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Sample records for effective tumor surveillance

  1. Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers

    International Nuclear Information System (INIS)

    Reizenstein, P.; Ogier, C.; Blomgren, H.; Petrini, B.; Wasserman, J.

    1985-01-01

    Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). 154 references

  2. Effects of Focal vs Total Cryotherapy and Minimum Tumor Temperature on Patient-reported Quality of Life Compared With Active Surveillance in Patients With Prostate Cancer.

    Science.gov (United States)

    Werneburg, Glenn T; Kongnyuy, Michael; Halpern, Daniel M; Salcedo, Jose M; Chen, Connie; LeSueur, Amanda; Kosinski, Kaitlin E; Schiff, Jeffrey T; Corcoran, Anthony T; Katz, Aaron E

    2018-03-01

    To investigate the effects of focal (hemiablation) or total cryotherapy and minimum tumor temperature on patient-reported quality of life (QoL) in patients with prostate cancer. An Institutional Review Board-approved database was reviewed for patients who underwent cryotherapy or active surveillance (AS). QoL questionnaire responses were collected and scores were analyzed for differences between focal and total cryotherapy and between very cold (total of 197 patients responded to a total of 547 questionnaires. Focal and total cryotherapy patients had initially lower sexual function scores relative to AS (year 1 mean difference focal: -31.7, P total: -48.1, P total cryotherapy sexual function scores were not statistically significantly different from the AS cohort by postprocedural year 4. Very cold and moderate-cold temperatures led to initially lower sexual function scores relative to AS (year 1 very cold: -38.1, P total cryotherapy and between very cold and moderate-cold temperature groups. Focal cryotherapy and moderate-cold (≥-76°C) temperature were associated with favorable sexual function relative to total cryotherapy and very cold temperature, respectively. No significant differences in urinary function or bowel habits were observed between groups. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Complement Receptor 3 Has Negative Impact on Tumor Surveillance through Suppression of Natural Killer Cell Function

    Directory of Open Access Journals (Sweden)

    Cheng-Fei Liu

    2017-11-01

    Full Text Available Complement receptor 3 (CR3 is expressed abundantly on natural killer (NK cells; however, whether it plays roles in NK cell-dependent tumor surveillance is largely unknown. Here, we show that CR3 is an important negative regulator of NK cell function, which has negative impact on tumor surveillance. Mice deficient in CR3 (CD11b−/− mice exhibited a more activated NK phenotype and had enhanced NK-dependent tumor killing. In a B16-luc melanoma-induced lung tumor growth and metastasis model, mice deficient in CR3 had reduced tumor growth and metastases, compared with WT mice. In addition, adaptive transfer of NK cells lacking CR3 (into NK-deficient mice mediated more efficient suppression of tumor growth and metastases, compared with the transfer of CR3 sufficient NK cells, suggesting that CR3 can impair tumor surveillance through suppression of NK cell function. In vitro analyses showed that engagement of CR3 with iC3b (classical CR3 ligand on NK cells negatively regulated NK cell activity and effector functions (i.e. direct tumor cell killing, antibody-dependent NK-mediated tumor killing. Cell signaling analyses showed that iC3b stimulation caused activation of Src homology 2 domain-containing inositol-5-phosphatase-1 (SHIP-1 and JNK, and suppression of ERK in NK cells, supporting that iC3b mediates negative regulation of NK cell function through its effects on SHIP-1, JNK, and ERK signal transduction pathways. Thus, our findings demonstrate a previously unknown role for CR3 in dysregulation of NK-dependent tumor surveillance and suggest that the iC3b/CR3 signaling is a critical negative regulator of NK cell function and may represent a new target for preserving NK cell function in cancer patients and improving NK cell-based therapy.

  4. Aberrant paramagnetic signals outside the tumor volume on routine surveillance MRI of brain tumor patients.

    Science.gov (United States)

    Yust-Katz, Shlomit; Inbar, Edna; Michaeli, Natalia; Limon, Dror; Siegal, Tali

    2017-09-01

    Late complications of cerebral radiation therapy (RT) involve vascular injury with acquired cavernous malformation, telangiectasias and damage to vascular walls which are well recognized in children. Its incidence in adults is unknown. Blood products and iron deposition that accompany vascular injury create paramagnetic effects on MRI. This study retrospectively investigated the frequency of paramagnetic lesions on routine surveillance MRI of adult brain tumor patients. MRI studies of 115 brain tumor patients were reviewed. Only studies containing sequences of either susceptibility weighted images or gradient echo or blood oxygenation level dependent imaging were included. Lesions inside the tumor volume were not considered. 68 studies fulfilled the above criteria and included 48 patients with previous RT (35 followed for >2 years and 13 for 1 year) and 20 patients who were not treated with RT. The median age at time of irradiation was 47 years. Aberrant paramagnetic lesions were found in 23/35 (65%) patients followed for >2 years after RT and in only 1/13 (8%) patients followed for 1-year after radiation (p = 0.03). The 1-year follow-up group did not differ from the control group [2/20 (9%)]. Most lesions were within the radiation field and none of the patients had related symptomatology. The number and incidence of these lesions increased with time and amounted to 75% over 3 years post RT. MRI paramagnetic signal aberrations are common findings in adult brain tumor patients that evolve over time after RT. The clinical significance of these lesions needs further investigation.

  5. Health effects and medical surveillance

    International Nuclear Information System (INIS)

    1998-01-01

    Source of ionizing radiations have innumerable applications in the work place. Usually, even where the work is performed safely, the employees involved inevitably receive small, regular exposures to radiation that are not manifestly harmful. This Module explains how ionizing radiations can interact with and affect human tissues, the various factors that influence the outcome and the detrimental effects that may result. The medical surveillance that is appropriate for those working with radiation sources, depending on the degree of hazard of the work, is described. The Manual will be of most benefit it if forms part of more comprehensive training or is supplemented by the advice of a medically qualified expert. Where medical surveillance is appropriate for radiation employees, the services of a qualified doctor, occupational physician or other trained medical staff will be required

  6. Health effects and medical surveillance

    International Nuclear Information System (INIS)

    2004-01-01

    This Practical Radiation Technical Manual is one of a series which has been designed to provide guidance on radiological protection for employers, Radiation Protection Officers, managers and other technically competent persons who have a responsibility to ensure the safety of employees working with ionizing radiation. The Manual may be used with the appropriate IAEA Practical Radiation Safety Manuals to provide adequate training, instruction or information on health effects and medical surveillance for all employees engaged in work with ionizing radiation. Sources of ionizing radiations have a large number of applications in the workplace. Usually, even where the work is performed safely, the employees involved inevitably receive small, regular exposures to radiation that are not harmful. Some applications involve sources that could deliver more significant radiation doses, particularly when poor methods are practised or an accident occurs. The radiations cannot be seen, felt or sensed by the human body in any way and excessive exposures may cause detriment to the health of a worker in a way that is not immediately apparent. When the symptoms occur, weeks or possibly years later, an untrained worker or inexperienced medical staff probably cannot recognize the effects to be due to the radiation exposure. This Manual explains how ionizing radiations can interact with and affect human tissues, the various factors that influence the outcome and the detrimental effects that may result. The medical surveillance that is appropriate for those working with radiation sources, depending on the degree of hazard of the work, is described. The Manual will be of most benefit if it forms part of more comprehensive training or is supplemented by the advice of a medically qualified expert. Where medical surveillance is appropriate for radiation employees, the services of a qualified doctor, occupational physician or other trained medical staff will be required

  7. Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors.

    Science.gov (United States)

    Cheung, Victoria; Segal, Devorah; Gardner, Sharon L; Zagzag, David; Wisoff, Jeffrey H; Allen, Jeffrey C; Karajannis, Matthias A

    2016-09-01

    Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.

  8. Cost effectiveness of surveillance for GI cancers.

    Science.gov (United States)

    Omidvari, Amir-Houshang; Meester, Reinier G S; Lansdorp-Vogelaar, Iris

    2016-12-01

    Gastrointestinal (GI) diseases are among the leading causes of death in the world. To reduce the burden of GI diseases, surveillance is recommended for some diseases, including for patients with inflammatory bowel diseases, Barrett's oesophagus, precancerous gastric lesions, colorectal adenoma, and pancreatic neoplasms. This review aims to provide an overview of the evidence on cost-effectiveness of surveillance of individuals with GI conditions predisposing them to cancer, specifically focussing on the aforementioned conditions. We searched the literature and reviewed 21 studies. Despite heterogeneity of studies in terms of settings, study populations, surveillance strategies and outcomes, most reviewed studies suggested at least some surveillance of patients with these GI conditions to be cost-effective. For some high-risk conditions frequent surveillance with 3-month intervals was warranted, while for other conditions, surveillance may only be cost-effective every 10 years. Further studies based on more robust effectiveness evidence are needed to inform and optimise surveillance programmes for GI cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. [Immunological mechanisms of graft versus tumor effect].

    Science.gov (United States)

    Ine, Shoji; Yamada, Minami; Miyamura, Koichi; Sasaki, Takeshi

    2003-09-01

    Lesson from hematopoietic stem cell transplantation demonstrated that donor immuno-surveillance system can eradicate tumor cells. This is so-call graft versus tumor(GVT) effect. Antigen presenting cells show peptide from minor antigen rather leukemic specific antigen in the context of major histocompatibility complex. The effector cells composed of CD8 T lymphocyte, CD4 T lymphocyte, natural killer cell and natural killer T cell. Death signal was transmitted from effector cells via granzyme/perforin system and FasL/Fas system, and recently TRAIL system seems most important for GVT effect.

  10. Risk effectiveness evaluation of surveillance testing

    International Nuclear Information System (INIS)

    Kim, I.S.; Samanta, P.K.; Martorell, S.; Vesely, W.E.

    1991-01-01

    To address the concerns about nuclear power plant surveillance tests, i.e., their adverse safety impact due to negative effects and too burdensome requirements, it is necessary to evaluate the safety significance or risk effectiveness of such tests explicitly considering both negative and positive effects. This paper defines the negative effects of surveillance testing from a risk perspective, and then presents a methodology to quantify the negative risk impact, i.e., the risk penalty or risk increase caused by the test. The method focuses on two important kinds of negative effects, namely, test-caused transients and test-caused equipment degradations. The concepts and quantitative methods for the risk evaluation can be used in the decision-making process to establish the safety significance of the tests and to screen the plant-specific surveillance test requirements. 6 refs., 2 figs., 2 tabs

  11. Surveillance

    DEFF Research Database (Denmark)

    Albrechtslund, Anders; Coeckelbergh, Mark; Matzner, Tobias

    Studying surveillance involves raising questions about the very nature of concepts such as information, technology, identity, space and power. Besides the maybe all too obvious ethical issues often discussed with regard to surveillance, there are several other angles and approaches that we should...... like to encourage. Therefore, our panel will focus on the philosophical, yet non-ethical issues of surveillance in order to stimulate an intense debate with the audience on the ethical implications of our enquiries. We also hope to provide a broader and deeper understanding of surveillance....

  12. Effective surveillance for homeland security balancing technology and social issues

    CERN Document Server

    Flammini, Francesco; Franceschetti, Giorgio

    2013-01-01

    Effective Surveillance for Homeland Security: Balancing Technology and Social Issues provides a comprehensive survey of state-of-the-art methods and tools for the surveillance and protection of citizens and critical infrastructures against natural and deliberate threats. Focusing on current technological challenges involving multi-disciplinary problem analysis and systems engineering approaches, it provides an overview of the most relevant aspects of surveillance systems in the framework of homeland security. Addressing both advanced surveillance technologies and the related socio-ethical issues, the book consists of 21 chapters written by international experts from the various sectors of homeland security. Part I, Surveillance and Society, focuses on the societal dimension of surveillance-stressing the importance of societal acceptability as a precondition to any surveillance system. Part II, Physical and Cyber Surveillance, presents advanced technologies for surveillance. It considers developing technologie...

  13. Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

    Directory of Open Access Journals (Sweden)

    Chávez Mireya

    2010-01-01

    Full Text Available Abstract Background von Hippel-Lindau (VHL disease is a hereditary cancer syndrome caused by germline mutations in the VHL gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children. Methods We tested 17 families (n = 109 individuals for VHL mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the VHL gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations. Results Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02. Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01. Conclusions The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening

  14. Is anatomic complexity associated with renal tumor growth kinetics under active surveillance?

    Science.gov (United States)

    Mehrazin, Reza; Smaldone, Marc C; Egleston, Brian; Tomaszewski, Jeffrey J; Concodora, Charles W; Ito, Timothy K; Abbosh, Philip H; Chen, David Y T; Kutikov, Alexander; Uzzo, Robert G

    2015-04-01

    Linear growth rate (LGR) is the most commonly employed trigger for definitive intervention in patients with renal masses managed with an initial period of active surveillance (AS). Using our institutional cohort, we explored the association between tumor anatomic complexity at presentation and LGR in patients managed with AS. Enhancing renal masses managed expectantly for at least 6 months were included for analysis. The association between Nephrometry Score and LGR was assessed using generalized estimating equations, adjusting for the age, Charlson score, race, sex, and initial tumor size. Overall, 346 patients (401 masses) met the inclusion criteria (18% ≥ cT1b), with a median follow-up of 37 months (range: 6-169). Of these, 44% patients showed progression to definitive intervention with a median duration of 27 months (range: 6-130). On comparing patients managed expectantly to those requiring intervention, no difference was seen in median tumor size at presentation (2.2 vs. 2.2 cm), whereas significant differences in median age (74 vs. 65 y, P anatomic tumor complexity at presentation and renal masses of LGR of clinical stage 1 under AS may afford a clinically useful cue to tailor individual patient radiographic surveillance schedules and warrants further evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Aneuploidy theory explains tumor formation, the absence of immune surveillance, and the failure of chemotherapy.

    Science.gov (United States)

    Rasnick, David

    2002-07-01

    The autocatalyzed progression of aneuploidy accounts for all cancer-specific phenotypes, the Hayflick limit of cultured cells, carcinogen-induced tumors in mice, the age distribution of human cancer, and multidrug-resistance. Here aneuploidy theory addresses tumor formation. The logistic equation, phi(n)(+1) = rphi(n) (1 - phi(n)), models the autocatalyzed progression of aneuploidy in vivo and in vitro. The variable phi(n)(+1) is the average aneuploid fraction of a population of cells at the n+1 cell division and is determined by the value at the nth cell division. The value r is the growth control parameter. The logistic equation was used to compute the probability distribution for values of phi after numerous divisions of aneuploid cells. The autocatalyzed progression of aneuploidy follows the laws of deterministic chaos, which means that certain values of phi are more probable than others. The probability map of the logistic equation shows that: 1) an aneuploid fraction of at least 0.30 is necessary to sustain a population of cancer cells; and 2) the most likely aneuploid fraction after many population doublings is 0.70, which is equivalent to a DNA(index)=1.7, the point of maximum disorder of the genome that still sustains life. Aneuploidy theory also explains the lack of immune surveillance and the failure of chemotherapy.

  16. Cost effectiveness of surveillance for GI cancers

    NARCIS (Netherlands)

    Omidvari, A.-H. (Amir-Houshang); R.G.S. Meester (Reinier); I. Lansdorp-Vogelaar (Iris)

    2016-01-01

    textabstractGastrointestinal (GI) diseases are among the leading causes of death in the world. To reduce the burden of GI diseases, surveillance is recommended for some diseases, including for patients with inflammatory bowel diseases, Barrett's oesophagus, precancerous gastric lesions, colorectal

  17. Information gaps in surveillance data and effects on the Ghanaian ...

    African Journals Online (AJOL)

    Information gaps in surveillance data and effects on the Ghanaian response to the ... for Medical Research to determine its completeness and appropriateness for ... on CRFs can significantly reduce the utility of results of laboratory analysis for ...

  18. Introduction to surveillance studies

    CERN Document Server

    Petersen, JK

    2012-01-01

    Introduction & OverviewIntroduction Brief History of Surveillance Technologies & TechniquesOptical SurveillanceAerial Surveillance Audio Surveillance Radio-Wave SurveillanceGlobal Positioning Systems Sensors Computers & the Internet Data Cards Biochemical Surveillance Animal Surveillance Biometrics Genetics Practical ConsiderationsPrevalence of Surveillance Effectiveness of Surveillance Freedom & Privacy IssuesConstitutional Freedoms Privacy Safeguards & Intrusions ResourcesReferences Glossary Index

  19. Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization

    Directory of Open Access Journals (Sweden)

    Giulia Ottaviani

    2016-09-01

    Full Text Available Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.

  20. Localization of higher grade tumor foci in potential candidates for active surveillance who opt for radical prostatectomy

    Science.gov (United States)

    Hong, Sung Kyu; Eastham, James A.; Fine, Samson W.

    2013-01-01

    Purpose: To investigate actual intraprostatic location of higher graded tumor foci undetected via standard transrectal ultrasound-guided prostate biopsy amongst patients who would be clinically considered appropriate candidates for active surveillance (AS) but underwent radical prostatectomy (RP). Methods: We reviewed entirely-submitted and whole-mounted RP specimens from 169 men who were deemed appropriate for AS clinically, but opted for RP and were found to have higher grade tumors. For each case, tumor nodules were circled and color-coded in a grade-specific manner and digitally scanned to created tumor maps. The locations of tumor foci with Gleason grade ≥4 were stratified by specific sites: anterior, anterolateral, lateral only (not clearly anterior or posterior), posterior, and posterolateral area. Results: Of 169 patients, 86% had clinical stage T1c and 14% T2a. RP Gleason score 7 in all but two men. Higher-grade tumor foci were localized to: anterior (n=66, 39%), anterolateral (n=4, 2%), lateral only (not clearly anterior or posterior) (n=5, 3%), posterior (n=52, 31%), and posterolateral (n=42, 25%) prostate, respectively. Conclusions: Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients. PMID:24392439

  1. Infant brain tumors: incidence, survival, and the role of radiation based on Surveillance, Epidemiology, and End Results (SEER) Data.

    Science.gov (United States)

    Bishop, Andrew J; McDonald, Mark W; Chang, Andrew L; Esiashvili, Natia

    2012-01-01

    To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation compared with those treated with surgery alone. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

    NARCIS (Netherlands)

    Kalish, Jennifer M.; Doros, Leslie; Helman, Lee J.; Hennekam, Raoul C.; Kuiper, Roland P.; Maas, Saskia M.; Maher, Eamonn R.; Nichols, Kim E.; Plon, Sharon E.; Porter, Christopher C.; Rednam, Surya; Schultz, Kris Ann P.; States, Lisa J.; Tomlinson, Gail E.; Zelley, Kristin; Druley, Todd E.

    2017-01-01

    A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America.

  3. Interval algebra: an effective means of scheduling surveillance radar networks

    CSIR Research Space (South Africa)

    Focke, RW

    2015-05-01

    Full Text Available Interval Algebra provides an effective means to schedule surveillance radar networks, as it is a temporal ordering constraint language. Thus it provides a solution to a part of resource management, which is included in the revised Data Fusion...

  4. Interval algebra - an effective means of scheduling surveillance radar networks

    CSIR Research Space (South Africa)

    Focke, RW

    2015-05-01

    Full Text Available Interval Algebra provides an effective means to schedule surveillance radar networks, as it is a temporal ordering constraint language. Thus it provides a solution to a part of resource management, which is included in the revised Data Fusion...

  5. Effects of Forgetting Phenomenon on Surveillance Test Interval

    International Nuclear Information System (INIS)

    Lee, Ho-Joong; Jang, Seung-Cheol

    2007-01-01

    Technical Specifications (TS) requirements for nuclear power plants (NPPs) define Surveillance Requirements (SRs) to assure safety during operation. SRs include surveillance test intervals (STIs) and the optimization of the STIs is one of the main issues in risk-informed applications. Surveillance tests are required in NPPs to detect failures in standby equipment to assure their availability in an accident. However, operating experience of the plants suggests that, in addition to the beneficial effects of detecting latent faults, the tests also may have adverse effects on plant operation or equipment; e.g., plant transient caused by the test and wear-out of safety system equipment due to repeated testing. Recent studies have quantitatively evaluated both the beneficial and adverse effects of testing to decide on an acceptable test interval. The purpose of this research is to investigate the effects of forgetting phenomenon on STI. It is a fundamental human characteristic that a person engaged in a repetitive task will improve his performance over time. The learning phenomenon is observed by the decrease in operation time per unit as operators gain experience by performing additional tasks. However, once there is a break of sufficient length, forgetting starts to take place. In surveillance tests, the most common factor to determine the amount of forgetting is the length of STI, where the longer the STI, the greater the amount of forgetting

  6. Cross-correlation enhanced stability in a tumor cell growth model with immune surveillance driven by cross-correlated noises

    International Nuclear Information System (INIS)

    Zeng Chunhua; Zhou Xiaofeng; Tao Shufen

    2009-01-01

    The transient properties of a tumor cell growth model with immune surveillance driven by cross-correlated multiplicative and additive noises are investigated. The explicit expression of extinction rate from the state of a stable tumor to the state of extinction is obtained. Based on the numerical computations, we find the following: (i) the intensity of multiplicative noise D and the intensity of additive noise α enhance the extinction rate for the case of λ ≤ 0 (i.e. λ denotes cross-correlation intensity between two noises), but for the case of λ > 0, a critical noise intensity D or α exists at which the extinction rate is the smallest; D and α at first weaken the extinction rate and then enhance it. (ii) The immune rate β and the cross-correlation intensity λ play opposite roles on the extinction rate, i.e. β enhances the extinction rate of the tumor cell, while λ weakens the extinction rate of the tumor cell. Namely, the immune rate can enhance the extinction of the tumor cell and the cross-correlation between two noises can enhance stability of the cancer state.

  7. Comprehensive effective and efficient global public health surveillance

    Directory of Open Access Journals (Sweden)

    McNabb Scott JN

    2010-12-01

    Full Text Available Abstract At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources. Three movements now set the stage for transformation of surveillance: 1 adoption by Member States of the World Health Organization (WHO of the revised International Health Regulations (IHR[2005]; 2 maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3 consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers. To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners. We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it’s needed, where it’s needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities

  8. Comprehensive effective and efficient global public health surveillance.

    Science.gov (United States)

    McNabb, Scott J N

    2010-12-03

    At a crossroads, global public health surveillance exists in a fragmented state. Slow to detect, register, confirm, and analyze cases of public health significance, provide feedback, and communicate timely and useful information to stakeholders, global surveillance is neither maximally effective nor optimally efficient. Stakeholders lack a globa surveillance consensus policy and strategy; officials face inadequate training and scarce resources.Three movements now set the stage for transformation of surveillance: 1) adoption by Member States of the World Health Organization (WHO) of the revised International Health Regulations (IHR[2005]); 2) maturation of information sciences and the penetration of information technologies to distal parts of the globe; and 3) consensus that the security and public health communities have overlapping interests and a mutual benefit in supporting public health functions. For these to enhance surveillance competencies, eight prerequisites should be in place: politics, policies, priorities, perspectives, procedures, practices, preparation, and payers.To achieve comprehensive, global surveillance, disparities in technical, logistic, governance, and financial capacities must be addressed. Challenges to closing these gaps include the lack of trust and transparency; perceived benefit at various levels; global governance to address data power and control; and specified financial support from globa partners.We propose an end-state perspective for comprehensive, effective and efficient global, multiple-hazard public health surveillance and describe a way forward to achieve it. This end-state is universal, global access to interoperable public health information when it's needed, where it's needed. This vision mitigates the tension between two fundamental human rights: first, the right to privacy, confidentiality, and security of personal health information combined with the right of sovereign, national entities to the ownership and stewardship

  9. Infant Brain Tumors: Incidence, Survival, and the Role of Radiation Based on Surveillance, Epidemiology, and End Results (SEER) Data

    International Nuclear Information System (INIS)

    Bishop, Andrew J.; McDonald, Mark W.; Chang, Andrew L.; Esiashvili, Natia

    2012-01-01

    Purpose: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Results: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). Conclusion: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation

  10. Autocrine Effects of Tumor-Derived Complement

    Directory of Open Access Journals (Sweden)

    Min Soon Cho

    2014-03-01

    Full Text Available We describe a role for the complement system in enhancing cancer growth. Cancer cells secrete complement proteins that stimulate tumor growth upon activation. Complement promotes tumor growth via a direct autocrine effect that is partially independent of tumor-infiltrating cytotoxic T cells. Activated C5aR and C3aR signal through the PI3K/AKT pathway in cancer cells, and silencing the PI3K or AKT gene in cancer cells eliminates the progrowth effects of C5aR and C3aR stimulation. In patients with ovarian or lung cancer, higher tumoral C3 or C5aR mRNA levels were associated with decreased overall survival. These data identify a role for tumor-derived complement proteins in promoting tumor growth, and they therefore have substantial clinical and therapeutic implications.

  11. Correlation between tumor size and surveillance of lymph node metastasis for IB and IIA cervical cancer by magnetic resonance images

    International Nuclear Information System (INIS)

    Kim, See Hyung; Lee, Hee Jung; Kim, Young Whan

    2012-01-01

    Purpose: To assess the feasibility of preoperative MRI based measurement of tumor size with regard to lymph node (LN) metastasis in early uterine cervical cancer. Material and Methods: A retrospective review of patients with FIGO stage IB–IIA cervical cancer who underwent lymphadenectomy was performed. Diagnostic accuracy of MRI in detecting LN metastasis and rate of LN recurrence in terms of tumor size (≤4 cm versus >4 cm) were analyzed. ROC curve analysis was used to determine LN size for differentiating LN metastasis in terms of tumor size. P 4 cm revealed higher diagnostic accuracy of MRI in detecting LN metastasis (85.4% versus 50.6%, P = 0.023) and rate of LN recurrence (20.0% versus 6.4%, P = 0.031) in than those with size with ≤4 cm, the differences were statistically significant. Discriminant analysis of LN size for the differentiation of metastasis from non-metastasis resulted in cut-off values (11.8 mm; size with >4 cm versus 8.3 mm; size with ≤4 cm) and diagnostic accuracy (84.0% of size with >4 cm versus 72.0% of size with ≤4 cm). Conclusion: MRI has limited sensitivity, but high specificity in predicting surveillance of LN metastasis in the preoperative early cervical cancer, especially useful tool for patients with tumor size with >4 cm.

  12. Evaluation of the Effectiveness and Cost-Effectiveness of Personalized Surveillance After Colorectal Adenomatous Polypectomy.

    Science.gov (United States)

    McFerran, Ethna; O'Mahony, James F; Fallis, Richard; McVicar, Duncan; Zauber, Ann G; Kee, Frank

    2017-01-01

    Lifetime risk of developing colorectal cancer is 5%, and 5-year survival at early stage is 92%. Individuals with precancerous lesions removed at primary screening are typically recommended surveillance colonoscopy. Because greater benefits are anticipated for those with higher risk of colorectal cancer, scope for risk-specific surveillance recommendations exists. This review assesses published cost-effectiveness estimates of postpolypectomy surveillance to consider the potential for personalized recommendations by risk group. Meta-analyses of incidence of advanced neoplasia postpolypectomy for low-risk cases were comparable to those without adenoma, with both rates under the lifetime risk of 5%. This group may not benefit from intensive surveillance, which risks unnecessary harm and inefficient use of often scarce colonoscopy capacity. Therefore, greater personalization through deintensified strategies for low-risk individuals could be beneficial. The potential for noninvasive testing, such as fecal immunochemical tests, combined with primary prevention or chemoprevention may reserve colonoscopy for targeted use in personalized risk-stratified surveillance. This review appraised evidence supporting a program of personalized surveillance in patients with colorectal adenoma according to risk group and compared the effectiveness of surveillance colonoscopy with alternative prevention strategies. It assessed trade-offs among costs, benefits, and adverse effects that must be considered in a decision to adopt or reject personalized surveillance. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Effects of Experimenter Surveillance on Reactive Self-Monitoring.

    Science.gov (United States)

    Belfiore, Phillip J.; And Others

    1989-01-01

    Worker reactivity patterns were examined in a study of two women with mild and moderate mental retardation who self-monitored their work productivity with and without external surveillance. Findings suggest that surveillance is a setting event that may be important in achieving and maintaining self-management program benefits. (MSE)

  14. Preliminary Porcine in vivo Evaluation of a Telerobotic System for Transurethral Bladder Tumor Resection & Surveillance.

    Science.gov (United States)

    Sarli, Nima; Del Giudice, Giuseppe; De, Smita; Dietrich, Mary S; Herrell, S Duke; Simaan, Nabil

    2018-03-27

    Transurethral Resection of Bladder Tumors (TURBT) can be a challenging procedure, primarily due to limitations in tool-tip dexterity, visualization and lack of tissue depth information. A transurethral robotic system was developed to revolutionize TURBT by addressing some of these limitations. The results of three pilot in-vivo porcine studies using the novel robotic system are presented and potential improvements are proposed based on experimental observations. A transvesical endoscope with a mounted optically-tracked camera was placed through the bladder of the swine under general anesthesia. Simulated bladder lesions were created by injecting HistoGel processing gel mixed with blue dye trans-abdominally into various locations in the bladder wall under endoscopic visualization. A seven-degree-of-freedom (DoF) robot was then used for transurethral resection/ablation of these simulated tumors. An independent two-DoF distal laser arm (DLA) was deployed through the robot for laser ablation and was assisted by a manually controlled gripper for en-bloc resection attempts. Lesions were successfully created and ablated using our novel endoscopic robot in the swine bladder. Full accessibility of the bladder, including the bladder neck and dome, was demonstrated without requiring bladder deflation or pubic compression. Simulated lesions were successfully ablated using the Holmium laser. En-bloc resection was demonstrated using the DLA and a manual grasper. Feasibility of robot-assisted en-bloc resection was demonstrated. Main challenges were lack of depth perception and visual occlusion induced by the transvesical endoscope presented challenges. Recommendations are given to enhance robot-assisted TURBT. Lessons learned through these pilot swine studies verify the feasibility of robot-assisted TURBT while informing designers about critical aspects needed for future successful clinical deployment.

  15. [Active surveillance for prostate cancer: usefulness of endorectal MR at 1.5 Tesla with pelvic phased array coil in detecting significant tumors].

    Science.gov (United States)

    Luyckx, F; Hallouin, P; Barré, C; Aillet, G; Chauveau, P; Hétet, J-F; Bouchot, O; Rigaud, J

    2011-02-01

    To describe and assess MRI signs of significant tumor in a series of patients who all underwent radical prostatectomy and also fulfilled criteria to choose active surveillance according to French "SurAcaP" protocol. The clinical reports of 681 consecutive patients operated on for prostate cancer between 2002 and 2007 were reviewed retrospectively. All patients had endorectal MR (1.5 Tesla) with pelvic phased array coil. (1.5 T erMR PPA). Sixty-one patients (8.9%) fulfilled "SurAcaP" protocol criteria. Preoperative data (MR+core biopsy) were assessed by comparison to whole-mount step section pathology. 85.3% of the 61 patients entering SurAcaP protocol had significant tumor at pathology. (Non Organ Confined Disease (Non OCD)=8.2%, Gleason sum score>6=39.2%). A new exclusion criterion has been assessed: T3MRI±NPS>1 as a predictor tool of significant tumor. ("T3MRI±NPS>1"=Non OCD at MR±number of positive sextants involved in tumor at MR and/or Core Biopsy > to 1). Sensitivity, specificity, PPV, NPV of the criterion "T3MRI±NPS>1" in predicting significant tumor were, respectively: 77%, 33%, 86%, 20%. Adding this criterion to other criteria of the "SurAcaP" protocol could allow the exclusion of all Non OCD, and a decrease in Gleason sum Score>6 rates (20%). Endorectal MR at 1.5 Tesla with pelvic-phased array coil should be considered when selecting patients for active surveillance in the management of prostate cancer. A criterion based upon MR and core biopsy findings, called "T3MR±NSP>1" may represent an exclusion citeria due to its ability to predict significant tumor. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  16. Anti-tumor effect of polysaccharides from rhizome of Curculigo ...

    African Journals Online (AJOL)

    The anti-tumor effect of PDC on cervical cancer was investigated in vivo in mice injected with Hela cells. The parameters measured were tumor volume and weight. In vitro anti-tumor effects of PDC were assessed by measuring expressions of caspase-3, caspase-9 and P53 proteins in Hela cells via ELISA assay. Thymus ...

  17. Effects of exercise on tumor physiology and metabolism

    DEFF Research Database (Denmark)

    Pedersen, Line; Christensen, Jesper Frank; Hojman, Pernille

    2015-01-01

    . Here, we review the body of literature describing exercise intervention studies performed in rodent tumor models and elaborate on potential mechanistic effects of exercise on tumor physiology. Exercise has been shown to reduce tumor incidence, tumor multiplicity, and tumor growth across numerous...... different transplantable, chemically induced or genetic tumor models. We propose 4 emerging mechanistic effects of exercise, including (1) vascularization and blood perfusion, (2) immune function, (3) tumor metabolism, and (4) muscle-to-cancer cross-talk, and discuss these in details. In conclusion......, exercise training has the potential to be a beneficial and integrated component of cancer management, but has yet to fully elucidate its potential. Understanding the mechanistic effects of exercise on tumor physiology is warranted. Insight into these mechanistic effects is emerging, but experimental...

  18. The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture

    Directory of Open Access Journals (Sweden)

    Federico Garrido

    2017-02-01

    Full Text Available Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL.

  19. Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.

    Directory of Open Access Journals (Sweden)

    Neil L Spector

    Full Text Available The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER in human tumors.Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally

  20. Anti-tumor effect of low dose radiation in mice

    International Nuclear Information System (INIS)

    Fan Zhengping; Lu Jiaben; Zhu Bingchai

    1997-01-01

    The author reports the effects of the total body irradiation of low dose radiation (LDR) and/or the local irradiation of large dose on average tumor weights and tumor inhibitory rates in 170 mice inoculated S 180 sarcoma cell, and the influence of LDR on average longevity in 40 tumor-bearing animals. Results show (1) LDR in the range of 75∼250 mGy can inhibit tumor growth to some extent; (2) fractionated irradiation of 75 mGy and local irradiation of 10 Gy may produce a synergism in tumor growth inhibition; and (3)LDR may enhance average longevity in ascitic tumor-bearing mice

  1. Oxygen diffusion and oxygen effect in tumor tissue

    International Nuclear Information System (INIS)

    Eissa, H.M.; Hehn, G.

    1979-06-01

    The diffusion of oxygen in tumor cords of bronchus carcinoma of the lung have been studied with refined computer methods for solving the diffusion equation in axis symmetric tumor structures. In this tumor configuration we may find three different regions consisting of euoxic cells, hypoxic tumor cells and necrotic parts. In the case of oxygen supply from a capillary inside a cylinder of tumor tissue with radius 200 μm or in a tumor cord of radius 300 μm with oxygen supply by capillaries outside, we get a relation of well oxygenated cells to hypoxic cells approximately as 1:8 or as 1:1.1 respectively. Of course most of the tumor cords observed in histological slices have smaller diameters, so that an average of approximately 20% hypoxic cells can be assumed. Based on the work of Ardenne, the diffusion of oxygen and glucose in a tumor of type DS-carcinosarcom has been investigated in both intact tumor and tumor treated with ionizing radiation. We can show that a strong reoxygenation effect takes place in that the well supplied regions may increase in some tumor configurations up to a factor of four by volume. The biological consequences of the oxygen pressure determined in tumor cells are discussed in detail. The investigation of oxygen diffusion in the intercapillary tumor region should give a quantitative physical basis for considering the oxygen effect with the aim to explain the advantages of neutron therapy against conventional radiotherapy. (orig./MG) [de

  2. Marital status is an independent prognostic factor for pancreatic neuroendocrine tumors patients: An analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

    Science.gov (United States)

    Zhou, Huaqiang; Zhang, Yuanzhe; Song, Yiyan; Tan, Wulin; Qiu, Zeting; Li, Si; Chen, Qinchang; Gao, Shaowei

    2017-09-01

    Marital status's prognostic impact on pancreatic neuroendocrine tumors (PNET) has not been rigorously studied. We aimed to explore the relationship between marital status and outcomes of PNET. We retrospectively investigated 2060 PNET cases between 2004 and 2010 from Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Chi 2 test, t-test as appropriate. Kaplan-Meier methods and COX proportional hazard models were used to ascertain independent prognostic factors. Married patients had better 5-year overall survival (OS) (53.37% vs. 42.27%, Pvs. 59.82%, P=0.001) comparing with unmarried patients. Multivariate analysis revealed marital status is an independent prognostic factor, with married patients showing better OS (HR=0.74; 95% CI: 0.65-0.84; Punmarried patients may be associated with a delayed diagnosis with advanced tumor stage, psychosocial and socioeconomic factors. Further studies are needed. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Positive predictive value and effectiveness of measles case-based surveillance in Uganda, 2012-2015.

    Directory of Open Access Journals (Sweden)

    Fred Nsubuga

    Full Text Available Disease surveillance is a critical component in the control and elimination of vaccine preventable diseases. The Uganda National Expanded Program on Immunization strives to have a sensitive surveillance system within the Integrated Disease Surveillance and Response (IDSR framework. We analyzed measles surveillance data to determine the effectiveness of the measles case-based surveillance system and estimate its positive predictive value in order to inform policy and practice.An IDSR alert was defined as ≥1 suspected measles case reported by a district in a week, through the electronic Health Management Information System. We defined an alert in the measles case-based surveillance system (CBS as ≥1 suspected measles case with a blood sample collected for confirmation during the corresponding week in a particular district. Effectiveness of CBS was defined as having ≥80% of IDSR alerts with a blood sample collected for laboratory confirmation. Positive predictive value was defined as the proportion of measles case-patients who also had a positive measles serological result (IgM +. We reviewed case-based surveillance data with laboratory confirmation and measles surveillance data from the electronic Health Management Information System from 2012-2015.A total of 6,974 suspected measles case-persons were investigated by the measles case-based surveillance between 2012 and 2015. Of these, 943 (14% were measles specific IgM positive. The median age of measles case-persons between 2013 and 2015 was 4.0 years. Between 2013 and 2015, 72% of the IDSR alerts reported in the electronic Health Management Information System, had blood samples collected for laboratory confirmation. This was however less than the WHO recommended standard of ≥80%. The PPV of CBS between 2013 and 2015 was 8.6%.In conclusion, the effectiveness of measles case-based surveillance was sub-optimal, while the PPV showed that true measles cases have significantly reduced in Uganda

  4. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    International Nuclear Information System (INIS)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub; Chung, Ui Seok; Koh, Won Gun

    2016-01-01

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors

  5. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Ui Seok; Koh, Won Gun [Dept. of Chemical and Biomolecular Engineering, Yonsei University, Seoul (Korea, Republic of)

    2016-09-15

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

  6. Anxiety, Culture, and Expectations: Oncologist-Perceived Factors Associated With Use of Nonrecommended Serum Tumor Marker Tests for Surveillance of Early-Stage Breast Cancer.

    Science.gov (United States)

    Hahn, Erin E; Munoz-Plaza, Corrine; Wang, Jianjin; Garcia Delgadillo, Jazmine; Schottinger, Joanne E; Mittman, Brian S; Gould, Michael K

    2017-01-01

    Breast cancer offers several opportunities for reducing use of ineffective practices based on American Society of Clinical Oncology guidelines. We assessed oncologist-perceived factors associated with use of one such practice-serum tumor markers for post-treatment breast cancer surveillance-focusing on medical oncologists with high, medium, or low test use. Using a mixed-methods design, we identified patients who had been treated for early-stage breast cancer diagnosed between January 1, 2009, and December 31, 2012, within Kaiser Permanente Southern California and calculated the number of tests ordered from January 1, 2010, to December 31, 2014. We identified oncologists with high, medium, or low use and subsequently performed semistructured interviews. We used patient satisfaction data to assess association between pattern of use and satisfaction score. We identified 7,363 patients, with 40,114 tests ordered. High-use oncologists were defined as those ordering at least one test annually for 35% of patients or more, low-use oncologists as those ordering at least one test for 5% of patients or less; 42% of oncologists were high, 27% low, and 31% medium users. We interviewed 17 oncologists: six high, eight low, and three medium users. Factors associated with high use included: perceived patient anxiety, oncologist anxiety, belief that there was nothing else to offer, concern about satisfaction, patient competition, peer use, and system barriers. Factors associated with low use included: beliefs about consequences (eg, causes harms) and medical center culture (eg, collective decision to follow guidelines). We found no association between satisfaction score and pattern of use. Barriers to deimplementation are numerous and complex. Traditional strategies of practice change alone are unlikely to be effective. Multifaceted, multilevel strategies deployed to address patient-, clinician-, and system-related barriers may be required.

  7. Radiation effects on tumor-specific DTH response, 2

    International Nuclear Information System (INIS)

    Nobusawa, Hiroshi; Hachisu, Reiko.

    1991-01-01

    Tumor-specific immunity was induced in C3H mice by immunizing with syngeneic MH134 hepatoma cells. Radiation sensitivity of anti-tumor activity of immunized spleen cells were examined and compared with the radiation sensitivity of the delayed-type hypersensitivity (DTH)-response. The spleen cells were irradiated in vitro, then mixed with the tumor cells. DTH-response intensity was determined from the footpad increment twenty-four hours after inoculation of tumor cells with immunized spleen cells. Anti-tumor activity of the spleen cells, based on growth inhibition of tumor cells, was measured by a cytostatic test in vivo with diffusion chambers. Tumor-specific DTH response was suppressed dose-dependently in the range of 12-24 Gy irradiation. No suppression was observed below 12 Gy. Without irradiation, growth of tumor cells was inhibited by immunized spleen cells more effectively than by normal spleen cells. Anti-tumor activity of immunized and normal spleen cells was diminished by irradiation doses of 20 Gy and 10 Gy, respectively. Comparing our report with others that analyzed the type of anti-tumor effector cells induced in this experimental system, we concluded that tumor-specific anti-tumor activity (tumor growth inhibition in vivo) that was radiosensitive at 10-20 Gy depended on a DTH-response. (author)

  8. An effective surveillance strategy for reactor pressure vessel assessment in the long term operation perspective

    International Nuclear Information System (INIS)

    Chaouadi, R.; Gerard, R.

    2015-01-01

    The reactor pressure vessel (RPV) irradiation embrittlement is monitored by means of surveillance capsules containing the RPV belt-line materials, inserted inside the reactor pressure vessel (RPV) before the start of operation. These capsules are placed at location where they receive a higher neutron flux than the vessel wall, by a factor of the order of 2 to 3. They are regularly retrieved and tested to evaluate the RPV irradiation embrittlement according to specific regulatory procedures and standards, in order to guarantee the safe operation of the RPV throughout its lifetime. These procedures are often relying on empirical but conservative concepts. In parallel, material research reactor (MTR) irradiations are often used to support the surveillance data and to develop a better understanding of irradiation effects, not only qualitatively but also quantitatively. Taking advantage of the increased understanding of irradiation effects, analytical tools were developed to improve the evaluation embrittlement and quality assurance of the RPV embrittlement assessment. In this framework, an alternative but complementary surveillance program assessment was developed in Belgium, the so-called enhanced surveillance, in order to benefit from the latest developments in the area of materials science and irradiation effects. The neutron flux and fracture properties of the surveillance materials can be reliably characterized and correlated to each other using physically-based rather than empirical concepts. The enhanced surveillance approach is complementary to the mandatory regulatory procedure and allows quantifying the conservatism of the regulatory approach. The enhanced surveillance approach that uses the reconstitution technology to fabricate additional small size specimens, appropriate modeling tools and microstructural examination when required, makes it possible to rationalize all available information in a physically-based way

  9. Effects of exercise on tumor physiology and metabolism.

    Science.gov (United States)

    Pedersen, Line; Christensen, Jesper Frank; Hojman, Pernille

    2015-01-01

    Exercise is a potent regulator of a range of physiological processes in most tissues. Solid epidemiological data show that exercise training can reduce disease risk and mortality for several cancer diagnoses, suggesting that exercise training may directly regulate tumor physiology and metabolism. Here, we review the body of literature describing exercise intervention studies performed in rodent tumor models and elaborate on potential mechanistic effects of exercise on tumor physiology. Exercise has been shown to reduce tumor incidence, tumor multiplicity, and tumor growth across numerous different transplantable, chemically induced or genetic tumor models. We propose 4 emerging mechanistic effects of exercise, including (1) vascularization and blood perfusion, (2) immune function, (3) tumor metabolism, and (4) muscle-to-cancer cross-talk, and discuss these in details. In conclusion, exercise training has the potential to be a beneficial and integrated component of cancer management, but has yet to fully elucidate its potential. Understanding the mechanistic effects of exercise on tumor physiology is warranted. Insight into these mechanistic effects is emerging, but experimental intervention studies are still needed to verify the cause-effect relationship between these mechanisms and the control of tumor growth.

  10. DVT surveillance program in the ICU: analysis of cost-effectiveness.

    Directory of Open Access Journals (Sweden)

    Ajai K Malhotra

    Full Text Available BACKGROUND: Venous Thrombo-embolism (VTE--Deep venous thrombosis (DVT and/or pulmonary embolism (PE--in traumatized patients causes significant morbidity and mortality. The current study evaluates the effectiveness of DVT surveillance in reducing PE, and performs a cost-effectiveness analysis. METHODS: All traumatized patients admitted to the adult ICU underwent twice weekly DVT surveillance by bilateral lower extremity venous Duplex examination (48-month surveillance period--SP. The rates of DVT and PE were recorded and compared to the rates observed in the 36-month pre-surveillance period (PSP. All patients in both periods received mechanical and pharmacologic prophylaxis unless contraindicated. Total costs--diagnostic, therapeutic and surveillance--for both periods were recorded and the incremental cost for each Quality Adjusted Life Year (QALY gained was calculated. RESULTS: 4234 patients were eligible (PSP--1422 and SP--2812. Rate of DVT in SP (2.8% was significantly higher than in PSP (1.3% - p<0.05, and rate of PE in SP (0.7% was significantly lower than that in PSP (1.5% - p<0.05. Logistic regression demonstrated that surveillance was an independent predictor of increased DVT detection (OR: 2.53 - CI: 1.462-4.378 and decreased PE incidence (OR: 0.487 - CI: 0.262-0.904. The incremental cost was $509,091/life saved in the base case, translating to $29,102/QALY gained. A sensitivity analysis over four of the parameters used in the model indicated that the incremental cost ranged from $18,661 to $48,821/QALY gained. CONCLUSIONS: Surveillance of traumatized ICU patients increases DVT detection and reduces PE incidence. Costs in terms of QALY gained compares favorably with other interventions accepted by society.

  11. Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

    1979-01-01

    C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

  12. Ultrasonic three-dimensional on-chip cell culture for dynamic studies of tumor immune surveillance by natural killer cells.

    Science.gov (United States)

    Christakou, Athanasia E; Ohlin, Mathias; Önfelt, Björn; Wiklund, Martin

    2015-08-07

    We demonstrate a simple method for three-dimensional (3D) cell culture controlled by ultrasonic standing waves in a multi-well microplate. The method gently arranges cells in a suspension into a single aggregate in each well of the microplate and, by this, nucleates 3D tissue-like cell growth for culture times between two and seven days. The microplate device is compatible with both high-resolution optical microscopy and maintenance in a standard cell incubator. The result is a scaffold- and coating-free method for 3D cell culture that can be used for controlling the cellular architecture, as well as the cellular and molecular composition of the microenvironment in and around the formed cell structures. We demonstrate the parallel production of one hundred synthetic 3D solid tumors comprising up to thousands of human hepatocellular carcinoma (HCC) HepG2 cells, we characterize the tumor structure by high-resolution optical microscopy, and we monitor the functional behavior of natural killer (NK) cells migrating, docking and interacting with the tumor model during culture. Our results show that the method can be used for determining the collective ability of a given number of NK cells to defeat a solid tumor having a certain size, shape and composition. The ultrasound-based method itself is generic and can meet any demand from applications where it is advantageous to monitor cell culture from production to analysis of 3D tissue or tumor models using microscopy in one single microplate device.

  13. General Surveillance of the soil ecosystem: An approach to monitoring unexpected adverse effects of GMO's

    NARCIS (Netherlands)

    Smit, E.; Bakker, P.A.H.M.; Bergmans, H.; Bloem, J.; Griffiths, B.; Rutgers, M.

    2012-01-01

    The commercial cultivation of genetically modified (GM) crops in the European Union (EU) necessitates, according to EU legislation, the setting up of a General Surveillance (GS) system that should be able to detect unanticipated effects of GM crops on the environment. Although the applicant is

  14. Reassessing the WIC Effect: Evidence from the Pregnancy Nutrition Surveillance System

    Science.gov (United States)

    Joyce, Ted; Racine, Andrew; Yunzal-Butler, Cristina

    2008-01-01

    Recent analyses differ on how effective the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) is at improving infant health. We use data from nine states that participate in the Pregnancy Nutrition Surveillance System to address limitations in previous work. With information on the mother's timing of WIC enrollment, we…

  15. Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

    Science.gov (United States)

    Bauer, Joseph A; Frye, Gerald; Bahr, Anne; Gieg, Jennifer; Brofman, Peter

    2010-10-01

    Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

  16. MORTICIA, a statistical analysis software package for determining optical surveillance system effectiveness.

    Science.gov (United States)

    Ramkilowan, A.; Griffith, D. J.

    2017-10-01

    Surveillance modelling in terms of the standard Detect, Recognise and Identify (DRI) thresholds remains a key requirement for determining the effectiveness of surveillance sensors. With readily available computational resources it has become feasible to perform statistically representative evaluations of the effectiveness of these sensors. A new capability for performing this Monte-Carlo type analysis is demonstrated in the MORTICIA (Monte- Carlo Optical Rendering for Theatre Investigations of Capability under the Influence of the Atmosphere) software package developed at the Council for Scientific and Industrial Research (CSIR). This first generation, python-based open-source integrated software package, currently in the alpha stage of development aims to provide all the functionality required to perform statistical investigations of the effectiveness of optical surveillance systems in specific or generic deployment theatres. This includes modelling of the mathematical and physical processes that govern amongst other components of a surveillance system; a sensor's detector and optical components, a target and its background as well as the intervening atmospheric influences. In this paper we discuss integral aspects of the bespoke framework that are critical to the longevity of all subsequent modelling efforts. Additionally, some preliminary results are presented.

  17. Practical, cost-effective method for real-time surveillance of widely-separated remote sites

    International Nuclear Information System (INIS)

    Braley, R.E.; Olson, A.W.; Rufer, R.P.

    1979-01-01

    Effective intrusion protection for uninhabited sites scattered widely throughout a large geographic area can be a difficult and expensive proposition. When the sites are important enough to require continuous surveillance, the problem is even worse. Roving patrols are not effective, and conventional alarms don't provide enough information to allow a meaningful response. Television systems have possibilities but also disadvantages: the usual system is both costly and inflexible. This paper describes our solution to the problem: a cost effective instrusion protection system used to simultaneously protect many sites scattered over many square miles, with realtime surveillance from a central point. The system is based on a state-of-the-art FM CATV concept that is capable of providing surveillance for multiple sites, is modular in design for quick setup, flexible, and easily maintained. A electronic motion detector is incorporated for each site under surveillance, with a visual and audible alarm to alert the observer at the central control console. The observer can then bring the intruded site up on a large-screen monitor for detailed assessment. The system is relatively economical as all equipment is commercially available and all installation is straight-forward and follows usual CATV construction practices

  18. Quantitative evaluation in tumor SPECT and the effect of tumor size. Fundamental study with phantom

    International Nuclear Information System (INIS)

    Togawa, Takashi; Yui, Nobuharu; Kinoshita, Fujimi; Yanagisawa, Masamichi

    1997-01-01

    An experimental study with phantoms was performed in order to evaluate the effect of the tumor volume on the quantitative estimation in tumor SPECT. The ratio of mean count/pixel in the phantom to that of the background (T/N ratio) was well correlated with the size of the phantom; even when the concentration of the Tc-99m O 4 - solution of globular phantoms with diameters of 29, 37 and 46 mm was constant, the greater the size of the phantom, the higher was the T/N ratio. This study showed that we should understand that the T/N ratio was certainly affected by the reduction of the tumor size itself whenever we evaluate treatment response or assess tumor viability after treatment by reference to the T/N ratio. (author)

  19. Effect of SPG (Sonifilan) immunotherapy and PDT on murine tumor

    International Nuclear Information System (INIS)

    Korbelik, M.; Krosl, G.; Dougherty, G.J.; Chaplin, D.J.

    1992-01-01

    PhotoDynamic Therapy of solid tumors is unique in eliciting a strong host immune response unparalleled in other cancer therapies. This immune response is manifested as an acute inflammatory reaction, and can be readily seen as redness and edema around the treated area. Destruction of typical solid tumor cannot be accomplished solely by direct phototoxic action. This was shown to be the case even with drugs more potent in this direct killing effect than Photofrin, the photosensitizer presently used in clinical PDT. Limiting factors seem to be regional insufficiencies in supply of molecular oxygen, needed for generation of phototoxic species. They can be ascribed to the existence of chronically and acute hypoxic tumor regions, oxygen consumption by the photodynamic process, and vascular shutdown induced during PDT. The remaining tumor mass is eradicated by an indirect effect, necrosis induced by destruction of tumor vasculature. Since most events in PDT treated tumor that lead to vascular collapse are, in fact, typical inflammatory manifestations, it was suggested that PDT-induced acute inflammatory reaction actually leads to vascular damage. In a related report characteristics are shown of cellular inflammatory infiltrate in PDT-treated murine tumor. This work examines the effect of combining PDT with immunotherapy, in an attempt to investigate a possibility of amplification of immune reaction to PDT and its direction towards more pervasive destruction of treated tumors. (authors). 6 refs

  20. Reduction of irradiated tumor cells viability under effect of hyperglycemia

    International Nuclear Information System (INIS)

    Meshcherikova, V.V.; Voloshina, E.A.

    1983-01-01

    On Ehrlich carcinoma cells adapted to growth in vivo and in vitro, cellular mechanisms of short-term hyperglycemia effect have been studied. It has been found that SH by itself leads to the loss of viability of a part of cells of ELD solid tumors manifesting during the first 24 hours upon irradiation according to the interphase death type. Tumor cell radiation injuries arising under the effect of irradiation, usually non realized up to the first division, under SH conditions potentiate its injury effect. The phenomena observed explain partially selective injury of tumoral cells in the course of irradiation under SH conditions which testifies to the prospects of its use in clinics

  1. Effects of low dose mitomycin C on experimental tumor radiotherapy

    International Nuclear Information System (INIS)

    Yang Jianzheng; Liang Shuo; Qu Yaqin; Pu Chunji; Zhang Haiying; Wu Zhenfeng; Wang Xianli

    2001-01-01

    Objective: To evaluate the possibility of low dose mitomycin C(MMC) as an adjunct therapy for radiotherapy. Methods: Change in tumor size tumor-bearing mice was measured. Radioimmunoassay was used to determine immune function of mice. Results: Low dose Mac's pretreatment reduced tumor size more markedly than did radiotherapy only. The immune function in mice given with low dose MMC 12h before radiotherapy was obviously higher than that in mice subjected to radiotherapy only (P<0.05), and was close to that in the tumor-bearing mice before radiotherapy. Conclusion: Low dose MMC could improve the radiotherapy effect. Pretreatment with low dose MMC could obviously improve the immune suppression state in mice caused by radiotherapy. The mechanism of its improvement of radiotherapeutic effect by low dose of MMC might be due to its enhancement of immune function and induction of adaptive response in tumor-bearing mice

  2. An Effective Approach for Immunotherapy Using Irradiated Tumor Cells

    International Nuclear Information System (INIS)

    Mostafa, D.M.B.

    2011-01-01

    This study has been aimed to investigate the effect of injection of Irradiated Ehrlich tumor cells alone or concurrent with immunomodulator in mice before and after challenge with viable Ehrlich tumor cells for enhancement of immune system. This study includes the estimation of survival, tumor size, lymphocyte count, LDH, MTT, granzyme B, and DNA fragmentation. In order to fulfill the target of this study, a total of 120 female swiss albino mice were used. They were divided into two classes vaccinated (injection of vaccine before challenge) and therapeutic class (injection of vaccine after challenge). Each class was divided into four groups, group (1) mice injected with viable Ehrlich tumor cells (G1), group (2) mice injected with irradiated tumor cells (G2), group (3) mice injected with immunomodulator (G3), and group (4) mice injected with irradiated tumor cells + immunomodulator (G4). Results obtained from this study demonstrated that, the lymphocyte count and granzyme B activity were increased in both the vaccinated and therapeutic classes compared with control group. LDH activity was decreased in all groups of vaccinated class and also in G2 and G4 groups of therapeutic class compared with control group. There was a significant increase in percent apoptosis of tumor cells cultured with spleenocytes of the groups of vaccinated class as compared with control group. Cellular DNA from Ehrlich tumor cell line cultured with spleenocytes of immunized groups was fragmented into discrete bands of approximate multiples of 200 bp. Revealing significant apoptosis in tumor cells due to vaccination. It is concluded that, vaccination with irradiated tumor cells is an effective approach in stimulation of immune system against viable tumor cells.

  3. Effects of hyperthermia, radiotherapy and thermoradiotherapy on tumor microvasculature

    International Nuclear Information System (INIS)

    Fujiwara, Kouji

    1987-01-01

    The therapeutic effects of hyperthermia (immersion of tumor-bearing leg in a water bath at 46 deg C for 60 min), radiotherapy (500 rad or 1000 rad) and thermoradiotherapy on VX-2 tumors of the rabbits were studied morphologically. Especially, vascular morphological changes and vascular permeability to ferritin after treatment were investigated by electron microscopy. As assessed by decrease in tumor volume, local hyperthermia potentiated the destructive effect of radiotherapy. The light microscopic pictures invariably suggested prolonged necrotic tendency of tumor cells following thermoradiotherapy. Electron microscopically, 1 day and 3 days after thermoradiotherapy, small blood vessels in the tumors showed swelling and protrusion of endothelial cells in the lumen. Similar morphological changes were obtained only at 3 days after radiotherapy. When vascular permeability to ferritin was examined by electron microscopy, an increase in tumor vascular permeability was occured at 1 day after hyperthermia or thermoradiotherapy, while at 3 days after radiotherapy. These results suggest that the early reaction of tumor microvasculature may be a contributing factor to delayed cell death in tumors after hyperthermia or thermoradiotherapy. (author)

  4. Localization of higher grade tumor foci in potential candidates for active surveillance who opt for radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Sung Kyu Hong

    2013-12-01

    Conclusions: Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients.

  5. SOA-surveillance Nederland

    NARCIS (Netherlands)

    Rijlaarsdam J; Bosman A; Laar MJW van de; CIE

    2000-01-01

    In May 1999 a working group was started to evaluate the current surveillance systems for sexually transmitted diseases (STD) and to make suggestions for a renewed effective and efficient STD surveillance system in the Netherlands. The surveillance system has to provide insight into the prevalence

  6. Containment and surveillance devices

    International Nuclear Information System (INIS)

    Campbell, J.W.; Johnson, C.S.; Stieff, L.R.

    The growing acceptance of containment and surveillance as a means to increase safeguards effectiveness has provided impetus to the development of improved surveillance and containment devices. Five recently developed devices are described. The devices include one photographic and two television surveillance systems and two high security seals that can be verified while installed

  7. The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

    Directory of Open Access Journals (Sweden)

    Stathopoulos Efstathios N

    2010-09-01

    effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo. Conclusion This is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and β-catenin expression.

  8. Atypical teratoid rhabdoid tumors: a population-based clinical outcomes study involving 174 patients from the Surveillance, Epidemiology, and End Results database (1973–2010

    Directory of Open Access Journals (Sweden)

    Lau CS

    2015-09-01

    Full Text Available Christine SM Lau,1,2 Krishnaraj Mahendraraj,1 Ronald S Chamberlain1–31Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George's University School of Medicine, Grenada, West Indies; 3Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Atypical teratoid rhabdoid tumors (ATRTs are rare, highly malignant embryonal tumors of the central nervous system (CNS accounting for 20% of CNS tumors in children under the age of 3. This study examines a large cohort of ATRT patients to determine demographic, clinical, and pathologic factors which impact prognosis and survival. Methods: Demographic and clinical data were abstracted on 174 ATRT patients (171 pediatric patients age <20 and 3 adult patients age ≥20 from the Surveillance, Epidemiology, and End Results database (1973–2010. Standard statistical methodology was used. Results: A total of 174 ATRT cases (mean age of 2.84 years were identified. ATRT had a higher incidence in males (56.3%, Caucasians (59.1%, and children <3 years of age (80.5%, P<0.001. The most common primary sites were the cerebellum (17.8%, ventricles (16.1%, and frontal lobe (12.6%. Mean overall survival was 3.2±0.4 years, while overall and cancer-specific mortality were 63.2% and 56.3%, respectively, P=0.005. Most ATRT cases were treated with surgery alone (58.0%, followed by a combination of surgery and radiation (34.3%, no treatment (6.5%, and radiation alone (1.2%. The use of combination therapy has increased significantly (16.1% since 2005 (P<0.001, while primary surgical resection and radiation therapy rates remain relatively unchanged. The longest survival was observed among ATRT patients receiving combination therapy (5.9±0.7 years, followed by radiation alone (2.8±1.2 years, and surgery alone (1.9±0.4 years, P<0.001. Multivariable analysis identified only distant metastases (OR =4.6 as independently associated with increased mortality

  9. Influenza surveillance

    Directory of Open Access Journals (Sweden)

    Karolina Bednarska

    2016-04-01

    Full Text Available Influenza surveillance was established in 1947. From this moment WHO (World Health Organization has been coordinating international cooperation, with a goal of monitoring influenza virus activity, effective diagnostic of the circulating viruses and informing society about epidemics or pandemics, as well as about emergence of new subtypes of influenza virus type A. Influenza surveillance is an important task, because it enables people to prepare themselves for battle with the virus that is constantly mutating, what leads to circulation of new and often more virulent strains of influenza in human population. As vaccination is the most effective method of fighting the virus, one of the major tasks of GISRS is developing an optimal antigenic composition of the vaccine for the current epidemic season. European Influenza Surveillance Network (EISN has also developed over the years. EISN is running integrated epidemiological and virological influenza surveillance, to provide appropriate data to public health experts in member countries, to enable them undertaking relevant activities based on the current information about influenza activity. In close cooperation with GISRS and EISN are National Influenza Centres - national institutions designated by the Ministry of Health in each country.

  10. Antiangiogenic Effects of Noscapine Enhance Radioresponse for GL261 Tumors

    International Nuclear Information System (INIS)

    Newcomb, Elizabeth W.; Lukyanov, Yevgeniy; Alonso-Basanta, Michelle; Esencay, Min; Smirnova, Iva; Schnee, Tona; Shao Yongzhao; Devitt, Mary Louise; Zagzag, David; McBride, William; Formenti, Silvia C.

    2008-01-01

    Purpose: To assess the effects of noscapine, a tubulin-binding drug, in combination with radiation in a murine glioma model. Methods and Materials: The human T98G and murine GL261 glioma cell lines treated with noscapine, radiation, or both were assayed for clonogenic survival. Mice with established GL261 hind limb tumors were treated with noscapine, radiation, or both to evaluate the effect of noscapine on radioresponse. In a separate experiment with the same treatment groups, 7 days after radiation, tumors were resected and immunostained to measure proliferation rate, apoptosis, and angiogenic activity. Results: Noscapine reduced clonogenic survival without enhancement of radiosensitivity in vitro. Noscapine combined with radiation significantly increased tumor growth delay: 5, 8, 13, and 18 days for control, noscapine alone, radiation alone, and the combination treatment, respectively (p < 0.001). To assess the effect of the combination of noscapine plus radiation on the tumor vasculature, tubule formation by the murine endothelial 2H11 cells was tested. Noscapine with radiation significantly inhibited tubule formation compared with radiation alone. By immunohistochemistry, tumors treated with the combination of noscapine plus radiation showed a decrease in BrdU incorporation, an increase in apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, and a decrease in tumor vessel density compared with tumors treated with radiation alone. Conclusion: Noscapine enhanced the sensitivity of GL261 glioma tumors to radiation, resulting in a significant tumor growth delay. An antiangiogenic mechanism contributed to the effect. These findings are clinically relevant, particularly in view of the mild toxicity profile of this drug

  11. The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b+ Ly6Chi cells to tumor tissue reduces tumor growth

    International Nuclear Information System (INIS)

    Deronic, Adnan; Leanderson, Tomas; Ivars, Fredrik

    2016-01-01

    Previous work has demonstrated immunomodulatory, anti-tumor, anti-metastatic and anti-angiogenic effects of the small molecule quinoline-3-carboxamide tasquinimod in pre-clinical cancer models. To better understand the anti-tumor effects of tasquinimod in transplantable tumor models, we have evaluated the impact of the compound both on recruitment of myeloid cells to tumor tissue and on tumor-induced myeloid cell expansion as these cells are known to promote tumor development. Mice bearing subcutaneous 4 T1 mammary carcinoma tumors were treated with tasquinimod in the drinking water. A BrdU-based flow cytometry assay was utilized to assess the impact of short-term tasquinimod treatment on myeloid cell recruitment to tumors. Additionally, long-term treatment was performed to study the anti-tumor effect of tasquinimod as well as its effects on splenic myeloid cells and their progenitors. Myeloid cell populations were also immune-depleted by in vivo antibody treatment. Short-term tasquinimod treatment did not influence the proliferation of splenic Ly6C hi and Ly6G hi cells, but instead reduced the influx of Ly6C hi cells to the tumor. Treatment with tasquinimod for various periods of time after tumor inoculation revealed that the anti-tumor effect of this compound mainly operated during the first few days of tumor growth. Similar to tasquinimod treatment, antibody-mediated depletion of Ly6C hi cells within that same time frame, caused reduced tumor growth, thereby confirming a significant role for these cells in tumor development. Additionally, long-term tasquinimod treatment reduced the splenomegaly and expansion of splenic myeloid cells during a later phase of tumor development. In this phase, tasquinimod normalized the tumor-induced alterations in myeloerythroid progenitor cells in the spleen but had only limited impact on the same populations in the bone marrow. Our results indicate that tasquinimod treatment reduces tumor growth by operating early after tumor

  12. Effect of misonidazole on radiosensitivity of Ehrlich ascites tumor cells

    International Nuclear Information System (INIS)

    Takeuchi, Hiroshi

    1986-01-01

    The effect of Misonidazole on radiosensitivity of Ehrlich ascites tumor cells was studied in vivo. Ehrlich ascites tumor cells growing intraperitoneally (ICR/SIC mice) for either 1, 4, 6 or 10 days were irradiated in vivo (whole body irradiation) with or without Misonidazole. Immediately after irradiation tumor cells were transplanted intraperitoneally into new animals. Four days later, the propagated surviving cells were removed and counted for analyses. Enhancement ratio of Misonidazole at the surviving fraction of 0.1 were 1.0 (for 1-day-old), 1.3 (for 4-day-old), 1.9 (for 6-day-old), 1.9 (for 10-day-old) and 2.8 (for anoxic cells) respectively. The gradual increase of the enhancement ratio of the ascites tumore cells during intraperitoneal growth from 1 through 10 days might be attributed to an increase of hypoxic tumor cells. Cytotoxicity was not observed at 0.1 mg per gram body weight of Misonidazole but was at 1 mg per gram body weight of Misonidazole in 6-day-old and 10-day-old Ehrlich ascites tumor cells which were supposed to contain hypoxic cells. These results suggest that Misonidazole may prove an effective radiosensitizer for hypoxic tumor cells. (author)

  13. Insights from a Systematic Search for Information on Designs, Costs, and Effectiveness of Poliovirus Environmental Surveillance Systems.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Zimmermann, Marita; Pallansch, Mark A; Thompson, Kimberly M

    2017-12-01

    Poliovirus surveillance plays a critical role in achieving and certifying eradication and will play a key role in the polio endgame. Environmental surveillance can provide an opportunity to detect circulating polioviruses prior to the observation of any acute flaccid paralysis cases. We completed a systematic review of peer-reviewed publications on environmental surveillance for polio including the search terms "environmental surveillance" or "sewage," and "polio," "poliovirus," or "poliomyelitis," and compared characteristics of the resulting studies. The review included 146 studies representing 101 environmental surveillance activities from 48 countries published between 1975 and 2016. Studies reported taking samples from sewage treatment facilities, surface waters, and various other environmental sources, although they generally did not present sufficient details to thoroughly evaluate the sewage systems and catchment areas. When reported, catchment areas varied from 50 to over 7.3 million people (median of 500,000 for the 25% of activities that reported catchment areas, notably with 60% of the studies not reporting this information and 16% reporting insufficient information to estimate the catchment area population size). While numerous studies reported the ability of environmental surveillance to detect polioviruses in the absence of clinical cases, the review revealed very limited information about the costs and limited information to support quantitative population effectiveness of conducting environmental surveillance. This review motivates future studies to better characterize poliovirus environmental surveillance systems and the potential value of information that they may provide in the polio endgame.

  14. Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation

    International Nuclear Information System (INIS)

    Fenton, Bruce M.

    1997-01-01

    Background and purpose: Numerous studies have demonstrated improvements in the oxygenation of tumor cells following both irradiation and carbogen breathing. The current studies were initiated to measure the combined effects of carbogen inhalation plus single and multi-dose irradiation on tumor oxygen availability, to better define the underlying physiological relationships. Materials and methods: Using KHT murine sarcomas, radiation was delivered to the tumor-bearing legs of non-anesthetized mice. Tumors were quick-frozen prior to or following single or multifraction irradiation and carbogen breathing, and intravascular HbO 2 saturation profiles were determined cryospectrophotometrically. Results: HbO 2 levels for blood vessels located near the tumor surface initially decreased following 10 Gy irradiation, then increased and remained elevated. Interior HbO 2 levels remained unchanged. Following 2.5 Gy, HbO 2 changes were minimal. At 24 h following 10 Gy, HbO 2 levels were significantly increased compared to non-irradiated controls, and carbogen breathing produced no additional benefit. At 24 h following five fractions of 2 Gy, HbO 2 levels throughout the tumor volume were significantly higher in carbogen breathing animals than in air breathing controls. Conclusions: Although peripheral blood vessels demonstrated substantial improvements in oxygenation following irradiation, oxygen availability nearer the tumor center remained at very low levels. The utility of carbogen in enhancing tumor oxygen availability was maintained following five clinically relevant fractions. At higher doses, radiation-induced enhancements in HbO 2 levels overshadowed the carbogen effect. For either air or carbogen breathing, a decrease in the percentage of vessels with very low oxygen content did not appear to be a major factor in the reoxygenation of the KHT tumor

  15. Cost-effectiveness of surveillance programs for families at high and moderate risk of hereditary non-polyposis colorectal cancer

    DEFF Research Database (Denmark)

    Olsen, Kim R.; Bojesen, Stig E.; Gerdes, Anne-Marie M.

    2007-01-01

    for the group at high risk. The aim of the present study is to determine cost-effectiveness of surveillance programs where families at both high and moderate risk of HNPCC participate. METHODS: A decision analytic model (Markov model) is developed to assess surveillance programs where families at high......OBJECTIVES: Surveillance programs are recommended to both families at high risk (Amsterdam-positive families with known- and unknown mutation) and moderate risk (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost-effectiveness has so far only been estimated...

  16. Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in a Preclinical Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan L. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Hanna, Alaa [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Raffel, Thomas R. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Wilson, George D. [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J. [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Marples, Brian, E-mail: Brian.Marples@beaumont.edu [Department of Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States)

    2016-09-01

    Purpose: To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts. Methods and Materials: Subcutaneous LLC tumors were established in C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation-induced tumor microenvironment changes were examined after treatment using flow cytometry and antibody-specific histopathology. Normal tissue effects were measured using noninvasive {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography after naïve animals were given whole-lung irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. Results: Over the 2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate (0.31 ± 0.02 mm{sup 3}/d and 0.55 ± 0.04 mm{sup 3}/d, respectively; P<.007). Histopathology showed a significant comparative reduction in the levels of Ki-67 (14.5% ± 3%), hypoxia (10% ± 3.5%), vascular endothelial growth factor (2.3% ± 1%), and stromal-derived factor-1α (2.5% ± 1.4%), as well as a concomitant decrease in CD45{sup +} bone marrow–derived cell (BMDC) migration (7.8% ± 2.2%) after PRT. The addition of AMD3100 also decreased CD45{sup +} BMDC migration in treated tumors (0.6% ± 0.1%). Higher vessel density was observed in treated tumors. No differences were observed in normal lung tissue after PRT or SRT. Conclusions: Pulsed RT–treated tumors exhibited slower growth and reduced hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by tumors in low oxygen microenvironments, including angiogenesis and recruitment of BMDCs.

  17. Studies on anti-tumor effect of electromagnetic waves

    International Nuclear Information System (INIS)

    Kadota, Ikuhito; Wakabayashi, Toshio; Ogoshi, Kyoji; Kamijo, Akemi

    1995-01-01

    Hyperthermia have treated cancer with thermal effect of electromagnetic waves for biological systems, but the expected effect is not shown. Also non-thermal effect of electromagnetic waves is out of consideration. If irradiation conditions of electromagnetic waves with non-thermal anti-tumor effect are obtained, we can expect newly spread in cancer therapy. We had in vivo experiments that electromagnetic waves were irradiated to mice. In some irradiation conditions, the non-thermal anti-tumor effect of electromagnetic waves showed. In order to specify the irradiation conditions, we had in vitro experiments. We found that activity ratio of tumor cells which was measured by MTT method depended on irradiation time and power of electromagnetic waves. These results are useful for the cancer therapy. (author)

  18. The Effectiveness of Ultrasound Surveillance for Hepatocellular Carcinoma in a Canadian Centre and Determinants of Its Success

    Directory of Open Access Journals (Sweden)

    Korosh Khalili

    2015-01-01

    Full Text Available BACKGROUND: The effectiveness of surveillance for hepatocellular carcinoma (HCC using ultrasound (US in North America has been questioned due to the predominance of patients of Caucasian ethnicity and larger body habitus.

  19. A Quantitative Diffuse Reflectance Imaging (QDRI System for Comprehensive Surveillance of the Morphological Landscape in Breast Tumor Margins.

    Directory of Open Access Journals (Sweden)

    Brandon S Nichols

    Full Text Available In an ongoing effort to address the clear clinical unmet needs surrounding breast conserving surgery (BCS, our group has developed a next-generation multiplexed optical-fiber-based tool to assess breast tumor margin status during initial surgeries. Specifically detailed in this work is the performance and clinical validation of a research-grade intra-operative tool for margin assessment based on diffuse optical spectroscopy. Previous work published by our group has illustrated the proof-of-concept generations of this device; here we incorporate a highly optimized quantitative diffuse reflectance imaging (QDRI system utilizing a wide-field (imaging area = 17 cm(2 49-channel multiplexed fiber optic probe, a custom raster-scanning imaging platform, a custom dual-channel white LED source, and an astronomy grade imaging CCD and spectrograph. The system signal to noise ratio (SNR was found to be greater than 40 dB for all channels. Optical property estimation error was found to be less than 10%, on average, over a wide range of absorption (μa = 0-8.9 cm(-1 and scattering (μs' = 7.0-9.7 cm(-1 coefficients. Very low inter-channel and CCD crosstalk was observed (2% max when used on turbid media (including breast tissue. A raster-scanning mechanism was developed to achieve sub-pixel resolution and was found to be optimally performed at an upsample factor of 8, affording 0.75 mm spatially resolved diffuse reflectance images (λ = 450-600 nm of an entire margin (area = 17 cm(2 in 13.8 minutes (1.23 cm(2/min. Moreover, controlled pressure application at the probe-tissue interface afforded by the imaging platform reduces repeated scan variability, providing <1% variation across repeated scans of clinical specimens. We demonstrate the clinical utility of this device through a pilot 20-patient study of high-resolution optical parameter maps of the ratio of the β-carotene concentration to the reduced scattering coefficient. An empirical cumulative

  20. Effects of low dose radiation on tumor-bearing mice

    International Nuclear Information System (INIS)

    Feng Li; Hou Dianjun; Huang Shanying; Deng Daping; Wang Linchao; Cheng Yufeng

    2007-01-01

    Objective: To explore the effects of low-dose radiation on tumor-bearing mice and radiotherapy induced by low-dose radiation. Methods: Male Wistar mice were implanted with Walker-256 sarcoma cells in the right armpit. On day 4, the mice were given 75 mGy whole-body X-ray radiation. From the fifth day, tumor volume was measured, allowing for the creation of a graph depicting tumor growth. Lymphocytes activity in mice after whole-body X-ray radiation with LDR was determinned by FCM. Cytokines level were also determined by ELISA. Results: Compared with the radiotherapy group, tumor growth was significantly slower in the mice pre-exposed to low-dose radiation (P<0.05), after 15 days, the average tumor weight in the mice pre- exposed to low-dose radiation was also significantly lower (P<0.05). Lymphocytes activity and the expression of the CK in mice after whole-body y-ray radiation with LDR increased significantly. Conclusions: Low-dose radiation can markedly improve the immune function of the lymphocyte, inhibit the tumor growth, increase the resistant of the high-dose radiotherapy and enhance the effect of radiotherapy. (authors)

  1. Proceedings of the 3. Muenster symposium on late effects after tumor therapy in childhood and adolescence. Abstracts

    International Nuclear Information System (INIS)

    Willich, Normann; Boelling, Tobias

    2009-01-01

    The volume on the 3rd Muenster Symposion on late effects after tumor therapy in childhood and adolescence contains 7 contributions: Evaluation of side effects after radiotherapy in childhood and adolescence; from retrospective case reports to a perspective, multicentric and transnational approach; late effects surveillance system after childhood cancer in Germany, Austria and parts of Switzerland - update 2009; second malignant neoplasm after childhood cancer in Germany - results from the long-term follow-up of the German childhood cancer registry; secondary neoplasm after Wilm's tumor in Germany; second cancer after total-body irradiation (TBI) in childhood; late toxicity in children undergoing hematopoietic stem cell transplantation with TBI-containing conditioning regimens for hematological malignancies; radiation toxicity following busulfan/melphalan high-dose chemotherapy in the EURO-EWING-99-trials: review of GPOH data

  2. Proceedings of the 3. Muenster symposium on late effects after tumor therapy in childhood and adolescence. Abstracts

    Energy Technology Data Exchange (ETDEWEB)

    Willich, Normann; Boelling, Tobias (eds.) [Univ. Hospital Muenster (Germany). Dept. of Radiotherapy

    2009-08-15

    The volume on the 3rd Muenster Symposion on late effects after tumor therapy in childhood and adolescence contains 7 contributions: Evaluation of side effects after radiotherapy in childhood and adolescence; from retrospective case reports to a perspective, multicentric and transnational approach; late effects surveillance system after childhood cancer in Germany, Austria and parts of Switzerland - update 2009; second malignant neoplasm after childhood cancer in Germany - results from the long-term follow-up of the German childhood cancer registry; secondary neoplasm after Wilm's tumor in Germany; second cancer after total-body irradiation (TBI) in childhood; late toxicity in children undergoing hematopoietic stem cell transplantation with TBI-containing conditioning regimens for hematological malignancies; radiation toxicity following busulfan/melphalan high-dose chemotherapy in the EURO-EWING-99-trials: review of GPOH data.

  3. A Quantitative Diffuse Reflectance Imaging (QDRI) System for Comprehensive Surveillance of the Morphological Landscape in Breast Tumor Margins.

    Science.gov (United States)

    Nichols, Brandon S; Schindler, Christine E; Brown, Jonathon Q; Wilke, Lee G; Mulvey, Christine S; Krieger, Marlee S; Gallagher, Jennifer; Geradts, Joseph; Greenup, Rachel A; Von Windheim, Jesko A; Ramanujam, Nirmala

    2015-01-01

    In an ongoing effort to address the clear clinical unmet needs surrounding breast conserving surgery (BCS), our group has developed a next-generation multiplexed optical-fiber-based tool to assess breast tumor margin status during initial surgeries. Specifically detailed in this work is the performance and clinical validation of a research-grade intra-operative tool for margin assessment based on diffuse optical spectroscopy. Previous work published by our group has illustrated the proof-of-concept generations of this device; here we incorporate a highly optimized quantitative diffuse reflectance imaging (QDRI) system utilizing a wide-field (imaging area = 17 cm(2)) 49-channel multiplexed fiber optic probe, a custom raster-scanning imaging platform, a custom dual-channel white LED source, and an astronomy grade imaging CCD and spectrograph. The system signal to noise ratio (SNR) was found to be greater than 40 dB for all channels. Optical property estimation error was found to be less than 10%, on average, over a wide range of absorption (μa = 0-8.9 cm(-1)) and scattering (μs' = 7.0-9.7 cm(-1)) coefficients. Very low inter-channel and CCD crosstalk was observed (2% max) when used on turbid media (including breast tissue). A raster-scanning mechanism was developed to achieve sub-pixel resolution and was found to be optimally performed at an upsample factor of 8, affording 0.75 mm spatially resolved diffuse reflectance images (λ = 450-600 nm) of an entire margin (area = 17 cm(2)) in 13.8 minutes (1.23 cm(2)/min). Moreover, controlled pressure application at the probe-tissue interface afforded by the imaging platform reduces repeated scan variability, providing operative time scales with improved sensitivity to regions of focal disease that may otherwise be overlooked.

  4. Anti-tumor effect of polysaccharides isolated from Taraxacum ...

    African Journals Online (AJOL)

    The effects of extraction temperature, liquid-solid ratio and extraction time on the yield of PTM were investigated using a Box-Behnken design (BBD). The in vitro anti-tumor effect of PTM on MCF-7 cells was investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, while the mechanism of PTM-induced ...

  5. Radiobiologic effect of intermittent radiation exposure in murine tumors

    International Nuclear Information System (INIS)

    Sugie, Chikao; Shibamoto, Yuta; Ito, Masato; Ogino, Hiroyuki; Miyamoto, Akihiko; Fukaya, Nobuyuki; Niimi, Hiroshige; Hashizume, Takuya

    2006-01-01

    Purpose: In stereotactic irradiation using a linear accelerator, the effect of radiation may be reduced during intermittent exposures owing to recovery from sublethal damage in tumor cells. After our previous in vitro study suggesting this phenomenon, we investigated the issue in murine tumors. Methods and Materials: We used EMT6 and SCCVII tumors approximately 1 cm in diameter growing in the hind legs of syngeneic mice. Three schedules of intermittent radiation were investigated. First, 2 fractions of 10 Gy were given at an interval of 15-360 min to investigate the pattern of recovery from sublethal damage. Second, 5 fractions of 4 Gy were given with interfraction intervals of 2.5-15 min each. Third, 10 fractions of 2 Gy were given with interfraction intervals of 1-7 min each. Doses of 15-20 Gy were also given without interruption to estimate the dose-modifying factors. Tumors were excised 20 h later, and tumor cell survival was determined by an in vivo-in vitro assay. Results: In the 2-fraction experiment, the increase in cell survival with elongation of the interval was much less than that observed in our previous in vitro study. In the 5- and 10-fraction experiments, no significant increase in cell survival was observed after the intermittent exposures. Moreover, cell survival decreased at most points of the 5-fraction experiments by interruption of radiation in both EMT6 and SCCVII tumors. In the 10-fraction experiment, cell survival also decreased when the interruption was 3 or 7 min in EMT6 tumors. Conclusion: The results of the present in vivo studies were different from those of our in vitro studies in which cell survival increased significantly when a few minutes or longer intervals were posed between fractions. This suggests that recovery from sublethal damage in vivo may be counterbalanced by other phenomena such as reoxygenation that sensitizes tumor cells to subsequent irradiation

  6. Internet surveillance, regulation, and chilling effects online: a comparative case study

    Directory of Open Access Journals (Sweden)

    Jonathon W. Penney

    2017-05-01

    Full Text Available With internet regulation and censorship on the rise, states increasingly engaging in online surveillance, and state cyber-policing capabilities rapidly evolving globally, concerns about regulatory “chilling effects” online—the idea that laws, regulations, or state surveillance can deter people from exercising their freedoms or engaging in legal activities on the internet have taken on greater urgency and public importance. But just as notions of “chilling effects” are not new, neither is skepticism about their legal, theoretical, and empirical basis; in fact, the concept remains largely un-interrogated with significant gaps in understanding, particularly with respect to chilling effects online. This work helps fill this void with a first-of-its-kind online survey that examines multiple dimensions of chilling effects online by comparing and analyzing responses to hypothetical scenarios involving different kinds of regulatory actions—including an anti-cyberbullying law, public/private sector surveillance, and an online regulatory scheme, based on the Digital Millennium Copyright Act (DMCA, enforced through personally received legal threats/notices. The results suggest not only the existence and significance of regulatory chilling effects online across these different scenarios but also evidence a differential impact—with personally received legal notices and government surveillance online consistently having the greatest chilling effect on people’s activities online—and certain online activities like speech, search, and personal sharing also impacted differently. The results also offer, for the first time, insights based on demographics and other similar factors about how certain people and groups may be more affected than others, including findings that younger people and women are more likely to be chilled; younger people and women are less likely to take steps to resist regulatory actions and defend themselves; and anti

  7. Effects of human errors on the determination of surveillance test interval

    International Nuclear Information System (INIS)

    Chung, Dae Wook; Koo, Bon Hyun

    1990-01-01

    This paper incorporates the effects of human error relevant to the periodic test on the unavailability of the safety system as well as the component unavailability. Two types of possible human error during the test are considered. One is the possibility that a good safety system is inadvertently left in a bad state after the test (Type A human error) and the other is the possibility that bad safety system is undetected upon the test (Type B human error). An event tree model is developed for the steady-state unavailability of safety system to determine the effects of human errors on the component unavailability and the test interval. We perform the reliability analysis of safety injection system (SIS) by applying aforementioned two types of human error to safety injection pumps. Results of various sensitivity analyses show that; 1) the appropriate test interval decreases and steady-state unavailability increases as the probabilities of both types of human errors increase, and they are far more sensitive to Type A human error than Type B and 2) the SIS unavailability increases slightly as the probability of Type B human error increases, and significantly as the probability of Type A human error increases. Therefore, to avoid underestimation, the effects of human error should be incorporated in the system reliability analysis which aims at the relaxations of the surveillance test intervals, and Type A human error has more important effect on the unavailability and surveillance test interval

  8. Tumor hypoxia - A confounding or exploitable factor in interstitial brachytherapy? Effects of tissue trauma in an experimental rat tumor model

    NARCIS (Netherlands)

    van den Berg, AP; van Geel, CAJF; van Hooije, CMC; van der Kleij, AJ; Visser, AG

    2000-01-01

    Purpose: To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model. Methods and Materials: Afterloading catheters (4) Here implanted in subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij

  9. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

    2003-08-01

    The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

  10. The effects of synoptic weather on influenza infection incidences: a retrospective study utilizing digital disease surveillance

    Science.gov (United States)

    Zhao, Naizhuo; Cao, Guofeng; Vanos, Jennifer K.; Vecellio, Daniel J.

    2018-01-01

    The environmental drivers and mechanisms of influenza dynamics remain unclear. The recent development of influenza surveillance-particularly the emergence of digital epidemiology-provides an opportunity to further understand this puzzle as an area within applied human biometeorology. This paper investigates the short-term weather effects on human influenza activity at a synoptic scale during cold seasons. Using 10 years (2005-2014) of municipal level influenza surveillance data (an adjustment of the Google Flu Trends estimation from the Centers for Disease Control's virologic surveillance data) and daily spatial synoptic classification weather types, we explore and compare the effects of weather exposure on the influenza infection incidences in 79 cities across the USA. We find that during the cold seasons the presence of the polar [i.e., dry polar (DP) and moist polar (MP)] weather types is significantly associated with increasing influenza likelihood in 62 and 68% of the studied cities, respectively, while the presence of tropical [i.e., dry tropical (DT) and moist tropical (MT)] weather types is associated with a significantly decreasing occurrence of influenza in 56 and 43% of the cities, respectively. The MP and the DP weather types exhibit similar close positive correlations with influenza infection incidences, indicating that both cold-dry and cold-moist air provide favorable conditions for the occurrence of influenza in the cold seasons. Additionally, when tropical weather types are present, the humid (MT) and the dry (DT) weather types have similar strong impacts to inhibit the occurrence of influenza. These findings suggest that temperature is a more dominating atmospheric factor than moisture that impacts the occurrences of influenza in cold seasons.

  11. Effect of skin tumor properties on laser penetration

    CSIR Research Space (South Africa)

    Karsten, AE

    2009-06-01

    Full Text Available Computer modeling can be a valuable tool to determine the absorption of laser light in different skin layers. For this study, the optical properties of three different skin tumors were used in the model to evaluate the effect on penetration depth...

  12. Cost-effectiveness analysis of optimal strategy for tumor treatment

    International Nuclear Information System (INIS)

    Pang, Liuyong; Zhao, Zhong; Song, Xinyu

    2016-01-01

    We propose and analyze an antitumor model with combined immunotherapy and chemotherapy. Firstly, we explore the treatment effects of single immunotherapy and single chemotherapy, respectively. Results indicate that neither immunotherapy nor chemotherapy alone are adequate to cure a tumor. Hence, we apply optimal theory to investigate how the combination of immunotherapy and chemotherapy should be implemented, for a certain time period, in order to reduce the number of tumor cells, while minimizing the implementation cost of the treatment strategy. Secondly, we establish the existence of the optimality system and use Pontryagin’s Maximum Principle to characterize the optimal levels of the two treatment measures. Furthermore, we calculate the incremental cost-effectiveness ratios to analyze the cost-effectiveness of all possible combinations of the two treatment measures. Finally, numerical results show that the combination of immunotherapy and chemotherapy is the most cost-effective strategy for tumor treatment, and able to eliminate the entire tumor with size 4.470 × 10"8 in a year.

  13. Combination effect of cisplatin and radiation in murine solid tumors

    International Nuclear Information System (INIS)

    Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

    1986-01-01

    The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

  14. Experimental studies on the effect of perfluorochemicals in tumor irradiation

    International Nuclear Information System (INIS)

    Shinoda, Jun; Iwai, Tomohiko; Hattori, Tatsuaki; Kondo, Hiroaki; Sakai, Noboru; Yamada, Hiroshi

    1984-01-01

    The effects of radiation therapy with Fluosol-DA on rat mammary tumors were studied. The tissue oxygen tension values of tumors in breathing mixed gas (5% carbon dioxide and 95% oxygen) with Fluosol-DA (25 ml/kg, i.v.) were significantly higher than those in room air without Fluosol-DA. The rats were divided into three groups: Group I received Fluosol-DA but no irradiation, Group II was treated with 1000 rads of irradiation using 60 Co without Fluosol-DA in room air and Group III received the same irradiation and Fluosol-DA in breathig mixed gas. In the latter group we observed a prolongation of the survival time and suppression of the tumor growth. (author)

  15. The Effect of Training Data Selection on Face Recognition in Surveillance Application

    Directory of Open Access Journals (Sweden)

    Jamal Ahmad DARGHAM

    2014-12-01

    Full Text Available Face recognition is an important biometric method because of its potential applications in many fields, such as access control and surveillance. In surveillance applications, the distance between the subject and the camera is changing. Thus, in this paper, the effect of the distance between the subject and the camera, distance class, the effect of the number of images per class, and also the effect of session used to acquire the images have been investigated. Three sessions are used to acquire the images in the database. The images in each session were equally divided into three distance classes: CLOSE, MEDIUM, and FAR, according to the distance of the subject from the camera. It was found that using images from the MEDIUM class for training gives better performance than using either the FAR or the CLOSE class. In addition, it was also found that using one image from each class for training gives the same recognition performance as using three images from the MEDIUM class for training. It was also found that as the number of images per class increases, the recognition performance also increases. Lastly, it was found that by using one image per class from all the available database sessions gives the best recognition performance.

  16. Epidemiological surveillance - air and health. Surveillance of effects on health linked to air pollution; Surveillance epidemiologique air et sante. Surveillance des effets sur la sante lies a la pollution atmospherique en milieu urbain

    Energy Technology Data Exchange (ETDEWEB)

    Quenel, Ph; Cassadou, S; Eilstein, D; Filleul, L; Le Goaster, C; Le Tertre, A; Medina, S; Pascal, L; Prouvost, H; Saviuc, Ph; Zeghnoun, A [Institut National de Veille Sanitaire, 94 - Saint Maurice (France); Declerq, Ch [Observatoire Regional de Sante Nord Pas de Calais (France)

    1999-03-01

    In the field of air pollution, the France is the first country to be endowed with a device of epidemiological surveillance allowing to to evaluate and monitor the impact of urban air pollution on the health of population. This new approach is based on the analysis of relationship between pollution indicators and health indicators, it leads to confirm the partnership between actors of environment and health, at the national level as well at the local level. It confirms the development of assessment in the field of environmental health. (N.C.)

  17. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  18. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Directory of Open Access Journals (Sweden)

    Sejal Desai

    Full Text Available Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2 and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper

  19. Estimating the effectiveness of early control measures through school absenteeism surveillance in observed outbreaks at rural schools in Hubei, China.

    Science.gov (United States)

    Fan, Yunzhou; Yang, Mei; Jiang, Hongbo; Wang, Ying; Yang, Wenwen; Zhang, Zhixia; Yan, Weirong; Diwan, Vinod K; Xu, Biao; Dong, Hengjin; Palm, Lars; Liu, Li; Nie, Shaofa

    2014-01-01

    School absenteeism is a common data source in syndromic surveillance, which allows for the detection of outbreaks at an early stage. Previous studies focused on its correlation with other data sources. In this study, we evaluated the effectiveness of control measures based on early warning signals from school absenteeism surveillance in rural Chinese schools. A school absenteeism surveillance system was established in all 17 primary schools in 3 adjacent towns in the Chinese region of Hubei. Three outbreaks (varicella, mumps, and influenza-like illness) were detected and controlled successfully from April 1, 2012, to January 15, 2014. An impulse susceptible-exposed-infectious-recovered model was used to fit the epidemics of these three outbreaks. Moreover, it simulated the potential epidemics under interventions resulting from traditional surveillance signals. The effectiveness of the absenteeism-based control measures was evaluated by comparing the simulated datasets. The school absenteeism system generated 52 signals. Three outbreaks were verified through epidemiological investigation. Compared to traditional surveillance, the school absenteeism system generated simultaneous signals for the varicella outbreak, but 3 days in advance for the mumps outbreak and 2-4 days in advance for the influenza-like illness outbreak. The estimated excess protection rates of control measures based on early signals were 0.0%, 19.0-44.1%, and 29.0-37.0% for the three outbreaks, respectively. Although not all outbreak control measures can benefit from early signals through school absenteeism surveillance, the effectiveness of early signal-based interventions is obvious. School absenteeism surveillance plays an important role in reducing outbreak spread.

  20. Safety and Antihypertensive Effect of Selara® (Eplerenone: Results from a Postmarketing Surveillance in Japan

    Directory of Open Access Journals (Sweden)

    Shoko Takahashi

    2016-01-01

    Full Text Available Prospective postmarketing surveillance of Selara (eplerenone, a selective mineralocorticoid receptor antagonist, was performed to confirm its safety and efficacy for hypertension treatment in Japan. The change in blood pressure after initiation of eplerenone treatment was also examined. Patients with essential hypertension who were eplerenone-naïve were recruited regardless of the use of other antihypertensive drugs. For examination of changes in blood pressure, patients were excluded if eplerenone was contraindicated or used off-label. Patients received 50–100 mg of eplerenone once daily and were observed for 12 weeks. No treatments including antihypertensive drugs were restricted during the surveillance period. Across Japan, 3,166 patients were included for safety analysis. The incidence of adverse drug reactions was 2.4%. The major adverse drug reactions observed were hyperkalemia (0.6%, dizziness, renal impairment, and increased serum potassium (0.2% each. The mean systolic blood pressure decreased from 152.1±19.0 mmHg to 134.8±15.2 mmHg at week 12, and the mean diastolic blood pressure decreased from 85.8±13.7 mmHg to 77.7±11.4 mmHg. There were no significant new findings regarding the type or incidence of adverse reactions, and eplerenone had a clinically significant antihypertensive effect, leading to favorable blood pressure control.

  1. Effective teaming of airborne and ground assets for surveillance and interdiction

    OpenAIRE

    Muratore, Mark J.

    2010-01-01

    Approved for public release; distribution is unlimited As Unmanned Aerial Vehicles (UAVs) become more prevalent on the battlefield, ground forces will have to increasingly rely on them for intelligence, surveillance, and reconnaissance (ISR), as well as target marking, and overwatch operations. The Situational Awareness for Surveillance and Interdiction Operations (SASIO) simulation analysis tool uses Design of Experiments (DOX) to study of aspects of UAV surveillance characteristics in co...

  2. Cost-Effectiveness Analysis of a Mobile Ear Screening and Surveillance Service versus an Outreach Screening, Surveillance and Surgical Service for Indigenous Children in Australia.

    Directory of Open Access Journals (Sweden)

    Kim-Huong Nguyen

    Full Text Available Indigenous Australians experience a high rate of ear disease and hearing loss, yet they have a lower rate of service access and utilisation compared to their non-Indigenous counterparts. Screening, surveillance and timely access to specialist ear, nose and throat (ENT services are key components in detecting and preventing the recurrence of ear diseases. To address the low access and utilisation rate by Indigenous Australians, a collaborative, community-based mobile telemedicine-enabled screening and surveillance (MTESS service was trialled in Cherbourg, the third largest Indigenous community in Queensland, Australia. This paper aims to evaluate the cost-effectiveness of the MTESS service using a lifetime Markov model that compares two options: (i the Deadly Ears Program alone (current practice involving an outreach ENT surgical service and screening program, and (ii the Deadly Ears Program supplemented with the MTESS service. Data were obtained from the Deadly Ears Program, a feasibility study of the MTESS service and the literature. Incremental cost-utility ratios were calculated from a societal perspective with both costs (in 2013-14 Australian dollars and quality-adjusted life years (QALYs discounted at 5% annually. The model showed that compared with the Deadly Ears Program, the probability of an acceptable cost-utility ratio at a willingness-to-pay threshold of $50,000/QALY was 98% for the MTESS service. This cost effectiveness arises from preventing hearing loss in the Indigenous population and the subsequent reduction in associated costs. Deterministic and probability sensitivity analyses indicated that the model was robust to parameter changes. We concluded that the MTESS service is a cost-effective strategy. It presents an opportunity to resolve major issues confronting Australia's health system such as the inequitable provision and access to quality healthcare for rural and remotes communities, and for Indigenous Australians

  3. Cost-Effectiveness Analysis of a Mobile Ear Screening and Surveillance Service versus an Outreach Screening, Surveillance and Surgical Service for Indigenous Children in Australia.

    Science.gov (United States)

    Nguyen, Kim-Huong; Smith, Anthony C; Armfield, Nigel R; Bensink, Mark; Scuffham, Paul A

    2015-01-01

    Indigenous Australians experience a high rate of ear disease and hearing loss, yet they have a lower rate of service access and utilisation compared to their non-Indigenous counterparts. Screening, surveillance and timely access to specialist ear, nose and throat (ENT) services are key components in detecting and preventing the recurrence of ear diseases. To address the low access and utilisation rate by Indigenous Australians, a collaborative, community-based mobile telemedicine-enabled screening and surveillance (MTESS) service was trialled in Cherbourg, the third largest Indigenous community in Queensland, Australia. This paper aims to evaluate the cost-effectiveness of the MTESS service using a lifetime Markov model that compares two options: (i) the Deadly Ears Program alone (current practice involving an outreach ENT surgical service and screening program), and (ii) the Deadly Ears Program supplemented with the MTESS service. Data were obtained from the Deadly Ears Program, a feasibility study of the MTESS service and the literature. Incremental cost-utility ratios were calculated from a societal perspective with both costs (in 2013-14 Australian dollars) and quality-adjusted life years (QALYs) discounted at 5% annually. The model showed that compared with the Deadly Ears Program, the probability of an acceptable cost-utility ratio at a willingness-to-pay threshold of $50,000/QALY was 98% for the MTESS service. This cost effectiveness arises from preventing hearing loss in the Indigenous population and the subsequent reduction in associated costs. Deterministic and probability sensitivity analyses indicated that the model was robust to parameter changes. We concluded that the MTESS service is a cost-effective strategy. It presents an opportunity to resolve major issues confronting Australia's health system such as the inequitable provision and access to quality healthcare for rural and remotes communities, and for Indigenous Australians. Additionally, it may

  4. NKT Cell Subsets Can Exert Opposing Effects in Autoimmunity, Tumor Surveillance and Inflammation

    Science.gov (United States)

    Viale, Rachael; Ware, Randle; Maricic, Igor; Chaturvedi, Varun; Kumar, Vipin

    2014-01-01

    The innate-like natural killer T (NKT) cells are essential regulators of immunity. These cells comprise at least two distinct subsets and recognize different lipid antigens presented by the MHC class I like molecules CD1d. The CD1d-dependent recognition pathway of NKT cells is highly conserved from mouse to humans. While most type I NKT cells can recognize αGalCer and express a semi-invariant T cell receptor (TCR), a major population of type II NKT cells reactive to sulfatide utilizes an oligoclonal TCR. Furthermore TCR recognition features of NKT subsets are also distinctive with almost parallel as opposed to perpendicular footprints on the CD1d molecules for the type I and type II NKT cells respectively. Here we present a view based upon the recent studies in different clinical and experimental settings that while type I NKT cells are more often pathogenic, they may also be regulatory. On the other hand, sulfatide-reactive type II NKT cells mostly play an inhibitory role in the control of autoimmune and inflammatory diseases. Since the activity and cytokine secretion profiles of NKT cell subsets can be modulated differently by lipid ligands or their analogs, novel immunotherapeutic strategies are being developed for their differential activation for potential intervention in inflammatory diseases. PMID:25288922

  5. Use of the vasodilator sodium nitroprusside during local hyperthermia: effects on tumor temperature and tumor response in a rat tumor model

    International Nuclear Information System (INIS)

    Krossnes, Baard Kronen; Mella, Olav; Dahl, Olav

    1996-01-01

    Purpose: The effect of a decrease in the mean arterial blood pressure (MAP) induced by sodium nitroprusside (SNP) on the tumor temperature during hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT 4 An tumor transplanted to the hind limb of BD IX rats. Experiments with two different anesthetics, pentobarbital and the midazolam/fentanyl/fluanisone combination (MFF), were performed to secure reliable conclusions. Methods and Materials: In the tumor response experiments local waterbath HT at 44.0 deg. C was given for 60 min. Sodium nitroprusside was administered as a continuous intravenous infusion to lower the MAP to 60 or 80 mmHg during HT. In two other experiments the temperature at the base of the tumor during HT was measured before and during SNP infusion. In animals without tumor the temperature was measured subcutaneously on the foot during HT with or without SNP-induced hypotension. Results: When SNP was given to lower the MAP to 60 mmHg during HT in MFF anesthetized animals, the median tumor growth time (TGT) was 70 days, compared to 14.5 days in the HT alone group. The corresponding figures were 127 and 12.1 days with pentobarbital anesthesia. In the HT + SNP group, more than 40% cure was observed in both experiments. No cures were seen in any of the other groups. Hyperthermia alone prolonged the TGT slightly, whereas SNP given alone had no effect, compared to controls. When the MAP was lowered to 80 mmHg by SNP infusion during HT (MFF anesthesia), the median TGT was 19.9 days, which was significantly longer than that in the HT alone group (10.9 days). In the MAP range from 60 to 120 mmHg, a nearly linear relationship between the MAP and the tumor temperature was found during HT in MFF anesthetized animals. With both anesthetics, the median temperature at the base of the tumor was about 0.8 deg. C higher during HT when the MAP was lowered to 60 mmHg by SNP. In animals without tumors, the temperature subcutaneously on the foot was 0

  6. PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth

    International Nuclear Information System (INIS)

    Daemen, B.J.; Elsinga, P.H.; Mooibroek, J.; Paans, A.M.; Wieringa, A.R.; Konings, A.W.; Vaalburg, W.

    1991-01-01

    Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-11C]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-[1-11C]tyrosine uptake data were compared to uptake data of L-[1-14C]tyrosine and with data on the incorporation of L-[1-14C]tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-14C]tyrosine into tumor proteins tallied with the L-[1-11C]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-11C]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth

  7. Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

  8. Effects of IL-6 on proliferation and apoptosis of tumor cells multi-irradiated for tumor-bearing mice

    International Nuclear Information System (INIS)

    Liu Yongbiao; Yao Side

    2004-01-01

    A study was carried out on effects of IL-6 on the proliferation and apoptosis of tumor cells and the expression of apoptosis relevant genes (p53, bcl-2) in tumor cells for three kinds of fractional total-body-irradiated tumor-bearing mice. The apoptotic index, proliferative index, S phase fraction of S 180 sarcoma, H 22 hepatocarcinoma and Lewis lung cancer cells were measured by flowcytometry (FCM) after total-body-irradiation and irradiation plus IL-6. The protein expression level of p53, bcl-2 in three kinds of tumors was also determined by the immunohisto-chemical method (UltraSensitive S-P). The results showed that the S phase fraction and proliferation index in Lewis lung cancer cells were lower in the irradiated plus IL-6 group than in the control, while apoptotic index was higher (P 180 sarcoma cells were opposite (P 22 hepatocarcinoma. These results revealed that IL-6 promoted the apoptosis of irradiated Lewis lung cancer cells (P 180 sarcoma (P 22 hepatocarcinoma (P>0.05). In Lewis lung cancer the expression level of p53 was lower in the IL-6 group and higher in S 180 sarcoma (P 22 hepatocarcinoma as compared with the control (P>0.05). It is considered that tumor cell's proportion in the cellular cycle is changed by IL-6 and the effects of IL-6 on the expression of p53, bcl-2 in different three kinds of tumors are different. IL-6 has radio-sensitive effects on some tumors and opposite effects on other tumors, it may be related to the expression of p53 and bcl-2 in tumor cells. (authors)

  9. Effects of surveillance on the rule of law, due process and the presumption of innocence

    NARCIS (Netherlands)

    Galetta, Antonella; de Hert, Paul; Wright, D.; Kreissl, R.

    2015-01-01

    This contribution focuses on the impact of surveillance on the rule of law, due process and the presumption of innocence, key values and principles of a democratic order. It illustrates how they are implemented and enforced in contemporary surveillance societies, while referring to European law and

  10. Combined cytotoxic effects of tumor necrosis factor-alpha with various cytotoxic agents in tumor cell lines that are drug resistant due to mutated p53

    NARCIS (Netherlands)

    Sleijfer, S; Le, T. K. P.; de Jong, S.; Timmer-Bosscha, H; Withoff, S; Mulder, NH

    Several studies suggest that tumor necrosis factor-alpha (TNF) is able to overcome drug resistance in tumors. Whether TNF is able to do so in tumor cell lines that are drug resistant due to a mutation in the tumor suppressor gene p53 is unclear. Therefore, we studied the in vitro cytotoxic effects

  11. Effect of selenium on malignant tumor cells of brain.

    Science.gov (United States)

    Zhu, Z; Kimura, M; Itokawa, Y; Nakatsu, S; Oda, Y; Kikuchi, H

    1995-07-01

    Some reports have demonstrated that selenium can inhibit tumorigenesis in some tissues of animal. However, little is known about the inhibitory effect on malignant tumor cells of brain. The purpose of our study was to determine the biological effect of selenium on growth of rat glioma and human glioblastoma cell lines. Cell lines C6 and A172 were obtained from Japanese Cancer Research Resources Bank, Tokyo, Japan (JCRB). Cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal calf serum at 37 degrees C in a humidified atmosphere of air and 5% CO2. Antiproliferative effects of selenium were evaluated using growth rate assay quantifying cell number by MTT assay. An antiproliferative effect of selenium was found in two cell lines, which was more effective on human A172 glioblastoma and less effective on rat C6 glioma.

  12. Effectiveness and Cost-benefit Evaluation of a Comprehensive Workers' Health Surveillance Program for Sustainable Employability of Meat Processing Workers

    NARCIS (Netherlands)

    Holland, van Berry J.; Reneman, Michiel F; Soer, Remko; Brouwer, Sandra; de Boer, Michiel R

    Objective To evaluate the effectiveness of a comprehensive workers' health surveillance (WHS) program on aspects of sustainable employability and cost-benefit. Methods A cluster randomized stepped wedge trial was performed in a Dutch meat processing company from february 2012 until march 2015. In

  13. Effectiveness and Cost-benefit Evaluation of a Comprehensive Workers' Health Surveillance Program for Sustainable Employability of Meat Processing Workers

    NARCIS (Netherlands)

    van Holland, Berry J; Reneman, Michiel F; Soer, Remko; Brouwer, Sandra; de Boer, Michiel R

    2017-01-01

    Objective To evaluate the effectiveness of a comprehensive workers' health surveillance (WHS) program on aspects of sustainable employability and cost-benefit. Methods A cluster randomized stepped wedge trial was performed in a Dutch meat processing company from february 2012 until march 2015. In

  14. Evidence for more cost-effective surveillance options for bovine spongiform encephalopathy (BSE) and scrapie in Great Britain.

    Science.gov (United States)

    Wall, Ben A; Arnold, Mark E; Radia, Devi; Gilbert, Will; Ortiz-Pelaez, Angel; Stärk, Katharina Dc; Van Klink, Ed; Guitian, Javier

    2017-08-10

    Transmissible spongiform encephalopathies (TSEs) are an important public health concern. Since the emergence of bovine spongiform encephalopathy (BSE) during the 1980s and its link with human Creutzfeldt-Jakob disease, active surveillance has been a key element of the European Union's TSE control strategy. Success of this strategy means that now, very few cases are detected compared with the number of animals tested. Refining surveillance strategies would enable resources to be redirected towards other public health priorities. Cost-effectiveness analysis was performed on several alternative strategies involving reducing the number of animals tested for BSE and scrapie in Great Britain and, for scrapie, varying the ratio of sheep sampled in the abattoir to fallen stock (which died on the farm). The most cost-effective strategy modelled for BSE involved reducing the proportion of fallen stock tested from 100% to 75%, producing a cost saving of ca GBP 700,000 per annum. If 50% of fallen stock were tested, a saving of ca GBP 1.4 million per annum could be achieved. However, these reductions are predicted to increase the period before surveillance can detect an outbreak. For scrapie, reducing the proportion of abattoir samples was the most cost-effective strategy modelled, with limited impact on surveillance effectiveness. This article is copyright of The Authors, 2017.

  15. Effect of anesthetics on the radiosensitivity of a murine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Sheldon, P.W.; Chu, A.M.

    1979-09-01

    The effect of four anesthetics on the single dose of x rays required to locally control 50% of implanted MT tumors was investigated. Compared with unanesthetized animals, no change in radiosensitivity was observed if mice were irradiated under either tribromoethanol or fentanyl-fluanisone-diazepam anesthesia. However, a small but significant degree of radioprotection was observed under chloral hydrate or pentobarbital anesthesia. Hypothermia or increased hypoxia are considered unlikely mechanisms for the protection, a direct chemical action being most probable. The preferred method for immobilizing the mice in order to locally irradiate the tumors was by simple physical restraint (with care taken to minimize physiological stress). However, if anesthesia was a necessity, the present work suggests that for the MT tumor at least the nonprotecting tribromoethanol and fentanyl-fluanisone-diazepam are preferable to the protecting chloral hydrate and pentobarbital. Tribromoethanol is preferable to fetanyl-fluanisone-diazepam in that it produces a smaller drop in temperature. However, it is only a short-acting anesthetic, and prolongation of the state of anesthesia by repeated doses simply prolongs the temperature decline so that there may be no real benefit over fentanyl-fluanisone-diazepam.

  16. Effect of anesthetics on the radiosensitivity of a murine tumor

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Chu, A.M.

    1979-01-01

    The effect of four anesthetics on the single dose of x rays required to locally control 50% of implanted MT tumors was investigated. Compared with unanesthetized animals, no change in radiosensitivity was observed if mice were irradiated under either tribromoethanol or fentanyl-fluanisone-diazepam anesthesia. However, a small but significant degree of radioprotection was observed under chloral hydrate or pentobarbital anesthesia. Hypothermia or increased hypoxia are considered unlikely mechanisms for the protection, a direct chemical action being most probable. The preferred method for immobilizing the mice in order to locally irradiate the tumors was by simple physical restraint (with care taken to minimize physiological stress). However, if anesthesia was a necessity, the present work suggests that for the MT tumor at least the nonprotecting tribromoethanol and fentanyl-fluanisone-diazepam are preferable to the protecting chloral hydrate and pentobarbital. Tribromoethanol is preferable to fetanyl-fluanisone-diazepam in that it produces a smaller drop in temperature. However, it is only a short-acting anesthetic, and prolongation of the state of anesthesia by repeated doses simply prolongs the temperature decline so that there may be no real benefit over fentanyl-fluanisone-diazepam

  17. [Winter surveillance of cold exposure effects on health among the homeless population in the Paris area: data from the Coordinated Health Surveillance of Emergency Department network (Organisation de la surveillance coordonnée des urgences [Oscour(®)])].

    Science.gov (United States)

    Rouquette, A; Mandereau-Bruno, L; Baffert, E; Laaidi, K; Josseran, L; Isnard, H

    2011-12-01

    A program for helping homeless individuals in winter is implemented from November 1(st) to March 31(st) each year in France. Its aim is to prevent morbidity and mortality in this population during cold spells and periods of severe cold. A health surveillance system of the homeless population in the Paris area has been proposed to evaluate the effectiveness of the program and to alert decision-makers if an unusual increase in cold-weather effects is observed. The goal of this study was the creation of an indicator for the proposed surveillance system based on emergency department activity in the Paris area (Oscour(®) Network - Organisation de la surveillance coordonnée des urgences). The winter 2007-2008 computer medical files of 11 emergency departments in the Paris area were examined to confirm diagnosis and ascertain patient-homelessness for each patient visit which was selected from the Oscour(®) database by the patient chief-complaint or diagnosis code referring to hypothermia or frostbites. The proposed indicator is based on the maximization of three criteria: the positive predictive value, the proportion of people identified as being homeless and the number of emergency department visits. A Shewhart control chart was applied to the indicator for the four winters between 2005 and 2009 in the Paris area. Values beyond the statistical threshold would indicate a need for an adjustment to the program strategy. Two hundred and sixteen medical files were analyzed. An indicator was created, "number of emergency department visits of 15 to 69-years-old persons with chief-complaint or diagnosis code referring to hypothermia". It had a positive predictive value estimated near 85 % and identified 61.7 % people as being homeless. In the winter of 2008-2009, the statistical threshold was reached in December during the first cold spell, and again at the beginning of January during a period of severe cold. Our results support the use of this health indicator

  18. Radiosensitizing effect of nitric oxide in tumor cells and experimental tumors irradiated with gamma rays and proton beams

    International Nuclear Information System (INIS)

    Policastro, Lucia L.; Duran, Hebe; Molinari, Beatriz L.; Somacal, Hector R.; Valda, Alejandro A.

    2003-01-01

    Nitric oxide (NO) has been reported to be a radiosensitizer of mammalian cells under hypoxic conditions. In a previous study, we demonstrated an enhancement in radiation response induced by NO in mouse tumor cells under aerobic conditions, with an increasing effect as a function of malignancy. The aim of the present study was to evaluate the effect of NO in tumor cells and in experimental tumors irradiated with γ rays and proton beams. Irradiations were performed with a 137 Cs γ source and with proton beams generated by the TANDAR accelerator. Tumor cells were treated with the NO donor DETA-NO and the sensitizer enhancement ratio (SER) was calculated using the α parameter of the survival curve fitted to the linear-quadratic model. Tumor cells irradiated with protons were radio sensitized by DETA-NO only in the more malignant cells irradiated with low LET protons (2.69±0.08 keV/μm). For higher LET protons there were no radiosensitizing effect. For human tumor cells pre-treated with DETA-NO and irradiated with γ rays, a significantly greater effect was demonstrated in the malignant cells (MCF-7) as compared with the near normal cells (HBL-100). Moreover, a significant decrease in tumor growth was demonstrated in mice pre-treated with the NO donor spermine and irradiated with γ rays and low LET protons as compared with mice irradiated without pre-treatment with the NO donor. In conclusion, we demonstrated a differential effect of NO as a radiosensitizer of malignant cells, both with γ rays and low LET protons. This selectivity, coupled to the in vivo inhibition of tumor growth, is of great interest for the potential use of NO releasing agents in radiotherapy. (author)

  19. Tumor blood flow modifying effects of electrochemotherapy. A potential vascular targeted mechanism

    International Nuclear Information System (INIS)

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

    2003-01-01

    Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut down of the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that, in addition to direct electroporation of tumor cells, other vascular targeted mechanisms are involved in electrochemotherapy with bleomycin or cisplatin, potentially mediated by tumor blood flow reduction, and enhanced tumor cell death as a result of endothelial damage by electrochemotherapy. (author)

  20. Effects of X-irradiation on membranes of tumor cells

    International Nuclear Information System (INIS)

    Fonck, K.

    1982-01-01

    The aim of the investigation was to gain more insight into the effect of ionizing radiation on biomembranes, especially the membrane phospholipids. A general outline of the experimental approach is given in the first chapter. The influence of membrane-active agents and hyperthermia on cell survival after irradiation was studied. Phospholipid turnover was followed by measuring the incorporation of radioactive precursors. The second chapter is an introduction to general radiobiology and to phospholipid metabolism. After the presentation of some physico-chemical properties of ionizing radiation, the effects on cells and cellular components are described. In chapters 3 to 6 the experimental part is described. Chapter 3 starts with the determination of the cellular survival of L5178Y lymphoma cells after X-irradiation. In chapter 4 the lipid composition of lymphosarcoma cell nuclei is presented and in chapter 5 studies on the effect of X-irradiation on the incorporation of palmitate and arachidonate into the phospholipids of lymphosarcoma cells are described. Chapter 6 describes experiments in which lymphosarcoma cells isolated from the spleens of tumor-bearing mice were used to study the effect of a low dose of X-rays (5 Gy) on the incorporation of [ 3 H]palmitate and [ 14 C]arachidonate into the lipids of the tumor cells. These fatty acids were rapidly incorporated especially into the phospholipids of the cells. Chapter 7 contains a general discussion on the experimental results. (Auth.)

  1. Effect of irradiation on microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers

    International Nuclear Information System (INIS)

    Mal'tseva, E.L.; Goloshchapov, A.N.; Pal'mina, N.P.; Burlakova, E.B.

    1982-01-01

    Changes of microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers with developing Ehrlich ascites tumor (EAT) at various terms after lethal irradiation (650 R) were studied by spin probe method. Two iminoxyl radicals localized mainly in lipid bilayer and near probein layers of membrane lipids were used. The character and the degree of microviscosity changes in different zones of nuclear membranes point to different responses towards effect of radiation of cells of tumor-carrier organ and tumor both in viscosity properties, and in change of lipid-protein relations. The significant contribution of near protein lipid layers into general change of nuclear membrane microviscosity is marked. Microviscosity of nuclear membrane causes different responses of cellular nuclear membranes of liver of tumor-carriers and healthy animals as well as considerable (3 times) dilution of nuclear membrane of EAT cells after irradiation. It is shown that temperature dependence of times of rotatory correlation of both probes is more expressed in EAT cells of irradiated tumor-carriers, than in liver

  2. Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Effect Treatment Outcome?

    DEFF Research Database (Denmark)

    Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

    risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

  3. Five-chlorodeoxycytidine, a tumor-selective enzyme-driven radiosensitizer, effectively controls five advanced human tumors in nude mice

    International Nuclear Information System (INIS)

    Greer, Sheldon; Alvarez, Marcy; Mas, Marisol; Wozniak, Chandra; Arnold, David; Knapinska, Anna; Norris, Christina; Burk, Ronald; Aller, Alex; Dauphinee, Michael

    2001-01-01

    Purpose: The study's goals were as follows: (1) to extend our past findings with rodent tumors to human tumors in nude mice, (2) to determine if the drug protocol could be simplified so that only CldC and one modulator, tetrahydrouridine (H 4 U), would be sufficient to obtain efficacy, (3) to determine the levels of deoxycytidine kinase and dCMP deaminase in human tumors, compared to adjacent normal tissue, and (4) to determine the effect of CldC on normal tissue radiation damage to the cervical spinal cord of nude mice. Methods and Materials: The five human tumors used were as follows: prostate tumors, PC-3 and H-1579; glioblastoma, SF-295; breast tumor, GI-101; and lung tumor, H-165. The duration of treatment was 3-5 weeks, with drugs administered on Days 1-4 and radiation on Days 3-5 of each week. The biomodulators of CldC were N-(Phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartyl transcarbamoylase, 5-fluorodeoxycytidine (FdC), resulting in tumor-directed inhibition of thymidylate synthetase, and H 4 U, an inhibitor of cytidine deaminase. The total dose of focused irradiation of the tumors was usually 45 Gy in 12 fractions. Results: Marked radiosensitization was obtained with CldC and the three modulators. The average days in tumor regrowth delay for X-ray compared to drugs plus X-ray, respectively, were: PC-3 prostate, 42-97; H-1579 prostate, 29-115; glioblastoma, 5-51; breast, 50-80; lung, 32-123. Comparative studies with PC-3 and H-1579 using CldC coadministered with H 4 U, showed that both PALA and FdC are dispensable, and the protocol can be simplified with equal and possibly heightened efficacy. For example, PC-3 with X-ray and (1) no drugs, (2) CldC plus the three modulators, (3) a high dose of CldC, and (4) escalating doses of CldC resulted in 0/10, 3/9, 5/10, and 6/9 cures, respectively. The tumor regrowth delay data followed a similar pattern. After treating mice only 1((1)/(2)) weeks with CldC + H 4 U, 92% of the PC-3 tumor cells were found

  4. Surveillance Culture

    DEFF Research Database (Denmark)

    2017-01-01

    What does it mean to live in a world full of surveillance? In this documentary film, we take a look at everyday life in Denmark and how surveillance technologies and practices influence our norms and social behaviour. Researched and directed by Btihaj Ajana and Anders Albrechtslund....

  5. Method of hyperthermia and tumor size influence effectiveness of doxorubicin release from thermosensitive liposomes in experimental tumors.

    Science.gov (United States)

    Willerding, Linus; Limmer, Simone; Hossann, Martin; Zengerle, Anja; Wachholz, Kirsten; Ten Hagen, Timo L M; Koning, Gerben A; Sroka, Ronald; Lindner, Lars H; Peller, Michael

    2016-01-28

    Systemic chemotherapy of solid tumors could be enhanced by local hyperthermia (HT) in combination with thermosensitive liposomes (TSL) as drug carriers. In such an approach, effective HT of the tumor is considered essential for successful triggering local drug release and targeting of the drug to the tumor. To investigate the effect of HT method on the effectiveness of drug delivery, a novel laser-based HT device designed for the use in magnetic resonance imaging (MRI) was compared systematically with the frequently used cold light lamp and water bath HT. Long circulating phosphatidyldiglycerol-based TSL (DPPG2-TSL) with encapsulated doxorubicin (DOX) were used as drug carrier enabling intravascular drug release. Experiments were performed in male Brown Norway rats with a syngeneic soft tissue sarcoma (BN 175) located on both hind legs. One tumor was heated while the second tumor remained unheated as a reference. Six animals were investigated per HT method. DPPG2-TSL were injected i.v. at a stable tumor temperature above 40°C. Thereafter, temperature was maintained for 60min. Total DOX concentration in plasma, tumor tissue and muscle was determined post therapy by HPLC. Finally, the new laser-based device was tested in a MRI environment at 3T using DPPG2-TSL with encapsulated Gd-based contrast agent. All methods showed effective DOX delivery by TSL with 4.5-23.1ng/mg found in the heated tumors. In contrast, DOX concentration in the non-heated tumors was 0.5±0.1ng/mg. Independent of used HT methods, higher DOX levels were found in the smaller tumors. In comparison water bath induced lowest DOX delivery but still showing fourfold higher DOX concentrations compared to the non-heated tumors. With the laser-based applicator, a 13 fold higher DOX deposition was possible for large tumors and a 15 fold higher for the small tumors, respectively. Temperature gradients in the tumor tissue were higher with the laser and cold light lamp (-0.3°C/mm to -0.5°C/mm) compared to

  6. Deployment Health Surveillance

    National Research Council Canada - National Science Library

    DeNicola, Anthony D

    2004-01-01

    ... of stress in causing chronic illness. The lack of comprehensive deployment health surveillance has made it difficult to determine possible causes of adverse health effects reported by Gulf War veterans...

  7. An investigation into the effect of surveillance drones on textile evidence at crime scenes.

    Science.gov (United States)

    Bucknell, Alistair; Bassindale, Tom

    2017-09-01

    With increasing numbers of Police forces using drones for crime scene surveillance, the effect of the drones on trace evidence present needs evaluation. In this investigation the effect of flying a quadcopter drone at different heights over a controlled scene and taking off at different distances from the scene were measured. Yarn was placed on a range of floor surfaces and the number lost or moved from their original position was recorded. It was possible to estimate "safe" distances above and take off distance from the bath mat (2m and 1m respectively), and carpet tile (3m and 1m) which were the roughest surfaces. The maximum distances tested of 5m above and 2m from was not far enough to prevent significant disturbance with the other floor surfaces. This report illustrates the importance of considering the impact of new technologies into a forensic workflow on established forensic evidence prior to implementation. Copyright © 2017 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.

  8. Tumor cell killing effect of boronated dipeptide. Boromethylglycylphenylalanine on boron neutron capture therapy for malignant brain tumors

    International Nuclear Information System (INIS)

    Takagaki, Masao; Ono, Koji; Masunaga, Shinichiro; Kinashi, Yuko; Kobayashi, Toru; Oda, Yoshifumi; Kikuchi, Haruhiko; Spielvogel, B.F.

    1994-01-01

    The killing effect of Boron Neutron Capture Therapy; BNCT, is dependant on the boron concentration ratio of tumor to normal brain (T/N ratio), and also that of tumor to blood (T/B ratio). The clinical boron carrier of boro-captate (BSH) showed the large T/N ratio of ca. 8, however the T/B ratio was around 1, which indicated nonselective accumulation into tumor. Indeed high boron concentration of blood restrict the neutron irradiation dose in order to circumvent the normal endothelial damage, especially in the case of deeply seated tumor. Phenylalanine analogue of para borono-phenylalanine (BPA) is an effective boron carrier on BNCT for malignant melanoma. For the BNCT on brain tumors, however, BPA concentration in normal brain was reported to be intolerably high. In order to improve the T/N ratio of BPA in brain, therefore, a dipeptide of boromethylglycylphenylalanine (BMGP) was synthesized deriving from trimethylglycine conjugated with BPA. It is expected to be selectively accumulated into tumor with little uptake into normal brain. Because a dipeptide might not pass through the normal blood brain barrier (BBB). Its killing effect on cultured glioma cell, T98G, and its distribution in rat brain bearing 9L glioma have been investigated in this paper. The BNCT effect of BMGP on cultured cells was nearly triple in comparison with DL-BPA. The neutron dose yielding 1% survival ratio were 7x10 12 nvt for BMGP and 2x10 13 nvt for BPA respectively on BNCT after boron loading for 16 hrs in the same B-10 concentration of 20ppm. Quantitative study of boron concentration via the α-auto radiography and the prompt gamma ray assay on 9L brain tumor rats revealed that T/N ratio and T/B ratio are 12.0 and 3.0 respectively. Those values are excellent for BNCT use. (author)

  9. Effects of IL-6 on proliferation and apoptosis of tumor cells multi-irradiated for tumor-bearing mice

    Energy Technology Data Exchange (ETDEWEB)

    Yongbiao, Liu [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Xuzhou Medical Univ., Xuzhou (China); Side, Yao [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Kai, Mei; Ying, Liu; Jie, Zhao; Xianwen, Zhang; Qiang, Zhou; Xingzhi, Hao [Xuzhou Medical Univ., Xuzhou (China)

    2004-05-15

    A study was carried out on effects of IL-6 on the proliferation and apoptosis of tumor cells and the expression of apoptosis relevant genes (p53, bcl-2) in tumor cells for three kinds of fractional total-body-irradiated tumor-bearing mice. The apoptotic index, proliferative index, S phase fraction of S{sub 180} sarcoma, H{sub 22} hepatocarcinoma and Lewis lung cancer cells were measured by flowcytometry (FCM) after total-body-irradiation and irradiation plus IL-6. The protein expression level of p53, bcl-2 in three kinds of tumors was also determined by the immunohisto-chemical method (UltraSensitive S-P). The results showed that the S phase fraction and proliferation index in Lewis lung cancer cells were lower in the irradiated plus IL-6 group than in the control, while apoptotic index was higher (P<0.05). However, the experimental results for S{sub 180} sarcoma cells were opposite (P<0.01). In addition, no significant effects were observed in H{sub 22} hepatocarcinoma. These results revealed that IL-6 promoted the apoptosis of irradiated Lewis lung cancer cells (P<0.05), while the apoptosis of S{sub 180} sarcoma (P<0.05) was restrained, and there was no significant effects on the cellular cycle of H{sub 22} hepatocarcinoma (P>0.05). In Lewis lung cancer the expression level of p53 was lower in the IL-6 group and higher in S{sub 180} sarcoma (P<0.05), while unvaried in H{sub 22} hepatocarcinoma as compared with the control (P>0.05). It is considered that tumor cell's proportion in the cellular cycle is changed by IL-6 and the effects of IL-6 on the expression of p53, bcl-2 in different three kinds of tumors are different. IL-6 has radio-sensitive effects on some tumors and opposite effects on other tumors, it may be related to the expression of p53 and bcl-2 in tumor cells. (authors)

  10. Comparison of the effect between an active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue and that using irradiated tumor cells

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji; Yamamoto, Yoichi; Morita, Masaru

    1983-01-01

    The effect of the active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was compared with that of irradiated (10,000 rads) tumor cells on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 6th day, irradiation with a dose of 3,000 rads was performed. On the 14th day, tumor cells and concomitant mononuclear cells which were separated from the low-dose irradiated tumor tissue (2,000 rads on the 6th day) were injected into the left hind paws of one group of the tumor-bearing mice. On the same day, irradiated MM46 tumor cells were injected into the left hind paws of another group of the tumor-bearing mice. Effectiveness of these two methods of active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. The active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was far more effective than irradiated tumor cells on this tumor system involved. (author)

  11. The anti-tumor effect and biological activities of the extract JMM6 ...

    African Journals Online (AJOL)

    Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the ...

  12. Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

    National Research Council Canada - National Science Library

    Tsan, Min-Fu; Gao, Baochong

    2005-01-01

    .... and whether depletion of tumor-associated macrophages has any effect on the tumor growth. The breast cancer model was established in BALB/c mice by subcutaneous injection of estrogen receptor-positive murine mammary tumor cells (4T1...

  13. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    KAUST Repository

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  14. Surveillance Pleasures

    DEFF Research Database (Denmark)

    Albrechtslund, Anders

    The notorious intensification and digitalization of surveillance technologies and practices in today’s society has brought about numerous changes. These changes have been widely noticed, described and discussed across many academic disciplines. However, the contexts of entertainment, play...

  15. Effects of sex on the incidence and prognosis of spinal meningiomas: a Surveillance, Epidemiology, and End Results study.

    Science.gov (United States)

    Westwick, Harrison J; Shamji, Mohammed F

    2015-09-01

    Most spinal meningiomas are intradural lesions in the thoracic spine that present with both local pain and myelopathy. By using the large prospective Surveillance, Epidemiology, and End Results (SEER) database, the authors studied the incidence of spinal meningiomas and examined demographic and treatment factors predictive of death. Using SEER*Stat software, the authors queried the SEER database for cases of spinal meningioma between 2000 and 2010. From the results, tumor incidence and demographic statistics were computed; incidence was analyzed as a function of tumor location, pathology, age, sex, and malignancy code. Survival was analyzed by using a Cox proportional hazards ratio in SPSS for age, sex, marital status, primary site, size quartile, treatment modality, and malignancy code. In this analysis, significance was set at a p value of 0.05. The 1709 spinal meningiomas reported in the SEER database represented 30.7% of all primary intradural spinal tumors and 7.9% of all meningiomas. These meningiomas occurred at an age-adjusted incidence of 0.193 (95% CI 0.183-0.202) per 100,000 population and were closely related to sex (337 [19.7%] male patients and 1372 [80.3%] female patients). The Cox hazard function for mortality in males was higher (2.4 [95% CI1.7-3.5]) and statistically significant, despite the lower lesion incidence in males. All-cause survival was lowest in patients older than 80 years. Primary site and treatment modality were not significant predictors of mortality. Spinal meningiomas represent a significant fraction of all primary intradural spinal tumors and of all meningiomas. The results of this study establish the association of lesion incidence and survival with sex, with a less frequent incidence in but greater mortality among males.

  16. Surveillance of adverse effects following vaccination and safety of immunization programs.

    Science.gov (United States)

    Waldman, Eliseu Alves; Luhm, Karin Regina; Monteiro, Sandra Aparecida Moreira Gomes; Freitas, Fabiana Ramos Martin de

    2011-02-01

    The aim of the review was to analyze conceptual and operational aspects of systems for surveillance of adverse events following immunization. Articles available in electronic format were included, published between 1985 and 2009, selected from the PubMed/Medline databases using the key words "adverse events following vaccine surveillance", "post-marketing surveillance", "safety vaccine" and "Phase IV clinical trials". Articles focusing on specific adverse events were excluded. The major aspects underlying the Public Health importance of adverse events following vaccination, the instruments aimed at ensuring vaccine safety, and the purpose, attributes, types, data interpretation issues, limitations, and further challenges in adverse events following immunization were describe, as well as strategies to improve sensitivity. The review was concluded by discussing the challenges to be faced in coming years with respect to ensuring the safety and reliability of vaccination programs.

  17. Adverse effect after external radiotherapy for brain tumors

    International Nuclear Information System (INIS)

    Yoshii, Yoshihiko; Takano, Shingo; Yanaka, Kiyoyuki

    1989-01-01

    This report discusses the effects on normal brain tissue of radiotherapy in relation to age and irradiation dose as determined from whole-brain sections of the autopsied brains with tumors. Twenty four patients (7 glioblastomas, 2 benign gliomas, 12 brain metastases, 2 malignant lymphomas, and 1 pituitary adenoma) older than 65 years (aged), and 17 younger than 65 years (non-aged) were treated by cobalt- or linear accelerator radiotherapy. Nine patients without brain disease (4 aged and 5 non-aged) were used as a control group. The histological findings were evaluated by grading the small and capillary vessels, fibrinoid necrosis, and myelination in the white matter in whole-brain sections. Those findings were compared to the irradiation doses within all radiation fields in whole-brain sections corresponding to CT scans. Hyalinization of the small vessels was observed within the postradiation 12 months in fields exposed to total doses of less than 800 neuret. Hyalinization of the capillary vessels was greater in the irradiated group than in the control group. Demyelination was observed within the postradiation 12 months in fields irradiated by more than 800 neuret in aged patients and in fields irradiated by less than 800 neuret in non-aged patients. Fibrinoid necrosis was observed after the post-radiation 12 months in fields irradiated by less than 800 neuret in aged patients and in fields irradiated by more than 800 neuret in non-aged patients. It is worth noting that in non-aged patients with brain tumors, adverse effects of radiotherapy on vessels and parenchyma were very high even in low-dose radiation areas; and in aged patients fibrinoid necrosis, which indicates irreversible damage of vessels, was observed in low-dose radiation areas. (author)

  18. Composition and mechanism of anti-tumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice

    Science.gov (United States)

    We investigated anti-tumor effects of the following four extracts of freeze-dried Hericium erinaceus mushrooms in Balb/c mice intracutaneously transplanted on the backs with CT-26 colon cancer cells: HWE, hot-water extraction by boiling in water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W...

  19. The effect of surveillance and appreciative inquiry on puerperal infections: a longitudinal cohort study in India.

    Directory of Open Access Journals (Sweden)

    Julia Hussein

    Full Text Available OBJECTIVE: To evaluate the effects of an intervention comprising surveillance and an organisational change called Appreciative Inquiry on puerperal infections in hospitals in Gujarat state, India. METHODS: This longitudinal cohort study with a control group was conducted over 16 months between 2010 and 2012. Women who delivered in six hospitals were followed-up. After a five month pre-intervention period, the intervention was introduced in three hospitals. Monthly incidence of puerperal infection was recorded throughout the study in all six hospitals. A chi-square test and logistic regression were used to examine for associations, trends and interactions between the intervention and control groups. FINDINGS: Of the 8,124 women followed up, puerperal infections were reported in 319 women (3.9% over the course of the study. Puerperal sepsis/genital tract infections and urinary tract infections were the two most common puerperal infections. At the end of the study, infection incidence in the control group halved from 7.4% to 3.5%. Levels in the intervention group reduced proportionately even more, from 4.3% to 1.7%. A chi-square test for trend confirmed the reduction of infection in the intervention and control groups (p<0.0001 but the trends were not statistically different from one another. There was an overall reduction of infection by month (OR = 0.94 95% CI 0.91-0.97. Risk factors like delivery type, complications or delivery attendant showed no association with infection. CONCLUSION: Interruption of resource flows in the health system occurred during the intervention phase, which may have affected the findings. The incidence of infection fell in both control and intervention groups during the course of the study. It is not clear if appreciative inquiry contributed to the reductions observed. A number of practical and methodological limitations were faced. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN03513186.

  20. Efficacy and biological effects of techniques used to induce hypoxia in tumors

    International Nuclear Information System (INIS)

    Rockwell, S.; Moulder, J.E.; Martin, D.F.

    1985-01-01

    The authors tested several aspects of the assumptions using BA1112 rat rhabdomyosacromas and EMT6 mouse mammary tumors. Both techniques were effective in producing hypoxia: survival curves for tumors made hypoxic by the 2 techniques were the same, and were indistinguishable from survival curves for hypoxic tumor cells in vitro. Induction of hypoxia for the 30-60 min necessary for irradiation did not alter the yield or clonogenicity of cells suspended from the tumors. Longer clamping was cytotoxic. Clamping did not alter tumor growth unless a major blood vessel was injured. However, clamping BA1112 tumors for 30 min and removing the clamp just before irradiation altered the tumor cell survival curve and TCD/sub 50/. Anesthesia or restrain, often used during clamping, can have major effects

  1. Effects of Acanthus ebracteatus Vahl on tumor angiogenesis and on tumor growth in nude mice implanted with cervical cancer

    International Nuclear Information System (INIS)

    Mahasiripanth, Taksanee; Hokputsa, Sanya; Niruthisard, Somchai; Bhattarakosol, Parvapan; Patumraj, Suthiluk

    2012-01-01

    The aim of this study was to examine the effects of the crude extract of Acanthus ebracteatus Vahl (AE) on tumor growth and angiogenesis by utilizing a tumor model in which nude mice were implanted with cervical cancer cells containing human papillomavirus 16 DNA (HPV-16 DNA). The growth-inhibitory effect of AE was investigated in four different cell types: CaSki (HPV-16 positive), HeLa (HPV-18 positive), hepatocellular carcinoma cells (HepG2), and human dermal fibroblast cells (HDFs). The cell viabilities and IC 50 values of AE were determined in cells incubated with AE for different lengths of time. To conduct studies in vivo, female BALB/c nude mice (aged 6–7 weeks, weighing 20–25 g) were used. A cervical cancer-derived cell line (CaSki) with integrated HPV-16 DNA was injected subcutaneously (1 × 10 7 cells/200 μL) in the middle dorsum of each animal (HPV group). One week after injection, mice were fed orally with AE crude extract at either 300 or 3000 mg/kg body weight/day for 14 or 28 days (HPV-AE groups). Tumor microvasculature and capillary vascularity were determined using laser scanning confocal microscopy. Tumor tissue was collected from each mouse to evaluate tumor histology and vascular endothelial growth factor (VEGF) immunostaining. The time-response curves of AE and the dose-dependent effect of AE on growth inhibition were determined. After a 48-hour incubation period, the IC 50 of AE in CaSki was discovered to be significantly different from that of HDFs (P < 0.05). A microvascular network was observed around the tumor area in the HPV group on days 21 and 35. Tumor capillary vascularity in the HPV group was significantly increased compared with the control group (P < 0.001). High-dose treatment of AE extract (HPV-3000AE group) significantly attenuated the increase in VEGF expression and tumor angiogenesis in mice that received either the 14- or 28-day treatment period (P < 0.001). Our novel findings demonstrated that AE crude extract could

  2. The effect of PPAR-γ agonist on 18F-FDG uptake in tumor and macrophages and tumor cells

    International Nuclear Information System (INIS)

    Kim, Se-Lim; Kim, Eun-Mi; Cheong, Su-Jin; Lee, Chang-Moon; Kim, Dong Wook; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Yim, Chang Yeol

    2009-01-01

    Purpose: The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors, and its role in adipogenesis and glucose metabolism has been well established. PPAR-γ agonists have been shown to inhibit many cytokines and to have anti-inflammatory effects. In pathologic conditions, enhanced fluoro-2-deoxy-D-glucose (FDG) uptake is observed not only in malignant tumors but also in inflammatory lesions, and this uptake occurs through the glucose transporter in these cells. Thus, the present study was undertaken to investigate the potential of using PPAR-γ's glucose uptake ability as a diagnostic tool to differentiate between macrophage and tumor cells. Materials and Methods: Cellular uptake studies were carried out on macrophage and two tumor cell lines for comparison by using 18 F-FDG. Western blot analysis was performed to determine the expression levels of both the glucose transporter and hexokinase protein. To confirm the possibility of differentiation between tumor and inflammatory lesions using rosiglitazone based on in vitro studies, 18 F-FDG (3.7x10 6 Bq) uptake in A549 and RAW 264.7 xenograft mice was compared. Results: The cellular uptake study findings were quite different for macrophages and tumor cells. 18 F-FDG uptakes by macrophages decreased by about 60% but was increased twofold in tumor cells after rosiglitazone treatment. Moreover, the expressions of proteins related to glucose uptake correlated well with cellular glucose accumulation in both cell types. Higher tumor uptake was observed after the injection of rosiglitazone in A549 xenograft mice (1.58±0.55 to 4.66±1.16), but no significant change of 18 F-FDG uptake was shown in RAW 264.7 xenograft mice (4.04±1.16 to 4.00±0.14). Conclusion: The present study demonstrates the roles of PPAR-γ agonist on FDG uptake in macrophages and tumor cells in vitro and in vivo. Our findings suggest that rosiglitazone has the

  3. Effect of anemia on tumor radiosensitivity under normo and hyperbaric conditions

    International Nuclear Information System (INIS)

    Rojas, A.; Stewart, F.A.; Smith, K.A.; Soranson, J.A.; Randhawa, V.S.; Stratford, M.R.; Denekamp, J.

    1987-01-01

    The effect of chronic anemia on tumor radiosensitivity in a murine tumor has been investigated. Anemia was induced by bilateral kidney irradiation given several months before tumor implantation. Anemic, anemic transfused, and normal non-anemic age-matched tumor bearing animals were irradiated with X rays (2 F/24 hr) either in air, air plus misonidazole, or under hyperbaric oxygen. The most resistant response was that of tumors grown in normal mice treated in air. Anemia produced an increase in radiosensitivity which was further enhanced by red blood cell replacement. The most sensitive overall response was seen in the anemic-transfused group treated with HBO

  4. Effect of administration route on FES uptake into MCF-7 tumors

    International Nuclear Information System (INIS)

    Downer, Joanna B.; Jones, Lynne A.; Katzenellenbogen, John A.; Welch, Michael J.

    2001-01-01

    We have observed that intraperitoneal administration of [ 18 F]fluoroestradiol (FES), a radiolabeled estrogen receptor ligand, results in higher abdominal organ uptake and slower blood clearance than intravenous administration in female mice. In SCID mice bearing MCF-7 human tumors SC, IP administration resulted in tumor uptake that was only about one third that obtained with IV administration. Thus, the route of administration of a radiopharmaceutical for imaging or radiotherapy of a tumor in the abdomen, an ovarian tumor, for example, could have a profound effect on the efficiency and selectivity of delivery of the agent to the tumor

  5. Effect of certain variables on the tumor and tissue distribution of tracers. Salicylates and vasoactive drugs

    International Nuclear Information System (INIS)

    Halpern, S.E.; Hagan, P.; Stern, P.; Gordon, R.; Dabbs, J.

    1981-01-01

    Attempts were made to increase the viable tumor concentration of 54Mn and 67Ga in a rat hepatoma model by administering rat angiotensin, tolazoline, and salicylates. Salicylates increased the tumor concentrations of 54Mn and improved 65Mn viable tumor/background ratios. 67Ga was not affected by the salicylates. The salicylate effect appeared to be mediated by intracellular mechanisms rather than alterations in plasma protein binding. Rat angiotensin slightly increased the concentrations of 67Ga in the tumors but not enough to suggest that it would be useful clinically. Tolazoline did not increase tumor uptake of the tracers

  6. Anti-tumor effect of total body irradiation of low doses on WHT/Ht mice

    International Nuclear Information System (INIS)

    Miyamoto, Miyako; Sakamoto, Kiyohiko

    1987-01-01

    The effect of low dose (0.05 - 1.0 Gy) of total body irradiation (TBI) on non-tumor bearing and tumor bearing mice were investigated. Mice received TBI of 0.1 Gy during 6 - 12 hours before tumor cell inoculation demonstrated to need larger number of tumor cells (approximately 2.5 times) for 50 per cent tumor incidence, compared to recipient mice not to receive TBI. On the other hand, in tumor bearing mice given 0.1 Gy of TBI only tumor cell killing effect was not detected, however enhancement of tumor cell killing effect and prolonged growth delay were observed when tumor bearing mice were treated with 0.1 Gy of TBI in combined with local irradiation on tumors, especially cell killing effect was remarkable in dose range over 6 Gy of local exposure. The mechanism of the effect of 0.1 Gy TBI is considered to be host mediated reactions from the other our experimental results. (author)

  7. Malignant central nervous system tumors among adolescents and young adults (15-39 years old) in 14 Southern-Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns.

    Science.gov (United States)

    Georgakis, Marios K; Papathoma, Paraskevi; Ryzhov, Anton; Zivkovic-Perisic, Snezana; Eser, Sultan; Taraszkiewicz, Łukasz; Sekerija, Mario; Žagar, Tina; Antunes, Luis; Zborovskaya, Anna; Bastos, Joana; Florea, Margareta; Coza, Daniela; Demetriou, Anna; Agius, Domenic; Strahinja, Rajko M; Themistocleous, Marios; Tolia, Maria; Tzanis, Spyridon; Alexiou, George A; Papanikolaou, Panagiotis G; Nomikos, Panagiotis; Kantzanou, Maria; Dessypris, Nick; Pourtsidis, Apostolos; Petridou, Eleni T

    2017-11-15

    Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15-39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern-Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program. Malignant CNS tumors diagnosed in AYAs during the period spanning 1990-2014 were retrieved from 14 population-based cancer registries in the SEE region (n = 11,438). Age-adjusted mortality rates were calculated and survival patterns were evaluated via Kaplan-Meier curves and Cox regression analyses, and they were compared with respective 1990-2012 figures from SEER (n = 13,573). Mortality rates in SEE (range, 11.9-18.5 deaths per million) were higher overall than the SEER rate (9.4 deaths per million), with decreasing trends in both regions. Survival rates increased during a comparable period (2001-2009) in SEE and SEER. The 5-year survival rate was considerably lower in the SEE registries (46%) versus SEER (67%), mainly because of the extremely low rates in Ukraine; this finding was consistent across age groups and diagnostic subtypes. The highest 5-year survival rates were recorded for ependymomas (76% in SEE and 92% in SEER), and the worst were recorded for glioblastomas and anaplastic astrocytomas (28% in SEE and 37% in SEER). Advancing age, male sex, and rural residency at diagnosis adversely affected outcomes in both regions. Despite definite survival gains over the last years, the considerable outcome disparities between the less affluent SEE region and the United States for AYAs with malignant CNS tumors point to health care delivery inequalities. No considerable prognostic deficits for CNS tumors are evident for AYAs versus children. Cancer 2017;123:4458-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. iNOS+ macrophages: potential alternate and tool for effective tumor therapy

    International Nuclear Information System (INIS)

    Prakash, Hridayesh; KIug, Felix; Jäger, Dirk; Hammerling, Gunter; Beckhove, Philipp

    2014-01-01

    Inefficient migration of immune effector cells in the tumor is a major limitation of effective therapy against solid tumors. This is due to immunosuppressive micro environment and impermissive endothelium which protects tumors from immune attack which is attributed to massive infiltration of tumors by macrophages which are known as tumor associated macrophages which are INOS low , Arginase- 1+ , Ym- 1+ , CD206 + (known as M2 or alternatively activated or tumor associated macrophages). Accumulation of M2 has been associated with the poor prognosis in the majority of cancer patients. Radiotherapy has recently been introduced as a potential strategy to improve cancer immunotherapy and tumor immune rejection. This is the only clinically advanced approach for noninvasive, site-specific intervention in cancer patients. Majority of cancer patients are routinely irradiated with therapeutic and high doses of γ-radiations which frequently manifest severe local/systemic acute. Low dose radiation (LDR) on the other hand may provide good alternatives of HDR for avoiding such toxicities. In this line, our pioneer study demonstrated that local/systemic low dose irradiation of tumors (2 Gy) effectively modified tumor micro environment and facilitated infiltration of peripheral immune effectors cells (T-cells) in neuroendocrine tumor of pancreas called insulinoma in RIP1-Tag5 (RT5) mice and primary human pancreatic carcinoma. Such tumor infiltration of T cells remained strictly dependent on iNOS + peritumoral macrophages. Our study also explicitly revealed that adoptive transfer of iNOS expressing macrophages in unirradiated RIP1-Tag5 (RT5) also offer a promising intervention to establish those populations of macrophages in the tumor tissue that enable therapeutic efficacy of cancer immunotherapy. We here demonstrate the critical role of iNOS + macrophages in joint regulation of tumor micro environment (angiogenesis) as well as effector T cell recruitment into tumor tissue and

  9. Inhibitory effect of sequential combined chemotherapy and radiotherapy on growth of implanted tumor in mice

    International Nuclear Information System (INIS)

    Okada, Kouji

    1983-01-01

    Sequential chemotherapy using FT-207, adriamycin and mitomycin C followed by radiotherapy was attempted to achieve effective inhibition against implanted tumor in C57BL/6 black mice bearing YM-12 tumors. Sequential combined chemotherapy was more effective than single drug chemotherapy or combined chemotherapy of other drugs. Addition of radiotherapy to the sequential combined chemotherapy was successful for enhancing therapeutic effect. (author)

  10. T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

    Directory of Open Access Journals (Sweden)

    Kim Tae-Sik

    2011-06-01

    Full Text Available Abstract Background Although the graft-versus-tumor (GVT effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

  11. Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors

    Directory of Open Access Journals (Sweden)

    Shanawaz Mohammed Ghouse

    2018-01-01

    Full Text Available Summary: High numbers of mast cells populate the stroma of many types of neoplasms, including human papilloma virus-induced benign and malignant tumors in man and mouse. Equipped with numerous pattern recognition receptors and capable of executing important pro-inflammatory responses, mast cells are considered innate sentinels that significantly impact tumor biology. Mast cells were reported to promote human papilloma virus (HPV-induced epithelial hyperproliferation and neo-angiogenesis in an HPV-driven mouse model of skin cancer. We analyzed HPV-induced epithelial hyperplasia and squamous cell carcinoma formation, as well as growth of tumors inoculated into the dermis, in mice lacking skin mast cells. Unexpectedly, the absence of mast cells had no effect on HPV-induced epithelial growth or angiogenesis, on growth kinetics of inoculated tumors, or on the immunological tumor micro-milieu. Thus, the conspicuous recruitment of mast cells into tumor tissues cannot necessarily be equated with important mast cell functions in tumor growth. : Mast cells accumulate in high numbers in many human tumors, and they are widely viewed as important promoters of tumor growth. Ghouse et al. show that growth, angiogenesis, and the immunological micro-milieu of tumors growing in mice genetically deficient for mast cells are unchanged compared to control tumors. Keywords: mast cells, HPV-induced skin cancer, tumor angiogenesis, tumor micro-milieu

  12. The Effect of Tumor-Prostate Ratio on Biochemical Recurrence after Radical Prostatectomy

    Directory of Open Access Journals (Sweden)

    Sung Yong Cho

    2016-08-01

    Full Text Available Purpose: Prostate tumor volume calculated after surgery using pathologic tissue has been shown to be an independent risk factor for biochemical recurrence. Nonetheless, prostate size varies among individuals, regardless of the presence or absence of cancer. We assumed to be lower margin positive rate in the surgical operation, when the prostate volume is larger and the tumor lesion is same. Thus, we defined the tumor-prostate ratio in the ratio of tumor volume to prostate volume. In order to compensate the prostate tumor volume, the effect of tumor-prostate ratio on biochemical recurrence was examined. Materials and Methods: This study included 251 patients who underwent open retropubic radical prostatectomy for prostate cancer in a single hospital. We analyzed the effects of tumor volume and tumor-prostate ratio, as well as the effects of known risk factors for biochemical recurrence, on the duration of disease-free survival. Results: In the univariate analysis, the risk factors that significantly impacted disease-free survival time were found to be a prostate-specific antigen level ≥10 ng/mL, a tumor volume ≥5 mL, tumor-prostate ratio ≥10%, tumor capsular invasion, lymph node invasion, positive surgical margins, and seminal vesicle invasion. In the multivariate analysis performed to evaluate the risk factors found to be significant in the univariate analysis, positive surgical margins (hazard ratio=3.066 and a tumor density ≥10% (hazard ratio=1.991 were shown to be significant risk factors for biochemical recurrence. Conclusions: Tumor-prostate ratio, rather than tumor volume, should be regarded as a significant risk factor for biochemical recurrence.

  13. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  14. Are We Digital Masters Or Captives? A Critical Evaluation Of Panoptic Versus Synoptic Effect Of Surveillance In Social Media

    Directory of Open Access Journals (Sweden)

    Erdem Öngün

    2014-12-01

    Full Text Available The era we are living in is the one where we are exposed to a massive attraction of social connectivity based widely on digital forms of media. The most common one of them is social media. Social media exposes us to a kind of virtual Panopticon where ‘the few’ watch ‘the many’ in architecture of surveillance. Another term related to surveillance is Synopticon, a system where ‘the many’ watch ‘the few’ in the “Viewer Society”.  In the light of the related literature of theory and practice in the area, the study aims at viewing social media tools and its users from a critical perspective in a descriptive manner. To be able to do this, the study develops a set of hypothetical questions whose answers are instrumented to find out whether there is truly such a thing as “Virtual Panopticon” or “Synopticon” and if so, to what extent and how the Panoptic versus Synoptic effect of social media are felt among its users in various applications in light of media and communication. Facebook, based on the current theoretical knowledge within the field of surveillance can be given as an example. The study concludes with an overview of both assumptions with further reflections and contemplations of the readers of the study, who implicitly or explicitly could also be the actors of social media as masters or captives.

  15. Effect of permanent 103Pd radioactive seed implantation on brachytherapy of malignant tumor

    International Nuclear Information System (INIS)

    Chen Ping; Wei Xianzhong; Liu Yanmin; Wu Kaijun; Liang Jianxin; Chen Hanzhang

    2003-01-01

    Objective: To investigate and assess the brachytherapeutic effectiveness of 103 Pd radioactive seeds in malignant tumor therapy. Methods: 196.1-2127.5 MBq 103 Pd seeds were implanted in 21 confirmed malignant tumor patients. The seeds were evenly scattered in 15/21 patients' tumors and peripherally in the remaining 6 cases' tumors. The size and shape, local recurrence and remote metastasis of the tumors were observed. Results: The brachytherapy of 103 Pd seeds in tumor patients resulted in obvious efficacy. No local recurrence and remote metastasis were observed. 19/21 (90.5%) patients scored 0 and 2/21 (9.5%) of them scored 1 in skin acute radiation morbidity scoring criteria within the observation period. Conclusion: The 103 Pd seeds can be safely used in brachytherapy of malignant tumors with lower or medium sensitivity to radiation therapy

  16. Combined Effects of Pericytes in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Aline Lopes Ribeiro

    2015-01-01

    Full Text Available Pericytes are multipotent perivascular cells whose involvement in vasculature development is well established. Evidences in the literature also suggest that pericytes display immune properties and that these cells may serve as an in vivo reservoir of stem cells, contributing to the regeneration of diverse tissues. Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME. In this review, we highlight the contribution of pericytes to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss how collectively these hallmarks could be tackled by therapies targeting pericytes, providing a rationale for cancer drugs aiming at the TME.

  17. Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

    Science.gov (United States)

    Kiyota, Tsuyoshi; Takahashi, Yuki; Watcharanurak, Kanitta; Nishikawa, Makiya; Ohara, Saori; Ando, Mitsuru; Watanabe, Yoshihiko; Takakura, Yoshinobu

    2014-05-05

    Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

  18. Effectiveness of community participation in a surveillance system initiative to prevent drowning in Thailand.

    Science.gov (United States)

    Sansiritaweesook, Getsara; Muangsom, Niramon; Kanato, Manop; Ratanasiri, Amornrat

    2015-03-01

    This study had a 2-group pre-post quasiexperimental design and was conducted in 2 selected areas of Ubon Ratchathani province, Thailand. The objective was to evaluate the extent to which the surveillance system that was developed helped in drowning prevention. The development process involved extensive participation from the community. System efficiency was evaluated, and the drowning rates were compared. The system demonstrated 82.8% system sensitivity and 87% positive-predictive value. There were 90.0% rescues with no injury during the study period. The relative risk of drowning injury suggests that the control area was at 5.6 times more at risk for drowning injury than the intervention area (95% CI = 1.58, 20.12). Local knowledge and participation from the community were found to be key issues in the success of the surveillance system, and such systems can be applied to other areas with similar problems. © 2013 APJPH.

  19. Improving the Effect and Efficiency of FMD Control by Enlarging Protection or Surveillance Zones

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Toft, Nils; Boklund, Anette

    2015-01-01

    An epidemic of foot-and-mouth disease (FMD) in a FMD-free country with large exports of livestock and livestock products would result in profound economic damage. This could be reduced by rapid and efficient control of the disease spread. The objectives of this study were to estimate the economic...... impact of a hypothetical FMD outbreak in Denmark based on changes to the economic assumptions of the model, and to investigate whether the control of an FMD epidemic can be improved by combining the enlargement of protection or surveillance zones with pre-emptive depopulation or emergency vaccination....... The stochastic spatial simulation model DTU-DADS was used to simulate the spread of FMD in Denmark. The control strategies were the basic EU and Danish strategy, pre-emptive depopulation, suppressive or protective vaccination, enlarging protection or surveillance zones, and a combination of pre...

  20. Surveillance Angels

    NARCIS (Netherlands)

    Rothkrantz, L.J.M.

    2014-01-01

    The use of sensor networks has been proposed for military surveillance and environmental monitoring applications. Those systems are composed of a heterogeneous set of sensors to observe the environment. In centralised systems the observed data will be conveyed to the control room to process the

  1. Effects of Androgen Ablation on Anti-Tumor Immunity

    National Research Council Canada - National Science Library

    Kast, Martin

    2004-01-01

    .... This AA induced autoimmune-like response exerts limited anti-tumor activity in a murine prostate cancer model, but could be synergistic with CTLA-4 blockade that promotes the development of autoreactive T cell...

  2. Fast neutron biological effects on normal and tumor chromatin

    International Nuclear Information System (INIS)

    Constantinescu, B.; Bugoi, Roxana; Paunica, Tatiana; Radu, Liliana

    1997-01-01

    the relative absorbencies (E/E 0 ) obtained for the thermal transitions of chromatin samples versus fast neutron dose, lower values at higher neutron dose, were observed, indicating a damaged chromatin DNA. The treatment with gyrostan accelerates the damage process, but adding thyroxine and D3 vitamin the negative effect is partially recovered. Some conclusions on the role of gyrostan and of thyroxine and D3 vitamin are presented. To study the influence of metal ions on DNA strand breakage induced by fast neutrons, chromatin irradiations with 100, 200 and 300 Gy were performed separately and in presence of CsCl, CuCl 2 and AlCl 3 in a 5 x 10 -2 M concentration. Fluorescence lifetime values for chromatin-ethidium bromide complexes were determined using a Fluorimeter Edinburgh Anal. Instr. FL-900 CD. Greater values denote a damaged chromatin DNA. The presence of metal cations strongly decreases the time of life values, acting as a trap for the water radiolysis products. Our results suggest a combination of fast neutron irradiation with anticancer drug gyrostan for tumor destruction enhancement and the use of metal ions with hormonal thyroxine and D3 vitamin for a normal cells better protection during neutron therapy.(authors)

  3. Increase of tumor oxygen tension and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride

    International Nuclear Information System (INIS)

    Amano, Morikazu; Monzen, Hajime; Suzuki, Takatoshi; Hasegawa, Takeo

    2004-01-01

    The effects of pentoxifylline (PTX), vinpocetine (VPT) and ticlopidine hydrochloride (TCD), each drug commonly used for vascular disorders in humans, on the pO 2 in SCC-7 (squamous cell carcinoma) tumors of C3H/HeJ mice on the radioresponse of SCC-7 tumors were investigated. When the SCC-7 implanted in the leg of C3H/HeJ mice grew about 100 mm 3 , the effects of PTX, VPT and TCD on the increase oxygen tension in the tumor was determined with polarography. The mice were injected intraperitoneally (ip) with 5 ml/kg PTX, 5 ml/kg VPT, or 10 ml/kg TCD, the tumor pO 2 increased slowly, peaked about 20-50 min postinjection, and returned to its original level in 60-80 min. When the C3H/HeJ mice bearing SCC-7 tumors in the legs were injected ip with 5 ml/kg PTX, 5 ml/kg VPT or 10 ml/kg TCD and tumors were X-irradiated 30 min later, the radiation induced growth delay of the tumor was greater than that caused by X-irradiation alone. The results in the present study, PTX, VPT and TCD increase the tumor pO 2 in rodent tumors strongly suggest that each drug may be useful for increasing the radiosensitivity of human tumor. (author)

  4. Effect of tumor necrosis factor-alpha infusion on the incretin effect in healthy volunteers

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumor necrosis factor-alpha (TNF-α). Whereas TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce...

  5. In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy.

    Science.gov (United States)

    Puvanakrishnan, Priyaveena; Park, Jaesook; Chatterjee, Deyali; Krishnan, Sunil; Tunnell, James W

    2012-01-01

    Gold nanoparticles (GNPs) have gained significant interest as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with near infrared light, produce sufficient heat to treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a function of the particle's geometric properties (eg, size) and dosing strategy (eg, number and amount of injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor targeting. Specifically, we investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss nu/nu mice with a subcutaneous tumor xenograft model that received intravenous administration for a single and multiple doses of GNS and GNR. We performed neutron activation analysis to quantify the gold present in the tumor and liver. We performed histology to determine if there was acute toxicity as a result of multiple dosing. Neutron activation analysis results showed that the smaller GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant increase in GNS and GNR accumulation in the liver for higher doses. However, multiple doses increased targeting efficiency with minimal effect beyond three doses of GNPs. These results suggest a significant effect of particle type and multiple doses on increasing particle accumulation and on tumor targeting ability.

  6. Effects of Low Intensity Continuous Ultrasound (LICU on Mouse Pancreatic Tumor Explants

    Directory of Open Access Journals (Sweden)

    Despina Bazou

    2017-12-01

    Full Text Available This paper describes the effects of low intensity continuous ultrasound (LICU on the inflammatory response of mouse pancreatic tumor explants. While there are many reports focusing on the application of low-intensity pulsed ultrasound (LIPUS on cell cultures and tissues, the effects of continuous oscillations on biological tissues have never been investigated. Here we present an exploratory study of the effects induced by LICU on mouse pancreatic tumor explants. We show that LICU causes significant upregulation of IFN-γ, IL-1β, and TNF-α on tumor explants. No detectable effects were observed on tumor vasculature or collagen I deposition, while thermal and mechanical effects were not apparent. Tumor explants responded as a single unit to acoustic waves, with spatial pressure variations smaller than their size.

  7. Programme of air surveillance and health 9 towns. Synthesis review. Surveillance of effects on the health in relation with air pollution in urban area. Phase 2; Programme de surveillance Air et Sante 9 villes. Revue de synthese. Surveillance des effets sur la sante lies a la pollution atmospherique en milieu urbain. Phase 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-06-15

    The InVS published its first results on the Nine-City Air and Health Surveillance Programme (PSAS-9) in March 1999. This phase I pointed out that it was possible for various specialists in the field of air pollution and health to gather around a common set of problems. They also found a link between the daily variations of all the urban air pollution indicators and the total, cardio-vascular and respiratory mortality which, based on French data, contributed to strengthen scientific knowledge in this field. Today's report presents the results of phase Il of the PSAS-9 programme which essentially aimed at assessing the short-term exposure-risk relationships between pollution indicators and hospital admission indicators. This second phase also allowed to confirm the results of phase I on the short-term effect of air pollution on mortality thanks to longer periods of study. Exploratory analysis using new indicators and sensitivity analysis on the pertinence of results were also conducted. Finally, methodological tools were developed in order to optimise data collection and statistical modelization. All these results enabled the quantification of the short-term health impact of air pollution on the PSAS-9 cities. PSAS-9 is now an ongoing epidemiological surveillance programme on the effects of urban air pollution on health, providing information tools to decision-makers and the general population. (author)

  8. Programme of air surveillance Air and Health 9 towns. Surveillance of effects on health in relation with air pollution in urban area. Phase 2; Programme de surveillance Air et Sante 9 villes. Surveillance des effets sur la sante lies a la pollution atmospherique en milieu urbain. Phase 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-06-15

    The InVS published its first results on the Nine-City Air and Health Surveillance Programme (PSAS-9) in March 1999. This phase I pointed out that it was possible for various specialists in the field of air pollution and health to gather around a common set of problems. They also found a link between the daily variations of all the urban air pollution indicators and the total, cardio-vascular and respiratory mortality which, based on French data, contributed to strengthen scientific knowledge in this field. Today's report presents the results of phase Il of the PSAS-9 programme which essentially aimed at assessing the short-term exposure-risk relationships between pollution indicators and hospital admission indicators. This second phase also allowed to confirm the results of phase I on the short-term effect of air pollution on mortality thanks to longer periods of study. Exploratory analysis using new indicators and sensitivity analysis on the pertinence of results were also conducted. Finally, methodological tools were developed in order to optimise data collection and statistical modelization. All these results enabled the quantification of the short-term health impact of air pollution on the PSAS-9 cities. PSAS-9 is now an ongoing epidemiological surveillance programme on the effects of urban air pollution on health, providing information tools to decision-makers and the general population. (author)

  9. The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

    Science.gov (United States)

    Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

    2013-01-01

    The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform

  10. The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

    Directory of Open Access Journals (Sweden)

    Gayle E. Woloschak

    2012-12-01

    Full Text Available The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.

  11. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    International Nuclear Information System (INIS)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng

    2015-01-01

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  12. Oroxin B selectively induces tumor-suppressive ER stress and concurrently inhibits tumor-adaptive ER stress in B-lymphoma cells for effective anti-lymphoma therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn

    2015-10-15

    Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.

  13. Brain tumor radiosurgery. Current status and strategies to enhance the effect of radiosurgery

    International Nuclear Information System (INIS)

    Niranjan, A.; Lunsford, L.D.; Gobbel, G.T.; Kondziolka, D.; Maitz, A.; Flickinger, J.C.

    2000-01-01

    First, the current status of brain tumor radiosurgery is reviewed, and radiosurgery for brain tumors, including benign tumors, malignant tumors, primary glial tumors, and metastatic tumors, is described. Rapid developments in neuroimaging, stereotactic techniques, and robotic technology in the last decade have contributed to improved results and wider applications of radiosurgery. Radiosurgery has become the preferred management modality for many intracranial tumors, including schwannomas, meningiomas, and metastatic tumors. Although radiosurgery provides survival benefits in patients with diffuse malignant brain tumors, cure is still not possible. Microscopic tumor infiltration into surrounding normal tissue is the main cause of recurrence. Additional strategies are needed to specifically target tumor cells. Next, strategies to enhance the effect of radiosurgery are reviewed. Whereas the long-term clinical results of radiosurgery have established its role in the treatment of benign tumors, additional strategies are needed to improve cell killing in malignant brain tumors and to protect normal surrounding brain. The first strategy included the use of various agents to protect normal brain while delivering a high dose to the tumor cells, but finding an effective radioprotective agent has been problematic. Pentobarbital and 21-aminosteroid (21-AS) are presented as examples. The second strategy for radiation protection aimed at the repair of radiation-induced damage to the normal brain. The cause of radiation-induced breakdown of normal tissue is unclear. The white matter and the cerebral vasculature appear to be particularly susceptible to radiation. Oligodendrocytes and endothelial cells may be critical targets of radiation. The authors hypothesize that radiation-induced damage to these cell types can be repaired by neural stem cells. They also describe the use of tumor necrosis factor alpha (TNF-alpha) and neural stem cells as a means of enhancing the effect of

  14. Effect of hyperthermia on blood flow in VX2 tumor transplanted in rabbit

    International Nuclear Information System (INIS)

    Arita, Takeshi

    1994-01-01

    Effect of hyperthermia on blood flow was evaluated using VX 2 rabbit carcinoma in both legs. Microwave energy at 2450 MHz was used to heat tumors for 40 minutes. An outer canula of 18 G Erasta was implanted in the depth of 2 cm in tumor to measure the temperature and to maintain at 43.0degC-44.0degC. The blood flow in tumors was evaluated by color doppler flow imaging and dynamic MRI. Disturbance of blood flow in the depth of surface 0 cm to 2 cm in tumors was showed at 10 minutes starting 43.0degC heating and at almost all sites disappearance of blood flow was showed at 40 minutes using color doppler flow imaging. But the blood flow beyond the depth of 2 cm was not so disturbed at 40 minutes, relatively. After hyperthermia T1WI and T2WI in heated tumor were no difference comparing with those in control tumor, but heated tumor showed no enhancement using dynamic MRI with TURBO-FLASH technique and post-enhanced T1WI. Histologically, there was extensive tumor necrosis and thrombus formation in heated tumor after 3 days and 1 week. Therefore color doppler flow imaging and dynamic MRI were considered to be useful for evaluation of blood flow in tumor after and during hyperthermia. (author)

  15. Modeling triple-negative breast cancer heterogeneity: effects of stromal macrophages, fibroblasts and tumor vasculature.

    Science.gov (United States)

    Norton, Kerri-Ann; Jin, Kideok; Popel, Aleksander S

    2018-05-08

    A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates. Copyright © 2018. Published by Elsevier Ltd.

  16. The applicability of animal health surveillance systems for post-market monitoring of potential adverse effects of genetically modified (GM) feed.

    Science.gov (United States)

    Vince, L; Kleter, G A; Kostov, K; Pfeiffer, D U; Guitian, J

    2018-04-20

    A facultative post market monitoring of potential health impacts of genetically modified (GM) feedstuffs on livestock consuming these feeds after pre-market risk assessment is under ongoing consideration. Within the IPAFEED database, scientific studies on health effects beyond performance in livestock and the results of a systematic search for evidence of outcome effects due to GM feed are consolidated. These outcomes were reviewed and checked for consistency in order to identify plausible syndromes suitable for conducting surveillance. The 24 selected studies showed no consistent changes in any health parameter. There were no repeated studies in any species by GM crop type and animal species. As such, there is insufficient evidence to inform the design of surveillance systems for detecting known adverse effects. Animal health surveillance systems have been proposed for the post market monitoring of potential adverse effects in animals. Such systems were evaluated for their applicability to the detection of hypothetical adverse effects and their strengths and weaknesses to detect syndromes of concern are presented. For known adverse effects, applied controlled post-market studies may yield conclusive and high-quality evidence. For detecting unknown adverse effects, the use of existing surveillance systems may still be of interest. A simulation tool developed within the project can be adapted and applied to existing surveillance systems to explore their applicability to the detection of potential adverse effects of GM feed. Copyright © 2018. Published by Elsevier Ltd.

  17. [Study of the immunological mechanism of anti-tumor effects of 5-FU by establishing EL4 tumor-bearing mouse models].

    Science.gov (United States)

    Li, Mo-Lin; Li, Chuan-Gang; Shu, Xiao-Hong; Li, Ming-Xia; Jia, Yu-Jie; Qin, Zhi-Hai

    2007-11-01

    To investigate the immunological mechanism of anti-tumor effect of 5-FU by establishing lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice, respectively. The mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, 5-FU of different doses was administered intraperitoneally to treat these wild type C57BL/6 tumor-bearing mice. The size of tumors in the wild type C57BL/6 mice was observed and recorded to explore the minimal dose of 5-FU that could cure the tumor-bearing mice. Then the same amount of EL4 tumor cells was inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, 5-FU of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tumor-bearing mice. The size of tumors in the two different types of mice was observed and recorded. A single dose of 5-FU (75 mg/kg) cured both the EL4 tumor-bearing wild type C57BL/6 mice and the EL4 tumor-bearing nude C57BL/6 mice in the first week. Two weeks after 5-FU treatment, all of the nude mice died of tumor relapse while most of the wild type C57BL/6 mice were fully recovered. A single dose of 5-FU has marked anti-tumor effects on lymphoma EL4 tumor-bearing C57BL/6 mice with or without T lymphocytes. The relapse of tumors after 5-FU treatment might be related to the function of T lymphocytes.

  18. Air surveillance

    International Nuclear Information System (INIS)

    Patton, G.W.

    1995-01-01

    This section of the 1994 Hanford Site Environmental Report summarizes the air surveillance and monitoring programs currently in operation at that Hanford Site. Atmospheric releases of pollutants from Hanford to the surrounding region are a potential source of human exposure. For that reason, both radioactive and nonradioactive materials in air are monitored at a number of locations. The influence of Hanford emissions on local radionuclide concentrations was evaluated by comparing concentrations measured at distant locations within the region to concentrations measured at the Site perimeter. This section discusses sample collection, analytical methods, and the results of the Hanford air surveillance program. A complete listing of all analytical results summarized in this section is reported separately by Bisping (1995)

  19. Air surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Patton, G.W.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the air surveillance and monitoring programs currently in operation at that Hanford Site. Atmospheric releases of pollutants from Hanford to the surrounding region are a potential source of human exposure. For that reason, both radioactive and nonradioactive materials in air are monitored at a number of locations. The influence of Hanford emissions on local radionuclide concentrations was evaluated by comparing concentrations measured at distant locations within the region to concentrations measured at the Site perimeter. This section discusses sample collection, analytical methods, and the results of the Hanford air surveillance program. A complete listing of all analytical results summarized in this section is reported separately by Bisping (1995).

  20. Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies.

    Science.gov (United States)

    Areia, Miguel; Carvalho, Rita; Cadime, Ana Teresa; Rocha Gonçalves, Francisco; Dinis-Ribeiro, Mário

    2013-10-01

    Cost-effectiveness studies are highly dependent on the models, settings, and variables used and should be based on systematic reviews. We systematically reviewed cost-effectiveness studies that address screening for gastric cancer and/or surveillance of precancerous conditions and lesions. A systematic review of cost-effectiveness studies was performed by conducting a sensitive search in seven databases (PubMed, Scopus, Web of Science, Current Contents Connect, Centre for Reviews and Dissemination, Academic Search Complete, and CINAHL Plus), independently evaluated by two investigators. Articles were evaluated for type of study, perspective, model, intervention, incremental cost-effectiveness ratio, clinical or cost variables, and quality, according to published guidelines. From 2395 abstracts, 23 articles were included: 19 concerning population screening and 4 on following up premalignant lesions. Studies on Helicobacter pylori screening concluded that serology was cost-effective, depending on cancer incidence and endoscopy cost (incremental cost-effectiveness ratio: 6264-25,881), and eradication after endoscopic resection was also cost-effective (dominant) based on one study. Studies on imaging screening concluded that endoscopy was more cost-effective than no screening (incremental cost-effectiveness ratio: 3376-26,836). Articles on follow-up of premalignant lesions reported conflicting results (incremental cost-effectiveness ratio: 1868-72,519 for intestinal metaplasia; 18,600-39,800 for dysplasia). Quality assessment revealed a unanimous lack of a detailed systematic review and fulfillment of a median number of 23 items (20-26) of 35 possible ones. The available evidence shows that Helicobacter pylori serology or endoscopic population screening is cost-effective, while endoscopic surveillance of premalignant gastric lesions presents conflicting results. Better implementation of published guidelines and accomplishment of systematic detailed reviews are needed

  1. Multicolor microRNA FISH effectively differentiates tumor types

    Science.gov (United States)

    Renwick, Neil; Cekan, Pavol; Masry, Paul A.; McGeary, Sean E.; Miller, Jason B.; Hafner, Markus; Li, Zhen; Mihailovic, Aleksandra; Morozov, Pavel; Brown, Miguel; Gogakos, Tasos; Mobin, Mehrpouya B.; Snorrason, Einar L.; Feilotter, Harriet E.; Zhang, Xiao; Perlis, Clifford S.; Wu, Hong; Suárez-Fariñas, Mayte; Feng, Huichen; Shuda, Masahiro; Moore, Patrick S.; Tron, Victor A.; Chang, Yuan; Tuschl, Thomas

    2013-01-01

    MicroRNAs (miRNAs) are excellent tumor biomarkers because of their cell-type specificity and abundance. However, many miRNA detection methods, such as real-time PCR, obliterate valuable visuospatial information in tissue samples. To enable miRNA visualization in formalin-fixed paraffin-embedded (FFPE) tissues, we developed multicolor miRNA FISH. As a proof of concept, we used this method to differentiate two skin tumors, basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC), with overlapping histologic features but distinct cellular origins. Using sequencing-based miRNA profiling and discriminant analysis, we identified the tumor-specific miRNAs miR-205 and miR-375 in BCC and MCC, respectively. We addressed three major shortcomings in miRNA FISH, identifying optimal conditions for miRNA fixation and ribosomal RNA (rRNA) retention using model compounds and high-pressure liquid chromatography (HPLC) analyses, enhancing signal amplification and detection by increasing probe-hapten linker lengths, and improving probe specificity using shortened probes with minimal rRNA sequence complementarity. We validated our method on 4 BCC and 12 MCC tumors. Amplified miR-205 and miR-375 signals were normalized against directly detectable reference rRNA signals. Tumors were classified using predefined cutoff values, and all were correctly identified in blinded analysis. Our study establishes a reliable miRNA FISH technique for parallel visualization of differentially expressed miRNAs in FFPE tumor tissues. PMID:23728175

  2. Rinderpest surveillance

    International Nuclear Information System (INIS)

    2003-01-01

    Rinderpest is probably the most lethal virus disease of cattle and buffalo and can destroy whole populations; damaging economies; undermining food security and ruining the livelihood of farmers and pastoralists. The disease can be eradicated by vaccination and control of livestock movement. The Department of Technical Co-operation is sponsoring a programme, with technical support from the Joint FAO/IAEA Division to provide advice, training and materials to thirteen states through the 'Support for Rinderpest Surveillance in West Asia' project. (IAEA)

  3. Health surveillance

    International Nuclear Information System (INIS)

    1981-01-01

    The Code includes a number of requirements for the health surveillance of employees associated with the mining and milling of radioactive ores. This guideline is particularly directed at determining the level of fitness of employees and prospective employees, detecting any symptom which might contraindicate exposure to the environment encountered in mine/mill situations, examination of any employee who may have been exposed to radiation in excess of defined limits and the accumulation and provision of data on the health of employees

  4. Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

    Energy Technology Data Exchange (ETDEWEB)

    Zawaski, Janice A. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Gaber, M. Waleed, E-mail: gaber@bcm.edu [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Sabek, Omaima M. [Department of Surgery, Methodist Hospital Research Institute, Houston, TX (United States); Wilson, Christy M. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Duntsch, Christopher D. [Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN (United States); Merchant, Thomas E. [School of Biomedical Engineering and Imaging, University of Tennessee Health Science Center, Memphis, TN (United States); Department of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2012-03-01

    Purpose: Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials: Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood-brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results: The presence of tumor alone increases permeability but has little effect on leukocyte-endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation.

  5. EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

    Science.gov (United States)

    Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

    2013-01-01

    Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

  6. The Effect of Electroacupuncture on Osteosarcoma Tumor Growth and Metastasis: Analysis of Different Treatment Regimens

    Directory of Open Access Journals (Sweden)

    Branden A. Smeester

    2013-01-01

    Full Text Available Osteosarcoma is the most common malignant bone tumor found in children and adolescents and is associated with many complications including cancer pain and metastasis. While cancer patients often seek complementary and alternative medicine (CAM approaches to treat cancer pain and fatigue or the side effects of chemotherapy and treatment, there is little known about the effect of acupuncture treatment on tumor growth and metastasis. Here we evaluate the effects of six different electroacupuncture (EA regimens on osteosarcoma tumor growth and metastasis in both male and female mice. The most significant positive effects were observed when EA was applied to the ST-36 acupoint twice weekly (EA-2X/3 beginning at postimplantation day 3 (PID 3. Twice weekly treatment produced robust reductions in tumor growth. Conversely, when EA was applied twice weekly (EA-2X/7, starting at PID 7, there was a significant increase in tumor growth. We further demonstrate that EA-2X/3 treatment elicits significant reductions in tumor lymphatics, vasculature, and innervation. Lastly, EA-2X/3 treatment produced a marked reduction in pulmonary metastasis, thus providing evidence for EA’s potential antimetastatic capabilities. Collectively, EA-2X/3 treatment was found to reduce both bone tumor growth and lung metastasis, which may be mediated in part through reductions in tumor-associated vasculature, lymphatics, and innervation.

  7. Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

    Science.gov (United States)

    Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

    2010-01-01

    Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

  8. Automated graphic image generation system for effective representation of infectious disease surveillance data.

    Science.gov (United States)

    Inoue, Masashi; Hasegawa, Shinsaku; Suyama, Akihiko; Meshitsuka, Shunsuke

    2003-11-01

    Infectious disease surveillance schemes have been established to detect infectious disease outbreak in the early stages, to identify the causative viral strains, and to rapidly assess related morbidity and mortality. To make a scheme function well, two things are required. Firstly, it must have sufficient sensitivity and be timely to guarantee as short a delay as possible from collection to redistribution of information. Secondly, it must provide a good representation of the results of the surveillance. To do this, we have developed a database system that can redistribute the information via the Internet. The feature of this system is to automatically generate the graphic images based on the numerical data stored in the database by using Hypertext Preprocessor (PHP) script and Graphics Drawing (GD) library. It dynamically displays the information as a map or bar chart as well as a numerical impression according to the real time demand of the users. This system will be a useful tool for medical personnel and researchers working on infectious disease problems and will save significant time in the redistribution of information.

  9. Anti-tumor effect of polysaccharides isolated from Taraxacum ...

    African Journals Online (AJOL)

    1Shandong University, Jinan 250013, 2Department of General Surgery, The Fourth People's Hospital of Jinan, Jinan 250031, ... 266555, 4Department of Respiration, 5Department of Breast and Thyroid Surgery, Jinan Central Hospital Affiliated to Shandong. University, Jinan .... Animals and in vivo tumor xenograft study.

  10. Tumor treatment by sustained intratumoral release of cisplatin: effects of drug alone and combined with radiation

    International Nuclear Information System (INIS)

    Yapp, Donald T.T.; Lloyd, David K.; Zhu, Julian; Lehnert, Shirley M.

    1997-01-01

    Purpose: The effect of intratumoral delivery of cisplatin to a mouse tumor model (RIF-1) by means of a biodegradable polymer implant with and without radiation was studied. Methods and Materials: The polymer bis(p-carboxyphenoxy)propane-sebacic acid (CPP:SA; 80:20) and its degradation products have been characterized. Polymer rods (8 x 0.5 mm) containing 17% cisplatin by weight were prepared by extrusion, and the in vitro degradation rate measured. The implants were placed into mouse tumors and their effect (with and without radiation) on tumor growth delay studied. The levels of Pt in the mouse kidney, tumor, and blood plasma at selected intervals after implant were also determined. These results were compared with those obtained when cisplatin was delivered systematically. Results: When cisplatin was delivered by the polymer implants, higher levels were present in the tumor for longer time periods (cf. systemic delivery of the drug). For both nonirradiated and irradiated tumors, those treated with the polymer implants had significantly longer tumor growth delays compared to nonimplanted controls and to systematically treated tumors. Conclusions: The results show that intratumoral delivery of cisplatin is more efficient than systemic delivery. Using the biodegradable polymer implant, higher doses of cisplatin can be tolerated by the animal as the drug is localized within the tumor, and the high levels of the drug in the tumor can be maintained for an extended period of time. When radiation is given in conjunction with cisplatin, the tumor response is supraadditive for all modes of cisplatin administration but is potentiated to a greater extent when cisplatin is delivered through the polymer implant. The greatest effect is seen for treatment with cisplatin delivered by polymer implant combined with fractionated radiation

  11. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    International Nuclear Information System (INIS)

    Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

    2013-01-01

    Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

  12. The effect of low-dose total body irradiation on tumor control

    International Nuclear Information System (INIS)

    Sakamoto, Kiyohiko; Miyamoto, Miyako; Watabe, Nobuyuki.

    1987-01-01

    Total body irradiation (TBI) is considered to bring about an immunosuppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. However, there are no data on how low-dose TBI affects an organism. Over the last five years, we have been studying the effects of low-dose TBI on normal or tumor-bearing mice and the immunological background of these effects. In experimental studies, an increase in the TD50 value (the number of cells required for a tumor incidence of 50 %) in mice exposed to 10 rad was recognized and showed a remarkable increase at 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. In order to clarify the mechanism of this kind of effect, some immunological studies were performed using several immunological procedures, and the results suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials in some patients with advanced tumors are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising, although it is too early to draw conclusions. (author)

  13. Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

    International Nuclear Information System (INIS)

    Ciria, HC; Quevedo, MS; Cabrales, LB; Bruzón, RP; Salas, MF; Pena, OG; González, TR; López, DS; Flores, JM

    2004-01-01

    In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 10 6 and 1 × 10 5 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm 3 , four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm 3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm 3 (27.0 C in 0.35 cm 3 ) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm 3 , two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm 3 , respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory

  14. Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles

    International Nuclear Information System (INIS)

    Polf, Jerimy C.; Gillin, Michael; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata

    2011-01-01

    The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%-20% for those cells containing internalized gold nanoparticles.

  15. Enhanced relative biological effectiveness of proton radiotherapy in tumor cells with internalized gold nanoparticles

    Science.gov (United States)

    Polf, Jerimy C.; Bronk, Lawrence F.; Driessen, Wouter H. P.; Arap, Wadih; Pasqualini, Renata; Gillin, Michael

    2011-01-01

    The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%–20% for those cells containing internalized gold nanoparticles. PMID:21915155

  16. Effects of low dose radiation on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein bcl-2 in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

    2003-01-01

    Objective: To study the effect of low dose radiation (LDR) on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein bcl-2 in tumor-bearing mice. Methods: Kunming stain male mice were implanted with S180 sarcoma cells in the left inguen subcutaneously as an in situ experimental animal model. Seven days after implantation, the mice were given 75 mGy whole-body γ-irradiation. At 24 and 48 h after irradiation, all mice were sacrificed to measure the tumor volume, and tumor cell apoptosis, cell cycle progression were analyzed by flow cytometry. The expression of apoptosis-related protein bcl-2 and the apoptotic rate of tumor cells were observed by immunohistochemistry and electron microscopy. Results: Tumor growth was significantly slowed down after LDR (P 1 phase and the expression of bcl-2 protein decreased at 24 h. Apoptotic rate of tumor cells increased significantly at 48 h after LDR. Conclusion: LDR could cause a G 1 -phase arrest and increase the apoptosis of tumor cells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. The organized immune function and anti-tumor ability are markedly increased after LDR. The study provides practical evidence of clinical application to cancer treatment

  17. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

    Directory of Open Access Journals (Sweden)

    Yoichi Takakusagi

    Full Text Available BACKGROUND: TH-302 is a hypoxia-activated prodrug (HAP of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. METHODOLOGY/RESULTS: The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2, with minimal effect under aerobic conditions (21% O2. Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3. Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3, significantly delayed tumor growth. CONCLUSIONS/SIGNIFICANCE: Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the

  18. Pyruvate induces transient tumor hypoxia by enhancing mitochondrial oxygen consumption and potentiates the anti-tumor effect of a hypoxia-activated prodrug TH-302.

    Science.gov (United States)

    Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; Kishimoto, Shun; Wojtkowiak, Jonathan W; DeGraff, William; Kesarwala, Aparna H; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Munasinghe, Jeeva P; Gillies, Robert J; Mitchell, James B; Hart, Charles P; Krishna, Murali C

    2014-01-01

    TH-302 is a hypoxia-activated prodrug (HAP) of bromo isophosphoramide mustard that is selectively activated within hypoxic regions in solid tumors. Our recent study showed that intravenously administered bolus pyruvate can transiently induce hypoxia in tumors. We investigated the mechanism underlying the induction of transient hypoxia and the combination use of pyruvate to potentiate the anti-tumor effect of TH-302. The hypoxia-dependent cytotoxicity of TH-302 was evaluated by a viability assay in murine SCCVII and human HT29 cells. Modulation in cellular oxygen consumption and in vivo tumor oxygenation by the pyruvate treatment was monitored by extracellular flux analysis and electron paramagnetic resonance (EPR) oxygen imaging, respectively. The enhancement of the anti-tumor effect of TH-302 by pyruvate treatment was evaluated by monitoring the growth suppression of the tumor xenografts inoculated subcutaneously in mice. TH-302 preferentially inhibited the growth of both SCCVII and HT29 cells under hypoxic conditions (0.1% O2), with minimal effect under aerobic conditions (21% O2). Basal oxygen consumption rates increased after the pyruvate treatment in SCCVII cells in a concentration-dependent manner, suggesting that pyruvate enhances the mitochondrial respiration to consume excess cellular oxygen. In vivo EPR oxygen imaging showed that the intravenous administration of pyruvate globally induced the transient hypoxia 30 min after the injection in SCCVII and HT29 tumors at the size of 500-1500 mm(3). Pretreatment of SCCVII tumor bearing mice with pyruvate 30 min prior to TH-302 administration, initiated with small tumors (∼ 550 mm(3)), significantly delayed tumor growth. Our in vitro and in vivo studies showed that pyruvate induces transient hypoxia by enhancing mitochondrial oxygen consumption in tumor cells. TH-302 therapy can be potentiated by pyruvate pretreatment if started at the appropriate tumor size and oxygen concentration.

  19. Paradox between angiogenesis and oxygen effect in the treatment of tumor

    International Nuclear Information System (INIS)

    Hayashi, Masanobu

    2008-01-01

    The paradox in the title is described on recent findings concerning the effects of anti-angiogenetic drugs on possible radiation resistance and sensitivity of tumor tissue. Suppression of angiogenesis leads to inhibition of tumor growth, based on which anti-tumor drugs like anti- vascular endotherial growth factor (VEGF) antibody bevacizumab to suppress the genesis have been developed and clinically used, but they conceivably increase the population of hypoxic tumor cells. Those drugs are essentially used in combination with other chemotherapeutic agents and/or radiation. Hypoxic tumor cells present in the tissue are generally radioresistant. There are reported findings, however, that the drugs sometimes elevate the efficacy of radiotherapy, which hypothesizes that the drugs induces a proangiogenetic state, where increased level of growth factors in the tissue is reduced to normalize the vasculature and thereby reoxygenation occurs, the oxygen effect. Because copper is a cofactor of growth factors like VEGF and basic fibroblast growth factor (bFGF) and essential for angiogenesis, authors have studied the effect of a Cu-chelator, trientine, on transplanted mouse tumors which has been shown to induce apoptosis of the target cells. Combination of the chelator with X-ray irradiation is found effective in tumor growth inhibition and in survival increase. For more effective combination therapy, the interaction occurring in combinations of regimen should be elucidated. (R.T.)

  20. Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy.

    Science.gov (United States)

    Mei, Ling; Liu, Yayuan; Rao, Jingdong; Tang, Xian; Li, Man; Zhang, Zhirong; He, Qin

    2018-05-30

    Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were achieved because of the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T cell responses protected mice from tumor recurrence.

  1. Novel "Elements" of Immune Suppression within the Tumor Microenvironment.

    Science.gov (United States)

    Gurusamy, Devikala; Clever, David; Eil, Robert; Restifo, Nicholas P

    2017-06-01

    Adaptive evolution has prompted immune cells to use a wide variety of inhibitory signals, many of which are usurped by tumor cells to evade immune surveillance. Although tumor immunologists often focus on genes and proteins as mediators of immune function, here we highlight two elements from the periodic table-oxygen and potassium-that suppress the immune system in previously unappreciated ways. While both are key to the maintenance of T-cell function and tissue homeostasis, they are exploited by tumors to suppress immuno-surveillance and promote metastatic spread. We discuss the temporal and spatial roles of these elements within the tumor microenvironment and explore possible therapeutic interventions for effective and promising anticancer therapies. Cancer Immunol Res; 5(6); 426-33. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. The effect of endostatin gene in combination with radiotherapy on rats with implanted tumor

    International Nuclear Information System (INIS)

    Li Yong; Jin Ning; Yang Haishan; Piao Chunji; Lv Zhe

    2005-01-01

    Objective: To study the combination therapy effect of the radiotherapy with endostatin gene therapy on the rats with implanted tumor. Methods: Immediate Walker-256 cancerous ascetic injection method was used to make a rat tumor-bearing model, then the tumor was treated with saline, endostatin gene, irradiation or endostatin gene plus irradiation. The tumor growth rate and weight were observed, Western blot and RT-PCR were adopted to check the expressions of endostatin mRNA and protein. Results: The expressions of endostatin mRNA and protein were significant in the gene therapy group and the gene plus radiotherapy group, but there was a significant difference between these two groups. As compared with the control group, the tumor growth rate and weight decreased significantly in all the therapy groups (P 0.05). Conclusion: After the pCMV-Endostatin was induced, the expressions of endostatin mRNA and protein was significant in Walker-256 tumor and the tumor growth was inhibited. However, the effect of the endostatin gene plus radiotherapy was obviously better than that of the endostatin gene therapy group or the radiotherapy group for inhibiting tumor growth. (authors)

  3. Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

    International Nuclear Information System (INIS)

    Wu Congmei; Li Xiuyi; Liu Shuzheng

    2001-01-01

    Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

  4. Effects of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Lu Yanda

    2001-01-01

    Objective: To study the effect of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in the tumor-bearing mice. Methods: Kunming strain male mice were implanted with S 180 sarcoma cells in the right inguen subcutaneously as an experimental in situ animal model. Six hours before implantation the mice were given 75 mG whole-body X-ray irradiation and tumor-formation rate was counted 5 days late. From then, every two days the tumor volume was measured to draw a tumor growth curve. Fifteen days later, all mice were killed to measure the tumor weight, observe the necrosis area and the tumor-infiltration lymphoreticular cells (TIL) in the tumor pathologically. At the same time, erythrocyte immune function and activity of SOD were tested. Results: (1) The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without a pre-exposed (P < 0.05). (2) The tumor growth slowed down significantly in mice receiving a low does irradiation; The average tumor weight in mice receiving a low dose irradiation was lighter too (P < 0.05). (3) The tumor necrosis areas were larger and TILs were more in the irradiation group than those of the control group. (4) The erythrocyte immune function and activity of SOD in the irradiation group were all higher significantly than those of the control group ( P < 0.05). Conclusion: Low dose radiation could markedly increase anti-tumor ability of the organism and improve the erythrocyte immune function and activity of SOD in red cells, suggesting it could be useful in clinical cancer treatment

  5. Nutritional surveillance.

    Science.gov (United States)

    Mason, J B; Mitchell, J T

    1983-01-01

    The concept of nutritional surveillance is derived from disease surveillance, and means "to watch over nutrition, in order to make decisions that lead to improvements in nutrition in populations". Three distinct objectives have been defined for surveillance systems, primarily in relation to problems of malnutrition in developing countries: to aid long-term planning in health and development; to provide input for programme management and evaluation; and to give timely warning of the need for intervention to prevent critical deteriorations in food consumption. Decisions affecting nutrition are made at various administrative levels, and the uses of different types of nutritional surveillance information can be related to national policies, development programmes, public health and nutrition programmes, and timely warning and intervention programmes. The information should answer specific questions, for example concerning the nutritional status and trends of particular population groups.Defining the uses and users of the information is the first essential step in designing a system; this is illustrated with reference to agricultural and rural development planning, the health sector, and nutrition and social welfare programmes. The most usual data outputs are nutritional outcome indicators (e.g., prevalence of malnutrition among preschool children), disaggregated by descriptive or classifying variables, of which the commonest is simply administrative area. Often, additional "status" indicators, such as quality of housing or water supply, are presented at the same time. On the other hand, timely warning requires earlier indicators of the possibility of nutritional deterioration, and agricultural indicators are often the most appropriate.DATA COME FROM TWO MAIN TYPES OF SOURCE: administrative (e.g., clinics and schools) and household sample surveys. Each source has its own advantages and disadvantages: for example, administrative data often already exist, and can be

  6. The effect of tumor location and respiratory function on tumor movement estimated by real-time tracking radiotherapy (RTRT) system

    International Nuclear Information System (INIS)

    Onimaru, Rikiya; Shirato, Hiroki; Fujino, Masaharu; Suzuki, Keishiro; Yamazaki, Kouichi; Nishimura, Masaharu; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo

    2005-01-01

    Purpose: The effects of tumor location and pulmonary function on the motion of fiducial markers near lung tumors were evaluated to deduce simple guidelines for determining the internal margin in radiotherapy without fiducial markers. Methods and Materials: Pooled data collected by a real-time tumor-tracking radiotherapy system on 42 markers in 39 patients were analyzed. The pulmonary functions of all patients were assessed before radiotherapy. Using chest X-ray film, the position of the marker was expressed relative to the geometry of the unilateral lung. Posterior location meant the area of the posterior half of the lung in a lateral chest X-ray film, and caudal location meant the caudal half of the chest X-ray film; these categories were determined by measuring the distance between the marker and anatomic landmarks, including the apex, costophrenic angle, midline of spinal canal, lateral, anterior, and posterior boundary of the lung. Results: Before the radiotherapy, 18 patients had obstructive respiratory dysfunction (ratio of forced expiratory volume in 1 s to forced vital capacity [FEV 1.0 /FVC] 1.0 /FVC and %VC were 97.0% and 66.5%, respectively. Median tumor movements in the x (left-right), y (anteroposterior), and z (craniocaudal) directions were 1.1 mm, 2.3 mm, and 5.4 mm, respectively. There was no significant correlation between respiratory function and magnitude of marker movement in any direction. Median marker movement in the z direction was 2.6 mm for the cranial location and 11.8 mm for the caudal location, respectively (p < 0.001). Median movement in the z direction was 11.8 mm for posterior location and 3.4 mm for anterior location, respectively (p < 0.01). Conclusions: Simple measurement of the relative location on plain chest X-ray film was related, but respiratory function test was not related, to the craniocaudal amplitude of the motion of the fiducial marker near lung tumors

  7. Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

    International Nuclear Information System (INIS)

    Zheng Chuansheng; Xia Xiangwen; Feng Gansheng; Li Xin; Liang Huimin; Liang Bin

    2010-01-01

    Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CI I L- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CI I L-12) to liver cancer cell HepG 2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX 2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-Cl I L-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

  8. 18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen

    2014-01-01

    INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...

  9. In vitro anti-proliferative effect of interferon alpha in solid tumors: A potential predicative test

    International Nuclear Information System (INIS)

    Fuchsberger, N.; Kubes, M.; Kontsek, P.; Borecky, L.; Hornak, M.; Silvanova; Godal, A.; Svec, J.

    1993-01-01

    An in vitro test for the anti-proliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to anti-proliferative effect of IFN between individual tumors of the same type were found. The potential of this anti-proliferative test for prediction of treatment response in IFN-therapy is discussed. (author)

  10. Effect of Depleting Tumor-Associated Macrophages on Breast Cancer Growth and Response to Chemotherapy

    National Research Council Canada - National Science Library

    Tsan, Min-Fu

    2004-01-01

    ...-encapsulated clodronate had no effect on the growth of subcutaneous breast cancer (4T1) model in mice. Whether liposome-encapsulated cloronate depletes tumor-assocaited macrophages in this model is currently under investigation.

  11. Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on Surveillance - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2013-2016.

    Science.gov (United States)

    Marder, Ellyn P; Cieslak, Paul R; Cronquist, Alicia B; Dunn, John; Lathrop, Sarah; Rabatsky-Ehr, Therese; Ryan, Patricia; Smith, Kirk; Tobin-D'Angelo, Melissa; Vugia, Duc J; Zansky, Shelley; Holt, Kristin G; Wolpert, Beverly J; Lynch, Michael; Tauxe, Robert; Geissler, Aimee L

    2017-04-21

    Foodborne diseases represent a substantial public health concern in the United States. CDC's Foodborne Diseases Active Surveillance Network (FoodNet) monitors cases reported from 10 U.S. sites* of laboratory-diagnosed infections caused by nine enteric pathogens commonly transmitted through food. This report describes preliminary surveillance data for 2016 on the nine pathogens and changes in incidences compared with 2013-2015. In 2016, FoodNet identified 24,029 infections, 5,512 hospitalizations, and 98 deaths caused by these pathogens. The use of culture-independent diagnostic tests (CIDTs) by clinical laboratories to detect enteric pathogens has been steadily increasing since FoodNet began surveying clinical laboratories in 2010 (1). CIDTs complicate the interpretation of FoodNet surveillance data because pathogen detection could be affected by changes in health care provider behaviors or laboratory testing practices (2). Health care providers might be more likely to order CIDTs because these tests are quicker and easier to use than traditional culture methods, a circumstance that could increase pathogen detection (3). Similarly, pathogen detection could also be increasing as clinical laboratories adopt DNA-based syndromic panels, which include pathogens not often included in routine stool culture (4,5). In addition, CIDTs do not yield isolates, which public health officials rely on to distinguish pathogen subtypes, determine antimicrobial resistance, monitor trends, and detect outbreaks. To obtain isolates for infections identified by CIDTs, laboratories must perform reflex culture † ; if clinical laboratories do not, the burden of culturing falls to state public health laboratories, which might not be able to absorb that burden as the adoption of these tests increases (2). Strategies are needed to preserve access to bacterial isolates for further characterization and to determine the effect of changing trends in testing practices on surveillance.

  12. Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

    Science.gov (United States)

    Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Murakami, Masahiro

    2017-05-01

    To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

  13. Cost-effectiveness of lobectomy versus genetic testing (Afirma®) for indeterminate thyroid nodules: Considering the costs of surveillance.

    Science.gov (United States)

    Balentine, Courtney J; Vanness, David J; Schneider, David F

    2018-01-01

    We evaluated whether diagnostic thyroidectomy for indeterminate thyroid nodules would be more cost-effective than genetic testing after including the costs of long-term surveillance. We used a Markov decision model to estimate the cost-effectiveness of thyroid lobectomy versus genetic testing (Afirma®) for evaluation of indeterminate (Bethesda 3-4) thyroid nodules. The base case was a 40-year-old woman with a 1-cm indeterminate nodule. Probabilities and estimates of utilities were obtained from the literature. Cost estimates were based on Medicare reimbursements with a 3% discount rate for costs and quality-adjusted life-years. During a 5-year period after the diagnosis of indeterminate thyroid nodules, lobectomy was less costly and more effective than Afirma® (lobectomy: $6,100; 4.50 quality-adjusted life- years vs Afirma®: $9,400; 4.47 quality-adjusted life-years). Only in 253 of 10,000 simulations (2.5%) did Afirma® show a net benefit at a cost-effectiveness threshold of $100,000 per quality- adjusted life-years. There was only a 0.3% probability of Afirma® being cost saving and a 14.9% probability of improving quality-adjusted life-years. Our base case estimate suggests that diagnostic lobectomy dominates genetic testing as a strategy for ruling out malignancy of indeterminate thyroid nodules. These results, however, were highly sensitive to estimates of utilities after lobectomy and living under surveillance after Afirma®. Published by Elsevier Inc.

  14. Effect of x irradiation on the vascularization of experimental animal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, Y; Ogawa, F; Nishiguchi, H; Tanaka, N; Murakami, K [Kyoto Prefectural Univ. of Medicine (Japan)

    1975-03-01

    The authors studied the effect of ionizing radiation on blood vessels and tumor growth in two animal tumor systems: a third generation isoplants of a mammary cancer and a spontaneously arising squamous cell carcinoma. Single cell suspensions were transplanted into a C3H and a C3Hf mouse respectively. They were irradiated once with 2000 rad when the tumors reached about 8 mm in diameter. Microangiography was performed at a constant temperature and pressure, and a contrast medium containing lead-oxide and gelatin was flushed the vena cava for 10 min. at 120 mmHg. Tumor shrinkage was followed by continuous regrowth. The basic vasculature of the mammary carcinoma consisted of abundant large and fine blood vessels corkscrewed or stretched from the periphery of the tumor to its center in complex reticular networks. One day after irradiation there were small scattered avascular areas which, by the third day formed a large central necrosis. Supervascularization was also observed, indicating that some hypoxic tumor cells could be reoxygenized. In 5 days vascularization was similar to that of a nonirradiated tumor. Conversely, The squamous cell carcinoma showed peripheral and central vascularization with abundant vascular and avascular areas and extravasion in the large avascular area. Two days after irradiation the vessels were dilated. At 3 days peripheral fine vessels were damaged but the central vasculature remained intact. Unlike the mammary carcinoma, supervascularization was not the typical finding. At 5 days, vascularization was similar to that of a nonirradiated tumor.

  15. A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation

    International Nuclear Information System (INIS)

    Kavanagh, Brian D.; Secomb, Timothy W.; Hsu, Richard; Lin, P.-S.; Venitz, Jurgen; Dewhirst, Mark W.

    2002-01-01

    Purpose: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. Methods and Materials: Hemoglobin affinity is expressed in terms of P 50 , the partial pressure of oxygen (Po 2 ) at half saturation. Effects of changing P 50 on arterial Po 2 are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. Results: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P 50 , but increases with further increases of P 50 , in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P 50 is predicted to improve tumor oxygenation. Conclusions: The results support the administration of synthetic agents to increase P 50 during radiation treatment of tumors

  16. Macrophage PPARγ inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone

    Science.gov (United States)

    Cheng, Wing Yin; Huynh, HoangDinh; Chen, Peiwen; Peña-Llopis, Samuel; Wan, Yihong

    2016-01-01

    Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARγ loss-of-function mutations, but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARγ tumor-suppressive functions. Here we report that macrophage PPARγ deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARγ target in macrophage whose expression is enhanced by PPARγ loss but repressed by PPARγ activation. Functionally, macrophage Gpr132 is pro-inflammatory and pro-tumor. Genetic Gpr132 deletion not only retards inflammation and cancer growth but also abrogates the anti-tumor effects of PPARγ and rosiglitazone. Pharmacological Gpr132 inhibition significantly impedes mammary tumor malignancy. These findings uncover macrophage PPARγ and Gpr132 as critical TAM modulators, new cancer therapeutic targets, and essential mediators of TZD anti-cancer effects. DOI: http://dx.doi.org/10.7554/eLife.18501.001 PMID:27692066

  17. Effect of carbon monoxide breathing on hypoxia and radiation response in the SCCVII tumor in vivo

    International Nuclear Information System (INIS)

    Grau, C.; Marianne, M.D.; Nordsmark, M.; Khalil, A.A.; Horsman, M.R.; Overgaard, J.

    1994-01-01

    The purpose of this study was the influence of a clinically relevant concentration of carbon monoxide (CO) on tumor oxygenation and responses to irradiation. The murine tumor model was the SCCVII squamous cell carcinoma transplanted to the feet of C3H/Km mice. Sixty minutes of breathing CO at 200 ppm resulted in a carboxyhemoglobin level of 15%. This resulted in a reduction in p50 (the oxygen partial pressure at which hemoglobin is 50% saturated) to 78% of the control value, and a decrease in tumor blood perfusion to 73% of the control value. The combined effect of a decrease in effective hemoglobin and blood perfusion resulted in a reduction in tumor oxygen supply to 62% of the control value. In agreement with this, intratumoral pO 2 measurements showed a significant increase in tumor hypoxia, such that the percentage of measurements with low pO 2 (≤ 5 mmHg) increased from 33% to 62%. The fraction of clonogenic hypoxic cells, measured radiobiologically by paired cell survival curves, similarly increased from 0.2% to 3.8%. Radiation sensitivity, evaluated from in vivo-in vitro excision assay, was significantly decreased by CO in 1, 4, 8, and 12 fractions were 0.71, 0.77, 0.83, and 0.71, respectively. The present SCCVII tumor data confirm the general experimental observation that CO breathing significantly increases tumor hypoxia and reduces the effectiveness of ionizing irradiation. 22 refs., 3 figs., 2 tabs

  18. Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

    Science.gov (United States)

    Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

    2015-01-01

    Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

  19. Attaching Hollywood to a Surveillant Assemblage: Normalizing Discourses of Video Surveillance

    Directory of Open Access Journals (Sweden)

    Randy K Lippert

    2015-10-01

    Full Text Available This article examines video surveillance images in Hollywood film. It moves beyond previous accounts of video surveillance in relation to film by theoretically situating the use of these surveillance images in a broader “surveillant assemblage”. To this end, scenes from a sample of thirty-five (35 films of several genres are examined to discern dominant discourses and how they lend themselves to normalization of video surveillance. Four discourses are discovered and elaborated by providing examples from Hollywood films. While the films provide video surveillance with a positive associative association it is not without nuance and limitations. Thus, it is found that some forms of resistance to video surveillance are shown while its deterrent effect is not. It is ultimately argued that Hollywood film is becoming attached to a video surveillant assemblage discursively through these normalizing discourses as well as structurally to the extent actual video surveillance technology to produce the images is used.

  20. Anti-tumor effects of (1→3)-β-d-glucan from Saccharomyces cerevisiae in S180 tumor-bearing mice.

    Science.gov (United States)

    Mo, Li; Chen, Yafei; Li, Wenjian; Guo, Shuai; Wang, Xuzhao; An, Hailong; Zhan, Yong

    2017-02-01

    (1→3)-β-d-Glucan from Saccharomyces cerevisiae is a typical polysaccharide with various biological effects and is considered a candidate for the prevention and treatment of cancer in vitro. Research into the function of (1→3)-β-d-glucan in tumor-bearing animals in vivo, however, is limited. Here, we investigated the effects of (1→3)-β-d-glucan from S. cerevisiae on S180 tumor-bearing mice and on the immunity of the tumor-bearing host. The molecular mechanisms underlying the observed effects were investigated. (1→3)-β-d-Glucan was shown to exert anti-tumor effects without toxicity in normal mouse cells. The volume and weight of S180 tumors decreased dramatically following treatment with (1→3)-β-d-glucan, and treatment with the polysaccharide was furthermore shown to increase the tumor inhibition rate in a dose-dependent manner. Spleen index, T lymphocyte subsets (CD 4 and CD 8 ), as well as interleukins (IL)-2, (IL-2, IL-6), and tumor necrosis factor-α were assayed to detect the immunoregulatory and anti-tumor effects after (1→3)-β-d-glucan intragastrical administration. (1→3)-β-d-Glucan was shown to significantly potentiate the mouse immune responses by, among other effects, decreasing the ratio of CD 4 to CD 8 . The expression levels of IL-2, IL-6, and TNF-α were also significantly increased by (1→3)-β-d-glucan. These results suggest that (1→3)-β-d-glucan enhances the host's immune function during the tumor inhibition process. S180 tumor cells treated with (1→3)-β-d-glucan also exhibited significant apoptotic characteristics. (1→3)-β-d-glucan increased the ratio of Bax to Bcl-2 at the translation level by up-regulating Bax expression and down-regulating Bcl-2 expression, resulting in the initiation of cell apoptosis in S180 tumor-bearing mice. Taken together, these results indicate that the anti-tumor effects exerted by (1→3)-β-d-glucan may be attributed to the polysaccharide's immunostimulating properties and apoptosis

  1. Inherent Tumor Characteristics That Limit Effective and Safe Resection of Giant Nonfunctioning Pituitary Adenomas.

    Science.gov (United States)

    Nishioka, Hiroshi; Hara, Takayuki; Nagata, Yuichi; Fukuhara, Noriaki; Yamaguchi-Okada, Mitsuo; Yamada, Shozo

    2017-10-01

    Surgical treatment of giant pituitary adenomas is sometimes challenging. We present our surgical series of giant nonfunctioning adenomas to shed light on the limitations of effective and safe tumor resection. The preoperative tumor characteristics, surgical approaches, outcome, and histology of giant nonfunctioning adenoma (>40 mm) in 128 consecutive surgical patients are reviewed. The follow-up period ranged from 19 to 113 months (mean 62.2 months). A transsphenoidal approach was used in the treatment of 109 patients and a combined transsphenoidal transcranial approach in 19 patients. A total of 93 patients (72.7%) underwent total resection or subtotal resection apart from the cavernous sinus (CS). The degree of tumor resection, excluding the marked CS invasion, was lower in tumors that were larger (P = 0.0107), showed massive intracranial extension (P = 0.0352), and had an irregular configuration (P = 0.0016). Permanent surgical complications developed in 28 patients (22.0%). Long-term tumor control was achieved in all patients by single surgery, including 43 patients with adjuvant radiotherapy. Most tumors were histologically benign, with a low MIB-1 index (inherent factors that independently limit effective resection. These high-risk tumors require an individualized therapeutic strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Antitumor effect of Ganoderma lucidum : Cytotoxicity and Tumor Growth Delay(1)

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyoung Cheol; Kim, Jung Soo [Chonbuk National University College of Medicine, Chonju (Korea, Republic of); Choi, Dong Seong [Chonju Woosuck Univ., Chonju (Korea, Republic of); Song, Chang Won [Univ. of Minnesota Medical School, Minneapolis (United States)

    1994-10-15

    Purpose: To investigate the effect of aqueous extract of Ganoderma lucidum(G.I.) on the survival of tumor cells in vitro and on the growth of tumors in vivo. Materials and Methods: Dried G.I. was made into powder, extracted with distilled water, filtered and diluted from a maximum concentration of 100 mg/ml in sequence. The cytotoxicity of G.O. in vitro was evaluated from its ability to reduce the clonogenicity of SCK tumor cells. For the tumor growth delay study, about 2x10{sup 5} of SCK tumor cells were subcutaneously inoculated in the legs of A/J mice. The first experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G/I. From the first day after tumor inoculation for 10 days. The second experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G.I. either once a day for 10 days or twice a day for 5 days beginning from the 7th day after tumor inoculation. Results: 1. Cytotoxicity in vitro; survival fraction, as judged from the curve, at G.I. concentration of 0.5, 1,5,10,25,50 and 100 mg/ml were 1.0, 0.74{+-}0.03, 0.18{+-}0.03, 0.15{+-}0.02, 0.006{+-}0.002, 0.015 and 0.0015, respectively. 2. Tumor growth delay in vivo; a) the time required for the mean tumor volume to grow to 1,000mm{sup 3} was 11 days in the control group and 14 days in the experimental group. b) the time required for tumor volume to increase 4 times was 11 days in the control group while it was 10.5 and 12 days in the groups injected with G.I. once a day and twice a day from the 7th day after tumor inoculation respectively. Conclusion: Aqueous extracts of G.I. showed a marked cytotoxicity on the SCK mammary cells in vitro. Tumor growth delay was statistically significant when G.I. injection was started soon after tumor inoculation, but it was not significant when injection was started after the tumors were firmly established.

  3. Antitumor effect of Ganoderma lucidum : Cytotoxicity and Tumor Growth Delay(1)

    International Nuclear Information System (INIS)

    Kwon, Hyoung Cheol; Kim, Jung Soo; Choi, Dong Seong; Song, Chang Won

    1994-01-01

    Purpose: To investigate the effect of aqueous extract of Ganoderma lucidum(G.I.) on the survival of tumor cells in vitro and on the growth of tumors in vivo. Materials and Methods: Dried G.I. was made into powder, extracted with distilled water, filtered and diluted from a maximum concentration of 100 mg/ml in sequence. The cytotoxicity of G.O. in vitro was evaluated from its ability to reduce the clonogenicity of SCK tumor cells. For the tumor growth delay study, about 2x10 5 of SCK tumor cells were subcutaneously inoculated in the legs of A/J mice. The first experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G/I. From the first day after tumor inoculation for 10 days. The second experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G.I. either once a day for 10 days or twice a day for 5 days beginning from the 7th day after tumor inoculation. Results: 1. Cytotoxicity in vitro; survival fraction, as judged from the curve, at G.I. concentration of 0.5, 1,5,10,25,50 and 100 mg/ml were 1.0, 0.74±0.03, 0.18±0.03, 0.15±0.02, 0.006±0.002, 0.015 and 0.0015, respectively. 2. Tumor growth delay in vivo; a) the time required for the mean tumor volume to grow to 1,000mm 3 was 11 days in the control group and 14 days in the experimental group. b) the time required for tumor volume to increase 4 times was 11 days in the control group while it was 10.5 and 12 days in the groups injected with G.I. once a day and twice a day from the 7th day after tumor inoculation respectively. Conclusion: Aqueous extracts of G.I. showed a marked cytotoxicity on the SCK mammary cells in vitro. Tumor growth delay was statistically significant when G.I. injection was started soon after tumor inoculation, but it was not significant when injection was started after the tumors were firmly established

  4. Effect of Audio Coaching on Correlation of Abdominal Displacement With Lung Tumor Motion

    International Nuclear Information System (INIS)

    Nakamura, Mitsuhiro; Narita, Yuichiro; Matsuo, Yukinori; Narabayashi, Masaru; Nakata, Manabu; Sawada, Akira; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

    2009-01-01

    Purpose: To assess the effect of audio coaching on the time-dependent behavior of the correlation between abdominal motion and lung tumor motion and the corresponding lung tumor position mismatches. Methods and Materials: Six patients who had a lung tumor with a motion range >8 mm were enrolled in the present study. Breathing-synchronized fluoroscopy was performed initially without audio coaching, followed by fluoroscopy with recorded audio coaching for multiple days. Two different measurements, anteroposterior abdominal displacement using the real-time positioning management system and superoinferior (SI) lung tumor motion by X-ray fluoroscopy, were performed simultaneously. Their sequential images were recorded using one display system. The lung tumor position was automatically detected with a template matching technique. The relationship between the abdominal and lung tumor motion was analyzed with and without audio coaching. Results: The mean SI tumor displacement was 10.4 mm without audio coaching and increased to 23.0 mm with audio coaching (p < .01). The correlation coefficients ranged from 0.89 to 0.97 with free breathing. Applying audio coaching, the correlation coefficients improved significantly (range, 0.93-0.99; p < .01), and the SI lung tumor position mismatches became larger in 75% of all sessions. Conclusion: Audio coaching served to increase the degree of correlation and make it more reproducible. In addition, the phase shifts between tumor motion and abdominal displacement were improved; however, all patients breathed more deeply, and the SI lung tumor position mismatches became slightly larger with audio coaching than without audio coaching.

  5. The long-term side effects of radiation therapy for benign brain tumors in adults

    International Nuclear Information System (INIS)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R.

    1990-01-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs

  6. The long-term side effects of radiation therapy for benign brain tumors in adults

    Energy Technology Data Exchange (ETDEWEB)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. (Univ. of Mississippi Medical Center, Jackson (USA))

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  7. Surveillance and Critical Theory

    Directory of Open Access Journals (Sweden)

    Christian Fuchs

    2015-09-01

    Full Text Available In this comment, the author reflects on surveillance from a critical theory approach, his involvement in surveillance research and projects, and the status of the study of surveillance. The comment ascertains a lack of critical thinking about surveillance, questions the existence of something called “surveillance studies” as opposed to a critical theory of society, and reflects on issues such as Edward Snowden’s revelations, and Foucault and Marx in the context of surveillance.

  8. Effects of low dose radiation combined with cyclophosphamide on tumor cell apoptosis, cell cycle and proliferation of bone marrow in tumor-bearing mice

    International Nuclear Information System (INIS)

    Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

    2004-01-01

    Objective: To study the effect of low dose radiation (LDR) combined with cyclophosphamide on tumor cell apoptosis, cell cycle, and proliferation of bone marrow in mice tumor-bearing mice. Methods: Kunming strain male mice were implanted with S180 sarcoma cells in the left hind leg subcutaneously as an experimental animal model. Five and 8 days after implantation, the mice were given 75 mGy whole-body γ-ray radiation and CTX(300 mg/kg) by intraperitoneal injection 36 hour after LDR. All mice were sacrificed to measure the tumor volume, tumor cell apoptosis, and cell cycle; the proliferation of bone marrow was analyzed by flow cytometry. Results: Tumor growth was significantly slowed down in the treated groups. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G 1 phase in CTX and CTX+LDR groups, more significantly in the latter group than in the former group. Concentration of bone marrow cells and proliferation index in CTX + LDR group were higher than those in CTX group, although concentration of bone marrow cells in CTX and CTX+LDR groups were much lower than that in normal mice. Conclusion: Low dose radiation combined with cyclophosphamide causes more significant G 1 -phase arrest than cyclophosphamide alone and enhances anti-tumor effect markedly. At the same time LDR significantly protects hematopoietic function of bone marrow, which is of practical significance as an adjuvant chemotherapy

  9. Synergy Effect of Combining Fluorescence and Mid Infrared Fiber Spectroscopy for Kidney Tumor Diagnostics

    Directory of Open Access Journals (Sweden)

    Andrey Bogomolov

    2017-11-01

    Full Text Available Matching pairs of tumor and non-tumor kidney tissue samples of four patients were investigated ex vivo using a combination of two methods, attenuated total reflection mid infrared spectroscopy and fluorescence spectroscopy, through respectively prepared and adjusted fiber probes. In order to increase the data information content, the measurements on tissue samples in both methods were performed in the same 31 preselected positions. Multivariate data analysis revealed a synergic effect of combining the two methods for the diagnostics of kidney tumor compared to individual techniques.

  10. A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy.

    Science.gov (United States)

    Xu, Shihe; Wei, Xiangqing; Zhang, Fangwei

    2016-01-01

    A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.

  11. A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy

    Directory of Open Access Journals (Sweden)

    Shihe Xu

    2016-01-01

    Full Text Available A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction-diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations.

  12. Effect of Curcuma zedoaria crude extract against tumor progression and immunomodulation

    Directory of Open Access Journals (Sweden)

    FR Carvalho

    2010-01-01

    Full Text Available The aim of the present work was to study the effect of the crude extract of Curcuma zedoaria on peripheral blood cells and tumor progression in C57Bl/6J mice injected with B16F10 murine melanoma cells. The intraperitoneal therapy showed a significant increase in total white and red blood cell counts, a decrease in peritoneal cell number and tumor volume reduction, whereas the oral administration revealed a noteworthy augmentation only in total leukocyte count. These results contribute to evaluate the importance of alternative treatments that employ phytotherapic compounds against tumor progression and its possible immunomodulation.

  13. Anti-tumor effects of an engineered 'killer' transfer RNA

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dong-hui [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Lee, Jiyoung; Frankenberger, Casey [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Geslain, Renaud, E-mail: rgeslain@depaul.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Department of Biology, DePaul University, Chicago, IL 60614 (United States); Rosner, Marsha, E-mail: m-rosner@uchicago.edu [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Pan, Tao, E-mail: taopan@uchicago.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer tRNA with anti-cancer effects. Black-Right-Pointing-Pointer tRNA induced protein misfolding. Black-Right-Pointing-Pointer tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA{sup Ser}(AAU) is an engineered human tRNA{sup Ser} with an anticodon coding for isoleucine. Here we test the possibility that tRNA{sup Ser}(AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA{sup Ser}(AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA{sup Ser}(AAU) in both tumorigenic and non-tumorigenic cells. tRNA{sup Ser}(AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA{sup Ser}(AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA{sup Ser}(AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA{sup Ser}(AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  14. Anti-tumor effects of an engineered “killer” transfer RNA

    International Nuclear Information System (INIS)

    Zhou, Dong-hui; Lee, Jiyoung; Frankenberger, Casey; Geslain, Renaud; Rosner, Marsha; Pan, Tao

    2012-01-01

    Highlights: ► tRNA with anti-cancer effects. ► tRNA induced protein misfolding. ► tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA Ser (AAU) is an engineered human tRNA Ser with an anticodon coding for isoleucine. Here we test the possibility that tRNA Ser (AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA Ser (AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA Ser (AAU) in both tumorigenic and non-tumorigenic cells. tRNA Ser (AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA Ser (AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA Ser (AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA Ser (AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  15. Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Rainer J Klement

    Full Text Available Currently ketogenic diets (KDs are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice.We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD. For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR or hazard ratio (HR between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI = [0.73, 0.97] and HR = 0.55 (95% HPDI = [0.26, 0.87], indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04].There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.

  16. Anti-tumor and Chemoprotective Effect of Bauhinia tomentosa by Regulating Growth Factors and Inflammatory Mediators.

    Science.gov (United States)

    Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2015-01-01

    Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and α-esterase activity. Extract treatment also attenuated any increases in serum levels of TNFα, iNOS, IL-1β, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.

  17. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  18. Delay equations modeling the effects of phase-specific drugs and immunotherapy on proliferating tumor cells.

    Science.gov (United States)

    Barbarossa, Maria Vittoria; Kuttler, Christina; Zinsl, Jonathan

    2012-04-01

    In this work we present a mathematical model for tumor growth based on the biology of the cell cycle. For an appropriate description of the effects of phase-specific drugs, it is necessary to look at the cell cycle and its phases. Our model reproduces the dynamics of three different tumor cell populations: quiescent cells, cells during the interphase and mitotic cells. Starting from a partial differential equations (PDEs) setting, a delay differential equations (DDE) model is derived for an easier and more realistic approach. Our equations also include interactions of tumor cells with immune system effectors. We investigate the model both from the analytical and the numerical point of view, give conditions for positivity of solutions and focus on the stability of the cancer-free equilibrium. Different immunotherapeutic strategies and their effects on the tumor growth are considered, as well.

  19. Effect of hyperthermia, radiation and adriamycin combinations on tumor vascular function

    International Nuclear Information System (INIS)

    Eddy, H.A.; Chmielewski, G.

    1982-01-01

    Pathophysiologic studies of tumor vascular responses to hyperthermia, radiation or adriamycin given alone or in specific combinations have been made in the cervical carcinoma grown in the transparent cheek pouch chamber of the Syrian hamster. A specially designed chamber containing a compartment for flowing water enabled controlled heating of the tumor and pouch to within 0.2 0 C; the desired temperatures were achieved within one minute. Heating at 42 0 C for 30 minutes was followed, at 1, 5 or 24 hours, by a second heating for 30 minutes at 42 0 C. In addition, the same period of heating was preceded or followed, at 1, 5 or 24 hour intervals, by a single exposure to 2000R or a single intravenous injectionof adriamycin given at a rate of 0.45 mg/100 gm body weight. Of the three modalities, heat appeared to have the greatest acute effect on the tumor vascular system. A single dose of heat produced a rapid but transient constriction followed by a prominent dilation of vessels. Two heating periods given at a 1 hour interval caused persistent stasis in the tumor which progressed to coagulation necrosis. Although heating prior to irradiation or adriamycin, in general, increased the vascular responses to these agents, this sequence gave no tumor control. Radiation or adriamycin given prior to heating had relatively little effect on the vascular response to heating and produced no tumor control except when heat was applied shortly after irradiation. These studies indicate that changes in the microvasculature and perfusion in tumors, in response to hyperthermia alone or combined in specific sequences with radiation, can alter the internal environment of the tumor to produce a greater degree of tumor control than can be attributed to direct cell killing by these agents

  20. The anti-tumor effect of ACNU and x-irradiation on mouse glioma

    International Nuclear Information System (INIS)

    Nakagawa, Hidemitsu; Hori, Masaharu; Hasegawa, Hiroshi; Mogami, Heitaro; Hayakawa, Toru.

    1979-01-01

    Anti-tumor activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and x-irradiation on methylcholanthrene induced glioma in C 57 BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and x-irradiation in M phase. As to the combined therapy of ACNU and x-irradiation, the anti-tumor effect was most remarkable when the cells were treated by x-irradiation in the G 2 , M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and x-irradiation on the cells in G 1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and x-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local x-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or x-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of x-ray was remarkably effective. Evidence obtained indicated that the combination therapy of ACNU and x-irradiation have synergistic anti-tumor effect on experimental mouse glioma. (author)

  1. Preventing the preventable through effective surveillance: the case of diphtheria in a rural district of Maharashtra, India.

    Science.gov (United States)

    Phalkey, Revati K; Bhosale, Rajesh V; Joshi, Abhijeet P; Wakchoure, Sushil S; Tambe, Muralidhar P; Awate, Pradip; Marx, Michael

    2013-04-08

    age despite consistently poor immunization coverage (below 50%) remains unclear. Concomitant efforts should now focus on improving and monitoring primary immunization and booster coverages across all age groups. Gradually introducing adult immunization at ten year intervals may become necessary to prevent future vulnerabilities. Laboratory networks for genotyping and toxigenicity testing are urgently mandated at district level given the endemicity of the disease in the surrounding region and its recent introduction in remote Dhule. Contingency funds with pre- agreements to obtain ADS and DT/Td vaccines at short notice and developing standard case management protocols at district level are necessary. Monitoring the disease, emerging strains and mutations, alongside drug resistance through robust and effective surveillance is a pragmatic way forward.

  2. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

    Science.gov (United States)

    Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  3. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    International Nuclear Information System (INIS)

    Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

    2012-01-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  4. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Plaga, Alexis; Shields, Lisa B.E. [Norton Neuroscience Institute, Louisville, KY (United States); Sun, David A.; Vitaz, Todd W. [Norton Neuroscience Institute, Louisville, KY (United States); Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Spalding, Aaron C., E-mail: acspalding1@gmail.com [Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Norton Cancer Institute, Radiation Center, Kosair Children' s Hospital, Louisville, KY (United States)

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  5. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    OpenAIRE

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and ...

  6. Differences in the effects of host suppression on the adoptive immunotherapy of subcutaneous and visceral tumors

    International Nuclear Information System (INIS)

    Chang, A.E.; Shu, S.Y.; Chou, T.; Lafreniere, R.; Rosenberg, S.A.

    1986-01-01

    A syngeneic transplantable sarcoma induced in C57BL/6 mice, MCA 105, was used in studies to examine host suppression on the adoptive immunotherapy of established intradermal and experimentally induced pulmonary and hepatic metastases. Fresh immune splenocytes were generated from mice immunized to the MCA 105 tumor by a mixture of viable tumor cells and Corynebacterium parvum. The adoptive immunotherapy of intradermal MCA 105 tumor with immune cells required prior immunosuppression of the recipient by sublethal irradiation with 500 R or T-cell depletion. The effect of whole-body sublethal irradiation appeared to eliminate a systemic host suppression mechanism, since partialbody irradiation involving the tumor-bearing area did not permit successful immunotherapy. Host irradiation was not required to achieve successful immunotherapy of experimentally induced pulmonary or hepatic metastases. In nonirradiated recipients bearing both intradermal and pulmonary tumors, host suppression did not affect the function of transferred immune cells to induce regression of pulmonary metastases. Thus, suppression of adoptive immunotherapy appears to be relevant to tumors confined to the skin and subcutaneous tissue but not to tumor in visceral sites, such as the lung and liver

  7. [Establishment of EL4 tumor-bearing mouse models and investigation on immunological mechanisms of anti-tumor effect of melphalan].

    Science.gov (United States)

    Li, Mo-lin; Li, Chuan-gang; Shu, Xiao-hong; Jia, Yu-jie; Qin, Zhi-hai

    2006-03-01

    To establish mouse lymphoma EL4 tumor-bearing mouse models in wild type C57BL/6 mice and nude C57BL/6 mice respectively, and to further investigate the immunological mechanisms of anti-tumor effect of melphalan. Mouse lymphoma EL4 cells were inoculated subcutaneously into wild type C57BL/6 mice (immune-competent mice). Twelve days later, melphalan of different doses were administered intraperitoneally to treat these wild type C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of melphalan that could cure the tuomr-bearing mice. Then the same amount of EL4 tumor cells were inoculated subcutaneously into wild type C57BL/6 mice and nude C57BL/6 mice (T cell-deficient mice) simultaneously, which had the same genetic background of C57BL/6. Twelve days later, melphalan of the minimal dose was given intraperitoneally to treat both the wild type and nude C57BL/6 tuomr-bearing mice. Tumor sizes were observed and recorded in these two different types of mice subsequently. A single dose of melphalan (7.5 mg/kg) could cure EL4 tumor-bearing wild type C57BL/6 mice, but could not induce tumor regression in EL4 tumor-bearing nude C57BL/6 mice. A single dose of melphalan has obvious anti-tumor effect on mouse lymphoma EL4 tumor-bearing wild type C57BL/6mice, which requires the involvement of T lymphocytes in the host probably related to their killing functions.

  8. Tumor necrosis factor alpha polymorphism correlates with deleterious effects of ultraviolet B light on cutaneous immunity

    NARCIS (Netherlands)

    Vincek, V.; Kurimoto, I.; Medema, J. P.; Prieto, E.; Streilein, J. W.

    1993-01-01

    Intradermally injected tumor necrosis factor alpha (TNF-alpha) mimics the effects of UV B light (UVB) radiation and neutralizing anti-TNF-alpha antibodies abolish the deleterious effects of UVB on induction of contact hypersensitivity suggesting that TNF-alpha is the major mediator of UVB effects on

  9. The combined effect of interferon synthesis inductors, radiosensitizing and antitumoral agents on solid tumors

    International Nuclear Information System (INIS)

    Leonidze, D.L.

    1987-01-01

    In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous inerferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Poly I; polyC was not shiown to influence the efficiency of hyperthermia combined with radiation with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation

  10. Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

    Science.gov (United States)

    MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

    2014-01-01

    The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

  11. Effect of pH on tumor cell uptake of radiogallium in vitro and in vivo

    International Nuclear Information System (INIS)

    Vallabhajosula, S.R.; Hartwig, J.F.; Wolf, W.

    1982-01-01

    When injected at tracer levels into the blood, radiogallium as 67 Ga-citrate binds to, and is transported to, the site of the tumor by transferrin. The process by which transferrin-bound Ga is converted to tumor-bound Ga is not fully unterstood, but may involve the differential physicology of neoplasmas compared with normal tissues. Based on the slight acidity known to be exhibited by the extracellular fluid of many animal and human tumors, we have studied the effect of pH on stability and dissociation of the Ga-transferrin complex and on the uptake of Ga by tumor cells in vitro and animal tumors in vivo. When plasma from rabbits injected with 67 Ga-citrate was dialyzed at pH 6.5-7.5, disociation of Ga from transferrin showed an inverse pH-dependence. A similar inverse dependence on pH was observed for the uptake of Ga by L1210 leukemia cells and Ehrlich ascites cells incubated with Ga-transferrin complex. Tumor uptake of Ga in rats bearing Walker-256 carcinosarcoma or Murphystum lymphosarcoma whose tumor pH had been further lowered by administration of glucose showed a statistically significant increase over control rats receiving no glucose. These results demonstrate that the stability of the Ga-transferrin complex is pH-dependent and suggest that dissociation of this complex due to decreased pH at the tumor site may be one factor involved in tumor localization and binding of Ga. (orig.)

  12. Effects of low dose radiation on antioxidant enzymes after radiotherapy of tumor-bearing mice

    International Nuclear Information System (INIS)

    Li Jin; Gao Gang; Wang Qin; Tang Weisheng; Liu Xiaoqiu; Wang Zhiquan

    2005-01-01

    Objective: To search for effects of low dose radiation on the activities of antioxidant enzymes after radiotherapy of tumor-bearing mice. Methods: Superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) were all determined by chemical colorimetry. Results: Low dose radiation increase the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) in serum of tumor-bearing mice more markedly than those in the unirradiated controls. The activities of antioxidant enzymes SOD, GST, CAT in serum of tumor-bearing mice (d 5 , d 3 ) irradiated with 5cGy 6h before 2.0 Gy radiation are obviously higher than those of the group (c 3 , c 5 ) given with radiotherapy only. Conclusion: The increase in the activities of antioxidant enzymes in serum of tumor-bearing mice triggered by low dose radiation could partly contribute to the protective mechanism. (authors)

  13. The Immunomodulatory Effects of Mesenchymal Stem Cell Polarization within the Tumor Microenvironment Niche

    Directory of Open Access Journals (Sweden)

    Cosette M. Rivera-Cruz

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs represent a promising tool for cell therapy, particularly for their antitumor effects. This cell population can be isolated from multiple tissue sources and also display an innate ability to home to areas of inflammation, such as tumors. Upon entry into the tumor microenvironment niche, MSCs promote or inhibit tumor progression by various mechanisms, largely through the release of soluble factors. These factors can be immunomodulatory by activating or inhibiting both the adaptive and innate immune responses. The mechanisms by which MSCs modulate the immune response are not well understood. Because of this, the relationship between MSCs and immune cells within the tumor microenvironment niche continues to be an active area of research in order to help explain the apparent contradictory findings currently available in the literature. The ongoing research aims to enhance the potential of MSCs in future therapeutic applications.

  14. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    International Nuclear Information System (INIS)

    Huang, Peigen; Allam, Ayman; Perez, Luis A.; Taghian, Alphonse; Freeman, Jill; Suit, Herman D.

    1995-01-01

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm 3 , mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD 50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD 50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

  15. An evaluation of anti-tumor effect and toxicity of PEGylated ursolic acid liposomes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qianqian; Zhao, Tingting; Liu, Yanping; Xing, Shanshan; Li, Lei; Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Yanshan University, Applying Chemistry Key Lab of Hebei Province, Department of Bioengineer (China)

    2016-02-15

    Therapy of solid tumors mediated by nano-drug delivery has attracted considerable interest. In our previous study, ursolic acid (UA) was successfully encapsulated into PEGylated liposomes. The study aimed to evaluate the tumor inhibition effect and cytotoxicity of the PEGylated UA liposomes by U14 cervical carcinoma-bearing mice. The liposomes were spherical particles with mean particle diameters of 127.2 nm. The tumor inhibition rate of PEGylated UA liposomes was 53.60 % on U14 cervical carcinoma-bearing mice, which was greater than those of the UA solution (18.25 %) and traditional UA liposome groups (40.75 %). The tumor cells apoptosis rate of PEGylated UA liposomes was 25.81 %, which was significantly higher than that of the traditional UA liposomes (13.37 %). Moreover, the kidney and liver did not emerge the pathological changes in UA therapeutic mice by histopathological analysis, while there were significant differences on tumor tissues among three UA formulation groups. The PEGylated UA liposomes exhibited higher anti-tumor activity and lower cytotoxicity, and the main reason was that the coating PEG layer improved UA liposome properties, such as enhancing the stability of liposomes, promoting the effect of slow release, and prolonging the time of blood circulation. This may shed light on the development of PEGylated nano-vehicles.

  16. Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography

    International Nuclear Information System (INIS)

    Ng, Q.-S.; Goh, Vicky; Milner, Jessica; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J.

    2007-01-01

    Purpose: To quantitatively assess the in vivo acute vascular effects of fractionated radiotherapy for human non-small-cell lung cancer using volumetric perfusion computed tomography (CT). Methods and Materials: Sixteen patients with advanced non-small-cell lung cancer, undergoing palliative radiotherapy delivering 27 Gy in 6 fractions over 3 weeks, were scanned before treatment, and after the second (9 Gy), fourth (18 Gy), and sixth (27 Gy) radiation fraction. Using 16-detector CT, multiple sequential volumetric acquisitions were acquired after intravenous contrast agent injection. Measurements of vascular blood volume and permeability for the whole tumor volume were obtained. Vascular changes at the tumor periphery and center were also measured. Results: At baseline, lung tumor vascularity was spatially heterogeneous with the tumor rim showing a higher vascular blood volume and permeability than the center. After the second, fourth, and sixth fractions of radiotherapy, vascular blood volume increased by 31.6% (paired t test, p = 0.10), 49.3% (p = 0.034), and 44.6% (p = 0.0012) respectively at the tumor rim, and 16.4% (p = 0.29), 19.9% (p = 0.029), and 4.0% (p = 0.0050) respectively at the center of the tumor. After the second, fourth, and sixth fractions of radiotherapy, vessel permeability increased by 18.4% (p = 0.022), 44.8% (p = 0.0048), and 20.5% (p = 0.25) at the tumor rim. The increase in permeability at the tumor center was not significant after radiotherapy. Conclusion: Fractionated radiotherapy increases tumor vascular blood volume and permeability in human non-small-cell lung cancer. We have established the spatial distribution of vascular changes after radiotherapy; greater vascular changes were demonstrated at the tumor rim compared with the center

  17. Effects of alkylating carcinogens on human tumor cells in culture

    International Nuclear Information System (INIS)

    Goth-Goldstein, R.; Hughes, M.

    1987-01-01

    In Escherichia coli 3-methyladenine and 3-methylguanine have been identified as lethal lesions, since two types of alkylating agent-sensitive mutants were deficient in repair of either of these lesions. Similar alkylation-sensitive human cell lines exist. These are the tumor cell lines of the complex Mer - phenotype. All Mer - cells examined were hypersensitive to killing by MNNG and other alkylating agents, and failed to repair O 6 -methylguanine. The widely studied HeLa S3 cell line has the Mer + phenotype, but a Mer - variant (HeLa MR) has arisen. This offers the possibility to study Mer - and Mer + cells of otherwise similar genetic background. We are using these two variants to analyze the Mer - phenotype further. When HeLa S3 and HeLa MR were treated with a highly dose of MNNG, and the surviving population exposed to a second dose of MNNG 2-3 weeks later, HeLa S3 (Mer + ) cells were equally or even slightly more sensitive to a second exposure of MNNG, whereas the surviving HeLa MR (Mer - ) population was much more resistant to MNNG. 1 fig., 1 tab

  18. Health surveillance - myth and reality

    International Nuclear Information System (INIS)

    Sharp, C.

    1998-01-01

    This paper discusses the principles, health benefit and cost-effectiveness of health surveillance in the occupational setting, which apply to exposure to ionising radiations in the same manner as to other hazards in the workplace. It highlights the techniques for undertaking health surveillance, discusses their relative advantages and disadvantages and illustrates these in relation to specific hazards. The responsibilities of the medical staff and of the worker are also discussed. (author)

  19. Increase in tumor oxygenation and potentiation of radiation effects using pentoxifylline, vinpocetine and ticlopidine hydrochloride

    International Nuclear Information System (INIS)

    Amano, Morikazu; Monzen, Hajime; Suzuki, Minoru; Terai, Kaoru; Andoh, Satoshi; Tsumuraya, Akio; Hasegawa, Takeo

    2005-01-01

    The purpose of the present study was to investigate the effects of Pentoxifylline (PTX), Vinpocetine (VPT) and Ticlopidine Hydrochloride (TCD), used commonly for vascular disorders in humans, on the pO 2 in SCCVII tumors of C3H/HeJ mice and on the radioresponse of SCCVII tumors. The pO 2 in the SCCVII tumors, which were measured 30 min after intraperioneal (i.p.) injection of PTX (5 mg/kg), VPT (5 mg/kg), or TCD (10 mg/kg) using polarography, was compared to that in saline-treated control tumors. All the three drugs, PTX, VPT and TCD, yielded significant increase of the pO 2 in the SCCVII tumors from 25.6 to 26.9 mmHg, from 18.6 to 22.9 mmHg, and from 22.6 to 25.9 mmHg, respectively. Frequency histogram of the pO 2 distribution in the saline-treated SCCVII tumors did not show hypoxic fraction of less than 10 mmHg. The radioresponses of the drugs were investigated by tumor growth delay assay. In the drug-treated groups, the SCCVII tumors were irradiated with a single dose of 15 Gy 30 min after injection of the drugs at the same doses as those used in the experiments for intratumoral pO 2 measurement. Compared with the irradiation alone group, significant tumor growth delays were observed in all the drug-treated groups. The time required to reach a four-fold increase in the initial tumor volume were 4 days in the saline-treated control group, 22 days in the irradiation (IR) alone group, 28 days in the PTX+IR group, 29 days in the VPT+IR group, and 32 days in TCD+IR group. In conclusion, VPT and TCD are potentially promising drugs for increasing the intratumoral pO 2 although the mechanism for radiopotentiation observed in the present study is unknown due to small hypoxic fraction in the SCCVII tumors. Further studies on other mechanisms for radiopotentiation of PTX, VPT or TCD, besides of increasing the pO 2 in the tumor, are needed. (author)

  20. Who is Surveilling Whom?

    DEFF Research Database (Denmark)

    Mortensen, Mette

    2014-01-01

    This article concerns the particular form of counter-surveillance termed “sousveillance”, which aims to turn surveillance at the institutions responsible for surveillance. Drawing on the theoretical perspectives “mediatization” and “aerial surveillance,” the article studies WikiLeaks’ publication...

  1. Issues ignored in laboratory quality surveillance

    International Nuclear Information System (INIS)

    Zeng Jing; Li Xingyuan; Zhang Tingsheng

    2008-01-01

    According to the work requirement of the related laboratory quality surveillance in ISO17025, this paper analyzed and discussed the issued ignored in the laboratory quality surveillance. In order to solve the present problem, it is required to understand the work responsibility in the quality surveillance correctly, to establish the effective working routine in the quality surveillance, and to conduct, the quality surveillance work. The object in the quality surveillance shall be 'the operator' who engaged in the examination/calibration directly in the laboratory, especially the personnel in training (who is engaged in the examination/calibration). The quality supervisors shall be fully authorized, so that they can correctly understand the work responsibility in quality surveillance, and are with the rights for 'full supervision'. The laboratory also shall arrange necessary training to the quality supervisor, so that they can obtain sufficient guide in time and are with required qualification or occupation prerequisites. (authors)

  2. Risk based surveillance for vector borne diseases

    DEFF Research Database (Denmark)

    Bødker, Rene

    of samples and hence early detection of outbreaks. Models for vector borne diseases in Denmark have demonstrated dramatic variation in outbreak risk during the season and between years. The Danish VetMap project aims to make these risk based surveillance estimates available on the veterinarians smart phones...... in Northern Europe. This model approach may be used as a basis for risk based surveillance. In risk based surveillance limited resources for surveillance are targeted at geographical areas most at risk and only when the risk is high. This makes risk based surveillance a cost effective alternative...... sample to a diagnostic laboratory. Risk based surveillance models may reduce this delay. An important feature of risk based surveillance models is their ability to continuously communicate the level of risk to veterinarians and hence increase awareness when risk is high. This is essential for submission...

  3. Comparison of the tumor inhibiting effects of three histamine H2-receptor antagonists.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1983-01-01

    Three histamine H2-receptor antagonists, Cimetidine, Metiamide and Ranitidine, were tested for their inhibitory effect on two experimental bowel cancer models. In the first model mitotic rates were measured in dimethylhydrazine-induced tumors of rat colon and in the second model volumetric changes in human large bowel cancer xenografts were assessed. In tumors of rat colon all three drugs were able to suppress mitotic activity, but the effects of Metiamide and Ranitidine were more prolonged than that of Cimetidine in each of two lines of human bowel cancer that were used. Metiamide and Ranitidine were also more effective growth inhibitors than was Cimetidine.

  4. Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects.

    Directory of Open Access Journals (Sweden)

    Tae Heung Kang

    Full Text Available Interleukin-2 (IL-2 has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci.

  5. Effects of perfluorochemical emulsion on the timing of administration and irradiation in tumor bearing mice

    International Nuclear Information System (INIS)

    Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

    1988-01-01

    Perfluorochemical content was examined periodically, in blood, tumor and some organs using gas chromatography, after Fluosol-DA saline 20 % (FDAS) was injected into LLC bearing mice. The blood half-life of FDAS in LLC bearing mice was 3.76 hrs (5 ml/kg injection) or 6.15 hrs (20 ml/kg injection) respectively, and FDAS almost disapeared from the blood after about 2 days (5 ml/kg) and 3 days (20 ml/kg) of FDAS-injection. Most of FDAS was accumulated into spleen and the liver. FDAS accumulation into the tumor tissue was 1 ∼ 6 % of injected-FDAS dose and the peak of FDAS accumulation was 1 ∼ 3 days after injection. The timing of FDAS-injection and irradiation in tumor bearing mice determined according to the results above (half-life and accumulation of FDAS in tumor). FDAS (5, 10, 20 ml/kg) was injected to LLC-bearing mice on 3, 2, 1 and 0 day before irradiation and they were irradiated 15 Gray under oxygen-breathing, respectively. FDAS-injected groups before irradiation (3, 2, 1 day before, respectively) showed a tendency of tumor growth delay, but didn't show significant difference as compared with oxygen-breathing group without FDAS, because they had not enough effective FDAS content in the blood. Although the FDAS-injected groups just before irradiation significantly showed the delay of tumor growth. These results demonstrate that oxygen and FDAS existing in the blood injected just before irradiation effectively delay tumor growth in which the lowest effective dose is 5 ml/kg. In the case of clinical application of FDAS, FDAS may be most effective, when administrated just before irradiation in every fractionated irradiation. (author)

  6. Surface-water surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Saldi, K.A.; Dirkes, R.L.; Blanton, M.L.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the Surface water on and near the Hanford Site is monitored to determine the potential effects of Hanford operations. Surface water at Hanford includes the Columbia River, riverbank springs, ponds located on the Hanford Site, and offsite water systems directly east and across the Columbia River from the Hanford Site, and offsite water systems directly east and across the Columbia River from the Hanford Site. Columbia River sediments are also included in this discussion. Tables 5.3.1 and 5.3.2 summarize the sampling locations, sample types, sampling frequencies, and sample analyses included in surface-water surveillance activities during 1994. Sample locations are also identified in Figure 5.3.1. This section describes the surveillance effort and summarizes the results for these aquatic environments. Detailed analytical results are reported by Bisping (1995).

  7. Surface-water surveillance

    International Nuclear Information System (INIS)

    Saldi, K.A.; Dirkes, R.L.; Blanton, M.L.

    1995-01-01

    This section of the 1994 Hanford Site Environmental Report summarizes the Surface water on and near the Hanford Site is monitored to determine the potential effects of Hanford operations. Surface water at Hanford includes the Columbia River, riverbank springs, ponds located on the Hanford Site, and offsite water systems directly east and across the Columbia River from the Hanford Site, and offsite water systems directly east and across the Columbia River from the Hanford Site. Columbia River sediments are also included in this discussion. Tables 5.3.1 and 5.3.2 summarize the sampling locations, sample types, sampling frequencies, and sample analyses included in surface-water surveillance activities during 1994. Sample locations are also identified in Figure 5.3.1. This section describes the surveillance effort and summarizes the results for these aquatic environments. Detailed analytical results are reported by Bisping (1995)

  8. Commercial Online Social Network Data and Statin Side-Effect Surveillance: A Pilot Observational Study of Aggregate Mentions on Facebook.

    Science.gov (United States)

    Huesch, Marco D

    2017-12-01

    Surveillance of the safety of prescribed drugs after marketing approval has been secured remains fraught with complications. Formal ascertainment by providers and reporting to adverse-event registries, formal surveys by manufacturers, and mining of electronic medical records are all well-known approaches with varying degrees of difficulty, cost, and success. Novel approaches may be a useful adjunct, especially approaches that mine or sample internet-based methods such as online social networks. A novel commercial software-as-a-service data-mining product supplied by Sysomos from Datasift/Facebook was used to mine all mentions on Facebook of statins and stain-related side effects in the US in the 1-month period 9 January 2017 through 8 February 2017. A total of 4.3% of all 25,700 mentions of statins also mentioned typical stain-related side effects. Multiple methodological weaknesses stymie interpretation of this percentage, which is however not inconsistent with estimates that 5-20% of patients taking statins will experience typical side effects at some time. Future work on pharmacovigilance may be informed by this novel commercial tool, but the inability to mine the full text of a posting poses serious challenges to content categorization.

  9. Occupational health of miners at altitude: adverse health effects, toxic exposures, pre-placement screening, acclimatization, and worker surveillance.

    Science.gov (United States)

    Vearrier, David; Greenberg, Michael I

    2011-08-01

    Mining operations conducted at high altitudes provide health challenges for workers as well as for medical personnel. To review the literature regarding adverse health effects and toxic exposures that may be associated with mining operations conducted at altitude and to discuss pre-placement screening, acclimatization issues, and on-site surveillance strategies. We used the Ovid ( http://ovidsp.tx.ovid.com ) search engine to conduct a MEDLINE search for "coal mining" or "mining" and "altitude sickness" or "altitude" and a second MEDLINE search for "occupational diseases" and "altitude sickness" or "altitude." The search identified 97 articles of which 76 were relevant. In addition, the references of these 76 articles were manually reviewed for relevant articles. CARDIOVASCULAR EFFECTS: High altitude is associated with increased sympathetic tone that may result in elevated blood pressure, particularly in workers with pre-existing hypertension. Workers with a history of coronary artery disease experience ischemia at lower work rates at high altitude, while those with a history of congestive heart failure have decreased exercise tolerance at high altitude as compared to healthy controls and are at higher risk of suffering an exacerbation of their heart failure. PULMONARY EFFECTS: High altitude is associated with various adverse pulmonary effects, including high-altitude pulmonary edema, pulmonary hypertension, subacute mountain sickness, and chronic mountain sickness. Mining at altitude has been reported to accelerate silicosis and other pneumoconioses. Miners with pre-existing pneumoconioses may experience an exacerbation of their condition at altitude. Persons traveling to high altitude have a higher incidence of Cheyne-Stokes respiration while sleeping than do persons native to high altitude. Obesity increases the risk of pulmonary hypertension, acute mountain sickness, and sleep-disordered breathing. NEUROLOGICAL EFFECTS: The most common adverse neurological

  10. Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

    NARCIS (Netherlands)

    Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

    2012-01-01

    Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

  11. Safety and effectiveness of rapid-acting intramuscular olanzapine for agitation associated with schizophrenia – Japan postmarketing surveillance study

    Directory of Open Access Journals (Sweden)

    Katagiri H

    2018-01-01

    Full Text Available Hideaki Katagiri,1 Masanori Taketsuna,2 Shinpei Kondo,3 Kenta Kajimoto,4 Etsuko Aoi,5 Yuka Tanji1 1Bio Medicine, 2Statistical Sciences, 3Post Marketing Study Management, 4Scientific Communications, Medicines Development Unit Japan, 5Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan Objective: The objective of this study was to evaluate the safety and effectiveness of rapid-acting intramuscular (IM olanzapine in the treatment of acute agitation associated with schizophrenia in real-world clinical settings in Japan.Methods: In this multicenter, postmarketing surveillance (PMS study, patients with acute agitation associated with schizophrenia were treated with IM olanzapine daily in a daily clinical setting. The observational period ranged from 1 to 7 days, including the day of initial administration. Safety was assessed by reporting treatment-emergent adverse events (TEAEs and adverse drug reactions (ADRs. The Positive and Negative Syndrome Scale – Excited Component (PANSS-EC score was used to evaluate effectiveness at baseline and at 2 hours (after each administration, 2 days, and 3 days (end of the observational period from the last administration of the IM olanzapine injection.Results: The safety analysis set included 999 patients, and the initial dose of 10 mg was administered to 955 patients. TEAEs were reported in 28 patients (36 events, the most common of which were dyslalia (5 patients, akathisia and somno­lence (4 patients each, hepatic function abnormal (3 patients, and constipation and dehydration (2 patients each. One serious adverse event of akathisia occurred during the observation period. The PANSS-EC score (mean ± standard deviation was 23.3±6.4 (n=625 at baseline, 16.9±7.0 (n=522 at 2 hours after initial injection, and 14.9±6.5 (n=650 at the last observation carried forward.Conclusion: The results of this Japanese PMS study demonstrated that IM olanzapine is safe and has a

  12. Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect.

    Science.gov (United States)

    Lugini, Luana; Federici, Cristina; Borghi, Martina; Azzarito, Tommaso; Marino, Maria Lucia; Cesolini, Albino; Spugnini, Enrico Pierluigi; Fais, Stefano

    2016-08-01

    Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice. Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.

  13. Long-term psychological effects in children treated for intracranial tumors

    International Nuclear Information System (INIS)

    Jannoun, L.; Bloom, H.J.

    1990-01-01

    The results are reported of the psychological assessment of 62 children who presented with primary intracranial tumors and who received radiotherapy at the Royal Marsden Hospital between 1963 and 1973. Evaluations were carried out 3-20 years after treatment. All patients were free from progressive tumor at testing. The average IQ of the total series was within the normal range (Full-Scale IQ 92) but 23% of the patients were functioning at an educationally subnormal level of intelligence (IQ less than 80). Sex, tumor type, tumor location and the radiotherapy volume and site of maximum dose were not found to have a significant effect on intellectual outcome. A significant correlation was found between intelligence and age at the time of treatment. Children who received treatment under the age of 5 years were more adversely affected (average IQ 72) than those who were aged 6-10 (average IQ 93) and those aged 11-15 years (average IQ 107). The incidence of neurological abnormalities and physical disability was significantly greater among patients with supratentorial tumors (72% of cases), compared with patients with infratentorial lesions (44% of cases). The results were discussed in terms of the management of young patients with intracranial tumors

  14. Effect of immunomodifier on radiation-induced antitumor immunity following local irradiation to tumor, 2

    International Nuclear Information System (INIS)

    Mukae, Shiro; Norimura, Toshiyuki; Tsuchiya, Takehiko

    1988-01-01

    This study was carried out to clarify whether or not the antitumor cell-mediated immunity of host is more effectively induced by the combined use of mouse interferon-α/β (MuIFN-α/β) with local irradiation than by simple local irradiation to tumor. C3H/He female mice, MM46 tumor cells and mouse interferon-α/β (MuIFN-α/β) were used in the experiment. Antitumor activity in mice was evaluated by the inhibition of tumor growth and mean survival days after treatment. Spleen cell killing activity to MM46 tumor cells was measured to evaluate the antitumor activity in vitro. In the case of single use of MuIFN-α/β, tumor growth was more rapid than in the non-treated group (control) in vivo. The mean survival days were also reduced. There was no siginificant difference in tumor growth inhibition between combined therapy using X-irradiation and MuIFN-α/β, and single therapy by local irradiation. However, in the case of administration of MuIFN-α/β after irradiation, the mean survival days was significantly increased compared with the group receiving X-ray irradiation only. (author)

  15. Genetic modification of T cells improves the effectiveness of adoptive tumor immunotherapy.

    Science.gov (United States)

    Jakóbisiak, Marek; Gołab, Jakub

    2010-10-01

    Appropriate combinations of immunotherapy and gene therapy promise to be more effective in the treatment of cancer patients than either of these therapeutic approaches alone. One such treatment is based on the application of patients' cytotoxic T cells, which can be activated, expanded, and genetically engineered to recognize particular tumor-associated antigens (TAAs). Because T cells recognizing TAAs might become unresponsive in the process of tumor development as a result of tumor evasion strategies, immunogenic viral antigens or alloantigens could be used for the expansion of cytotoxic T cells and then redirected through genetic engineering. This therapeutic approach has already demonstrated promising results in melanoma patients and could be used in the treatment of many other tumors. The graft-versus-leukemia, or more generally graft-versus-tumor, reaction based on the application of a donor lymphocyte infusion can also be ameliorated through the incorporation of suicide genes into donor lymphocytes. Such lymphocytes could be safely and more extensively used in tumor patients because they could be eliminated should a severe graft-versus-host reaction develop.

  16. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    International Nuclear Information System (INIS)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon; Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung

    2012-01-01

    Arsenic trioxide (As 2 O 3 ) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As 2 O 3 on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As 2 O 3 (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA ± 35; 90 ± 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 ± 28.9 mm 2 (group A), 119 ± 31.7 (group B), and 92 ± 17.4 (group C, p 2 ) than both group B (50 ± 19.4, p = 0.02) and group C (28 ± 2.2, p 2 O 3 . The intraarterial administration of As 2 O 3 seems to be helpful for the selective ablation of the tumor.

  17. Late effects of treatment on the intelligence of children with posterior fossa tumors

    International Nuclear Information System (INIS)

    Duffner, P.K.; Cohen, M.E.; Thomas, P.

    1983-01-01

    This retrospective pilot study was undertaken to evaluate the late effects of treatment on intelligence in a population of children with posterior fossa tumors. Ten children with posterior fossa tumors treated with radiation and chemotherapy received intellectual evaluations at least one year following diagnosis. Six children had medulloblastomas, one child had a fourth ventricular ependymoma, two children had brainstem gliomas, and one child had a recurrent cerebellar astrocytoma. Children with supratentorial tumors were specifically excluded from the study in order to eliminate the possible influence of the tumor on intellectual functioning. Four children had had intelligence testing in school prior to treatment of their tumor. In each case results following treatment revealed a deterioration of full scale IQ of at least 25 points. Six children did not have prior testing; of these, two had IQ's less than 20. Overall, 50% of the patients had IQ's of less than 80 and 20% had IQ's of greater than 100. Furthermore, four children with normal intelligence (IQ greater than 80) have learning problems requiring special classes. Thus, of the ten children evaluated, all have either dementia, learning disabilities, or evidence of intellectual retardation. This study suggests that aggressive treatment of children with brain tumors may improve survivals but may be associated with significant long-term disabilities

  18. Semi-automated CCTV surveillance: the effects of system confidence, system accuracy and task complexity on operator vigilance, reliance and workload.

    Science.gov (United States)

    Dadashi, N; Stedmon, A W; Pridmore, T P

    2013-09-01

    Recent advances in computer vision technology have lead to the development of various automatic surveillance systems, however their effectiveness is adversely affected by many factors and they are not completely reliable. This study investigated the potential of a semi-automated surveillance system to reduce CCTV operator workload in both detection and tracking activities. A further focus of interest was the degree of user reliance on the automated system. A simulated prototype was developed which mimicked an automated system that provided different levels of system confidence information. Dependent variable measures were taken for secondary task performance, reliance and subjective workload. When the automatic component of a semi-automatic CCTV surveillance system provided reliable system confidence information to operators, workload significantly decreased and spare mental capacity significantly increased. Providing feedback about system confidence and accuracy appears to be one important way of making the status of the automated component of the surveillance system more 'visible' to users and hence more effective to use. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  19. Anti-tumor effects of 125I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice

    International Nuclear Information System (INIS)

    Xiao Zhongdi; Liang Chunlin; Zhang Guoli; Jing Yue; Zhang Yucheng; Gai Baodong

    2011-01-01

    Objective: To study the anti-tumor effects of 125 I radioactive particles implantation on transplantated tumor model of human breast cancer cells in nude mice and clarify their anti-tumor mechanisms. Methods 120 nude mice transplantated with human breast cancer cells MCF-7 were randomly divided into 3 groups (n=40): 125 I radioactive particles implanted group, non-radioactive particles implanted group and non-particles implanted group. The articles were implanted into mice according to Pairs system principle. The expressions of Fas mRNA and protein and the activaties of caspase-3 and caspase-8 enzyme were detected by RT-PCR and Western blotting. The changes of cell cycle were detected by flow cytometry. Results: Compared with non-radioactive particles implanted group and non-particles implanted group, the size of cancer tissues in 125 I radioactive particles implanted group was reduced significantly (P 0 /G 1 phase was significantly increased (P 125 I radioactive particles into transplantated tumor model of human breast cancer cells can kill tumor cells, inhibit the growth cycle of tumor cells and induce the apoptosis of tumor cells in nude mice. (authors)

  20. Adrenal neoplasms: Effectiveness and safety of CT-guided ablation of 23 tumors in 22 patients

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Farrah J.; Dupuy, Damian E.; Machan, Jason T. [Department of Diagnostic Imaging and the Office of Research Administration, Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 (United States); Mayo-Smith, William W., E-mail: wmayo-smith@lifespan.org [Department of Diagnostic Imaging and the Office of Research Administration, Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903 (United States)

    2012-08-15

    Purpose: To retrospectively evaluate the effectiveness and safety of image-guided ablation of adrenal tumors. Materials and methods: : This HIPAA-compliant study was IRB approved and informed consent was waived. From 5/1999-6/2008, 20 consecutive adrenal metastases (mean diameter 4.2 cm; range, 2-8) and 3 hormonally active primary adrenal tumors (mean diameter 2.3 cm; range, 1-4), including an aldosteronoma and 2 pheochromocytomas in 22 patients (14 men, 8 women; mean age 61 years; range 40-84) were ablated in 23 sessions. Bilateral metastases were treated in a single patient. Radiofrequency ablation was used to treat 16 adrenal metastases and the 3 hyperfunctioning tumors. Microwave ablation was used to treat 4 metastases. Successful treatment was defined as a lack of both enhancement on follow-up contrast enhanced CT and/or up-take on FDG PET-CT and for functioning tumors, resolution of biochemical abnormalities. Results: Technical success was achieved in all sessions. Mean follow-up was 45.1 months (range, 1-91) Local tumor progression (focal enhancement at ablation site {>=}1 cm in short axis) was detected in 4 of 23 tumors, two of which were identified bilaterally in a single patient prompting re-treatment. Of 19 patients with metastatic disease, 16 had fatal extra-adrenal disease progression, and 3 remain alive. Two of the 3 patients who underwent ablation of hyperfunctioning tumors remain alive, including the patient with an aldosteronoma who had recurrent symptoms 91 months post ablation. Intra-ablative hypertension occurred in 9% (2/23) of sessions and was successfully treated pharmacologically. Conclusion: Ablation of metastatic and hyperfunctioning adrenal tumors is safe and may provide local control and treatment of pathologic biochemical activity.

  1. Adrenal neoplasms: Effectiveness and safety of CT-guided ablation of 23 tumors in 22 patients

    International Nuclear Information System (INIS)

    Wolf, Farrah J.; Dupuy, Damian E.; Machan, Jason T.; Mayo-Smith, William W.

    2012-01-01

    Purpose: To retrospectively evaluate the effectiveness and safety of image-guided ablation of adrenal tumors. Materials and methods: : This HIPAA-compliant study was IRB approved and informed consent was waived. From 5/1999-6/2008, 20 consecutive adrenal metastases (mean diameter 4.2 cm; range, 2–8) and 3 hormonally active primary adrenal tumors (mean diameter 2.3 cm; range, 1–4), including an aldosteronoma and 2 pheochromocytomas in 22 patients (14 men, 8 women; mean age 61 years; range 40–84) were ablated in 23 sessions. Bilateral metastases were treated in a single patient. Radiofrequency ablation was used to treat 16 adrenal metastases and the 3 hyperfunctioning tumors. Microwave ablation was used to treat 4 metastases. Successful treatment was defined as a lack of both enhancement on follow-up contrast enhanced CT and/or up-take on FDG PET-CT and for functioning tumors, resolution of biochemical abnormalities. Results: Technical success was achieved in all sessions. Mean follow-up was 45.1 months (range, 1–91) Local tumor progression (focal enhancement at ablation site ≥1 cm in short axis) was detected in 4 of 23 tumors, two of which were identified bilaterally in a single patient prompting re-treatment. Of 19 patients with metastatic disease, 16 had fatal extra-adrenal disease progression, and 3 remain alive. Two of the 3 patients who underwent ablation of hyperfunctioning tumors remain alive, including the patient with an aldosteronoma who had recurrent symptoms 91 months post ablation. Intra-ablative hypertension occurred in 9% (2/23) of sessions and was successfully treated pharmacologically. Conclusion: Ablation of metastatic and hyperfunctioning adrenal tumors is safe and may provide local control and treatment of pathologic biochemical activity.

  2. Effects of MRI-assayed microvascular permeability on the accumulation of vinorelbine in xenograft tumors

    International Nuclear Information System (INIS)

    Raatschen, H.J.; Fu, Y.; Rogut, V.; Brasch, R.C.; Simon, G.H.; Sennino, B.; Wolf, K.J.

    2010-01-01

    Purpose: To determine the effects of MRI-assayed vascular leakiness on the delivery of macro-molecular therapeutics to tumors. Materials and Methods: MDA-MB 435 tumors, subcutaneously implanted into nude rats were treated with a single dose of bevacizumab at levels of 0.1 mg (n = 5) or 1.0 mg (n = 10) or received saline (control animals, n = 8). After 24 hours, albumin-(Gd-DTPA) 30 -enhanced MRI was performed. Just prior to MRI, the cytotoxic drug vinorelbine was administered intravenously. Upon completion of the MR experiment, tumor vinorelbine concentrations were quantified by high performance liquid chromatography (HPLC). Vascular leakiness (K PS ) was calculated based on the MRI data using a pharmacokinetic model. Results: K PS was calculated as 3.70 ± 1.12 (control tumors), 1.95 ± 0.70 (0.1 mg group) and 0.75 ± 0.46 μl min -1 cm -3 (1.0 mg group). K PS was significantly higher in the control group compared to the 1.0 mg bevacizumab group. Vinorelbine concentrations were measured as 409.4 ± 109.7 (control tumors), 387.5 ± 47.5 (0.1 mg group) and 250.7 ± 71.9 (1.0 mg group). These differences were not significant. A moderate and significant correlation was found between K PS and Vinorelbine concentrations in tumors (r = 0.49, p PS based on dynamic MRI enhanced by albumin-(Gd-DTPA) 30 correlated significantly with vinorelbine accumulation in experimental xenograft tumors under angiogenesis inhibition. Thus, the MRI technique applied in our study could potentially help to predict accumulation of macromolecular cytotoxic drugs and to optimize individual therapeutic regimes in tumors. (orig.)

  3. Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.

    Science.gov (United States)

    Renaud, Stéphanie; Corcé, Vincent; Cannie, Isabelle; Ropert, Martine; Lepage, Sylvie; Loréal, Olivier; Deniaud, David; Gaboriau, François

    2015-08-01

    Tumor cell growth requires large iron quantities and the deprivation of this metal induced by synthetic metal chelators is therefore an attractive method for limiting the cancer cell proliferation. The antiproliferative effect of the Quilamine HQ1-44, a new iron chelator vectorized toward tumor cells by a polyamine chain, is related to its high selectivity for the Polyamine Transport System (PTS), allowing its preferential uptake by tumoral cells. The difference in PTS activation between healthy cells and tumor cells enables tumor cells to be targeted, whereas the strong dependence of these cells on iron ensures a secondary targeting. Here, we demonstrated in vitro that HQ1-44 inhibits DNA synthesis and cell proliferation of HCT116 cells by modulating the intracellular metabolism of both iron and polyamines. Moreover, in vivo, in xenografted athymic nude mice, we found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects. Furthermore, as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ1-44. These data support the need for further studies to assess the value of HQ1-44 as an adjuvant treatment in cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.

    Science.gov (United States)

    Yamaguchi, Sachiko; Ogiue-Ikeda, Mari; Sekino, Masaki; Ueno, Shoogo

    2006-01-01

    We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.

  5. The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

    Science.gov (United States)

    Pierie, J P; Choudry, U; Muzikansky, A; Yeap, B Y; Souba, W W; Ott, M J

    2001-04-01

    Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor

  6. Cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii.

    Science.gov (United States)

    Yu, Siran; Ye, Xuewei; Chen, Lu; Xie, Xin; Zhou, Qian; Lian, Xiao-Yuan; Zhang, Zhizhen

    2015-11-15

    Whether sulfated saponins from Holothuria moebii inhibit the proliferation of colorectal cancer cells and have anti-colorectal tumor effects in animal model has not been investigated. To evaluate the cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii. (1) Column chromatography was used to prepare the total and individual saponins and HPLC was applied to define the components of the total saponins; (2) the activity of the total and individual saponins inhibiting the proliferation of human colorectal cancer cells was determined by SRB assay and the apoptosis induced by the saponins was qualified using cytometric analysis with Annexin V-FITC/PI double staining; and (3) the antitumor effects of the sulfated saponins on colorectal CT-26 tumor-bearing Balb/c mice were tested. The total and individual sulfated saponins significantly inhibited the proliferation of four different human colorectal cancer cells with IC50 values ranging from 1.04 to 4.08 μM (or 1.46 to 3.24 μg/ml for total saponins) and induced late apoptosis at an early treatment time in cancer cells. The total saponins (120 mg/kg) had antitumor activity in colorectal CT-26 tumor-bearing Balb/c mice. The sulfated saponins from H. moebii remarkably inhibited the proliferation of different human colorectal cancer cells and had significant anti-colorectal tumor activity in animal model. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Peigen; Allam, Ayman; Perez, Luis A; Taghian, Alphonse; Freeman, Jill; Suit, Herman D

    1995-04-30

    Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-{alpha}) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-{alpha} with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm{sup 3}, mice were randomly assigned to treatment: rHuTNF-{alpha} alone compared with normal saline control; or local radiation plus rHuTNF-{alpha} vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-{alpha} on this tumor. The TCD{sub 50} (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-{alpha} with local radiation. Results: Tumor growth in mice treated with a dose of 150 {mu}g/kg body weight rHuTNF-{alpha}, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-{alpha} also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-{alpha} starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD{sub 50} from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-{alpha} exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD{sub 50} value in the treatment vs. the

  8. Constructing TC-1-GLUC-LMP2 Model Tumor Cells to Evaluate the Anti-Tumor Effects of LMP2-Related Vaccines

    Science.gov (United States)

    Sun, Liying; Hao, Yanzhe; Wang, Zhan; Zeng, Yi

    2018-01-01

    Epstein-Barr virus (EBV) is related to a variety of malignant tumors, and its encoded protein, latent membrane protein 2 (LMP2), is an effective target antigen that is widely used to construct vector vaccines. However, the model cells carrying LMP2 have still not been established to assess the oncolytic effect of LMP2-related vaccines at present. In this study, TC-1-GLUC-LMP2 tumor cells were constructed as target cells to evaluate the anti-tumor effects of LMP2-assosiated vaccines. The results showed that both LMP2 and Gaussia luciferase (GLuc) genes could be detected by polymerase chain reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR) in TC-1-GLUC-LMP2 cells. Western blot results showed that the LMP2 and Gaussia luciferase proteins were stably expressed in tumor cells for at least 30 generations. We mixed 5 × 104 LMP2-specific mouse splenic lymphocytes with 5 × 103 TC-1-GLUC-LMP2 target cells and found that the target cells were killed as the specific killing effect was obviously enhanced by the increased quantities of LMP2-peptide stimulated spleens. Furthermore, the tumor cells could not be observed in the mice inoculated TC-1-GLUC-LMP2 cells after being immunized with vaccine-LMP2, while the vaccine-NULL immunized mice showed that tumor volume gradually grew with increased inoculation time. These results indicated that the TC-1-GLUC-LMP2 cells stably expressing LMP2 and GLuc produced tumors in mice, and that the LMP2-specific cytotoxic T lymphocyte (CTL) effectively killed the cells in vitro and in vivo, suggesting that TC-1-GLUC-LMP2 cells can be used as model cells to assess the immune and antitumor effects of LMP2-related vaccines. PMID:29570629

  9. Preclinical validation of electrochemotherapy as an effective treatment for brain tumors

    DEFF Research Database (Denmark)

    Agerholm-Larsen, Birgit; Iversen, Helle K; Ibsen, Per

    2011-01-01

    treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment...... to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool...

  10. Post-marketing surveillance of the safety and effectiveness of tacrolimus in 3,267 Japanese patients with rheumatoid arthritis.

    Science.gov (United States)

    Takeuchi, Tsutomu; Kawai, Shinichi; Yamamoto, Kazuhiko; Harigai, Masayoshi; Ishida, Kota; Miyasaka, Nobuyuki

    2014-01-01

    A post-marketing surveillance (PMS) program was implemented to assess the safety and effectiveness of tacrolimus (TAC) in Japanese rheumatoid arthritis (RA) patients and to identify risk factors related to adverse drug reactions (ADRs). Patients were registered centrally and monitored for all adverse events (AEs) for 24 weeks. Effectiveness was evaluated using the Disease Activity Score 28-CRP (DAS28-CRP). Data from 3,172 patients (mean age 62.2 years) were evaluated in the safety analysis. Of the safety population, 78.5 %were female and 25.9 % were in Steinbrocker's functional class 3 or 4. TAC was prescribed as monotherapy in 52.5 % and the most common concomitant disease modifying antirheumatic drug (DMARD) was methotrexate, used in 28.9 % of the patients. The incidence of AEs, serious AEs (SAEs), ADRs and serious ADRs were 41.2, 6.4, 36.0, and 4.9 %, respectively. The most frequent serious ADR category was infections and infestations. Age ≥ 65 years, concurrent renal dysfunction, and concurrent diabetes mellitus were identified as significant risk factors for ADR. Based on EULAR response criteria, 65.4 % of the patients showed moderate or good response. The results demonstrate that TAC is well tolerated by Japanese patients with active RA, including those receiving concomitant methotrexate, in the real world.

  11. Effect of Routine Surveillance Imaging on the Outcomes of Patients With Classical Hodgkin Lymphoma After Autologous Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Kapke, Jonathan T; Epperla, Narendranath; Shah, Namrata; Richardson, Kristin; Carrum, George; Hari, Parameswaran N; Pingali, Sai R; Hamadani, Mehdi; Karmali, Reem; Fenske, Timothy S

    2017-07-01

    Patients with relapsed and refractory classical Hodgkin lymphoma (cHL) are often treated with autologous hematopoietic cell transplantation (auto-HCT). After auto-HCT, most transplant centers implement routine surveillance imaging to monitor for disease relapse; however, there is limited evidence to support this practice. In this multicenter, retrospective study, we identified cHL patients (n = 128) who received auto-HCT, achieved complete remission (CR) after transplantation, and then were followed with routine surveillance imaging. Of these, 29 (23%) relapsed after day 100 after auto-HCT. Relapse was detected clinically in 14 patients and with routine surveillance imaging in 15 patients. When clinically detected relapse was compared with to radiographically detected relapse respectively, the median overall survival (2084 days [range, 225-4161] vs. 2737 days [range, 172-2750]; P = .51), the median time to relapse (247 days [range, 141-3974] vs. 814 days [range, 96-1682]; P = .30) and the median postrelapse survival (674 days [range, 13-1883] vs. 1146 days [range, 4-2548]; P = .52) were not statistically different. In patients who never relapsed after auto-HCT, a median of 4 (range, 1-25) surveillance imaging studies were performed over a median follow-up period of 3.5 years. A minority of patients with cHL who achieve CR after auto-HCT will ultimately relapse. Surveillance imaging detected approximately half of relapses; however, outcomes were similar for those whose relapse was detected using routine surveillance imaging versus detected clinically in between surveillance imaging studies. There appears to be limited utility for routine surveillance imaging in cHL patients who achieve CR after auto-HCT. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Antioxidants Impair Anti-Tumoral Effects of Vorinostat, but Not Anti-Neoplastic Effects of Vorinostat and Caspase-8 Downregulation

    OpenAIRE

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat...

  13. Relationship between α/β and radiosensitivity and biologic effect of fractional irradiation of tumor cells

    International Nuclear Information System (INIS)

    Guo Chuanling; Chinese Academy of Sciences, Beijing; Wang Jufang; Jin Xiaodong; Li Wenjian

    2006-01-01

    Five kinds of malignant human tumor cells, i.e. SMMC-7721, HeLa, A549, HT29 and PC3 cell lines, were irradiated by 60 Co γ-rays to 1-6 Gy in a single irradiation or two irradiations of half dose. The radiosensitivity was compared with the dose-survival curves and D 50 and D 10 values. Differences in the D 50 and D 10 between the single and fractional irradiation groups showed the effect of fractional irradiation. Except for PC3 cells, all the cell lines showed obvious relationship between radiosensitivity and biologic effect of fractional irradiation and the α/β value. A cell line with bigger α/β was more radiation sensitive, with less obvious effect of fractional irradiation. The results indicate that there were obvious differences in radiosensitivity, repair ability and biologic effect of fractional irradiation between tumor cells from different tissues. To some tumor cell lines, the relationship between radiosensitivity, biologic effect of fractional irradiation and repair ability was attested. The α/β value of single irradiation can be regarded as a parameter to investigate the radiosensitivity and biologic effect of fractional irradiation of tumor cells. (authors)

  14. Radiosensitizing effect of nitric oxide in tumor cells and experimental tumors irradiated with gamma rays and proton beams; Efecto radiosensibilizador del oxido nitrico en celulas tumorales y en tumores experimentales irradiados con radiacion gamma y con haces de protones

    Energy Technology Data Exchange (ETDEWEB)

    Policastro, Lucia L; Duran, Hebe; Molinari, Beatriz L [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Radiobiologia; Schuff, Juan A; Kreiner, Andres J; Burlon, Alejandro A; Debray, Mario E; Kesque, Jose M; Ozafran, Mabel J; Vazquez, Monica E [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Fisica; Davidson, Jorge; Davidson, Miguel [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires (Argentina); Somacal, Hector R; Valda, Alejandro A [Universidad Nacional de General San Martin , Villa Ballester (Argentina). Escuela de Ciencia y Tecnologia

    2003-07-01

    Nitric oxide (NO) has been reported to be a radiosensitizer of mammalian cells under hypoxic conditions. In a previous study, we demonstrated an enhancement in radiation response induced by NO in mouse tumor cells under aerobic conditions, with an increasing effect as a function of malignancy. The aim of the present study was to evaluate the effect of NO in tumor cells and in experimental tumors irradiated with {gamma} rays and proton beams. Irradiations were performed with a {sup 137}Cs {gamma} source and with proton beams generated by the TANDAR accelerator. Tumor cells were treated with the NO donor DETA-NO and the sensitizer enhancement ratio (SER) was calculated using the {alpha} parameter of the survival curve fitted to the linear-quadratic model. Tumor cells irradiated with protons were radio sensitized by DETA-NO only in the more malignant cells irradiated with low LET protons (2.69{+-}0.08 keV/{mu}m). For higher LET protons there were no radiosensitizing effect. For human tumor cells pre-treated with DETA-NO and irradiated with {gamma} rays, a significantly greater effect was demonstrated in the malignant cells (MCF-7) as compared with the near normal cells (HBL-100). Moreover, a significant decrease in tumor growth was demonstrated in mice pre-treated with the NO donor spermine and irradiated with {gamma} rays and low LET protons as compared with mice irradiated without pre-treatment with the NO donor. In conclusion, we demonstrated a differential effect of NO as a radiosensitizer of malignant cells, both with {gamma} rays and low LET protons. This selectivity, coupled to the in vivo inhibition of tumor growth, is of great interest for the potential use of NO releasing agents in radiotherapy. (author)

  15. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  16. Effect of surgical resection combined with transcatheter arterial chemoembolization on postoperative serum tumor marker levels and stem cell characteristics during tumor recurrence

    Directory of Open Access Journals (Sweden)

    Sen Yang

    2017-05-01

    Full Text Available Objective: To study the effect of surgical resection combined with transcatheter arterial chemoembolization (TACE on postoperative serum tumor marker levels and stem cell characteristics during tumor recurrence. Methods: A total of 98 patients with liver cancer who received radical resection in our hospital between May 2013 and July 2015 were reviewed and divided into TACE group and control group according to whether they received TACE within two months after surgical resection. Serum levels of tumor markers were detected 4 weeks after operation; the tumor recurrence was followed up within 3 years after operation, and the expression of stem cell marker molecules and cell proliferation molecules in recurrent lesions were detected. Results: 4 weeks after radical hepatectomy, serum AFP, AFP-L3, GP73 and GPC3 levels in TACE group were significantly lower than those in control group; Nanog, CD133, EpCAM, PICK1, CyclinD1, C-myc and Survivin expression in surgically removed lesions of TACE group were not different from those of control group while Nanog, CD133, EpCAM, PICK1, CyclinD1, C-myc and Survivin expression in recurrent lesions were significantly lower than those of control group. Conclusion: Surgical resection combined with TACE can more effectively remove liver cancer lesions, reduce the tumor marker levels and inhibit the tumor stem cell characteristics and cell proliferation activity in recurrent lesions.

  17. The effect of environmental chemicals on the tumor microenvironment

    NARCIS (Netherlands)

    Casey, Stephanie C.; Vaccari, Monica; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Barcellos-Hoff, Mary Helen; Brown, Dustin G.; Chapellier, Marion; Christopher, Joseph; Curran, Colleen S.; Forte, Stefano; Hamid, Roslida A.; Heneberg, Petr; Koch, Daniel C.; Krishnakumar, P. K.; Laconi, Ezio; Maguer-Satta, Veronique; Marongiu, Fabio; Memeo, Lorenzo; Mondello, Chiara; Raju, Jayadev; Roman, Jesse; Roy, Rabindra; Ryan, Elizabeth P.; Ryeom, Sandra; Salem, Hosni K.; Scovassi, A. Ivana; Singh, Neetu; Soucek, Laura; Vermeulen, Louis; Whitfield, Jonathan R.; Woodrick, Jordan; Colacci, Annamaria; Bisson, William H.; Felsher, Dean W.

    2015-01-01

    Potentially carcinogenic compounds may cause cancer through direct DNA damage or through indirect cellular or physiological effects. To study possible carcinogens, the fields of endocrinology, genetics, epigenetics, medicine, environmental health, toxicology, pharmacology and oncology must be

  18. The Mental Vitality @ Work study: design of a randomized controlled trial on the effect of a workers' health surveillance mental module for nurses and allied health professionals

    OpenAIRE

    Gärtner, Fania R; Ketelaar, Sarah M; Smeets, Odile; Bolier, Linda; Fischer, Eva; van Dijk, Frank JH; Nieuwenhuijsen, Karen; Sluiter, Judith K

    2011-01-01

    Abstract Background Employees in health care service are at high risk for developing mental health complaints. The effects of mental health complaints on work can have serious consequences for the quality of care provided by these workers. To help health service workers remain healthy and productive, preventive actions are necessary. A Workers' Health Surveillance (WHS) mental module may be an effective strategy to monitor and promote good (mental) health and work performance. The objective o...

  19. Ideology, Critique and Surveillance

    Directory of Open Access Journals (Sweden)

    Heidi Herzogenrath-Amelung

    2013-11-01

    Full Text Available The 2013 revelations concerning global surveillance programmes demonstrate in unprecedented clarity the need for Critical Theory of information and communication technologies (ICTs to address the mechanisms and implications of increasingly global, ubiquitous surveillance. This is all the more urgent because of the dominance of the “surveillance ideology” (the promise of security through surveillance that supports the political economy of surveillance. This paper asks which theoretical arguments and concepts can be useful for philosophically grounding a critique of this surveillance ideology. It begins by examining how the surveillance ideology works through language and introduces the concept of the ‘ideological packaging’ of ICTs to show how rhetoric surrounding the implementation of surveillance technologies reinforces the surveillance ideology. It then raises the problem of how ideology-critique can work if it relies on language itself and argues that Martin Heidegger’s philosophy can make a useful contribution to existing critical approaches to language.

  20. Stimulatory effect of low dose radiation on the immune function in tumor-bearing mice

    International Nuclear Information System (INIS)

    Zhang Ying; Li Xiujuan; Li Xiuyi; Liu Shuzheng

    1999-01-01

    Objective: The author aims at investigating the effect of whole body irradiation (WBI) with low dose radiation on immune function in tumor-bearing mice. Methods: C57BL/6J mine implanted with Lewis lung carcinoma cells in the right thighs were used as an experimental animal model. WBI with 75 mGy X-rays was given at the 10 th day after implantation and immunological parameters were detected 18 hours after irradiation. The immunological parameters included the spontaneous incorporation of 3 H-TdR into thymocytes, the number of splenocytes, the reaction of splenocytes to ConA and LPS, the splenic production of IL-2, the cytotoxic activities of natural killer (NK) and lymphokine activated killer cells (LAK) as well as specific cytotoxic T lymphocytes (CTL). Results: The immunological parameters of irradiated tumor-bearing mice were significantly increased compared with those of sham-irradiated tumor-bearing mice (P<0.05∼0.01). Conclusion: Low dose radiation could significantly increase the immune function of tumor-bearing mice, and this stimulatory effect may be of some potential significance in tumor therapy

  1. Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin tumor response and neurotoxicity

    International Nuclear Information System (INIS)

    Moore, J.L.; Biol, F.I.; Patterson, I.C.M.; Dawes, P.J.D.K.; Henk, J.M.

    1982-01-01

    In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed an initial peripheral neuropathy rate of 55%, despite a dose limitation of 12 g/m 2 of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970's. Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed

  2. Effect of certain variables on the tumor and tissue distribution of tracers. III. Salicylates and vasoactive drugs

    International Nuclear Information System (INIS)

    Halpern, S.E.; Hagan, P.; Stern, P.; Gordon, R.; Dabbs, J.

    1981-01-01

    Attempts were made to increase the viable tumor concentration of 54 Mn and 67 Ga in a rat hepatoma model by administering rat angiotensin, tolazoline, and salicylates. Salicylates increased the tumor concentrations of 54 Mn and improved 65 Mn viable tumor/background ratios. 67 Ga was not affected by the salicylates. The salicylate effect appeared to be mediated by intracellular mechanisms rather than alterations in plasma protein binding. Rat angiotensin slightly increased the concentrations of 67 Ga in the tumors but not enough to suggest that it would be useful clinically. Tolazoline did not increase tumor uptake of the tracers

  3. A cost-effectiveness analysis of three components of a syndromic surveillance system for the early warning of epidemics in rural China.

    Science.gov (United States)

    Ding, Yan; Sauerborn, Rainer; Xu, Biao; Shaofa, Nie; Yan, Weirong; Diwan, Vinod K; Dong, Hengjin

    2015-11-14

    Syndromic surveillance systems (SSSs) collect non-specific syndromes in early stages of disease outbreaks. This makes an SSS a promising tool for the early detection of epidemics. An Integrated Surveillance System in rural China (ISSC project), which added an SSS to the existing Chinese surveillance system for the early warning of epidemics, was implemented from April 2012 to March 2014 in Jiangxi and Hubei Provinces. This study aims to measure the costs and effectiveness of the three components of the SSS in the ISSC project. The central measures of the cost-effectiveness analysis of the three components of the syndromic surveillance system were: 1) the costs per reported event, respectively, at the health facilities, the primary schools and the pharmacies; and 2) the operating costs per surveillance unit per year, respectively, at the health facilities, the primary schools and the pharmacies. Effectiveness was expressed by reporting outputs which were numbers of reported events, numbers of raw signals, and numbers of verified signals. The reported events were tracked through an internal data base. Signal verification forms and epidemiological investigation reports were collected from local country centers for disease control and prevention. We adopted project managers' perspective for the cost analysis. Total costs included set-up costs (system development and training) and operating costs (data collection, quality control and signal verification). We used self-designed questionnaires to collect cost data and received, respectively, 369 and 477 facility and staff questionnaires through a cross-sectional survey with a purposive sampling following the ISSC project. All data were entered into Epidata 3.02 and exported to Stata for descriptive analysis. The number of daily reported events per unit was the highest at pharmacies, followed by health facilities and finally primary schools. Variances existed within the three groups and also between Jiangxi and Hubei

  4. Inhibitory effects of 3-bromopyruvate on human gastric cancer implant tumors in nude mice.

    Science.gov (United States)

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2014-01-01

    Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p0.05), but there was between the 5-FU and high dose groups (p<0.05). This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice .

  5. Effect of maternal death on child survival in rural West Africa: 25 years of prospective surveillance data in The Gambia.

    Directory of Open Access Journals (Sweden)

    Susana Scott

    Full Text Available The death of a mother is a tragedy in itself but it can also have devastating effects for the survival of her children. We aim to explore the impact of a mother's death on child survival in rural Gambia, West Africa.We used 25 years of prospective surveillance data from the Farafenni Health and Demographic surveillance system (FHDSS. Mortality rates per 1,000 child-years up to ten years of age were estimated and Kaplan-Meier survival curves plotted by maternal vital status. Cox proportional hazard models were used to examine factors associated with child survival.Between 1st April 1989 and 31st December 2014, a total of 2, 221 (7.8% deaths occurred during 152,906 child-years of follow up. Overall mortality rate was 14.53 per 1,000 child-years (95% CI: 13.93-15.14. Amongst those whose mother died, the rate was 25.89 (95% CI: 17.99-37.25 compared to 14.44 (95% CI: 13.84-15.06 per 1,000 child-years for those whose mother did not die. Children were 4.66 (95% CI: 3.15-6.89 times more likely to die if their mother died compared to those with a surviving mother. Infants whose mothers died during delivery or shortly after were up to 7 times more likely to die within the first month of life compared to those whose mothers survived. Maternal vital status was significantly associated with the risk of dying within the first 2 years of life (p-value <0.05, while this was no longer observed for children over 2 years of age (P = 0.872. Other factors associated with an increased risk of dying were living in more rural areas, and birth spacing and year of birth.Mother's survival is strongly associated with child survival. Our findings highlight the importance of the continuum of care for both the mother and child not only throughout pregnancy, and childbirth but beyond 6 weeks post-partum.

  6. Assessment of immune surveillance among inhabitants of high natural background radiation areas in Ramsar-Iran

    International Nuclear Information System (INIS)

    Sileh, Sajad Borzouei; Monfared, Ali Shabestani; Mostafazade, Amrollah; Abedian, Said

    2010-01-01

    In this study by Multi-parameter flow cytometry, immunologic analyze is performed on peripheral blood, NK cells, most effective cells in innate immune and the proportion of TCD8/TCD4 cells that is effective in cellular immune system will be determined. Lysosomal-associated membrane protein-1 (LAMP-1 or CD107a) is used as a functional marker for the identification of natural killer cell activity. Immune surveillance and immune system role in tumoral defense in Ramsar inhabitants will be determined. Radiation dose rate in Talesh mahalle is very high and was many times greater than Chaparsar (another region in Ramsar). Immune surveillance and immune system role in tumoral defense in Talesh mahalle inhabitants will be compared to Chaparsar inhabitants. If this doesn't have significant difference, we should think about some other aspects such as free radical scavengers that will study later

  7. Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.

    Science.gov (United States)

    Zawaski, Janice A; Sabek, Omaima M; Voicu, Horatiu; Eastwood Leung, Hon-Chiu; Gaber, M Waleed

    2017-11-15

    Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. 1 H magnetic resonance spectroscopy ( 1 H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. 1 H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. Our data indicate that tumor presence during radiation significantly affects long-term functional

  8. Dosimetric effect of intrafraction tumor motion in phase gated lung stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    Zhao Bo; Yang Yong; Li Tianfang; Li Xiang; Heron, Dwight E.; Huq, M. Saiful

    2012-01-01

    Purpose: A major concern for lung intensity modulated radiation therapy delivery is the deviation of actually delivered dose distribution from the planned one due to simultaneous movements of multileaf collimator (MLC) leaves and tumor. For gated lung stereotactic body radiotherapy treatment (SBRT), the situation becomes even more complicated because of SBRT's characteristics such as fewer fractions, smaller target volume, higher dose rate, and extended fractional treatment time. The purpose of this work is to investigate the dosimetric effect of intrafraction tumor motion during gated lung SBRT delivery by reconstructing the delivered dose distribution with real-time tumor motion considered. Methods: The tumor motion data were retrieved from six lung patients. Each of them received three fractions of stereotactic radiotherapy treatments with Cyberknife Synchrony (Accuray, Sunnyvale, CA). Phase gating through an external surrogate was simulated with a gating window of 5 mm. The resulting residual tumor motion curves during gating (beam-on) were retrieved. Planning target volume (PTV) was defined as physician-contoured clinical target volume (CTV) surrounded by an isotropic 5 mm margin. Each patient was prescribed with 60 Gy/3 fractions. The authors developed an algorithm to reconstruct the delivered dose with tumor motion. The DMLC segments, mainly leaf position and segment weighting factor, were recalculated according to the probability density function of tumor motion curve. The new DMLC sequence file was imported back to treatment planning system to reconstruct the dose distribution. Results: Half of the patients in the study group experienced PTV D95% deviation up to 26% for fractional dose and 14% for total dose. CTV mean dose dropped by 1% with tumor motion. Although CTV is almost covered by prescribed dose with 5 mm margin, qualitative comparison on the dose distributions reveals that CTV is on the verge of underdose. The discrepancy happens due to tumor

  9. Involvement of the Warburg effect in non-tumor diseases processes.

    Science.gov (United States)

    Chen, Zhe; Liu, Meiqing; Li, Lanfang; Chen, Linxi

    2018-04-01

    Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases. © 2017 Wiley Periodicals, Inc.

  10. Toxic effect of C60 fullerene-doxorubicin complex towards tumor and normal cells in vitro

    Directory of Open Access Journals (Sweden)

    Prylutska S. V.

    2014-09-01

    Full Text Available Creation of new nanostructures possessing high antitumor activity is an important problem of modern biotechnology. Aim. To evaluate cytotoxicity of created complex of pristine C60 fullerene with the anthracycline antibiotic doxorubicin (Dox, as well as of free C60 fullerene and Dox, towards different cell types – tumor, normal immunocompetent and hepatocytes. Methods. Measurement of size distribution for particles in C60 + Dox mixture was performed by a dynamic light scattering (DLS technique. Toxic effect of C60 + Dox complex in vitro towards tumor and normal cells was studied using the MTT assay. Results. DLS experiment demonstrated that the main fraction of the particles in C60 + Dox mixture had a diameter in the range of about 132 nm. The toxic effect of C60 + Dox complex towards normal (lymphocytes, macrophages, hepatocytes and tumor (Ehrlich ascites carcinoma, leukemia L1210, Lewis lung carcinoma cells was decreased by ~10–16 % and ~7–9 %, accordingly, compared with the same effect of free Dox. Conclusions. The created C60 + Dox composite may be considered as a new pharmacological agent that kills effectively tumor cells in vitro and simultaneously prevents a toxic effect of the free form of Dox on normal cells.

  11. Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan.

    Science.gov (United States)

    Saida, Takahiko; Yokoyama, Kazumasa; Sato, Ryusuke; Makioka, Haruki; Iizuka, Yukihiko; Hase, Masakazu; Ling, Yan; Torii, Shinichi

    2017-12-01

    Natalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis. During the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs). The safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing-remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period. The safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation. Biogen Japan Ltd (Tokyo, Japan).

  12. Safety and effectiveness of certolizumab pegol in patients with rheumatoid arthritis: Interim analysis of post-marketing surveillance.

    Science.gov (United States)

    Kameda, Hideto; Nishida, Keiichiro; Nannki, Toshihiro; Watanabe, Akira; Oshima, Yukiya; Momohara, Shigaki

    2017-01-01

    Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis. Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal. The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response. In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

  13. Effects of Ligustilide on Tumor Growth and Immune Function in ...

    African Journals Online (AJOL)

    Results: LIG significantly increased thymus and spleen index, macrophage phagocytosis, serum hemolysin concentration, spleen lymphocyte proliferation and CTL and NK cell activities in normal ICR mice, but inhibited the growth of transplantable H22 hepatoma. The effect was dose-related but not in a linear fashion.

  14. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    Directory of Open Access Journals (Sweden)

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  15. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

  16. Effectiveness and tolerability of parenteral testosterone undecanoate: a post-marketing surveillance study.

    Science.gov (United States)

    Wolf, Jan; Keipert, Dieter; Motazedi, Heiko; Ernst, Michael; Nettleship, Joanne; Gooren, Louis

    2017-12-01

    This observational post-marketing study of parenteral testosterone undecanoate (TU) in a non-selected population aimed to: examine the effectiveness of TU as treatment of hypogonadism; record adverse drug reactions (ADR) quantitatively particularly regarding polycythemia, prostate safety and cardiovascular-related metabolic risk factors; and verify whether recommended injection intervals apply to routine clinical practice. Eight hundred and seventy subjects from 259 outpatient units scheduled to visit the clinic six times were included. Effectiveness and tolerability of TU administration were assessed on a 4-point scale. Body weight, waist girth, blood pressure, hemoglobin levels, hematocrit, prostate-specific antigen (PSA), and digital rectal prostate examination were assessed. Over 90% of subjects completed the observational duration of 52.8 ± 9.7 weeks (mean ± SD) and 56% judged effectiveness as very good, 30.8% as good. 63.1% judged tolerability as very good, and 24.4% as good. No adverse effects on indicators of cardiovascular risk were observed. Polycythemia occurred in one subject and a supranormal hematocrit in one subject. Four subjects developed supranormal PSA levels. Prostate carcinoma was found in one subject, one subject had recurrence of a previously surgically treated prostate carcinoma, and the other two showed no indication of malignancy. Parenteral TU is safe, effective, and well-tolerated in clinical practice proving a good therapeutic option for hypogonadism.

  17. Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

    Directory of Open Access Journals (Sweden)

    Ana Flávia C. Ribeiro

    2012-04-01

    Full Text Available The aim of this study was to investigate the effect of Arrabidaea chica (Humb. & Bonpl. B. Verl., Bignoniaceae, extracts on Ehrlich solid tumor development in Swiss mice. Leaves of A. chica were extracted with two distinct solvents, ethanol and water. The phytochemical analysis of the extracts indicated different classes of secondary metabolites like as anthocyanidins, flavonoids, tannins and saponins. Ethanol (EE and aqueous (AE extracts at 30 mg/kg reduced the development of Ehrlich solid tumor after ten days of oral treatment. The EE group presented increase in neutrophil count, α1 and β globulin values, and decrease of α2 globulin values. Furthermore, EE reduced the percentage of CD4+ T cells in blood but did not alter the percentage of inflammatory mononuclear cells associated with tumor suggesting a direct action of EE on tumor cells. Reduced tumor development observed in AE group was accompanied by a lower percentage of CD4+ T lymphocytes in blood. At the tumor microenvironment, this treatment decreased the percentage of CD3+ T cells, especially due to a reduction of CD8+ T subpopulation and NK cells. The antitumor activity presented by the AE is possibly related to an anti-inflammatory activity. None of the extracts produced toxic effects in animals. In conclusion, the ethanol and aqueous extracts of A. chica have immunomodulatory and antitumor activities attributed to the presence of flavonoids, such as kaempferol. These effects appear to be related to different mechanisms of action for each extract. This study demonstrates the potential of A. chica as an antitumor agent confirming its use in traditional popular medicine.

  18. Do the benefits outweigh the side effects of colorectal cancer surveillance? A systematic review.

    Science.gov (United States)

    Augestad, Knut Magne; Rose, Johnie; Crawshaw, Benjamin; Cooper, Gregory; Delaney, Conor

    2014-05-15

    Most patients treated with curative intent for colorectal cancer (CRC) are included in a follow-up program involving periodic evaluations. The survival benefits of a follow-up program are well delineated, and previous meta-analyses have suggested an overall survival improvement of 5%-10% by intensive follow-up. However, in a recent randomized trial, there was no survival benefit when a minimal vs an intensive follow-up program was compared. Less is known about the potential side effects of follow-up. Well-known side effects of preventive programs are those of somatic complications caused by testing, negative psychological consequences of follow-up itself, and the downstream impact of false positive or false negative tests. Accordingly, the potential survival benefits of CRC follow-up must be weighed against these potential negatives. The present review compares the benefits and side effects of CRC follow-up, and we propose future areas for research.

  19. [Protective effect of polysaccharides extracts from corn silk against cyclophosphamide induced host damages in mice bearing H22 tumors].

    Science.gov (United States)

    Wu, Xian-chuang; Du, Gang-jun; Song, Xiao-yong; Zhang, Yong-zhou; Liu, Yu-xin

    2014-10-01

    To study the protective effect of polysaccharides from corn silk (PCS) against cyclophosphamide (CTX) induced host damages in mice bearing H22 tumors. The ascitic and solid tumor bearing mice model were established to investigate the anti-tumor effects of different dose of PCS (100, 200 and 300 mg/kg). The effects of PCS alone and with combination of CTX on tumor weight, survival time, thymus and spleen index, white blood cell, nucleated cell of marrow, serum ALT and AST level were tested. The high-dose PCS (300 mg/kg) had significant inhibitory effects on tumor. After combination with CTX, the tumor inhibitory ratio was enhanced to 68.71%, the survival time of tumor-burdened ascites tumor mice was significantly prolonged to 72.07% compared with CTX group. The Q value of combination group was 0.997. Thymus and spleen index, white blood cell, nucleated cell of marrow decreased by CTX were ameliorated significantly. The level of ALT and AST increased by CTX were reduced by combination with PCS. PCS has a potent inhibitory effect on the growth of implanted H22 tumors in mice and has a synergetic effect and an attenuated toxic effect in combination with CTX.

  20. The effect of steroid on FDG uptake in experimental tumors, granulomatous and inflammatory lesions

    International Nuclear Information System (INIS)

    Zhao Songji; Yuji Kuge; Kunihiro Nakada; Masayuki Sato; Toshiki Takei; Zhao Yan; Nagara Tamaki; Masashi Kohanawa; Ken-ichi Seki

    2004-01-01

    Objectives: FDG accumulates not only in malignant tumors but also inflammatory lesions, especially in granulomatous lesions, which makes differentiate malignant tumors from benign lesions difficult. To obtain a clue for differentiating malignant lesions from benign ones by FDG-PET, we determined the effect of steroid on FDG uptake in granulomatous and inflammatory lesions, and compared them with those in malignant tumors in rats. Methods: Rats were inoculated with a suspension of allogenic hepatoma cells (KDH-8), Bacille bili e de Calmette-Guerin-(BCG) or Staphylococcus aureus (S. aureus), or with turpentine oil into the left calf muscle. Two weeks after KDH-8, 19 days after BCG, or one week after S. aureus or turpentine oil inoculations, the rats were fasted overnight and divided into two subgroups (n=5-6, in each group): Prednisolone (PRE)-pretreated (Methylprednisolone acetate, 8 mg/kg body weight, i.m. injection 20 hour before the FDG intravenous injection) and control (untreated) groups. Radioactivity in tissues was determined one hour after i.v. injection of FDG. FDG uptake in tissues were expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). Results: FDG uptake in the tumor, granulomatous and inflammatory lesions were shown in Table. In the untreated animals, remarkably higher accumulations of FDG were observed in the tumor and granulomatous lesions, compared with those in the inflammatory lesions induced by S. aureus and turpentine oil. There was no significant difference in the level of FDG uptake between the tumor and granulomatous lesions, and between the two inflammatory lesions. PRE pre-treatment significantly decreased the level of FDG uptake in granulomatous lesions induced by BCG, inflammatory lesions induced by S. aureus and turpentine oil to 52%, 73% and 76% of the control value, respectively. The level of FDG uptake in the tumor was not significantly decreased by PRE

  1. Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (2). Combination effect on MM102 syngeneic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Shiio, Tsuyoshi; Ohishi, Kazuo; Tsuchiya, Yoshiharu; Niitsu, Iwayasu; Hayashibara, Hiromi; Yoshihama, Takashi; Moriyuki, Hirobumi

    1988-03-01

    C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.

  2. Effectiveness of chemotherapy in measurable granulosa cell tumors: a retrospective study and review of literature

    NARCIS (Netherlands)

    van Meurs, Hannah S.; Buist, Marrije R.; Westermann, Anneke M.; Sonke, Gabe S.; Kenter, Gemma G.; van der Velden, Jacobus

    2014-01-01

    Patients with irresectable granulosa cell tumors (GCTs) often receive chemotherapy. The effectiveness of this approach, however, is uncertain. The aim of our study was to assess the response rate to chemotherapy for residual and recurrent inoperable GCT. All consecutive chemotherapy-naive patients

  3. Evaluation of Anti-tumor and Chemoresistance-lowering Effects of ...

    African Journals Online (AJOL)

    Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer. Mingqian Lu, Xinhua Xu, Hongda Lu, Zhongxin Lu, Bingqing Xu, Chao Tan, Kezhi Shi, Rong Guo, Qingzhi Kong ...

  4. Boron neutron capture therapy (BNCT) using fast neutrons: Effects in two human tumor cell lines

    International Nuclear Information System (INIS)

    Sauerwein, W.; Ziegler, W.; Szypniewski, H.; Streffer, C.

    1990-01-01

    The results demonstrate that the effect of fast neutrons on cell survival in cell culture can be enhanced by boron neutron capture reaction. Even with lower enhancement ratios, the concept of NCT assisted fast neutron therapy may successfully be applied for tumor treatment with the Essen cyclotron. (orig.)

  5. Divergent effects of tumor necrosis factor alpha on apoptosis of human neutrophils

    NARCIS (Netherlands)

    van den Berg, J. M.; Weyer, S.; Weening, J. J.; Roos, D.; Kuijpers, T. W.

    2001-01-01

    Apoptosis of neutrophils is a key mechanism to control the intensity of the acute inflammatory response. Previously, the cytokine tumor necrosis factor alpha (TNF-alpha) was reported by some to have pro-apoptotic and by others to have antiapoptotic effects on neutrophils. The aim of this study was

  6. Effects of daily treatment with a radioprotector WR-2721 on Ehrlich's ascites tumors in mice

    International Nuclear Information System (INIS)

    Ikebuchi, Makoto; Shinohara, Shigeo; Kimura, Hiroshi; Morimoto, Kunio; Shima, Akihiro

    1981-01-01

    Mice were injected daily with a radioprotector WR-2721 (S-2-[3-aminopropyl-amino]ethylphosphorothioic acid) after inoculation with Ehrlich's ascites tumor cells. Increases in weight of mice, volume of ascitic fluid and number of ascitic cells per mouse were reduced by the daily administration of 5 mg/mouse of the drug, indicating a suppressive effect of WR-2721 on growth of ascitic cells. But daily treatment with 5 mg/mouse of WR-2721 caused earlier death of tumor-bearing mice. (author)

  7. Radiomodifying effect of hyperglycemia: correlation between a glucose dose and a tumor size

    International Nuclear Information System (INIS)

    Ul'yanenko, S.E.; Polityukova, N.A.

    1991-01-01

    Experiments were made on rats with trasplantable sarcoma-45 and sarcoma M-1. Dose correlation was established during a study of hyperglycemic radiomodifying action. Glucose injection at a dose of 6-17.5 g/kg was shown to enhance irradiation action. Glucose injection below or above these doses might cause worse radiotherapy results or even the death of animals. The best effect was obtained with small-size tumors. Large tumors(over 2 cm 3 ) were less sensitive to hyperglycemia combined with irradiation. Skin radioprotective action of hyperglycemia before irradiation increased with an increase in a dose

  8. Investigations about late effects of exclusive radiotherapy of tumors of the epipharynx

    Energy Technology Data Exchange (ETDEWEB)

    Richter, E

    1982-09-01

    The late effects of ionizing radiation after radiotherapeutic healing of malignant tumors are of great interest. A report is given on sixteen patients with a malignant tumor of the epipharynx, who had been exclusively treated by radiotherapy and are regarded as cured. Only four of these patients had no complaints when examined, the others presented symptoms which were partly due to radiotherapy. The most important symptoms were rhinitis sicca and pharyngitis sicca induced by radiation. The complaints now indicated by the patients and the results of thorough clinical examinations are discussed and compared to communications of literature.

  9. Effects of extracellular calcium on calcium transport during hyperthermia of tumor cells.

    Science.gov (United States)

    Anghileri, L J; Marcha, C; Crone-Escanyé, M C; Robert, J

    1985-08-01

    The effects of different concentrations of extracellular ion calcium on the transport of calcium by tumor cells have been studied by means of the uptake of radiocalcium. Tumor cells incubated at 45 degrees C take up 4-10 times the amount of radioactivity incorporated by cells incubated at 37 degrees C. The difference is still greater (up to 100 times) for the intracellular incorporation as assessed by elimination of the membrane-bound calcium by EGTA treatment. The possible mechanisms involved in this differential behavior are discussed.

  10. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille

    2012-01-01

    in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis. Mechanistically, calcium electroporation caused acute ATP depletion likely due to a combination of increased cellular use of ATP......, decreased production of ATP due to effects on the mitochondria, as well as loss of ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load cancer cells with calcium as an efficient anticancer treatment...

  11. Effect of lymphokine-activated killer cells with or without radiation therapy against malignant brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, Kunio; Kamezaki, Takao; Shibata, Yasushi; Tsunoda, Takashi; Meguro, Kotoo; Nose, Tadao [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

    1995-01-01

    The use of autologous lymphokine-activated killer (LAK) cells to treat malignant brain tumors was evaluated in 10 patients, one with metastatic malignant melanoma and nine with malignant glioma. LAK cells were obtained by culturing autologous peripheral blood lymphocytes with human recombinant interleukin-2 (rIL-2) for 7-28 days. All patients underwent surgery to remove as much tumor as possible and an Ommaya reservoir was implaced in the tumor cavity. Two of the 10 patients had received radiotherapy elsewhere, so were treated with LAK cells alone. Eight patients were treated with a combination of LAK cells and radiotherapy, using 1.8-2.0 Gy fractions given five times a week with a total dosage between 54 and 65 Gy. LAK cells and rIL-2 were injected to the tumor cavity via the Ommaya reservoir once a week for inpatients and once a month for outpatients. The duration of the LAK therapy ranged from 3 to 23 months (mean 13.7 mos). Neuroimaging evaluation revealed two complete responses, three partial responses, four no changes, and one progressive disease. In one patient with pontine glioma, the Karnofsky performance score was raised from 20 to 60. There were no side effects after the injection of LAK cells and rIL-2. The results suggest low-dose LAK therapy is a useful and safe treatment modality for malignant brain tumors. (author).

  12. Estimation of the effectivity of gamma teletherapy with fractionated daily doses in inoperable malignant tumors

    International Nuclear Information System (INIS)

    Mardynskij, Yu.S.; Leskov, V.P.

    1982-01-01

    131 patients with lung, esophagus, rectum and mandibulofacial tumors, most of them being inoperable, were treated with fractionated gamma teletherapy. The daily focus dose of 2-2.2 Gy was applied in 2 fractions with an interval of 4-6 h. The total focus dose of one course of treatment was 40-70 Gy. In 56 patients (42.7%) a complete regression of the tumors and of the increased regional lymph nodes was obtained. The irradiation by the mentioned technique showed the highest effectivity for tumors of the lung and the esophagus. The diminished frequency and an easier progress of the radiation reactions are important because they often prevent to carry out a radical therapy. (author)

  13. Stabilization of neurotensin analogues: effect on peptide catabolism, biodistribution and tumor binding

    Energy Technology Data Exchange (ETDEWEB)

    Bruehlmeier, Matthias E-mail: peter.blaeuenstein@psi.ch; Garayoa, Elisa Garcia; Blanc, Alain; Holzer, Barbara; Gergely, Suzanne; Tourwe, Dirk; Schubiger, Pius August; Blaeuenstein, Peter

    2002-04-01

    Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [{sup 99m}Tc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (N{alpha}His)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH{sub 2}NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.

  14. Paracrine Apoptotic Effect of p53 Mediated by Tumor Suppressor Par-4

    Directory of Open Access Journals (Sweden)

    Ravshan Burikhanov

    2014-01-01

    Full Text Available The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53−/− or Par-4−/− mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 induced Par-4 secretion by suppressing the expression of its binding partner, UACA, which sequesters Par-4. Thus, normal cells can be empowered by p53 activation to induce Par-4 secretion for the inhibition of therapy-resistant tumors.

  15. The anti-tumor effect of bee honey in Ehrlich ascite tumor model of mice is coincided with stimulation of the immune cells.

    Science.gov (United States)

    Attia, W Y; Gabry, M S; El-Shaikh, K A; Othman, G A

    2008-01-01

    Honey is thought to exhibit a broad spectrum of therapeutic properties including antibacterial, antifungal, cytostatic and anti-inflammatory activity and has been used for the treatment of gastric ulcers, burns, and for storage of skin grafts. The present study investigated the antitumor effect of bee honey against Ehrlich ascites tumor in mice and the possible mode of antitumor action. Peroral administration of mice with honey (10, 100 or 1000 mg/ 100 g BW) every other day for 4 weeks before intraperitoneal inoculation with Ehrlich ascites tumor (EAT, 1 x 10(6) cells) increased the number bone marrow cells as well as peritoneal macrophages, but not peripheral blood leukocytes nor splenocytes. The phagocytic function of macrophages as well as the T- and B-cell functions were also increased. Honey pre-treatment also recovered the total lipids, total proteins, as well as liver and kidney enzyme activities in EAT-bearing mice. In vitro studies on EAT cells demonstrated inhibitory effect of honey on tumor cell proliferation, viability % of tumor cells as well as the size of solid tumor. The present results indicate that the preventive treatment with honey is considerably effective against EAT in mice both in vivo and in vitro. The antitumor activity of honey may occur through the activation of macrophages, T-cells and B-cells.

  16. Biometeorological forecasts for health surveillance and prevention of meteor-tropic effects

    Science.gov (United States)

    Lecha Estela, Luis B.

    2018-05-01

    An early method of biometeorological forecasts was developed for Cuba during the late 90s. It was based on the relationship between the daily occurrence of massive health crisis and the magnitude of the 24-h differences of partial density of oxygen in the air (PODA index). Ten years later, applying new technological facilities, a new model was developed in order to offer operational biometeorological forecast to Cuban health institutions. After a satisfactory validation process, the official bioforecast service to health institutions in Villa Clara province began on February of 2012. The effectiveness had different success levels: for the bronchial asthma crisis (94%), in the hypertensive crisis (88%), with the cerebrovascular illnesses (85%), as well as migraines (82%) and in case of cardiovascular diseases (75%) were acceptable. Since 2008, the application of the model was extended to other regions of the world, including some national applications. Furthermore, it allowed the beginning of regional monitoring of meteor-tropic effects, following the occurrence and movement of areas with higher weather contrasts, defined according to the normalized scale of PODA index. The paper describes the main regional results already available, with emphasis in the observed meteor-tropic effects increasing in all regions during recent years. It coincides with the general increase of energy imbalance in the whole climate system. Finally, the paper describes the current development of new global biometeorological forecast services.

  17. The effect of TACE with endostatin on hemodynamics in hepatic implantation tumor using Doppler ultrasonography

    International Nuclear Information System (INIS)

    Zhou Guangli; Wu Yuanyuan; Wang Bin; Liu Yan; Zheng Chuanli; Sang Li; Liu Feng

    2009-01-01

    Objective: To investigate the hemodynamic changes in the rabbit liver and VX2 hepatic implantation tumor after treatment by transcatheter arterial chemoembolization (TACE)/endostatin using Doppler ultrasonography. Methods: Twenty rabbits with VX2 hepatic tumor were randomly distributed into the control group (n=10) and the anti- angiogenesis group (n=10). The rabbits were administered with endostatin and adriamycin-lipiodol in the anti-angiogenesis group and with 37℃ saline in the control group via hepatic artery. The hemodynamic changes of the tumors, hepatic artery, and portal vein were recorded with Doppler ultrasonography 1 week after the treatment. The results before and after the treatment were compared. Results: In the control group, the maximal hepatic artery blood flow velocity was significantly higher than that before the treatment (P<0.05). However, the resistance index and the portal vein blood flow velocities had no significantly change compared with those before the treatment (P>0.05). In the anti-angiogenesis group, the hepatic artery blood flow velocity was significantly lower than that before the treatment (P<0.05), and the resistance index was increased (P<0.05). However, the portal vein blood flow velocity had no significantly change (P>0.05). The blood flow signal in all tumors was rich before embolization. After TACE, the blood flow signal was significantly decreased, even partly disappeared in the anti-angiogenesis group. Conclusion: TACE with endostatin can effectively block the blood supplement of VX2 hepatic implantation tumor. Doppler ultrasonography can detected the blood flow changes and can be used in evaluating the therapeutic effect in hepatic implantation tumor. (authors)

  18. Tumor-specific antivascular effect of TZT-1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy

    International Nuclear Information System (INIS)

    Natsume, Tsugitaka; Watanabe, Junichi; Kobayashi, Motohiro; Ogawa, Kenji; Yasumura, Kazuhiko

    2007-01-01

    TZT-1027 (soblidotin), an antimicrotubule agent, has previously been evaluated in terms of its antivascular effects. In this study, Evans blue perfusion, magnetic resonance imaging (MRI), and confocal laser scanning microscopy (CLSM) were utilized to further elucidate the antivascular effect of TZT-1027 in female nude mice and rats bearing human breast tumor MX-1, as well as in female Sprague-Dawley rats that developed breast tumors induced by dimethylbenz(a)anthracene (DMBA). Therapeutic doses of TZT-1027 caused nearly complete regression of implanted MX-1 tumors in nude mice and rats as well as DMBA-induced tumors in rats. The perfusion in MX-1 tumor implanted in nude mice was drastically reduced within 30 min after TZT-1027 administration and was completely inhibited after 6 h or more, although not reduced in normal tissue of kidney. The study using MRI demonstrated that rich blood flow within tumors was remarkably reduced 1-3 h after TZT-1027 administration both in nude rats bearing MX-1 tumors and in rats with DMBA-induced tumors. Furthermore, the study with CLSM in nude mice bearing MX-1 tumors revealed a disruption of tumor microvessels at 1 h and a destruction of tumor microvessel network at 3 h after TZT-1027 administration. In contrast, these types of vascular disorders were not observed in heart and kidney. These results suggest that TZT-1027 specifically damages tumor vasculatures, leading to extensive tumor necrosis within tolerable dose range, and confirms earlier observations that TZT-1027 exerts a considerable antivascular effect in addition to an excellent cytotoxic effect. (author)

  19. Neurocognitive effects of therapeutic irradiation for base of skull tumors

    International Nuclear Information System (INIS)

    Meyers, Christina A.; Geara, Fady; Wong Peifong; Morrison, William H.

    2000-01-01

    Purpose: To determine whether radiation therapy delivered to the paranasal sinuses causes any long-term impairment in neurocognitive function as a result of incidental brain irradiation. Methods and Materials: Nineteen patients who received paranasal sinus irradiation at least 20 months and up to 20 years before assessment were given a battery of neuropsychologic tests of cognitive function. Radiation was delivered by a three-field (one anteroposterior and two lateral) technique. The median radiation dose was 60 Gy (range 50-68 Gy) in fractions of 1.8 to 2 Gy. The volume of irradiated brain was calculated from planning computed tomography slices or simulation films. The results of the neuropsychologic tests were compared to normative control values. Results: Memory impairment was found in 80% of the patients, and one-third manifested difficulty with visual-motor speed, frontal lobe executive functions, and fine motor coordination. Two of the patients had frank brain necrosis with resultant dementia and blindness, and three had evidence of brain atrophy. Three of the fourteen patients without documented cerebral atrophy or necrosis were disabled from their normal activities. Three patients also developed pituitary dysfunction. Neurocognitive symptoms were related to the total dose of radiation delivered but not to the volume of brain irradiated, side of radiation boost, or chemotherapy treatment. The pattern of test findings was consistent with radiation injury to subcortical white matter. Conclusions: Radiation therapy for paranasal sinus cancer may cause delayed neurocognitive side effects. Currently, however, the development of severe adverse effects appears to be decreasing because of improvements in the techniques used to deliver radiation. Lowering the total dose and improving dose distributions should further decrease the incidence of delayed brain injury due to radiation

  20. An effective tumor-targeting strategy utilizing hypoxia-sensitive siRNA delivery system for improved anti-tumor outcome.

    Science.gov (United States)

    Kang, Lin; Fan, Bo; Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Gao, Zhonggao

    2016-10-15

    Hypoxia is a feature of most solid tumors, targeting hypoxia is considered as the best validated yet not extensively exploited strategy in cancer therapy. Here, we reported a novel tumor-targeting strategy using a hypoxia-sensitive siRNA delivery system. In the study, 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazole (AI) through bioreduction under hypoxic conditions, was conjugated to the alkylated polyethyleneimine (bPEI1.8k-C6) to form amphiphilic bPEI1.8k-C6-NI polycations. bPEI1.8k-C6-NI could self-assemble into micelle-like aggregations in aqueous, which contributed to the improved stability of the bPEI1.8k-C6-NI/siRNA polyplexes, resulted in increased cellular uptake. After being transported into the hypoxic tumor cells, the selective nitro-to-amino reduction would cause structural change and elicit a relatively loose structure to facilitate the siRNA dissociation in the cytoplasm, for enhanced gene silencing efficiency ultimately. Therefore, the conflict between the extracellular stability and the intracellular siRNA release ability of the polyplexes was solved by introducing the hypoxia-responsive unit. Consequently, the survivin-targeted siRNA loaded polyplexes shown remarkable anti-tumor effect not only in hypoxic cells, but also in tumor spheroids and tumor-bearing mice, indicating that the hypoxia-sensitive siRNA delivery system had great potential for tumor-targeted therapy. Hypoxia is one of the most remarkable features of most solid tumors, and targeting hypoxia is considered as the best validated strategy in cancer therapy. However, in the past decades, there were few reports about using this strategy in the drug delivery system, especially in siRNA delivery system. Therefore, we constructed a hypoxia-sensitive siRNA delivery system utilizing a hypoxia-responsive unit, 2-nitroimidazole, by which the unavoidable conflict between improved extracellular stability and promoted intracellular si

  1. Genetically engineered endostatin-lidamycin fusion proteins effectively inhibit tumor growth and metastasis

    International Nuclear Information System (INIS)

    Jiang, Wen-guo; Zhen, Yong-su; Lu, Xin-an; Shang, Bo-yang; Fu, Yan; Zhang, Sheng-hua; Zhou, Daifu; Li, Liang; Li, Yi; Luo, Yongzhang

    2013-01-01

    Endostatin (ES) inhibits endothelial cell proliferation, migration, invasion, and tube formation. It also shows antiangiogenesis and antitumor activities in several animal models. Endostatin specifically targets tumor vasculature to block tumor growth. Lidamycin (LDM), which consists of an active enediyne chromophore (AE) and a non-covalently bound apo-protein (LDP), is a member of chromoprotein family of antitumor antibiotics with extremely potent cytotoxicity to cancer cells. Therefore, we reasoned that endostatin-lidamycin (ES-LDM) fusion proteins upon energizing with enediyne chromophore may obtain the combined capability targeting tumor vasculature and tumor cell by respective ES and LDM moiety. In this study, we designed and obtained two new endostatin-based fusion proteins, endostatin-LDP (ES-LDP) and LDP-endostatin (LDP-ES). In vitro, the antiangiogenic effect of fusion proteins was determined by the wound healing assay and tube formation assay and the cytotoxicity of their enediyne-energized analogs was evaluated by CCK-8 assay. Tissue microarray was used to analyze the binding affinity of LDP, ES or ES-LDP with specimens of human lung tissue and lung tumor. The in vivo efficacy of the fusion proteins was evaluated with human lung carcinoma PG-BE1 xenograft and the experimental metastasis model of 4T1-luc breast cancer. ES-LDP and LDP-ES disrupted the formation of endothelial tube structures and inhibited endothelial cell migration. Evidently, ES-LDP accumulated in the tumor and suppressed tumor growth and metastasis. ES-LDP and ES show higher binding capability than LDP to lung carcinoma; in addition, ES-LDP and ES share similar binding capability. Furthermore, the enediyne-energized fusion protein ES-LDP-AE demonstrated significant efficacy against lung carcinoma xenograft in athymic mice. The ES-based fusion protein therapy provides some fundamental information for further drug development. Targeting both tumor vasculature and tumor cells by endostatin

  2. Investigating the expression, effect and tumorigenic pathway of PADI2 in tumors

    Directory of Open Access Journals (Sweden)

    Guo W

    2017-03-01

    Full Text Available Wei Guo,1,2,* Yabing Zheng,2,* Bing Xu,1 Fang Ma,1 Chang Li,3 Xiaoqian Zhang,4 Yao Wang,1 Xiaotian Chang1 1Medical Research Center, Shandong Provincial Qianfoshan Hospital, 2Obstetrical Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 3Pathology Department, Tengzhou Central People’s Hospital, Tengzhou, 4Clinical Laboratory, PKU Care Luzhong Hospital, Zibo, Shandong, People’s Republic of China *These authors contributed equally to this work Background: Peptidylarginine deiminase (PAD catalyzes the conversion of arginine residues to citrulline residues, termed citrullination. Recent studies have suggested that PAD isoform 2 (PADI2 plays an important role in tumors, although its tumorigenic effect and mechanism are largely unknown. Materials and methods: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA were used to investigate the expression level of PADI2 in various tumor tissues and patient blood samples, respectively. MNK-45 and Bel-7402 tumor cell lines originating from gastric and liver tumors, respectively, were treated with anti-PADI2 siRNA, and the subsequent cell proliferation, apoptosis and migration were observed. Polymerase chain reaction (PCR arrays, including Cancer PathwayFinder, Oncogenes and Tumor Suppressor Genes, p53 Signaling Pathway, Signal Transduction Pathway and Tumor Metastasis PCR arrays, were used to investigate the tumorigenic pathway of PADI2 in the siRNA-treated tumor cells. This analysis was verified by real-time PCR. Results: Immunohistochemistry detected significantly increased expression of PADI2 in invasive breast ductal carcinoma, cervical squamous cell carcinoma, colon adenocarcinoma, liver hepatocellular carcinoma, lung cancer, ovarian serous papillary adenocarcinoma and papillary thyroid carcinoma samples. ELISA detected a twofold increase in PADI2 expression in the blood of 48.3% of patients with liver cancer, 38% of patients with cervical

  3. Looking for trouble: Adherence to late-effects surveillance among childhood cancer survivors.

    Science.gov (United States)

    Reppucci, Marina L; Schleien, Charles L; Fish, Jonathan D

    2017-02-01

    Childhood cancer survivors (CCSs) are at high risk of morbidity and mortality from long-term complications of their cancer treatment. The Children's Oncology Group developed screening guidelines to enable the early identification of and intervention for late effects of cancer treatment. There is a paucity of data on the adherence of CCSs to screening recommendations. A retrospective analysis of medical records to evaluate the rate of adherence of CCSs to the personalized, risk-based recommendations provided to them in the context of a structured long-term follow-up program over a 3-year period. Two hundred eighty-six CCSs visited the survivorship clinic 542 times during the 3-year study period. The overall rate of adherence to recommended screening was 74.2%. Using a univariate model and greater age at diagnosis and at screening recommendation were associated with decreased screening adherence. Gender, cancer diagnosis, radiation therapy, anthracycline exposure, and hematopoietic stem cell transplant were not significantly associated with adherence. In a multivariate model, age over 18 years at the time of the visit was significantly associated with decreased adherence (P < 0.0329) (odds ratio: 1.53, 95% confidence interval: 1.04-2.25). Adherence to recommended screening tests is suboptimal among CCSs, with lower rates of adherence in CCSs older than 18 years of age compared with those younger than 18 years of age. Given the morbidity and mortality from the late effects of therapy among young adult CCSs, it is critically important to identify and remove barriers to late-effects screening among CCSs. © 2016 Wiley Periodicals, Inc.

  4. Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Hong-Mei Yang

    2017-02-01

    Full Text Available Bleomycin (BLM, a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22 tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

  5. SNSA surveillance over the ageing effects and ability for long term operation at Krsko NPP

    International Nuclear Information System (INIS)

    Savli, S.; Ferjancic, M.; Pavlin, D.; Lovincic, D.

    2007-01-01

    The paper presents the Slovenian Nuclear Safety Administration (SNSA) tools used for verification the adequacy of management of ageing effects and assuring suitability for long term operation at the Krsko NPP. In addition to tools commonly used as PSR (Periodic Safety Review), assessment of plant modifications, regular inspections, the SNSA applies some special methods like monitoring the condition of important plant structures, systems and components (SSC) through special designed software, review and assessment of important plant programmes and its own set of performance indicators

  6. Correcting for day of the week and public holiday effects: improving a national daily syndromic surveillance service for detecting public health threats.

    Science.gov (United States)

    Buckingham-Jeffery, Elizabeth; Morbey, Roger; House, Thomas; Elliot, Alex J; Harcourt, Sally; Smith, Gillian E

    2017-05-19

    As service provision and patient behaviour varies by day, healthcare data used for public health surveillance can exhibit large day of the week effects. These regular effects are further complicated by the impact of public holidays. Real-time syndromic surveillance requires the daily analysis of a range of healthcare data sources, including family doctor consultations (called general practitioners, or GPs, in the UK). Failure to adjust for such reporting biases during analysis of syndromic GP surveillance data could lead to misinterpretations including false alarms or delays in the detection of outbreaks. The simplest smoothing method to remove a day of the week effect from daily time series data is a 7-day moving average. Public Health England developed the working day moving average in an attempt also to remove public holiday effects from daily GP data. However, neither of these methods adequately account for the combination of day of the week and public holiday effects. The extended working day moving average was developed. This is a further data-driven method for adding a smooth trend curve to a time series graph of daily healthcare data, that aims to take both public holiday and day of the week effects into account. It is based on the assumption that the number of people seeking healthcare services is a combination of illness levels/severity and the ability or desire of patients to seek healthcare each day. The extended working day moving average was compared to the seven-day and working day moving averages through application to data from two syndromic indicators from the GP in-hours syndromic surveillance system managed by Public Health England. The extended working day moving average successfully smoothed the syndromic healthcare data by taking into account the combined day of the week and public holiday effects. In comparison, the seven-day and working day moving averages were unable to account for all these effects, which led to misleading smoothing

  7. Correcting for day of the week and public holiday effects: improving a national daily syndromic surveillance service for detecting public health threats

    Directory of Open Access Journals (Sweden)

    Elizabeth Buckingham-Jeffery

    2017-05-01

    Full Text Available Abstract Background As service provision and patient behaviour varies by day, healthcare data used for public health surveillance can exhibit large day of the week effects. These regular effects are further complicated by the impact of public holidays. Real-time syndromic surveillance requires the daily analysis of a range of healthcare data sources, including family doctor consultations (called general practitioners, or GPs, in the UK. Failure to adjust for such reporting biases during analysis of syndromic GP surveillance data could lead to misinterpretations including false alarms or delays in the detection of outbreaks. The simplest smoothing method to remove a day of the week effect from daily time series data is a 7-day moving average. Public Health England developed the working day moving average in an attempt also to remove public holiday effects from daily GP data. However, neither of these methods adequately account for the combination of day of the week and public holiday effects. Methods The extended working day moving average was developed. This is a further data-driven method for adding a smooth trend curve to a time series graph of daily healthcare data, that aims to take both public holiday and day of the week effects into account. It is based on the assumption that the number of people seeking healthcare services is a combination of illness levels/severity and the ability or desire of patients to seek healthcare each day. The extended working day moving average was compared to the seven-day and working day moving averages through application to data from two syndromic indicators from the GP in-hours syndromic surveillance system managed by Public Health England. Results The extended working day moving average successfully smoothed the syndromic healthcare data by taking into account the combined day of the week and public holiday effects. In comparison, the seven-day and working day moving averages were unable to account for all

  8. Effectiveness and Cost-benefit Evaluation of a Comprehensive Workers' Health Surveillance Program for Sustainable Employability of Meat Processing Workers.

    Science.gov (United States)

    van Holland, Berry J; Reneman, Michiel F; Soer, Remko; Brouwer, Sandra; de Boer, Michiel R

    2018-03-01

    Objective To evaluate the effectiveness of a comprehensive workers' health surveillance (WHS) program on aspects of sustainable employability and cost-benefit. Methods A cluster randomized stepped wedge trial was performed in a Dutch meat processing company from february 2012 until march 2015. In total 305 workers participated in the trial. Outcomes were retrieved during a WHS program, by multiple questionnaires, and from company registries. Primary outcomes were sickness absence, work ability, and productivity. Secondary outcomes were health, vitality, and psychosocial workload. Data were analyzed with linear and logistic multilevel models. Cost-benefit analyses from the employer's perspective were performed as well. Results Primary outcomes sickness absence (OR = 1.40), work ability (B = -0.63) and productivity (OR = 0.71) were better in the control condition. Secondary outcomes did not or minimally differ between conditions. Of the 12 secondary outcomes, the only outcome that scored better in the experimental condition was meaning of work (B = 0.18). Controlling for confounders did not or minimally change the results. However, our stepped wedge design did not enable adjustment for confounding in the last two periods of the trial. The WHS program resulted in higher costs for the employer on the short and middle term. Conclusions Primary outcomes did not improve after program implementation and secondary outcomes remained equal after implementation. The program was not cost-beneficial after 1-3 year follow-up. Main limitation that may have contributed to absence of positive effects may be program failure, because interventions were not deployed as intended.

  9. Role of immunological surveillance in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Sado, Toshihiko

    2003-01-01

    The immune system is known to be highly susceptible to various physical, chemical, and biological insults. The studies on the immediate and long-term effects of radiation on immune system of mice indicated very clearly that there was a dose-dependent reduction in the number of T and B cells, depression of antibody and cytotoxic T cell responses as well as proliferative responses of spleen cells to T and B cell mitogens shortly after irradiation, but they all recovered to the control level within a few months. Immunosuppression observed shortly after irradiation had little influence on the development of radiogenic tumors. The effects of radiation on the incidence of Friend leukemia virus (FLV)-induced leukemias are examined by using young adult B6C3F 1 male mice which are normally resistant to FLV-induced leukemogenesis. There was a clear threshold dose of 2 Gy below which the development of FLV induced leukemias was not observed but after exposure to >3 Gy high incidence of leukemias was observed. Fractionated, weekly exposure of young C57BL strain mice to 1.6 Gy of X-rays for four successive weeks causes most of the exposed mice to develop thymic lymphomas between 3 and 10 months. However, when the exposed mice are grafted with bone marrow cells from normal donors, the development of thymic lymphomas on the exposed mice is greatly inhibited. There was a clear dose response relationship between the number of bone marrow cells injected and the inhibition of the development of thymic lymphomas. It now appears clear that T cell-mediated immunological surveillance against newly arising neoplasms conceived by Thomas and Burnet does not hold true anymore in the original form, although virus-infected host cells and other host cells expressing altered-self' markers on their cell surfaces are constantly monitored by the immunological surveillance mechanism. A surveillance function against newly arising neoplasms may be a property of surrounding normal tissue cells rather

  10. Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis

    DEFF Research Database (Denmark)

    Bugge, Anna; Grøntved, Anders; Tolstrup, Janne Schurmann

    2015-01-01

    and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. METHODS: We used data from 96 population-based health examination surveys that had measured at least two...... assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. FINDINGS: Population prevalence of diabetes based on FPG-or-2hOGTT was correlated with prevalence based on FPG alone (r=0·98), but was higher by 2-6 percentage points at different......BACKGROUND: Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA1c. We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes...

  11. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  12. Super enhanced permeability and retention (SUPR) effects in tumors following near infrared photoimmunotherapy

    Science.gov (United States)

    Kobayashi, Hisataka; Choyke, Peter L.

    2016-06-01

    To date, the delivery of nano-sized therapeutic agents to cancers largely relies on enhanced permeability and retention (EPR) effects that are caused by the leaky nature of cancer vasculature. However, nano-sized agents delivered in this way have demonstrated limited success in oncology due to the relatively small magnitude of the EPR effect. For achieving superior delivery of nano-sized agents, super-enhanced permeability and retention (SUPR) effects are needed. Near infrared photo-immunotherapy (NIR-PIT) is a recently reported therapy that treats tumors with light therapy and subsequently causes an increase in nano-drug delivery up to 24-fold compared with untreated tumors in which only the EPR effect is present. SUPR effects could enhance delivery into tumor beds of a wide variety of nano-sized agents including particles, antibodies, and protein binding small molecular agents. Therefore, taking advantage of the SUPR effects after NIR-PIT may be a promising avenue to utilize a wide variety of nano-drugs in a highly effective manner.

  13. Effect of carbogen on tumor oxygenation: combined fluorine-19 and proton MRI measurements

    International Nuclear Information System (INIS)

    Fan Xiaobing; River, Jonathan N.; Zamora, Marta; Al-Hallaq, Hania A.; Karczmar, Gregory S.

    2002-01-01

    Purpose: Blood oxygen level dependent (BOLD) contrast in magnetic resonance imaging (MRI) has been widely used for noninvasive evaluation of the effects of tumor-oxygenating agents. However, there have been few tests of the validity of this method. The goal of the present work was to use the T 1 of fluorine-19 in perfluorocarbon (PFC) emulsions as a 'gold standard' for comparison with BOLD MRI. Methods and Materials: Rats bearing R3230AC tumors implanted in the hind limb were injected with an emulsion of perfluoro-15-crown-5-ether for 2-3 days before experiments, which ensured that the PFC emulsion concentrated in the tumors. We correlated changes in tumor oxygenation caused by carbogen inhalation measured by 1 H BOLD MRI with quantitative 19 F measurements. The 19 F spin-lattice relaxation rate R 1 (= 1/T 1 ) was measured to determine initial oxygen tension (pO 2 ) in each image pixel containing the PFC, and changes in pO 2 during carbogen (95% O 2 , 5% CO 2 ) breathing. In a second carbogen breathing period, changes in water signal linewidth were measured using high spectral and spatial resolution imaging. 19 F and 1 H measurements were used to classify pixels as responders to carbogen (pixels where oxygen increased significantly) or nonresponders (no significant change in tumor oxygenation). Results: The 19 F and 1 H measurements agreed in 65% ± 11% of pixels (n = 14). Agreement was even stronger among pixels where 1 H showed increased oxygenation; 19 F measurements agreed with 1 H measurements in over 79% ± 11% of these pixels. Similarly, there was strong agreement between the two modalities in pixels where 19 F reported no change in pO 2 ; 1 H also showed no changes in 76% ± 18% of these pixels. Quantitative correlation of changes T 2 * (ΔT 2 *) in 1 H and changes R 1 (ΔR 1 ) in 19 F was weak during carbogen breathing, and averaged over the whole tumor was ∼0.40 for 14 experiments. However, the spatial patterns of 1 H and 19 F changes were qualitatively

  14. Hypothalamic tumor

    Science.gov (United States)

    ... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

  15. Human prealbumin fraction: effects on cell-mediated immunity and tumor rejection

    International Nuclear Information System (INIS)

    Leung, K.H.; Ehrke, M.J.; Bercsenyi, K.; Mihich, E.

    1982-01-01

    The effect of human prealbumin fraction as allogeneic cell-mediated immunity in primary sensitization cultures of murine spleen cells was studied by 3H-thymidine uptake and specific 51Cr release assays. Prealbumin caused a dose-dependent augmentation of these responses. Human serum albumin, bovine serum albumin, and calf-thymosin fraction 5 had little effect. Prealbumin was active when added on day 0 or 1 but not thereafter. Prealbumin added to effector cells from immunized mice did not change their lytic activity. Prealbumin, but not human serum albumin or thymosin fraction 5, augmented secondary cell-mediated immunity in culture after primary immunization in mice. A slow growing mammary tumor line, which originated as a spontaneous mammary tumor in a DBA/2 HaDD breeder mouse, initially grows in 100% of DBA/2J mice but is then rejected in 10 to 20% of them. When prealbumin (59 microgram/day) was given subcutaneously for 2 weeks to DBA/2J mice and the tumor implanted 2 weeks later. 78% of the mice rejected the tumor and were then resistant to a rechallenge

  16. A review of endocrine late effects in children after brain tumor therapy

    International Nuclear Information System (INIS)

    Marx, M.; Langer, T.; Beck, J.D.; Doerr, H.G.

    1999-01-01

    Background: Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Method: Own data and literature review. Results: Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 G. With some delay, other hypothalamopituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Conclusion: Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved. (orig.) [de

  17. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    International Nuclear Information System (INIS)

    Mellas, J.; Hammerman, M.R.

    1986-01-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

  18. Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow

    International Nuclear Information System (INIS)

    Ono, K.; Wandl, E.; Sasai, K.; Tsutsui, K.; Shibamoto, Y.; Takahashi, M.; Abe, M.; Vienna Univ.

    1990-01-01

    The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 μg/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, D q decreased from 3.3 Gy to 1.4 Gy without changing D 0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1>p>0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination. (orig.)

  19. Selective effects of whey protein concentrate on glutathione levels and apoptosis in rats with mammary tumors.

    Science.gov (United States)

    Cheng, Shih-Hsuan; Tseng, Yang-Ming; Wu, Szu-Hsien; Tsai, Shih-Meng; Tsai, Li-Yu

    2017-09-01

    Glutathione (GSH) plays an important role in antioxidant defense and regulation of apoptosis. GSH deficiency is related to many diseases, including cancer, and increased GSH levels in cancer cells are associated with chemotherapy resistance because of resistance to apoptosis. In this study, we investigated the effects of whey protein concentrate (WPC), a precursor of GSH, in rats with mammary tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA). DMBA treatment results in cellular changes that mimic the initiation and promotion of carcinogenesis of breast tissue. We aimed to examine the possible preventive effects of diets containing whey protein on DMBA-induced mammary tumors in rats. The results indicate that WPC (0.334 g/kg) supplementation significantly increased the liver GSH levels by 92%, and were accompanied by low Bax/Bcl-2 ratio (from 5 to 3) and cleaved caspase-3/procaspase-3 ratio (from 2.4 to 1.2) in DMBA-treated rats. Furthermore, tumor GSH levels were decreased by 47% in WPC-supplemented rats, which resulted in increased Bax/Bcl-2 ratio (from 0.9 to 2) and cleaved caspase-3/procaspase-3 ratio (from 1.1 to 2.7). In conclusion, supplementation with WPC could selectively deplete tumor GSH levels and, therefore, WPC supplementation might be a promising strategy to overcome treatment resistance in cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes.

    Science.gov (United States)

    Fasehee, Hamidreza; Zarrinrad, Ghazaleh; Tavangar, Seyed Mohammad; Ghaffari, Seyed Hamidollah; Faghihi, Shahab

    2016-06-01

    The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. The administration of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor routes is investigated using animal model. Disulfiram shows strong cytotoxicity against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S phase time-dependently. The encapsulated disulfiram shows higher activity in apoptosis induction as compared to free drug. In nontoxic dose of encapsulated disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is observed for intravenous injection and intraperitoneal injection. It is suggested that administration of disulfiram by targeted PLGA nanoparticles using intravenous injection would present an alternative therapeutic approach for solid tumor treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Curcumin and Turmeric Modulate the Tumor-Promoting Effects of Iron In Vitro.

    Science.gov (United States)

    Messner, Donald J; Robinson, Todd; Kowdley, Kris V

    2017-04-01

    Free or loosely chelated iron has tumor-promoting properties in vitro. Curcumin, a polyphenol derived from the food spice turmeric (Curcuma longa), is a potent antioxidant that binds iron. The primary aim of this study was to investigate whether curcuminoids prevent tumor-promoting effects of iron in T51B cells, a non-neoplastic rat liver epithelial cell line. Purified curcuminoids (curcumin) or a standardized turmeric extract similarly reduced oxidative stress and cytotoxicity associated with iron overload (IC 50 values near 10 μM, P turmeric for 16 wk in culture; subsequently assayed by soft agar colony formation) was nearly complete at 20 μM of total curcuminoids (P turmeric extract were taken up better by cells, had a longer half-life, and appeared more effective in blocking tumor promotion (P < 0.01), suggesting enhanced curcuminoid delivery to cells in culture. The primary finding that curcuminoids can inhibit tumor promotion caused by iron in T51B cells is tempered by evidence for an underlying increase in neoplastic transformation at lower concentrations.

  2. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    Science.gov (United States)

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  3. Effect of tumor promoters on ultraviolet light-induced mutation and mitotic recombination in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Kunz, B.A.; Hannan, M.A.; Haynes, R.H.

    1980-01-01

    Recently, it has been suggested that mitotic recombination is involved in tumor promotion. On this basis, one might expect tumor promoters to be recombinagenic. D7 is a diploid strain of yeast in which both mutation and mitotic recombination can be measured. We have used this strain to assay the known tumor promoters, iodacetate, anthralin, and 12-0-tetradecanoylphorbol-13-acetate, and the cocarcinogen, catechol, for mutagenicity, recombinagenicity, and the ability to enhance ultraviolet light (UV)-induced genetic events. In the absence of preirradiation with UV, iodoacetate was found to be recombinagenic whereas catechol was mutagenic; however, in both cases, the effects were small. Iodoacetate, anthralin, and catechol potentiated UV-induced mitotic crossing-over, aberrant colony formation, and mutation, while catechol also increased UV-induced gene conversion. We were unable to detect any mutagenic or recombinagenic effect of 12-0-tetradecanoyl-phorbol-13-acetate in either whole cells or spheroplasts. Our results do not indicate any consistent correlation between tumor-promoting activity and the ability of an agent to induce mitotic recombination in yeast. However, the ability to potentiate UV-induced mutation and mitotic recombination may reflect the cocarcinogenic activity of certain promoters

  4. Hyperbaric pressure effects measured by growth of a transplantable tumor in the C3H/HeN mouse.

    Science.gov (United States)

    Herndon, B L; Lally, J J

    1984-09-01

    Both hypobaric exposure at 0.5 atmospheres absolute (ATA) and hyperbaric pressure exposure at 3.5-8 ATA slowed transplantable tumor growth. These experiments detailed the hyperbaric pressure exposure. C3H/HeN-MTV+ mice, bearing the 16/C transplantable murine mammary adenocarcinoma and exposed to 18 days' treatment by a hyperbaric chamber at 3.5-8 ATA, had tumor weights that averaged 50-75% less than the tumor weights in mice caged at ambient ("sea level") pressure. A series of experiments was run to investigate this response to hyperbaric pressure exposure. After mice underwent continuous exposure to 3.5-8 ATA normoxic (normal oxygen) hyperbaric pressure with use of either argon or nitrogen inert gas, which began 3 days after tumor inoculation, tumors were removed at about 3 weeks' growth from these pressure-exposed mice and measured for growth by weighing. Final tumor weight in pressure-exposed experimental mice was significantly less than tumor weight in paired groups of tumor-bearing controls that received no hyperbaric pressure. Tumor weight was inversely related to pressure "dose," although the small pressure range produced an effect at all pressures used. The number of compression-decompression cycles to which the animals were subjected, however, was related positively to tumor weight at necropsy. Continued tumor growth in mice subjected to frequent pressure change (in conjunction with pressure exposure that otherwise limited tumor size) was unexplained by these experiments. The greatest difference between tumor weights in controls and pressure-exposed animals was seen with 2 weeks' continuous pressure exposure. A limited profile of blood tests was performed, and these reflected only minor, expected change in the pressure-exposed experimental animals. The data at hand did not suggest a mechanism by which chronic normoxic hyperbaric pressure limited tumor size.

  5. Using FDG-PET activity as a surrogate for tumor cell density and its effect on equivalent uniform dose calculation

    International Nuclear Information System (INIS)

    Zhou Sumin; Wong, Terence Z.; Marks, Lawrence B.

    2004-01-01

    The concept of equivalent uniform dose (EUD) has been suggested as a means to quantitatively consider heterogeneous dose distributions within targets. Tumor cell density/function is typically assumed to be uniform. We herein propose to use 18 F-labeled 2-deoxyglucose (FDG) positron emission tomography (PET) tumor imaging activity as a surrogate marker for tumor cell density to allow the EUD concept to include intratumor heterogeneities and to study its effect on EUD calculation. Thirty-one patients with lung cancer who had computerized tomography (CT)-based 3D planning and PET imaging were studied. Treatment beams were designed based on the information from both the CT and PET scans. Doses were calculated in 3D based on CT images to reflect tissue heterogeneity. The EUD was calculated in two different ways: first, assuming a uniform tumor cell density within the tumor target; second, using FDG-PET activity (counts/cm 3 ) as a surrogate for tumor cell density at different parts of tumor to calculate the functional-imaging-weighted EUD (therefore will be labeled fEUD for convenience). The EUD calculation can be easily incorporated into the treatment planning process. For 28/31 patients, their fEUD and EUD differed by less than 6%. Twenty-one of these twenty-eight patients had tumor volumes 3 . In the three patients with larger tumor volume, the fEUD and EUD differed by 8%-14%. Incorporating information from PET imaging to represent tumor cell density in the EUD calculation is straightforward. This approach provides the opportunity to include heterogeneity in tumor function/metabolism into the EUD calculation. The difference between fEUD and EUD, i.e., whether including or not including the possible tumor cell density heterogeneity within tumor can be significant with large tumor volumes. Further research is needed to assess the usefulness of the fEUD concept in radiation treatment

  6. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

    Science.gov (United States)

    Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

    2010-04-01

    Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

  7. Haploidentical hematopoietic SCT increases graft-versus-tumor effect against renal cell carcinoma.

    Science.gov (United States)

    Budak-Alpdogan, T; Sauter, C T; Bailey, C P; Biswas, C S; Panis, M M; Civriz, S; Flomenberg, N; Alpdogan, O

    2013-08-01

    Allogeneic hematopoietic SCT (HSCT) has been shown to be an effective treatment option for advanced renal cell cancer (RCC). However, tumor resistance/relapse remains as the main post transplant issue. Therefore, enhancing graft-versus-tumor (GVT) activity without increasing GVHD is critical for improving the outcome of HSCT. We explored the GVT effect of haploidentical-SCT (haplo-SCT) against RCC in murine models. Lethally irradiated CB6F1 (H2K(b/d)) recipients were transplanted with T-cell-depleted BM cells from B6CBAF1 (H2K(b/k)) mice. Haplo-SCT combined with a low-dose haploidentical (HI) T-cell infusion (1 × 10(5)) successfully provided GVT activity without incurring GVHD. This effect elicited murine RCC growth control and consequently displayed a comparative survival advantage of haplo-SCT recipients when compared with MHC-matched (B6D2F1CB6F1) and parent-F1 (B6CB6F1) transplant recipients. Recipients of haplo-SCT had an increase in donor-derived splenic T-cell numbers, T-cell proliferation and IFN-γ-secreting donor-derived T-cells, a critical aspect for anti-tumor activity. The splenocytes from B6CBAF1 mice had a higher cytotoxicity against RENCA cells than the splenocytes from B6 and B6D2F1 donors after tumor challenge. These findings suggest that haplo-SCT might be an innovative immunotherapeutic platform for solid tumors, particularly for renal cell carcinoma.

  8. Effective surveillance for early classical swine fever virus detection will utilize both virus and antibody detection capabilities.

    Science.gov (United States)

    Panyasing, Yaowalak; Kedkovid, Roongtham; Thanawongnuwech, Roongroje; Kittawornrat, Apisit; Ji, Ju; Giménez-Lirola, Luis; Zimmerman, Jeffrey

    2018-03-01

    Early recognition and rapid elimination of infected animals is key to controlling incursions of classical swine fever virus (CSFV). In this study, the diagnostic characteristics of 10 CSFV assays were evaluated using individual serum (n = 601) and/or oral fluid (n = 1417) samples collected from -14 to 28 days post inoculation (DPI). Serum samples were assayed by virus isolation (VI), 2 commercial antigen-capture enzyme-linked immunosorbent assays (ELISA), virus neutralization (VN), and 3 antibody ELISAs. Both serum and oral fluid samples were tested with 3 commercial real-time reverse transcription-polymerase chain reaction (rRT-PCR) assays. One or more serum samples was positive by VI from DPIs 3 to 21 and by antigen-capture ELISAs from DPIs 6 to 17. VN-positive serum samples were observed at DPIs ≥ 7 and by antibody ELISAs at DPIs ≥ 10. CSFV RNA was detected in serum samples from DPIs 2 to 28 and in oral fluid samples from DPIs 4 to 28. Significant differences in assay performance were detected, but most importantly, no single combination of sample and assay was able to dependably identify CSFV-inoculated pigs throughout the 4-week course of the study. The results show that effective surveillance for CSFV, especially low virulence strains, will require the use of PCR-based assays for the detection of early infections (<14 days) and antibody-based assays, thereafter. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

    International Nuclear Information System (INIS)

    Vern-Gross, Tamara Z.; Shivnani, Anand T.; Chen, Ke; Lee, Christopher M.; Tward, Jonathan D.; MacDonald, O. Kenneth; Crane, Christopher H.; Talamonti, Mark S.; Munoz, Louis L.; Small, William

    2011-01-01

    Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

  10. Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

    Science.gov (United States)

    Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

    2017-07-01

    Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors. We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras G12D/+ /Trp53 R172H/+ /Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses. In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels

  11. Suppressive versus augmenting effect of the same pretreatment regimen in two murine tumor systems with distinct effector mechanisms

    International Nuclear Information System (INIS)

    Fujiwara, Hiromi; Hamaoka, Toshiyuki; Kitagawa, Masayasu

    1978-01-01

    The effect of presensitization with x-irradiated tumor cells on the development of host's immune resistance against the tumor-associated transplantation antigens (TATA) was investigated in two syngeneic tumor systems with distinct effector mechanisms. When X5563 plasmacytoma, to which immune resistance was mediated exclusively by killer T lymphocytes, was intravenously inoculated into syngeneic C3H/He mice with lower number after 7000 R x-irradiation, the mice failed to exhibit any protective immunity against the subsequent challenge with viable tumor cells. Moreover, these mice lost their capability to develop any immune resistance even after an appropriate immunization procedure. The immunodepression induced by such a pretreatment regimen was specific for X5563 tumor. While no suppressor cell activity was detected in the above pretreated mice, serum factor(s) from these mice was virtually responsible for this suppression. When the serum factor mediating this tumor-specific suppression was fractionated on the Sephadex G-200 column, the suppressive activity was found in albumin-corresponding fraction, free of any immunoglobulin component. In contrast, in MM102 mammary tumor system, in which immune resistance is solely mediated by tumor-specific antibody, the pretreatment with x-irradiated MM102 cells augmented the induction of anti-tumor immunity. These results indicate that while tumor antigens given in the form of x-irradiated tumor cells suppress the induction of killer T cell-mediated immunity in one system, the same presensitization regimen of tumor antigens augments the antibody-mediated immunity in another system, thus giving a divergent effect on the distinct effector mechanisms of syngeneic tumor immunity. (author)

  12. Aiding surveillance

    International Development Research Centre (IDRC) Digital Library (Canada)

    arashid

    8 See, for example, the work of the Center for Global Development, ..... toward social protection, cash transfer, or social safety net programs as effective tools for .... that the [MIS] will fit within the users' work environment and be useful to them.

  13. Influenza epidemiology and influenza vaccine effectiveness during the 2014–2015 season: annual report from the Global Influenza Hospital Surveillance Network

    Directory of Open Access Journals (Sweden)

    Joan Puig-Barberà

    2016-08-01

    Full Text Available Abstract The Global Influenza Hospital Surveillance Network (GIHSN has established a prospective, active surveillance, hospital-based epidemiological study to collect epidemiological and virological data for the Northern and Southern Hemispheres over several consecutive seasons. It focuses exclusively on severe cases of influenza requiring hospitalization. A standard protocol is shared between sites allowing comparison and pooling of results. During the 2014–2015 influenza season, the GIHSN included seven coordinating sites from six countries (St. Petersburg and Moscow, Russian Federation; Prague, Czech Republic; Istanbul, Turkey; Beijing, China; Valencia, Spain; and Rio de Janeiro, Brazil. Here, we present the detailed epidemiological and influenza vaccine effectiveness findings for the Northern Hemisphere 2014–2015 influenza season.

  14. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-03-15

    Arsenic trioxide (As{sub 2}O{sub 3}) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As{sub 2}O{sub 3} on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As{sub 2}O{sub 3} (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA {+-} 35; 90 {+-} 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 {+-} 28.9 mm{sup 2} (group A), 119 {+-} 31.7 (group B), and 92 {+-} 17.4 (group C, p < 0.04). The ablation area of the tumor was significantly larger in group A (73 {+-} 19.7 mm{sup 2}) than both group B (50 {+-} 19.4, p = 0.02) and group C (28 {+-} 2.2, p < 0.01). The ratios of the tumoral ablation area to the overall ablation area were larger in group A (47 {+-} 10.5%) than that of the other groups (42 {+-} 7.3% in group B and 32 {+-} 5.6% in group C) (p < 0.03). Radiofrequency-induced ablation area can be increased with intraarterial or intravenous administration of As{sub 2}O{sub 3}. The intraarterial administration of As{sub 2}O{sub 3} seems to be helpful for the selective ablation of the tumor.

  15. P53 function influences the effect of fractionated radiotherapy on glioblastoma tumors

    International Nuclear Information System (INIS)

    Haas-Kogan, Daphne A.; Kogan, Scott S.; Yount, Garret; Hsu, Jennie; Haas, Martin; Deen, Dennis F.; Israel, Mark A.

    1999-01-01

    Purpose: Glioblastoma multiforme brain tumors (GM) are treated with a spectrum of fractionation regimens based on the clinical and anatomical characteristics of the tumor but rarely based on the molecular characteristics of the individual neoplasm. This study tests the hypothesis that the response of cell lines derived from GM to fractionated radiotherapy depends on the function of wild-type p53 (wt p53), a tumor suppressor gene frequently mutated in GM tumors. Methods and Materials: Isogenic derivatives of glioblastoma cells differing only in p53 function were prepared using a retroviral vector expressing a dominant negative mutant of p53 (mt p53). Radiation survival in vitro was quantitated using linear quadratic and repair-saturation mathematical models. Apoptosis was assayed by a terminal deoxynucleotide transferase-labeling technique and chromatin morphology. Results: We have previously reported the generation of isogenic GM cell lines differing only in p53 function. U87-175.4, lacking wt p53 function, had a significantly lower α/β value than U87-LUX.8, expressing functional wt p53, leading us to hypothesize that fractionated irradiation would preferentially spare GM cells harboring mt p53 compared with those expressing functional, wt p53. Survival curves following either 2.0 Gy or 3.5 Gy/fraction demonstrated that lack of functional wt p53 was associated with resistance to fractionated irradiation. Radiation-induced apoptosis could not account for the observed differences in clonogenic survival. Rather, our data suggested that a deficit in the G1-checkpoint contributed to increased resistance to fractionated irradiation of cells expressing mutant p53. Conclusions: The effect of fractionated radiotherapy in GM may depend on the function of the tumor suppressor gene p53. A potential clinical consequence of these findings is that hyperfractionation regimens may provide a therapeutic advantage specifically for tumors expressing wt p53 whereas a radiotherapy

  16. Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

    Directory of Open Access Journals (Sweden)

    W.M. Quinteiro-Filho

    2009-10-01

    Full Text Available Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days isogenic BALB/c mice in each experiment. Cyhalothrin i increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05, concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05, and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05; ii increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05, and iii decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05 and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05 in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.

  17. The Effects of Computerized Auditory Feedback on Electronic Article Surveillance Tag Placement in an Auto-Parts Distribution Center

    Science.gov (United States)

    Goomas, David T.

    2008-01-01

    In this report from the field, computerized auditory feedback was used to inform order selectors and order selector auditors in a distribution center to add an electronic article surveillance (EAS) adhesive tag. This was done by programming handheld computers to emit a loud beep for high-priced items upon scanning the item's bar-coded Universal…

  18. Effect of a mouse mammary tumor virus-derived protein vaccine on primary tumor development in mice

    NARCIS (Netherlands)

    Creemers, P.; Ouwehand, J.; Bentveizen, P.

    1978-01-01

    The vaccines used in this study were derived from purified murine mammary tumor virus (MuMTV) preparations. Approximately 60% of the protein fractions consisted of the major viral membrane glycoprotein gp52. Inoculation sc of 10 pg MuMTV-S-derived vaccine significantly delayed the appearance of

  19. Evaluation of HIV Surveillance System in Rivers State, Nigeria ...

    African Journals Online (AJOL)

    Sony Computer (Iby)

    HIV surveillance system generates information for timely and appropriate ..... active type of surveillance.14 Nonetheless, it requires training, supervision and motivation ... very effectively.14 The introduction of reward-system could be included.

  20. Effects of whole-body irradiation on neonatally thymectomized mice. Incidence of benign and malignant tumors

    International Nuclear Information System (INIS)

    Anderson, R.E.; Howarth, J.L.; Troup, G.M.

    1978-01-01

    The individual and combined effects of neonatal thymectomy and whole-body irradiation on the prevalence of benign and malignant tumors in germ-free female mice of the Charles Rivers line were studied to determine if a portion of the tumorigenic effects of irradiation can be attributed to injury of the thymic-dependent component of the immune response. Neonatal thymectomy increased (a) the incidence of benign and malignant tumors and (b) the prevalence of multiple primary neoplasms in an individual mouse. Whole-body exposure to 700 rad at 6 weeks of age further increased the incidence of tumors, but the relative magnitude of this increase was less pronounced than in sham-operated controls. Thus, the cumulative effects of thymectomy plus irradiation are less pronounced than the sum of the individual effects. One of several possible explanations for this observation is that a portion of the carcinogenic effects of whole-body irradiation is mediated by suppression of the thymic-dependent component of the immune response

  1. Effect of administration route and dose of streptavidin or biotin on the tumor uptake of radioactivity in intraperitoneal tumor with multistep targeting

    International Nuclear Information System (INIS)

    Zhang Meili; Yao Zhengsheng; Sakahara, Harumi; Saga, Tsuneo; Nakamoto, Yuji; Sato, Noriko; Zhao Songji; Nakada, Hiroshi; Yamashina, Ikuo; Konishi, Junji

    1998-01-01

    The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (IV) or IP in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, IP-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than IV-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, IP injection also gave a higher tumor uptake of radiolabeled biotin than IV injection. In conclusion, IP administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods

  2. Surveillance of colorectal cancer: effectiveness of early detection of intraluminal recurrences on prognosis and survival of patients treated for cure.

    Science.gov (United States)

    Barillari, P; Ramacciato, G; Manetti, G; Bovino, A; Sammartino, P; Stipa, V

    1996-04-01

    The authors evaluate the effectiveness of routine colonoscopy and marker evaluation in diagnosis of intraluminal recurrent cancer. Chart review was conducted on 481 patients who underwent curative resection for colorectal cancer between 1980 and 1990. Clinical visits were scheduled and carcinoembryonic antigen evaluation was performed every three months, and colonoscopy was performed preoperatively, 12 to 15 months after surgical treatment, and then with intervals of 12 to 24 months or when symptoms appeared. About 10 percent of patients developed intraluminal recurrences. More than one-half of metachronous lesions arose within the first 24 months, and median time to diagnosis was 25 months. Patients with left-sited tumors in the advanced stage had a higher risk of developing recurrent intraluminal disease. Twenty-nine patients underwent a second surgical operation, of which 17 cases were radical. In this group, the five-year survival was 70.6 percent, although no nonradically treated or nonresected patients survived longer than 31 months. Twenty-two patients were asymptomatic at time of diagnosis of recurrence, and of these, 12 patients underwent radical operation; on the other hand, of the 24 symptomatic patients, only 5 were treated radically. Carcinoembryonic antigen was the first sign of recurrence in eight cases. Colonoscopy must be performed within the first 12 to 15 months after operation, whereas an interval of 24 months between examinations seems sufficient to guarantee early detection of metachronous lesions. Serial tumor marker evaluation is of help in earlier diagnosis of local recurrences. Asymptomatic patients more frequently undergo another operation for cure and thus have a better survival rate.

  3. Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Peila Chen

    2010-05-01

    Full Text Available Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2-/- tumors. In vitro, PyV MT/jnk2-/- cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1 and p21(Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.

  4. The Effects of Angelica Sinensis Polysaccharide on Tumor Growth and Iron Metabolism by Regulating Hepcidin in Tumor-Bearing Mice

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    Feng Ren

    2018-05-01

    Full Text Available Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC, and enzyme-linked immunosorbent assay (ELISA were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6, JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

  5. Effect of immunomodulation on the fate of tumor cells in the central nervous system and systemic organs of mice. Distribution of [125I]5-iodo-2'-deoxyuridine-labeled KHT tumor cells after left intracardial injection

    International Nuclear Information System (INIS)

    Conley, F.K.

    1982-01-01

    The effect of systemic immunomodulation on tumor cell arrest and retention in the central nervous system was studied by following radioactively labeled tumor cells. KHT mouse sarcoma tumor cells were labeled in vitro with [ 125 I]IdUrd, and 1x10 5 tumor cells were injected into the left side of the hearts of syngeneic C3H mice. Experimental groups consisted of untreated normal mice, mice pretreated iv with Corynebacterium parvum, and mice chronically infected with Toxoplasma gondii; in this model both groups of immunomodulated mice are protected from developing systemic metastatic tumor, but only Toxoplasma-infected mice have protection against metastatic brain tumor. At time intervals from 1 to 96 hours, groups of mice from each experimental group were killed, and the brain and other organs were monitored for radioactivity to determine the number of viable tumor cells that had been present at the time of death. Normal mice demonstrated significant retention of tumor cells in the brain and kidneys plus adrenals at 96 hours. By contrast, in both groups of immunomodulated mice tumor cells were rapidly eliminated from systemic organs, but tumor cells were significantly retained in the central nervous system even at 96 hours after tumor cell injections. The results indicated that generalized immunomodulation had more effect in elimination of tumor cells from systemic organs than from the brain and that the elimination of tumor cells from the brain in Toxoplasma-infected mice was a delayed phenomenon

  6. Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment.

    Science.gov (United States)

    Guzman-Rojas, Liliana; Rangel, Roberto; Salameh, Ahmad; Edwards, Julianna K; Dondossola, Eleonora; Kim, Yun-Gon; Saghatelian, Alan; Giordano, Ricardo J; Kolonin, Mikhail G; Staquicini, Fernanda I; Koivunen, Erkki; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2012-01-31

    Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.

  7. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

    Directory of Open Access Journals (Sweden)

    Sharma Kamal

    2008-12-01

    Full Text Available Abstract Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

  8. Bcl-2 inhibitors potentiate the cytotoxic effects of radiation in Bcl-2 overexpressing radioresistant tumor cells

    International Nuclear Information System (INIS)

    Hara, Takamitsu; Omura-Minamisawa, Motoko; Chao Cheng; Nakagami, Yoshihiro; Ito, Megumi; Inoue, Tomio

    2005-01-01

    Purpose: Bcl-2, an inhibitor of apoptosis frequently shows elevated expression in human tumors, thus resulting in resistance to radiation therapy. Therefore, inhibiting Bcl-2 function may enhance the radiosensitivity of tumor cells. Tetrocarcin A (TC-A) and bcl-2 antisense oligonucleotides exhibit antitumor activity by inhibiting Bcl-2 function and transcription, respectively. We investigated whether these antitumor agents would enhance the cytotoxic effects of radiation in tumor cells overexpressing Bcl-2. Methods and materials: We used HeLa/bcl-2 cells, a stable Bcl-2-expressing cell line derived from wild-type HeLa (HeLa/wt) cells. Cells were incubated with TC-A and bcl-2 antisense oligonucleotides for 24 h after irradiation, and cell viability was then determined. Apoptotic cells were quantified by flow cytometric assay. Results: The HeLa/bcl-2 cells were more resistant to radiation than HeLa/wt cells. At concentrations that are not inherently cytotoxic, both TC-A and bcl-2 antisense oligonucleotides increased the cytotoxic effects of radiation in HeLa/bcl-2 cells, but not in HeLa/wt cells. However, in HeLa/bcl-2 cells, additional treatment with TC-A in combination with radiation did not significantly increase apoptosis. Conclusions: The present results suggest that TC-A and bcl-2 antisense oligonucleotides reduce radioresistance of tumor cells overexpressing Bcl-2. Therefore, a combination of radiotherapy and Bcl-2 inhibitors may prove to be a useful therapeutic approach for treating tumors that overexpress Bcl-2

  9. Elements of quality assurance in environmental surveillance

    International Nuclear Information System (INIS)

    Johnson, L.J.

    1975-01-01

    Qualities of an environmental surveillance program requiring control or assurance are reviewed. Requirements of accuracy, reproducibility, sensitivity, acceptability, and time and cost effectiveness are qualities discussed. The controls applicable to sample collection, handling, chemical analysis, measurement and data presentation are identified and discussed as they pertain to environmental monitoring. Quality assurance program recommendations for developing and reporting environmental surveillance data are provided

  10. Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas

    International Nuclear Information System (INIS)

    Rush, Stephen; Cooper, Paul R.

    1997-01-01

    This study reports the outcome of 70 patients who were treated by a consistent treatment plan of surgery and postoperative radiotherapy (RT) for pituitary macroadenomas in the modern era [computed tomographic scan or magnetic resonance imaging (MRI), dopamine agonist therapy (DA) added as indicated, and immunohistochemical staining]. Sixty-two patients underwent transsphenoidal surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions postoperatively (vs. other dose fractionation schemes). Twenty-four patients received DA for prolactin-secreting tumors. With a median follow-up of 8 years (range 2-15), 68 patients have experienced continuous control of their tumors. Most symptoms related to mass effect abated, while physiologic symptoms such as amenorrhea from markedly elevated prolactin levels tended to persist. Treatment-induced hypopituitarism occurred in 42% of the patients at risk. No patients in this series have died as a result of their pituitary tumor. No gross neuropsychologic dysfunction after treatment has been noted. While it is possible at this time with serial MRI to withhold postoperative RT and observe some patients who have had a 'gross total' resection of a macroadenoma, the therapeutic ratio for surgery and adjuvant radiotherapy for patients with nonfunctional tumors as well as select patients with secretory macroadenomas is favorable

  11. Anti-tumor effects of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase α

    International Nuclear Information System (INIS)

    Maeda, Naoki; Kokai, Yasuo; Ohtani, Seiji; Sahara, Hiroeki; Kuriyama, Isoko; Kamisuki, Shinji; Takahashi, Shunya; Sakaguchi, Kengo; Sugawara, Fumio; Yoshida, Hiromi; Sato, Noriyuki; Mizushina, Yoshiyuki

    2007-01-01

    In the screening of selective inhibitors of eukaryotic DNA polymerases (pols), dehydroaltenusin was found to be an inhibitor of pol α from a fungus (Alternaria tennuis). We succeeded in chemically synthesizing dehydroaltenusin, and the compound inhibited only mammalian pol α with IC 50 value of 0.5 μM, and did not influence the activities of other replicative pols such as pols δ and ε, but also showed no effect on pol α activity from another vertebrate, fish, or from a plant species. Dehydroaltenusin also had no influence on the other pols and DNA metabolic enzymes tested. The compound also inhibited the proliferation of human cancer cells with LD 50 values of 38.0-44.4 μM. In an in vivo anti-tumor assay on nude mice bearing solid tumors of HeLa cells, dehydroaltenusin was shown to be a promising suppressor of solid tumors. Histopathological examination revealed that increased tumor necrosis and decreased mitotic index were apparently detected by the compound in vivo. Therefore, dehydroaltenusin could be of interest as not only a mammalian pol α-specific inhibitor, but also as a candidate drug for anti-cancer treatment

  12. Late radiation effects on hearing, vestibular function, and taste in brain tumor patients

    International Nuclear Information System (INIS)

    Johannesen, Tom B.; Rasmussen, Kjell; Winther, Finn Oe.; Halvorsen, Ulf; Lote, Knut

    2002-01-01

    Purpose: To investigate late radiation effects on hearing, vestibular function, and taste after conventional radiotherapy in brain tumor patients. Methods and Materials: Hearing, vestibular function, and taste were assessed in 33 brain tumor patients irradiated unilaterally to the tumor-bearing hemisphere and the temporal bone. Median observation time after completion of radiotherapy was 13 years; the fraction dose was 1.8 Gy, and mean radiation dose was 53.1 Gy. Results: Deep ulceration in the external ear canal and osteoradionecrosis on the irradiated side was seen in three patients. Reduced hearing was found for air and bone conduction of the irradiated side compared to the opposite side (0.25-2 kHz: 6.1 dB, 4 kHz: 10.3 dB, 6 kHz: 15.6 dB, and 8 kHz: 16.5 dB). For bone conduction, the corresponding figures were 0.25-2 kHz: 5.5 dB and 4 kHz: 8.2 dB. Three patients had a canal paresis of the irradiated side, and three patients had affection of the chorda tympani. Conclusion: Irradiation of the temporal bone with doses usually given in the treatment of patients with brain tumors may cause osteoradionecrosis, sensorineural hearing loss, dysfunction of the vestibular inner ear, and loss of taste. Head-and-neck examination should be included in the follow-up of long-term survivors

  13. Adult Central Nervous System Tumors Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Adult central nervous system tumor treatment may include surgery, radiosurgery, radiation therapy, chemotherapy, surveillance, and targeted therapy. Treatment depends on the tumor type. Learn more about brain and spinal tumor treatment in this expert-reviewed summary.

  14. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  15. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Horsman, Michael R

    2002-01-01

    LDF, using a 41 degrees C heated custom-built LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by NIRS, using light guide coupled reflectance measurements at 800+/-10 nm. FAA, DMXAA, CA4DP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73......The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice......%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CA4DP caused no change in the tumor blood volume, indicating...

  16. 18F-FDG and 18F-FLT-PET imaging for monitoring everolimus effect on tumor-growth in neuroendocrine tumors: studies in human tumor xenografts in mice.

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    Camilla Bardram Johnbeck

    Full Text Available The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors and evaluated the performance of 18F-FDG and the proliferation tracer 18F-FLT for treatment response assessment by PET imaging.The effect of everolimus on the human carcinoid cell line H727 was examined in vitro with the MTT assay and in vivo on H727 xenograft tumors. The mice were scanned at baseline with 18F-FDG or 18F-FLT and then treated with either placebo or everolimus (5 mg/kg daily for 10 days. PET/CT scans were repeated at day 1,3 and 10.Everolimus showed significant inhibition of H727 cell proliferation in vitro at concentrations above 1 nM. In vivo tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group at day 3 (126±6% vs. 152±6%; p = 0.016, day 7 (164±7% vs. 226±13%; p<0.001 and at day 10 (194±10% vs. 281±18%; p<0.001. Uptake of 18F-FDG and 18F-FLT showed little differences between control and treatment groups, but individual mean uptake of 18F-FDG at day 3 correlated with tumor growth day 10 (r2 = 0.45; P = 0.034, 18F-FLT mean uptake at day 1 correlated with tumor growth day 7 (r2 = 0.63; P = 0.019 and at day 3 18F-FLT correlated with tumor growth day 7 (r2 = 0.87; P<0.001 and day 10 (r2 = 0.58; P = 0.027.Everolimus was effective in vitro and in vivo in human xenografts lung carcinoid NETs and especially early 18F-FLT uptake predicted subsequent tumor growth. We suggest that 18F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders and non-responders.

  17. Effective compounds screening from Rabdosia serra (Maxim) Hara against HBV and tumor in vitro.

    Science.gov (United States)

    Chen, Cheng; Chen, Yang; Zhu, Hongyuan; Xiao, Yiyun; Zhang, Xiuzhen; Zhao, Jingfeng; Chen, Yuxiang

    2014-01-01

    The aim of this study was to screen and investigate the anti-HBV and anti-tumor activities of separated compounds from Rabdosia serra (Maxim.) Hara to lay the basis for further isolate active entity. Three kinds of extractions from Rabdosia serra using different solvents (petroleum ether, acetidin, butyl alcohol) were prepared and used to analyze their anti-HBV activity in HepG2.2.15 cells for further separation. The cytotoxicity of each extraction was tested by MTT assay, the levels of HBsAg, HBeAg and HBV DNA in supernatants from HepG2.2.15 cells were detected by ELISA and real-time quantitative polymerase chain reaction (PCR). Then, the most effective extraction was further separated, the anti-HBV activities of separated compounds were also tested by MTT and ELISA, and three compounds with highest cytotoxicity were selected to further identify their anti-tumor activities on MCF-7, BGC-823 and HepG2 cells. Acetidin extraction C2 had the most effective anti-HBV activity that was used to be further separated, it led to statistically significant reduction in HBsAg and HBeAg secretion and HBV DNA. The separation of C2 resulted in 14 compounds, A3 and A5 markedly inhibited HBsAg secretion, while A9 inhibited HBeAg secretion in a dose-dependent manner with higher TI comparing with C2. A6, A7, A11 had different anti-tumor activity against different tumor cells. These data showed that the extraction and their separated effective compounds had strong inhibitory effect on HBV replication so as to have anti-HBV activity, and further separation and purification could enhance anti-HBV activity. Meanwhile, some compounds have high cytotoxicities on different tumor cells. Our study could provide a theoretical basis for the next clinical use and the development of potential and efficient drugs for HBV and tumor therapy from Rabdosia serra.

  18. Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies.

    Science.gov (United States)

    van den Bijgaart, Renske J E; Eikelenboom, Dylan C; Hoogenboom, Martijn; Fütterer, Jurgen J; den Brok, Martijn H; Adema, Gosse J

    2017-02-01

    Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4 + and CD8 + T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.

  19. Surveillance-guided selective digestive decontamination of carbapenem-resistant Enterobacteriaceae in the intensive care unit: A cost-effectiveness analysis.

    Science.gov (United States)

    You, Joyce H S; Li, Hong-Kiu; Ip, Margaret

    2018-03-01

    Clinical findings have shown effectiveness and safety of selective digestive decontamination (SDD) for eradication of carbapenem-resistant Enterobacteriaceae (CRE) in high-risk carriers. We aimed to evaluate the cost-effectiveness of SDD guided by CRE surveillance in the intensive care unit (ICU). Outcomes of surveillance-guided SDD (test-guided SDD) and no screening (control) in the ICU were compared by Markov model simulations. Model outcomes were CRE infection and mortality rates, direct costs, and quality-adjusted life year (QALY) loss. Model inputs were estimated from clinical literature. Sensitivity analyses were conducted to examine the robustness of base case results. Test-guided SDD reduced infection (4.8% vs 5.0%) and mortality (1.8% vs 2.1%) rates at a higher cost ($1,102 vs $1,074) than the control group in base case analysis, respectively. Incremental cost per QALY saved (incremental cost-effectiveness ratio [ICER]) by the test-guided SDD group was $557 per QALY. Probabilistic sensitivity analysis showed that test-guided SDD was effective in saving QALYs in 100% of 10,000 Monte Carlo simulations, and cost-saving 59.1% of time. The remaining 40.9% of simulations found SDD to be effective at an additional cost, with ICERs accepted as cost-effective per the willingness-to-pay threshold. Surveillance-guided SDD appears to be cost-effective in reducing CRE infection and mortality with QALYs saved. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  20. Informatics enables public health surveillance

    Directory of Open Access Journals (Sweden)

    Scott J. N McNabb

    2017-01-01

    Full Text Available Over the past decade, the world has radically changed. New advances in information and communication technologies (ICT connect the world in ways never imagined. Public health informatics (PHI leveraged for public health surveillance (PHS, can enable, enhance, and empower essential PHS functions (i.e., detection, reporting, confirmation, analyses, feedback, response. However, the tail doesn't wag the dog; as such, ICT cannot (should not drive public health surveillance strengthening. Rather, ICT can serve PHS to more effectively empower core functions. In this review, we explore promising ICT trends for prevention, detection, and response, laboratory reporting, push notification, analytics, predictive surveillance, and using new data sources, while recognizing that it is the people, politics, and policies that most challenge progress for implementation of solutions.

  1. Effect of homeopathic treatment on gene expression in Copenhagen rat tumor tissues.

    Science.gov (United States)

    Thangapazham, Rajesh L; Rajeshkumar, N V; Sharma, Anuj; Warren, Jim; Singh, Anoop K; Ives, John A; Gaddipati, Jaya P; Maheshwari, Radha K; Jonas, Wayne B

    2006-12-01

    Increasing evidence suggests that the inability to undergo apoptosis is an important factor in the development and progression of prostate cancer. Agents that induce apoptosis may inhibit tumor growth and provide therapeutic benefit. In a recent study, the authors found that certain homeopathic treatments produced anticancer effects in an animal model. In this study, the authors examined the immunomodulating and apoptotic effects of these remedies. The authors investigated the effect of a homeopathic treatment regimen containing Conium maculatum, Sabal serrulata, Thuja occidentalis, and a MAT-LyLu Carcinosin nosode on the expression of cytokines and genes that regulate apoptosis. This was assessed in prostate cancer tissues, extracted from animals responsive to these drugs, using ribonuclease protection assay or reverse transcription polymerase chain reaction. There were no significant changes in mRNA levels of the apoptotic genes bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, FasL, or the cytokines interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-beta, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-alpha, IL-2, and interferon-gamma in prostate tumor and lung metastasis after treatment with homeopathic medicines. This study indicates that treatment with the highly diluted homeopathic remedies does not alter the gene expression in primary prostate tumors or in lung metastasis. The therapeutic effect of homeopathic treatments observed in the in vivo experiments cannot be explained by mechanisms based on distinct alterations in gene expression related to apoptosis or cytokines. Future research should explore subtle modulations in the expression of multiple genes in different biological pathways.

  2. Clinical Evaluation and Cost-Effectiveness Analysis of Serum Tumor Markers in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2013-01-01

    Full Text Available The detection of serum tumor markers is valuable for the early diagnosis of lung cancer. Tumor markers are frequently used for the management of cancer patients. However, single markers are less efficient but marker combinations increase the cost, which is troublesome for clinics. To find an optimal serum marker combination panel that benefits the patients and the medical management system as well, four routine lung cancer serum markers (SCCA, NSE, CEA, and CYFRA21-1 were evaluated individually and in combination. Meanwhile, the costs and effects of these markers in clinical practice in China were assessed by cost-effectiveness analysis. As expected, combinations of these tumor markers improved their sensitivity for lung cancer and different combination panels had their own usefulness. NSE + CEA + CYFRA21-1 was the optimal combination panel with highest Youden’s index (0.64, higher sensitivity (75.76%, and specificity (88.57%, which can aid the clinical diagnosis of lung cancer. Nevertheless, the most cost-effective combination was SCCA + CEA, which can be used to screen the high-risk group.

  3. Effects of hyperthermia, x-ray irradiation and their combination on ascites tumor cells of mice

    International Nuclear Information System (INIS)

    Kaneko, Itsuo

    1982-01-01

    Fibrosarcoma ascites tumor cells (PB8) from NMRI mice were used to investigate cell loss by hyperthermia and/or x-ray irradiation. The tumor cells were labelled by an injection of 125 I-deoxyuridine to the abdominal cavity of the donors 2 days before the physical treatments. The labelled cells, transfered in test tubes, were heated at 44 0 C for 10-20 min and/or irradiated by x-ray at 250-1612 rad, and were transplanted in the recipient abdominal cavity as soon as possible after the treatments. The radioactivity of the tumor cells, as an indicator of cell loss, was measured with a gamma spectrometer. In the irradiated group, the ratio of cell loss increased in a dose-dependent manner, starting from the 4th day after the transplantation to the 9th day. In the heated group, the ratio of cell loss increased in proportion to the heating time, starting without delay after transplantation. In the combination group, the effect of the treatments was more marked than that by each single treatment. In the early stage of this group, cell loss was by heating and then, from the 4th day, the irradiation effect mostly dominated. It is concluded from the above results that cell loss by heating or irradiation is independent and that the effect of the combination is additive. (author)

  4. Characterization and anti-tumor effects of chondroitin sulfate-chitosan nanoparticles delivery system

    Science.gov (United States)

    Hu, Chieh-Shen; Tang, Sung-Ling; Chiang, Chiao-Hsi; Hosseinkhani, Hossein; Hong, Po-Da; Yeh, Ming-Kung

    2014-11-01

    We prepared chondroitin sulfate (ChS)-chitosan (CS) nanoparticles (NPs) as a delivery carrier, and doxorubicin (Dox) was used as a model drug. The physicochemical properties and biological activities of the Dox-ChS-CS NPs including the release profile, cell cytotoxicity, cellular internalization, and in vivo anti-tumor effects were evaluated. The ChS-CS NPs and Dox-ChS-CS NPs had a mean size of 262.0 ± 15.0 and 369.4 ± 77.4 nm, and a zeta potential of 30.2 ± 0.9 and 20.6 ± 3.1 mV, respectively. In vitro release tests showed that the 50 % release time for the Dox-ChS-CS NPs was 20 h. Two hepatoma cell models, HepG2 and HuH6, were used for evaluating the cytotoxicity and cell uptake efficiency of the Dox-ChS-CS NPs. A significant difference was observed between doxorubicin solution and the Dox-ChS-CS NPs in the cellular uptake within 60 min ( p < 0.01). For the in vivo human xenograft-nude mouse model, the Dox-ChS-CS NPs were more effective with less body weight loss and anti-tumor growth suppression in comparison with the Dox solution. The prepared Dox-ChS-CS NPs offer a new effective targeting nanoparticle delivery system platform for anti-tumor therapy.

  5. Sonoma Persistent Surveillance System

    Energy Technology Data Exchange (ETDEWEB)

    Pennington, D M

    2006-03-24

    Sonoma offers the first cost-effective, broad-area, high-resolution, real-time motion imagery system for surveillance applications. Sonoma is unique in its ability to provide continuous, real-time video imagery of an area the size of a small city with resolutions sufficient to track 8,000 moving objects in the field of view. At higher resolutions and over smaller areas, Sonoma can even track the movement of individual people. The visual impact of the data available from Sonoma is already causing a paradigm shift in the architecture and operation of other surveillance systems. Sonoma is expected to cost just one-tenth the price of comparably sized sensor systems. Cameras mounted on an airborne platform constantly monitor an area, feeding data to the ground for real-time analysis. Sonoma was designed to provide real-time data for actionable intelligence in situations such as monitoring traffic, special events, border security, and harbors. If a Sonoma system had been available in the aftermath of the Katrina and Rita hurricanes, emergency responders would have had real-time information on roads, water levels, and traffic conditions, perhaps saving many lives.

  6. Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

    Science.gov (United States)

    Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria

    2017-07-01

    Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Cecília P Popolin

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1 [Ru(SO4(dppb(bipy], (2 [Ru(CO3(dppb(bipy], (3 [Ru(C2O4(dppb(bipy] and (4 [Ru(CH3CO2(dppb(bipy]PF6 [where dppb = 1,4-bis(diphenylphosphinobutane and bipy = 2,2'-bipyridine], on proliferation of TNBC (MDA-MB-231, estrogen-dependent breast tumor cells (MCF-7 and a non-tumor breast cell line (MCF-10A. Complex (4 was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4 was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4 was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4 should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment.

  8. Detecting Vascular-Targeting Effects of the Hypoxic Cytotoxin Tirapazamine in Tumor Xenografts Using Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Bains, Lauren J.; Baker, Jennifer; Kyle, Alastair H.; Minchinton, Andrew I.; Reinsberg, Stefan A.

    2009-01-01

    Purpose: To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI). Methods and Materials: MR images of HCT-116 xenograft-bearing mice were acquired at 7 Tesla before and 24 hours after intraperitoneal injections of tirapazamine. Quantitative dynamic contrast-enhanced MRI analyses were performed to evaluate changes in tumor perfusion using two biomarkers: the volume transfer constant (K trans ) and the initial area under the concentration-time curve (IAUC). We used novel implanted fiducial markers to obtain cryosections that corresponded to MR image planes from excised tumors; quantitative immunohistochemical mapping of tumor vasculature, perfusion, and necrosis enabled correlative analysis between these and MR images. Results: Conventional histological analysis showed lower vascular perfusion or greater amounts of necrosis in the central regions of five of eight tirapazamine-treated tumors, with three treated tumors showing no vascular dysfunction response. MRI data reflected this result, and a striking decrease in both K trans and IAUC values was seen with the responsive tumors. Retrospective evaluation of pretreatment MRI parameters revealed that those tumors that did not respond to the vascular-targeting effects of tirapazamine had significantly higher pretreatment K trans and IAUC values. Conclusions: MRI-derived parameter maps showed good agreement with histological tumor mapping. MRI was found to be an effective tool for noninvasively monitoring and predicting tirapazamine-mediated central vascular dysfunction.

  9. The effect of tumor size on F-18-labeled fluorodeoxyglucose and fluoroerythronitroimidazole uptake in a murine sarcoma model

    International Nuclear Information System (INIS)

    Chung, June-Key; Chang, Young Soo; Lee, Yong Jin; Kim, Young Ju; Jeong, Jae Min; Lee, Dong Soo; Jang, Ja June; Lee, Myung Chul

    1999-01-01

    The purpose of this study was to evaluate the effect of tumor size on the uptake of 18 F-fluorodeoxyglucose (FDG) and fluoroerythronitroimidazole (FETNIM) in a murine sarcoma model. ICR mice were xenografted with sarcoma 180 cell line and tumors were allowed to grow to a weight of 0.26-5.82 grams. 18 F-FDG and 18 F-FETNIM were injected intravenously in separate groups of mice, and after 1 hr, the tumors were excised and radiotracer uptake was measured. In another group of mice tumors were autoradiographically analyzed and subjected to H and E staining. In both the FDG and FETNIM group, per-gram radiotracer uptake by a tumor was inversely proportional to tumor weight. 18 F-FETNIM correlated more (r=-0.593, p 18 F-FDG (r=-0.447, p 18 F-FETNIM, a direct correlation between tumor weight and the no-uptake-area to total-tumor-area was demonstrated. We concluded that increased tumor size is associated with decreased uptake of 18 F-FDG and FETNIM, though this depends on the type of radiotracers and distribution of necrosis. (author)

  10. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. V. Bleomycin

    International Nuclear Information System (INIS)

    Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

    1979-01-01

    Experiments have been carried out to determine the effect of different time intervals between the administration of x-radiation (1200 rad) and bleomycin (20 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered by the intraperitoneal route either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level, bleomycin alone did not produce a significant growth delay in any of the tumors. In the RIF-1 tumor, growth delays following combination treatments were equal to the addition of the single agent growth delays. In two experiments with EMT6, contrary results were obtained, one producing longer delays following combination treatments than predicted and the other producing shorter delays. This is apparently due to the variability in the growth delay after treatment with radiation alone for this tumor. For the KHT tumor, only small differences from the addition of single agent delays were seen

  11. β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer.

    Science.gov (United States)

    Yu, Xiaomu; Xu, Maoyi; Li, Na; Li, Zongjuan; Li, Hongye; Shao, Shujuan; Zou, Kun; Zou, Lijuan

    2017-08-19

    Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene. Moreover, β-elemene regulated the polarization of macrophages from M2 to M1. β-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate β-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

    Science.gov (United States)

    Golubovskaya, Vita; Berahovich, Robert; Zhou, Hua; Xu, Shirley; Harto, Hizkia; Li, Le; Chao, Cheng-Chi; Mao, Mike Ming; Wu, Lijun

    2017-10-21

    CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

  13. Luteolin and its inhibitory effect on tumor growth in systemic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kapoor, Shailendra, E-mail: shailendrakapoor@yahoo.com [74 crossing place, Mechanicsville, VA (United States)

    2013-04-01

    Lamy et al have provided interesting data in their recent article in your esteemed journal. Luteolin augments apoptosis in a number of systemic malignancies. Luteolin reduces tumor growth in breast carcinomas. Luteolin mediates this effect by up-regulating the expression of Bax and down-regulating the expression of Bcl-xL. EGFR-induced MAPK activation is also attenuated. As a result there is increased G2/ M phase arrest. These effects have been seen both in vivo as well as in vitro. It also reduces ERα expression and causes inhibition of IGF-1 mediated PI3K–Akt pathway. Luteolin also activates p38 resulting in nuclear translocation of the apoptosis-inducing factor. Simultaneously it also activates ERK. As a result there is increased intra-tumoral apoptosis which is caspase dependent as well as caspase independent. - Highlights: ► Luteolin and tumor growth in breast carcinomas. ► Luteolin and pulmonary cancer. ► Luteolin and colon cancer.

  14. The inhibitory effect of anti- tumor polysaccharide from Punica granatum on metastasis.

    Science.gov (United States)

    Varghese, Sheeja; Joseph, Manu M; S R, Aravind; B S, Unnikrishnan; Sreelekha, T T

    2017-10-01

    Galactomannan (PSP001) isolated from the fruit rind of Punica granatum was demonstrated as an excellent antioxidant, immunomodulatory and anticancer agent both in vitro and in vivo models. Since the most lethal and debilitating attribute of cancer cells is their ability to evolve to a state of malignancy, with key features like increased angiogenesis, invasion, migration, colony formation, and metastasis, the present study focused on evaluating the effects of the galactomannan on tumor and malignancy. PSP001 effectively reduced the neovascularization in chick embryos highlighting its potential as an angiogenic inhibitor. Furthermore, the invasion, migration and clonogenic capacity of human and murine cancer cells were dramatically inhibited by PSP001. Evaluation of the molecular mechanism of its unique potential revealed the down regulation of key players including VEGF, MMP-2, and MMP-9 with marked elevation of TIMP-1 and TIMP-2. The anti-metastatic potential of PSP001 tested in pulmonary metastasis C57BL/6 mice model deciphered the combinatorial administration with vincristine deliberated better survival rates and decreased metastatic index. The angiogenic inhibition potential of PSP001 was further proved with peritoneal angiogenesis assay in BALB/c mice ascitic tumor model. The outcomes of the current investigation highlight the mode of action of antitumor galactomannan in the reduction of tumor malignancy. Copyright © 2017. Published by Elsevier B.V.

  15. Acute Effects of Vascular Modifying Agents in Solid Tumors Assessed by Noninvasive Laser Doppler Flowmetry and Near Infrared Spectroscopy

    Directory of Open Access Journals (Sweden)

    Michael Kragh

    2002-01-01

    Full Text Available The potential of noninvasive laser Doppler flowmetry (LDF and near infrared spectroscopy (NIRS to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (∼200 mm3 in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg, 5,6-dimethylxanthenone-4acetic acid (DMXAA, 20 mg/kg, combretastatin A-4 disodium phosphate (CAMP, 250 mg/kg, hydralazine (HDZ, 5 mg/kg, or nicotinamide (NTA, 500 mg/kg. Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41°C heated custombuilt LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by MRS, using light guide coupled reflectance measurements at 800±10 nm. FAA, DMXAA, CAMP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CAMP caused no change in the tumor blood volume, indicating that the mechanism of action of CAMP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and MRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

  16. Effectiveness and Cost Efficiency of Different Surveillance Components for Proving Freedom and Early Detection of Disease: Bluetongue Serotype 8 in Cattle as Case Study for Belgium, France and the Netherlands.

    Science.gov (United States)

    Welby, S; van Schaik, G; Veldhuis, A; Brouwer-Middelesch, H; Peroz, C; Santman-Berends, I M; Fourichon, C; Wever, P; Van der Stede, Y

    2017-12-01

    Quick detection and recovery of country's freedom status remain a constant challenge in animal health surveillance. The efficacy and cost efficiency of different surveillance components in proving the absence of infection or (early) detection of bluetongue serotype 8 in cattle populations within different countries (the Netherlands, France, Belgium) using surveillance data from years 2006 and 2007 were investigated using an adapted scenario tree model approach. First, surveillance components (sentinel, yearly cross-sectional and passive clinical reporting) within each country were evaluated in terms of efficacy for substantiating freedom of infection. Yearly cross-sectional survey and passive clinical reporting performed well within each country with sensitivity of detection values ranging around 0.99. The sentinel component had a sensitivity of detection around 0.7. Secondly, how effective the components were for (early) detection of bluetongue serotype 8 and whether syndromic surveillance on reproductive performance, milk production and mortality data available from the Netherlands and Belgium could be of added value were evaluated. Epidemic curves were used to estimate the timeliness of detection. Sensitivity analysis revealed that expected within-herd prevalence and number of herds processed were the most influential parameters for proving freedom and early detection. Looking at the assumed direct costs, although total costs were low for sentinel and passive clinical surveillance components, passive clinical surveillance together with syndromic surveillance (based on reproductive performance data) turned out most cost-efficient for the detection of bluetongue serotype 8. To conclude, for emerging or re-emerging vectorborne disease that behaves such as bluetongue serotype 8, it is recommended to use passive clinical and syndromic surveillance as early detection systems for maximum cost efficiency and sensitivity. Once an infection is detected and eradicated

  17. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  18. Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model

    Directory of Open Access Journals (Sweden)

    Yoshiharu Okamoto

    2012-10-01

    Full Text Available We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa, intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa and high-molecular-weight fucoidan (HMWF: 300–330 kDa. The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet. The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food.

  19. Identification of anti-tumoral effect of a polypeptide isolated from Scorpionfish Scorpaena plumieri venom and assessment of its potential use for tumor diagnosis

    International Nuclear Information System (INIS)

    Soprani, Juliana

    2008-01-01

    Cancer has killed millions of people worldwide. Despite the increasing knowledge about the molecular basis of tumor development, few advances have been reached in clinical therapy and diagnoses, which shows the importance of new drugs development for therapeutic and diagnosis purpose. Venomous creatures have been studied as potential sources of pharmacological agents and physiological tools. A lot of work has been done about biological activity of terrestrial animals, but comparatively less research has been undertaken on venomous marine creature, particularly fish, which means that marine toxins represent a vast and unexplored source of novel molecules with therapeutical potential. In this work, the scorpion fish Scorpaena plumieri crude venom (SPB) and a gelatinolytic protease purified from this venom (SPGP) were evaluated for their applicability for in vivo tumor detection. In vitro results showed that both. SPB and SPGP, possess a powerful antitumor effects on p53-wild-type glioblastoma cells (LD 50 = 3,9 ± 0,98μg/mL and 8,00 x 10 -12 ± 2,94 x 10 -12 M, respectively) and Ehrlich ascites carcinoma cells (LD 50 =14,05 ± 2,95 μg/mL and 1,22 x 10 -11 ± 6,56 x 10 -12 M, respectively). P53 mutant glioblastoma cells were more resistant to both, SPB and SPGP treatment (LD 50 > 125 μg/mL and LD 50 > 1,39 x 10 -9 M, respectively). The morphological changes observed in the cell lines treated with SPB and SPGP, and the data of DAPI staining, indicate that the antitumor effect of these substances occurs via apoptosis. Radioactive probes of SPB ([ 99m Tc] SPB) and SPGP ([ 125 I] SPGP) with high specific activity and high radiochemical purity were synthesized. Data of biodistribution studies, performed by intravenous injections in Swiss mice bearing Ehrlich carcinoma cells, showed that SPB has poor uptake in tumor region. On the other hand, SPGP had a substantial uptake in tumor at ali analyzed times. Intratumoral administration of [ 125 I]SPGP increased its uptake by

  20. Combined anti-tumor therapeutic effect of targeted gene, hyperthermia, radionuclide brachytherapy in breast carcinoma

    International Nuclear Information System (INIS)

    Chen Daozhen; Tang Qiusha; Xiang Jingying; Xu Fei; Zhang Li; Wang Junfeng

    2011-01-01

    Objective: To investigate the antitumor therapeutic effect of combined therapy of magnetic induction heating by nano-magnetic particles, herpes simplex virus thymidine kinase gene (HSV-tk suicide gene) and internal radiation in mice bearing MCF-7 breast carcinoma. Methods: The transfection reagents, plasmids heat shock protein-HSV-tk (pHSP-HSV-tk), ferroso-ferric oxide nano-magnetic fluid flow and 188 Re-ganciclovir-bovine serum albumin-nanopaticles (GCV-BSA-NP) were prepared. The heating experiments in vivo were carried out using ferroso-ferric oxide nano-magnetic fluid flow. Sixty mice tumor models bearing MCF-7 breast carcinoma were established and randomly divided into six groups. Group A was the control group, B was gene transfection therapy group, C was hyperthermia group, D was gene transfection therapy combined with radionuclide brachytherapy group, E was gene therapy combined with hyperthermia group, and F was gene therapy, hyperthermia combined with radionuclide brachytherapy group. The tumor growth, tumor mass and histopathological changes were evaluated. The expression of HSV-tk in the groups of B, D, E and F was detected by RT-PCR. Poisson distribution and one-way analysis of variance (ANOVA) were used for statistical analysis by SPSS 10.0 software. Results: In the animal heating experiments, the temperature of tumor increased up to 39.6 degree C, 43.2 degree C, and 48.1 degree C quickly with different injected doses (2, 4 and 6 mg respectively) of nano-magnetic particles and maintained for 40 min. The temperature of tumor tissue reduced to 36.8 degree C, 37.5 degree C and 37.8 degree C in 10 min when alternating magnetic field (AMF) stopped. The tumor mass in Groups C ((452.50±30.29) mg), D ((240.98±35.32)mg), E((231.87±27.41) mg) and F ((141.55±23.78) mg) were much lower than that in Group A ((719.12±22.65) mg) (F=800.07, P<0.01), with the most significant treatment effect in Group F.The tumor mass in Group B((684.05±24.02) mg) was higher than

  1. Redefining syndromic surveillance

    Directory of Open Access Journals (Sweden)

    Rebecca Katz

    2011-12-01

    Full Text Available With growing concerns about international spread of disease and expanding use of early disease detection surveillance methods, the field of syndromic surveillance has received increased attention over the last decade. The purpose of this article is to clarify the various meanings that have been assigned to the term syndromic surveillance and to propose a refined categorization of the characteristics of these systems. Existing literature and conference proceedings were examined on syndromic surveillance from 1998 to 2010, focusing on low- and middle-income settings. Based on the 36 unique definitions of syndromic surveillance found in the literature, five commonly accepted principles of syndromic surveillance systems were identified, as well as two fundamental categories: specific and non-specific disease detection. Ultimately, the proposed categorization of syndromic surveillance distinguishes between systems that focus on detecting defined syndromes or outcomes of interest and those that aim to uncover non-specific trends that suggest an outbreak may be occurring. By providing an accurate and comprehensive picture of this field’s capabilities, and differentiating among system types, a unified understanding of the syndromic surveillance field can be developed, encouraging the adoption, investment in, and implementation of these systems in settings that need bolstered surveillance capacity, particularly low- and middle-income countries.

  2. Airborne Video Surveillance

    National Research Council Canada - National Science Library

    Blask, Steven

    2002-01-01

    The DARPA Airborne Video Surveillance (AVS) program was established to develop and promote technologies to make airborne video more useful, providing capabilities that achieve a UAV force multiplier...

  3. Handbook of surveillance technologies

    CERN Document Server

    Petersen, JK

    2012-01-01

    From officially sanctioned, high-tech operations to budget spy cameras and cell phone video, this updated and expanded edition of a bestselling handbook reflects the rapid and significant growth of the surveillance industry. The Handbook of Surveillance Technologies, Third Edition is the only comprehensive work to chronicle the background and current applications of the full-range of surveillance technologies--offering the latest in surveillance and privacy issues.Cutting-Edge--updates its bestselling predecessor with discussions on social media, GPS circuits in cell phones and PDAs, new GIS s

  4. Effects of interferon-gamma and tumor necrosis factor-alpha on macrophage enzyme levels

    Science.gov (United States)

    Pierangeli, Silvia S.; Sonnenfeld, Gerald

    1989-01-01

    Murine peritoneal macrophages were treated with interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF). Measurements of changes in acid phosphatase and beta-glucuronidase levels were made as an indication of activation by cytokine treatment. IFN-gamma or TNF-gamma treatment resulted in a significant increase in the activities of both enzymes measured in the cell lysates. This increase was observable after 6 h of incubation, but reached its maximum level after 24 h of incubation. The effect of the treatment of the cell with both cytokines together was additive. No synergistic effect of addition of both cytokines on the enzyme levels was observed.

  5. Intelligent agents for adaptive security market surveillance

    Science.gov (United States)

    Chen, Kun; Li, Xin; Xu, Baoxun; Yan, Jiaqi; Wang, Huaiqing

    2017-05-01

    Market surveillance systems have increasingly gained in usage for monitoring trading activities in stock markets to maintain market integrity. Existing systems primarily focus on the numerical analysis of market activity data and generally ignore textual information. To fulfil the requirements of information-based surveillance, a multi-agent-based architecture that uses agent intercommunication and incremental learning mechanisms is proposed to provide a flexible and adaptive inspection process. A prototype system is implemented using the techniques of text mining and rule-based reasoning, among others. Based on experiments in the scalping surveillance scenario, the system can identify target information evidence up to 87.50% of the time and automatically identify 70.59% of cases depending on the constraints on the available information sources. The results of this study indicate that the proposed information surveillance system is effective. This study thus contributes to the market surveillance literature and has significant practical implications.

  6. Microprocessor-based integrated LMFBR core surveillance

    International Nuclear Information System (INIS)

    Gmeiner, L.

    1984-06-01

    This report results from a joint study of KfK and INTERATOM. The aim of this study is to explore the advantages of microprocessors and microelectronics for a more sophisticated core surveillance, which is based on the integration of separate surveillance techniques. Due to new developments in microelectronics and related software an approach to LMFBR core surveillance can be conceived that combines a number of measurements into a more intelligent decision-making data processing system. The following techniques are considered to contribute essentially to an integrated core surveillance system: - subassembly state and thermal hydraulics performance monitoring, - temperature noise analysis, - acoustic core surveillance, - failure characterization and failure prediction based on DND- and cover gas signals, and - flux tilting techniques. Starting from a description of these techniques it is shown that by combination and correlation of these individual techniques a higher degree of cost-effectiveness, reliability and accuracy can be achieved. (orig./GL) [de

  7. Combination use of lentinan with x-ray therapy in mouse experimental tumor system, (3). Combination effect on the metastatic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shiio, Tsuyoshi; Ohishi, Kazuo; Niitsu, Iwayasu; Hayashibara, Hiromi; Tsuchiya, Yoshiharu; Yoshihama, Takashi; Moriyuki, Hirobumi

    1988-03-01

    Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF/sub 1/ mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamus cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmorary metastasis system of Lewis lung carcinoma, a marked suppressin of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

  8. Three surveillance strategies for vancomycin-resistant enterococci in hospitalized patients: detection of colonization efficiency and a cost-effectiveness model.

    Science.gov (United States)

    Lee, Todd A; Hacek, Donna M; Stroupe, Kevin T; Collins, Susan M; Peterson, Lance R

    2005-01-01

    To evaluate the cost-effectiveness and detection sensitivity associated with three active surveillance strategies for the identification of patients harboring vancomycin-resistant enterococci (VRE) to determine which is the most medically and economically useful. Culture for VRE from 200 consecutive stool specimens submitted for Clostridium difficile culture. Following this, risk factors were assessed for patients whose culture yielded VRE, and a cost-effectiveness evaluation was performed using a decision analytic model with a probabilistic analysis. A 688-bed, tertiary-care facility in Chicago, Illinois, with approximately 39,000 annual admissions, 7,000 newborn deliveries, 56,000 emergency department visits, and 115,000 home care and 265,000 outpatient visits. All stool specimens submitted to the clinical microbiology laboratory for C. difficile culture from hospital inpatients. From 200 stool samples submitted for C. difficile testing, we identified 5 patients with VRE in non-high-risk areas not screened as part of our routine patient surveillance. Medical record review revealed that all 5 had been hospitalized within the prior 2 years. Three of 5 had a history of renal impairment. The strategy that would involve screening the greatest number of patients (all those with a history of hospital admission in the prior 2 years) resulted in highest screening cost per patient admitted (dollars 2.48), lower per patient admission costs (dollars 480), and the best survival rates. An expanded VRE surveillance program that encompassed all patients hospitalized within the prior 2 years was a cost-effective screening strategy compared with a more traditional one focused on high-risk units.

  9. Smart sensing surveillance system

    Science.gov (United States)

    Hsu, Charles; Chu, Kai-Dee; O'Looney, James; Blake, Michael; Rutar, Colleen

    2010-04-01

    An effective public safety sensor system for heavily-populated applications requires sophisticated and geographically-distributed infrastructures, centralized supervision, and deployment of large-scale security and surveillance networks. Artificial intelligence in sensor systems is a critical design to raise awareness levels, improve the performance of the system and adapt to a changing scenario and environment. In this paper, a highly-distributed, fault-tolerant, and energy-efficient Smart Sensing Surveillance System (S4) is presented to efficiently provide a 24/7 and all weather security operation in crowded environments or restricted areas. Technically, the S4 consists of a number of distributed sensor nodes integrated with specific passive sensors to rapidly collect, process, and disseminate heterogeneous sensor data from near omni-directions. These distributed sensor nodes can cooperatively work to send immediate security information when new objects appear. When the new objects are detected, the S4 will smartly select the available node with a Pan- Tilt- Zoom- (PTZ) Electro-Optics EO/IR camera to track the objects and capture associated imagery. The S4 provides applicable advanced on-board digital image processing capabilities to detect and track the specific objects. The imaging detection operations include unattended object detection, human feature and behavior detection, and configurable alert triggers, etc. Other imaging processes can be updated to meet specific requirements and operations. In the S4, all the sensor nodes are connected with a robust, reconfigurable, LPI/LPD (Low Probability of Intercept/ Low Probability of Detect) wireless mesh network using Ultra-wide band (UWB) RF technology. This UWB RF technology can provide an ad-hoc, secure mesh network and capability to relay network information, communicate and pass situational awareness and messages. The Service Oriented Architecture of S4 enables remote applications to interact with the S4

  10. 2-methoxyestradiol-mediated anti-tumor effect increases osteoprotegerin expression in osteosarcoma cells.

    Science.gov (United States)

    Benedikt, Michaela B; Mahlum, Eric W; Shogren, Kristen L; Subramaniam, Malayannan; Spelsberg, Thomas C; Yaszemski, Michael J; Maran, Avudaiappan

    2010-04-01

    Osteosarcoma is a bone tumor that frequently develops during adolescence. 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol, induces cell cycle arrest and cell death in human osteosarcoma cells. To investigate whether the osteoprotegrin (OPG) protein plays a role in 2-ME actions, we studied the effect of 2-ME treatment on OPG gene expression in human osteosarcoma cells. 2-ME treatment induced OPG gene promoter activity and mRNA levels. Also, Western blot analysis showed that 2-ME treatment increased OPG protein levels in MG63, KHOS, 143B and LM7 osteosarcoma cells by 3-, 1.9-, 2.8-, and 2.5-fold, respectively, but did not affect OPG expression in normal bone cells. In addition, increases in OPG protein levels were observed in osteosarcoma cell culture media after 3 days of 2-ME treatment. The effect of 2-ME on osteosarcoma cells was ligand-specific as parent estrogen, 17beta-estradiol and a tumorigenic estrogen metabolite, 16alpha-hydroxyestradiol, which do not affect osteosarcoma cell cycle and cell death, had no effect on OPG protein expression. Furthermore, co-treating osteosarcoma cells with OPG protein did not further enhance 2-ME-mediated anti-tumor effects. OPG-released in 2-ME-treated cultures led to an increase in osteoblastic activity and a decrease in osteoclast number, respectively. These findings suggest that OPG is not directly involved in 2-ME-mediated anti-proliferative effects in osteosarcoma cells, but rather participates in anti-resorptive functions of 2-ME in bone tumor environment. Copyright 2010 Wiley-Liss, Inc.

  11. Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

    Directory of Open Access Journals (Sweden)

    Wang Cun

    2012-05-01

    Full Text Available Abstract Background Despite recent advances in the treatment of hepatocellular carcinoma (HCC, the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. Methods The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Results Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth

  12. Time until initiation of tumor growth is an effective measure of the anti-angiogenic effect of TNP-470 on human glioblastoma in nude mice

    DEFF Research Database (Denmark)

    Kragh, M; Spang-Thomsen, M; Kristjansen, P E

    1999-01-01

    , 11, or 15 days after inoculation. The time from inoculation until initiation of exponential tumor growth was determined along with the post-therapeutic growth delay and the initial tumor doubling time (TD) for each individual tumor (n=103) on the basis of tumor volume growth curves. We found that: i......) the onset of growth of U87 xenografts was effectively inhibited by concurrent treatment with TNP-470 beyond the first three days after inoculation, ii) this effect was fully reversible upon termination of therapy, and iii) the post-therapeutic growth delay was independent of the accumulated dose...

  13. CD147 stimulates hepatoma cells escaping from immune surveillance of T cells by interaction with Cyclophilin A.

    Science.gov (United States)

    Ren, Yi-Xin; Wang, Shu-Jing; Fan, Jian-Hui; Sun, Shi-Jie; Li, Xia; Padhiar, Arshad Ahmed; Zhang, Jia-Ning

    2016-05-01

    T cells play an important role in tumor immune surveillance. CD147 is a member of immunoglobulin superfamily present on the surface of many tumor cells and mediates malignant cell behaviors. Cyclophilin A (CypA) is an intracellular protein promoting inflammation when released from cells. CypA is a natural ligand for CD147. In this study, CD147 specific short hairpin RNAs (shRNA) were transfected into murine hepatocellular carcinoma Hepa1-6 cells to assess the effects of CD147 on hepatoma cells escaping from immune surveillance of T cells. We found extracellular CypA stimulated cell proliferation through CD147 by activating ERK1/2 signaling pathway. Downregulation of CD147 expression on Hepa1-6 cells significantly suppressed tumor progression in vivo, and decreased cell viability when co-cultured with T cells in vitro. Importantly, knockdown of CD147 on Hepa1-6 cells resulted in significantly increased T cells chemotaxis induced by CypA both in vivo and in vitro. These findings provide novel mechanisms how tumor cells escaping from immune surveillance of T cells. We provide a potential therapy for hepatocellular carcinoma by targeting CD147 or CD147-CypA interactions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

    Science.gov (United States)

    Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

    2015-01-01

    Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

  15. Effects of continued psychological care toward brain tumor patients and their family members' negative emotions.

    Science.gov (United States)

    Xiao, Ning; Zhu, Dan; Xiao, Shuiyuan

    2018-01-01

    Numerous studies have confirmed that brain tumor patients and their family members frequently exhibit negative emotional reactions, such as anxiety and depression, during diagnosis and treatment of the disease. Family members experience increasing pressure as the year of survival of patient progress. The aim of this study was to investigate the effects of the continued psychological care (CPC) toward the brain tumor patients and their family members' emotions. The asynchronous clinical control trial was performed, and 162 brain tumor patients and their family members were divided into the control group and the intervention group. The control group was only performed the telephone follow-up toward the patients. Beside this way, the intervention group was performed the CPC toward the patients and their family member. The self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used to measure the negative emotions of the patients and their family members, and the patients' treatment compliance and the incidence of seizures were compared. The SAS and SDS scores of the intervention group on the 14 days, 28 days and 3 months of the CPC were significantly lower than the control group (P family members.

  16. Premature drug release of polymeric micelles and its effects on tumor targeting.

    Science.gov (United States)

    Miller, Tobias; Breyer, Sandra; van Colen, Gwenaelle; Mier, Walter; Haberkorn, Uwe; Geissler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

    2013-03-10

    Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Dll4 blockade potentiates the anti-tumor effects of VEGF inhibition in renal cell carcinoma patient-derived xenografts.

    Directory of Open Access Journals (Sweden)

    Kiersten Marie Miles

    Full Text Available The Notch ligand Delta-like 4 (Dll4 is highly expressed in vascular endothelium and has been shown to play a pivotal role in regulating tumor angiogenesis. Blockade of the Dll4-Notch pathway in preclinical cancer models has been associated with non-productive angiogenesis and reduced tumor growth. Given the cross-talk between the vascular endothelial growth factor (VEGF and Delta-Notch pathways in tumor angiogenesis, we examined the activity of a function-blocking Dll4 antibody, REGN1035, alone and in combination with anti-VEGF therapy in renal cell carcinoma (RCC.Severe combined immunodeficiency (SCID mice bearing patient-derived clear cell RCC xenografts were treated with REGN1035 and in combination with the multi-targeted tyrosine kinase inhibitor sunitinib or the VEGF blocker ziv-aflibercept. Immunohistochemical and immunofluorescent analyses were carried out, as well as magnetic resonance imaging (MRI examinations pre and 24 hours and 2 weeks post treatment. Single agent treatment with REGN1035 resulted in significant tumor growth inhibition (36-62% that was equivalent to or exceeded the single agent anti-tumor activity of the VEGF pathway inhibitors sunitinib (38-54% and ziv-aflibercept (46%. Importantly, combination treatments with REGN1035 plus VEGF inhibitors resulted in enhanced anti-tumor effects (72-80% growth inhibition, including some tumor regression. Magnetic resonance imaging showed a marked decrease in tumor perfusion in all treatment groups. Interestingly, anti-tumor efficacy of the combination of REGN1035 and ziv-aflibercept was also observed in a sunitinib resistant ccRCC model.Overall, these findings demonstrate the potent anti-tumor activity of Dll4 blockade in RCC patient-derived tumors and a combination benefit for the simultaneous targeting of the Dll4 and VEGF signaling pathways, highlighting the therapeutic potential of this treatment modality in RCC.

  18. Dietary administration of scallion extract effectively inhibits colorectal tumor growth: cellular and molecular mechanisms in mice.

    Directory of Open Access Journals (Sweden)

    Palanisamy Arulselvan

    Full Text Available Colorectal cancer is a common malignancy and a leading cause of cancer death worldwide. Diet is known to play an important role in the etiology of colon cancer and dietary chemoprevention is receiving increasing attention for prevention and/or alternative treatment of colon cancers. Allium fistulosum L., commonly known as scallion, is popularly used as a spice or vegetable worldwide, and as a traditional medicine in Asian cultures for treating a variety of diseases. In this study we evaluated the possible beneficial effects of dietary scallion on chemoprevention of colon cancer using a mouse model of colon carcinoma (CT-26 cells subcutaneously inoculated into BALB/c mice. Tumor lysates were subjected to western blotting for analysis of key inflammatory markers, ELISA for analysis of cytokines, and immunohistochemistry for analysis of inflammatory markers. Metabolite profiles of scallion extracts were analyzed by LC-MS/MS. Scallion extracts, particularly hot-water extract, orally fed to mice at 50 mg (dry weight/kg body weight resulted in significant suppression of tumor growth and enhanced the survival rate of test mice. At the molecular level, scallion extracts inhibited the key inflammatory markers COX-2 and iNOS, and suppressed the expression of various cellular markers known to be involved in tumor apoptosis (apoptosis index, proliferation (cyclin D1 and c-Myc, angiogenesis (VEGF and HIF-1α, and tumor invasion (MMP-9 and ICAM-1 when compared with vehicle control-treated mice. Our findings may warrant further investigation of the use of common scallion as a chemopreventive dietary agent to lower the risk of colon cancer.

  19. Wilms Tumor

    Science.gov (United States)

    ... a child's general health and to detect any adverse side effects (such as low red or white blood cell ... medicine needed, which helps reduce long-term side effects. The most common ... can be completely removed by surgery. About 41% of all Wilms tumors are stage ...

  20. Effect of immunomodulators and cytostatics in 125I-deoxyuridine and tumor catabolism (a rapid method of antitumour immunomodulators screening)

    International Nuclear Information System (INIS)

    Obernikhin, S.S.; Fuks, B.B.

    1992-01-01

    E1-4 and P-815 murine tumor cells labelled by 125 I-deoxyuridine or 51 Cr were administered in 7-day subcutaneous syngeneic tumors or subcutaneosly. At the same time different groups of mice were treated by immunomodulators and cytostatics. It was shown that cytostatics and immunomodulators significantly delayed catabolism and withdrawing of 125 I-deoxyuridine (that has not been incorporated in DNA) from tumor cells. This delay was correlated with the inhibition of tumor nodes growth rate. It is concluded that influence of cytostatics and immunomodulators on catabolism and withdrawing rate of 125 I-deoxyuridine from tumor cells relates to their cytostatic effect and may be used at the earliest screening step of immunomodulator analysis

  1. Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression

    International Nuclear Information System (INIS)

    Woodfield, Sarah E.; Zhang, Linna; Scorsone, Kathleen A.; Liu, Yin; Zage, Peter E.

    2016-01-01

    Novel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models. Levels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes. Both primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC 50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib. Neuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify

  2. Effect of fractionated radiotherapy using a hypoxic cell radiosensitizer, RK-28, on experimental murine tumor

    International Nuclear Information System (INIS)

    Tanaka, Shukaku

    1990-01-01

    The effect of a hypoxic cell radiosensitizer RK-28, on fractionated radiotherapy was studied using mice with implanted tumors. Experimental animal tumors were third generation isoplants of a mammary carcinoma which arose spontaneously in a C 3 H/He mouse. RK-28 was given to the mice at two dosages: 0.4 mg/g,b.wt. and 0.2 mg/g.b.wt. Total dose of irradiation was 20 Gy which was divided into the first 10 Gy irradiation and the second 10 Gy performed after a proper time interval such as 1, 24, 48 and 72 hours after the first 10 Gy irradiation. Tumor growth was evaluated by TGT 50 /3 times, which was defined as the time required for 50% of the tumors to regrow to the 3 times value of its initial volume. Tumor volume was measured every day and TGT 50 /3 times was calculated by logit analysis method. No significant differences were found in the TGT 50 /3 times among the groups treated by radiation alone, those treated by RK-administration alone and those without any treatment. TGT 50 value of control group without any treatment was 3.40 (days). TGT 50 value of another group treated by RK-28 alone was 3.46. and TGT 50 value of 20 Gy X-ray irradiation alone was 10.23. Under the fractionated X-ray irradiation alone, TGT 50 values of the various time interval such as 9, 14, 48 and 72 hours were 11.26, 10.42, 12.14 and 1.10. Under the combined treatment of the fractionated X-ray irradiation and RK-28 administration, TGT 50 values were 17.84, 16.42, 16.59 and 17.49. These TGT 50 /3 times values showed that RK-28 had a radiosensitizing effect when given with fractionated radiotherapy even at lower doses of RK-28 administration and radiation. Therefore, it was suggested that fractionated radiotherapy using RK-28 was useful in the cancer treatment. (author) 52 refs

  3. Meeting the challenge of homogenous boron targeting of heterogeneous tumors for effective boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    Heber, Elisa M.; Trivillin, Veronica A.; Itoiz, Maria E.; Rebagliati, J. Raul; Batistoni, Daniel; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.; Gonzalez, Beatriz N.

    2006-01-01

    BNCT is a tumor cell targeted radiation therapy. Inadequately boron targeted tumor populations jeopardize tumor control. Meeting the to date unresolved challenge of homogeneous targeting of heterogeneous tumors with effective boron carriers would contribute to therapeutic efficacy. The aim of the present study was to evaluate the degree of variation in boron content delivered by boronophenylalanine (BPA), GB-10 (Na 2 10 B 10 H 10 ) and the combined administration of (BPA+GB-10) in different portions of tumor, precancerous tissue around tumor and normal pouch tissue in the hamster cheek pouch oral cancer model. Boron content was evaluated by ICP-AES. The degree of homogeneity in boron targeting was assessed in terms of the coefficient of variation ([S.D./Mean]x100) of boron values. Statistical analysis of the results was performed by one-way ANOVA and the least significant difference test. GB-10 and GB-10 plus BPA achieved respectively a statistically significant 1.8-fold and 3.3-fold increase in targeting homogeneity over BPA. The combined boron compound administration protocol contributes to homogeneous targeting of heterogeneous tumors and would increase therapeutic efficacy of BNCT by exposing all tumor populations to neutron capture reactions in boron. (author)

  4. Smart sensing surveillance system

    Science.gov (United States)

    Hsu, Charles; Chu, Kai-Dee; O'Looney, James; Blake, Michael; Rutar, Colleen

    2010-04-01

    Unattended ground sensor (UGS) networks have been widely used in remote battlefield and other tactical applications over the last few decades due to the advances of the digital signal processing. The UGS network can be applied in a variety of areas including border surveillance, special force operations, perimeter and building protection, target acquisition, situational awareness, and force protection. In this paper, a highly-distributed, fault-tolerant, and energyefficient Smart Sensing Surveillance System (S4) is presented to efficiently provide 24/7 and all weather security operation in a situation management environment. The S4 is composed of a number of distributed nodes to collect, process, and disseminate heterogeneous sensor data. Nearly all S4 nodes have passive sensors to provide rapid omnidirectional detection. In addition, Pan- Tilt- Zoom- (PTZ) Electro-Optics EO/IR cameras are integrated to selected nodes to track the objects and capture associated imagery. These S4 camera-connected nodes will provide applicable advanced on-board digital image processing capabilities to detect and track the specific objects. The imaging detection operations include unattended object detection, human feature and behavior detection, and configurable alert triggers, etc. In the S4, all the nodes are connected with a robust, reconfigurable, LPI/LPD (Low Probability of Intercept/ Low Probability of Detect) wireless mesh network using Ultra-wide band (UWB) RF technology, which can provide an ad-hoc, secure mesh network and capability to relay network information, communicate and pass situational awareness and messages. The S4 utilizes a Service Oriented Architecture such that remote applications can interact with the S4 network and use the specific presentation methods. The S4 capabilities and technologies have great potential for both military and civilian applications, enabling highly effective security support tools for improving surveillance activities in densely crowded

  5. [Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

    Science.gov (United States)

    Ueki, H

    1987-11-01

    We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

  6. Low-temperature plasma-induced antiproliferative effects on multi-cellular tumor spheroids

    International Nuclear Information System (INIS)

    Plewa, Joseph-Marie; Yousfi, Mohammed; Eichwald, Olivier; Merbahi, Nofel; Frongia, Céline; Ducommun, Bernard; Lobjois, Valérie

    2014-01-01

    Biomedical applications of low-temperature plasmas are of growing interest, especially in the field of plasma-induced anti-tumor effects. The present work is aimed at investigating the regionalized antiproliferative effects of low-temperature plasmas on a multicellular tumor spheroid (MCTS), a model that mimics the 3D organization and regionalization of a microtumor region. We report that a low-temperature plasma jet, using helium flow in open air, inhibits HCT116 colon carcinoma MCTS growth in a dose-dependent manner. This growth inhibition is associated with the loss of Ki67, and the regionalized accumulation of DNA damage detected by histone H2AX phosphorylation. This regionalized genotoxic effect leads to massive cell death and loss of the MCTS proliferative region. The use of reactive oxygen species (ROS), scavenger N-acetyl cysteine (NAC) and plasma-conditioned media demonstrate that the ROS generated in the media after exposure to low-temperature plasma play a major role in these observed effects. These findings strengthen the interest in the use of MCTS for the evaluation of antiproliferative strategies, and open new perspectives for studies dedicated to demonstrate the potential of low-temperature plasma in cancer therapy

  7. Low-temperature plasma-induced antiproliferative effects on multi-cellular tumor spheroids

    Science.gov (United States)

    Plewa, Joseph-Marie; Yousfi, Mohammed; Frongia, Céline; Eichwald, Olivier; Ducommun, Bernard; Merbahi, Nofel; Lobjois, Valérie

    2014-04-01

    Biomedical applications of low-temperature plasmas are of growing interest, especially in the field of plasma-induced anti-tumor effects. The present work is aimed at investigating the regionalized antiproliferative effects of low-temperature plasmas on a multicellular tumor spheroid (MCTS), a model that mimics the 3D organization and regionalization of a microtumor region. We report that a low-temperature plasma jet, using helium flow in open air, inhibits HCT116 colon carcinoma MCTS growth in a dose-dependent manner. This growth inhibition is associated with the loss of Ki67, and the regionalized accumulation of DNA damage detected by histone H2AX phosphorylation. This regionalized genotoxic effect leads to massive cell death and loss of the MCTS proliferative region. The use of reactive oxygen species (ROS), scavenger N-acetyl cysteine (NAC) and plasma-conditioned media demonstrate that the ROS generated in the media after exposure to low-temperature plasma play a major role in these observed effects. These findings strengthen the interest in the use of MCTS for the evaluation of antiproliferative strategies, and open new perspectives for studies dedicated to demonstrate the potential of low-temperature plasma in cancer therapy.

  8. Soil and vegetation surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Antonio, E.J.

    1995-06-01

    Soil sampling and analysis evaluates long-term contamination trends and monitors environmental radionuclide inventories. This section of the 1994 Hanford Site Environmental Report summarizes the soil and vegetation surveillance programs which were conducted during 1994. Vegetation surveillance is conducted offsite to monitor atmospheric deposition of radioactive materials in areas not under cultivation and onsite at locations adjacent to potential sources of radioactivity.

  9. Between visibility and surveillance

    DEFF Research Database (Denmark)

    Uldam, Julie

    As activists move from alternative media platforms to commercial social media platforms they face increasing challenges in protecting their online security and privacy. While government surveillance of activists is well-documented in both scholarly research and the media, corporate surveillance...

  10. Reassembling Surveillance Creep

    DEFF Research Database (Denmark)

    Bøge, Ask Risom; Lauritsen, Peter

    2017-01-01

    We live in societies in which surveillance technologies are constantly introduced, are transformed, and spread to new practices for new purposes. How and why does this happen? In other words, why does surveillance “creep”? This question has received little attention either in theoretical developm......We live in societies in which surveillance technologies are constantly introduced, are transformed, and spread to new practices for new purposes. How and why does this happen? In other words, why does surveillance “creep”? This question has received little attention either in theoretical...... development or in empirical analyses. Accordingly, this article contributes to this special issue on the usefulness of Actor-Network Theory (ANT) by suggesting that ANT can advance our understanding of ‘surveillance creep’. Based on ANT’s model of translation and a historical study of the Danish DNA database......, we argue that surveillance creep involves reassembling the relations in surveillance networks between heterogeneous actors such as the watchers, the watched, laws, and technologies. Second, surveillance creeps only when these heterogeneous actors are adequately interested and aligned. However...

  11. Functional and morphological effects of diazepam and midazolam on tumor vasculature in the 9L gliosarcoma brain tumor model using dynamic susceptibility contrast MRI: a comparative study

    Directory of Open Access Journals (Sweden)

    Yan N

    2017-10-01

    Full Text Available Nuo Yan,1 Yuzhen Zheng,2 Cheng Yang1 1Second Department of Anesthesiology, The Affiliated Hospital to Logistics University of PAP, Tianjin, 2Department of Anesthesiology, Tianjin Huanhu Hospital, Tianjin, China Abstract: Antiangiogenic therapy attenuates tumor growth by reducing vascularization. Diazepam (DZP and midazolam (MZL have antiangiogenic properties in human umbilical vein endothelial cells. Thus, we investigated the antiangiogenic activity of DZP and MZL in the rat 9L gliosarcoma brain tumor model. The effect on tumor vasculature was evaluated using dynamic susceptibility contrast magnetic resonance imaging with gradient-echo (GE and spin-echo (SE to assess perfusion parameters, including cerebral blood volume (CBV, cerebral blood flow (CBF, mean transit time (MTT, and mean vessel diameter. The GE-normalized CBF (nCBF in the tumors of untreated controls was significantly lower than that in normal brain tissue, whereas the CBV and MTT were higher. DZP- and MZL-treated rats had higher CBF and lower CBV and MTT values than did untreated controls. The tumor size decreased significantly to 33.5% in DZP-treated rats (P<0.001 and 22.5% in MZL-treated rats (P<0.01 relative to controls. The SE-normalized CBV was lower in DZP-treated (32.9% and MZL-treated (10.6% rats compared with controls. The mean vessel diameter decreased significantly by 32.5% in DPZ-treated and by 24.9% in MZL-treated rats compared with controls (P<0.01. The GE and SE nCBF values were higher in DZP-treated (49.9% and 40.1%, respectively and MZL-treated (41.2% and 32.1%, respectively rats than in controls. The GE- and SE-normalized MTTs were lower in DZP-treated (48.2% and 59.8%, respectively and MZL-treated (40.5% and 51.2%, respectively rats than in controls. Both DZP and MZL had antiangiogenic effects on tumor perfusion and vasculature; however, the antiangiogenic activity of DZP is more promising than that of MZL. Keywords: diazepam, midazolam, 9L gliosarcoma

  12. Approaches to canine health surveillance.

    Science.gov (United States)

    O'Neill, Dan G; Church, David B; McGreevy, Paul D; Thomson, Peter C; Brodbelt, Dave C

    2014-01-01

    Effective canine health surveillance systems can be used to monitor disease in the general population, prioritise disorders for strategic control and focus clinical research, and to evaluate the success of these measures. The key attributes for optimal data collection systems that support canine disease surveillance are representativeness of the general population, validity of disorder data and sustainability. Limitations in these areas present as selection bias, misclassification bias and discontinuation of the system respectively. Canine health data sources are reviewed to identify their strengths and weaknesses for supporting effective canine health surveillance. Insurance data benefit from large and well-defined denominator populations but are limited by selection bias relating to the clinical events claimed and animals covered. Veterinary referral cl