-off but is also critically important for correlating CAE models, in order to investigate design alternatives. There is also a major initiative today to integrate the individual components into a process, by linking applications and providing a framework to communicate information as well as manage all the data involved in the entire process. Although a single process is presented, the details of the process can vary significantly for different products and applications. Recent applications that highlight different parts of the durability process are given. As well as an example of how integration of software tools between different disciplines (MBD, FE and fatigue) not only simplifies the process, but also significantly improves it. (author)

  2. Highly Dispersed Alloy Catalyst for Durability

    Energy Technology Data Exchange (ETDEWEB)

    Murthi, Vivek S.; Izzo, Elise; Bi, Wu; Guerrero, Sandra; Protsailo, Lesia

    2013-01-08

    Achieving DOE's stated 5000-hr durability goal for light-duty vehicles by 2015 will require MEAs with characteristics that are beyond the current state of the art. Significant effort was placed on developing advanced durable cathode catalysts to arrive at the best possible electrode for high performance and durability, as well as developing manufacturing processes that yield significant cost benefit. Accordingly, the overall goal of this project was to develop and construct advanced MEAs that will improve performance and durability while reducing the cost of PEMFC stacks. The project, led by UTC Power, focused on developing new catalysts/supports and integrating them with existing materials (membranes and gas diffusion layers (GDLs)) using state-of-the-art fabrication methods capable of meeting the durability requirements essential for automotive applications. Specifically, the project work aimed to lower platinum group metals (PGM) loading while increasing performance and durability. Appropriate catalysts and MEA configuration were down-selected that protects the membrane, and the layers were tailored to optimize the movements of reactants and product water through the cell to maximize performance while maintaining durability.

  3. Renal angiomyoadenomatous tumour: Imaging features

    Science.gov (United States)

    Sahni, V. Anik; Hirsch, Michelle S.; Silverman, Stuart G.

    2012-01-01

    Renal angiomyoadenomatous tumour is a rare, recently described neoplasm with a distinctive histological appearance. Although reported in the pathology literature, to our knowledge, no prior reports have described its imaging appearance. We describe the computed tomography and magnetic resonance imaging features of an incidentally detected renal angiomyoadenomatous tumour that appeared as a well-marginated, solid T2-hypointense enhancing mass, in a 50-year-old woman. It is indistinguishable from a variety of benign and malignant renal neoplasms. PMID:23093565

  4. Paediatric laryngeal granular cell tumour

    Directory of Open Access Journals (Sweden)

    Dauda Ayuba

    2009-01-01

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

  5. Surgical approach to pineal tumours.

    Science.gov (United States)

    Pluchino, F; Broggi, G; Fornari, M; Franzini, A; Solero, C L; Allegranza, A

    1989-01-01

    During a period of 10 years (1977-1986) 40 cases of tumour of the pineal region have been treated at the Istituto Neurologico "C. Besta"-of Milan. Out of these 40 cases, 27 (67.5%) were in the paediatric (10-15 years) or juvenile (15-20 years) age at the time of operation. Since 1983 a specific diagnostic and therapeutic protocol has been adopted and thereafter direct surgical removal of the tumour was performed only when the neuroradiological investigations were highly suggestive of a benign extrinsic lesion. Sixteen cases in this series underwent direct surgical removal; in the remaining 24 cases stereotactic biopsy of the tumour was performed in the first instance. On the basis of the histological diagnosis obtained by this procedure surgical excision of the tumour (9 cases) or radiotherapy (15 cases) was then performed. 25 cases underwent surgical removal of the lesion. In all the cases the infratentorial supracerebellar approach as introduced by Krause and then modified by Stein was adopted. On analysis of the data of this series it was observed that in 25% of the cases completely benign resectable tumours were found; in 25% of the cases astrocytoma (grade I-II) which could be treated at least by partial removal were present; in 30% of the cases radiosensitive lesions were encountered. In the remaining 20% of the cases highly malignant tumours were found which should be treated only by radiotherapy and/or chemotherapy.

  6. MRI characteristics of midbrain tumours

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  7. Psychiatric manifestations of brain tumours: a review | Magoha | East ...

    African Journals Online (AJOL)

    Clinicians must have high index of suspicion when managing psychiatric symptoms that are atypical, new-onset, anxiety, or with poor response and resistance to known and efficacious psychopharmaco-therapy treatment regimes, as there may be an underlying brain tumour responsible for the symptomatology. This must ...

  8. Increase of cyclic durability of pressure vessels

    International Nuclear Information System (INIS)

    Vorona, V.A.; Zvezdin, Yu.I.

    1980-01-01

    The durability of multilayer pressure vessels under cyclic loading is compared with single-layer vessels. The relative conditional durability is calculated taking into account the assumption on the consequent destruction of layers and viewing a vessel wall as an indefinite plate. It is established that the durability is mainly determined by the number of layers and to a lesser degree depends on the relative size of the defect for the given layer thickness. The advantage of the multilayer vessels is the possibility of selecting layer materials so that to exclude the effect of agressive corrosion media on the strength [ru

  9. Pituitary tumour causing gigantism. Morphology and in vitro hormone secretion.

    Science.gov (United States)

    Anniko, M; Ritzén, E M

    1986-01-01

    True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in a 13-year-old boy. The clinical history indicated that the tumour had caused an oversecretion of GH since the age of 4-5 years. At diagnosis, the sella turcica was markedly enlarged. No infiltrative growth was noted at surgery. Endocrine investigations showed elevated GH and PRL secretion. Light and electron microscopy of tumour tissue revealed densely packed pleomorphic cells of both GH and PRL type. In addition, oncocyte-like cells were observed. Organ culture of pieces of tumour tissue demonstrated continued secretion of GH and PRL into the medium for more than 5 days in vitro. Addition of bromocriptine to the medium caused a rapid decline in PRL secretion while GH secretion remained the same. X-ray irradiation in vitro also caused a decrease in PRL secretion. These effects of bromocriptine and X-ray on hormone secretion in vitro mirrored the corresponding effect of treatment, when the patient showed signs of tumour recurrence after pituitary surgery. It is concluded that also in childhood, the in vitro response of tumour tissue to various treatments may be explored as a possible way to predict the efficacy of pharmacological or irradiation treatment of pituitary tumours.

  10. Quantifying heterogeneity in human tumours using MRI and PET.

    Science.gov (United States)

    Asselin, Marie-Claude; O'Connor, James P B; Boellaard, Ronald; Thacker, Neil A; Jackson, Alan

    2012-03-01

    Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity. In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. The Askin tumour. Neuroactodermic tumour of the thoracic wall

    International Nuclear Information System (INIS)

    Velazquez, P.; Nicolas, A. I.; Vivas, I.; Damaso Aquerreta, J.; Martinez-Cuesta, A.

    1999-01-01

    The Askin tumours is an extremely rare and malignant process in the thoracic pulmonary region during infancy and youth. The differential diagnosis has to be considered with other thoracic wall tumours that are more common in pediatrics like the undifferentiated neuroblastoma, the embionic rabdomiosarcoma, the Ewing sarcoma and the linfoma. A retrospective examination was carried out on 473 thoracic wall tumours from 1994 to 1997 at our centre, resulting in 4 patients with an anatomopathologically tested Askin tumour (ages from 13-21). All the cases were studied using simple radiography and CT. In two cases MRI was also used. The most common clinical manifestation was a palpable painful mass in the thoracic wall. In the simple radiograph the main finding was a large mass of extrapleural soft material, with costal destruction ( n=3) and a pleural effusion (n=2). In the CT study the mass was heterogeneous, with internal calcifications in one case. CT and MRI showed invasion in the mediastinum (n=1), medular channel (n=1) and phrenic and sulphrenic extension (n=1). The Askin tumour should be included in the differential diagnosis of thoracic wall masses in infant-youth ages. There are no specific morphological characteristics. Both CT and MRI are useful for the diagnosis, staging and follow up. (Author) 11 refs

  12. Quick test for durability factor estimation.

    Science.gov (United States)

    2010-03-01

    The Missouri Department of Transportation (MoDOT) is considering the use of the AASHTO T 161 Durability Factor (DF) as an endresult : performance specification criterion for evaluation of paving concrete. However, the test method duration can exceed ...

  13. Childhood Adrenocortical Tumours: a Review

    Directory of Open Access Journals (Sweden)

    Marques-Pereira Rosana

    2006-05-01

    Full Text Available Abstract Childhood adrenocortical tumour (ACT is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6% or mixed with Cushing's syndrome (42.0% was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.

  14. Recent Advances in Durability and Damage Tolerance Methodology at NASA Langley Research Center

    Science.gov (United States)

    Ransom, J. B.; Glaessgen, E. H.; Raju, I. S.; Harris, C. E.

    2007-01-01

    Durability and damage tolerance (D&DT) issues are critical to the development of lighter, safer and more efficient aerospace vehicles. Durability is largely an economic life-cycle design consideration whereas damage tolerance directly addresses the structural airworthiness (safety) of the vehicle. Both D&DT methodologies must address the deleterious effects of changes in material properties and the initiation and growth of damage that may occur during the vehicle s service lifetime. The result of unanticipated D&DT response is often manifested in the form of catastrophic and potentially fatal accidents. As such, durability and damage tolerance requirements must be rigorously addressed for commercial transport aircraft and NASA spacecraft systems. This paper presents an overview of the recent and planned future research in durability and damage tolerance analytical and experimental methods for both metallic and composite aerospace structures at NASA Langley Research Center (LaRC).

  15. Optimal Monetary Policy with Durable Consumption Goods and Factor Demand Linkages

    DEFF Research Database (Denmark)

    Petrella, Ivan; Santoro, Emiliano

    of production in both sectors, according to an input-output matrix calibrated on the US economy. As shown in a number of recent contributions, this roundabout technology allows us to reconcile standard two-sector New Keynesian models with the empirical evidence showing co-movement between durable and non......-durable spending in response to a monetary policy shock. A main result of our monetary policy analysis is that strategic complementarities generated by factor demand linkages amplify social welfare loss. As the degree of interconnection between sectors increases, the cost of misperceiving the correct production......This paper deals with the implications of factor demand linkages for monetary policy design. We develop a dynamic general equilibrium model with two sectors that produce durable and non-durable goods, respectively. Part of the output produced in each sector is used as an intermediate input...

  16. International Conference on Durability of Critical Infrastructure

    CERN Document Server

    Cherepetskaya, Elena; Pospichal, Vaclav

    2017-01-01

    This book presents the proceedings of the International Conference on Durability of Critical Infrastructure. Monitoring and Testing held in Satov, Czech Republic from 6 to 9 December 2016. It discusses the developments in the theoretical and practical aspects in the fields of Safety, Sustainability and Durability of the Critical Infrastructure. The contributions are dealing with monitoring and testing of structural and composite materials with a new methods for their using for protection and prevention of the selected objects.

  17. Mechanistic Enhancement of SOFC Cathode Durability

    Energy Technology Data Exchange (ETDEWEB)

    Wachsman, Eric [Univ. of Maryland, College Park, MD (United States)

    2016-02-01

    Durability of solid oxide fuel cells (SOFC) under “real world” conditions is an issue for commercial deployment. In particular cathode exposure to moisture, CO2, Cr vapor (from interconnects and BOP), and particulates results in long-term performance degradation issues. Here, we have conducted a multi-faceted fundamental investigation of the effect of these contaminants on cathode performance degradation mechanisms in order to establish cathode composition/structures and operational conditions to enhance cathode durability.

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

    International Nuclear Information System (INIS)

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

    1993-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-11-01

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

  20. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    International Nuclear Information System (INIS)

    Lawton, P.A.

    1995-01-01

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

  1. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, P.A.

    1995-12-31

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  3. Alpha particles induce expression of immunogenic markers on tumour cells

    International Nuclear Information System (INIS)

    Gorin, J.B.; Gouard, S.; Cherel, M.; Davodeau, F.; Gaschet, J.; Morgenstern, A.; Bruchertseifer, F.

    2013-01-01

    The full text of the publication follows. Radioimmunotherapy (RIT) is an approach aiming at targeting the radioelements to tumours, usually through the use of antibodies specific for tumour antigens. The radiations emitted by the radioelements then induce direct killing of the targeted cells as well as indirect killing through bystander effect. Interestingly, it has been shown that ionizing radiations, in some settings of external radiotherapy, can foster an immune response directed against tumour cells. Our research team is dedicated to the development of alpha RIT, i.e RIT using alpha particle emitters, we therefore decided to study the effects of such particles on tumour cells in regards to their immunogenicity. First, we studied the effects of bismuth 213, an alpha emitter, on cellular death and autophagy in six different tumour cell lines. Then, we measured the expression of 'danger' signals and MHC molecules at the cell surface to determine whether irradiation with 213 Bi could cause the tumour cells to be recognized by the immune system. Finally a co-culture of dendritic cells with irradiated tumour cells was performed to test whether it would induce dendritic cells to mature. No apoptosis was detected within 48 hours after irradiation in any cell line, however half of them exhibited signs of autophagy. No increase in membrane expression of 'danger' signals was observed after treatment with 213 Bi, but we showed an increase in expression of MHC class I and II for some cell lines. Moreover, the co-culture experiment indicated that the immunogenicity of a human adenocarcinoma cell line (LS 174T) was enhanced in vitro after irradiation with alpha rays. These preliminary data suggest that alpha particles could be of interest in raising an immune response associated to RIT. (authors)

  4. Spatio-temporal cell dynamics in tumour spheroid irradiation

    International Nuclear Information System (INIS)

    Kempf, H.; Bleicher, M.; Meyer-Hermann, M.; Kempf, H.; Bleicher, M.; Kempf, H.; Meyer-Hermann, M.

    2010-01-01

    Multicellular tumour spheroids are realistic in vitro systems in radiation research that integrate cell-cell interaction and cell cycle control by factors in the medium. The dynamic reaction inside a tumour spheroid triggered by radiation is not well understood. Of special interest is the amount of cell cycle synchronization which could be triggered by irradiation, since this would allow follow-up irradiations to exploit the increased sensitivity of certain cell cycle phases. In order to investigate these questions we need to support irradiation experiments with mathematical models. In this article a new model is introduced combining the dynamics of tumour growth and irradiation treatments. The tumour spheroid growth is modelled using an agent-based Delaunay/Voronoi hybrid model in which the cells are represented by weighted dynamic vertices. Cell properties like full cell cycle dynamics are included. In order to be able to distinguish between different cell reactions in response to irradiation quality we introduce a probabilistic model for damage dynamics. The overall cell survival from this model is in agreement with predictions from the linear-quadratic model. Our model can describe the growth of avascular tumour spheroids in agreement to experimental results. Using the probabilistic model for irradiation damage dynamics the classic 'four Rs' of radiotherapy can be studied in silico. We found a pronounced reactivation of the tumour spheroid in response to irradiation. A majority of the surviving cells is synchronized in their cell cycle progression after irradiation. The cell synchronization could be actively triggered and should be exploited in an advanced fractionation scheme. Thus it has been demonstrated that our model could be used to understand the dynamics of tumour growth after irradiation and to propose optimized fractionation schemes in cooperation with experimental investigations. (authors)

  5. Genomic aberrations in spitzoid tumours and their implications for diagnosis, prognosis and therapy

    Science.gov (United States)

    Wiesner, Thomas; Kutzner, Heinz; Cerroni, Lorenzo; Mihm, Martin J.; Busam, Klaus J.; Murali, Rajmohan

    2016-01-01

    Summary Histopathological evaluation of melanocytic tumours usually allows reliable distinction of benign melanocytic naevi from melanoma. More difficult is the histopathological classification of Spitz tumours, a heterogeneous group of tumours composed of large epithelioid or spindle-shaped melanocytes. Spitz tumours are biologically distinct from conventional melanocytic naevi and melanoma, as exemplified by their distinct patterns of genetic aberrations. Whereas conventional naevi and melanoma often harbour BRAF mutations, NRAS mutations, or inactivation of NF1, Spitz tumours show HRAS mutations, inactivation of BAP1 (often combined with BRAF mutations), or genomic rearrangements involving the kinases ALK, ROS1, NTRK1, BRAF, RET, and MET. In Spitz naevi, which lack significant histological atypia, all of these mitogenic driver aberrations trigger rapid cell proliferation, but after an initial growth phase, various tumour suppressive mechanisms stably block further growth. In some tumours, additional genomic aberrations may abrogate various tumour suppressive mechanisms, such as cell-cycle arrest, telomere shortening, or DNA damage response. The melanocytes then start to grow in a less organised fashion, may spread to regional lymph nodes, and are termed atypical Spitz tumours. Upon acquisition of even more aberrations, which often activate additional oncogenic pathways or reduce and alter cell differentiation, the neoplastic cells become entirely malignant and may colonise and take over distant organs (spitzoid melanoma). The sequential acquisition of genomic aberrations suggests that Spitz tumours represent a continuous biological spectrum, rather than a dichotomy of benign versus malignant, and that tumours with ambiguous histological features (atypical Spitz tumours) might be best classified as low-grade melanocytic tumours. The number of genetic aberrations usually correlates with the degree of histological atypia and explains why existing ancillary genetic

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

    Science.gov (United States)

    Fais, S

    2010-05-01

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

  7. Imaging in unilateral Wilms tumour

    International Nuclear Information System (INIS)

    Brisse, Herve J.; Smets, Anne M.; Kaste, Sue C.; Owens, Catherine M.

    2008-01-01

    Wilms tumour is one of the most common malignancies in children, with an excellent prognosis after therapy. There is a very diverse approach to treatment according to geographical location. This variation in therapeutic attitude toward Wilms tumour, particularly between the United States and Europe, has consequences for the choice of imaging modality at diagnosis. In Europe, the International Society of Paediatric Oncology (SIOP) treatment protocol is based on chemotherapy followed by surgery. Imaging (US, CT and MRI), clinical history and examination will help predict whether the findings are consistent with Wilms tumour. Furthermore, in the UK preoperative image-guided biopsy is advised to help identify the small group of patients who, despite typical imaging features of Wilms tumour, have other types of neoplasia that require alternative management. In the United States, the National Wilms Tumor Study (NWTS) advises surgery prior to chemo- and radiotherapy. Hence imaging must provide detailed anatomical information for surgical planning. This article discusses the role of imaging at diagnosis and the relative strengths and weaknesses of the available radiological techniques. We also focus on imaging the lung for metastatic disease and the consequences (to the patient's ultimate outcome) of CT-diagnosed small pulmonary nodules and discuss the radiological diagnosis and consequences of tumour rupture present at diagnosis. (orig.)

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  9. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  10. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  11. Multispectral imaging for highly accurate analysis of tumour-infiltrating lymphocytes in primary melanoma

    NARCIS (Netherlands)

    Vasaturo, A.; Di Blasio, S.; Verweij, D.; Blokx, W.A.M.; Krieken, J.H.J.M. van; Vries, I.J.M. de; Figdor, C.G.

    2017-01-01

    AIMS: The quality and quantity of the infiltration of immune cells into tumour tissues have substantial impacts on patients' clinical outcomes, and are associated with response to immunotherapy. Therefore, the precise analysis of tumour-infiltrating lymphocytes (TILs) is becoming an important

  12. Tocopherol in irradiation of temporary hypoxic tumours

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  13. Pitfalls in colour photography of choroidal tumours

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  14. Pitfalls in colour photography of choroidal tumours.

    Science.gov (United States)

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  15. High clinical and morphologic response using {sup 90}Y-DOTA-octreotate sequenced with {sup 177}Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Grace; Callahan, Jason; Pattison, David A.; Akhurst, Tim; Eu, Peter [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); Hofman, Michael S. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Parkville (Australia); Michael, Michael [Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia)

    2017-03-15

    Bulky disease is an adverse prognostic factor for {sup 177}Lu-DOTA-octreotate ({sup 177}Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). {sup 90}Y-DOTA-octreotate ({sup 90}Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than {sup 177}Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of {sup 90}Y-DOTATATE followed by 2-3 cycles of {sup 177}Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq {sup 90}Y-DOTATATE, and 21 GBq {sup 177}Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with {sup 90}Y -DOTATATE followed by {sup 177}Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either

  16. Skull base tumours part I: Imaging technique, anatomy and anterior skull base tumours

    International Nuclear Information System (INIS)

    Borges, Alexandra

    2008-01-01

    Advances in cross-sectional imaging, surgical technique and adjuvant treatment have largely contributed to ameliorate the prognosis, lessen the morbidity and mortality of patients with skull base tumours and to the growing medical investment in the management of these patients. Because clinical assessment of the skull base is limited, cross-sectional imaging became indispensable in the diagnosis, treatment planning and follow-up of patients with suspected skull base pathology and the radiologist is increasingly responsible for the fate of these patients. This review will focus on the advances in imaging technique; contribution to patient's management and on the imaging features of the most common tumours affecting the anterior skull base. Emphasis is given to a systematic approach to skull base pathology based upon an anatomic division taking into account the major tissue constituents in each skull base compartment. The most relevant information that should be conveyed to surgeons and radiation oncologists involved in patient's management will be discussed

  17. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  18. Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour

    International Nuclear Information System (INIS)

    Cavanagh, L.L.; Sluyter, R.; Henderson, K.G.; Barnetson, R.St.C.; Halliday, G.M.

    1996-01-01

    Lanerghans' cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia + EC and was tumour specific. Thus Ia + epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author)

  19. Pentavalent 99Tcm - DMSA SPECT in primary brain tumours of glial cell origin

    International Nuclear Information System (INIS)

    Chung, D.K.; Evans, S.G.; Larcos, G.; Gruenewald, S.; Kumar, V.; Barton, M.

    1999-01-01

    Full text: 99 Tc m (V)-DMSA [DMSA(V)] has shown promise in brain tumour imaging. This study aimed to assess the role of DMSA(V) brain SPET in glioma for: (1) predicting the histopathological grade of malignancy, (2) monitoring response to therapy and (3) discriminating recurrent tumour from post-radiotherapy necrosis. Twenty-three patients (pts) (14 men, 9 women) of mean age 57 years (range 20-79) were referred with a lesion on CT/MRI (14 new presentations, 5 known and 4 suspected tumour recurrence). Up to 555 MBq of 99 Tc m (V)DMSA were administered and SPET was acquired at 3 h. Tumour uptake ratio (UR) was calculated by the ratio of activity in the tumour to a region in the contralateral brain. All 19 pts with known tumour showed DMSA(V) uptake. The 14 pts with new tumours (10 grade IV, I grade III, 2 grade II and 1 necrotic tumour) had a pre-therapy mean UR of 7.7 (range 2.8-13.6). The 3 lower-grade tumours were scattered widely within this range. Four pts completed radiotherapy and returned for a post-therapy scan, where the UR was less than the pre-therapy UR in 2, unchanged in 1 and greater in 1. The 5 known recurrent tumours had a mean UR of 13.5 (range 7.3-24.9). In the 4 pts with suspected recurrence, the DMSA(V) scan result agreed with clinical course or PET in 3 but was falsely positive in 1. In summary, 99 Tc m (V)-DMSA: (1) showed uptake in all known glial cell tumours in this series, however the UR did not correlate with the histopathological grade; (2) may be useful for discriminating tumour recurrence from post-radiotherapy necrosis; and (3) may have a role in predicting post-therapy prognosis

  20. Heterogeneity as Biomarker in Tumour Imaging (abstract only)

    NARCIS (Netherlands)

    Alić, L.; Veenland, J.F.

    2013-01-01

    PURPOSE: Tumour heterogeneity could be a valuable biomarker for differentiation, grading, response monitoring and outcome prediction. Many quantification techniques have been described, however in clinical practice these methods are scarcely used. The aim of this study is to evaluate the performance

  1. Cognitive deficits in adult patients with brain tumours.

    NARCIS (Netherlands)

    Taphoorn, M.J.B.; Klein, M.

    2004-01-01

    Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient's clinical situation and adverse treatment effects. Radiotherapy has been regarded as the

  2. Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils

    DEFF Research Database (Denmark)

    Tovar, Cesar; Pye, Ruth J; Kreiss, Alexandre

    2017-01-01

    Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil (Sarcophilus harrisii) population. The cancer cell is the 'infectious' agent transmitted as an allograft by biting. Animals usually die within a few months with no evidence of antibody or immune cell...... responses against the DFTD allograft. This lack of anti-tumour immunity is attributed to an absence of cell surface major histocompatibility complex (MHC)-I molecule expression. While the endangerment of the devil population precludes experimentation on large experimental groups, those examined in our study...... indicated that immunisation and immunotherapy with DFTD cells expressing surface MHC-I corresponded with effective anti-tumour responses. Tumour engraftment did not occur in one of the five immunised Tasmanian devils, and regression followed therapy of experimentally induced DFTD tumours in three Tasmanian...

  3. Tumour markers in gynaecological practice

    International Nuclear Information System (INIS)

    Adewole, I.F.

    1999-02-01

    Gynaecological cancers are fairly common in developing countries and represent about 26 % f all cancers. Application of cervical cytology screening nationally has made cervical cancer one of the most preventable malignant diseases thus eliminating the challenges of advanced cancer management. Tumour markers has played a most crucial role in this respect

  4. Non-invasive vascular imaging: assessing tumour vascularity

    International Nuclear Information System (INIS)

    Delorme, S.; Knopp, M.V.

    1998-01-01

    Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

  5. Mohs micrographic surgery of rare cutaneous tumours

    NARCIS (Netherlands)

    Flohil, S.C.; Lee, C.B. van; Beisenherz, J.; Mureau, M.A.M.; Overbeek, L.I.H.; Nijsten, T.; Bos, R.R.

    2017-01-01

    BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated

  6. A generalized definition for waste form durability

    International Nuclear Information System (INIS)

    Fanning, T. H.; Bauer, T. H.; Morris, E. E.; Wigeland, R. A.

    2002-01-01

    When evaluating waste form performance, the term ''durability'' often appears in casual discourse, but in the technical literature, the focus is often on waste form ''degradation'' in terms of mass lost per unit area per unit time. Waste form degradation plays a key role in developing models of the long-term performance in a repository environment, but other factors also influence waste form performance. These include waste form geometry; density, porosity, and cracking; the presence of cladding; in-package chemistry feedback; etc. The paper proposes a formal definition of waste form ''durability'' which accounts for these effects. Examples from simple systems as well as from complex models used in the Total System Performance Assessment of Yucca Mountain are provided. The application of ''durability'' in the selection of bounding models is also discussed

  7. Durability analysis of gneiss using wear resistance

    Directory of Open Access Journals (Sweden)

    José Luiz Ernandes Dias Filho

    2014-01-01

    Full Text Available This paper presents a study conducted in gneiss in Santo Antonio de Pádua, RJ, BR, including durability analysis of the rock using slake durability test. Rocks in the region of Pádua are mostly used for ornamental purposes. A lab equipment was developed to evaluate the influence of rotation in the test, allowing for the speed variation of 7 RPM to 238 RPM. This study could be implemented in a wide variety of rock materials, targeting them according to their lifetime in the project. With variation of the wear levels, increasing weight loss was observed until the inertia moment in which the sample holds to the machine wall. The results indicate an increase in linear mass loss. These procedures allow a more precise analysis of durability than can be applied in different different regions of the world.

  8. Pyramiding for Resistance Durability: Theory and Practice.

    Science.gov (United States)

    Mundt, Chris

    2018-04-12

    Durable disease resistance is a key component of global food security, and combining resistance genes into "pyramids" is an important way to increase durability of resistance. The mechanisms by which pyramids impact durability are not well known. The traditional view of resistance pyramids considers the use of major resistance gene (R-gene) combinations deployed against pathogens that are primarily asexual. Interestingly, published examples of the successful use of pyramids in the traditional sense are rare. In contrast, most published descriptions of durable pyramids in practice are for cereal rusts, and tend to indicate an association between durability and cultivars combining major R-genes with incompletely expressed, adult plant resistance genes. Pyramids have been investigated experimentally for a diversity of pathogens, and many reduce disease levels below that of the single best gene. Resistance gene combinations have been identified through phenotypic reactions, molecular markers, and challenge against effector genes. As resistance genes do not express equally in all genetic backgrounds, however, a combination of genetic information and phenotypic analyses provide the ideal scenario for testing of putative pyramids. Not all resistance genes contribute equally to pyramids, and approaches have been suggested to identify the best genes and combinations of genes for inclusion. Combining multiple resistance genes into a single plant genotype quickly is a challenge that is being addressed through alternative breeding approaches, as well as through genomics tools such as resistance gene cassettes and gene editing. Experimental and modeling tests of pyramid durability are in their infancy, but have promise to help direct future studies of pyramids. Several areas for further work on resistance gene pyramids are suggested.

  9. Bilateral disease and new trends in Wilms tumour

    Energy Technology Data Exchange (ETDEWEB)

    Owens, Catherine M.; Olsen, Oeystein E. [Great Ormond Street Hospital for Children NHS Trust, Department of Radiology, London (United Kingdom); Brisse, Herve J. [Institut Curie, Service de Radiodiagnostic, Paris (France); Begent, Joanna [University College Hospital, Paediatric Oncology, London (United Kingdom); Smets, Anne M. [Academic Medical Center Amsterdam, Department of Radiology, Amsterdam (Netherlands)

    2008-01-15

    Wilms tumour is a great therapeutic success story within paediatric oncology; its prognosis is excellent. Although mainly sporadic, occurring in otherwise well children, it occurs in a small number of genetically predisposed children. Thus regular surveillance imaging is performed in predisposed children in parts of the USA and Europe. The risks and benefits of surveillance are unclear, as the existing ad-hoc surveillance protocols are lacking in consistency of practice and equity of provision. We present guidelines for Wilms tumour surveillance based on a review of current practice and available evidence, outlined by a multidisciplinary working group in the UK. Wilms tumours are bilateral in 4-13% of affected children. Bilateral synchronous nephroblastomas are observed in 5% of affected children and are usually associated with the presence of nephrogenic rests, congenital malformations and predisposing syndromes. The major challenge in bilateral disease is to achieve a cure and at the same time to preserve sufficient functional renal tissue for normal growth and development. The association among Wilms tumour, nephrogenic rests and nephroblastomatosis makes detection and characterization of renal lesions with imaging extremely important. We discuss the relative strengths and weaknesses of the different modalities used for diagnosis and follow-up in bilateral renal disease. We also discuss newly emerging diagnostic imaging tests such as {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET). This technique, when fused with CT (PET-CT), allows accelerated metabolic activity to be accurately anatomically localised and so is potentially useful for staging, assessment of treatment response, and for surgical and radiotherapy planning. In addition, quantitative MRI techniques have been proved to be valuable in intracranial tumours, but no such role has been validated in abdominal disease. Diffusion-weighted imaging with calculation of ADC maps is feasible in

  10. Bilateral disease and new trends in Wilms tumour

    International Nuclear Information System (INIS)

    Owens, Catherine M.; Olsen, Oeystein E.; Brisse, Herve J.; Begent, Joanna; Smets, Anne M.

    2008-01-01

    Wilms tumour is a great therapeutic success story within paediatric oncology; its prognosis is excellent. Although mainly sporadic, occurring in otherwise well children, it occurs in a small number of genetically predisposed children. Thus regular surveillance imaging is performed in predisposed children in parts of the USA and Europe. The risks and benefits of surveillance are unclear, as the existing ad-hoc surveillance protocols are lacking in consistency of practice and equity of provision. We present guidelines for Wilms tumour surveillance based on a review of current practice and available evidence, outlined by a multidisciplinary working group in the UK. Wilms tumours are bilateral in 4-13% of affected children. Bilateral synchronous nephroblastomas are observed in 5% of affected children and are usually associated with the presence of nephrogenic rests, congenital malformations and predisposing syndromes. The major challenge in bilateral disease is to achieve a cure and at the same time to preserve sufficient functional renal tissue for normal growth and development. The association among Wilms tumour, nephrogenic rests and nephroblastomatosis makes detection and characterization of renal lesions with imaging extremely important. We discuss the relative strengths and weaknesses of the different modalities used for diagnosis and follow-up in bilateral renal disease. We also discuss newly emerging diagnostic imaging tests such as 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). This technique, when fused with CT (PET-CT), allows accelerated metabolic activity to be accurately anatomically localised and so is potentially useful for staging, assessment of treatment response, and for surgical and radiotherapy planning. In addition, quantitative MRI techniques have been proved to be valuable in intracranial tumours, but no such role has been validated in abdominal disease. Diffusion-weighted imaging with calculation of ADC maps is feasible in

  11. Probabilistic Durability Analysis in Advanced Engineering Design

    Directory of Open Access Journals (Sweden)

    A. Kudzys

    2000-01-01

    Full Text Available Expedience of probabilistic durability concepts and approaches in advanced engineering design of building materials, structural members and systems is considered. Target margin values of structural safety and serviceability indices are analyzed and their draft values are presented. Analytical methods of the cumulative coefficient of correlation and the limit transient action effect for calculation of reliability indices are given. Analysis can be used for probabilistic durability assessment of carrying and enclosure metal, reinforced concrete, wood, plastic, masonry both homogeneous and sandwich or composite structures and some kinds of equipments. Analysis models can be applied in other engineering fields.

  12. Durability of cracked fibre reinforced concrete structures

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan De Place; Nielsen, Laila

    1997-01-01

    (capillary water uptake) is used, involving an in-situ method and a laboratory method. Three different concrete qualities as well as steel fibres (ZP) and polypropylene fibres (PP) are used. Results of the durability tests on cracked FRC-beams are compared to results for uncracked FRC-beams and beams without......Durability studies are carried out by subjecting FRC-beams to combined mechanical and environmental load. Mechanical load is obtained by exposing beams to il-point bending until a predefined crack width is reached, using a newly developed test setup. As environmental load, exposure to water...

  13. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

    2011-10-15

    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  14. Tumours of the fetal body: a review

    Energy Technology Data Exchange (ETDEWEB)

    Avni, Fred E.; Massez, Anne; Cassart, Marie [University Clinics of Brussels - Erasme Hospital, Department of Medical Imaging, Brussels (Belgium)

    2009-11-15

    Tumours of the fetal body are rare, but lesions have been reported in all spaces, especially in the mediastinum, the pericardial space, the adrenals, the kidney, and the liver. Lymphangioma and teratoma are the commonest histological types encountered, followed by cardiac rhabdomyoma. Adrenal neuroblastoma is the commonest malignant tumour. Imaging plays an essential role in the detection and work-up of these tumours. In addition to assisting clinicians it also helps in counselling parents. Most tumours are detected by antenatal US, but fetal MRI is increasingly used as it brings significant additional information in terms of tumour extent, composition and complications. (orig.)

  15. A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.

    Science.gov (United States)

    Frascoli, Federico; Flood, Emelie; Kim, Peter S

    2017-06-01

    We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  16. MRI of primary meningeal tumours in children

    International Nuclear Information System (INIS)

    Yoon, H.K.; Na, D.G.; Byun, H.S.; Han, B.K.; Kim, S.S.; Kim, I.O.; Shin, H.J.

    1999-01-01

    Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours. (orig.)

  17. Primary bone tumours of the hand

    International Nuclear Information System (INIS)

    Kozlowski, K.; Azouz, E.M.; Campbell, J.; Marton, D.; Morris, L.; Padovani, J.; Sprague, P.; Beluffi, G.; Berzero, G.F.; Cherubino, P.; Adelaide Children's Hospital; Hospital for Children, Perth; Montreal Children's Hospital, Quebec; Saint Justine Hospital, Montreal, Quebec; Children's Hospital, Denver, CO; Hopital des Enfants, 13 - Marseille; Pavia Univ.; Pavia Univ.

    1988-01-01

    Twenty-one primary bone tumours of the hand in children from 8 paediatric hospitals are reported. Osteochondromas and enchondromas were not included. Our material consisted of 16 patients with common tumours (3 Ewing's sarcoma, 5 aneurysmal bone cyst, 6 osteoid osteoma and 2 epithelioma) and 5 patients with uncommon tumours (osteoma, simple bone cyst, haemangiopericytoma, capillary angiomatous tumour and benign ossifying fibroma or osteoblastoma). The X-ray diagnosis of the common tumours should have high concordance with histology, whereas that of uncommon tumours in much more difficult and uncertain. The characteristic features of Ewing's sarcoma are stressed as all our children with this tumour had a delayed diagnosis and a fatal outcome. Differential diagnosis with other short tubular bone lesions of the hand - specifically osteomyelitis - is discussed and the posibilities of microscopic diagnosis are stressed. (orig.)

  18. Radiodiagnosis of tumours of gastrointestinal tract

    International Nuclear Information System (INIS)

    Sokolov, Yu.N.; Antonovich, V.B.

    1981-01-01

    Systematic description of X-ray picture of tumours of gastrointestinal tract organs is given. The possibilities of contemporary methods of X-ray examination in their revealing are shown. Clinical and X-ray trend of tumour diagnosis is underlined. The basic and accessory symptoms are analyzed from which X-ray semiotics of tumours is turned out. The expressiveness of X-ray symptoms is shown in relation to morphological forms and localization of the tumours. Much attention is given to radiodiagnosis of early tumours of stomach. Differential diagnosis of tumours with non-tumoural diseases is given. X-ray semiotics of lesions of gastrointestinal tract organs in malignant diseases of blood system is presented [ru

  19. Teratoid Wilms tumour with chemotherapy resistance

    Directory of Open Access Journals (Sweden)

    Renuka Gahine

    2015-01-01

    Full Text Available We present a case of Teratoid Wilms tumour (a rare histologic variant in a 4 year old male who presented with an abdominal lump. Wilms Tumour with paracaval lymphadenopathy and tumour thrombi in right renal vein and inferior vena cava was made radiologically. FNAC report was suggestive of Wilms tumour and patient was subjected to 6 cycles of chemotherapy with not much reduction in size. Post nephrectomy histological diagnosis of Teratoid Wilms tumour was established. Resistance to chemotherapy and radiotherapy is thought to be due to presence of well differentiated histologic appearance. Teratoid Wilms tumour is usually not an aggressive neoplasm and prognosis is comparatively neoplasm and prognosis is comparatively good if the tumour is excised completely thus surgery being the best treatment.

  20. CNS embryonal tumours: WHO 2016 and beyond.

    Science.gov (United States)

    Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

    2018-02-01

    Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

  1. Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Christensen, Rikke Kølby

    2010-01-01

    BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may ther...... immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.......BACKGROUND: Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may...... therefore play an essential role in the progression of a malignant tumour.The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment...

  2. The prospective buyer of consumer durables

    NARCIS (Netherlands)

    Jonge, Leendert de; Oppedijk van Veen, Walle Melis

    1982-01-01

    In this book, an empirical investigation is reported wich aims at the specification of models of individual households’ purchase behaviour for particular consumer durable goods, such as private passenger cars and television sets. In particular, the focus is on models wich can be used for predicting

  3. Durable Glass For Thousands Of Years

    International Nuclear Information System (INIS)

    Jantzen, C.

    2009-01-01

    The durability of natural glasses on geological time scales and ancient glasses for thousands of years is well documented. The necessity to predict the durability of high level nuclear waste (HLW) glasses on extended time scales has led to various thermodynamic and kinetic approaches. Advances in the measurement of medium range order (MRO) in glasses has led to the understanding that the molecular structure of a glass, and thus the glass composition, controls the glass durability by establishing the distribution of ion exchange sites, hydrolysis sites, and the access of water to those sites. During the early stages of glass dissolution, a 'gel' layer resembling a membrane forms through which ions exchange between the glass and the leachant. The hydrated gel layer exhibits acid/base properties which are manifested as the pH dependence of the thickness and nature of the gel layer. The gel layer ages into clay or zeolite minerals by Ostwald ripening. Zeolite mineral assemblages (higher pH and Al 3+ rich glasses) may cause the dissolution rate to increase which is undesirable for long-term performance of glass in the environment. Thermodynamic and structural approaches to the prediction of glass durability are compared versus Ostwald ripening.

  4. Advantage from Funding Durable Centers Leasing

    Directory of Open Access Journals (Sweden)

    Alina Zając

    2009-09-01

    Full Text Available In present market conditions huge number of businessmen has problems from gain over from banks capital on purchase of durable centers not only, but also on develop - ment and operating activity Individual can use with different forms funding investment, it which is between different leasing.

  5. Enhancing composite durability : using thermal treatments

    Science.gov (United States)

    Jerrold E. Winandy; W. Ramsay Smith

    2007-01-01

    The use of thermal treatments to enhance the moisture resistance and aboveground durability of solid wood materials has been studied for years. Much work was done at the Forest Products Laboratory in the last 15 years on the fundamental process of both short-and long-term exposure to heat on wood materials and its interaction with various treatment chemicals. This work...

  6. 40 CFR 610.33 - Durability tests.

    Science.gov (United States)

    2010-07-01

    ....33 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY... problems, deterioration in spark plug life, increase in carburetor or combustion chamber deposits, or..., then a durability run may be made as described in subpart E, in which fuel economy and exhaust...

  7. DURABLE GLASS FOR THOUSANDS OF YEARS

    Energy Technology Data Exchange (ETDEWEB)

    Jantzen, C.

    2009-12-04

    The durability of natural glasses on geological time scales and ancient glasses for thousands of years is well documented. The necessity to predict the durability of high level nuclear waste (HLW) glasses on extended time scales has led to various thermodynamic and kinetic approaches. Advances in the measurement of medium range order (MRO) in glasses has led to the understanding that the molecular structure of a glass, and thus the glass composition, controls the glass durability by establishing the distribution of ion exchange sites, hydrolysis sites, and the access of water to those sites. During the early stages of glass dissolution, a 'gel' layer resembling a membrane forms through which ions exchange between the glass and the leachant. The hydrated gel layer exhibits acid/base properties which are manifested as the pH dependence of the thickness and nature of the gel layer. The gel layer ages into clay or zeolite minerals by Ostwald ripening. Zeolite mineral assemblages (higher pH and Al{sup 3+} rich glasses) may cause the dissolution rate to increase which is undesirable for long-term performance of glass in the environment. Thermodynamic and structural approaches to the prediction of glass durability are compared versus Ostwald ripening.

  8. Durability of wood-plastic composite lumber

    Science.gov (United States)

    Rebecca E. Ibach

    2010-01-01

    Wood-plastic composite (WPC) lumber has been marketed as a low-maintenance, high-durability product. Retail sales in the United States were slightly less than $1 billion in 2008. Applications include docking, railing, windows, doors, fencing, siding, moldings, landscape timbers, car interior parts, and furniture. The majority of these products are used outdoors and...

  9. [Awake craniotomy for brain tumours].

    Science.gov (United States)

    Milos, Peter; Metcalf, Kerstin; Vigren, Patrick; Lindehammar, Hans; Nilsson, Malin; Boström, Sverre

    2016-10-11

    Awake craniotomy for brain tumours  Awake neurosurgery is a useful method in lesions near eloquent brain areas, particularly low-grade gliomas.The aim is to maximise tumour resection and preserve neurological function. We performed 40 primary awake surgeries and 8 residual surgeries. Patients were operated awake throughout the procedure or with a laryngeal mask and general anaesthesia during the opening stage and then awake during intracerebral surgery. Language and motor function were mapped with direct cortical stimulation, motor evoked potential and standardised neurological testing. Radiologically, complete resection was achieved in 18 out of 40 patients in the primary surgeries. Full neurological recovery at three months was observed in 29 patients. Of the 11 patients with persisting neurological deficits at three months, symptoms were present preoperatively in 9 patients. We conclude that awake surgery, combined with intraoperative neurophysiological methods, is a safe method to improve treatment for low-grade gliomas.

  10. DURABILITY OF FLEXIBLE PAVEMENTS: A CASE STUDY OF ...

    African Journals Online (AJOL)

    user

    years, ranking, predominant factors affecting pavement durability and the estimate of durability. In this regard .... subgrade soil into the base course and provide the drainage of ..... [3] Oguara T. M. “A management model for road infrastructure ...

  11. Reconstructive options in pelvic tumours

    Directory of Open Access Journals (Sweden)

    Mayilvahanan N

    2005-01-01

    Full Text Available Background: Pelvic tumours present a complex problem. It is difficult to choose between limb salvage and hemipelvectomy. Method: Forty three patients of tumours of pelvis underwent limb salvage resection with reconstruction in 32 patients. The majority were chondrosarcomas (20 cases followed by Ewing sarcoma. Stage II B was the most common stage in malignant lesions and all the seven benign lesions were aggressive (B3. Surgical margins achieved were wide in 31 and marginal in 12 cases. Ilium was involved in 51% of cases and periacetabular involvement was seen in 12 patients. The resections done were mostly of types I &II of Enneking′s classification of pelvic resection. Arthrodesis was attempted in 24 patients. Customized Saddle prosthesis was used in seven patients and no reconstruction in 12 patients. Adjuvant chemotherapy was given to all high-grade malignant tumours, combined with radiotherapy in 7 patients. Results: With a mean follow up of 48.5 months and one patient lost to follow up, the recurrence rate among the evaluated cases was 16.6%. Oncologically, 30 patients were continuously disease free with 7 local recurrences and 4 deaths due to disseminated disease and 2 patients died of other causes. During the initial years, satisfactory functional results were achieved with prosthetic replacement. Long-term functional result of 36 patients who were alive at the time of latest follow up was satisfactory in 75% who underwent arthrodesis and in those where no reconstruction was used. We also describe a method of new classification of pelvic resections that clarifies certain shortcomings of the previous systems of classification. Conclusion: Selection of a procedure depends largely on the patient factors, the tumour grade, the resultant defect and the tissue factors. Resection with proper margins gives better functional and oncological results

  12. Targeting Chromosomal Instability and Tumour Heterogeneity in HER2-Positive Breast Cancer

    DEFF Research Database (Denmark)

    Burrell, Rebecca A.; Birkbak, Nicolai Juul; Johnston, Stephen R.

    2010-01-01

    Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population. In this article we consider evidence suggesting that CIN may be targeted and may influence...... response to distinct chemotherapy regimens, using HER2-positive breast cancer as an example. Pre-clinical models have indicated a role for HER2 signalling in initiating CIN and defective cell-cycle control, and evidence suggests that HER2-targeting may attenuate this process. Anthracyclines and platinum...... agents may target tumours with distinct patterns of karyotypic complexity, whereas taxanes may have preferential activity in tumours with relative chromosomal stability. A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel...

  13. Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

    Science.gov (United States)

    Goh, Felicia; Duhig, Edwina E; Clarke, Belinda E; McCaul, Elizabeth; Passmore, Linda; Courtney, Deborah; Windsor, Morgan; Naidoo, Rishendren; Franz, Louise; Parsonson, Kylie; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

    2017-10-01

    Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. Allograft in bone tumour surgery

    International Nuclear Information System (INIS)

    Sengupta, S.

    1999-01-01

    In the last twenty years, there has been a vast improvement in the prognosis of primary malignant tumours of bone. This is due to many factors including early detection, staging and classification of tumours as a result of better staining and imaging techniques, better surgical technology, e.g. endoprosthesis and most importantly adjuvant treatment with cytotoxic drugs. As a result of long term survival, amputation of limb has more or less been replaced by limb salvage surgery. This procedure consists of two parts. Primary objective is of course complete removal of the tumour by adequate soft tissue cover and secondarily by reconstruction of the locomotor system, If possible with retention of the function of the limb. These procedures include endo-prosthetic replacement or arthroplasty and arthrodesis using autologus grafts, allograft or combination. With the development of bone banks and assured safety of preserved bones, reconstructive limb salvage surgery using massive allograft is gradually replacing prosthetic implants. The advantages include replacement of articular surfaces, incorporation of the graft to the host bone, attachment of bone tissue and increased probably permanent survival. Allograft can be used for intercalary replacement, osteo-articular arthroplasty arthrodesis or filling large cavities. Inherent complication of massive allograft are disease transmission, infection, delayed and non-union, pathological fractures, mechanical failure and joint destruction. Several limb salvage procedures using allografts have been carried out in our institution with one failure due to infection. Paucity of available allograft has restricted more such procedures to be carried out

  15. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  16. Facultative or obligate anaerobic bacteria have the potential for multimodality therapy of solid tumours.

    Science.gov (United States)

    Wei, Ming Q; Ellem, Kay A O; Dunn, Paul; West, Malcolm J; Bai, Chun Xue; Vogelstein, Bert

    2007-02-01

    Recent understanding of the unique pathology of solid tumours has shed light on the difficult and disappointing nature of their clinical treatment. All solid tumours undergo angiogenesis that results in biological changes and adaptive metabolisms, i.e. formation of defective vessels, appearance of hypoxic areas, and emergence of an heterogeneous tumour cell population. This micro-milieu provides a haven for anaerobic bacteria. The strictly anaerobic clostridia have several advantages over other facultative anaerobes such as salmonella or lactic acid-producing, Gram-positive, obligate, anaerobic bifidobacteria. Both pathogenic and non-pathogenic clostridia have been demonstrated to specifically colonise and destroy solid tumours. Early trials of non-pathogenic strains in humans had shown plausible safety. Genetic modifications and adaptation of pathogenic and non-pathogenic strains have further created improved features. However, these manipulations rarely generate strains that resulted in complete tumour control alone. Combined modalities of therapies with chemo and radiation therapies, on the other hand, often perform better, including 'cure' of solid tumours in a high percentage of animals. Considering that clostridia have unlimited capacities for genetic improvement, we predict that designer clostridia forecast a promising future for the development of potent strains for tumour destruction, incorporating mechanisms such as immunotherapy to overcome immune suppression and to elicit strong anti-tumour responses.

  17. Putting tumours in context

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J.; Radisky, Derek

    2001-10-01

    progresses, the normal organization of the organ is replaced by a functional disorder. If there are pre-existing epithelial cells within this changing context that possess tumorigenic potential, they can start to proliferate. Alternatively, the abnormal interactions might lead to genomic instability within the epithelial cells and the acquisition of tumorigenic potential. The proliferating cancer cells can then interact with their microenvironment and enhance the abnormal interactions. At this point, the tumor has become its own organ, with a distinct context that now defines all its cellular responses. Here, we will examine how the mechanisms that contribute to the normal context also act to suppress developing tumors, how disruption of this context initiates and supports the process of tumorigenicity, and how some cells with a tumorigenic genotype can become phenotypically normal if the context is appropriately manipulated.

  18. AAV2-mediated in vivo immune gene therapy of solid tumours

    LENUS (Irish Health Repository)

    Collins, Sara A

    2010-12-20

    Abstract Background Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of AAV2 mediated immunotherapy of growing tumours was examined, in isolation and combined with anti-angiogenic therapy. Methods Immune-competent Balb\\/C or C57 mice bearing subcutaneous JBS fibrosarcoma or Lewis Lung Carcinoma (LLC) tumour xenografts respectively were treated by intra-tumoural administration of AAV2 vector encoding the immune up-regulating cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) and the co-stimulatory molecule B7-1 to subcutaneous tumours, either alone or in combination with intra-muscular (IM) delivery of AAV2 vector encoding Nk4 14 days prior to tumour induction. Tumour growth and survival was monitored for all animals. Cured animals were re-challenged with tumourigenic doses of the original tumour type. In vivo cytotoxicity assays were used to investigate establishment of cell-mediated responses in treated animals. Results AAV2-mediated GM-CSF, B7-1 treatment resulted in a significant reduction in tumour growth and an increase in survival in both tumour models. Cured animals were resistant to re-challenge, and induction of T cell mediated anti-tumour responses were demonstrated. Adoptive transfer of splenocytes to naïve animals prevented tumour establishment. Systemic production of Nk4 induced by intra-muscular (IM) delivery of Nk4 significantly reduced subcutaneous tumour growth. However, combination of Nk4 treatment with GM-CSF, B7-1 therapy reduced the efficacy of the immune therapy. Conclusions Overall, this study demonstrates the potential for in vivo AAV2 mediated immune gene therapy, and provides data on the inter-relationship between tumour

  19. The influence of humidity on strengths and durability of light guides fibers

    International Nuclear Information System (INIS)

    Karimov, S.N.; Kuksenko, V.S.; Sultonov, U.; Abdumanonov, A.; Shamsidinov, M.I.

    1993-01-01

    Humidity influence on durability and light water durability fibres is studied are studied in this article. Humidity energy under influence of process destruction decreases activity, durability and durability decreases is shown

  20. Variation of tumour radiosensitivity with time after anaesthetic

    Energy Technology Data Exchange (ETDEWEB)

    Nias, A.H.W.; Perry, P.M. (Saint Thomas' Hospital, London (UK). Richard Dimbleby Research Lab.)

    1989-10-01

    Transplanted C{sub 3}H mouse mammary tumours were given single doses of X irradiation in air or oxygen at 1 atmosphere (atm) with or without anaesthesia of recipient mice by ketamine and diazepam. The radiation response to single doses of 25 Gy was determined in terms of time taken to reach 3.5 times the treatment volume. Under all conditions there was more growth delay in tumours irradiated in pure oxygen than in air. In air and oxygen, the radiation response for anaestheitized animals tended to fall below the level for non-anaesthetized ones when only 10 min had elapsed after administration of anaesthesia. After 25 min, the response in air was back to the level for non-anaesthetized animals but the oxygen group then showed significant sensitization compared with the oxygen without anaesthetic group. After 40 min, the air group showed slight sensitization and the oxygen group still showed significant sensitization by the anaesthetic. (author).

  1. Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo

    International Nuclear Information System (INIS)

    Anesti, Anna-Maria; Simpson, Guy R; Price, Toby; Pandha, Hardev S; Coffin, Robert S

    2010-01-01

    Delivery of small interfering RNA (siRNA) to tumours remains a major obstacle for the development of RNA interference (RNAi)-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV) OncoVEX GM-CSF , we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV. To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA) or artificial microRNA (miRNA) against the reporter genes green fluorescent protein (eGFP) and β-galactosidase (lacZ). These vectors were tested in non-tumour cell lines in vitro and tumour cells that are moderately susceptible to HSV infection both in vitro and in mice xenografts in vivo. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting. Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cells in vitro and tumours in vivo, with the viruses expressing artificial miRNA being comprehensibly more effective. This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cells in vitro and in vivo. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen in human clinical trials

  2. Tumour regrowth after irradiation. An experimental approach

    Energy Technology Data Exchange (ETDEWEB)

    Yamaura, H; Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1979-03-01

    Structural changes in irradiated tumours and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm/sup 3/ of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumours were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 300 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed.

  3. Imaging of solid kidney tumours in children

    International Nuclear Information System (INIS)

    Hugosson, C.; Nyman, R.; Jacobsson, B.; Jorulf, H.; Sackey, K.; McDonald, P.

    1995-01-01

    Eighteen children aged 6 months to 12 years with 20 solid renal tumours; 13 Wilms' tumours (WT), 2 clear cell sarcomas of the kidney, 1 malignant rhabdoid tumour of the kidney and 2 cases of bilateral nephroblastomatosis with Wilms' tumour underwent evaluation with US, CT and MR imaging. Contrast-enhanced CT and non-enhanced MR were equally accurate in determining the size and origin of the tumour but were unreliable in separation of stages I, II and III. US could only accurately assess the size of the tumours. MR characteristics varied somewhat between WTs and non-WTs but contrast-enhanced MR imaging might be useful for separation of WTs from nephroblastomatosis. (orig.)

  4. An unusual presentation of a glomus tumour.

    LENUS (Irish Health Repository)

    Nugent, N

    2011-02-01

    Glomus tumours are benign, soft tissue tumours, usually of fingertips. Classically they present with severe pain, temperature sensitivity and localised tenderness. The diagnosis is often delayed due to sometimes non-specific symptoms and rarity of the disorder. While usually a clinical diagnosis, imaging may be necessary for diagnosis and localisation. We present a case of glomus tumour of the fingertip with an unusual history.

  5. Surgical management of epithelial parotid tumours

    International Nuclear Information System (INIS)

    Obaid, M.A.; Yusuf, A.

    2004-01-01

    Objective: To describe the clinicopathological presentation and treatment options in epithelial parotid tumours with emphasis on surgery. Subjects and Methods: Epithelial parotid tumours diagnosed and operated by an ENT surgeon and a general surgeon in 10 years during their posting in different teaching hospitals were included in the study. Clinical presentation, preoperative investigations, operative procedure, histopathology report, postoperative complications and further management were recorded. The data was collected and reviewed from the records of all the patients maintained by the authors. Results: Fifty-two patients presented with parotid tumour. Average age was 38 years. Commonest presentation was painless lump over the parotid region (85%), pain (15%), facial palsy, and enlarged neck nodes. Majority of tumours were benign, only two were recurrent. Parotid pleomorphic Adenoma (PPA) was the commonest benign tumour, others being Warthin's tumour and monomorphic adenoma. Adenoid cystic carcinoma was the commonest malignant tumour 29% followed by mucoepidermoid carcinoma. Others were carcinoma in PPA squamous cell carcinoma, malignant mixed tumour, malignant Iymphoepithelioma and undifferentiated carcinoma. Superficial parotidectomy (SP) was the commonest operation performed in 69%. Other procedures were total conservative parotidectomy in 11%, total radical surgery in 9% and enucleation in only one patient earliest in the series. Neck node dissection was done in 2 patients. Except for one child, rest of the 13 patients received postoperative radiotherapy and one patient of Iymphoepithelioma received chemotherapy in addition. Commonest postoperative complication was temporary facial weakness in 35% (18/52). Permanent facial palsy occurred in 08 patients. Of these 07 had a malignant process and only one patient had excision biopsy. Conclusion: Benign and malignant epithelial parotid tumours can be diagnosed by there clinical presentation . supplemented with

  6. Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy.

    Science.gov (United States)

    Lin, Han; Chen, Yu; Shi, Jianlin

    2018-03-21

    Tumour chemotherapy employs highly cytotoxic chemodrugs, which kill both cancer and normal cells by cellular apoptosis or necrosis non-selectively. Catalysing/triggering the specific chemical reactions only inside tumour tissues can generate abundant and special chemicals and products locally to initiate a series of unique biological and pathologic effects, which may enable tumour-specific theranostic effects to combat cancer without bringing about significant side effects on normal tissues. Nevertheless, chemical reaction-initiated selective tumour therapy strongly depends on the advances in chemistry, materials science, nanotechnology and biomedicine. This emerging cross-disciplinary research area is substantially different from conventional cancer-theranostic modalities in clinics. In response to the fast developments in cancer theranostics based on intratumoural catalytic chemical reactions, this tutorial review summarizes the very-recent research progress in the design and synthesis of representative nanoplatforms with intriguing nanostructures, compositions, physiochemical properties and biological behaviours for versatile catalytic chemical reaction-enabled cancer treatments, mainly by either endogenous tumour microenvironment (TME) triggering or exogenous physical irradiation. These unique intratumoural chemical reactions can be used in tumour-starving therapy, chemodynamic therapy, gas therapy, alleviation of tumour hypoxia, TME-responsive diagnostic imaging and stimuli-responsive drug release, and even externally triggered versatile therapeutics. In particular, the challenges and future developments of such a novel type of cancer-theranostic modality are discussed in detail to understand the future developments and prospects in this research area as far as possible. It is highly expected that this kind of unique tumour-specific therapeutics by triggering specific in situ catalytic chemical reactions inside tumours would provide a novel but efficient

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

  8. Effects of combined heat and x-rays on tumours in mice

    International Nuclear Information System (INIS)

    Hill, S.A.

    1980-08-01

    The therapeutic potential of combined hyperthermia and radiation was investigated in six different types of experimental mouse tumour. Their response to hyperthermia alone and combined heat and X-ray treatments was assessed by delay in tumour regrowth. Thermal sensitivity was found to vary from tumour to tumour. The importance of the order of application and the time interval between treatments was investigated, and the tumour response compared with that of mouse skin as an example of a normal tissue. A therapeutic gain was not seen for X-rays and heat in close sequence. It was however seen when heat was applied several hours after irradiation. Constriction of the tumour blood supply, either artificially, or naturally by implantation into a constricted site, was found to increase thermal sensitivity dramatically. Possible reasons for this are discussed. Heat applied immediately before irradiation may result in a small increase in metastatic spread. Heat applied at other times did not influence the metastatic incidence. Immersion in hot water was examined as a method of heating experimental mouse tumours, and was found to be inadequate in terms of the temperature uniformity achieved. The influence of this factor on results using water bath heating are discussed. (author)

  9. The chemical durability of alkali aluminosilicate glasses

    International Nuclear Information System (INIS)

    Tait, J.C.; Mandolesi, D.L.

    1983-09-01

    The aqueous durabilities of a series of glasses based on the sodium aluminosilicate system (Na 2 O-Al 2 O 3 -SiO 2 ) have been studied. The effects of molecular substitution of K 2 O or CaO for Na 2 O, and B 2 O 3 for Al 2 O 3 have been investigated. The temperature dependence of leaching in the Na 2 O-B 2 O 3 -Al 2 O 3 -SiO 2 system was studied with glasses containing 2 wt percent simulated UO 2 fuel recycle waste. The results confirm that aluminosilicate glasses are more durable than their borosilicate counterparts. The leaching results are explained in terms of glass structure and bonding, and a general leaching mechanism for aluminosilicate glasses is presented

  10. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    Science.gov (United States)

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

  11. Predicting parenting stress in caregivers of children with brain tumours.

    Science.gov (United States)

    Bennett, Emily; English, Martin William; Rennoldson, Michael; Starza-Smith, Arleta

    2013-03-01

    The purpose of the study was to identify factors that contribute to parenting stress in caregivers of children diagnosed with brain tumours. The study was cross-sectional and recruited 37 participants from a clinical database at a specialist children's hospital. Parents were sent questionnaires, which were used to measure factors related to stress in caregivers of children diagnosed with a brain tumour. Stress levels were measured using the Parenting Stress Index-Short Form (PSI/SF). Correlation analysis and multiple linear regression were used to examine the associations between parenting stress and coping styles, locus of control, parent-perceived child disability and time since diagnosis. Results revealed that 51% of parents were experiencing clinically significant levels of stress. The mean stress level of parents in the study was significantly higher than the PSI/SF norms (t = 4.7, p parenting stress. Other styles of coping, child behaviour problems and the amount of time since diagnosis were not found to be predictive of levels of parenting stress. There was a high prevalence of parenting stress in caregivers of children with a brain tumour. An external locus of control and coping by accepting responsibility increased the likelihood of elevated levels of stress. Results emphasised the importance of ongoing support for parents of children with brain tumours. Intervention might helpfully be centred on strategies to increase parents' internal locus of control. Copyright © 2012 John Wiley & Sons, Ltd.

  12. Detection of apoptotic cells in tumour paraffin sections

    International Nuclear Information System (INIS)

    Pizem, J.; Coer, A.

    2003-01-01

    Apoptosis is a distinct form of cell death characterised by specific morphological features and regulated by complex molecular mechanisms. Its deregulation is fundamental for tumour growth and progression and, moreover, anticancer therapies suppress tumour growth mainly by induction of apoptosis. Since the extent of apoptosis in a tumour may have prognostic as well as therapeutic implications, much effort has been invested in developing specific methods that can be routinely used to detect apoptotic cells in archival formalin- fixed paraffin-embedded tissue. Complex molecular pathways are involved in the regulation of apoptosis. Pro-apoptotic signals trigger activation of caspases that specifically cleave target proteins. Cleavage of proteins (caspase substrates) is responsible for morphological changes of apoptotic cells and DNA fragmentation. In the last decade, detection of apoptotic cells in formalin-fixed tumour tissue sections has been based mainly on morphology and characteristic DNA fragmentation. Recently, specific antibodies to activated caspases and cleaved target proteins (including cytokeratin 18, actin and PARP) have been produced that enable accurate detection of apoptosis in paraffin sections. (author)

  13. A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

    Science.gov (United States)

    Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack; Bortell, Rita; Greiner, Dale L; Shultz, Leonard D; Han, Gang; McCormick, Beth A

    2016-07-25

    Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.

  14. Tumours of the pineal region in childhood

    International Nuclear Information System (INIS)

    Herrmann, H.D.; Schulte, F.J.; Winkler, D.; Mueller, D.

    1988-01-01

    36 patients with tumours in the pineal region were treated between 1980 and 1986, 19 of whom were under 20 years of age. Diagnosis was based on cranial CT, supplemented to by MRI as from 1986. Preoperative angiography was peformed on all patients to demonstrate tumour vascularization and type of vascular supply. Stereotactic biopsies were complemented by intraoperative ventriculography. Stereotactic biopsy only was performed in 13 patients out of the total group to verify tumour histology. 23 patients were directly operated on primarily. 3 of these died postoperative. In cases of germ-cell tumours and pineal blastomas the total brain and the vertebral canal were irradiated. (orig./MG) [de

  15. 131I-MIBG and neuroendocrine tumours

    International Nuclear Information System (INIS)

    Oliva Gonzalez, Juan Perfecto; Gonzalez Gonzalez, Joaquin Jorge; Calderon Marin, Carlos Fabian

    2012-01-01

    Neuroendocrine tumours are neoplasms that arise from various tissues closely linked to the neural crest by their common embryological origin. These tumours have the ability to synthesize neurotransmitter peptides and hormones, as well as to store catecholamines. Some of these tumours express somatostatin receptors at their membranes, what have allowed nuclear medicine to be involved in their diagnosis, treatment and monitoring. Since they arise from different and varied types of tissues, these tumours have a wide range of signs and symptoms different for every one of them. These signs and symptoms mainly depend on their biochemical characteristics, given by the substances they secrete, as well as by their location, and consequently, they also depend on the place where the tumour appears, its local infiltration, and potential long-distance metastasis resulting from the tumour). Neuroendocrine tumours are diagnosed by means of nuclear medicine images, which are obtained by using different techniques and radiopharmaceuticals such as 99 mTc dimercaptosuccinic acid (DMSA(V)), 99 mTc-methoxy-isobutyl-isonitrile (MIBI), metaiodobenzylguanidine (MIBG) labelled with 131 I or 123 I ( 131 I-MIBG or 123 I -MIBG), 111 In-labelled octreotide, positron emission tomography, using 68 Ga-labelled somatostatin analogues and carcinoembryonic antigen monoclonal antibodies. Nuclear medicine uses mainly somatostatin analogues labelled with 90 Y or 177 Lu for the treatment of these tumours. This paper is aimed at showing our experience in the use of 131 I-MIBG for the diagnosis and treatment of neuroendocrine tumours.(author)

  16. Peptide receptor radionuclide therapy of neuroendocrine tumours

    International Nuclear Information System (INIS)

    Bodei, L.; Giammarile, F.

    2009-01-01

    Neuroendocrine tumours are considered relatively rare tumours that have the characteristic property of secreting bioactive substances, such as amines and hormones. They constitute a heterogeneous group, characterized by good prognosis, but important disparities of the evolutionary potential. In the aggressive forms, the therapeutic strategies are limited. The metabolic or internal radiotherapy, using radiolabelled peptides, which can act at the same time on the primary tumour and its metastases, constitutes a tempting therapeutic alternative, currently in evolution. The prospects are related to the development of new radiopharmaceuticals, with the use of other peptide analogues whose applications will overflow the framework of the neuro-endocrine tumours. (authors)

  17. Elevated tumour marker: an indication for imaging?

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

  18. Treatment Of Brain Tumours In Childhood

    International Nuclear Information System (INIS)

    Stancokova, T.

    2007-01-01

    Children tumours are the second most common oncologic diseases in childhood (20 %) with highest incidence of mortality in children oncology. Brain tumours form a heterogenous group of tumours with their classification,diagnostic criteria and therapeutic modalities. General principles of treatment involve neurosurgery, which is a prognostic factor, its radicality depends on localization. Radiotherapy has limitations in children until 3 years for possible late effects. Chemotherapy is effective in tumours with high growing rate. These days challenge is to improve therapeutic outcomes and minimalize toxicity of therapy. (author)

  19. Mankiw's Puzzle on Consumer Durables: A Misspecification

    OpenAIRE

    Tam Bang Vu

    2005-01-01

    Mankiw (1982) shows that consumer durables expenditures should follow a linear ARMA(1,1) process, but the data analyzed supports an AR(1) process instead; thus, a puzzle. In this paper, we employ a more general utility function than Mankiw's quadratic one. Further, the disturbance and depreciation rate are respecified, respectively, as multiplicative and stochastic. The analytical consequence is a nonlinear ARMA(infinity,1) process, which implies that the linear ARMA(1,1) is a misspecificatio...

  20. OPTIONS D'INTENSIFICATION DURABLE DES CULTURES ...

    African Journals Online (AJOL)

    (Received 14 August, 2001 ; accepted 10 May, 2002) RÉSUMÉ Pour intensifier de manière durable les cultures vivrières dans les zones de terres de barre dégradées au sud du Togo, plusieurs options ont été évaluées avec les paysans. Grâce à des entretiens collectifs de type participatif, sept différents groupes ...

  1. Durability 2007. Injection grout investigations. Background description

    International Nuclear Information System (INIS)

    Orantie, K.; Kuosa, H.

    2008-12-01

    The aim of this project was to evaluate the durability risks of injection grouts. The investigations were done with respect to the application conditions, materials and service life requirements at the ONKALO underground research facility. The study encompassed injection grout mixtures made of ultrafine cement with and without silica fume. Some of the mixtures hade a low pH and thus a high silica fume content. The project includes a background description on durability literature, laboratory testing programme, detailed analysis of results and recommendations for selecting of ideal grout mixtures. The background description was made for the experimental study of low-pH and reference rock injection grouts as regards pore- and microstructure, strength, shrinkage/swelling and thus versatile durability properties. A summary of test methods is presented as well as examples, i.e. literature information or former test results, of expected range of results from the tests. Also background information about how the test results correlate to other material properties and mix designs is presented. Besides the report provides basic information on the pore structure of cement based materials. Also the correlation between the pore structure of cement based materials and permeability is shortly discussed. The test methods included in the background description are compressive strength, measurement of bulk drying, autogenous and chemical shrinkage and swelling, hydraulic conductivity / permeability, capillary water uptake test, mercury intrusion porosimetry (MIP) and thin section analysis. Three main mixtures with water-binder ratio of 0.8, 1.0 and 1.4 and silica fume content of 0, 15 and 40% were studied in the laboratory. Besides two extra mixtures were studied to provide additional information about the effect of varying water-dry-material ratio and silica fume content on durability. The evaluation of water tightness based on water permeability coefficient and micro cracking was

  2. Intermediate Ethanol Blends Catalyst Durability Program

    Energy Technology Data Exchange (ETDEWEB)

    West, Brian H; Sluder, Scott; Knoll, Keith; Orban, John; Feng, Jingyu

    2012-02-01

    In the summer of 2007, the U.S. Department of Energy (DOE) initiated a test program to evaluate the potential impacts of intermediate ethanol blends (also known as mid-level blends) on legacy vehicles and other engines. The purpose of the test program was to develop information important to assessing the viability of using intermediate blends as a contributor to meeting national goals for the use of renewable fuels. Through a wide range of experimental activities, DOE is evaluating the effects of E15 and E20 - gasoline blended with 15% and 20% ethanol - on tailpipe and evaporative emissions, catalyst and engine durability, vehicle driveability, engine operability, and vehicle and engine materials. This report provides the results of the catalyst durability study, a substantial part of the overall test program. Results from additional projects will be reported separately. The principal purpose of the catalyst durability study was to investigate the effects of adding up to 20% ethanol to gasoline on the durability of catalysts and other aspects of the emissions control systems of vehicles. Section 1 provides further information about the purpose and context of the study. Section 2 describes the experimental approach for the test program, including vehicle selection, aging and emissions test cycle, fuel selection, and data handling and analysis. Section 3 summarizes the effects of the ethanol blends on emissions and fuel economy of the test vehicles. Section 4 summarizes notable unscheduled maintenance and testing issues experienced during the program. The appendixes provide additional detail about the statistical models used in the analysis, detailed statistical analyses, and detailed vehicle specifications.

  3. Amenagements sportifs et developpement durable : Des enjeux ...

    African Journals Online (AJOL)

    ... contredite » éprouvée par (Jeu, 1977), comme l'apanage d'une double hybridation culturelle des pays en développement. Derrière l'apparence de la dislocation des héritages, doit émerger une définition nouvelle sur les rapports que les sports devraient entretenir avec l'environnement pour un développement durable.

  4. Targeted radiotherapy with Sm-153-EDTMP in nine cases of canine primary bone tumours

    Directory of Open Access Journals (Sweden)

    R.J. Milner

    1998-07-01

    Full Text Available Nine dogs with primary bone tumours were treated with Samarium-153-EDTMP (Sm-153- EDTMP. Conventional treatment protocols were precluded by the size of the dogs and the owners' refusal of limb amputation. All the tumours were of the appendicular skeleton; 4 were confirmed osteosarcomas. The other 5 tumours were radiologically suspect for osteosarcoma. Bone scans were performed on all dogs using Technetium-99m-methylene diphosphonate (Tc-99m-MDP before administration of Sm-153-EDTMP. Regions of interest were identified over the contralateral limb at the same site as the tumour and counts per pixel were recorded for the tumour and contralateral limb and expressed as a ratio. The dogs were given 1 injection of 37 MBq/kg (1 mCi/kg of Sm-153-EDTMP intravenously. Thoracic and primary tumour site radiographs were taken at monthly or 2-monthly intervals to monitor progression of the primary tumour and search for evidence of metastasis. Two dogs showed no response to treatment, with an increase in bone pain, and were euthanased within 1 month. In 1 dog, a tumour of the scapula underwent complete involution and the dog is considered free of disease at 20 months post Sm-153-EDTMP treatment. The overall tumourcidal effect of a single dose of Sm-153-EDTMP on primary bone tumours was difficult to evaluate in this group of dogs, as, with one exception, all the primary tumours progressed over time and the dogs were euthanased. Pain control, for which Sm-155-EDTMP is used in man, was not evident, except in the dog that responded completely to treatment.

  5. Recyclable magnetite-silver heterodimer nanocomposites with durable antibacterial performance

    Directory of Open Access Journals (Sweden)

    Chunyan Yong

    2018-03-01

    Full Text Available There is a significant need for magnetite-silver nanocomposites that exhibit durable and recyclable antimicrobial activity. In this study, magnetic iron oxide nanoparticles (Fe3O4 NPs coated with ethylenediamine-modified chitosan/polyacrylic acid copolymeric layer (Fe3O4@ECS/PAA were fabricated. Subsequently, directly deposited silver (Ag NPs procedure was carried out to form the antibacterial heterodimers of Fe3O4@ECS/PAA-Ag NPs. The composition and morphology of the resultant nanostructures were confirmed by FT-IR, XRD, TEM and TGA. The overall length of the heterodimers was approximately 45 nm, in which the mean diameter of Fe3O4@ECS/PAA NPs reached up to 35 nm, and that of Ag NPs was around 15 nm. The mass fraction of silver NPs in the nanocomposites was about 63.1%. The obtained Fe3O4@ECS/PAA NPs exhibited good colloidal stability, and excellent response to additional magnetic field, making the NPs easy to recover after antibacterial tests. In particular, the Fe3O4@ECS/PAA-Ag NPs retained nearly 100% biocidal efficiency (106–107 CFU/mg nanoparticles for both Gram-negative bacteria E. coli and Gram-positive bacteria S. aureus throughout ten cycles without washing with any solvents or water, exhibiting potent and durable antibacterial activity.

  6. Durability of heavyweight concrete containing barite

    International Nuclear Information System (INIS)

    Binici, Hanifi

    2010-01-01

    The supplementary waste barite aggregates deposit in Osmaniye, southern Turkey, has been estimated at around 500 000 000 tons based on 2007 records. The aim of the present study is to investigate the durability of concrete incorporating waste barite as coarse and river sand (RS), granule blast furnace slag (GBFS), granule basaltic pumice (GBP) and ≤ 4 mm granule barite (B) as fine aggregates. The properties of the fresh concrete determined included the air content, slump, slump loss and setting time. They also included the compressive strength, flexural and splitting tensile strengths and Young's modulus of elasticity, resistance to abrasion and sulphate resistance of hardened concrete. Besides these, control mortars were prepared with crushed limestone aggregates. The influence of waste barite as coarse aggregates and RS, GBFS, GBP and B as fine aggregates on the durability of the concretes was evaluated. The mass attenuation coefficients were calculated at photon energies of 1 keV to 100 GeV using XCOM and the obtained results were compared with the measurements at 0.66 and 1.25 MeV. The results showed the possibility of using these waste barite aggregates in the production of heavy concretes. In several cases, some of these properties have been improved. Durability of the concrete made with these waste aggregates was improved. Thus, these materials should be preferably used as aggregates in heavyweight concrete production. (orig.)

  7. Creep Behavior and Durability of Cracked CMC

    Science.gov (United States)

    Bhatt, R. T.; Fox, Dennis; Smith, Craig

    2015-01-01

    To understand failure mechanisms and durability of cracked Ceramic matrix composites (CMCs), Melt Infiltration (MI) SiCSiC composites with Sylramic-iBN fibers and full Chemical vapour infiltration SiCSiC composites with Sylramic-ion bombarded BN (iBN) and Hi-Nicalon -S fibers were pre-cracked between 150 to 200 megapascal and then creep and Sustained Peak Low Cycle Fatigue (SPLCF) tested at 13150 C at stress levels from 35 to 103 megapascal for up to 200 hours under furnace and burner rig conditions. In addition creep testing was also conducted on pre-cracked full Chemical vapour infiltration SiCSiC composites at 14500 C between 35 and 103 megapascal for up to 200 hours under furnace conditions. If the specimens survived the 200 hour durability tests, then they were tensile tested at room temperature to determine their residual tensile properties. The failed specimens were examined by Scanning electron microscope (SEM) to determine the failure modes and mechanisms. The influence of crack healing matrix, fiber types, crack density, testing modes and interface oxidation on durability of cracked Ceramic matrix composites (CMCs) will be discussed.

  8. Durability evaluation of reversible solid oxide cells

    Science.gov (United States)

    Zhang, Xiaoyu; O'Brien, James E.; O'Brien, Robert C.; Housley, Gregory K.

    2013-11-01

    An experimental investigation on the performance and durability of single solid oxide cells (SOCs) is under way at the Idaho National Laboratory. Reversible operation of SOCs includes electricity generation in the fuel cell mode and hydrogen generation in the electrolysis mode. Degradation is a more significant issue when operating SOCs in the electrolysis mode. In order to understand and mitigate the degradation issues in high temperature electrolysis, single SOCs with different configurations from several manufacturers have been evaluated for initial performance and long-term durability. Cells were obtained from four industrial partners. Cells from Ceramatec Inc. and Materials and Systems Research Inc. (MSRI) showed improved durability in electrolysis mode compared to previous stack tests. Cells from Saint Gobain Advanced Materials Inc. (St. Gobain) and SOFCPower Inc. demonstrated stable performance in the fuel cell mode, but rapid degradation in the electrolysis mode, especially at high current density. Electrolyte-electrode delamination was found to have a significant impact on degradation in some cases. Enhanced bonding between electrolyte and electrode and modification of the electrode microstructure helped to mitigate degradation. Polarization scans and AC impedance measurements were performed during the tests to characterize cell performance and degradation.

  9. Effects of Irradiation on Albite's Chemical Durability.

    Science.gov (United States)

    Hsiao, Yi-Hsuan; La Plante, Erika Callagon; Krishnan, N M Anoop; Le Pape, Yann; Neithalath, Narayanan; Bauchy, Mathieu; Sant, Gaurav

    2017-10-19

    Albite (NaAlSi 3 O 8 ), a framework silicate of the plagioclase feldspar family and a common constituent of felsic rocks, is often present in the siliceous mineral aggregates that compose concrete. When exposed to radiation (e.g., in the form of neutrons) in nuclear power plants, the crystal structure of albite can undergo significant alterations. These alterations may degrade its chemical durability. Indeed, careful examinations of Ar + -implanted albite carried out using Fourier transform infrared spectroscopy (FTIR) and molecular dynamics simulations show that albite's crystal structure, upon irradiation, undergoes progressive disordering, resulting in an expansion in its molar volume (i.e., a reduction of density) and a reduction in the connectivity of its atomic network. This loss of network connectivity (i.e., rigidity) results in an enhancement of the aqueous dissolution rate of albite-measured using vertical scanning interferometry (VSI) in alkaline environments-by a factor of 20. This enhancement in the dissolution rate (i.e., reduction in chemical durability) of albite following irradiation has significant impacts on the durability of felsic rocks and of concrete containing them upon their exposure to radiation in nuclear power plant (NPP) environments.

  10. Effect Of Climatic Conditions On Durability

    Directory of Open Access Journals (Sweden)

    Ibrahem M. Al Kiki

    2013-04-01

    Full Text Available Durability is one of the most important subjects in the soil stabilization. Since there is no specifications concerned the durability of lime stabilized soils, several factors were selected to show their effects on the durability, namely: wetting, drying, freezing, thawing and slaking.The effect of each one of the above factors as well as the combined effect of two or more factors, were studied on the volume change and soil strength and weight loss of soil samples stabilized with optimum lime content except the slaking test at which soil samples stabilized with different lime content.Tests results showed that the higher the lime content the lower the slaking effect, also its found the soil strength decreased when the period of immersion or freezing increased. The strength of the lime stabilized soils decreased when subjected to the cycles of wetting and drying or to the cycles freezing and thawing. However, the  combined effect of wetting, drying, freezing and thawing has a pronounced effect on reduction of the lime stabilized clayey soil. The worst condition recorded when lime stabilized soil undergo to freezing then drying then wetting which should be avoided in the field

  11. Role of tumour initiating cells in the radiation resistance of osteosarcoma

    International Nuclear Information System (INIS)

    Klymenko, Olena

    2014-01-01

    In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

  12. Role of tumour initiating cells in the radiation resistance of osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Klymenko, Olena

    2014-02-26

    In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

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

    Directory of Open Access Journals (Sweden)

    Maini PK

    2010-04-01

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

  14. Diagnostic utility of Wilms′ tumour-1 protein (WT-1 immunostaining in paediatric renal tumours

    Directory of Open Access Journals (Sweden)

    Surbhi Goyal

    2016-01-01

    Interpretation & conclusions: WT1 helps to differentiate Wilms′ tumour from other paediatric renal tumours. It may help in differentiating the two subgroups of Wilms′ tumour which have distinct molecular pathogenesis and biological behaviour, however, further prospective studies are required for validation of this hypothesis.

  15. Granular cell tumour of the neurohypophysis: a rare sellar tumour with specific radiological and operative features.

    LENUS (Irish Health Repository)

    Aquilina, K

    2012-02-03

    Symptomatic granular cell tumours of the neurohypophysis are rare sellar lesions. Preoperative prediction of the diagnosis on the basis of radiological appearance is useful as these tumours carry specific surgical difficulties. This is possible when the tumour arises from the pituitary stalk, rostral to a normal pituitary gland. This has not been emphasized previously.

  16. Experimental study on durability improvement of fly ash concrete with durability improving admixture.

    Science.gov (United States)

    Quan, Hong-zhu; Kasami, Hideo

    2014-01-01

    In order to improve the durability of fly ash concrete, a series of experimental studies are carried out, where durability improving admixture is used to reduce drying shrinkage and improve freezing-thawing resistance. The effects of durability improving admixture, air content, water-binder ratio, and fly ash replacement ratio on the performance of fly ash concrete are discussed in this paper. The results show that by using durability improving admixture in nonair-entraining fly ash concrete, the compressive strength of fly ash concrete can be improved by 10%-20%, and the drying shrinkage is reduced by 60%. Carbonation resistance of concrete is roughly proportional to water-cement ratio regardless of water-binder ratio and fly ash replacement ratio. For the specimens cured in air for 2 weeks, the freezing-thawing resistance is improved. In addition, by making use of durability improving admixture, it is easier to control the air content and make fly ash concrete into nonair-entraining one. The quality of fly ash concrete is thereby optimized.

  17. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Aboagye, Eric O.; Kenny, Laura M.; Myers, Melvyn [Imperial College London, Department of Surgery and Cancer, Faculty of Medicine, London (United Kingdom); Gilbert, Fiona J. [University of Cambridge, Radiology Department, Cambridge (United Kingdom); Fleming, Ian N. [University of Aberdeen, NCRI PET Research Network, Aberdeen Bioimaging Centre, Aberdeen (United Kingdom); Beer, Ambros J. [Technische Universitaet Munchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany); Cunningham, Vincent J. [University of Aberdeen, Institute of Medical Sciences, Aberdeen (United Kingdom); Marsden, Paul K. [St. Thomas' Hospital, Division of Imaging Sciences, PET Imaging Centre, London (United Kingdom); Visvikis, Dimitris [INSERM National Institute of Health and Clinical Sciences LaTIM, CHU Morvan, Brest (France); Gee, Antony D. [St. Thomas' Hospital, Division of Imaging Sciences, The Rayne Institute, London (United Kingdom); Groves, Ashley M. [University College London, University College Hospital, Institute of Nuclear Medicine, London (United Kingdom); Cook, Gary J. [St. Thomas' Hospital, KCL Division of Imaging, Sciences and Biomedical Engineering, PET Imaging Centre, London (United Kingdom); Kinahan, Paul E. [University of Washington, 222 Old Fisheries Center (FIS), Box 357987, Seattle, WA (United States); Clarke, Larry [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States)

    2012-07-15

    The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [{sup 15}O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics. (orig.)

  18. Malignant tumours of the vulva

    International Nuclear Information System (INIS)

    Simonsen, E.

    1983-01-01

    The thesis analyses 317 patients with vulvar malignancies treated at the University Hospital, Lund, during 1960-1979. The three most common histological types of malignancy have been analysed. The oncological clinic in Lund has since the 1960's used a surgical technique where the primary tumour and the regional lymph nodes are operated on in two separate surgical seances. The vulvectomy is performed with tarm knife technique, and the wound is left open. The 5-year crude survival rate for the entire patient material treated with curative intention was over 60 %, which agrees well with reports from other centres. Our surgical approach using two separate seances has, however, much lower rates of postoperative complications and mortality than the rates in other reports. The overall most important prognostic factors for the patients with invasive vulvar malignancies are the presence of lymphatic metastases at the time of surgery, and the surgical radicality of the primary surgery. The treatment at most stages of tumour development and most histological types should include total vulvectomy preoperative irradiation of the inguinal lymph nodes, and inguinal lymphadenectomy. Only local extirpation and hemivulvectomy are, however, indicated for small microinvasively growing squamous cell carcinoma and basal cell carcinoma. Samll invasive onesided squamous cell carcinoma is best treated with ipsilateral surgery combined with preoperative irradiation of the inguinal lymph nodes. Patients with metastases in the inguinal lymph nodes should receive additional irradiation of the inguinal and pelvic lymph node stations. (Author)

  19. Therapy of HPV 16-associated carcinoma with dendritic cell-based vaccines: In vitro priming of the effector cell responses by DC pulsed with tumour lysates and synthetic RAHYNIVTF peptide

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Bubeník, Jan; Šímová, Jana; Vonka, V.; Němečková, Š.; Mendoza, Luis; Reiniš, Milan

    2001-01-01

    Roč. 7, č. 1 (2001), s. 97-100 ISSN 1107-3756 R&D Projects: GA MZd NC5526; GA MZd NC45011; GA ČR GA312/98/0826; GA ČR GA312/99/0542; GA ČR GA301/00/0114; GA AV ČR IAA7052002 Institutional research plan: CEZ:AV0Z5052915 Keywords : tumour vaccines * HPV 16 * dendritic cells Subject RIV: FD - Oncology ; Hematology Impact factor: 1.689, year: 2001

  20. Merkel cell tumour of the face successfully treated with radical radiotherapy

    International Nuclear Information System (INIS)

    Pople, I.K.

    1988-01-01

    A case of Merkel cell tumour of the face and its dramatic response to a course of radical radiotherapy is presented below. The patient has been free of recurrence for 18 months and has suffered minimal side-effects from the treatment. This suggests that radical radiotherapy, as opposed to the standard wide excision, may be preferred first-line treatment for at least some of these rare, but highly malignant tumours. (author)

  1. REPORT OF SEVEN CASES OF METASTATIC TUMOURS

    African Journals Online (AJOL)

    Major Adebayo

    Metastatic lesions may mimic odontogenic infections and other disease conditions in the oral cavity in presentation leading to late diagnosis by the unwary clinician. In Nigeria, reports on jaw tumours from metastasis elsewhere are quite scarce. This report presents a series of histologically verified metastatic tumours to the ...

  2. Second primary tumours in oral cancer

    NARCIS (Netherlands)

    van der Waal, I.; de Bree, R.

    2010-01-01

    Second primary tumours in patients treated for oral cancer occur at a rate of 3% to 7% per year. The majority of these tumours show up at least six months after the detection of the primary and are often located in the upper aerodigestive tract. Cessation of smoking habits may reduce the risk of the

  3. Tumour cell expansion in bladder epithelium

    NARCIS (Netherlands)

    J.M.J. Rebel (Annemarie)

    1995-01-01

    textabstractBladder cancer is common in western society. The major problem of patients with superficial bladder cancer is the high recurrence rate and multifocality of these tumours. In 70 % of the patients superficial bladder cancer recurs after local resection of the tumour within 15 years. The

  4. Tumour screening by means of tomography methods

    International Nuclear Information System (INIS)

    Diederich, S.

    2005-01-01

    Tomography methods such as computer tomography (CT), magnetic resonance tomography (MRT), and sonography/ultrasound examinations make it possible to detect small asymptomatic tumours, thus potentially preventing their manifestation at an advanced stage and improving survival prospects for the patients concerned. There are data available on various common tumours which show that modern tomography methods are capable of detecting not only small asymptomatic tumours but also their benign precursors (e.g. polyps of the large intestine). This has been demonstrated for lung cancer, colon cancer and breast cancer. However, it has not been possible to date to show for any tomography method or any type of tumour that the systematic use of such diagnostic procedures does anything to lower the mortality rate for that tumour. For other types of tumour (pancreatic cancer, kidney cancer, ovary cancer) the above named methods are either not sufficiently sensitive or the body of data that has accumulated on their respective use is too small to judge the benefit of tomography screenings. Current technical developments make it appear probable that for many types of cancer the reliability with which small tumours can be detected will improve in future. Studies aimed at clarifying the potential of screenings for reducing mortality rates are already underway for lung cancer and would be worthwhile performing for other tumour types

  5. CASE REPORT Paraspinal primitive neuroectodermal tumour (PNET)

    African Journals Online (AJOL)

    could be confirmed on the lateral lumbar spine X-ray. The T11 inter- pedicular distance was ... Department of Diagnostic Radiology, University of Limpopo, Medunsa Campus. CASE REPORT. 18. SA JOURNAL OF ... tumours from neural crest origin.1-4,6 PNET and ES are classified together into the Ewing family of tumours ...

  6. Neurofibromatosis type 1: brain stem tumours

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

    1997-01-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

  7. Skull base tumours part I: Imaging technique, anatomy and anterior skull base tumours

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Servico de Radiologia, Rua Professor Lima Basto, 1093 Lisboa Codex (Portugal)], E-mail: borgesalexandra@clix.pt

    2008-06-15

    Advances in cross-sectional imaging, surgical technique and adjuvant treatment have largely contributed to ameliorate the prognosis, lessen the morbidity and mortality of patients with skull base tumours and to the growing medical investment in the management of these patients. Because clinical assessment of the skull base is limited, cross-sectional imaging became indispensable in the diagnosis, treatment planning and follow-up of patients with suspected skull base pathology and the radiologist is increasingly responsible for the fate of these patients. This review will focus on the advances in imaging technique; contribution to patient's management and on the imaging features of the most common tumours affecting the anterior skull base. Emphasis is given to a systematic approach to skull base pathology based upon an anatomic division taking into account the major tissue constituents in each skull base compartment. The most relevant information that should be conveyed to surgeons and radiation oncologists involved in patient's management will be discussed.

  8. The desmoid tumour: Therapeutic results of surgical intervention as compared to those achieved with radiotherapy

    International Nuclear Information System (INIS)

    Weindler, J.

    1983-01-01

    Discussion of the case reports of nine patients treated for desmoid tumours in the light of 62 such cases described in the relevant literature between 1975 and 1979. Among the patients analysed for the purposes of this study 9 had desmoid tumours treated at our clinic, while the other 60 cases were described in the relevant literature of the past 5 years. The methods used in this cohort were surgery for 37 patients, radiation for 20 patients, excision and post-surgical radiation for 5 patients and various other treatments for the remaining cases. Careful analysis and assessment of the results led to the conclusion that the vast majority of desmoids can be expected to show a satisfactory response to radiation, even though no clear therapeutic superiority could be established for either radical excision or radiation. If surgery is chosen, this should be carried out with the aim of removing all of the tumour. In circumstances precluding radical excision it appears wise to use post-surgical radiation. Follow-up examinations should be carried out in all patients so as to permit immediate diagnosis and treatment of any recurrent tumours. Each desmoid tumour is to be treated on an individual basis. In small tumours it is safer to remove not only the lesion itself but also some of the surrounding intact tissue, tumours at a more advanced stage should be subjected to radiation or both surgery and subsequent radiotherapy. (orig./MG) [de

  9. Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

    Science.gov (United States)

    Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

    2015-01-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  10. Multidisciplinary team working across different tumour types: analysis of a national survey.

    Science.gov (United States)

    Lamb, B W; Sevdalis, N; Taylor, C; Vincent, C; Green, J S A

    2012-05-01

    Using data from a national survey, this study aimed to address whether the current model for multidisciplinary team (MDT) working is appropriate for all tumour types. Responses to the 2009 National Cancer Action Team national survey were analysed by tumour type. Differences indicate lack of consensus between MDT members in different tumour types. One thousand one hundred and forty-one respondents from breast, gynaecological, colorectal, upper gastrointestinal, urological, head and neck, haematological and lung MDTs were included. One hundred and sixteen of 136 statements demonstrated consensus between respondents in different tumour types. There were no differences regarding the infrastructure for meetings and team governance. Significant consensus was seen for team characteristics, and respondents disagreed regarding certain aspects of meeting organisations and logistics, and patient-centred decision making. Haematology MDT members were outliers in relation to the clinical decision-making process, and lung MDT members disagreed with other tumour types regarding treating patients with advanced disease. This analysis reveals strong consensus between MDT members from different tumour types, while also identifying areas that require a more tailored approach, such as the clinical decision-making process, and preparation for and the organisation of MDT meetings. Policymakers should remain sensitive to the needs of health care teams working in individual tumour types.

  11. Unravelling the biology of human papillomavirus (HPV) related tumours to enhance their radiosensitivity

    International Nuclear Information System (INIS)

    Vozenin, M.C.; Lord, H.K.; Deutsch, E.; Vozenin, M.C.; Hartl, D.

    2010-01-01

    HPV infection is associated with most squamous cell carcinomas (SCC) of the uterine cervix and many head and neck SCC. While recent understanding of the mechanisms of HPV-induced carcinogenesis has lead to the development of prophylactic vaccines, the principal modality of treatment is radiotherapy and despite concurrent chemotherapy, outcomes remain suboptimal. Improving the radiotherapeutic index thus remains an important challenge as well as defining predictive assays for treatment outcome of HPV-related tumours. Therefore elucidating the influence of the HPV virus on tumour radiosensitivity is of major interest due to the prevalence of HPV-related tumours worldwide and due to evidence that head and neck HPV-tumours have markedly different clinical outcomes compared to non-HPV-related tumours. This difference may allow for different treatment strategies to be developed. The present review aims to summarize the current understanding of radiosensitivity and HPV-related tumour biology in order to subsequently develop new approaches to enhance the therapeutic index. This review also emphasizes the relevance of E6 and E7 onco-proteins to tumour cell response to radiotherapy suggesting that specific targeted approaches such as concomitant modulation of additional pathways using targeted therapies should offer new therapeutic avenues. (authors)

  12. lmmunohistochemical study of effect of ionizing radiation on human malignant tumours

    International Nuclear Information System (INIS)

    Adomaitiene, D. I.; Aleknavicius, E.; Valuckas, K. and others

    2000-01-01

    Cell proliferation-associated tumour markers are considered to have a valuable clinical significance. The current study was designed to investigate changes in immunohistochemical (IH) expression of proliferating cell nuclear antigen PCNA in human malignant tumour tissue samples obtained before and after preoperative radiotherapy. Tumour tissue samples were obtained from 26 patients with rectal carcinoma, from 22 patients with carcinoma corporis uteri and from 82 patients with breast cancer. Tumour samples were processed for IH examination by using monoclonal antibodies (MoAbs) PC10 against PCNA. IH analysis of histological specimens of carcinoma corporis uteri and rectal carcinoma obtained before and after preoperative radiotherapy has revealed heterogeneity of biological response to irradiation. The great majority of tumour specimens after irradiation showed a high PCNA expression level in cell population. Only minority of tumour specimens (15-20%) exhibited reduced immunoreactivity with MoAbs PC10. PCNA positivity rate in breast cancer specimens obtained during surgery from 55 patients after preoperative radiotherapy in comparison to biomarker expression pattern in tumour specimens from 27 unirradiated patients (control group) was found to be tended to decrease. These in vivo findings are discussed in terms of radiation-induced cell death, followed after proliferation, and PCNA role in DNA repair. (author)

  13. Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

    Directory of Open Access Journals (Sweden)

    Christopher R S Banerji

    2015-03-01

    Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

  14. Occurrence studies of intracranial tumours

    Energy Technology Data Exchange (ETDEWEB)

    Larjavaara, S.

    2011-07-01

    Intracranial tumours are a histopathologically heterogeneous group of tumours. This thesis focused on three types of intracranial tumours; gliomas, meningiomas and vestibular schwannomas (VS). The main objectives of the dissertation were to estimate the occurrence of intracranial tumours by different subtypes, and to assess the validity and completeness of the cancer registry data. The specific aims of the publications were to evaluate the validity of reported incidence rates of meningioma cases, to describe the trends of VS incidence in four Nordic countries, and to define the anatomic distribution of gliomas and to investigate their location in relation to mobile phone use. Completeness of meningioma registration was examined by comparing five separate sources of information, and by defining the frequencies of cases reported to the Finnish Cancer Registry (FCR). Incidence trends of VS were assessed in the four Nordic countries over a twenty-one-year period (1987 - 2007) using cancer registry data. The anatomic site of gliomas was evaluated using both crude locations in the cerebral lobes and, in more detail, a three-dimensional (3D) distribution in the brain. In addition, a study on specific locations of gliomas in relation to the typical position of mobile phones was conducted using two separate approaches: a case-case and a case-specular analysis. The thesis was based on four sets of materials. Data from the international Interphone study were used for the studies on gliomas, while the two other studies were register-based. The dataset for meningiomas included meningioma cases from the FCR and four clinical data sources in Tampere University Hospital (neurosurgical clinic, pathology database, hospital discharge register and autopsy register). The data on VS were obtained from the national cancer registries of Denmark, Finland, Norway and Sweden. The coverage of meningiomas was not comprehensive in any of the data sources. The completeness of FCR was

  15. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

    Science.gov (United States)

    Renault, Anne-Laure; Mebirouk, Noura; Fuhrmann, Laetitia; Bataillon, Guillaume; Cavaciuti, Eve; Le Gal, Dorothée; Girard, Elodie; Popova, Tatiana; La Rosa, Philippe; Beauvallet, Juana; Eon-Marchais, Séverine; Dondon, Marie-Gabrielle; d'Enghien, Catherine Dubois; Laugé, Anthony; Chemlali, Walid; Raynal, Virginie; Labbé, Martine; Bièche, Ivan; Baulande, Sylvain; Bay, Jacques-Olivier; Berthet, Pascaline; Caron, Olivier; Buecher, Bruno; Faivre, Laurence; Fresnay, Marc; Gauthier-Villars, Marion; Gesta, Paul; Janin, Nicolas; Lejeune, Sophie; Maugard, Christine; Moutton, Sébastien; Venat-Bouvet, Laurence; Zattara, Hélène; Fricker, Jean-Pierre; Gladieff, Laurence; Coupier, Isabelle; Chenevix-Trench, Georgia; Hall, Janet; Vincent-Salomon, Anne; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2018-04-17

    The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22-23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially 'druggable' genes that would allow patients to be directed towards tailored therapeutic strategies. Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological

  16. Parotid gland tumours: a six years experience

    International Nuclear Information System (INIS)

    Malik, K.A.

    2006-01-01

    To find out the different types of Parotid tumours in out setup and their prevalence in different age groups. All patients admitted with Parotid swellings, irrespective of age and sex. The detailed data of the patients was collected and analyzed. A total of 27 patients, 15 males and 12 females, with ages ranging from 15 to 65 years were included in the study. Most of the patients were in the 31-50 years of age group. Pleomorphic adenoma was the commonest benign tumour with an incidence of 66.6%, while Mucoepidermoid Carcinoma with an incidence of 11.11% was the most common malignant tumour. Parotid gland is the principal site of salivary gland tumours. Males are affected more and Pleomorphic adenoma is the most common benign and Mucoepidermoid carcinoma the most common malignant tumour. (author)

  17. Molecular pathology of bone tumours: diagnostic implications.

    Science.gov (United States)

    Puls, Florian; Niblett, Angela J; Mangham, D Chas

    2014-03-01

    Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

  18. Musculoskeletal desmoid tumours: Diagnostic imaging appearances

    International Nuclear Information System (INIS)

    Liu, Daniel; Perera, Warren; Schlicht, Stephen; Choong, Peter; Slavin, John; Pianta, Marcus

    2015-01-01

    This study aimed to discuss the role medical imaging has on diagnosis of musculoskeletal desmoid tumours and to describe their radiological appearances on various imaging modalities. Imaging of histologically proven cases of desmoid tumours at St. Vincent's Hospital Melbourne were obtained via picture archiving communication system (PACS) and then assessed by two musculoskeletal radiologists. Suitable imagings were obtained from PACS. All imaging chosen was de-identified. Desmoid tumours can occur in many areas of the body. Imaging plays an important role in the diagnosis of these tumours and magnetic resonance imaging has been the gold standard for imaging and is the most accurate in terms of assessing tumour margins and involvement of surrounding structure.

  19. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  20. Assessment of the residual tumour of colorectal liver metastases after chemotherapy: diffusion-weighted MR magnetic resonance imaging in the peripheral and entire tumour

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Mathilde; Doblas, Sabrina; Giraudeau, Celine [Paris Diderot University, INSERM, UMR 1149, Clichy (France); Ronot, Maxime; Van Beers, Bernard; Vilgrain, Valerie [Paris Diderot University, INSERM, UMR 1149, Clichy (France); Radiology Department, Beaujon Hospital, University Hospitals Paris Nord Val de Seine, Assistance Publique-Hopitaux de Paris, APHP, Clichy (France); Belghiti, Jacques [Hepatobiliary Surgery Department, Beaujon Hospital, University Hospitals Paris Nord Val de Seine, Assistance Publique-Hopitaux de Paris, APHP, Clichy (France); Paradis, Valerie [Pathology Department, Beaujon Hospital, University Hospitals Paris Nord Val de Seine, Assistance Publique-Hopitaux de Paris, APHP, Clichy (France)

    2016-01-15

    To evaluate the value of diffusion-weighted imaging (DWI) in detecting residual tumours (RTs) in colorectal liver metastases (CLMs) following chemotherapy, with a focus on tumour periphery. From January 2009-January 2012, 57 patients who underwent liver resection for CLMs with preoperative MRI (<3 months) including DWI were retrospectively included. CLMs were classified into three response groups on pathology: (1) major histological (MHR, RTs ≤ 10 %), (2) partial histological (PHR, RT = 10-49 %), and (3) no histological (NHR, RT ≥ 50 %). On DWI, regions of interest (ROIs) were drawn around the entire tumour and tumour periphery. Apparent diffusion (ADC) and pure diffusion (D) coefficients were calculated using a monoexponential fit, and compared using Kruskal-Wallis test on a lesion-per-lesion analysis. 111 CLMs were included. Fourteen (12.5 %), 42 (38 %) and 55 (49.5 %) CLMs presented a MHR, PHR and NHR, respectively. ADC and D of the peripheral ROIs were significantly higher in the MHR group (P = 0.013/P = 0.013). ADC and D from the entire tumour were not significantly different among the groups (P = 0.220/P = 0.103). In CLM treated with chemotherapy, ADC and D values from the entire tumour are not related to the degree of RT, while peripheral zone diffusion parameters could help identify metastases with MHR. (orig.)

  1. Tumour location within the breast: Does tumour site have prognostic ability?

    Science.gov (United States)

    Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

    2015-01-01

    Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

  2. Low power consumption and high temperature durability for radiation sensor

    International Nuclear Information System (INIS)

    Matsumoto, Yoshinori; Ueno, Hiroto

    2015-01-01

    Low power consumption and high temperature operation are important in an environmental monitoring system. The power consumption of 3 mW is achieved for the radiation sensor using low voltage operational amplifier and comparator in the signal processing circuit. The leakage reverse current of photodiode causes the charge amplifier saturation over 50degC. High temperature durability was improved by optimizing the circuit configuration and the values of feedback resistance and capacitance in the charge amplifier. The pulse response of the radiation sensor was measured up to 55degC. The custom detection circuit was designed by 0.6 μm CMOS process at 5-V supply voltage. The operation temperature was improved up to 65degC. (author)

  3. Durability properties for adhesively bonded structural aerospace applications

    International Nuclear Information System (INIS)

    Shaffer, D.K.; Davis, G.D.; McNamara, D.K.; Shah, T.K.; Desai, A.

    1992-01-01

    This paper reports on the importance of good bond durability of adhesively joined aerospace components which has been recognized for many years. Military and civilian aircraft are exposed to harsh environments in addition to severe thermal and stress cycles during their service lives. Moisture is responsible for the majority of bond failures in the field. The presence of surface contaminants (e.g., fluoride, silicones) and the non-neutral pH of poor rinse water are common causes of adhesion problems in production environments. Honeycomb panels, stringer skins, doubler plates and core cowl assemblies are bonded joint structures that are subject to environmental- or contaminant-induced debonding. The identification and characterization of the causes of such bond failures leads to improved production quality, yield and cost reduction

  4. Microcracking and durability of high strength concretes

    International Nuclear Information System (INIS)

    Yssorche, M.P.

    1995-07-01

    Durability of 28 days compressive strength concrete of 20 to 120 MPa has been studied. The ability of concrete to transport aggressive agents has been determined for four properties: the air permeability, the chloride diffusivity, the water absorption and the carbonation. A chloride migration test for high and very high strength concrete (HSC and VHSC) has been built. The relationship between transport properties and the compressive strength after one and 28 days of humid curing has always the same shape: transport decreases when strength increases. However, transport properties often vary in the ordinary concrete field. Beyond, the domain is much more limited. The relationship between transport properties and strength valid for ordinary concrete can not be simply extrapolated for HSC and VHSC. To determine the part of microcracking of HSC and VHSC, concrete behaviour stored in two mediums has been studied: the ones shaming the storing condition of concrete in auto-desiccation, the others reproducing the storing conditions of concrete in desiccation. Auto-desiccation (measuring relative humidity at balance) and desiccation (measuring mass losses) have been showed. Microcracks and shrinkage strains have been measured. It has been showed that auto-desiccation microcracks proving in HSC or VHSC don't question the durability. Microcracks, as for permeability, do not develop between 28 days and one year. On the contrary, desiccation microcracks observed in HSC and VHSC, increase with transport properties between 28 days and 1.5 year. Thus, a bulk concrete is always more durable than a cover concrete. At last, the good influence of increase of curing of 1 to 28 days on the transport of all concretes has been emphasized. (author)

  5. Durable fear memories require PSD-95

    Science.gov (United States)

    Fitzgerald, Paul J.; Pinard, Courtney R.; Camp, Marguerite C.; Feyder, Michael; Sah, Anupam; Bergstrom, Hadley; Graybeal, Carolyn; Liu, Yan; Schlüter, Oliver; Grant, Seth G.N.; Singewald, Nicolas; Xu, Weifeng; Holmes, Andrew

    2014-01-01

    Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. While overly persistent fear memories underlie anxiety disorders such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Post-synaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Employing a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95GK), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95GK mice to retrieve remote cued fear memories was associated with hypoactivation of the infralimbic cortex (IL) (not anterior cingulate (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated PSD-95 virus-mediated knockdown in the IL, not ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories. PMID:25510511

  6. Tumour-induced osteomalacia’

    Science.gov (United States)

    Munoz, Javier; Michel Ortega, Rosa; Celzo, Florence; Donthireddy, Vijayalakshmi

    2012-01-01

    A 60-year-old man presented 2 years before his diagnosis with long-standing muscle cramping, progressive generalised weakness and chronic hip pain. The patient was found to have bilateral femoral neck pathologic fractures therefore, underwent reamed intramedullary nailing of both femurs. Laboratory studies showed hypophosphataemia. Bone marrow biopsy was negative for malignancy. Positron emission tomography demonstrated fludeoxyglucose uptake only in the posterior neck. Bone scan showed innumerable foci of increased activity throughout the skeleton consistent with pseudofractures seen in osteomalacia. Fine needle aspiration from the mass in the neck revealed a phosphaturic mesenchymal tumour of mixed connective tissue type. Resection of the mass in the neck resulted in resolution of generalised complaints with no evidence of recurrence with a follow-up of 12 months. PMID:22736784

  7. The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer.

    Science.gov (United States)

    Patel, Meera; McSorley, Stephen T; Park, James H; Roxburgh, Campbell S D; Edwards, Joann; Horgan, Paul G; McMillan, Donald C

    2018-03-06

    There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer. Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H&E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and lymphocyte:monocyte ratio (LMR). Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P=0.001), deficient MMR (P=0.005), higher T stage (Plocation was consistently associated with a high SIR, mGPS (Plocation, adjuvant chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P=0.509) but was associated with higher T stage (P=0.001), venous invasion (P=0.036), CD3 + at the invasive margin (P=0.033) and CD3 + within cancer nests (P=0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group. Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and

  8. Durability Testing of Idlers for Belt Conveyors

    Directory of Open Access Journals (Sweden)

    Andrzej Pytlik

    2013-01-01

    On the basis of the durability tests carried out on both of these idlers it can be concluded that the applied research methodology describes the test conditions of idlers, in a manner as close as possible to their actual operational conditions, which were subject to a variety of factors for a total time of 116 hours, they included: dust, water, loads and variable rotational speed. This methodology allowed us to determine, even at the stage of laboratory tests, the suitability of a particular idler to certain operational conditions.

  9. Advanced Face Gear Surface Durability Evaluations

    Science.gov (United States)

    Lewicki, David G.; Heath, Gregory F.

    2016-01-01

    The surface durability life of helical face gears and isotropic super-finished (ISF) face gears was investigated. Experimental fatigue tests were performed at the NASA Glenn Research Center. Endurance tests were performed on 10 sets of helical face gears in mesh with tapered involute helical pinions, and 10 sets of ISF-enhanced straight face gears in mesh with tapered involute spur pinions. The results were compared to previous tests on straight face gears. The life of the ISF configuration was slightly less than that of previous tests on straight face gears. The life of the ISF configuration was slightly greater than that of the helical configuration.

  10. Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients.

    Science.gov (United States)

    Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; De Lena, M; Allegra, C J; Johnston, P G

    2000-02-01

    The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy.

  11. Awake craniotomy and electrophysiological mapping for eloquent area tumours.

    Science.gov (United States)

    Chacko, Ari George; Thomas, Santhosh George; Babu, K Srinivasa; Daniel, Roy Thomas; Chacko, Geeta; Prabhu, Krishna; Cherian, Varghese; Korula, Grace

    2013-03-01

    An awake craniotomy facilitates radical excision of eloquent area gliomas and ensures neural integrity during the excision. The study describes our experience with 67 consecutive awake craniotomies for the excision of such tumours. Sixty-seven patients with gliomas in or adjacent to eloquent areas were included in this study. The patient was awake during the procedure and intraoperative cortical and white matter stimulation was performed to safely maximize the extent of surgical resection. Of the 883 patients who underwent craniotomies for supratentorial intraaxial tumours during the study period, 84 were chosen for an awake craniotomy. Sixty-seven with a histological diagnosis of glioma were included in this study. There were 55 men and 12 women with a median age of 34.6 years. Forty-two (62.6%) patients had positive localization on cortical stimulation. In 6 (8.9%) patients white matter stimulation was positive, five of whom had responses at the end of a radical excision. In 3 patients who developed a neurological deficit during tumour removal, white matter stimulation was negative and cessation of the surgery did not result in neurological improvement. Sixteen patients (24.6%) had intraoperative neurological deficits at the time of wound closure, 9 (13.4%) of whom had persistent mild neurological deficits at discharge, while the remaining 7 improved to normal. At a mean follow-up of 40.8 months, only 4 (5.9%) of these 9 patients had persistent neurological deficits. Awake craniotomy for excision of eloquent area gliomas enable accurate mapping of motor and language areas as well as continuous neurological monitoring during tumour removal. Furthermore, positive responses on white matter stimulation indicate close proximity of eloquent cortex and projection fibres. This should alert the surgeon to the possibility of postoperative deficits to change the surgical strategy. Thus the surgeon can resect tumour safely, with the knowledge that he has not damaged

  12. Tumour-induced osteomalacia: a literature review and a case report.

    Science.gov (United States)

    Dadoniene, Jolanta; Miglinas, Marius; Miltiniene, Dalia; Vajauskas, Donatas; Seinin, Dmitrij; Butenas, Petras; Kacergius, Tomas

    2016-01-08

    Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report.

  13. DURABILITY OF ASPHALT CONCRETE MIXTURES USING DOLOMITE AGGREGATES

    Directory of Open Access Journals (Sweden)

    Imad Al-Shalout

    2015-12-01

    Full Text Available This study deals with the durability of asphalt concrete, including the effects of different gradations, compaction temperatures and immersion time on the durability potential of mixtures. The specific objectives of this study are: to investigate the effect of compaction temperature on the mechanical properties of asphalt concrete mixtures; investigate the effect of bitumen content and different aggregate gradations on the durability potential of bituminous mixtures.

  14. Durability of capital goods: taxes and market structure

    Energy Technology Data Exchange (ETDEWEB)

    Raviv, A [Carnegie-Mellon Univ., Pittsburgh; Zemel, E

    1977-04-01

    This paper examines the durability of capital goods produced under different market structures when tax considerations are included. Since investment tax credit and depreciation allowances are realized by the owner of the durable good, the durability of products produced by an industry which sells its output differs from that of an industry which rents. For each of these two commercial forms, both monopolistic and competitive market structure are considered. Potential gains from different forms of regulation are discussed.

  15. The household decision making process in replacement of durable goods

    OpenAIRE

    Marell Molander, Agneta

    1998-01-01

    As durables are essential in many households, the level of ownership is high and, due to the high degree of penetration, a vast proportion of the current sales are replacement purchases. Even though a lot of research attention has been paid to decision making and decision processes many models are oriented towards non-durable goods and although a majority of purchases of many durable goods are replacements, few studies seem to make a distinction between a replacement purchase decision and a d...

  16. Intrahousehold Bargaining and the Demand for Consumer Durables in Brazil

    OpenAIRE

    Polato e Fava, Ana Claudia; Arends-Kuenning, Mary P.

    2013-01-01

    In Brazil, wives do most of the household work. About sixty percent of them also work outside the household, working a total of about 10 hours more per week than men. Because of this unequal distribution of household work, husbands and wives might have different priorities regarding the purchase of durable goods. Although both husbands and wives enjoy entertainment durable goods, wives might have a relative preference for household-production durable goods such as washing machines over entert...

  17. Standardised tumour, node and metastasis reporting of oncology CT scans

    International Nuclear Information System (INIS)

    Gormly, K. L. M.

    2009-01-01

    Full text: The oncology CT report is a vital piece of communication between the radiologist and the treating clinician and often determines patient management. The use of a standardised report that follows the tumour, node and metastasis (TNM) structure makes it easier for the radiologist to include all of the necessary information in an easy-to-read format. Presenting the results under the headings of primary tumour, lymph nodes, metastases, and other findings follows a similar pattern to that used by pathologists and also follows the thought process of the treating clinician. Standardised templates for TNM-based oncology CT reports were introduced into public and private institutions. An audit of 199 reports demonstrated a significant increase in the presence of measurements and conclusions in the template reports. While there was a non-significant increase in the use of correct Response Evaluation Criteria In Solid Tumours terminology for template reports, there was an improved attempt to describe the disease response. Saving measurements as a summary series on PACS also assists follow-up reporting

  18. Giant Cell Tumour of Tendon Sheath Masquerading As Trigger Finger

    Directory of Open Access Journals (Sweden)

    N Rahimawati

    2010-11-01

    Full Text Available We report a case of a 59-year-old female who presented in the general orthopaedic clinic with triggering of her right middle finger. She did not respond to conventional treatment methods; subsequently she underwent surgical open release under local anaesthesia. Five months postoperatively, the patient presented with signs and symptoms of acute flexor tenosynovitis, and was thought to have a postoperative infection. Re-examination by a hand surgeon raised the possibility of a different aetiology. Based on clinical findings and response to initial treatment, giant cell tumour of the flexor tendon sheath was suspected and later confirmed following surgical biopsy. A high index of suspicion and knowledge of the variegated presentations of giant cell tumour in the hand are beneficial in these types of cases.

  19. Interferon treatment of neuroendocrine tumour xenografts as monitored by MRI

    International Nuclear Information System (INIS)

    Elvin, A.; Oeberg, K.; Lindgren, P.G.; Lundkvist, M.; Wilander, E.; Ericsson, A.; Hemmingsson, A.

    1994-01-01

    The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 nude mice (Balb/c). The purpose of the present study was to establish an animal model that would allow monitoring with magnetic resonance imaging (MRI) of changes induced by interferon (IFN) therapy and to evaluate whether the therapeutic response, as expressed by changes in MR signal characteristics and tumour proliferative activity, could be modulated by different IFN dosages. IFN did not seem to have any obvious antiproliferative effect on the LCC-18 tumour cell line transplanted to nude mice and no convincing treatment-related changes in rho values or T1 and T2 relaxation values were observed. The animal model was probably unsuitable for demonstration of IFN effects. (orig.)

  20. MRI of pineal region tumours: relationship between tumours and adjacent structures

    International Nuclear Information System (INIS)

    Satoh, H.; Kurisu, K.

    1995-01-01

    A variety of tumours may arise in the pineal region; accurate diagnosis is important in the selection of treatment and prognosis. A retrospective analysis of the MRI studies of 25 patients with pathologically proven pineal region tumours was performed, focused on the relationship between the tumour and neighbouring structures. Compression of the tectal plate was classified as expansive or invasive, and compression of the corpus callosum as inferior, anterior or posterior. In 10 of the 14 patients (71 %) with germ cell tumours tectal compression was of the invasive type; 8 patients (57 %) had multiple tumours and in 13 (93 %) the tumour margins were irregular. Teratomas were readily diagnosed because of characteristic heterogeneous signal intensity. Pineal cell tumours were differentiated from germ cell tumours by their rounded shape, solid nature, sharp margins, and expansive type of tectal compression. Meningiomas were characterised by their falcotentorial attachments, posterior callosal compression, and a low-intensity rim on T2-weighted images. Gd-DTPA injection enabled clear demonstration of the site and extent of tumour spread and was useful in differentiating cystic and solid components. The appearances described, while not pathognomonic, are helpful in the differential diagnosis of pineal region tumours, and valuable in planning appropriate treatment. (orig.). With 4 figs., 6 tabs

  1. The potential of proton beam radiation therapy in intracranial and ocular tumours

    Energy Technology Data Exchange (ETDEWEB)

    Blomquist, Erik [Univ. Hospital, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology; Bjelkengren, Goeran [Univ. Hospital, Malmoe (Sweden). Dept. of Oncology; Glimelius, Bengt [Karolinska Inst., Stockholm (Sweden). Dept. of Oncology and Pathology; Akademiska sjukhuset, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology

    2005-12-01

    A group of oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In intracranial benign and malignant tumours, it is estimated that between 130 and 180 patients each year are candidates for proton beam therapy. Of these, between 50 and 75 patients have malignant glioma, 30-40 meningeoma, 20-25 arteriovenous malformations, 20-25 skull base tumours and 10-15 pituitary adenoma. In addition, 15 patients with ocular melanoma are candidates.

  2. Phase congruency map driven brain tumour segmentation

    Science.gov (United States)

    Szilágyi, Tünde; Brady, Michael; Berényi, Ervin

    2015-03-01

    Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.

  3. Evaluation of models of waste glass durability

    International Nuclear Information System (INIS)

    Ellison, A.

    1995-01-01

    The main variable under the control of the waste glass producer is the composition of the glass; thus a need exists to establish functional relationships between the composition of a waste glass and measures of processability, product consistency, and durability. Many years of research show that the structure and properties of a glass depend on its composition, so it seems reasonable to assume that there also is relationship between the composition of a waste glass and its resistance to attack by an aqueous solution. Several models have been developed to describe this dependence, and an evaluation their predictive capabilities is the subject of this paper. The objective is to determine whether any of these models describe the ''correct'' functional relationship between composition and corrosion rate. A more thorough treatment of the relationships between glass composition and durability has been presented elsewhere, and the reader is encouraged to consult it for a more detailed discussion. The models examined in this study are the free energy of hydration model, developed at the Savannah River Laboratory, the structural bond strength model, developed at the Vitreous State Laboratory at the Catholic University of America, and the Composition Variation Study, developed at Pacific Northwest Laboratory

  4. Durability of cement and geopolimer composites

    Science.gov (United States)

    Błaszczyński, T.; Król, M.

    2017-10-01

    Concrete structures are constantly moving in the direction of improving the durability. This main feature depends on many factors, which are the composition of concrete mix, the usage of additives and admixtures and the place, where material will work and carry the load. The introduction of new geopolymer binders for geopolymer structures adds a new aspect that is type of used activator. This substance with strongly alkaline reaction is divided because of the physical state, the alkaline degree and above all the chemical composition. Taking into account, that at present the geopolymer binders are made essentially from waste materials or by products from the combustion of coal or iron ore smelting, unambiguous determination of the effect of the activator on the properties of the geopolymer material requires a number of trials, researches and observation. This paper shows the influence of the most alkaline activators on the basic parameters of the durability of geopolymer binders. In this study there were used a highly alkaline hydroxides, water glasses and granules, which are waste materials in a variety of processes taking place in a chemical plants. As the substrate of geopolymer binders there were used fly ash which came from coal and high calcium ash from the burning of lignite.

  5. Durability of composites in a marine environment

    CERN Document Server

    Rajapakse, Yapa

    2014-01-01

    Composites are widely used in marine applications. There is considerable experience of glass reinforced resins in boats and ships but these are usually not highly loaded. However, for new areas such as offshore and ocean energy there is a need for highly loaded structures to survive harsh conditions for 20 years or more. High performance composites are therefore being proposed. This book provides an overview of the state of the art in predicting the long term durability of composite marine structures. The following points are covered: •       Modelling water diffusion •       Damage induced by water •       Accelerated testing •       Including durability in design •       In-service experience. This is essential reading for all those involved with composites in the marine industry, from initial design and calculation through to manufacture and service exploitation. It also provides information unavailable elsewhere on the mechanisms involved in degradation and how to t...

  6. Durability of coconut shell powder (CSP) concrete

    Science.gov (United States)

    Leman, A. S.; Shahidan, S.; Senin, M. S.; Shamsuddin, S. M.; Anak Guntor, N. A.; Zuki, S. S. Mohd; Khalid, F. S.; Azhar, A. T. S.; Razak, N. H. S.

    2017-11-01

    The rising cost of construction in developing countries like Malaysia has led concrete experts to explore alternative materials such as coconut shells which are renewable and possess high potential to be used as construction material. Coconut shell powder in varying percentages of1%, 3% and 5% was used as filler material in concrete grade 30 and evaluated after a curing period of 7 days and 28days respectively. Compressive strength, water absorption and carbonation tests were conducted to evaluate the strength and durability of CSP concrete in comparison with normal concrete. The test results revealed that 1%, 3% and 5% of CSP concrete achieved a compressive strength of 47.65 MPa, 45.6 MPa and 40.55% respectively. The rate of water absorption of CSP concrete was recorded as 3.21%, 2.47%, and 2.73% for 1%, 3% and 5% of CSP concrete respectively. Although CSP contained a carbon composition of 47%, the carbonation test showed that CSP no signs of carbon were detected inside the concrete. To conclude, CSP offers great prospects as it demonstrated relatively high durability as a construction material.

  7. Durability of thin-walled concrete structures

    International Nuclear Information System (INIS)

    Salomon, M.; Gallias, J.L.

    1991-01-01

    The aim of the present document is to draw up a survey of knowledge of the problems of ageing of reinforced concrete shell structure atmospheric coolers. The exposure conditions are particularly favourable to the induction and development of degradation which, because of the thinness of the reinforced concrete can compromise the stability and the durability of coolers. The study will be axed on the link between the specific characteristics of coolers from the point of view of operation, design and environment, also the durability of reinforced concrete. The set of factors exerting their influence on the reinforced concrete of the shell structure (condensates, rain water, temperature and humidity gradients, dynamic loads, weathering, etc.) is particularly complex. The principal degradation reactions involved are classified according to the chemical and physical action on concrete and on the reinforcement. Particular emphasis is placed on the analysis of degradation processes and the influence of the characteristics of the materials and of the medium. The aim is to determine the mechanisms which present the greatest risk for coolers. The interaction between the degradation to concrete and the change in mechanical characteristics is also studied [fr

  8. Durability of high performance concrete in seawater

    International Nuclear Information System (INIS)

    Amjad Hussain Memon; Salihuddin Radin Sumadi; Rabitah Handan

    2000-01-01

    This paper presents a report on the effects of blended cements on the durability of high performance concrete (HPC) in seawater. In this research the effect of seawater was investigated. The specimens were initially subjected to water curing for seven days inside the laboratory at room temperature, followed by seawater curing exposed to tidal zone until testing. In this study three levels of cement replacement (0%, 30% and 70%) were used. The combined use of chemical and mineral admixtures has resulted in a new generation of concrete called HPC. The HPC has been identified as one of the most important advanced materials necessary in the effort to build a nation's infrastructure. HPC opens new opportunities in the utilization of the industrial by-products (mineral admixtures) in the construction industry. As a matter of fact permeability is considered as one of the fundamental properties governing the durability of concrete in the marine environment. Results of this investigation indicated that the oxygen permeability values for the blended cement concretes at the age of one year are reduced by a factor of about 2 as compared to OPC control mix concrete. Therefore both blended cement concretes are expected to withstand in the seawater exposed to tidal zone without serious deterioration. (Author)

  9. Durable and Robust Solid Oxide Fuel Cells

    DEFF Research Database (Denmark)

    Hjalmarsson, Per; Knibbe, Ruth; Hauch, Anne

    project had as one of its’ overarching goals to improve durability and robustness of the Danish solid oxide fuel cells. The project focus was on cells and cell components suitable for SOFC operation in the temperature range 600 – 750 °C. The cells developed and/or studied in this project are intended......The solid oxide fuel cell (SOFC) is an attractive technology for the generation of electricity with high efficiency and low emissions. Risø DTU (now DTU Energy Conversion) works closely together with Topsoe Fuel Cell A/S in their effort to bring competitive SOFC systems to the market. This 2-year...... for use within the CHP (Combined Heat and Power) market segment with stationary power plants in the range 1 – 250 kWe in mind. Lowered operation temperature is considered a good way to improve the stack durability since corrosion of the interconnect plates in a stack is lifetime limiting at T > 750 °C...

  10. Intradermal Immunization of Leishmania donovani Centrin Knock-Out Parasites in Combination with Salivary Protein LJM19 from Sand Fly Vector Induces a Durable Protective Immune Response in Hamsters.

    Directory of Open Access Journals (Sweden)

    Jacqueline Araújo Fiuza

    2016-01-01

    Full Text Available Visceral leishmaniasis (VL is a neglected tropical disease and is fatal if untreated. There is no vaccine available against leishmaniasis. The majority of patients with cutaneous leishmaniasis (CL or VL develop a long-term protective immunity after cure from infection, which indicates that development of an effective vaccine against leishmaniasis is possible. Such protection may also be achieved by immunization with live attenuated parasites that do not cause disease. We have previously reported a protective response in mice, hamsters and dogs with Leishmania donovani centrin gene knock-out parasites (LdCen-/-, a live attenuated parasite with a cell division specific centrin1 gene deletion. In this study we have explored the effects of salivary protein LJM19 as an adjuvant and intradermal (ID route of immunization on the efficacy of LdCen-/- parasites as a vaccine against virulent L. donovani.To explore the potential of a combination of LdCen-/- parasites and salivary protein LJM19 as vaccine antigens, LdCen-/- ID immunization followed by ID challenge with virulent L. donovani were performed in hamsters in a 9-month follow up study. We determined parasite burden (serial dilution, antibody production (ELISA and cytokine expression (qPCR in these animals. Compared to controls, animals immunized with LdCen-/- + LJM19 induced a strong antibody response, a reduction in spleen and liver parasite burden and a higher expression of pro-inflammatory cytokines after immunization and one month post-challenge. Additionally, a low parasite load in lymph nodes, spleen and liver, and a non-inflamed spleen was observed in immunized animals 9 months after the challenge infection.Our results demonstrate that an ID vaccination using LdCen-/-parasites in combination with sand fly salivary protein LJM19 has the capability to confer long lasting protection against visceral leishmaniasis that is comparable to intravenous or intracardial immunization.

  11. MRI appearances of borderline ovarian tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

    2009-04-15

    This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

  12. Radiopharmaceuticals as probes to characterize tumour tissue

    International Nuclear Information System (INIS)

    Alam, Israt S.; Arshad, Mubarik A.; Nguyen, Quang-De; Aboagye, Eric O.

    2015-01-01

    Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal 'Hallmarks of Cancer' review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours. (orig.)

  13. Carcinoid tumour of the middle ear

    LENUS (Irish Health Repository)

    Baig, Salman

    2012-09-01

    A case of middle ear mass in a young female from Ireland is described, who presented with left ear hearing loss and intermittent bloody discharge from the same ear. Examination under microscope revealed occlusive polyp in the left ear and a biopsy had been taken under general anaesthesia. Histopathology report described an adenoma \\/ carcinoid tumour of the middle ear confirmed by positive immunohistochemical staining. CT temporal bones revealed the extension of the disease. The patient underwent left tympanotomy and excision of the tumour. In general, these tumours are regarded as benign but may be mistaken for adenocarcinomas because of their histological heterogenecity.

  14. Evaluation of tumour necrosis during chemotherapy with diffusion-weighted MR imaging: preliminary results in osteosarcomas

    International Nuclear Information System (INIS)

    Uhl, Markus; Saueressig, Ulrich; Bley, Thorsten; Langer, Mathias; Koehler, Gabriele; Kontny, Udo; Niemeyer, Charlotte; Reichardt, Wilfried; Ilyasof, Kamil

    2006-01-01

    During successful chemotherapy of osteosarcomas tumour size does not diminish significantly because the therapy has limited impact on the mineralized matrix of the tumour. Treatment response is considered successful if, histologically, more than 90% of tumour cells show necrosis. To determine if osteosarcomas change their water diffusion during preoperative chemotherapy in relation to the amount of tumour necrosis. Eight patients (age 11-19 years) with histologically proven limb osteosarcoma underwent T1-weighted, fat-suppressed T2-weighted and contrast-enhanced T1-weighted spin-echo imaging together with diffusion-weighted EPI sequences (b = 700) at 1.5 T before and after five cycles of standard chemotherapy. Tumour volume and apparent diffusion coefficient (ADC) maps were calculated before and after chemotherapy. The degree of tumour necrosis after chemotherapy was assessed using the histological Salzer-Kuntschik classification (grades 1-6). During chemotherapy, the ADC values of osteosarcomas changed significantly. The ADC of untreated tumour was 2.1 ± 0.4 x 10 -3 mm 2 /s (mean ± SD) (95% CI 1.6-2.0). The ADC of chemotherapy-treated sarcomas was 2.5 ± 0.4 x 10 -3 mm 2 /s (95% CI 1.8-2.2). Necrotic areas, which were confirmed by macroscopic examination, showed ADC values up to 2.7 x 10 -3 mm 2 /s. Four patients with little viable tumour tissue within the neoplasm (Salzer-Kuntschik grades 1-2) had an increase in ADC of 0.4 up to 0.7 x 10 -3 mm 2 /s. Four patients with larger areas of viable tumour (Salzer-Kuntschik grade 4) showed a lesser increase in ADC of 0.0 up to 0.3 x 10 -3 mm 2 /s. The differences in ADC values in tumour tissue before and after chemotherapy were highly significant (P = 0.01). During chemotherapy of osteosarcomas, tumour ADC changes are related to the degree of tumour necrosis. (orig.)

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

    Science.gov (United States)

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

    2011-12-01

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

  16. First-order model for durability of Hanford waste glasses as a function of composition

    International Nuclear Information System (INIS)

    Hrma, P.; Piepel, G.F.; Schweiger, M.J.; Smith, D.E.

    1992-04-01

    Two standard chemical durability tests, the static leach test MCC-1 and product consistency test PCT, were conducted on simulated borosilicate glasses that encompass the expected range of compositions to be produced in the Hanford Waste Vitrification Plant (HWVP). A first-order empirical model was fitted to the data from each test method. The results indicate that glass durability is increased by addition of Al 2 O 3 , moderately increased by addition of ZrO 2 and SiO 2 , and decreased by addition of Li 2 O, Na 2 O, B 2 O 3 , and MgO. Addition of Fe 2 O 3 and CaO produce an indifferent or reducing effect on durability according to the test method. This behavior and a statistically significant lack of fit are attributed to the effects of multiple chemical reactions occurring during glass-water interaction. Liquid-liquid immiscibility is suspected to be responsible for extremely low durability of some glasses

  17. Hyperthermic treatment at 56 °C induces tumour-specific immune protection in a mouse model of prostate cancer in both prophylactic and therapeutic immunization regimens.

    Science.gov (United States)

    De Sanctis, Francesco; Sandri, Sara; Martini, Matteo; Mazzocco, Marta; Fiore, Alessandra; Trovato, Rosalinda; Garetto, Stefano; Brusa, Davide; Ugel, Stefano; Sartoris, Silvia

    2018-06-14

    Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs. Treatment at 56 °C of tumour cells was shown to induce DAMPs secretion rather than their cell surface expression, improving DC activation and CTL cross priming in vitro. Thus we tested the relevance of this finding in vivo on the generation of a tumour-specific memory immune response, in the TRAMP-C2 mouse prostate carcinoma transplantable model. TRAMP-C2 tumour cells treated at 56 °C were able not only to activate DCs in vitro but also to trigger a tumour-specific CTL-dependent immune response in vivo. Prophylactic vaccination with 56 °C-treated TRAMP-C2 tumour cells alone provided protection against TRAMP-C2 tumour growth in vivo, whilst in the therapeutic regimen, control of tumour growth was achieved combining immunization with adjuvant chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. A forgotten facial nerve tumour: granular cell tumour of the parotid and its implications for treatment.

    Science.gov (United States)

    Lerut, B; Vosbeck, J; Linder, T E

    2011-04-01

    We present a rare case of a facial nerve granular cell tumour in the right parotid gland, in a 10-year-old boy. A parotid or neurogenic tumour was suspected, based on magnetic resonance imaging. Intra-operatively, strong adhesions to surrounding structures were found, and a midfacial nerve branch had to be sacrificed for complete tumour removal. Recent reports verify that granular cell tumours arise from Schwann cells of peripheral nerve branches. The rarity of this tumour within the parotid gland, its origin from peripheral nerves, its sometimes misleading imaging characteristics, and its rare presentation with facial weakness and pain all have considerable implications on the surgical strategy and pre-operative counselling. Fine needle aspiration cytology may confirm the neurogenic origin of this lesion. When resecting the tumour, the surgeon must anticipate strong adherence to the facial nerve and be prepared to graft, or sacrifice, certain branches of this nerve.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-12-01

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

  20. Primitive neuroectodermal tumour of the kidney: radiologic-pathological correlations.

    Science.gov (United States)

    Chea, Y W; Agrawal, Rashi; Poh, Angeline C C

    2008-06-01

    A primitive neuroectodermal tumour of the kidney is a rare malignancy. We report the computed tomographic features and the histopathological correlation of such a tumour occurring in a middle-aged man. Although the radiological appearance has significant overlap with other renal tumours, this tumour should be included in the differential diagnosis of a large renal mass in younger patients.

  1. Testicular tumours in prepubertal children: About eight cases ...

    African Journals Online (AJOL)

    Conclusion: In prepubertal children, most testicular tumours are benign. If tumour markers were negative testis-preserving surgery can be proposed, complete excision of the tumour should be ascertained. In the case of testicular teratoma, the possibility of contralateral tumour should be considered in the follow-up.

  2. Primary malignant bone tumour in a tropical African University ...

    African Journals Online (AJOL)

    Bone tumours are relatively rare tumours as compared with all other tumours. The relative frequency has not been well documented in this environment. The aim of the study was to define the frequency of primary malignant bone tumours in an African University teaching hospital in Ibadan. The medical records of 114 ...

  3. Childhood vascular Tumours in Benin City, Nigeria | Igbe | Annals of ...

    African Journals Online (AJOL)

    Background: Vasoformative tumours are one of the commonest tumours in childhood. The patterns of these tumours in Benin City, however, are not known. Objective: To determine the incidence and morphological patterns of childhood vascular tumours as seen in the Department of Pathology University of Benin Teaching ...

  4. Ovarian yolk sac tumour in a girl - case report.

    Science.gov (United States)

    Sharma, Charu; Shah, Hemanshi; Sisodiya Shenoy, Neha; Makhija, Deepa; Waghmare, Mukta

    2017-01-01

    Yolk sac tumours are rare ovarian malignancies accounting for less than 1% of malignant ovarian germ cell tumours. They are mostly seen in adolescents and young women and are usually unilateral making fertility preservation imperative. Raised alpha-feto protein level is the hallmark of this tumour. We describe stage III yolk sac tumour in a girl child.

  5. Neonatal testicular tumour presenting as an acute scrotum ...

    African Journals Online (AJOL)

    Juvenile granulosa cell tumour (JGCT) is a rare benign stromal cell tumour of the testis accounting for approximately 1% of all paediatric testicular tumours. Presenting primarily as a painless testicular mass, the tumour may be associated with undescended testis, hydrocele or testicular torsion. Abnormal karyotype has also ...

  6. Neonatal testicular tumour presenting as an acute scrotum

    African Journals Online (AJOL)

    Neonatal testicular tumour presenting as an acute scrotum. Joyce M. Muhlschlegel, Alice L. Mears and Rowena J. Hitchcock. Juvenile granulosa cell tumour (JGCT) is a rare benign stromal cell tumour of the testis accounting for approximately 1% of all paediatric testicular tumours. Presenting primarily as a painless ...

  7. Converting dose distributions into tumour control probability

    International Nuclear Information System (INIS)

    Nahum, A.E.

    1996-01-01

    The endpoints in radiotherapy that are truly of relevance are not dose distributions but the probability of local control, sometimes known as the Tumour Control Probability (TCP) and the Probability of Normal Tissue Complications (NTCP). A model for the estimation of TCP based on simple radiobiological considerations is described. It is shown that incorporation of inter-patient heterogeneity into the radiosensitivity parameter a through s a can result in a clinically realistic slope for the dose-response curve. The model is applied to inhomogeneous target dose distributions in order to demonstrate the relationship between dose uniformity and s a . The consequences of varying clonogenic density are also explored. Finally the model is applied to the target-volume DVHs for patients in a clinical trial of conformal pelvic radiotherapy; the effect of dose inhomogeneities on distributions of TCP are shown as well as the potential benefits of customizing the target dose according to normal-tissue DVHs. (author). 37 refs, 9 figs

  8. Converting dose distributions into tumour control probability

    Energy Technology Data Exchange (ETDEWEB)

    Nahum, A E [The Royal Marsden Hospital, London (United Kingdom). Joint Dept. of Physics

    1996-08-01

    The endpoints in radiotherapy that are truly of relevance are not dose distributions but the probability of local control, sometimes known as the Tumour Control Probability (TCP) and the Probability of Normal Tissue Complications (NTCP). A model for the estimation of TCP based on simple radiobiological considerations is described. It is shown that incorporation of inter-patient heterogeneity into the radiosensitivity parameter a through s{sub a} can result in a clinically realistic slope for the dose-response curve. The model is applied to inhomogeneous target dose distributions in order to demonstrate the relationship between dose uniformity and s{sub a}. The consequences of varying clonogenic density are also explored. Finally the model is applied to the target-volume DVHs for patients in a clinical trial of conformal pelvic radiotherapy; the effect of dose inhomogeneities on distributions of TCP are shown as well as the potential benefits of customizing the target dose according to normal-tissue DVHs. (author). 37 refs, 9 figs.

  9. Pancreatic pseudopapillary tumour: A rare misdiagnosed entity.

    Science.gov (United States)

    Affirul, C A; Qisti, F N; Zamri, Z; Azlanuddin, A; Hairol, A O; Razman, J

    2014-01-01

    Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. We discuss the presentations, diagnosis and pathology findings of this rare pathology. The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Simulating tumour removal in neurosurgery.

    Science.gov (United States)

    Radetzky, A; Rudolph, M

    2001-12-01

    In this article the software system ROBO-SIM is described. ROBO-SIM is a planning and simulation tool for minimally invasive neurosurgery. Different to the most other simulation tools, ROBO-SIM is able to use actual patient's datasets for simulation. Same as in real neurosurgery a planning step, which provides more functionality as up-to-date planning systems on the market, is performed before undergoing the simulated operation. The planning steps include the definition of the trepanation point for entry into the skull and the target point within the depth of the brain, checking the surgical track and doing virtual trepanations (virtual craniotomy). For use with an intra-operative active manipulator, which is guided by the surgeon during real surgery (robotic surgery), go- and non-go-areas can be defined. During operation, the robot restricts the surgeon from leaving these go-areas. After planning, an additional simulation system, which is understood as an extension to the planning step, is used to simulate whole surgical interventions directly on the patient's anatomy basing on the planning data and by using the same instruments as for the real intervention. First tests with ROBO-SIM are performed on a phantom developed for this purpose and on actual patient's datasets with ventricular tumours.

  11. Influence Of Density On The Durabilities Of Three Ghanaian Timbers ...

    African Journals Online (AJOL)

    Review of factors influencing wood durability shows although density varies depending on trunk position, its role appears controversial for many timber species. Thus, for the first time, the influence of density on the durability of three Ghanaian timbers (Nauclea diderrichii (de Wild.) Merr., Nesogordonia papaverifera (A. Chev ...

  12. Adhesives for Achieving Durable Bonds with Acetylated Wood

    Science.gov (United States)

    Charles Frihart; Rishawn Brandon; James Beecher; Rebecca Ibach

    2017-01-01

    Acetylation of wood imparts moisture durability, decay resistance, and dimensional stability to wood; however, making durable adhesive bonds with acetylated wood can be more difficult than with unmodified wood. The usual explanation is that the acetylated surface has fewer hydroxyl groups, resulting in a harder-to-wet surface and in fewer hydrogen bonds between wood...

  13. Chemical durability of glasses containing radioactive fission product waste

    International Nuclear Information System (INIS)

    Mendel, J.E.; Ross, W.A.

    1974-04-01

    Measurements made to determine the chemical durability of glasses for disposal of radioactive waste are discussed. The term glass covers materials varying from true glass with only minute quantities of crystallites, such as insoluble RuO 2 , to quasi glass-ceramics which are mostly crystalline. Chemical durability requirements and Soxhlet extractor leach tests are discussed

  14. Effect of Unprofessional Supervision on Durability of Buildings.

    Science.gov (United States)

    Yahaghi, Javad

    2018-02-01

    The durability of buildings which depends on the nature of the supervisory system used in their construction is an important feature of the construction industry. This article tries to draw the readers' attention to the effect of untrained and unprofessional building supervisors and their unethical performance on the durability of buildings.

  15. Pre-Treatment Deep Curettage Can Significantly Reduce Tumour Thickness in Thick Basal Cell Carcinoma While Maintaining a Favourable Cosmetic Outcome When Used in Combination with Topical Photodynamic Therapy

    International Nuclear Information System (INIS)

    Christensen, E.; Mork, C.; Foss, O. A.

    2011-01-01

    Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0-4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage (ρ≤0.001) . Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.

  16. Application of magnetic resonance techniques for imaging tumour physiology

    International Nuclear Information System (INIS)

    Stubbs, M.

    1999-01-01

    Magnetic resonance (MR) techniques have the unique ability to measure in vivo the biochemical content of living tissue in the body in a dynamic, non-invasive and non-destructive manner. MR also permits serial investigations of steady-state tumour physiology and biochemistry, as well as the response of a tumour to treatment. Magnetic resonance imaging (MRI), Magnetic resonance spectroscopy (MRS) and a mixture of the two techniques (spectroscopic imaging) allow some physiological parameters, for example pH, to be 'imaged'. Using these methods, information on tissue bioenergetics and phospolipid membrane turnover, pH, hypoxia, oxygenation, and various aspects of vascularity including blood flow, angiogenesis, permeability and vascular volume can be obtained. In addition, MRS methods can be used for monitoring anticancer drugs (e.g. 5FU, ifosfamide) and their metabolites at their sites of action. The role of these state-of-the-art MR methods in imaging tumour physiology and their potential role in the clinic are discussed. (orig.)

  17. Angiographic appearances of rare renal tumours

    International Nuclear Information System (INIS)

    Schmidt, M.; Taenzer, V.

    1980-01-01

    Oncocytomas, called oxyphil proximal tubular adenomas in the Anglo Saxon literature, and benign hypernephromas are non-malignant, usually symptomless, rare tumours belonging to the renal adenomas. Oncocytomas have angiographic appearances sufficiently uniform to permit a tentative diagnosis. Histologically benign hypernephromas do not possess characteristic angiographic appearances and, in the presence of tumour in the renal vein or necrotic avascular areas, must be regarded as potentially malignant. (orig.) [de

  18. Durable solid oxide electrolysis cells and stacks

    Energy Technology Data Exchange (ETDEWEB)

    Ming Chen

    2010-08-15

    The purpose of this project was to make a substantial contribution to development of a cost competitive electrolysis technology based on solid oxide cells. The strategy was to address what had been identified as the key issues in previous research projects. Accordingly five lines of work were carried out in the here reported project: 1) Cell and stack element testing and post test characterization to identify major degradation mechanisms under electrolysis operation. 2) Development of interconnects and coatings to allow stable electrolysis operation at approx850 deg. C or above. 3) Development of seals with reduced Si emission. 4) Development of durable SOEC cathodes. 5) Modeling. Good progress has been made on several of the planned activities. The outcome and most important achievements of the current project are listed for the five lines of the work. (LN)

  19. Durability of Silicate Glasses: An Historical Approach

    International Nuclear Information System (INIS)

    Farges, Francois; Etcheverry, Marie-Pierre; Haddi, Amine; Trocellier, Patrick; Curti, Enzo; Brown, Gordon E. Jr.

    2007-01-01

    We present a short review of current theories of glass weathering, including glass dissolution, and hydrolysis of nuclear waste glasses, and leaching of historical glasses from an XAFS perspective. The results of various laboratory leaching experiments at different timescales (30 days to 12 years) are compared with results for historical glasses that were weathered by atmospheric gases and soil waters over 500 to 3000 years. Good agreement is found between laboratory experiments and slowly leached historical glasses, with a strong enrichment of metals at the water/gel interface. Depending on the nature of the transition elements originally dissolved in the melt, increasing elemental distributions are expected to increase with time for a given glass durability context

  20. Glass Durability Modeling, Activated Complex Theory (ACT)

    International Nuclear Information System (INIS)

    CAROL, JANTZEN

    2005-01-01

    The most important requirement for high-level waste glass acceptance for disposal in a geological repository is the chemical durability, expressed as a glass dissolution rate. During the early stages of glass dissolution in near static conditions that represent a repository disposal environment, a gel layer resembling a membrane forms on the glass surface through which ions exchange between the glass and the leachant. The hydrated gel layer exhibits acid/base properties which are manifested as the pH dependence of the thickness and nature of the gel layer. The gel layer has been found to age into either clay mineral assemblages or zeolite mineral assemblages. The formation of one phase preferentially over the other has been experimentally related to changes in the pH of the leachant and related to the relative amounts of Al +3 and Fe +3 in a glass. The formation of clay mineral assemblages on the leached glass surface layers ,lower pH and Fe +3 rich glasses, causes the dissolution rate to slow to a long-term steady state rate. The formation of zeolite mineral assemblages ,higher pH and Al +3 rich glasses, on leached glass surface layers causes the dissolution rate to increase and return to the initial high forward rate. The return to the forward dissolution rate is undesirable for long-term performance of glass in a disposal environment. An investigation into the role of glass stoichiometry, in terms of the quasi-crystalline mineral species in a glass, has shown that the chemistry and structure in the parent glass appear to control the activated surface complexes that form in the leached layers, and these mineral complexes ,some Fe +3 rich and some Al +3 rich, play a role in whether or not clays or zeolites are the dominant species formed on the leached glass surface. The chemistry and structure, in terms of Q distributions of the parent glass, are well represented by the atomic ratios of the glass forming components. Thus, glass dissolution modeling using simple

  1. Durability of Silicate Glasses: An Historical Approach

    Energy Technology Data Exchange (ETDEWEB)

    Farges, Francois; /Museum Natl. Hist. Natur. /Stanford U., Geo. Environ. Sci.; Etcheverry, Marie-Pierre; /Marne la Vallee U.; Haddi, Amine; /Marne la Valle U.; Trocellier,; /Saclay; Curti, Enzo; /PSI, Villigen; Brown, Gordon E., Jr.; /SLAC, SSRL

    2007-01-02

    We present a short review of current theories of glass weathering, including glass dissolution, and hydrolysis of nuclear waste glasses, and leaching of historical glasses from an XAFS perspective. The results of various laboratory leaching experiments at different timescales (30 days to 12 years) are compared with results for historical glasses that were weathered by atmospheric gases and soil waters over 500 to 3000 years. Good agreement is found between laboratory experiments and slowly leached historical glasses, with a strong enrichment of metals at the water/gel interface. Depending on the nature of the transition elements originally dissolved in the melt, increasing elemental distributions are expected to increase with time for a given glass durability context.

  2. Lightweight, durable lead-acid batteries

    Science.gov (United States)

    Lara-Curzio, Edgar; An, Ke; Kiggans, Jr., James O; Dudney, Nancy J; Contescu, Cristian I; Baker, Frederick S; Armstrong, Beth L

    2013-05-21

    A lightweight, durable lead-acid battery is disclosed. Alternative electrode materials and configurations are used to reduce weight, to increase material utilization and to extend service life. The electrode can include a current collector having a buffer layer in contact with the current collector and an electrochemically active material in contact with the buffer layer. In one form, the buffer layer includes a carbide, and the current collector includes carbon fibers having the buffer layer. The buffer layer can include a carbide and/or a noble metal selected from of gold, silver, tantalum, platinum, palladium and rhodium. When the electrode is to be used in a lead-acid battery, the electrochemically active material is selected from metallic lead (for a negative electrode) or lead peroxide (for a positive electrode).

  3. Durable bistable auxetics made of rigid solids

    Science.gov (United States)

    Shang, Xiao; Liu, Lu; Rafsanjani, Ahmad; Pasini, Damiano

    2018-02-01

    Bistable Auxetic Metamaterials (BAMs) are a class of monolithic perforated periodic structures with negative Poisson's ratio. Under tension, a BAM can expand and reach a second state of equilibrium through a globally large shape transformation that is ensured by the flexibility of its elastomeric base material. However, if made from a rigid polymer, or metal, BAM ceases to function due to the inevitable rupture of its ligaments. The goal of this work is to extend the unique functionality of the original kirigami architecture of BAM to a rigid solid base material. We use experiments and numerical simulations to assess performance, bistability and durability of rigid BAMs at 10,000 cycles. Geometric maps are presented to elucidate the role of the main descriptors of BAM architecture. The proposed design enables the realization of BAM from a large palette of materials, including elastic-perfectly plastic materials and potentially brittle materials.

  4. Durable fiber reinforced self-compacting concrete

    International Nuclear Information System (INIS)

    Corinaldesi, V.; Moriconi, G.

    2004-01-01

    In order to produce thin precast elements, a self-compacting concrete was prepared. When manufacturing these elements, homogenously dispersed steel fibers instead of ordinary steel-reinforcing mesh were added to the concrete mixture at a dosage of 10% by mass of cement. An adequate concrete strength class was achieved with a water to cement ratio of 0.40. Compression and flexure tests were carried out to assess the safety of these thin concrete elements. Moreover, serviceability aspects were taken into consideration. Firstly, drying shrinkage tests were carried out in order to evaluate the contribution of steel fibers in counteracting the high concrete strains due to a low aggregate-cement ratio. Secondly, the resistance to freezing and thawing cycles was investigated on concrete specimens in some cases superficially treated with a hydrophobic agent. Lastly, both carbonation and chloride penetration tests were carried out to assess durability behavior of this concrete mixture

  5. Sustainability and durability analysis of reinforced concrete structures

    Science.gov (United States)

    Horáková, A.; Broukalová, I.; Kohoutková, A.; Vašková, J.

    2017-09-01

    The article describes an assessment of reinforced concrete structures in terms of durability and sustainable development. There is a short summary of findings from the literature on evaluation methods for environmental impacts and also about corrosive influences acting on the reinforced concrete structure, about factors influencing the durability of these structures and mathematical models describing the corrosion impacts. Variant design of reinforced concrete structure and assessment of these variants in terms of durability and sustainability was performed. The analysed structure was a concrete ceiling structure of a parking house for cars. The variants differ in strength class of concrete and thickness of concrete slab. It was found that in terms of durability and sustainable development it is significantly preferable to use higher class of concrete. There are significant differences in results of concrete structures durability for different mathematical models of corrosive influences.

  6. Aqp 9 and Brain Tumour Stem Cells

    Directory of Open Access Journals (Sweden)

    Guri Fossdal

    2012-01-01

    Full Text Available Several studies have implicated the aquaporins (aqp 1, 4, and 9 in the pathogenesis of malignant brain tumours, suggesting that they contribute to motility, invasiveness, and oedema formation and facilitate metabolism in tumour cells under hypoxic conditions. We have studied the expression of aqp1, 4, and 9 in biopsies from glioblastomas, isolated tumour stem cells grown in a tumoursphere assay and analyzed the progenitor and differentiated cells from these cultures. We have compared these to the situation in normal rat brain, its stem cells, and differentiated cells derived thereof. In short, qPCR in tumour tissue showed presence of aqp1, 4, and 9. In the tumour progenitor population, aqp9 was markedly more highly expressed, whilst in tumour-derived differentiated cells, aqp4 was downregulated. However, immunostaining did not reveal increased protein expression of aqp9 in the tumourspheres containing progenitor cells; in contrast, its expression (both mRNA and protein was high in differentiated cultures. We, therefore, propose that aquaporin 9 may have a central role in the tumorigenesis of glioblastoma.

  7. Cytotoxic effects of radiation and docetaxel in human tumour cells

    International Nuclear Information System (INIS)

    Dunne, A.L.

    2000-12-01

    Data from both single institutions and from randomised multicentre trials have demonstrated that the combination of chemotherapy with radiotherapy can increase the survival of cancer patients. Treatment regimens consisting of taxanes (paclitaxel and docetaxel), a potent class of new chemotherapeutic agents, combined with radiotherapy have recently undergone preclincal investigation. Overall, these studies show that taxanes can enhance the radiation sensitivity of tumour cells. However, data on docetaxel is very limited and the mechanism of radiosensitisation by docetaxel remains largely unknown. The chief purpose of this thesis was to investigate the ability of docetaxel to radiosensitise human tumour cells and investigate potential mechanisms for radiosensitisation. The results reported here for docetaxel indicate that for the cell fines examined this drug does have a synergistic effect and is thus a radiosensitising agent. The degree of radiosensitisation seen seems to be largely dependent on drug concentration. A mechanism involving docetaxel potentiation of radiation-induced apoptosis is also suggested. The second purpose of this thesis is to investigate the potential usefulness of an apoptosis assay and the comet assay as biological indicators for cellular radiosensitivity. Many scientists and clinicans have highlighted the need for development of new rapid, predictive assays of radiation responses. If the radiosensitivity of tumours could be predicted, it may eventually allow the individualisation of patient treatment by radiotherapy. In summary, initial DNA damage measured using the comet assay was successful in predicting the radiosensitivity of colorectal tumour cells. The results suggest that the comet assay appears more suitable than the detection of apoptosis for the prediction of radiosensitivity. We conclude that the results obtained from this thesis will contribute to the current attempts to improve the radiotherapeutic management of cancer. (author)

  8. Quantify and improve PEM fuel cell durability. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Grahl-Madsen, L.; Odgaard, M.; Munksgaard Nielsen, R. (IRD Fuel Cell A/S, Svendborg (Denmark)); Li, Q.; Jensen, Jens Oluf (Technical Univ. of Denmark, Dept. of Chemistry, Kgs. Lyngby (Denmark)); Andersen, Shuang Ma; Speder, J.; Skou, E. (Syddansk Univ. (SDU), Odense (Denmark))

    2010-07-01

    The aim of the present project is to systematically quantify and improve the durability of the PEM FC including the following three PEM FC variants: LT PEM FC, DMFC, and HT PEM FC. Different factors influencing dissolution properties of noble metal catalyst platinum and platinum-ruthenium alloy has been studied. The dissolution was found to increase by increasing the CV cycle upper potential limit, number of potential cycles, solution acidity, oxygen partial pressure, involvement of chloride, and temperature. Ruthenium was found to deteriorate ten (10) times faster than platinum catalyst; and carbon supported catalyst (Pt: 20%, Ru: up to 100%) deteriorate ten (10) times faster than non-supported catalyst (Pt: 2%, Ru: 30%) at the same condition. Loss of sulphonic acid groups and fluoride from perfluorinated sulfonic acid membrane was confirmed by different techniques, which locally leads to loss of acidity, and consequently enhances dissolution of noble metal catalyst. Degradation of Nafion ionomer in the electrode was enhanced by noble metal catalyst and the thermal decomposition properties has synergetic effect with carbon degradation. Hydrophobicity of GDL and electrode on GDL were found to degrade e.g. radical attack, oxidation, and physical wear out. The very top micro surface structure turned out to be responsible for wetting property after chemical ageing. Optimal catalyst and ionomer ratio is also reflected in contact angle value, which can be understood in terms of catalyst/carbon - ionomer affinity and layered structure. Long-term tested and 'virgin' LT PEM MEAs have been characterised with respect to SEM, TEM, EDS, and XRD. Both failed and well-functioning MEAs have been characterised. The Post Mortem analysis has shown and quantified degradation mechanisms like catalyst growth and carbon corrosion. Furthermore, the effect of fuel starvation was shown by pronounced Ru-catalyst band within the membrane. The catalyst coarsening observed after

  9. Durability of an inorganic polymer concrete coating

    Science.gov (United States)

    Wasserman, Kenneth

    The objective of the research program reported in this thesis is to evaluate the durability of an inorganic polymer composite coating exposed to freeze/thaw cycling and wet-dry cycling. Freeze/thaw cycling is performed following ASTM D6944-09 Standard Practice for Resistance of Cured Coatings to Thermal Cycling and wet/dry cycling is performed following guidelines set forth in a thesis written by Ronald Garon at Rutgers University. For both sets of experiments, four coating mixture proportions were evaluated. The variables were: silica/alumina ratio, mixing protocol using high shear and normal shear mixing, curing temperatures of 70 and 120 degrees Fahrenheit and use of nano size constituent materials. The mix with highest silica/alumina ratio was designated as Mix 1 and mixes with lower ratios were designated as Mix 2 and Mix 3. Mix 4 had nano silica particles. Four prisms were used for each variable including control that had no coating. The performance of the coating was evaluated using adhesion strength measured using: ASTM D7234 Test Method for Pull-Off Strength of Coatings on Concrete Using Portable Adhesion Testers. Tests were performed after every five consecutive cycles of thermal conditioning and six consecutive cycles of wet-dry exposure. Results from the thermal cycling and wet-dry testing demonstrate that all coating formulations are durable. The minimum adhesion strength was 300 psi even though a relatively weak base concrete surface was chosen for the study. The weak surface was chosen to simulate aged concrete surfaces present in actual field conditions. Due to the inherent nature of the test procedure the variation in test results is high. However, based on the test results, high shear mixer and high temperature curing are not recommended. As expected nano size constituent materials provide better performance.

  10. Perfusion imaging of parotid gland tumours: usefulness of arterial spin labeling for differentiating Warthin's tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki; Watanabe, Haruo [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Gifu University Hospital, High-level Imaging Diagnosis Center, Gifu (Japan); Kajita, Kimihiro [Gifu University Hospital, High-level Imaging Diagnosis Center, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan); Okuaki, Tomoyuki [Philips Healthcare, Tokyo (Japan)

    2015-11-15

    To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours. We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies. SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p <.01) and malignant tumours (p <.01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p <.01) and malignant tumours (p <.05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7 %, 94.7 %, and 93.5 %, respectively. ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours. (orig.)

  11. Residual DNA double strand breaks in perfused but not in unperfused areas determine different radiosensitivity of tumours

    International Nuclear Information System (INIS)

    Menegakis, Apostolos; Eicheler, Wolfgang; Yaromina, Ala; Thames, Howard D.; Krause, Mechthild; Baumann, Michael

    2011-01-01

    Purpose: Micromilieu-dependent quantification of γH2AX after irradiation in vivo and correlation with local tumour control. Materials and methods: Local tumour control was evaluated after irradiation of FaDu and SKX xenografts with ambient single doses. γH2AX foci were quantified in perfused and unperfused regions after different irradiation doses and at different time points. Results: The TCD 50 of FaDu was 2-times higher compared to SKX (28.0 Gy [95% C.I. 24.6; 31.3 Gy] for FaDu; 14.9 Gy [10.9; 18.9] for SKX, p < 0.001). The induction of foci did not differ between the tumour models. Residual foci were twice higher in perfused SKX regions compared to FaDu, no difference was observed in the non-perfused region between both tumour models. The number of residual foci increased with a 2-times higher slope in perfused SKX-regions compared to FaDu, while no difference was detected in unperfused regions. Already within the perfused regions, this slope decreased with distance from perfused vessels. Conclusion: The dose-response of residual γH2AX foci is highly dependent on tumour cell oxygenation in well perfused areas. This dependence decreases further away from tumour vessels. Only γH2AX evaluation in perfused tumour areas can distinguish between the different radiocurability of the two tumour models.

  12. 75 FR 51245 - Agency Information Collection Activities; Proposed Collection; Comment Request; Durable Nursery...

    Science.gov (United States)

    2010-08-19

    ... CONSUMER PRODUCT SAFETY COMMISSION [Docket No. CPSC-2010-0088] Agency Information Collection Activities; Proposed Collection; Comment Request; Durable Nursery Products Exposure Survey AGENCY: Consumer... efforts on durable infant and toddler products. The draft Durable Nursery Products Exposure Survey...

  13. Primary pleuro-pulmonary malignant germ cell tumours.

    Directory of Open Access Journals (Sweden)

    Vaideeswar P

    2002-01-01

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

  14. Combined treatment of the immunoconjugate bivatuzumab mertansine and fractionated irradiation improves local tumour control in vivo

    International Nuclear Information System (INIS)

    Gurtner, Kristin; Hessel, Franziska; Eicheler, Wolfgang; Dörfler, Annegret; Zips, Daniel; Heider, Karl-Heinz; Krause, Mechthild; Baumann, Michael

    2012-01-01

    Background and purpose: To test whether BIWI 1 (bivatuzumab mertansine), an immunoconjugate of the humanized anti-CD44v6 monoclonal antibody BIWA 4 and the maytansinoid DM1, given simultaneously to fractionated irradiation improves local tumour control in vivo compared with irradiation alone. Material and methods: For growth delay, FaDu tumours were treated with 5 intravenous injections (daily) of phosphate buffered saline (PBS, control), BIWA 4 (monoclonal antibody against CD44v6) or BIWI 1 (bivatuzumab mertansine) at two different dose levels (50 μg/kg DM1 and 100 μg/kg DM1). For local tumour control, FaDu tumours received fractionated irradiation (5f/5d) with simultaneous PBS, BIWA 4 or BIWI 1 (two dose levels). Results: BIWI 1 significantly improved local tumour control after irradiation with 5 fractions already in the lower concentration. The dose modifying factor of 1.9 is substantial compared to the majority of other modifiers of radiation response. Conclusion: Because of the magnitude of the curative effect, this approach is highly promising and should be further evaluated using similar combinations with improved tumour-specificity.

  15. A multi-scale investigation of the mechanical behavior of durable sisal fiber cement composites

    OpenAIRE

    Silva, Flávio de Andrade; Toledo Filho, Romildo D.; Mobasher, Barzin; Chawla, Nikhilesh

    2010-01-01

    Durable sisal fiber cement composites reinforced with long unidirectional aligned fibers were developed and their mechanical behavior was characterized in a multi-scale level. Tensile tests were performed in individual sisal fibers. Weibull statistics were used to quantify the degree of variability in fiber strength at different gage lengths. The fiber-matrix pull-out behavior was evaluated at several curing ages and embedded lengths. The composite's mechanical response was measured under dir...

  16. Effects of rate-of-return regulation on the intensity of use and durability of capital

    Energy Technology Data Exchange (ETDEWEB)

    Epple, D [Carnegie-Mellon Univ., Pittsburgh, PA; Zelenitz, A

    1979-10-01

    It has been suggested that rate-of-return regulation reduces the incentives for technically efficient management, because regulation eliminates much of the gain firms might normally expect to realize from such efficiency. Rather than relying upon notions of managerial slack or X-inefficiency, this paper demonstrates that under-utilization of existing capital and a suboptimal choice of the capital stock's durability can be explained as rational profit-maximizing responses to the regulatory incentives. 11 references.

  17. High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours

    International Nuclear Information System (INIS)

    Jalali, Rakesh; Budrukkar, Ashwini; Sarin, Rajiv; Sharma, Dayananda S.

    2005-01-01

    Background and purpose: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. Materials and methods: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV + 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. Results: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. Conclusion: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data

  18. EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours.

    Science.gov (United States)

    Toosi, Behzad M; El Zawily, Amr; Truitt, Luke; Shannon, Matthew; Allonby, Odette; Babu, Mohan; DeCoteau, John; Mousseau, Darrell; Ali, Mohsin; Freywald, Tanya; Gall, Amanda; Vizeacoumar, Frederick S; Kirzinger, Morgan W; Geyer, C Ronald; Anderson, Deborah H; Kim, TaeHyung; Welm, Alana L; Siegel, Peter; Vizeacoumar, Franco J; Kusalik, Anthony; Freywald, Andrew

    2018-04-27

    Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, and do not overexpress the HER2 receptor represent the most aggressive breast cancer subtype, which is characterised by the resistance to therapy in frequently relapsing tumours and a high rate of patient mortality. This is likely due to the resistance of slowly proliferating tumour-initiating cells (TICs), and understanding molecular mechanisms that control TICs behaviour is crucial for the development of effective therapeutic approaches. Here, we present our novel findings, indicating that an intrinsically catalytically inactive member of the Eph group of receptor tyrosine kinases, EPHB6, partially suppresses the epithelial-mesenchymal transition in TNBC cells, while also promoting expansion of TICs. Our work reveals that EPHB6 interacts with the GRB2 adapter protein and that its effect on enhancing cell proliferation is mediated by the activation of the RAS-ERK pathway, which allows it to elevate the expression of the TIC-related transcription factor, OCT4. Consistent with this, suppression of either ERK or OCT4 activities blocks EPHB6-induced pro-proliferative responses. In line with its ability to trigger propagation of TICs, EPHB6 accelerates tumour growth, potentiates tumour initiation and increases TIC populations in xenograft models of TNBC. Remarkably, EPHB6 also suppresses tumour drug resistance to DNA-damaging therapy, probably by forcing TICs into a more proliferative, drug-sensitive state. In agreement, patients with higher EPHB6 expression in their tumours have a better chance for recurrence-free survival. These observations describe an entirely new mechanism that governs TNBC and suggest that it may be beneficial to enhance EPHB6 action concurrent with applying a conventional DNA-damaging treatment, as it would decrease drug resistance and improve tumour elimination.

  19. Assessment of lymph node tumour from CT scans: how good is diameter and visual assessment

    International Nuclear Information System (INIS)

    Kumar, Pratik; Rehani, M.M.; Anand, Vikram; Raina, Vinod; Rao, Keshava

    1995-01-01

    The evaluation response of tumours requires quantification of tumour mass in terms of volume or maximum diameter. In normal practice changes in maximum diameter of tumour are assessed visually on follow-up CT films. This may lead to erroneous results. Twenty one patients of testicular cancer in stage II A to II D with retroperitoneal lymphadenopathy were scanned by CT for 3 to 5 times during the course of treatment. Tumour size was assessed in terms of diameter as per practice followed routinely. A very important observation was that actual measurement of diameter instead of visual assessment resulted in change of stage of cancer in 42.8% (9 out of 21) cases. Moreover, in 6 out of these 21 cases (28%) there occurred a change in stage from II C to II D which assumes significance due to change in treatment protocol from BEP (Bleomycin, Etoposide, Cisplatinum) to BOP-VIP (Bleomycin, Vincristin, Cisplatinum , VP-16, Ifosfamide, Cisplatinum). Tumour volume estimated on the basis of visual method differed considerably from the calculated one. In 16 out of 21 scans, the difference was between 6.4% to 42.9%. The acceptable difference of 5% was seen only in 4 out of 21 cases indicating the importance of volume measurement. The method of volume estimation was validated and found to be within ± 5% of actual volume. The correlation between diameter and volume shows that tumours with similar range of diameter have 20% to 100% more volume. Many times increase in diameter was found associated with actually reduced tumour volume, difference being as much as 515%. This has not been documented earlier in clinical situations. Thus, the study underscores the role of measuring the diameter of tumour for staging and highlights the need for actual volume estimation rather than depending on maximum transverse diameter alone in follow-up studies. (author). 9 refs., 4 figs., 4 tabs

  20. EVALUATION OF BRAIN TUMOURS USING COMPUTED TOMOGRAPHY

    Directory of Open Access Journals (Sweden)

    B. Vinod Kumar

    2016-07-01

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

  1. Resistance to treatment in gastrointestinal stromal tumours: What radiologists should know

    International Nuclear Information System (INIS)

    Tirumani, S.H.; Jagannathan, J.P.; Hornick, J.L.; Ramaiya, N.H.

    2013-01-01

    Gastrointestinal stromal tumour resistance to treatment with imatinib occurs due to pre-existing or acquired mutations. Computed tomography and positron-emission tomography play an essential role in prompt recognition of resistance to treatment. Primary resistance to treatment, which is encountered in the first 6 months of treatment, is associated with specific mutations. Imaging of these tumours shows no anatomical or metabolic response to treatment. Secondary resistance to treatment, which develops after an initial response, is associated with a variety of mutations acquired after the start of treatment. Imaging findings of secondary resistance are of disease progression

  2. Synchronous and Metachronous Malignant Tumours expect the un-expected

    International Nuclear Information System (INIS)

    Mehdi, I.; Shah, A.H.; Moona, M.S.; Verma, K.; Abussa, A.; Elramih, R.; El-Hashmi, H.

    2010-01-01

    Objective: To evaluate occurrence of synchronous and metachronous malignant tumours, to find tumour types, age group, and relationship to treatment received. Methods: Previously diagnosed first primary tumour cases experiencing a synchronous or metachronous tumour, seen at AOI from February 2003 to August 2009 (78 months) were included. The cases were analyzed for morphology/histology of first primary tumour, age and gender of patient, treatment received for first tumour, time interval between the first and second primary tumour, morphology/histology of second tumour, and the treatment conferred for second tumour. Results: The second synchronous and metachronous tumours were 46/4025 (1.14%), in 18 males and 28 females (M:F 1:1.6). The age range was 16-75 years (median 43 years). The follow up time was 24-150 months. The time to second primary tumour was 2-132 months. The first primary tumours were breast, ovary, GIT and urinary bladder. The patients received surgery, radiotherapy, chemotherapy, and hormonal therapy alone or as multi-modality treatment for the first tumours. The frequent second tumours were breast, ovary and Gastro Intestinal tumours. Conclusion: It is imperative that patients with a primary malignant tumour should be thoroughly, closely, and regularly followed. Genetic counseling, risk estimation, cancer screening and hemo prevention must be emphasized. Every subsequent occurring tumour should be biopsied. The effect of first tumour on the second or vice versa are still not fully understood and need exploration. The second primary tumour is usually more aggressive, treatment resistant, and metastasizes early requiring a more aggressive treatment strategy. (author)

  3. Tumours and tumour-like conditions of the jaw seen in Zaria, Nigeria ...

    African Journals Online (AJOL)

    %) ameloblastomas; 33 (23.4%) fibrous dysplasia; 31 (22.0%) cemento-osseous dysplasia; 9 (6.4%) myxomas; 8 (5.7%) ameloblastic fibroma; and 3 (2.1%) adenomatoid odontogenic tumours; and 9 (6.4%) unclassified tumours. The benign ...

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

    NARCIS (Netherlands)

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

    1991-01-01

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

  5. Tumour resistance to cisplatin: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I; Doorn, T van

    2005-01-01

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

  6. Tumour resistance to cisplatin: a modelling approach

    Energy Technology Data Exchange (ETDEWEB)

    Marcu, L [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Bezak, E [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Olver, I [Faculty of Medicine, University of Adelaide, North Terrace, SA 5000 (Australia); Doorn, T van [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia)

    2005-01-07

    Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

  7. Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours.

    Science.gov (United States)

    Buhles, Alexandra; Collins, Sara A; van Pijkeren, Jan P; Rajendran, Simon; Miles, Michelle; O'Sullivan, Gerald C; O'Hanlon, Deirdre M; Tangney, Mark

    2009-03-09

    The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate

  8. Towards a durability test for washing-machines.

    Science.gov (United States)

    Stamminger, Rainer; Tecchio, Paolo; Ardente, Fulvio; Mathieux, Fabrice; Niestrath, Phoebe

    2018-04-01

    Durability plays a key role in enhancing resource conservation and contributing to waste minimization. The washing-machine product group represents a relevant case study for the development of a durability test and as a potential trigger to systematically address durability in the design of products. We developed a procedure to test the durability performance of washing-machines as a main objective of this research. The research method consisted of an analysis of available durability standards and procedures to test products and components, followed by an analysis of relevant references related to frequent failures. Finally, we defined the criteria and the conditions for a repeatable, relatively fast and relevant endurance test. The durability test considered the whole product tested under conditions of stress. A series of spinning cycles with fixed imbalanced loads was run on two washing-machines to observe failures and performance changes during the test. Even though no hard failures occurred, results clearly showed that not all washing-machines can sustain such a test without abrasion or performance deterioration. However, the attempt to reproduce the stress induced on a washing-machine by carrying out a high number of pure spinning cycles with fixed loads did not allow equal testing conditions: the actions of the control procedure regarding imbalanced loads differ from machine to machine. The outcomes of this research can be used as grounds to develop standardised durability tests and to, hence, contribute to the development of future product policy measures.

  9. The development of the Canberra symptom scorecard: a tool to monitor the physical symptoms of patients with advanced tumours

    International Nuclear Information System (INIS)

    Barresi, Margherita J; Shadbolt, Bruce; Byrne, Don; Stuart-Harris, Robin

    2003-01-01

    Patients with a